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The objective of this review have been to provide the reader with explicit laboratory methods for preparing agents/ intermediates of interest, testing methods used to assay material efficacy, and ...

The objective of this review have been to provide the reader with explicit laboratory methods for preparing agents/ intermediates of interest, testing methods used to assay material efficacy, and analytical data for structural conformation.
The text format has been designed to be used as a reference and synthetic guide

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    Advances in-polymer-chemistry-and-methods-reported-in-recent-us-patents Advances in-polymer-chemistry-and-methods-reported-in-recent-us-patents Document Transcript

    • ADVANCES IN POLYMER CHEMISTRY AND METHODS REPORTED IN RECENT US PATENTS
    • ADVANCES IN POLYMER CHEMISTRY AND METHODS REPORTED IN RECENT US PATENTS THOMAS F. DEROSA
    • Copyright 2008 by John Wiley & Sons, Inc. All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permission. Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com. Library of Congress Cataloging-in-Publication Data DeRosa, Thomas F. Advances in polymer chemistry and methods reported in recent US patents / Thomas F. DeRosa. p. cm. Includes index. ISBN 978-0-470-31286-5 (cloth) 1. Polymers. 2. Polymerization. I. Title. QD381.D47 2009 668.9–dc22 2008009439 Printed in the United States of America 10 9 8 7 6 5 4 3 2 1
    • Dedicated in Loving Memory to My Father, John G. DeRosa November 27, 1921 – January 6, 1980
    • CONTENTS Preface ................................................................................................ xix I. ADDITIVES Controlled Radical Acrylic Copolymer Thickeners ............................... 1 Polymer-Filler Coupling Additives ..................................................... 5 II. ADHESIVES (Meth)acrylate Block Copolymer Pressure Sensitive Adhesives ............. 11 Absorbable a-Cyanoacrylate Compositions......................................... 15 Use of Polybenzoxazoles (PBOS) for Adhesion................................... 20 III. BIOACTIVE A. Bioabsorbables Segmented Urea and Siloxane Copolymers and Their Preparation Methods ............................................................... 25 Functionalized Polymers for Medical Applications ......................... 28 Degradable Polyacetal Polymers .................................................. 31 Lactone Bearing Absorbable Polymers.......................................... 35 B. Contact Lenses Low Polydispersity Poly-HEMA Compositions .............................. 40 C. Drug Delivery Amphiphilic Block Copolymers and Nanoparticles Comprising the Same .............................................................. 44 Heterofunctional Copolymers of Glycerol and Polyethylene Glycol, Their Conjugates and Compositions ............................... 48 Polyalkylene Glycol Acid Additives ............................................. 51 Thermosensitive Biodegradable Copolymer ................................... 55 Polyamide Graft Copolymers....................................................... 58 Bioerodible Poly(Ortho Esters) from Dioxane-Based Di(Ketene Acetals) and Block Copolymers Containing Them ....... 61 Water-Soluble Polymer Alkanals .................................................. 65 vii
    • Biodegradable Aliphatic Polyester Grafted with Poly(Ethylene Glycol) Having Reactive Groups and Preparation Method Thereof............................................... 69 Coumarin End-Capped Absorbable Polymers ................................. 72 Block Copolymers for Multifunctional Self-assembled Systems........ 76 Methods of Making Functional Biodegradable Polymers ................. 80 Monofunctional Polyethylene Glycol Aldehydes ............................ 84 IV. COATINGS A. Anionic Glycopolymers and Free Radical Polymerization Methods ............... 89 B. Aqueous Method of Making Novel Water-Soluble and Self-doped Polyaniline Graft Copolymers ............................ 93 Oxyfluorination ......................................................................... 97 Aqueous Dispersions of Crystalline Polymers and Uses................... 99 C. Fluorine Multifunctional (Meth)Acrylate Compound, Photocurable Resin Composition and Article ............................ 102 D. Hydrophilic Polyoxyalkylene Phosphonates and Improved Process for Their Synthesis .................................................... 105 E. Hydrophobic Polymers and Polymer Coatings ................................................. 108 Photochemical Crosslinkers for Polymer Coatings and Substrate Tie-Layer............................................ 112 Use of Poly(Dimethyl Ketone) to Manufacture Articles in Direct Contact with a Humid or Aqueous Medium................. 116 F. Thermally Stable Polyaryleneetherketone Phosphine Oxide Compositions Incorporating Cycloaliphatic Units for Use as Polymeric Binders in Thermal Control Coatings and Method for Synthesizing Same........................................................... 118 G. Vapor Deposition of Polymers Functionalization of Porous Materials by Vacuum Deposition of Polymers ......................................................... 121 viii Contents
    • H. Succinic Anhydride Derivatives Light Absorbent Agent Polymer for Organic Anti-reflective Coating and Preparation Method and Organic Anti-reflective Coating Composition Comprising the Same ........ 124 V. COSMETICS Water-Soluble or Water-Dispersible Graft Polymers, Their Preparation and Use........................................................... 129 VI. DENTAL A. Cement (Meth)Acrylate-Substituted Iminooxidiazine Dione Derivatives ................................................................. 133 B. Dental Composites (Meth)Acrylic Ester Compound and Use Thereof ......................... 138 VII. ELECTROACTIVE A. Charge Transport Materials Hole Transport Polymers and Devices Made with Such Polymers ... 143 Acrylic Polymer and Charge Transport Material ........................... 147 B. Dielectric Materials Thermosetting Aromatic Dielectric Material ................................ 150 C. Donor-Acceptor Complexes Polyester Having p-Conjugated Group in Side Chain and Charge Transporting Material Using the Same .................... 155 D. Electroconductive Halogenated Thiophene Monomer for the Preparation of Regioregular Polythiophenes .............................................. 158 Electrically Conductive Polymeric Biomaterials, the Process for Their Preparation and Use in Biomedical and Health Care Fields ................................................................ 161 Dibenzodiazocine Polymers....................................................... 164 Redox-Active Polymer and Electrode Comprising the Same ............................................................ 168 Contents ix
    • Use of Sulphonic, Phosphonic and Phosphoric Acids as Dopants for Polyaniline and for Conductive Polyaniline-Based Composite Materials ................................ 172 3,4-Alkylenedioxy-Thiophene Copolymers ............................... 177 E. Electroluminescence Electroactive Polymer, Device Made Therefrom and Method ...... 180 Polymers and Oligomers, Their Synthesis, and Electronic Devices Incorporating the Same........................................... 185 Process for Preparing Poly(Arylene Ethers) with Pendant Crosslinkable Groups ......................................................... 190 F. Semiconductors Mono-, Oligo-, and Polythieno[2,3-b]Thiophenes ...................... 196 Poly(Arylene Ether) Dielectrics............................................... 201 Polythiophenes and Devices ................................................... 205 Mono-, Oligo- and Polymers Comprising Fluorene and Aryl Groups................................................................ 211 VIII. ENERGETIC POLYMERS Glycidyl Dinitropropyl Formal, Poly(Glycidyl Dinitropropyl Formal), and Preparation Method Thereof .................................. 217 Synthesis of Energetic Thermoplastic Elastomers Containing Both Polyoxirane and Polyoxetane Blocks ................. 220 IX. FIBERS Rigid-Rod Benzobisazole Polymers Incorporating Naphthalene-1,5-Diyl Structure Units ........................................ 223 Polybenzazole Fiber and Use Thereof ........................................... 227 X. FLUORINE A. Critical Polymerization Process for Producing Fluoropolymer ...................................... 231 B. High Strength Fluorinated Terpolymer.......................................................... 234 C. Low Molecular Weight Directly Polymerized Low Molecular Weight Granular Polytetrafluoroethylene....................................................... 237 x Contents
    • Fluoroelastomers Containing Copolymerized Units of Vinyl Esters ............................................................... 241 D. Low Surface Energy Amorphous Polyether Glycols Based on bis-Substituted Oxetane and Tetrahydrofuran Monomers............................... 244 E. Silicon Fluids Cyclic Siloxane Compounds and Making Method...................... 247 F. Surfactants Fluorinated Organosilicon Compounds and Fluorochemical Surfactants ........................................... 251 XI. GELS A. Gelling Agent Ferrocene-Containing, Organic Gelling Compound, and Gel and Cast Film Using the Same................................. 255 B. Hydrogels Random Block Copolymers .................................................... 259 (Meth)Acrylic Esters of Polyalkoxylated Trimethylolpropane...... 262 Prepolymers for Improved Surface Modification of Contact Lenses .................................................................. 265 Preparation of High Molecular Weight Polysuccinimides ............ 269 Degradable Crosslinkers and Degradable Crosslinked Hydrogels Comprising Them............................................... 272 C. Sol-gel Thermosensitive Poly(Organophosphazenes), Preparation Method Thereof and Injectable Thermosensitive Polyphosphazene Hydrogels Using the Same ......................... 278 XII. IMAGING AGENT Polymerization Method for the Synthesis of Polypeptide Imaging Agents ...................................................................... 283 XIII. INK Process for Preparing Chain Extended Thermoplastic Guanidinium Polymers ............................................................ 289 Contents xi
    • XIV. LIQUID CRYSTALS A. Liquid Crystal Aligner Diamines, Polyimide Precursors, and Polyimides Produced by Using the Diamines and Liquid Crystal Aligning Agents .... 293 Photosensitive Polyimides for Optical Alignment of Liquid Crystals .............................................................. 298 B. Liquid Crystal Materials Homopolymers That Exhibit a High Level of Photo-inducable Birefringence .................................................................... 303 Liquid Crystalline Compound, Liquid Crystalline Composition, and Retardation Film ...................................... 307 Perfluoroallyloxy Compound and Liquid Crystal Composition Containing the Same ....................................... 315 Liquid Crystal Polymers......................................................... 318 XV. NANOPARTICLES A. Carbon Nanotubes Method of Coating a Substrate with a Polymer Having a Combination of Crown Ether and Carbon Nanotubes Having Guanidine Groups................................................... 325 Process for Derivatizing Carbon Nanotubes with Diazonium Species ..................................................... 329 Carbon Nanotube Adducts and Methods of Making the Same...... 333 Modification of Nanotubes by Oxidation with Peroxygen Compounds................................................ 336 Arylcarbonylated Vapor-Grown Carbon Nanofibers.................... 339 B. Inorganic Nanotubes Polymeric and Carbon Compositions with Metal Nanoparticles ... 343 Metal Oxide Nanotube and Process for Production Thereof......... 347 C. Nanotube Dispersant Methods for the Synthesis of Modular Poly(Phenyleneethynlenes) and Fine-Tuning the Electronic Properties Thereof for the Functionalization of Nanomaterials ............................................................... 351 XVI. NEW SYNTHETIC METHODS A. Compounds Solid-Phase Preparation of [18 F] Fluorohaloalkanes ................... 357 xii Contents
    • Vinyl Sulphone Modified Polymer.......................................... 362 Ketone Peroxide Derivatives, Their Preparation and Use............ 367 B. Polymers Simplified Method of Producing Biodegradable Aliphatic Polyesters .......................................................... 371 Hydroaminomethylation of Olefins ......................................... 373 Perdeuterated Polyiimides, Their Process of Preparation, and Their Use as Materials Which Are Transparent within the Region from 2500 to 3500 cmÀ1 .................................... 376 Polybutadiene (Meth)Acrylate Composition and Method ........... 379 Soluble Aniline-Thiophene Copolymers .................................. 381 Process for the Preparation of Di- and Polyamines of the Diphenylmethane Series ........................................... 384 Method for Preparing Polymer Maleimides.............................. 386 Method for Preparing Polymers Containing Cyclopentanone Structures................................................. 389 Polypropylene Having a High Maleic Anhydride Content .......... 392 Polyamide Graft Copolymers................................................. 395 Guerbet Polymers................................................................. 398 Polymerization Method......................................................... 401 Process for Producing Polymerizable Polybranched Polyester..... 406 N-Vinylformamide Derivatives, Polymers Formed Therefrom and Synthesis Thereof ....................................................... 409 Polymers............................................................................. 413 Star-Shaped Polymer, Multiple Star Polymer, and Their Preparation Methods ......................................................... 417 XVII. OPTICAL MATERIALS Second-Order Nonlinear Optical Materials Polymers Having Pendant Nonlinear Optical Chromophores and Electrooptic Devices Therefrom.................................... 419 XVIII. PHOTOACTIVE POLYMERS A. Photoluminscence Polymeric Compound and Organic Luminescence Device.......... 427 Electroactive Fluorene Copolymers and Devices Made with Such Polymers .......................................................... 432 Light-Emitting Polymers ....................................................... 437 Modified Suzuki-Method for Polymerization of Aromatic Monomers ..................................................... 444 Contents xiii
    • Block Copolymer and Polymeric Luminescent Element ............ 448 Soluble Poly(Aryl-Oxadiazole) Conjugated Polymers ............... 453 B. Photorefraction Fullerene-Containing Polymer, Producing Method Thereof, and Photorefractive Composition ........................................ 458 XIX. POLYMERIZATION METHODS A. Anionic Method for Anionic Polymerization of Oxiranes ...................... 463 Amido-Organoborate Initiator Systems ................................... 465 Process for Manufacturing Vinyl-rich Polybutadiene Rubber ............................................................................ 467 Catalyst for Synthesizing High Transpolymers......................... 469 Method for the Preparation of Poly(a)-Methylstyrene ............... 472 Use of Sulfur Containing Initiators for Anionic Polymerization of Monomers ................................................................... 474 Production Method of Polyisocyanate by End-Capping with Acyl Chloride ........................................................... 478 B. Catalytic Agents Methods for Making Functionalized Polymers ......................... 481 C. Cationic Polymerization of i-Butene in Hydrocarbon Media Using bis(Borane) Co-Initiators .......................................... 486 Copolymers of Tetrahydrofuran, Ethylene Oxide, and an Additional Cyclic Ether ........................................... 489 D. Chain Transfer Agents Dithiocarbamic Esters .......................................................... 492 E. Emulsifing Agents Amphiphilic Copolymers Useful Especially as Emulsifiers........ 497 Anionic Copolymers Prepared in an Inverse Emulsion Matrix and Their Use in Preparing Cellulosic Fiber Compositions ............................................ 501 F. Free Radical Polymerization Perfluorodiacylperoxides as Polymerization Initiators ............... 504 G. Macroinitators Polymeric Photoinitiators...................................................... 507 xiv Contents
    • Radical Polymerization Method Performed in the Presence of Disulfide Compounds .............................. 511 Copolymers of Maleic Anhydride by Stable Free Radical Polymerization...................................................... 514 H. Macromolecular Depolymerization Catalysts Catalysts and Methods for Polymerizing Macrocyclic Oligomers........................................................................ 517 Catalytic Systems................................................................ 520 I. Metallocene Catalysts Metallocene Catalysts Containing a Cyclopentadienyl Ligand Substituted by a Siloxy or Germiloxy Group Containing an Olefinic Residue........................................................... 523 J. Ring-Opening Metathesis Catalyst Photochromic Polymers and Methods of Synthesizing Same...... 528 Synthesis of A,B-Alternating Copolymers by Olefin Metathesis Reactions of Cyclic Olefins or Olefinic Polymers with an Acyclic Diene .................................................................. 533 K. Ziegler–Natta High 1,4-cis Polybutadiene-Polyurethane Copolymer and Preparation Method Thereof......................................... 539 Process for Producing Polymer ............................................. 542 Polymerization Catalyst Composition .................................... 546 Synthetic Polyisoprenes and a Process for Their Preparation ..... 550 Polymerization Catalyst ....................................................... 552 Use of Stannylenes and Germylenes as Polymerization Catalysts for Heterocycles.................................................. 557 Process for Producing Polar Olefin Copolymer and Polar Olefin Copolymer Obtained Thereby ................................... 560 Carborane Trianion-Based Catalyst........................................ 565 Catalyst for Polymerization of Norbornene ............................. 569 XX. REGULATORS A. Chain Transfer Agents Method for the Production of Homo-, Co-, and Block Copolymers ...................................................... 575 Method for Radical Polymerization in the Presence of a Chain Transfer Agent.................................................. 577 Use of C4-C6-Polymercaptopolyols as Regulators in Solution or Precipitation Polymerization .......................... 581 Contents xv
    • S-(a,a0 -Disubstituted-a00 -Acetic Acid) Substituted Dithiocarbonate Derivatives for Controlled Radical Polymerizations, Process, and Polymers Made Therefrom ...... 584 B. Chain Transfer Processes Chain Transfer Agents for RAFT Polymerization in Aqueous Media............................................................. 588 Hindered Spiro-Ketal Nitroxides............................................ 592 Controlled Polymerization .................................................... 595 N-Alkoxy-4,4-Dioxy-Polyalkyl-Piperidines as Radical Polymerization Inhibitors................................................... 600 C. Photolytic Regulating Agents Method for Producing Polymers with Controlled Molecular Weight and End-Group Functionality Using Photopolymerization in Microemulsions .............................. 604 Ring-Opened Azlactone Photoiniferters for Radical Polymerization ................................................................. 606 XXI. PHOTORESISTS A. Fluorine Containing Monomer Having Fluorine-Containing Acetal or Ketal Structure, Polymer Thereof, and Chemical-Amplification-Type Resist Composition as Well as Process for Formation of Pattern with Use of the Same ........................................ 611 Polymers, Resist Compositions, and Patterning Process ............ 616 Fluorine-Containing Polymerizable Cyclic Olefin Compound .... 623 Photoresist Composition ....................................................... 627 B. Norbornene Norbornene-Type Monomers and Polymers Containing Pendent Lactone or Sultone Groups .................................... 632 Photoresists Containing Sulfonamide Component..................... 636 C. Adamantane Tertiary (Meth)Acrylates Having Lactone Structure, Polymers, Resist Compositions, and Patterning Process ........................ 642 Chemical Amplification Type Positive Resist Composition........ 647 D. Diamantane Acrylate Positive Photosensitive Composition and Pattern-Forming Method Using the Same .................................................... 651 xvi Contents
    • XXII. SEPARATIONS A. Gases Dithiolene Functionalized Polymer Membrane for Olefin/Paraffin Separation ............................................. 657 B. Solutions Tethered Polymer Ligands .................................................... 662 Isolatable, Water-Soluble, and Hydrolytically Stable Active Sulfones of Poly(Ethylene Glycol) and Related Polymers for Modification of Surfaces and Molecules ..................................................... 665 Optically Active Maleimide Derivatives, Optically Active Polymaleimide Derivatives, Process for Their Production, Separating Media Comprising the Optically Active Polymaleimide Derivatives, and Method of Separating Optically Active Compounds Using Them............................ 669 Polymeric Membranes and Uses Thereof ................................ 674 Separating Agent Including a Polysaccharide Derivative Having a Polycyclic Structure............................................. 678 Functionalized Polymers for Binding to Solutes in Aqueous Solutions ........................................................ 683 XXIII. THERMOSETS A. Poly(Ethyl a-Acetoxyacrylate) Acrylic Copolymer ............................................................. 687 B. Polyethersulfone High-Heat Polyethersulfone Compositions .............................. 689 C. Polynorborene Novel (Co)polymer, Process for Producing the Same, and Process for Producing Carboxylated (Co)polymer ........... 692 D. Polyformals Polyformals and Copolyformals with Reduced Water Absorption, Production, and Use Thereof.................... 695 E. Styrene and Zinc Diacrylate Ionomers Branched Ionomers.............................................................. 699 F. Polycyclodiene Copolymer of Conjugated Cyclodiene .................................... 702 Contents xvii
    • G. a-Aromatic Ketones Poly(Aralkyl Ketone)s and Methods of Preparing the Same ....... 705 H. Polyimide Sulfones Polyimide Sulfones, Method and Articles Made Therefrom ....... 708 I. Benzoxazine Resins Method for Producing Benzoxazine Resin............................... 712 J. Acrylonitrile Block Copolymer ................................................................. 714 K. Polycarbonates Aliphatic Diol Polycarbonates and Their Preparation ................ 717 L. Poly(Silarylene-Siloxane-Acetylene) High-Temperature Elastomers from Linear Poly(Silarylene-Siloxane-Acetylene) ................................... 721 Contributors Academic Contributors ....................................................................... 725 Government Contributors.................................................................... 725 Industrial Contributors........................................................................ 726 Index ................................................................................................ 729 xviii Contents
    • PREFACE Much has changed in polymer chemistry since the first resin/polymer patent issued. US Patent 125 (February 10, 1817) describes a method of waterproofing boots and shoes reported by inventor Patrick G. Nagel. The method entailed: Taking two pounds of balsam-copiba, five pounds of the essence of the myrtle- tree, one pound of gum-copal, two pounds of rosin, and three pounds of rendered suet. The objective of this investigation has been to provide readers with current polymer chemistry research trends from academic, governmental, and industrial sources reported in US patents for the years 2006 to 2007. Twenty-three broad subject areas were reviewed as provided below: Additives Fibers Optical materials Adhesives Fluorine Photoactive polymers Bioactive Gels Polymerization methods Coatings Imaging agents Regulators Cosmetics Ink Photoresists Dental Liquid crystals Separations Electroactive Nanoparticles Thermosets Energetic polymers New synthetic methods Another objective of this review have been to provide the reader with explicit laboratory methods for preparing agents/intermediates of interest, testing methods used to assay material efficacy, and analytical data for structural conformation. The text format has been designed to be used as a reference and synthetic guide for polymer and organic chemists as well as graduate students. The text, however, is not restricted to polymer chemistry. In many instances—and with only marginal mod- ifications—intermediates and products are readily convertible into other agents in related or dissimilar research concentrations. To underscore this point, structural depictions of reagents, intermediates, and products are provided to allow the researcher to more easily visualize other/future material applications. Finally I thoroughly enjoyed compiling this review and trust the reader will find it useful. THOMAS F. DEROSA December, 2007 xix
    • I. ADDITIVES Title: Controlled Radical Acrylic Copolymer Thickeners Author: S. C. Schmidt et al., US Patent Application 2007-0082827 (April 12, 2007) Assignee: Arkema, Inc. (Philadelphia, PA) SIGNIFICANCE Di- and triblock polymers have been prepared by nitric oxide mediated polymer- ization using t-butyl 1-diethylphosphono-2,2-dimethylpropyl nitroxide. Materials prepared from this process are useful as paint thickeners and viscosity index improvers in paint. REACTION c OCH3O OCH3O O OC12H25 OCH3O a b Note 1 i EXPERIMENTAL Preparation of Poly(Methacrylate-b-(Dodecyl Methacrylate- co-Methacrylate)) A steel resin kettle was charged with t-butyl 1-diethylphosphono-2,2-dimethylpropyl nitroxide (30.0 mmol) and methyl acrylate (6.97 mol) and then heated to 110 C for 3 hours, at which point the reaction had reached 50% conversion. The reaction mixture was cooled to ambient temperature and the Mw determined to be 12,600 daltons. In a Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 1
    • glassreactordodecylmethacrylate(159.4 mmol)washeatedto100 Candtreatedwith the previously prepared polymer mixture (25.3 g) and methyl acrylate (25.3 mmol). This mixture was then treated with polymethacrylate (12.65 g) and methyl acrylate (4.83 g) and heated to 100 C to 105 C for several hours. The resultant viscous liquid was diluted with an equal volume of THF and precipitated into cold stirring methanol; the product was isolated having a Mw of 56,500 daltons and Mn of 39,600 daltons. DERIVATIVES NOTES 1. The nitric oxide mediated polymerization agent t-butyl 1-diethylphosphono- 2,2-dimethylpropyl nitroxide, (I), was prepared according to the method of Gillet [1] as illustrated below: t-C4H9 H O N H t-C4H9 P t-C4H9 OC2H5 O OC2H5 N t-C4H9 P t-C4H9 OC2H5 O OC2H5 O i ii (I) i: t-Butylamine, diethyl phosphate ii: 3-Chloroperbenzoic acid 2. Random copolymers effective as paint viscosity index improvers were prepared by Shoaf as provided in Table 2. TABLE 1. Selected di- and triblock polymers prepared by controlled free radical polymerization using t-butyl 1-diethylphosphono-2,2-dimethylpropyl nitroxide. Entry Polymer*1 Mn PDI Notes 1C PDDMA-b-PS 28,000 1.6 PS ¼ 16% 1D PDDMA-b-PS-b-PDDMA 31,600 1.7 PS ¼ 35% 1E (PDDMA-co-PS)-b-PS-b-(PS-co-PDDMA) 31,600 1.7 PS ¼ 48% 1F PDDMA-b-PMA-b-PDDMA 23,000 1.5 PMA ¼ 48% 1I PDDMA-b-PMA-b-PDDMA 76,000 2.0 PMA ¼ 60% Note: All materials were used as viscosity index improvers in paint. *1 PDDMA ¼ Polydodecyl methacrylate PMA ¼ Polymethacrylate 2 Controlled Radical Acrylic Copolymer Thickeners
    • 3. Blankenship [3] prepared polyethylene glycol carbamate, (II), as paint thick- eners containing poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) and either 1,6-hexamethylene diisocyanate or 4,40 -methylene bis-(isocyanatocy- clohexane). Polycarbamates were also prepared by Bauer [4] using a block polymer initiated by stearyl alcohol and consisting of poly(ethylene oxide-b- propylene oxide-b-butylene oxide-b-dodecene oxide-b-tetradecene oxide) coupled with the diisocyanate, Desmodur NÒ . a O O H N O 6 265 (II) 4. Polycarbamates, (III), prepared by Martin [5] consisting of toluene diisocya- nate, methoxypolyethylene glycol, polypropylene glycol, and dihydroxy- methyl propanoic acid were also effective as paint thickeners and viscosity index modifiers. c H N NH O OO O O H N O OO H3CO a b (III) TABLE 2. Random copolymers used as viscosity index improvers and thickeners in paints. Entry Polymer*1 Monomer Ratio*2 (wt%) 1 PS-co-PEHA-co-PAAEM-co-PMAA 51.8/22.7/8.0/2.5 5 PS-co-PEHA-co-PAAEM-co-PMAA-co-PAA 45.9/21.1/8.0/1.25/3.75 7 PS-co-PEHA-co-PMAA 63.7/18.9/2.5 *1 AA ¼ Acrylic acid AAEM ¼ Acetoacetoxy ethyl methacrylate EHA ¼ 2-Hydroxylethyl acrylate MMA ¼ Methylmethacrylate *2 The remainder of the composition consisted of alkyd. Notes 3
    • References 1. J.-P. Gillet et al., US Patent 6,624,322 (September 23, 2003) 2. G.L. Shoaf et al., US Patent Application 2006-0270769 (November 30, 2006) 3. R.M. Blankenship et al., US Patent Application 2006-0106153 (May 18, 2006) 4. S. Bauer et al., US Patent 7,189,772 (March 13, 2007) 5. E. Martin et al., US Patent 7,144,945 (December 5, 2006) 4 Controlled Radical Acrylic Copolymer Thickeners
    • Title: Polymer-Filler Coupling Additives Author: A. Fukushima et al., US Patent 7,186,845 (March 6, 2007) Assignee: Bridgestone Corporation (Tokyo, JP) SIGNIFICANCE A method for preparing and covalently bonding either 4-(2-oxazolyl)-phenyl- or methyl-N-phenylnitrone to natural rubber in automotive tires is described. The effect has been a 40% overall reduction in tire hysteresis and superior performance over existing polyamine formulations. REACTION O Cl O H O HO N N HO N O i ii iii Model reaction product O NH O H HO iv N O O N Notes 1,2 i: 2-Aminoethanol, CCl3H ii: Sulfuric acid, sodium hydroxide, CCl3H iii: N-Phenyl-hydroxyamine, ethanol iv: Cyclododecene 5
    • EXPERIMENTAL 1. Preparation of 4-Formyl-N-(2-Hydroxyethyl)-Benzamide Asolutionof4-formyl-benzoylchloride(1eq)in300 mlofCCl3Hwasaddeddropwise at À10 C to a solution of 2-aminoethanol (2 eq), dissolved in 200 ml of CCl3H, and then stirred at 25 C for 2 hours. The mixturewas filtered, dried, and concentrated, and 17.4 g of product were isolated as a yellow liquid. 2. Preparation of 4-(2-Oxazolyl)-Benzaldehyde The Step 1 product (17.4 g) was treated dropwise with 50 ml of 18 M H2SO4 and then heated to 100 C for 60 minutes. The mixture was added dropwise with stirring to 500 ml 20% sodium hydroxide and 500 ml of CCl3H while the solution temperature was kept below 15 C. The organic phase was separated and dried, and 6.3 g of product were isolated. 3. Preparation of 4-(2-Oxazolyl)-Phenyl-N-Phenylnitrone AmixtureoftheStep2product(1eq)andN-phenyl-hydroxyamine(1eq)wasrefluxed in 100 ml of ethanol for 30 minutes and then concentrated to 50 ml. The concentrate was treated with 50 ml of water and cooled in a refrigerator to 5 C overnight. White crystals were obtained; these were isolated by filtration, dried, and 6.7 g of product were isolated. 4. Model Reaction: Reactivity of 4-(2-Oxazolyl)-Phenyl-N-Phenylnitrone with Cyclododecene In selected amounts the Step 3 product was mixed with 1 ml cyclododecene and then heated to 171 C. The amount of recoverable Step 3 compound at various timeperiodsduringthereactionwithcyclododecenewasanindicationofthereactivity of this product with unsaturated carbon–carbon bonds. Scoping results are provided in Table 1. DERIVATIVES 4-(2-Oxazolyl)-phenyl-N-methylnitrone, (I), was also prepared: N HO N O (I) 6 Polymer-Filler Coupling Additives
    • TESTING 1. Reactivities Reactivities of the Step 3 product and 4-(2-oxazolyl)-phenyl-N-methylnitrone, (I), with cyclododecene at 170 C are provided in Table 1. N HO N R O 2. Tan d The effect of the experimental agents on natural rubber hysteresis was determined by measuring tan d at 5% strain using an ARES-A Rheometer at 50 C and 15 Hz. Testing results are provided in Table 2. TABLE 1. Percent incorporation of the Step 3 product and derivative into cyclododecene at 170 C. Entry R Heating Time @ 170 C (min) Nitrone Amount (mg) Amount of Incorporated Experimental Nitrone (%) 2 Phenyl 5 5.52 97 4 Phenyl 15 5.65 100 5 Phenyl 30 5.60 100 7 Methyl 5 4.09 39 9 Methyl 15 3.83 78 10 Methyl 30 4.05 98 Note: No characterization data for either experimental agents or cyclododecene addition products were provided by author. Testing 7
    • NOTES 1. In a subsequent investigation by the author [1] styrene butadiene rubber functionalized with the Step 3 product was prepared and was effective in lowering tire hysteresis. 2. Bis-[2-2-thiazolyl-phenyl]disulfide, (I), derivatives were also prepared by the author [2] in a subsequent investigation and were effective in reducing tire hysteresis. S N S S S N (I) TABLE 2. Effect of experimental additives on tan d of natural rubber at various treatment levels. N HO N R O R Nitrone Dosage (mmol) Tan d Unadditized — 0.21 Reference*1 0.16 0.20 Phenyl 0.2 0.18 Phenyl 0.4 0.16 Phenyl 0.8 0.14 Phenyl 1.6 0.13 Methyl 0.2 0.2 Methyl 0.4 0.19 Methyl 0.8 0.16 Methyl 1.6 0.20 Note: Lower tan d values are preferred. *1 SumifineÒ 1162 ¼ (N,N0 -di(2-nitro-2-methyl-propyl)-hexamethylenediamine 8 Polymer-Filler Coupling Additives
    • 3. Polymer nanostrings consisting of block terpolymers of butadiene, styrene, and divinyl-benzene having a Mn of 46,744 daltons were prepared Wang [3] and used as additives in natural and synthetic automotive tires. The nano strings were then postmodified to enhance tire surface and bulk performance. 4. Parker [4] end-group functionalized poly(1,3-butadiene) polymers with iso- propyl hydroxyl-amines to improve the affinity and interaction with carbon black and silica fillers to extend tire lifetime. References 1. A. Fukushima et al., US Patent Application 2006-0084730 (August 20, 2006) 2. S. C. Schmidt et al., US Patent Application (2007-0161756 (July 12, 2007) 3. X. Wang et al., US Patent 7,179,864 (February 20, 2007) 4. D.K. Parker,US Patent Application 2007-0004869 (January 4, 2007) Notes 9
    • II. ADHESIVES Title: (Meth)acrylate Block Copolymer Pressure Sensitive Adhesives Author: A. I. Everaerts et al., US Patent 7,255,920 (August 14, 2007) Assignee: 3M Innovative Properties Company (St. Paul, MN) SIGNIFICANCE Block terpolymers consisting of butyl acrylate with either methylmethacrylate or methyl acrylate have been prepared where the end segments are at least 10,000 daltons and the center segment is at least 60,000 daltons. These materials were coated onto a polycarbonate surface and used to prepare an optical film and an optically clear pressure–sensitive adhesive layer that resists bubble formation when adhered to an outgassing substrate. REACTION O O n-C4H9 OO n-C4H9 O O n-C4H9 OCH3 O OCH3 O 60K10K 60K 10K i ii i: Copper (I) bromide, 1,4-dibromoadipate, n-butyl acrylate, anisole, hexadecane, tris[2-(dimethyl-amino)ethyl]amine ii: Copper (I) chloride, n-butyl acetate, 1,1,4,7,10,10-hexamethyl-triethylenetetra- mine), methylethylketone, methylmethacrylate Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 11
    • EXPERIMENTAL 1. Preparation of a 60K Poly(Butyl Acrylate) Midblock Macroinitiator A reactor was charged with a mixture consisting of CuBr (0.00478 g), 1,4-dibromoa- dipate (0.06 g), n-butyl acrylate (10.0 g), anisole (0.5 g), 0.5 ml of hexadecane, and 9.0 ml of tris[2-(dimethylamino)ethyl]amine. The mixture was heated to 60 C for 20 hours, and the product was isolated having a molecular weight of 60,000 daltons. 2. Preparation Poly[(Methylmethacrylate)-b-Poly(Butyl Acrylate)-b- Poly(Methyl Methacrylate)] The Step 1 product was dissolved in roughly 10 ml of n-butyl acetate and then treated with CuCl (0.0396 g) complexed with 108.8 ml of 1,1,4,7,10,10-hexamethyl-triethy- lenetetramine), 2 ml of methylethylketone, and 4 ml of methylmethacrylate. The mixture was then heated to 60 C for 24 hours, cooled, dissolved in THF to 20% solids, and filtered through alumina to remove residual catalyst. The product poly(methyl- methacrylate)-b-poly(butyl acrylate)-b-poly(methylmethacrylate) was isolated hav- ing molecular weight segments of 10,000/60,000/10,000 daltons, respectively. DERIVATIVES TESTING Accelerated aging testing and dynamic mechanical analysis were used to evaluate the stability of coated laminates. Testing results are provided in Table 2. TABLE 1. Selected block terpolymers and corresponding segmented molecular weights. Entry Polymer*1 Segment Molecular Weights (daltons) 1 PolyMMA-b-polyBA-b-polyMMA 10K–60K–10K 3 PolyMMA-b-polyBA-b-polyMMA 14K–120K–14K 6 PolyMMA-b-polyBA-b-polyMMA 14K–60K–14 7 pMMA-b-p(BA/MA)-b-pMMA 10K–60K–10 10 (pBA-b-pMMA)3 (30K–10K)3 Note: Entry 10 is a tri-arm block copolymer. *1 MMA ¼ Methylmethacrylate BA ¼ n-Butyl acrylate MA ¼ Methyl acrylate 12 (Meth)acrylate Block Copolymer Pressure Sensitive Adhesives
    • NOTES 1. In an earlier investigation by Yang [1] triblock urethane acrylate oligomers terminated with acrylic acid were prepared and used in curable pressure sensitive adhesive compositions. 2. Additional block terpolymers containing propyl acrylate and star block terpo- lymers containing styrene were previously prepared by the author [2] and used in hot-melt pressure-sensitive and heat-activatable adhesives. 3. Random terpolymers consisting of ethyl, butyl, and behenyl acrylate were prepared by the author [3] and used as heat-activatable adhesives. Randon terpolymers consisting of iso-octyl/acrylic acid/styrene macromonomer, 92/4/ 4 mol%, respectively, were prepared by Joseph [4] and used as a reinforced pressure sensitive adhesive. 4. Linear and star diblock polymers consisting of methyl and n-butyl acrylates were prepared by Paul [5] and used as high performance, low viscosity hot-melt adhesives. A single star block terpolymer containing 2-ethylhexyl acrylate was also prepared. 5. Husemann [6] prepared UV-transparent adhesives consisting of acrylic acid, acrylamide, and 2-ethylhexyl acrylate that were effective as pressure-sensitive adhesives. TABLE 2. Thermal aging stability and storage modulus analysis of laminates coated with selected experimental agents using PMMA or PC as the coating substrate. Entry Substrate 90 C Aging Test Results 80 C with 90% Humidity Test Results Log (G0 ) at 25 C (Pascals) Log (G0 ) at 150 C (Pascals) 1 PC*1 Pass Marginal 5.34 4.84 1 PMMA Pass Pass — — 3 PC Bubbles Bubbles 4.63 4.22 3 PMMA Bubbles Bubbles — — 6 PC Pass Pass — — 6 PMMA Pass Pass 7 PC Pass Bubbles — — 7 PMMA Marginal Pass — — 10 PC Bubbles Pass 5.60 4.83 10 PMMA Pass Pass — — *1 PC ¼ Polycarbonate Notes 13
    • References 1. J. Yang et al., US Patent 6,887,917 (May 3, 2005) 2. A.I. Everaerts et al., US Patent 7,084,209 (August 1, 2006) and US Patent 6,806,320 (October 19, 2004) 3. A.I. Everaerts et al., US Patent 7,008,680 (March 7, 2006) 4. E.G. Joseph et al., US Patent 6,994,904 (February 7, 2006) 5. C.W. Paul et al., US Patent Application 2004-0122161 (June 24, 2004) 6. M. Husemann et al., US Patent 7,144,928 (December 5, 2006) 14 (Meth)acrylate Block Copolymer Pressure Sensitive Adhesives
    • Title: Absorbable a-Cyanoacrylate Compositions Author: H. Liu, US Patent 7,238,828 (July 3, 2007) Assignee: Ethicon, Inc. (Somerville, NJ) SIGNIFICANCE Polymerizable3-(2-cyano-acryloyloxy)-butyricacidethylesterhasbeenpreparedina two-stepprocessusing3-hydroxybutyrateand cyanoaceticacid followedbytreatment with formaldehyde. This and related alkyl ester a-cyanoacrylate monomers are useful as tissue adhesives/sealants in surgical and related medical applications. REACTION OH O O NC O O O O i ii O O O O CN CN O O O O Note 1 a Oligomeric intermediate i: Cyanoacetic acid, 4-dimethylaminopyridine, CH2Cl2, DMF, dicyclo- hexylcarbodiimide ii: Paraformaldehyde, piperidine, benzene, phosphorous pentoxide 15
    • EXPERIMENTAL 1. Preparation of 3-(2-Cyano-Acetoxy)-Butyric Acid Ethyl Ester A reactor was charged with ethyl-3-hydroxybutyrate (194.0 g), cyanoacetic acid (149.83 g), 4-dimethylaminopyridine (10.76 g), and 1500 ml of CH2Cl2 and then treated with 75 ml of DMF. The solution was chilled in an ice-water bath and treated with dicyclohexylcarbodiimide (363.45 g) dissolved in 600 ml of CH2Cl2. A white precipitate formed within five minutes after the start of the addition, and the mixture was stirred overnight. The precipitate was then removed by filtration and the filtrate concentrated. The product was isolated in 73% yield after being distilled twice under vacuum, bp ¼ 100–109 C/0.20–0.27 mmHg. 2. Preparation of 3-(2-Cyano-Acryloyloxy)-Butyric Acid Ethyl Ester A mixture consisting of the Step 1 product (39.84 g), paraformaldehyde (6.6 g), 0.06 ml of piperidine, and 150 ml of benzene was stirred in a 250 ml round bottomed flask containing a Dean–Stark trap and refluxed overnight. The solution was then concentrated, and aviscous residue that turned into a solid gel after cooling to ambient temperature was isolated. The solid oligomer was de-polymerized by treating with hydroquinone (0.20 g)andphosphorouspentoxideand byheating to160 C.Thecrude monomerwasdistilledundervacuumandtheproductisolatedin20%yield,bp ¼ 114– 115 C/0.17 mmHg A very small amount of this monomer product was placed between two moist fingertips and bonded the fingertips strongly within one minute. TESTING 1. General Procedure for Lap Shear Testing Using Pig Skin Fresh pigskin was harvestedfrom the backofa pigwithin 5hourspostsacrifice and the fat attached to the inside skin surface trimmed away. The skin was cut into 2 00 Â 1 00 coupons and covered by saline moist paper towels before use. The external surface of the skin was used as the bonding surface to prepare the lap shear joint samples. The coupons were dried prior to forming a lap shear joint. About 100 ml of the experimental adhesive was deposited to one coupon and smoothed to cover a 1=2 00 Â 1 00 area. Another coupon was placed over the area of the initial coupon and a l lb weight placed on top. It was cured for 20 to 30 min and the strength of the joint 1 H NMR (CDCl3) d: 7.03(s, 1H), 6.60(s, 1H), 5.43(m, 1H), 4.15(q, 2H), 2.65(m, 2H), 1.40(d, 3H), 1.23(t, 3H) GC-MS: 98.3% 1 H NMR (CDCl3) d 5.39(m, 1H), 4.16(q, 2H), 3.42(s, 2H), 2.62(m, 2H), 1.37(d, 3H), 1.27(t, 3H) GC-MS: 99.4% 16 Absorbable a-Cyanoacrylate Compositions
    • evaluated using an Instron (Model 5544) with a pulling rate of 5 mm/min. A summary of testing results is provided in Table 1. 2. In vitro Degradation Testing of Polymeric Films A 1 Â 1 inch Prolene mesh was rinsed with 0.5 wt% of NaHCO3 and dried. The mesh was then placed on a freshly prepared Agar plate in a petri dish and roughly 100 mg of a selected experimental adhesive applied across the mesh. The selected adhesive was cured overnight then sealed with parafilm; the film thickness was about 0.6 mm. The film was then placed into a hydrolysis chamber with 100 ml of water while the temperature of the solution was maintained at 75 C. The pH of the solution was maintained at 7.27 with addition of 0.05 M of a NaOH solution throughout the degradationofthepolymerfilm.Thedegradationtimewasdefinedasthetimerequired for the medium to consume 90% of the total consumed NaOH solution. The degradation and glass transition temperatures of each polymer are summarized in Table 2. TABLE 1. Instron lap shear testing results for selected a-cyanoacrylate monomeric derivatives. Entry Source Structure Load Strength (lb) 1B Invention O CN O O O 4.09 2B Invention O CN O O O 4.49 Et-e-CPL-CA Comparison O O CN O O 3.68 Et-a-CPL-CA Comparison O O CN O O 1.29 Testing 17
    • NOTES 1. The polymerization was conducted accorded to the method of Leung [1]. 2. Bioabsorbable adhesive compounds and compositions containing a polyalk- ylene oxide backbone having branched or multi-arm structure derived from reacting with two or more isocyanate substituents were prepared by Roby [2] and used as surgical adhesives and sealants. 3. Photochemical tissue bonding comprising a skin graft and Rose Bengal to form a skin tissue-RB complex with fibrin or a fibrinogen adhesive were prepared by Redmond [3]. The material was crosslinked by the application of electromag- netic energy having a wavelength of at least 488 nm and was used as an adhesive for repairing musculoskeletal tissue damaged by a laceration or rupture in humans. TABLE 2. In vitro degradation and glass transition temperatures of selected a-cyanoacrylate polymeric derivatives. Entry Source Precursor Monomer Polymer Degradation Time (h) Tg ( C) 1B Invention O CN O O O 54.6 32 2B Invention O CN O O O 39.4 À11 Bu-Lac-CA Comparison O CN O O O 49.4 52 Note: Polymers formed from compositions having Tg’s lower than body temperature (37 C) are particularly preferred for medical applications. 18 Absorbable a-Cyanoacrylate Compositions
    • 4. An absorbable a-cyanoacrylate adhesive composition, (I), was prepared by Jonn [4] and used as a soft tissue adhesive. CN O O O O C4H9 (I) References 1. J.C. Leung et al., US Patent 5,928,611 (July 12, 1994) 2. M.S. Roby,US Patent 7,241,846 (July 10, 2007) and US Patent 7,129,300 (October 31, 2006) 3. R.W. Redmond et al., US Patent 7,073,510 (July 11, 2006) 4. J.Y. Jonn et al., US Patent 6,620,846 (September 16, 2003) Notes 19
    • Title: Use of Polybenzoxazoles (PBOS) for Adhesion Author: A. Walter et al., US Patent 7,052,936 (May 30, 2006) Assignee: Infineon Technologies AG (Munich, DE) SIGNIFICANCE A single-step method for preparing polybenzoxazole adhesives is described. These agents are particularly useful in the semiconductor industry for chip and wafer stack applications. REACTION O O HO H2N OH NH2 O O O N N O O i O O HO H2N N O O O O N N O O O O OH NH N O Not isolated O Notes 1,2 a a i: Phosphorus (V) oxide, methane sulfonic acid, 4,40 -hydroxycarbonyl dipheny- lether, methacrylic acid 20
    • EXPERIMENTAL Preparation of Polybenzoxazole End-capped with Methacrylic Acid A reaction vessel was charged with 9,9-diphenyl-(4-amino-3-hydroxyl)dipheny- lether)fluorene (0.3 mol) and 800 ml of methane sulfonic acid and then treated with the dropwise addition of 4,40 -hydroxycarbonyl diphenylether (0.24) dissolved in 400 ml of methane sulfonic acid. The solution was heated for 5 hours at 80 C. After cooling to 40 C, the mixture was treated with the dropwise addition of methacrylic acid (0.12 mol) dissolved in 100 ml of methane sulfonic acid and heated an additional 6 hours at 100 C. The reaction product was isolated by filtering through a glass frit and the filtrate added dropwise to a mixture of 2 liter of water, 2 kg of ice, and 200 ml of this 12 M NH4OH; additional NH4OH was added during the filtration to ensure that the pH did not fall below 8. During the neutralization procedure the rate was such that the temperature did not exceed 30 C. The precipitated polymer was isolated by filtration and washed with 3 liter of cold water. Thereafter the solid was stirred in 3 liter 3% NH4OH at ambient temperature for 1 hour and then suspended repeatedly in water. After filtration and drying, 219 g of product were isolated. DERIVATIVES TABLE 1. Polybenzoxazole derivatives prepared using aminophenols and dicarboxylic acids with selected endcapping agents. Entry Aminophenol Reagent Diacid Reagent End-capping Agents 3 F3C CF3 H2N HO NH2 OH O2 S HO2C CO2H — 4 H2N NH2 HO OH NHO2C CO2H HO2C 5 O2 S H2N HO NH2 OH HO2C CO2H — (continued) Derivatives 21
    • TESTING A 4-inch silicon wafer was sputtered with a titanium nitride layer 50 nm thick and then a selected polybenzoxazole adhesive applied by spin-coating. Following a short softbake at 120 C for 1 minute and at 200 C for 2 minutes on a hotplate, a second 50 nm titanium nitride was sputtered onto the surface. A force of 2 N was then applied to the polybenzoxazole film at 340 C. The sample was further heated to 400 C in an oven under a nitrogen atmosphere for 60 minutes. After cooling to ambient temperature the adhesion test was carried out by means of a shear tester using a Dage Series 400. Testing results are provided in Tables 2 through 4. Entry Aminophenol Reagent Diacid Reagent End-capping Agents 6 F3C CF3 H2N HO NH2 OH HO2C CO2H O O O 8 O O HO H2N OH NH2 NHO2C CO2H O — 10 F3C CF3 H2N HO NH2 OH O2 S HO2C CO2H O OH TABLE 2. Average shear force of polybenzoxazole bonded to a titanium nitride surface. Polybenzoxazole Adhesive Shear Force (N/mm2 ) Coating Type 3 17.94 Spray 4 20.67 Spin coat 5 18.69 Spray TABLE 1. (Continued) 22 Use of Polybenzoxazoles (PBOS) for Adhesion
    • NOTES 1. In an earlier investigation by the author [1] phenyl-linked polyoxazole deri- vatives, (I), were prepared and converted into cyanates by reacting with isocyanate derivates. Cyanate derivatives were used as dielectrics because of their good adhesive and filling properties. O O O N N O O O HO H2N N O O O O N N O (I) a b 2. Polyhydroxyamides, (II), prepared by Halik [2] were converted into polybenzoxazole-based adhesives by curing at 300 C to 350 C. Polyhydroxy- amides, (III), were also prepared and converted into the corresponding TABLE 3. Average shear force of polybenzoxazole bonded to a tantalum nitride surface. Polybenzoxazole Adhesive Shear Force (N/mm2 ) Coating Type 6 17.03 Spray 8 18.47 Spray 10 17.26 Spin coat TABLE 4. Average shear force of polybenzoxazole bonded to a copper surface. Polybenzoxazole Adhesive Shear Force (N/mm2 ) Coating Type Step 1 product 21.28 Brushing 3 20.06 Powder melting Notes 23
    • polybenzoxazoles by curing 60 minutes at 425 C. a a CO O N H CH OH H N OH O (II) OH H N OH N H O O N H O (III) 3. Hall [4] prepared crossliked polymers that were effective as adhesives by UV curing of the neutralization product of diallylamine with selected carboxylic acids, (IV). Additional UV curable diallyl amine adhesives, (V), were prepared by Milne [5]. NH2 O2C CO2H (IV) O O N N (V) References 1. A. Walter et al., US Patent 6,824,642 (November 30, 2004) 2. M. Halik et al., US Patent 7,064,176 (June 20, 2006) 3. R. Sezi et al., US Patent 7,108,807 (September 19, 2006) 4. A.W. Hall, US Patent 7,112, 639 (September 26, 2006) 5. P.E. Milne et al., US Patent 7,026,419 (April 11, 2006) 24 Use of Polybenzoxazoles (PBOS) for Adhesion
    • III. BIOACTIVE A. Bioabsorbables Title: Segmented Urea and Siloxane Copolymers and Their Preparation Methods Author: I. Yilgor et al., US Patent 7,262,260 (August 28, 2007) Assignee: Virginia Tech Intellectual Properties, Inc. (Blacksburg, VA) SIGNIFICANCE Copolymersandterpolymerscontainingsiloxane-ureasegmentshavebeenpreparedby condensing a,o-N-methylaminopropyl terminated polydimethyl-siloxane with bis(4- isocyanatocyclohexyl) methane then postreacting with a,o-N-methylaminopropyl terminated polypropylene oxide. Polymeric biocompatible materials including mem- branes and adhesives obtained in this process had controlled modulus, high ultimate tensile strength, and favorable refractive index properties. REACTION b a aO Si O N H N H O Si O N H N H N H O N H N H O H N N H H NPPO O O PPO i i: a,oÀN-Methylaminopropyl terminated polydimethylsiloxane, isopropylamine, bis (4-isocyanatocyclohexyl) methane, a,oÀN-methylaminopropyl terminated poly- propylene oxide Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 25
    • EXPERIMENTAL Preparation of Poly(Dimethylsiloxane-Urea-Propylene Oxide) A mixture consisting of a,o-N-methylaminopropyl terminated polydimethylsiloxane (80 mol%) having a Mn of 2500 daltons dissolved in isopropylamine and bis(4- isocyanatocyclohexyl)-methane (20 mol%) were mixed at ambient temperature then posttreated with a,o-N-methylaminopropyl terminated polypropylene oxide. The reaction extent was determined by FTIR spectroscopy by monitoring the disappear- ance of the isocyanate peak at 2270 cmÀ1 . Reaction mixtures were always homoge- neous and usually clear throughout the reactions. No precipitation was observed. DERIVATIVES AND TESTING TABLE 1. Comparison of tensile properties of bis(4-isocyanatocyclohexyl) methane- basedpolydimethylsiloxane-urea and polyether/polydimethylsiloxane-urea segmented copolymers. Entry Polyether Polyether Mn (daltons) Polymer Urea Content (wt%) [Z] (dL/g) Modulus (MPa) Tensile Strength (MPa) Elongation (%) 1 PDMS*1 2500 20 0.48 20.6 7.90 205 3 PDMS 2500 19 0.54 21.3 8.30 180 4 PEO 2000 20 0.81 4.30 25.4 1320 6 PEO 2000 19 0.72 4.50 26.5 1450 *1 Polydimethylsiloxane NOTES 1. High purity and high molecular weight siloxane-urea/urethane copolymers, (I), were prepared by Kuepfer [1] at ambient temperature using dibutyl tin diacetate as catalyst under anhydrous conditions. Additional siloxane-urea/urethane copolymer derivatives were prepared by Schafer [2]. Si O Si N H O H N O N H O O N H O H N O O a (I) 26 Segmented Urea and Siloxane Copolymers and Their Preparation Methods
    • 2. Mixed urea block copolymers consisting of amine-terminated polydimethyl- siloxane were prepared by Sherman [3] and used as pressure sensitive adhe- sives. Other urea-based pressure sensitive adhesives containing polydimethyl- siloxanes are described by Zhou [4]. 3. Brandt [5] prepared a nontacky spray on bandage—“patch in a bottle”— consisting of the reaction product of isophorone diisocyanate, polydimethyl- siloxane diamine having a Mn of 5400 daltons, and polypropylene oxide diamine having a Mn of 2000 daltons. References 1. J. Kuepfer et al., US Patent 7,153,924 (December 26, 2006) 2. O. Schafer et al., US Patent 7,026,424 (April 11, 2006) 3. A.A. Sherman et al., US Patent 7,012,110 (March 14, 2006) 4. Z. Zhou et al., US Patent 7,090,922 (August 15, 2006) 5. A. Brandt et al., US Patent 6,958,154 (October 25, 2005) Notes 27
    • Title: Functionalized Polymers for Medical Applications Author: A. Nathan, US Patent 7,253,248 (August 7, 2007) Assignee: Ethicon, Inc. (Somerville, NJ) SIGNIFICANCE Biodegradable and biocompatible a,b-unsaturated polyesters have been prepared by condensing maleic anhydride with monoleoyl glycerol alone or in combination with monoleoyl glycerol polyethylene glycol. Mercaptoethylamine was then free radically incorporated into the a,b-unsaturated site using azobisisobutyronitrile. These poly- meric agents were used to prepare medical devices including sutures, staples, surgical tacks, clips, and plates. REACTION O OHOH C17H30 O O OO C17H30 O O O O O O O O OO C17H30 O O O O O O O S S H2N NH2 i ii aa i: Monoleoyl glycerol, maleic anhydride ii: DMF, 2,20 -azobisisobutyronitrile, mercaptoethylamine EXPERIMENTAL 1. Preparation of Poly(Monooleoyl Glyceride-co-Maleic Anhydride) Areactorwaschargedwithmonoleoylglycerol(142.6 g)andthenheatedto140 Cand treated with maleic anhydride (39.2 g). The reaction mixture was further heated to 28
    • 190 C for 3 hours and cooled to ambient temperature. The product was isolated as a pale yellow viscous liquid having a Mn of 1383 daltons and a Mw of 6435 daltons. 2. Addition of Mercaptoethylamine to Poly(Monooleoyl Glyceride-co-Maleic Anhydride) A mixture consisting of the Step 1 product (5.0 g), 0.85 ml of mercaptoethylamine, 11 mlofDMF,and2,20 -azobisisobutyronitrile(54 mg)washeatedto60 Cfor24hours and then cooled to ambient temperature. The polymer was diluted with 10 ml of EtOAc, washed once with 0.01 M of NaOH, twice with brine, dried with MgSO4, and filtered. The solution was concentrated, and the product was isolated as a yellow, transparent viscous liquid. DERIVATIVES NOTES 1. Poly(monostearoyl glycerol-co-succinate) containing upto 5% polyethylene glycol, (I), was prepared by Arnold [1] and Nathan [2] and used as a bioabsorbable and biocompatible polymeric wax. Poly(monostearoyl- glyceride-co-succinate) containing 5% N-methyl diethanoamine, (II), was prepared by the author [3] in an earlier investigation. OO O O C17H35 O O O O 5 mol% (I) 95 mol% TABLE 1. Co-components used in reacting with maleic anhydride forming the corresponding a,b-unsaturated polyester and corresponding physical properties. Entry Co-component – 1 Co-Component – 2 Mn (daltons) Mw (daltons) 2 Monooleoyl glycerol 5 mol% PEG-400 1122 5647 3 Monooleoyl glycerol 25 mol% PEG-400 1230 4481 1 HNMR (CD3Cl, ppm): d 0.86 triplet (3H), 1.26 multiplet (22H), 1.61 multiplet (2H), 2.00 multiplet (4H), 2.30 multiplet (2H), 2.80 multiplet (2H), 3.60 multiplet (2H), 4.20 multiplet (3H), 5.38 multiplet (2H); no a,b-unsaturated ester remaining in the polymer FTIR (ZnS, cmÀ1 ): 3346, 2920, 2860, 1745, 1660, 1456, 1168 Notes 29
    • 95 mol% OO O O C17H35 O O O N H O (II) 5 mol% 2. The biodegradable and biocompatible polymer poly(monostearoyl glyceride- co-succinate-co-caprolactone), (III), was prepared by Nathan [4] and used in medical devices. O N H O O O O C17H35 O O (III) a 3. Block copolymers, (IV), consisting of succinic acid coupled with propylene glycol and then capped with hexamethylene diisocyanate and reacted with polylactic acid were prepared by Imamura [5] and used as biodegradable containers. O OO O O O H N O H N O O O O O a c (IV) b References 1. S. Arnold et al., US Patent 7,034,037 (April 25, 2006) 2. A. Nathan et al., US Patent 7,030,127 (April 18, 2006) 3. A. Nathan et al., US Patent 6,866,860 (March 15, 2005) 4. A. Nathan et al., US Patent 6,967,234 (November 22, 2005) 5. S. Imamura et al., US Patent 7,223,815 (May 29, 2007) 30 Functionalized Polymers for Medical Applications
    • Title: Degradable Polyacetal Polymers Author: S. J. Brocchini et al., US Patent 7,220,414 (May 22, 2007) Assignee: A. P. Pharma, Inc. (Redwood City, CA) SIGNIFICANCE Polyacetal polymers containing polyethylene glycol have been prepared which are stable at physiological pH but which readily degrade at lower pH’s. Bolton Hunter reagent conjugates prepared from these materials showed a favorable bio- distribution profile of the 125 I product. REACTION a a a HO OH NH2 HO OH HN O O O HN O O OO OO OO 3 360 O NH2 OO OO OO 3 360 O HN OO OO OO 3 360 O I HO I i ii iiiiv 125 125 i: Sodium hydroxide, N-(9-fluorenylmethoxycarbonyl)chloride, CH2Cl2 ii: Polyethylene glycol, p-toluene sulfonic acid, divinyl tri(ethylene glycol),THF, triethylamine 31
    • iii: Piperidine, CH2Cl2 iv: N-Succinimidyl 3-(4-hydroxy 5-[125 I]iodophenyl) propionate), benzene, DMF, sodium hydroxide EXPERIMENTAL 1. Preparation of N-(9-Fluorenylmethoxycarbonyl) Intermediate A reactor containing 2-amino-1,3-propanediol (10.0 mmol) and 25 ml of 1M NaOH was cooled to 0.2 C and treated with N-(9-fluorenylmethoxycarbonyl)chloride (13.1 mmol) dissolved in 10 ml of CH2Cl2 over a 1 hour period. The solution was stirred for 1 hour at 0 C and 4 hours at ambient temperature. The organic solvent was evaporated and the aqueous residue poured into 70 ml of EtOAc. The organic phase was isolated, washed with 5% aqueous HCl, dilute NaHCO3, brine, and dried. The mixture was concentrated, the residue re-crystallized in chloroform, and the product was isolated. 2. Preparation of Polyether N-(9-Fluorenylmethoxycarbonyl) Intermediate Polyethylene glycol having a Mn of 3400 daltons (1.47 mmol) and p-toluene sulfonic acid (0.012 g) were added to a 100-ml flask and heated to 80 C to 90 C for 3 hours at 0.5to 1.0 torr.The mixturewas cooled and treated with the Step 1product (1.47 mmol) and 10.0 ml of THF; it was further treated with divinyl tri(ethylene glycol) (2.94 mmol) in 10 ml of THF. This reaction mixture was stirred for 2 hours at ambient temperature and then treated with 0.3 ml triethylamine. The reaction mixturewasprecipitatedin100 mlofhexane,andtheproductwasisolatedhavingaMn of 25,000 daltons. 3. Preparation of Polyether Acetal Amine Intermediate A solution of the Step 2 product (2.050 g) in 20% piperidine containing 10 ml of CH2Cl2 was stirred at ambient temperature and monitored by thin layer chromatog- raphy. The amino functionalized polyacetal was then isolated by partitioning the piperidine into hexane and next CH2Cl2. The residue was dissolved in THF, and the polymer was precipitated by pouring into 100 ml of hexane. The product was isolated having a Mn of 23,000 daltons. 4. Preparation of 125 I Polyether Acetal The Step 3 product (50 mg) was dissolved in 10 mg/ml of 0.1M borate with a pH 8.5 bufferbytheadditionofasmallamountofNaOHandthentreatedwithN-succinimidyl 3-(4-hydroxy5-[125 I]iodophenyl)propionate),500 mCi,dissolvedinbenzenecontain- ing DMF, and stirred for 15 minutes at ambient temperature. The mixture was diluted 32 Degradable Polyacetal Polymers
    • with phosphate buffer solution to 10 ml, transferred to dialysis tubing, and dialyzed against water until no radioactivity was found in the dialysate, and the product was isolated. DERIVATIVES Three additional divinyl ether derivatives were prepared as illustrated below. O N H H N O N H O O O N H O N H O O O N H O N H O O NH2 NOTES 1. Bleach resistant polyacetals consisting of 98% trioxane and 2% dioxolane was prepared by Notorgiacomo [1] and used in molding compositions. 2. Branched polyformals and copolyformals, (I), were prepared Heuer [2] and used in the production of molded articles. O O O Oa b c (I) 3. Polyvinyl butyral resins, (II), were prepared by Miyake [3] and used in heat- developable photosensitive material film. O O (II) a b Notes 33
    • 4. Polyacetal resin compositions having excellent wear resistance were pre- pared by Kim [4]. These resins consisted of polyoxymethylene polymer, ethylene vinylacetate, melamine, triethyleneglycol-bis-3-(3-t-butyl-4-hydroxy- 5-methylphenyl)-propionate, and hydroxyl pentaerythritol fatty acid ester. References 1. V.J. Notorgiacomo et al., US Patent 7,223,809 (May 29, 2007) 2. H.-W. Heuer et al., US Patent 7,208,564 (April 24, 2007) and US Patent 7,199,208 (April 3, 2007) 3. Y. Miyake, US Patent 7,176,257 (February 13, 2007) 4. T.-K. Kim et al., US Patent 7,098,262 (August 29, 2006) 34 Degradable Polyacetal Polymers
    • Title: Lactone Bearing Absorbable Polymers Author: F. X Ingnatious, US Patent 7,205,378 (April 17, 2007) Assignee: Societe de Conseils de Recherches et d’Applications Scientifiques (Paris, FR) SIGNIFICANCE A procedure for the slow and sustained release of the growth hormone inhibitor LanreotideÒ is described. The method entails incorporating LanreotideÒ to the isocitric acid lactone component on the backbone of a polyester block copolymer using sodium hydroxide as the saponification agent. REACTION a O HO2C CO2H O O O O O O OHO O H O O O O O OHO O O O O O H R R O O O O O OHO O O O O O H R R Lanreotide(R) a b a b i ii iii R = H or CH3 NH3 O Na Note 1 i: Propanediol, benzene ii: dl-Lactide, glycolide, stannous octanoate, toluene iii: Sodium hydroxide, acetone, LanreotideÒ 35
    • EXPERIMENTAL 1. Preparation of Poly(isocitric Acid Lactone-co-Propanediol) A reactor containing a Dean–Stark trap was charged with isocitric acid lactone (14.3 mmol), propanediol (15.7 mmol), and benzene was then refluxed at 90 C overnight. The mixture was concentrated and a viscous liquid isolated that solidified on cooling. 2. Preparation of Poly[(Isocitric Acid Lactone-co-Propanediol)- block-(Glycolide-co-Lactide)] The reaction vessel containing the Step 1 product was transferred to a dry box and treated with dl-lactide (25.2 g), glycolide (7.25 g), and 0.2 ml of stannous octanoate solution in toluene. The polymerization reaction was performed at 160 C for 8 hours and then quenched in liquid nitrogen. The polymer was isolated, dissolved in acetone, and precipitated in cold water, with the product isolated having a Mn of 3790 daltons and Mw of 7040 daltons. 3. Preparation of Poly[(Isocitric Acid Lactone-co-Propanediol)- block-(Glycolide-co-Lactide)] Ionically Complexed with LanreotideR The Step 2 product (1 g) was dissolved in acetone and treated with 0.45 ml of 1M NaOH, then stirred for 20 minutes, and further treated with LanreotideÒ (0.29 g) dissolved in 2 ml of 1:1 acetone/water. The polymer solution was left stirring for 2 hours and then precipitated in cold water. The product was filtered and dried; the product isolated had a 17.6% nitrogen content. DERIVATIVES No additional derivatives were prepared. TESTING In vivo Testing The Step 3 product was ground and sieved with a mortar and pestle and passed through a 125 m sieve. Rats were administered 6.75 mg of the experimental agent by injection in a medium consisting of 2% carboxymethylcellulose, 1% Tween 20Ò , and saline. Blood samples were collected at various time intervals, and the plasma levels of LanreotideÒ was determined by radioimmuno assay. Test results for are provided in Table 1. 36 Lactone Bearing Absorbable Polymers
    • NOTES 1. LanreotideÒ has the formula H-b-D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr- NH2, where, the two Cys are bonded by a disulfide bond. LanreotideÒ is a somatostatin analogue that inhibits the release of growth hormones. 2. In a subsequent investigation by the author [1] biodegradable microparticles such as poly(l-lactic-co-glycolic-co-d,l-malic acid), (I), were prepared and used as a drug delivery agent for the acetate salt of LanreotideÒ . baO O O O R O R O O O Lanreotide NH3 R = H or CH3 (I) OAc 3. Shalaby [2] prepared ionic molecular conjugates of the hydrolyzed drug delivery agent chitosan and SomatulineÒ , (II), in the treatment of acromegaly. TABLE 1. In vivo test results for LanreotideÒ in plasma levels using radioimmuno assay. Sample LanreotideÒ Levels after 6 Hours (ng/ml) LanreotideÒ Levels after 8 Days (ng/ml) LanreotideÒ Levels after 22 Days (ng/ml) Step 3 product 21 – 4.5 30.2 – 7.5 0.05 – 0.02 Entry 4*1 24.4 – 5.2 20.8 – 7.2 0.141 – 0.09 *1 Entry 4 was obtained by replacing NaOH with an equivalent amount of NaHCO3 in Step 3. Notes 37
    • a O OO O HO NH3 OH OH NH3 CO2 OH HO O HO CO2 NH3 OH CO2 CO2 CO2 CO2 Somatuline NH3 NH3 NH3Somatuline Somatuline (II) 4. Li [3] prepared ionic complexes of aminated polyrotaxanes with bulky bio- cleavable end caps as a method for delivering nucleic acids. 5. Polyfunctional monomers, (III), prepared by Li [4] were used to synthesize cationic polymers having degradable crosslinks for therapy involving the delivery of nucleic acids into cells. O O O OO O O O O O O O (III) 6. Leong [5] and Dang [6] used cyclic phosphate monomers, (IV), and either lactide or caprolactone monomers to prepared phosphate based biodegradable polymers, (V), illustrated below, that were then converted into microspheres and used as drug deliver agents for anti-neoplastic medicaments. O P O H3CO O O O P O O O O O OCH3 (IV) (V) i a b i: d,l-Lactide, benzene, methanol 38 Lactone Bearing Absorbable Polymers
    • References 1. F.X Ingnatious et al., US Patent Application 2006-0121120 (June 8, 2006) 2. S.W. Shalaby et al., US Patent 7,005,420 (February 28, 2006) 3. J. Li et al., US Patent Application 2006-0211643 (September 21, 2006) 4. S. Li et al., US Patent 7,163,677 (January 16, 2007) 5. K.W. Leong et al., US Patent 6,805,876 (October 19, 2004) 6. W. Dang et al., US Patent 6,800,672 (October 5, 2004) Notes 39
    • B. Contact Lenses Title: Low Polydispersity Poly-HEMA Compositions Author: T. Kindt-Larsen et al., US Patent 7,256,246 (August 14, 2007) Assignee: Johnson & Johnson Vision Care, Inc (Jacksonville, FL) SIGNIFICANCE Cross-linked pre-polymers having fractionalized molecular weights between 35,000 and 70,000 daltons with polydispersity indexes of less than 3.4 have been prepared by the free radical addition of 2-hydroxethyl methacrylate, HEMA, with 2% methacrylic acidorglycerolmethacrylate.Oncecrosslinked,thesematerialsareparticularlyuseful as contact lenses because of their limited shrinkage and expansion. REACTION O O OH O O OO OH O O O OH i ii Fractionalization a b c d Note 2 Note 1 i: Ethanol, dodecyl mercaptan, methacrylic acid, 2,20 -azobis (2-methylbutyronitrile) ii: Ethanol, hexane EXPERIMENTAL 1. Preparation of Poly(2-Hydroxethyl Methacrylate-co-Methacrylic Acid) (poly-HEMA) A 5-liter stainless steel reactor was charged with ethanol (1911.6 g), 2-hydroxethyl methacrylate (1056.6 g), dodecyl mercaptan (3.00 g), and methacrylic acid (21.00 g) 40
    • at 25 C. The temperature was raised to 68 C and then the mixture treated with 2,20 -azobis(2-methylbutyronitrile) (7.50 g). After heating for 18 hours at 68 C the mixture was heated to 80 C an additional 22 hours then cooled. The product was isolated with a solid content of 37.2% with a Mn of 68,000 daltons and a PDI of 3.75. 2. Fractionalization of Poly(2-Hydroxethyl Methacrylate-co-Methacrylic Acid) Step 1 Fractionalization Process The Step 1 product was initially diluted with ethanol to give a 10% solution of poly- HEMA in ethanol. The solution initially became turbid at 24 C and clear and homogeneous at 40 C. The solution was cooled to 21 C; the solution then separated into two clear phases after three days. The bottom fraction had a molecular weight of 144,000 daltons with a polydispersity of 3.34 and was discarded. The top soluble layer had a molecular weight of 64,000 daltons with a polydispersity of 2.28 and was further fractionated at 8 C. After 24 hours the solution was again separated into two phases. The bottom phase constituted 15 vol% of the total solution and contained 35.7 wt% of poly-HEMAhavingamolecularweightof83,800daltonswithapolydispersityof2.18 that was further fractionated. Step 2 Fractionalization Process After addition of 2% hexane to the lower layer, the solution had a cloud point at 31 C. The mixture was heated to 40 C to make it homogeneous, and then it stood at 28 C for five days before it separated into two clear phases. The top phase contained 77.1% of the polymer and was siphoned off, and the bottom phase was discarded. Step 3 Fractionalization Process The amount of hexane in the top phase was adjusted to 7%, which resulted in a cloud point of 54 C. The solution was re-heated to 57 C to make it homogeneous, and after four days at 29 C the solution separated into two clear phases. The top phase containing the low molecular weight fraction of the polymer was siphoned off, and the bottom phase was given a third fractionation. Step 4 Fractionalization Process In this procedure the hexane concentration was adjusted to 8%, and the solution stood for four days at 30 C. The top phase containing the low molecular weight fraction of the polymer was siphoned off, and the lower retained as the Step 1 fractionalized product. Experimental 41
    • FRACTIONALIZATION PROFILE DERIVATIVES Poly(2-hydroxethyl methacrylate-co-glycerol methacrylate) was also prepared hav- ing a molecular weight of 41,000 daltons with a PDI of 2.80. NOTES 1. The preparation of molded contact lenses using the polymers of the current invention are described by the author [1] in an earlier investigation. 2. Ford [2] determined that isopropanol, dipropylene glycol dimethyl ether, dipropylene glycol methyl ether acetate, dipropylene glycol methyl ether, and tripropylene glycol methyl ether were also effective in fractionating analogues of the current invention. 3. Wettable polymer silicon hydrogels were prepared by Laredo, (I), [3] and Zanini, (II), [4], respectively, and used in contact lenses. O O N H O O O Si O O N H O NH O O CH2CF2(OCF2)aCF3 26 (I) Si O O Si OSi(CH3)3 (H3C)3SiO OH O OH (H3C)3SiO OSi(CH3)3 (II) TABLE 1. Fractionalization effectiveness for poly(2-hydroxethyl methacrylate- co-methacrylic acid) using selected extraction solvents. Entry Fractionalization Temperature ( C) Fractionalization Solvent Molecular Weight (daltons) PDI 5 82 2-Propanol 35,000 3.4 6 78 2-Propanol 40,000 3.4 7 74 Ethanol 50,000 2.6 8 72 Ethanol 60,000 3.6 9 68 Ethanol 70,000 3.3 42 Low Polydispersity Poly-HEMA Compositions
    • 4. Biocompatible contact lenses having high oxygen and water permeability were prepared by Nicolson [5] by reacting the polysiloxane macromonomer, (III), with ethylene glycol, and 2% 2-hydroxyethyl methacrylate. O Si OOHN O OCN O H N O NCO (III) a b References 1. T. Kindt-Larsen et al., US Patent 6,846,892 (January 25, 2005) 2. J.D. Ford et al., US Patent 7,112,652 (September 26, 2006) 3. W.R. Laredo et al., US Patent 7,249,848 (July 31, 2007) 4. D. Zanini et al., US Patent 7,214,809 (May 8, 2007) 5. P.C. Nicolson et al., US Patent 7,045,248 (October 4, 2005) Notes 43
    • C. Drug Delivery Title: Amphiphilic Block Copolymers and Nanoparticles Comprising the Same Author: M.-F. Hsieh et al., US Patent Application 2007-0104654 (May 10, 2007) Assignee: Industrial Technology Research Institute (Hsinchu, TW) SIGNIFICANCE A biocompatible and biodegradable amphiphilic block copolymer consisting of hydrophobic and hydrophilic segments containing zwitterions has been prepared. This agent is useful as a drug delivery agent for water-insoluble drugs, including growth factors and genes, and in cosmetic formulations. REACTION O O H3CO O O H H3CO O O P O O O H3CO O O P O O O N(CH3)3a b aa b iii iii O O O ivNanoparticles i: Poly(ethylene glycol), stannous 2-ethylhexanoate ii: Triethylamine, 2-chloro-2-oxo-1,3,2-dioxaphospholane, CH2Cl2 iii: Acetonitrile, trimethylamine, CH2Cl2 EXPERIMENTAL 1. Preparation of Poly(Ethylene Glycol-b-Valerolactone) A glass reactor was charged with poly(ethylene glycol) (60g; 5000 daltons) and d-valerolactone (12g), which was gradually heated until dissolved. This mixture was 44
    • then treated with 0.38ml of stannous 2-ethylhexanoate and heated for 8 hours at 160 C. ThereafterthemixturewasdissolvedinCH2Cl2 andprecipitatedbyaddingdiethylether. The white precipitate was washed and dried, and the block copolymer was isolated. 2. Preparation of Poly(Ethylene Glycol-b-Valerolactone)-2-oxo-1,3,2- Dioxaphospholane The Step 1 product (5 g) and triethylamine (0.43 g) were dissolved in 70 ml of CH2Cl2 at 0 C, then added dropwise to 2-chloro-2-oxo-1,3,2-dioxaphospholane (3.5 g) dis- solved in 30 ml of CH2Cl2 and stirred at 0 C for 6 hours. The resulting solution was warmed to ambient temperature, filtered through 0.45 mm filter paper, and concen- trated, and the product was isolated. 3. Preparation of Poly(Ethylene Glycol-b-Valerolactone)- Trimethylammonium Phosphate The Step 2 product was dissolved in 70 ml of acetonitrile at ambient temperature and then treated with 10 ml of 33% trimethylamine in ethanol and heated for 24 hours at 60 C. The solution was next concentrated and extracted three times with CH2Cl2/ water. After re-concentrating and drying, the product was isolated as a white solid. 4. Preparation of Polymeric Nanoparticles Ten milligrams of the Step 3 product were dissolved in 1 ml of dimethyl sulfoxide and then removed by freeze-drying. Thereafter 1 ml of 10% sucrose was added to the hydrate, and the freeze-dried solids were re-dissolved to form a suspension. After ultra-sonicating for 10 minutes, polymer nanoparticles were formed. DERIVATIVES Two additional derivatives were prepared as illustrated below. H3CO O O O a b NHR H2C N SO3 O O HC CO2H N N R________________ Derivatives 45
    • TESTING Micelle Formation A solution of 10 mg of a selected polymer dissolved in 1 ml THF was gradually added to 30 ml deionized water and stirred. The solution was placed in a dialysis membrane for 24 hours to form a micelle solution. Then the 3 to 5 ml micelle of the solution was placed in an acrylic cuvette to measure micelle sizes and their distribution by photon correlation spectroscopy. Testing results are provided in Table 1. NOTES 1. Amphiphilic block copolymers consisting of polyethylene glycol and poly- lactide, (I), were prepared by Seo [1] and used as drug delivery agents for PaclitaxelÒ . H3CO O O O O O O 44 24 (I) 2. Block cationomers, (II), consisting of polyisobutylene and poly(2-dimethyl- amino)ethyl methacrylate) were prepared by Kennedy [2] and used as timed release agents for pharmaceuticals. O Br OO N(CH3)3 I(II) a Polyisobutylene TABLE 1. Effect of terminus and block segment composition in poly(ethylene-glycol-b-valerolactone) on CMC formation. Polymer Terminus PEO Block (daltons) Lactone Block (daltons) CMC (10À2 wt%) Trimethylammonium phosphate 5000 1900 3.26 5000 1100 17.92 Dimethylammonium sulfate 2000 1000 1.46 2000 2000 4.47 5000 2500 3.95 5000 3700 7.76 46 Amphiphilic Block Copolymers and Nanoparticles Comprising the Same
    • 3. Wang [3] prepared the amphiphilic biocompatible cyclodextrin graft polymer, poly(ethylene glycol-g-cyclodextrin), (III), containing modified cyclodextrin which was used as a bioactive drug delivery agent. O O NHO S S HN Cyclodextrin a b (III) 4. Dai [4] modified oxidized carbon nanotubes, (IV), and these were subsequently used as transporters for the delivery of biologically active agents into cells. aN H O O N H O S NH HN O H H Oxidized nanotube (IV) References 1. M.-H. Seo et al., US Patent 7,217,770 (May 15, 2007) 2. J.P. Kennedy et al., US Patent 7,196,142 (March 27, 2007) 3. L. Wang et al., US Patent 7,141,540 (November 28, 2006) 4. H. Dai et al., US Patent Application 2006-0275371 (December 7, 2006) Notes 47
    • Title: Heterofunctional Copolymers of Glycerol and Polyethylene Glycol, Their Conjugates and Compositions Author: F. Ignatious, US Patent 7,196,145 (March 27, 2007) Assignee: SmithKline Beecham Corporation (Philadephia, PA) SIGNIFICANCE Block- and copolymers consisting of ethylene oxide and glycidol were prepared anionically containing an d-hydroxy butyric acid terminus. The acidic terminus was then converted into a-succinimidyl and conjugated with the protein, Grob-t, and the lipid, di-stearoyl phosphatidyl-ethanolamine. REACTION O O O O O OH OH O HO O O O O O O OH OH O O N O O O O O O O OH OH H N O O O O O O OH OH t-Grob-HN O Di-stearoyl phosphatidyl O i ii iii iv b aa b a b a b Note 1 i: 4-Hydroxy butyric acid-sodium salt, potassium, glycidol, THF ii: N,N0 -Dicyclohexyl carbodiimide, N-hydroxysuccinimide, CH2Cl2 iii: Grob-t, Dulbeccu’s phosphate, hydrochloric acid iv: Di-stearoyl phosphatidyl-ethanolamine, triethylamine, CCl3H 48
    • EXPERIMENTAL 1. Preparation of a-Carboxyl-d-Hydroxyl Poly(Ethylene Oxide-block- Polyglycidol) A reactor was charged with 4-hydroxy butyric acid-sodium salt (0.045 mol) and potassium (0.046 mol) in 400 ml of THF, refluxed 12 hours, and transferred to a high-pressure reactor. The reactor temperature was lowered to À10 C and treated with 95 ml of ethylene oxide using a stainless steel capillary and the solution stirred at 50 C for 24 hours. Glycidol previously dissolved in THF was slowly added through a stainless steel capillary, and the solution was stirred at 50  C for 12 hours. The reactor was cooled, and the contents were poured into 5 ml 35% hydrochloric acid whereupon KCl precipitated. The solution was filtered. Then the filtrate, was precipitated in cold 2-propanol containing 20% hexanes and a light yellow precipitate was isolated. The dried residue was dissolved in 500 ml distilled water and extracted with CH2Cl2 to remove the unreacted initiator. After removal of the solvent, the product was washed twice with water and isolated. 2. Preparation of d-Hydroxy-a-Succinimidyl Poly(Ethylene Oxide-block-Polyglycidol) A reactor was charged with the Step 1 product (0.011 mol), N,N0 -dicyclohexylcarbo- diimide(0.0176 mol),and N-hydroxysuccinimide (0.0176 mol)dissolvedin150 ml of CH2Cl2 and then stirred overnight at ambient temperature. A cloudy heterogeneous white formed, which was removed by filtration and the filtrate concentrated. The residue was precipitated in cold diethyl ether and the product isolated after re- crystallization with ethanol. 3. Conjugation of d-Hydroxy-a-Succinimidyl Poly(Ethylene Oxide-block-Glycidol) to Grob-t The Step 2 product was added to a 2.5 mg/ml solution of Grob-t in Dulbeccu’s phosphate buffered at pH 7.0 at a molar ratio of the Step 2 product/protein 2:1, 4:1, or 10:1, respectively. The reaction was stirred for 3 hours at 40 C and quenched with 0.5 M glycine, and then the pH was lowered to 4.5 with 3 M of hydrochloric acid. The conjugate was isolated after purification by diafiltration. 4. Conjugation of d-Hydroxy-a-Succinimidyl Poly(Ethylene Oxide-block-Polyglycidol) to a Lipid The Step 2 product (0.8 mmol) dissolved in CCl3H was treated with di-stearoyl phosphatidyl-ethanolamine (0.70 mmol) containing triethylamine (1.4 mmol) and heated to 40 C to 45 C for 2 hours. The conjugate was isolated after purification by diafiltration. Experimental 49
    • DERIVATIVES Poly(ethylene oxide-co-glycidol) was also prepared. NOTES 1. In a subsequent investigation by the author [1], the aldehyde-terminated Step 1 analogue was prepared and used as a conjugate with selected biomolecules. O O O O O OH OH H O ba OH (I) 2. Miyanaga [2] prepared moderate molecular weight polyglycidol ethers, (II), by polymerizing the corresponding glycidol ether with samarium triisopropoxide, samarium tris(tetramethyl heptanedionate), and yttrium tris(tetramethyl hep- tanedionate) with methyl aluminoxane. O O R a R a OH 760 CH3 700 Steryl 820 CH2C8F17 250 (II) 3. Polyglycidol containing cyanoethyl, (III), trimethylsilylacetyl, and cyanoben- zoyl termini were prepared by Sata [3] and used as a component in ion- conductive polymer electrolyte compositions. O ONC O CN (III) CN a References 1. F. Ignatious et al., US Patent Application 2005-0048650 (March 3, 2005) 2. S. Miyanaga et al., US Patent 6,906,167 (June 14, 2005) and US Patent 6,800,723 (October 5, 2004) 3. T. Sato, US Patent 6,472,106 (October 29, 2002) and US Patent 6,469,107 (October 22, 2002) 50 Heterofunctional Copolymers of Glycerol and Polyethylene Glycol
    • Title: Polyalkylene Glycol Acid Additives Author: P. S. Bailon et al., US Patent 7,193,031 (March 20, 2007) Assignee: Hoffmann-La Roche, Inc. (Nutley, NJ) SIGNIFICANCE A new class of activated biological conjugates has been prepared. Methoxy polyeth- ylene glycol having a molecular weight of 2000 daltons was converted into the corresponding valeric acid succinimidyl ester then conjugated with AZT, T-20 polypeptide, and human erythropoietin. These conjugates materials produced biolog- ically active agents useful in pharmaceutical applications. REACTION H3CO O O OH H3CO O O O OC2H5 O H3CO O O O OH O H3CO O O O O O N O O H3CO O O O O O NO HN O i ii iiiiv 20 20 20 20 20 Note 1 i: Toluene, ethyl-5-bromovalerate ii: Sodium hydroxide iii: N-hydroxy-succinimide, dicyclohexylcarbodiimide iv: 30 -Azido-30 -deoxy-thymidine, 1-hydroxybenzotriazole, (4-dimethylamino)pyr- idine, dicyclohexylcarbodiimide 51
    • EXPERIMENTAL 1. Preparation of Methoxy-Polyethylene Glycol Valeric Ethyl Ester Areactorwaschargedwithpolyethyleneglycol(0.5 mol;Mn 10,000),andtreatedwith 50 ml of toluene, and azeotropically dried by refluxing for 2 hours. The resulting mixture was dissolved in 30 ml of THF and treated dropwise with sodium hydride (5 mmol) dissolved in 20 ml of THF and refluxed overnight. This mixture was then treated with ethyl-5-bromovalerate (5 mmol) and refluxed overnight and concentrat- ed. The residue was precipitated by the addition of 2-propanol/diethyl ether, 1:1, and then filtered to yield 4.5 g of isolated product. 2. Preparation of Methoxy-Polyethylene Glycol Valeric Acid The Step 1 product (4 g) was dissolved in 100 ml of 1 M NaOH and stirred at ambient temperature overnight. The pH of the mixture was adjusted to 2.5 using 6 M hydrochloric acid; the mixture extracted using 50 ml, 40 ml, and 30 ml of CH2Cl2, dried with Na2SO4, and concentrated. The concentrate was precipitated in diethyl ether, and 3 g of product were isolated. 3. Preparation of Methoxy-Polyethylene Glycol Valeric Acid Succinimidyl Ester The Step 2 product (0.2 mmol) was dissolved in 10 ml of CH2Cl2 and treated with N-hydroxy-succinimide (0.41 mmol) and dicyclohexylcarbodiimide (0.42 mmol). The mixture was stirred overnight at ambient temperature and then filtered and con- centrated. The residue was precipitated in 2-propanol/diethyl ether, 1:1, and filtered to yield 1.6 g of isolated product. 4. Preparation of PEG-AZT Conjugate TheStep3product(0.02 mmol)wasdissolvedin2 mlofDMFandtreatedwith30 -azido- 30 -deoxy-thymidine (0.04mmol), 1-hydroxybenzotriazole (0.04 mmol), 4-dimethyla- minopyridine (0.042mmol), and dicyclohexylcarbodiimide (0.046mmol) and stirred overnightatambienttemperature.Themixturewasfiltered,concentrated,precipitatedin 2-propanol/diethyl ether, 1:1, and 0.17g product was isolated. 1 H-NMR (d6-DMSO) d 1.18 ppm (m, 3H, H1); 1.51 ppm (m, 2H, H9); 2.23 ppm (m, 1H, H4); 2.37 ppm (t, 2H, H8); 3.21 ppm (s, H12); 3.5 ppm (s, H11). 4.2 ppm (m, 1H, H5); 6.12 ppm (m, H3, H6); 7.45 ppm (s, 1H, H2); 11.35 ppm (br, 1H, H10) 1 H-NMR (d6-DMSO) d 1.50 ppm (q, 2H, –CH2CH2–COOH); 2.21 ppm (t, 2H, –CH2CH2–COOH); 3.21 ppm (s, –OCH3); 3.5 ppm (s, –O–CH2CH2–O–). 1 H-NMR (d6-DMSO) d 1.58 1.67 ppm (m, 4H, –CH2CH2CH2–COO–); 2.69 ppm (t, 2H, –CH2CH2CH2– COO–); 2.81 ppm (s, 4H, NHS); 3.21 ppm (s, –OCH3); 3.5 ppm (s, –O–CH2CH2–O–). 52 Polyalkylene Glycol Acid Additives
    • DERIVATIVES Two linear derivatives were prepared using the Step 4 product: H3CO O O O G O 20 G = T-20 polypeptide, human erythropoietin One branched derivative was also prepared. H3CO O O H N O NH O O H3CO O N O O 20 20 NOTES 1. In subsequent investigations by the author [1] and Ley [2] the Step 4 product was used as a conjugate for the granulocyte colony stimulating factor and Kunitz domain polypeptides, respectively. 2. In other investigations by the author [3–5] an aldehyde terminated Step 4 analogue (I) was prepared and used as conjugates for T-20 polypeptide, human erythropoietin, and T1249 polypeptide, respectively. H3CO O O O CHO 20 (I) 3. A blended composition for facilitating delivery of a biologically active conju- gated material was prepared by Kabanov [6] and consisted of a block copolymer of ethylene oxide and acrylic acid salt of cetylpyridinium bromide, (II). O OO N176 186 14 (II) 4. Oh [7] prepared biodegradable lactide derivatives, (III), for conjugation with biologically active agents for use as drug delivery agents. Notes 53
    • aHO O O O O O O O O O NO2 (III) 5. Roberts [8] prepared polyethylene glycol 2-pyridylthioester derivatives, (IV) for conjugating with a-amine polypeptides. H3CO O O S O Na (IV) References 1. P.S. Bailon, US Patent Application 2005-0196378 (September 8, 2005) 2. A.C. Ley, US Patent Application 2007-0041959 (February 22, 2007) 3. P.S. Bailon et al., US Patent 7,049,415 (May 23, 2006) 4. P.S. Bailon et al., US Patent 6,583,272 (June 24, 2003) 5. P.S. Bailon et al., US Patent Application 2004-0171542 (September 2, 2004) 6. A.V. Kabanov et al., US Patent 7,169,411 (January 30, 2007) 7. J.E. Oh et al., US Patent 7,163,698 (January 16, 2007) 8. J.H. Roberts et al., US Patent 7,078,496 (July 18, 2006) 54 Polyalkylene Glycol Acid Additives
    • Title: Thermosensitive Biodegradable Copolymer Author: K.-Y. Chang et al., US Patent 7,179,867 (February 20, 2007) Assignee: Industrial Technology Research Institute (Hsinchu, TW) SIGNIFICANCE A method for increasingthe biodegradability of low cytotoxic poly(ethyleneglycol-b- (lactide-co-glycolide)) derivatives is described. The block copolymers are thermo- sensitive and can be easily implanted into the human body through injection for timed release of biologically active agents. REACTION H3CO O O OH O O O O O O H3CO O O O O O O a b c a b c 11 i ii i: Lactide, methoxypolyethylene glycol, tin octanate ii: Lauric acid, dicyclohexylcarbodiimide, CH2Cl2, CHCl3 EXPERIMENTAL 1. Preparation of Poly(Ethylene Glycol-b-(Lactide-co-Glycolide)) A reaction vessel was heated under nitrogen until the temperature reached 110 C and then treated with lactide (50.0 g), glycolide (11.36 g), and methoxypolyethylene glycol (24.02 g). After the monomers had melted, the contents were treated with 0.05% tin octanate while the temperature slowly increased to 160 C for 9 hours; the vessel was then cooled to ambient temperature. The solid was dissolved in 80 ml of CH2Cl2,thenpouredinton-hexane/ether,9:1,respectively,andstirredfor3hours.The solution was next separated into two phases. The upper liquid was discarded, the bottom liquid was washed three times with n-hexane/diethyl ether, dried, and the product was isolated. 55
    • 2. Preparation of Poly(Ethylene Glycol-b-(Lactide-co-Glycolide)) Lauric Ester Separate solutions of lauric acid (1.53 g) and dicyclohexylcarbodiimide (1.58 g) were prepared by dissolving each into 30 ml and 20 ml of CH2Cl2, respectively. The two solutions were mixed and stirred for 30 minutes and then added to the Step 1 product (10 g)dissolvedin50 mlof CHCl3.Thismixturewastreatedwithtriethylamine(1.5 g) and stirred for 24 hours. The mixture was filtered and washed with n-hexane/diethyl ether, and the product was isolated after drying. DERIVATIVES The cholic acid analogue of the Step 1 product was also prepared. H3CO O O O O O a b c OHHO OH O TESTING Gel Formation Data collection were correlated with viscosity, time, thermocouple temperature, and rheometer torque. The rotation speed of the rheometer was adjusted so that torque value fell between 80% to 100%. The gel formation time was defined as the time needed for a sample to increase its viscosity up to 10000 cP from its starting viscosity. Viscosity testing results are provided in Table 1. 1 H-NMR(CCl3D)d1.58(d,J ¼ 6.5 Hz,H-4),3.39(s,–OCH3),4.29(m,H-1,2),4.80(m,H-5),5.14(m,H-3) 1 H-NMR(CCl3D)d0.86(t,J ¼ 6.8 Hz,H-8),1.23(m,H-7),1.58(d,J ¼ 6.5 Hz,H-4),2.38(m,H-6),3.39(s, –OCH3), 4.29 (m, H-1,2), 4.80 (m, H-5), 5.14 (m, H-3) TABLE 1. Gel formation for the Step 2 product at varying times and temperatures. Time (s) Temperature ( C) 15 wt% Solution Viscosity (cp) 25 wt% Solution Viscosity (cp) 33 wt% Solution Viscosity (cp) 8 5 Fluid Fluid Fluid 9 10 7,500 Fluid Fluid 10 13 17,000 Fluid Fluid 11 15 — Fluid Fluid 12 18 — 7,500 5,000 13 20 — >25,000 >25,000 56 Thermosensitive Biodegradable Copolymer
    • NOTES 1. Amphiphilic block copolymers consisting of polylactic acid or poly(lactic acid- b-glycolic acid) terminated with tocopherol or cholesterol were prepared by Seo [1] and used as drug delivery agents for PaclitaxelÒ . 2. Negatively charged amphiphilic block copolymers, (I), prepared by Seo [2] were effective as cationic drug carriers and provided the advantages of increased blood concentration and improved drug stability. Stable polymeric micelle-type drug compositions were prepared by Seo [3]. H3CO O O O O O a b c X X = PO3 - Na+ = SO3 - Na+ (I) 3. Thermosensitive block terpolymers consisting of poly(ethylene oxide-b-gly- colide-b-dl-lactide) were prepared by Piao [4] and used as drug delivery agents for insulin. 4. Block terpolymers prepared by Cheng [5] consisting of poly(N-isopropyl acrylamide-b-polyethyleneoxide-b-N-isopropyl acrylamide), (II), were effec- tive as thermally reversible gels and used as subcutaneous implants, joint or tissue spacers, and biological filler for wrinkles or cosmetic implants. Metha- crylamide analogues were prepared by Gutowska [6]. aa O OHN O NH 113 (II) References 1. M.H. Seo et al., US Patent Application 2005-0201972 (September 15, 2005) 2. M.H. Seo et al., US Patent 6,890,560 (May 10, 2005) 3. M.H. Seo et al., US Patent 7,217,770 (May 15, 2007) 4. A-Z. Piao et al., US Patent 7,135,190 (November 14, 2006) 5. Y.-L. Cheng et al., US Patent 7,160,931 (January 9, 2007) 6. A. Gutowska, US Patent 6,979,464 (December 27, 2005) Notes 57
    • Title: Polyamide Graft Copolymers Author: A. B. Brennan et al., US Patent 7,169,853 (January 30, 2007) Assignee: University of Florida Research Foundation, Inc. (Gainesville, FL) SIGNIFICANCE Polyamide copolymers containing a macromolecular graft substituent were prepared by condensing 4-amino-benzoic acid or a mixture of 1,4-phenylene diamine and adipic acid with 33%, 66%, and 90% S-(poly(n-butylacrylate)cysteine macromonomer. A second macromolecular monomer, S-(poly(methyl methacrylate)-cysteine, was also prepared and free radically copolymerized with perfluoromethyl methacrylate. REACTION O O n-C4H9 H2N OH S O Poly(butyl acrylate) N H N H S OO Poly(butyl acrylate) i ii a i: 2,20 -Azobisisobutyronitrile, cysteine, THF, hydrochloric acid ii: Triphenylphosphite, lithium chloride, pyridine, N-methyl-pyrrolidinone EXPERIMENTAL 1. Preparation of S-(Poly(n-Butyl Acrylate)-Cysteine Macromonomer The synthesis of poly(butyl acrylate) in the presence of cysteine was carried out using THF, ethyl alcohol, and water where the molar ratio of butyl acrylate monomer/ cysteine/azobisisobutyronitrile was 1000:30:1, respectively. The mixture was then refluxed for 6 hours at 65 C while under constant stirring. After cooling the cysteine- modified product consisted of a white precipitate dispersed within poly(butyl acry- late). The precipitate was isolated from the polymer by dissolving the poly(butyl acrylate) in THF and filtering. 58
    • 2. Preparation of Poly(4-Amino-Benzoic Acid-co-(Cysteine-g-Poly (n-Butyl Acrylate)) The Step 1 product (1.37 g; Mn 26,000 daltons), 4-aminobenzoic acid (2.24 mmol), triphenylphosphite (5 mmol), and LiCl (0.09 g) were dissolved in 30 ml N-methyl- pyrrolidinone/pyridine solution, 80:20, and heated to 100 C for 4 hours. The reaction mixturewasthenprecipitatedinanexcessofwater/methanol,1:1,filtered,andwashed with methanol. The material was dried overnight under vacuum at 40 C, and the product was quantitatively isolated. DERIVATIVES TABLE 1. Selected comonomers reacted with cysteine macromolecular comonomer and corresponding macromolecular content. Cysteine Macromolecular Component Comonomer(s) Macromolecule Content In Copolymer (wt%) Poly(butyl acrylate) 4-Amino-benzoic acid 33 Poly(butyl acrylate) 4-Amino-benzoic acid 66 Poly(butyl acrylate) 1,4-Phenylene diamine and adipic acid 66 Poly(butyl acrylate) 1,4-Phenylene diamine/adipic acid 90 Poly(methyl methacrylate) Perfluoromethyl methacrylate 65 Note: Polymers derived from 4-amino-benzoic acid were insoluble in all solvents except concentrated sulfuric acid. Elemental analysis for all experimental agents supplied by author. NOTES 1. Polylysine-g-histidine derivatives, (I), prepared by Pack [1] were effective as biocompatible endosomolytic delivery agents. H N NH2 O HN O NH2 N N H a b (I) b = 10%–100% Notes 59
    • 2. Kaneko [2] prepared compatibilizing agents consisting of methacrylate, (II), and styryl, (III), macromolecules. These materials were polymerized using titanium-based Ziegler–Natta catalysts. O O R R = Polyethylene Polypropylene Poly(ethylene-co-propylene) O R (II) (III) 3. TEMPO-modified poly(ethylene-co-propylene-g-maleic anhydride), (IV), and poly((ethylene-co-1-decene)-g-alkylacrylates), (V), were prepared by Matsugi [3] and used as polymer blend compatibilizing agents. O O R R = CH3 CH(CH3)CH2CH3 O O O O N O O N (V) (IV) 7 a b a b c References 1. D.W. Pack et al., US Patent Application 2001-0006817 (July 5, 2001) 2. H. Kaneko et al., US Patent 7,067,587 (June 27, 2006) 3. T. Matsugi et al., US Patent 7,022,763 (April 4, 2006) 60 Polyamide Graft Copolymers
    • Title: Bioerodible Poly(Ortho Esters) from Dioxane-Based Di(Ketene Acetals) and Block Copolymers Containing Them Author: J. Heller et al., US Patent 7,163,694 (January 16, 2007) Assignee: A.P. Pharma, Inc. (Redwood City, CA) SIGNIFICANCE Bioerodible poly(ortho ester) copolymers containing hydrophilic and hydrophobic blocks have been prepared from di(ketene acetals) and oligomeric diols. These materials form micelles in aqueous solution making them useful as hydrophobic encapsulation agents or as bioerodible matrices for the sustained release of medicaments. REACTION HO HO O C2H5C2H5 OH OH O O O C2H5C2H5 O O O O O C2H5 C2H5 O O iii iii O O O C2H5C2H5 O O O C2H5 O O C2H5 O O a3 3 i: Toluene, di(trimethylolpropane), acrolein diethyl acetal, pyridinium p-toluene- sulfonate, potassium t-butoxide ii: Pentane, iron pentacarbonyl, triethylamine iii: Triethylene glycol, triethylene glycol monoglycolide, THF, salicylic acid, triethylamine 61
    • EXPERIMENTAL 1. Preparation of Di[(5-Ethyl-2-Vinyl-[1,3]Dioxan-5-yl)Methyl]Ether A reactor containing 300 ml of toluene was charged with di(trimethylolpropane) (120 mmol), 45.6 ml of acrolein diethyl acetal, and pyridinium p-toluenesulfonate (6 mmol), and then refluxed for 4 hours and cooled to ambient temperature. The mixture was further treated with potassium t-butoxide (6 mmol), and then concen- trated under reduced pressure; the residue was distilled in a Kugelrohr apparatus to give 91% yield of the two crude isomers. The crude product was purified by chromatography using Silica Gel 60 and eluting with EtOAc/heptane, 20:80, and 71% yield of di[(5-ethyl-2-vinyl-[1,3]dioxan-5-yl)methyl]ether isolated as a light yellow oil. This material was re-purified by a second chromatographic separation using Silica Gel 60 while eluting with EtOAc/heptane, 10:90, and the product was isolated in 42% yield. 2. Preparation of Di[(5-Ethyl-2-Ethylidene-[1,3]Dioxan-5-yl)Methyl]Ether The Step 1 product (43.9 mmol) was added to a photochemical reactor containing 220 ml pentane and degassed by refluxing vigorously for 20 minutes and then treating with iron pentacarbonyl (0.87 mmol). The mixture was further refluxed and irradiated for 1 hour until no evidence of vinyl signals were detected using 1 H-NMR. It was cooledtoambienttemperature,treatedwith0.5 mltriethylamine,andspargedwithdry air for 4 hours. This mixture was concentrated under reduced pressure, distilled in a Kugelrohr apparatus, and a 63% yield of product was isolated as a colorless oil. 3. Preparation of Poly(Ortho Esters) Containing Triethylene Glycol A reactor was charged with the Step 2 product (3.5 mmol), triethylene glycol (4.95 mmol), triethylene glycol monoglycolide (0.05 mmol), and 5 ml of THF. The mixturewasthenpolymerizedusingsalicylicacidsolutioninTHFascatalyst.After30 minutes 0.1 ml of triethylamine was added, and the product was isolated in 99% yield after the mixture was concentrated. MS (observed): 363, 345 for C18H35O7 and C18H33O6 MS (calculated) 345 for C18H33O6 DERIVATIVES O O O C2H5C2H5 O O O C2H5 O O C2H5 A a3 62 Bioerodible Poly(Ortho Esters) from Dioxane-Based Di(Ketene Acetals)
    • NOTES 1. In other investigations by the author [1] bioerodible block copoly(ortho esters), (I), consisting of the Step 2 produce and polyethylene oxide were prepared and used as controlled drug release agents. O O O C2H5C2H5 O O O C2H5C2H5 O 45 45 (I) a 2. Ng [2,3] prepared bioerodible copoly(ortho esters) consisting of the Step 2 product with monomethyl polyethylene glycol ether termini and 1,4-cyclohex- anedimethanol and either an a-hydroxy carboxylic acid, (II), or N-methyl-di- ethanol amine (III), for use as bioerodible matrices for the sustained release of biologically active agents. Other dioxalane bioerodible analogues were pre- pared by Ng [4] in an earlier investigation. O O O C2H5 C2H5 O O O C2H5 O O O C2H5 OH3CO 3 45 O a (II) TABLE 1. Selected poly(ortho ester) copolymers having bioerodible matrices used for the sustained release of medicaments. Entry A Mn (daltons) Viscosity (poise) 3 O–(CH2)10–O 5,700 78,000 4 (OCH2CH2)3 4,700 32,000 6 O O 11,400 — 7 (OCH2CH2)45 — — Note: Only limited characterization data supplied by author. Notes 63
    • O O O C2H5 C2H5 O O O C2H5 N O C2H5 OH3CO 45 O a (III) 3. Biocompatible ortho aromatic polyanhydrides, (IV), prepared by Uhrich [5] were used in drug delivery systems and as scaffolding implants for tissue reconstruction. a = 6, 8 (IV) b a O O O O O O O O References 1. J. Heller et al., US Patent 7,045,589 (May 16, 2006) and US Patent Application 2006-0155101 (July 13, 2006) 2. S.Y. Ng et al., US Patent Application 2003-0152630 (August 14, 2003) 3. S.Y.Nget al.,US PatentApplication2003-0138474(July24,2003)andUSPatent 6,946,145(September 20, 2005) 4. S.Y. Ng et al., US Patent 6,822,000 (November 23, 2004) 5. K.E. Uhrich,US Patent 7,122,615 (October 17, 2006) and US Patent Application 2004-0096476 (March 20, 2004) 64 Bioerodible Poly(Ortho Esters) from Dioxane-Based Di(Ketene Acetals)
    • Title: Water-Soluble Polymer Alkanals Author: A. Kozlowski US Patent 7,157,546 (January 2, 2007) Assignee: Nektar Therapeutics AL Corporation (Hunstville, AL) SIGNIFICANCE A high yielding method for preparing methoxypolyethylene glycol alkylaldehydes through an acetal intermediate is described. Drug delivery conjugates were then prepared from these aldehydes by condensing with biologically active peptides or proteins such as IFNs-a, b, and j, factors VII, VIII, and IX, insulin, or erythropoietin. REACTION H3CO O O H H3CO O O O OC2H5 OC2H5 H3CO O O O H O H3CO O O O NH Erythropoietin 750 750 750750 i ii iii Note 1 i: Toluene, butylated hydroxytoluene, potassium t-butoxide, t-butanol, 4-chloro- butyraldehyde diethyl acetal, potassium bromide, CH2Cl2, diethyl ether ii: Water, phosphoric acid, sodium chloride, sodium hydroxide iii: Erthropoietin, sodium acetate, sodium cyanoborohydride EXPERIMENTAL 1. Preparation of Methoxypolyethylene Glycol-Butyraldehyde Diethyl Acetal A mixture consistingof methoxypolyethyleneglycol (30,000 daltons;60% solution in toluene; 3.30 g), 30 ml of toluene, and butylated hydroxytoluene (0.004 g) were azeotropically dried by distilling off toluene under reduced pressure. Dried methoxy- polyethylene glycol was then dissolved in 15 ml toluene and treated with 4 ml of 1.0M potassium t-butoxide in t-butanol, 4-chloro-butyraldehyde diethyl acetal (0.00277 mol), and potassium bromide (0.05 g). The mixture was stirred overnight 65
    • at 105  C. The mixture was filtered, concentrated, and the crude was product was dissolved in 20 ml of CH2Cl2. The product was isolated by precipitation in 300 ml diethyl ether, and 1.92 g was isolated with a purity of 95%. 2. Preparation of Methoxypolyethylene Glycol-Butyraldehyde A mixture of the Step 1 product (1.0 g), 20 ml of deionized water, and 5% phosphoric acid was stirred for 3 hours at ambient temperature and then treated with sodium chloride (1.0 g) and sufficient 0.1M sodium hydroxide to obtain a pH of 6.8. The product was extracted three times with 20 ml of CH2Cl2, dried with MgSO4, concentrated, and 82 g of product were isolated. 3. Preparation of Methoxypolyethylene Glycol-Butyl Amine-Erythropoietin Erythropoietin (2 mg) was dissolved in 1 ml of 0.1 mM sodium acetate with a pH of 5, and then treated with the Step 2 product (10 mmol) and cyanoborohydride and stirred for 24 hours at 4 C. Confirmation of N-terminal modification was determined by peptide mapping. Increasing the ratio of methoxyPEG-butyraldehyde to eythro- poietin increased the degree of erythropoietin incorporation. NOTES 1. In an earlier investigation by the author [1] 1-benzotriazolyl carbonate esters of poly(ethylene glycol), (I), were prepared and used as drug delivery templates for lysine and lysozyme. H3CO O O O O N O N N a = 200–4000 a (I) 1 H-NMR (d6-DMSO): d 1.75 ppm (p, –CH2–CH2–CHO–) 2.44 ppm (dt, –CH2–CHO), 3.24 ppm (s –OCH3), 3.51 ppm (s, PEG backbone), 9.66 ppm (t, –CHO) 1 H-NMR (d6-DMSO): d 1.09 ppm (t, CH3–C–) 1.52 ppm (m, C–CH2–CH2–), 3.24 ppm (s, –OCH3), 3.51ppm (s, PEG backbone), 4.46 (t, –CH, acetal) 66 Water-Soluble Polymer Alkanals
    • 2. A drug delivery template consisting of methoxypolyethylene glycol containing succinimidyl esters, (II), was prepared by Harris [2] and used to form amides from the amine portion of proteins. O O O H3CO H N O O O O O N N O O O O (II) a 3. Bhatt [3] prepared antineoplastic agents consisting of poly-L-glutamic acid-- camptothecin conjugates, (III) and (IV), as a method for improving the limited solubility of 20(S)-camptothecin and analogues in aqueous medium. N N O O O O O N N O O HO OO O Poly-L-glutamic acid (III) (IV) Poly-L-glutamic acid 4. Polydipeptides consisting of glutamic acid with alanine, asparagine, (V), glycine, or glutamine were prepared by Xu [4] and used as biodegradable polymeric carriers to which was covalently attached the cytotoxic agent, PaclitaxelÒ . Notes 67
    • HO O O O O OH O O O O O HO NHO O H N N H O CO2H O a Paclitaxel(R) Biodegradable dipeptide (V) References 1. A. Kozlowski, US Patent 7,101,932 (September 5, 2006) 2. J.M. Harris et al., US Patent 7,030,278 (April 18, 2006) 3. R. Bhatt et al., US Patent 7,153,864 (December 26, 2006) 4. J. Xu,US Patent Application 2001-0041189 (November 15, 2001) 68 Water-Soluble Polymer Alkanals
    • Title: Biodegradable Aliphatic Polyester Grafted with Poly(Ethylene Glycol) Having Reactive Groups and Preparation Method Thereof Author: J.-K. Park et al., US Patent 7,151,142 (December 19, 2006) Assignee: Korea Advanced Institute of Science and Technology (Daejeon, KR) SIGNIFICANCE Poly[lactide-g-butene)-g-poly(ethylene glycol)] has been prepared by initially copo- lymerizingL-lactideand1,2-epoxy-5-hexeneformingpoly(lactide-g-butene)contain- ingpendent1-butene,thenpost-reactingwithpoly(ethyleneglycol)methacrylate.The product was both hydrophilic and biodegradable and used as a drug delivery agent and in biochips. REACTION O O O O O O O O O O O O O O O O OH i ii a a b b c i: 1,2-Epoxy-5-hexene, toluene, triethylaluminum pentahydrate ii: Poly(ethylene glycol) methacrylate, THF, 2,20 -azobisisobutyronitrile 69
    • EXPERIMENTAL 1. Preparation of Poly(Lactide-g-Butene) Three 500-ml reflux flasks were each charged with a mixture of L-lactide (5.88 g) and 1,2-epoxy-5-hexene (4.12 g) dissolved in 50 ml of toluene, and then treated with triethylaluminum pentahydrate (98.6 mg). Each vessel was then sealed and heated to 90  C for 12, 24, and 36 hours, respectively, and the contents were precipitated in diethyl ether. The polymers obtained were washed with diethyl ether three times and dried in avacuum oven for 1 day. The polymers were shown to have a double bond content of 7.0, 7.5, and 8.1 mol%, respectively, with a Mn of roughly 10,000 daltons. 2. Preparation of Poly[Lactide-g-Butene)-g-Poly(Ethylene Glycol)] Three 500-ml flasks were each charged with a mixture consisting of the Step 1 product (1 g) having an 8.1 mol% double bond content, poly(ethylene glycol) methacrylate (3.6 g; Mn ¼ 360 daltons), and 50 ml of THF. The flasks were placed into a bath heated to 70 C. Each mixturewasthen treated with 2,20 -azobisisobutyronitrile (2.7 mg, 9 mg, and 18 mg, respectively) and heated 25 hours and precipitated in methanol. The polymers were then washed three times with methanol, dried, and the poly(ethylene glycol) content determined to be 16.6, 18.4, and 7.0 mol%, respectively. Polyethylene glycol incorporation scoping reactions are provided in Table 1. RESULTS NOTES 1. Arnold [1] prepared the hydrophilic and bioabsorbable copolyester, poly (monostearoyl glycerol-co-succinate) (I), which was used in the sustained release of RisperidoneÒ . TABLE 1. Scoping reactions to determine the effect of 2,20 -azobisisobutyronitrile and reaction times on the incorporation of poly(ethylene methacrylate) into the Step 1 product, poly(lactide-g-butene). Entry Butene Content (mol%) Reaction Time (h) AIBN (mg) Graft Ratio of PEG (mol%) 1 7.0 48 8 9.5 2 7.0 48 3.0 10.0 3 7.5 48 8.0 19.5 4 7.5 48 3.0 15.0 5 8.1 25 2.7 16.6 6 8.1 25 9.0 18.4 7 8.1 25 18.0 7.0 70 Biodegradable Aliphatic Polyester Grafted with Poly(Ethylene Glycol)
    • O OO O O 16 a (I) 2. Wilson [2] prepared biodegradable copolymers that were hydrolysable at pH > 10, consisted of ethylene and selected monomers, (II–V), and were used as components in disposable syringes. O O O O Si O Si O O O O (II) (III) (IV) (V) 3. Polymer films prepared by Hayes [3] consisting of bis(2-hydroxyethyl)tere- phthalate, lactic acid, tris(2-hydroxyethyl)trimellitate, ethylene glycol, poly (ethylene glycol), and the colorant titanium dioxide were both biodegradable and compostable. 4. Biodegradable polymers, (VI), containing the hydrophobic biodegradable polyester block and hydrophilic polyethylene glycol block segment were prepared by Piao [4] and used as drug release agents. The gel matrix erosion rates reflected the hydrophobic/hydrophilic content, monomer ratios, and molecular weights. H O O O O O O a bc ab O O O OH (VI) References 1. S. Arnold et al., US Patent 7,034,037 (April 25, 2006) 2. R.B. Wilson Jr. et al., US Patent 7,037,992 (May 2, 2006) 3. R.A. Hayes, US Patent 7,144,972 (December 5, 2006) 4. A.-Z. Piao et al., US Patent 7,018,645 (March 28, 2006) Notes 71
    • Title: Coumarin End-Capped Absorbable Polymers Author: T. Matsuda et al., US Patent 7,144,976 (December 5, 2006) Assignee: Ethicon, Inc. (Somerville, NJ) SIGNIFICANCE Poly(lactone-co-trimethylene carbonates) containing photocurable coumarin ester end groups have been prepared which are crosslinkable upon irradiation with ultra- violet light by a [2 þ 2] cycloaddition. These materials are useful in the preparation of in vivo implants. REACTION OHO O OO O C2H5O O OO O HO O OO O Cl O O O O O O Oa b c OO O O O O O O O Oa b c OO O O i ii iii iv Note 1 O O O O O O O O O O a b c v i: Ethyl bromoacetate, potassium carbonate, acetone ii: 1,4-Dioxane, sodium hydroxide, hydrochloric acid iii: Thionyl chloride 72
    • iv: Poly(e-caprolactone-co-trimethylene carbonate), pyridine, CH2Cl2 v: CH2Cl2 EXPERIMENTAL 1. Preparation of 7-Coumarin Ethyl Acetate Ether A mixture consisting of 7-hydroxycoumarin (0.125 mol), K2CO3 (0.179 mol), ethyl bromoacetate (0.150 mol), and 450 ml of acetone were refluxed for 2 hours and then filtered.Themixturewasconcentrated, theresidue re-crystallizedfrom ethanol,dried, and the product was isolated in 89% yield. 1 HNMR (270 MHz, DMSO-d6) d 1.18 (3H, triplet, J ¼ 8.1 Hz), 4.16 (2H, quartet, J ¼ 8.1 Hz), 4.91 (2H, singlet), 6.28 (1H, doublet, J ¼ 9.9 Hz), 6.96 (1H, doublet, J ¼ 2.0 Hz), 6.98 (1H, quartet, J ¼ 2.0, and 8.9 Hz), 7.61 (1H, doublet, J ¼ 8.9 Hz), 7.96 (1H, doublet, J ¼ 9.9 Hz) 2. Preparation of 7-Coumarin Acetic Acid Ether The Step 1 product (27.9 mmol), 280 ml of 1,4-dioxane, and NaOH (0.405 mol) were stirred overnight at ambient temperature then acidified with 12 M HCl. The mixture was extracted into a mixture of CCl3H and methanol and then concentrated by distillation under reduced pressure. The residue was re-crystallized from ethanol, and the product was isolated in 90% yield. 1 HNMR (270 MHz, DMSO-d6) d 4.83 (2H, singlet), 6.28 (1H, doublet, J ¼ 9.9 Hz), 6.95 (1H, doublet, J ¼ 2.0 Hz), 6.97 (1H, doublet, J ¼ 2.0, and 8.9 Hz), 7.62 (1H, doublet, J ¼ 8.9 Hz), 7.97 (1H, doublet, J ¼ 9.9 Hz), 13.13 (1H, s) 3. Preparation of 7-Chlorocarbonylmethoxycoumarin The Step 2 product (17.1 mmol) and thionyl chloride (0.277 mol) were refluxed 3 hours. Excess thionyl chloride was removed by distillation, and the crude product was isolated in 98% yield and used without additional purification. 1 HNMR (270MHz, DMSO-d6) d 4.83 (2H, singlet), 6.28 (1H, doublet, J ¼ 9.9 Hz), 6.94(1H, doublet, J ¼ 2.0 Hz), 6.96 (1H, quartet, J¼ 2.0, and 8.9Hz), 7.62 (1H, doublet, J¼ 8.9Hz), 7.97 (1H, doublet, J ¼ 9.9Hz) 4. Preparation of Coumarin Ester End-Capped Poly(å-Caprolactone-co-Trimethylene Carbonate) A mixture consisting of poly(e-caprolactone-co-trimethylene carbonate) (0.129 mmol), the Step 3 product (1.79 mmol), pyridine (0.62 mmol), and 20.5 ml of CH2Cl2 were stirred overnight at ambient temperature. The end-capped polymer was precipitated in diethyl ether and then purified by fractionation using DMF and diethyl ether/methanol, 8:2; the product was isolated in 86% yield. FTIR (KBr, cmÀ1 ) 2953, 2866, 1743, 1614, 1250, 1164, and 1036 1 HNMR coumarin groups (270 MHz, CDCl3) d 4.69 (2H, doublet), 6.26 (1H, doublet, J ¼ 9.3 Hz), 6.79 (1H, doublet, J ¼ 2.4 Hz), 6.87 (1H, quartet, J ¼ 2.4, and 8.3 Hz), 7.39 (1H, doublet, J ¼ 8.3 Hz), 7.62 (1H, doublet, J ¼ 9.3 Hz) UV Polymer equivalent weight 3.65 Â 104 daltons Experimental 73
    • 5. Photogelation of Coumarin Ester End-Capped Poly(å-Caprolactone-co-Trimethylene Carbonate) Using Ultraviolet Light The Step 4 product (40 mg) was dissolved in 1.00 ml CH2Cl2 and 150 ml and placed onto a 14.5 mm diameter cover glass. CH2Cl2 was then removed under reduced pressure to prepare a thin film having a thickness of roughly 0.03 mm. The film was irradiated with ultraviolet light of varying intensities and times from a Hg–Xe lamp. The polymeric network or gel that formed was washed with CH2Cl2, dried under reduced pressure to constant weight, and isolated. RESULTS NOTES 1. The preparation of poly(e-lactone-co-trimethylene carbonate) is described by the author using the procedure of Bezwada [1]. 2. The preparation of other in vivo implants using photocurable coumarin end- groups and at least one lactone monomer selected from e-caprolactone, glycolide, or DL-lactide is described by the author [2]. 3. Additional crosslinkable macromolecules are described by the author [3] in an earlier investigation. 4. Crosslinkable monomers N-[3-(7-methyl-9-oxothioxanthene-3-carboxamido)- propyl]methacrylamide, (I), and poly(e-caprolactone-co-trimethylene carbon- ate) (II), were prepared by Chudzik [4] and used in UV photo-crosslinkable implants. O HN O S O (I) TABLE 1. Effect on molecular weight of poly(å-caprolactone-co-trimethylene carbonate) end capped with coumarin after a [2 þ 2] photo cycloaddition using UV irradiation. Mn Poly(e-Caprolactone- co-Trimethylene Carbonate) (daltons) OH value (mol/g) Mn of Post UV Cured End-Capped Poly(e-Caprolactone-co-Trimethylene Carbonate) Coumarin Ester (daltons) 2900 8.34 Â 10À4 3600 4200 5.88 Â 10À4 5100 6100 3.52 Â 10À4 8500 5900 3.55 Â 10À4 8500 74 Coumarin End-Capped Absorbable Polymers
    • O O O O O Oa b c O O O O O O O O O (II) 5. Rhee [5] prepared crosslinkable macromolecules containing collagens, (III), and glycosamino-glycans using a bi-succinimidyl intermediate, (IV); the macromolecules were then used in biomaterial compositions. S S O O NH–Collagen Collagen–NH (III) O S S O N O O N O O O O(IV) 6. Crosslinkable bioresorbable hydrogel block copolymer compositions, (V), were prepared by Loomis [6] for implantable prostheses and as scaffolding for tissue engineering applications. O O O O O ba a = 50–300 b = 10–100 (V) References 1. R.S. Bezwada et al., US Patent 5,468,253 (November 21, 1995) 2. T. Matsuda et al., US Patent 7,144,976 (December 5, 2006) 3. T. Matsuda et al., US Patent 7,105,629 (September 12, 2006) 4. S.J. Chudzik et al., US Patent 7,094,418 (August 22, 2006) and US Patent 6,924,370 (August 2, 2005) 5. W. Rhee, US Patent 7,129,209 (October 31, 2006) 6. G.L. Loomis et al., US Patent 7,109,255 (September 19, 2006) Notes 75
    • Title: Block Copolymers for Multifunctional Self-assembled Systems Author: J. A. Hubbell et al., US Patent 7,132,475 (November 7, 2006) Assignee: Ecole Polytechnique Federale de Lausanne (Lausanne, CH) SIGNIFICANCE A block copolymer effective as a controlled release agents of biologically active materials have been prepared. This agent consisted of ethylene oxide-propylene sulfide-ethylene oxide terpolymer that had been end-capped with a selected cysteine- containing peptide. These materials resist degradation prior to reaching their intended targets because they behave as multilamellar vesicles. REACTION H3CO O OH H3CO O O O 2 S H3CO O S O H3CO O S S O O O 16 16 1616 i ii iii H3CO O S S O O O 16 iv Cystein-containing peptide 25 8 Note 1 iv 25 8 i: Triethylamine, p-toluene sulfonyl chloride, CH2Cl2 ii: Potassium thioacetate, acetone iii: Sodium methoxide, methanol, propylene sulfide, poly(ethylene glycol) monoacrylate iv: Triethanolamine, HEPES buffered saline, hydrochloric acid 76
    • EXPERIMENTAL 1. Preparation of Methoxypoly(Ethylene Glycol) Tosylate Methoxypoly(ethylene glycol) (7 Â 10À3 mol) was dissolved in 30 ml of CH2Cl2 and then treated with triethylamine (0.016 mol) and p-toluene sulfonyl chloride (0.0135 mol). The mixture was stirred for 24 hours at ambient temperature. The mixture was then filtered to remove precipitated triethylammonium hydrochloride, concentrated, and the product was isolated after precipitation in cold diethyl ether. 2. Preparation of Methoxypoly(Ethylene Glycol) Thioacetate The Step 1 product (2.22 Â 10À3 mol) was dissolved in 30 ml of acetone and treated with potassium thioacetate (6.67 Â 10À3 mol), it was stirred overnight at ambient temperature. The mixture was filtered, concentrated, and precipitated in cold diethyl ether. The residue was dissolved in CH2Cl2, extracted with water, dried using Na2SO4, and the product was isolated after re-precipitation in cold diethyl ether. 3. Preparation of Methoxy-Poly[Ethylene Glycol-b-Propylene Sulfide-b-(Ethylene Glycol) Monoacrylate)] The Step 2 product was dissolved in THF and treated with one equivalent of 0.5 M sodium methoxide in methanol at ambient temperature. The mixture was then treated with between 25 and 50 equivalents of propylene sulfide and polymerized for 30 minutes. It was further treated with approximately 10 equivalents of poly (ethylene glycol) monoacrylate as the end-capping agent. The reaction mixture was stirred overnight at ambient temperature and isolated by precipitation in methanol. 4. Preparation of Methoxy-Poly[Ethylene Glycol-b-Propylene Sulfide-b-(Ethylene Glycol) Monoacrylate)]-Cysteine-Containing Peptide End Functionalized The Step 3 product (230 mmol) was dissolved in HEPES buffered saline (10 mmol HEPES; 8 g/l NaCl; pH ¼ 7.4) and then treated with triethanolamine (5.3 ml/ml), and the pH adjusted to pH 8 using 6 M HCl. Cysteine-containing peptides dissolved in 5 ml of HEPES buffered saline were next added to 40 ml of the Step 3 product with stirring and incubated for 6 hours. The solution was dialyzed against pure water for 24 hours and freeze-dried. The polymer was dissolved in 5 ml of CH2Cl2, and the product was isolated after precipitation in hexane. DERIVATIVES Only the single derivative was prepared. Derivatives 77
    • NOTES 1. Block copolymers containing acrylate termini, (I), were prepared by Cellesi [1], and they were subjected to either a Michael-type addition or were photo- polymerized and used as drug delivery agents or biomaterials. O O O O O O a b a (I) 2. Polymers, (II) and (III), containing hydrolytically susceptible segments at a physiological pH between 6.5 and 7.5 were previously prepared by the author [2] and used as viscoelastic liquids containing gel microparticles. O O O O O O O OPEG 2 a (II) S O O O O O O S (III) a 2 3. Poly(ethylene glycol)-poly(glutamic acid) block copolymers containing cis- diamine-dichloroplatinum, (IV), were prepared by Kataoka [3]. The micelle diameters were roughly 22 nm, and these block copolymers were used as antineoplastic drug delivery agents. O N H H N O CO2 Pt(NH2)(NH3)Cl2 5 a (IV) a = 40, 79 78 Block Copolymers for Multifunctional Self-assembled Systems
    • 4. Ho [4] prepared nanoscale helical microstructuresand channels from poly(aryl- TEMPO-b-L-lactide) block copolymers, (V). O N X O O O O O (V) X = CH, N a b References 1. F. Cellesi et al., US Patent Application 2003-0044468 (March 6, 2003) 2. J.A. Hubbell et al., US Patent 6,943,211 (September 13, 2005) 3. K. Kataoka et al., US Patent 7,125,546 (October 24, 2006) 4. R.-M. Ho et al., US Patent 7,135,523 (November 14, 2006) Notes 79
    • Title: Methods of Making Functional Biodegradable Polymers Author: Y. Huage et al., US Patent 7,037,983 (May 2, 2006) Assignee: Kimberly-Clark Worldwide, Inc. (Neenah, WI) SIGNIFICANCE Acrylic acid and derivatives have been free radically grafted onto the backbone of biodegradable polycaprolactone and poly(lactic-co-glycolic acid). These functiona- lized biocompatible materials are useful as drug delivery agents. REACTION O O O O O O O O O OH O O a b a b c d i i: Acrylic acid, 2,20 -azobisisobutyronitrile EXPERIMENTAL 1. Preparation of Poly[(Lactic-co-Glycolic Acid)-g-Acrylic Acid] To prepare the graft copolymer, poly[(lactic-co-glycolic acid) (5.7 g) was dissolved in acrylicacid(5.7 g)and,upondissolution,treatedwith98%2,20 -azobisisobutyronitrile (0.014 g). The mixture was then heated to 70 C and continued heating until the reaction mixture solidified. The solid was then placed into a vacuum oven to remove unreacted acrylic acid, and the product was isolated. 80
    • DERIVATIVES TESTING The solution behavior of the Step1productwasevaluatedusinga Coultertester.In this test NaOH was used to raise the solution’s pH to 9.6 whereupon a milky solution with an average particle size of 2 mwas formed. By one additional day, particle aggregation and precipitation became significant. When the solution pH was raised to 13.7, a clear solution formed with an average particle size of 347 nm. NOTES 1. In another investigation by the author [1], poly(acrylic acid)-g-poly(lactic acid), (I), was prepared and used as a bioadhesive conjugated with bio- degradable components in drug delivery systems. a b c OO O OHO (I) TABLE 1. Biodegradable poly[(lactic-co-glycolic acid) substrates free radically functionalized with grafted acrylic acid or 2-hydroxylethyl acrylate. Entry Drug Delivery Agent Structure 2 Polycaprolactone- g-acrylic acid O O O O HO O a b c 3 Poly[(lactic- co-glycolic acid)- g-2-hydroxylethyl acrylate O O O O O O O O a b c d OH Notes 81
    • 2. Wang used reactive-extrusion polymerization with 2,5-di-methyl-2,5-di-t-bu- tylperoxy hexane to prepared a graft copolymer, (II), by free radically grafting polyethylene-glycol malonic acid onto the biodegradable substrate of poly(b- hydroxybutyrate-co-b-hydroxyvalerate). a b d O O O O O O O O O O c (II) 3. Langer [3] coupled 1,4-butanediol diacrylate with poly(N,N0 -dimethylethyl- enediamine), (III), piperazine, and 4,40 -trimethylenedipiperidine to prepare poly(b-amino esters) that were particularly suited for the delivery of poly- nucleotides. Nanoparticles containing polymer/polynucleotide complexes were also prepared. Hubbell [4] and Zhao [5] prepared polymeric biomaterials by the nucleophilic addition of cysteine, (IV), and polyethylenimine, (V), respectively, to a,b-unsaturated macromolecular diacrylates. O N N O O O (III) O O O S O O O H H2N a (IV) N N H O N O O NH2 O O7 7 (V) a b n c 82 Methods of Making Functional Biodegradable Polymers
    • 4. Acrylated terminated multi-block micelle-forming biodegradable macromo- lecular hydrogels, (VI), prepared by Pathak [6], were used in drug delivery devices and as tissue coatings. O O O O O O O O O O O O aba b 182 a = 4, b = 1 a = 3, b = 2 a = 2, b = 3 a = 1, b = 4 (VI) References 1. Y. Huage et al., US Patent Application 2003-0232088 (December 18, 2003) 2. J.H. Wang et al., US Patent 7,053,151 (May 30, 2006) 3. R.S. Langer et al., US Patent 6,998,115 (February 14, 2006) 4. J.A. Hubbell et al., US Patent 7,119,125 (October 10,2006) 5. G. Zhao et al., US Patent Application 2006-0258751 (November 16, 2006) 6. C.P. Pathak et al., US Patent 7,094,849 (August 22, 2007) Notes 83
    • Title: Monofunctional Polyethylene Glycol Aldehydes Author: P. Rosen et al., US Patent 7,041,855 (May 9, 2006) Assignee: Sun Bio, Inc. (Orinda, CA) SIGNIFICANCE Monofunctionalmethoxypolypropyleneglycolaldehydes werepreparedinafive-step synthetic route. These materials are useful as protein conjugates, and they induce very mild immunogenic responses. REACTION H3CO O O OH H3CO O O O O O C2H5 H3CO O O O OH O H3CO O O O O O N O O H3CO O O O O O H N OC2H5 OC2H5 H3CO O O O O O H N O H i ii iiiiv v 452452 452452 452452 Notes 1,2 i: Potassium t-butoxide, ethyl bromoacetate, t-butyl alcohol ii: Sodium hydroxide iii: CH2Cl2, N-hydroxysuccinimide, dicyclohexylcarbodimide iv: CH2Cl2, 1-amino-3,3-diethoxypropane v: Phosphoric acid, sodium bicarbonate EXPERIMENTAL 1. Preparation of Polyethylene Glycol Ethyl Acetate Methoxypolyethylene glycol and potassium t-butoxide were dissolved in t-butyl alcohol, stirred at 60 C, and then next treated with ethyl bromoacetate. The mixture was next stirred an additional 15 hours at between 80 C and 85 C, filtered, and 84
    • concentrated. The residue was dissolved in distilled water, washed with diethyl ether, andextractedtwicewithCH2Cl2.TheextractwasdriedoverMgSO4 andconcentrated. Precipitation was induced by the addition of diethyl ether to the residue, and the mixture was filtered. The solid was dried under vacuum, and the product was isolated as a white powder. 2. Preparation of Polyethylene Glycol Acetic Acid The Step 1 product was dissolved in 1 M sodium hydroxide and stirred for 15 hours at ambient temperature. The reaction mixture pH was then adjusted to 2 using 1 M hydrochloric acid and extracted twice with CH2Cl2. The mixture was worked up as described in Step 1, and the product was isolated as a white powder. 3. Preparation of Polyethylene Glycol Succinimidyl Acetate A solution of the Step 2 product dissolved in CH2Cl2 was cooled up to 5 C and treated with N-hydroxysuccinimide followed by a solution of dicyclohexylcarbodimide dissolved in CH2Cl2. The mixture was stirred for 15 hours at ambient temperature and then filtered and concentrated, and the residue was re-crystallized from EtOAc. The product was washed twice with diethyl ether was dried, and the product was isolated as a white powder. 4. Preparation of Polyethylene Glycol Diethyl Acetal The Step 3 product was dissolved in CH2Cl2, treated with 1-amino-3,3-diethoxypro- pane dissolved in CH2Cl2, and stirred 2 hours at ambient temperature. Precipitation was then induced by the addition of diethyl ether. The mixture was filtered, re- crystallized using EtOAc, and dried; the product was isolated as a white powder. 5. Preparation of Polyethylene Glycol Aldehyde The Step 4 product was dissolved in an aqueous solution containing phosphoric acid at pH1andstirredfor2hoursatbetween40 Cand50 C.Aftercoolingthereactionmixture to ambient temperature, the pH was raised to 6 using 5% aqueous NaHCO3 solution. Brinewasthenadded,andtheresultingmixtureextractedtwicewithCH2Cl2.Theextract was dried over MgSO4, filtered, and concentrated. Precipitation was induced by the addition of diethyl ether to the residue, and the product was isolated as a white powder. ALTERNATIVE SYNTHETIC PATHWAY PROPOSED BY THE AUTHOR OH OH HO O O HO O O O O O2N O OO H N O O O H3CO O H O H N O O O H3CO i iiiii iv aa Alternative Synthetic Pathway Proposed by the Author 85
    • i: 4-Toluene sulfonic acid, acetone, light petroleum ether ii: 4-Nitrophenyl chloroformate, acetonitrile, 4-dimethylaminopyridine iii: Polyethylene glycol 2-ethylamine, 4-dimethylaminopyridine, CH2Cl2 iv: Hydrochloric acid, hydroperiodate acid NOTES 1. In an earlier investigation by the author [1] methoxypolyethylene glycol derivatives containing pendant aldehydes, (I), were prepared as illustrated below. H3CO O O OH a H3CO O O OH a OH O H3CO O O O H O O N O O a H3CO O O OH NH O a O O C2H5C2H5 H3CO O O OH NH O a O H (I) i ii iiiiv i: Acrylic acid, t-butyl peroxybenzoate ii: CH2Cl2, N-hydroxysuccinimide, dicyclohexylcarbodimide iii: CH2Cl2,1-amino-3,3-diethoxypropane iv: Phosphoric acid, water 2. In a subsequent investigation by the author [2] bi-functional polyethylene glycol derivatives, (II), were prepared. A O O B a (II) A B SO2CH=CH2 CONHCH2CH2CHO Malimide–CH2CO Malimide–CH2CO Malimide–CH2CO CONHCH2CH2CHO CONHCH2CH2CHO CONHCH2CH2CHO 3. Additional methoxypolyethylene glycol derivatives, (III), were prepared by Harris [3] in earlier investigations. H N O O H3CO a R R R CH2OCH2C6H5 CH2OH CH2SCH2CH2OH CH2SCH=CH2(III) 86 Monofunctional Polyethylene Glycol Aldehydes
    • 4. Acid-terminated methoxypolyethylene glycol, (IV), was prepared by Whitlow [4] and used to conjugate single-chain polypeptides. H3CO O O O a O OH O (IV) 5. Hydroxyl/carboxylic acid terminated polyethylene glycol derivatives, (V), were prepared by Varshney [5] and used as intermediates. HO2C O O OH (V) 3 a 6. Azide- and acetylene-terminated polyethylene glycol derivatives were pre- pared by Wilson [6] and used in biomedical applications. References 1. P. Rosen et al., US Patent 6,956,135 (October 18, 2005) 2. P. Rosen et al., US Patent 7,217,845 (May 15, 2007) 3. J.M. Harris et al., US Patent 6,541,543 (April 1, 2003) and US Patent 6,362,254 (March 26, 2002) 4. M. Whitlow et al., US Patent 7,150,872 (December 19, 2006) 5. S.K. Varshney et al., US Patent 7,009,033 (March 7, 2006) 6. T.E. Wilson, US Patent 7,230,068 (June 12, 2007) Notes 87
    • IV. COATINGS A. Anionic Title: Glycopolymers and Free Radical Polymerization Methods Author: E. L. Chaikof et al., US Patent 7,244,830 (July 17, 2007) Assignee: Emory University (Atlanta, GA) SIGNIFICANCE Heparin-like copolymers containing up to 100 units of sulfonated glucose or lactose havebeen prepared bypolymerizing with acrylamide using arenediazonium salts with cyanate anions to form a thrombo-resistant heparinized surface. REACTION O HO HO HO NH Ac OH O HO HO HO NH Ac O O HO HO HO NH Ac O+ Separate O HO HO HO NH Ac O O O3SO O3SO O3SO NH Ac O Cl OH2N OCN OO O3SO O3SO O3SO NH Ac a b i iiiii Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 89
    • i: 4-Penten-1-ol, 10-camphorsulfonic ii: Sulfur trioxide trimethylamine complex iii: 4-Chloroaniline, sodium nitrite, boron trifluoride hydrogen fluoride, cyanate ions EXPERIMENTAL 1. Preparation of N-Acetyl-d-Glucosamine Glycomonomer N-Acetyl-d-glucosamine was treated with 4-penten-1-ol in the presence of 10-camphorsulfonic acid as catalyst. This provided an a- and b-anomeric mixture of the corresponding C4-spacer arm containing the glycomonomer. The a- and b-anomers were separated by column chromatography with CHCl3 and methyl alcohol and were isolated in 31% and 11% yields, respectively. 2. Preparation of N-Acetyl-D-Glucosamine Glycomonomer Persulfates Chemoselective sulfation of the hydroxy groups of the Step 1 a-anomer was obtained using SO3–NMe3 complex and the product purified by anion-exchange and size- exclusion chromatography. 3. Preparation of Glycopolymers Cyanoxyl radicals were generated in situ by an electron-transfer reaction between cyanate anions and p-chlorobenzenediazonium cations; arenediazonium salts were previously prepared in water through the diazotization reaction of p-chloroaniline. Copolymerizations were performed using the Step 2 product and acrylamide at 50 C with ClC6H4N2 þ BF4À /NaOCN as the initiating system. Copolymers were isolated by precipitation in a 10-fold excess of methanol and characterized. DERIVATIVES Lactose-based glycomonomers were also prepared as illustrated below. O O3HSO O3SO O3SO O3SO O O O3SO O3SO O3SO O 90 Glycopolymers and Free Radical Polymerization Methods
    • NOTES 1. In a subsequent investigation by the author [1] multivalent glycopolymers with chain-terminating binding groups, (I), were prepared and used in carbohydrate- mediated biomolecular recognition processes. HN NH S O H N O NCO HN O O O HO OH OH O O HO OH OH OH CONH2 a bc (I) 2. Antithrombonic polymers consisting of poly(vinylidene fluoride-co- hexafluoropropylene-co-vinyl pyrrolidone), (II), 80/15/5 molar ratio, respectively, were prepared by Pacetti [2] and used as shunts in treating atherosclerosis and thrombosis. C F2 F2 C CF CF3 N O a cb (II) 3. Antithrombonic esters, including co-poly-(N,N0 -sebacoyl-bis-(L-leucine)-1,6- hexylene diester), (III), and polyethylene glycol derivatives, (IV), were pre- pared by Pacetti [3] and Hossainy [4], respectively, and used as bio-absorbable stent coatings. N H O O N H O O O O 8 6 n (III) Notes 91
    • O O O PEG300 O O O O O (IV) 4 4a b References 1. E.L. Chaikof et al., US Patent Application 2005-0180945 (August 18, 2005) 2. S.D. Pacetti, US Patent 7,244,443 (June 17, 2007) 3. S.D. Pacetti et al., US Patent 7,220,816 (May 22, 2007) and US Patent 7,202,325 (May 22, 2007) 4. S.F.A. Hossainy et al., US Patent 7,186,789 (March 6, 2007) and US Patent 7,169,404 (January 30, 2007) 92 Glycopolymers and Free Radical Polymerization Methods
    • B. Aqueous Title: Method of Making Novel Water-Soluble and Self-doped Polyaniline Graft Copolymers Author: W.-H. Jo et al., US Patent 7,229,574 (June 12, 2007) Assignee: Seoul National University Industry Foundation (Seoul, KR) Cheil Industries, Inc. (Kyeonggi-do, KR) SIGNIFICANCE Polyaniline has been grafted onto the poly(styrenesulfonic acid-co-aminostyrene) backbone using aniline, ammonium persulfate, and hydrochloric acid. The graft copolymer is water soluble and self-doping and can be used in electrical and marine anticorrosive applications. 93
    • REACTION NH BOC NH BOC SO3Na NH3Cl SO3H NH SO3 NH NH NH i ii iii Not Isolated ... a baba b Note 1 i: Styrene-4-sulfonic acid sodium, DMSO, 2,20 -azobisisobutyronitrile ii: Aniline, ammonium persulfate, hydrochloric acid EXPERIMENTAL 1. Preparation of Poly(Styrene-4 Sulfonic Acid Sodium-co-Styrene- 4-Amino-Butyl Carbonate) A reactor was charged with styrene-4-sulfonic acid sodium (5 g), styrene-4-amino-t- butyl carbonate (0.5 g), and 2,20 -azobisisobutyronitrile (0.1 g) dissolved in 60 ml of DMSO and polymerized for 15 hours at 80 C. The mixture was then precipitated in acetone, filtered, washed several times with acetone, dried, and the product was isolated. 2. Preparation of Self-doped Polyaniline Graft Copolymer Aniline and the Step 1 product were mixed with water and then treated with the dropwise addition of 20 ml 1 M ammonium persulfate and hydrochloric acid at 80 C where the molar ratio ofammonium persulfate/anilinewas 1.0. After standard workup the polymer was isolated. Aniline grafting lengths greater than 20 units could not be solubilized in water. 94 Method of Making Novel Water-Soluble and Self-doped Polyaniline Graft Copolymers
    • NOTES 1. Polyaniline was converted into N-t-BOC polyaniline, (I), by Lee [1] to reduce intermolecular hydrogen bonding when used in conductive polymer appli- cations. N NH N N a b BOC c (I) 2. Hwang [2] grafted polyaniline onto carbon nanocapsules having a diameter between 3-100 nm using ammonium persulfate and hydrochloric acid. 3. Polyaniline-grafted carbon black was prepared by Srinivas [3] and then platinized with chloroplatinic acid, as illustrated below, and used as a fuel cell component. Sulfurized analogues, (II), were prepared by Srinivas [4] and were also used as fuel cell components. NH2 NH NH i a Carbon black PtPt H2PtCl6 ii NaBH4 / H2 i: Ammonium persulfate, hydrochloric acid NH NH a Carbon black HO3S HO3S (II) Notes 95
    • References 1. S.-H. Lee et al., US Patent 7,067,229 (June 27, 2006) 2. G.-L. Hwang et al., US Patent 7,217,748 (May 15, 2007) 3. B. Srinivas, US Patent 7,195,834 (March 27, 2007) 4. B. Srinivas et al., US Patent Application 20040169165 (September 2, 2004) 96 Method of Making Novel Water-Soluble and Self-doped Polyaniline Graft Copolymers
    • Title: Oxyfluorination Author: I. deVilliers Louw et al., US Patent 7,225,561 (June 5, 2007) Assignee: South African Nuclear Energy Corporation, Ltd. (ZA) SIGNIFICANCE Polypropylene has been oxyfluorinated using a gas mixture consisting of fluorine, nitrogen, and water. When cured with mortar slurry, oxyfluorinated surfaces had 20% greater shear bond strength than fluorinated surfaces. REACTION Polypropylene OF OFOF i FF Note 1 i: Fluorine, nitrogen, water EXPERIMENTAL 1. Preparation of Polypropylene-g-Hypofluorite Monofilament polypropylene fibres were prepared by direct extrusion having a rectangular cross section of 0.5 Â 1.3 mm, a length of 40 mm, a specific gravity of 0.91, a tensile strength of 120 MPa,and an elongation at break of 14%. The fibers were placed under 18% humidity at ambient temperature air and then treated with 20% F2 and 80% N2 at a pressure of 45 kPaat 38 C for 2.5 hours. Thereafter the reactionvessel was evacuated, and the product was isolated. 97
    • TESTING NOTES 1. Oxyfluorination of polypropylene was previously done by Hruska [1], and the material was used as an oxidative surface treatment method in electrophotography. 2. Mori [2] developed a method for solid bonding without using a bonding agent by surface hydrofluorinating metal or glass in the presence of water vapor. 3. Oxyfluoropolymers-adhesive composites have also been prepared by Vargo [3] using a radio frequency glow discharge of polytetrafluorineethylene. 4. Surface oxyfluorination was also performed on poly(methyl methacrylate) by Jolet [4] as a method for manufacturing the outer panel of craze-resistant windows. References 1. Z. Hruska, US Patent 6,503,989 (January 7, 2003) 2. Y. Morietal., US Patent Application 2001-0009176 (July26,2001)andUS Patent 6,620,282 (September 16, 2003) 3. T.G. Vargo et al., US Patent 6,790,526 (September 14, 2004) 4. L. Joret et al., US Patent 7,211,290 (May 1, 2007) TABLE 1. Shear bond testing of surface modified polypropylene after oxyfluorination curing in mortar slurry. Entry Shear Bond Strength at 7 Days (MPa) Shear Bond Strength at 28 Days (MPa) 1 0.48 0.46 Control 0.40 0.39 Note: The Control sample was prepared under anhydrous conditions. 98 Oxyfluorination
    • Title: Aqueous Dispersions of Crystalline Polymers and Uses Author: R. F. Stewart et al., US Patent 7,175,832 (February 13, 2007) Assignee: Landec Corporation (Menlo Park, CA) SIGNIFICANCE Aqueousdispersionsofcrosslinkedcrystallinepolymerscontainingbothhydrophobic and hydrophilic components have been prepared. The hydrophobic components consist of C6-, C12-, C14-, and C16-acrylates while methyacrylic acid constituted the hydrophilic comonomer. These dispersions are useful as coatings, particularly on human hair. REACTION O O O O O OC16H33 O OC6H13 OC16H33 O C16H330 O C16H33O O O OC6H13 OC16H33 O O C16H33O OC16H33 O i a b c d e j g f ih i: Water, ethyl alcohol, hexyl acrylate, methyacrylic acid, 1,14-tetradecanediol, sodium dodecyl sulfate, ammonium dodecyl benzene sulfonate, potassium persulfate 99
    • EXPERIMENTAL A mixture consisting of water (190 g), ethyl alcohol (10 g), hexadecyl acrylate (70 g), hexyl acrylate (25 g), methyacrylic acid (5 g), 3.2% sodium dodecyl sulfate, and ammonium dodecyl benzene sulfonate (5 g) was charged into a reactor and degassed for 30 minutes. Potassium persulfate (0.4 g) was then added, and the polymerization was conducted for 4 hours at 70 C under nitrogen. After the polymer was isolated, a sharp DSC endotherm was observed at 22.5 C. REACTION SCOPING TABLE 1. Effects on terpolymer Tm for materials crosslinked with 1,14 tetradecyldiol using varying amounts of surfactant and co-solvents. Reaction Components Example 1 Example 3 Example 5 Example 7 Water (g) 200 190 200 180 C16 Acrylate (g) 70 70 70 70 C6 Acrylate (g) 25 25 25 25 Methyacrylic acid (g) 5 5 5 5 1,14 Tetradecyldiol (g) 2 1.5 — — Sodium dodecyl sulfate (g) 5 5 2.5 2.5 Ammonium dodecyl benzene sulfonate (g) 5 5 2.5 2.5 Potassium persulfate (g) 0.4 0.4 0.4 0.4 Ethyl acetate (g) — 20 — 20 Ethanol (g) 10 — — — Tm ( C) 30.7 21.9 33.0 32.6 Tm Peak appearance Broad Sharp Multiple peaks Sharp TABLE 2. Effects on the polymer Tm after eliminating the amorphorous effects of both of C6-acrylate and 1,14 tetradecyldiol. Reaction Components Example 9 Example 10 Example 11 Example 12 Water (g) 200 190 400 400 C16 Acrylate (g) 35 35 70 — C14 Acrylate (g) — — — 95 C12 Acrylate (g) 60 60 120 95 Methyacrylic acid (g) 5 5 10 10 Sodium dodecyl sulfate (g) 2 2 8 8 DOSS (g) 2 2 8 8 Potassium persulfate (g) 2 0.4 1.6 1.5 Ethyl acetate (g) — 10 — — Dodecyl mercaptan (g) — — 0.1 Tm ( C) 2.0 and 33.7 2.7 13.9 16.1 Tm Peak appearance Two peaks Broad peak Sharp peak Sharp peak 100 Aqueous Dispersions of Crystalline Polymers and Uses
    • NOTES 1. Bitler [1] prepared sharply melting crystalline polymers consisting of C8–C30 urea-ethyl-methacrylate, (I), and C22-acrylate, which reflected high side chain crystallinity and which were used as temperature-dependent coating agents. O O H N O O C8H17 - C30H61 (I) 2. Copolymers, (II), consisting of 75% to 80%–C16-acrylate and 2-hydroxyethyl acrylate having high side chain crystallinity were prepared by Bitler [2] and used as oil thickeners. O O O OC16H33 O O OC16H33 O OC16H33 O a b c d OH OH OC16H33 OO OC16H33 (II) References 1. S.P. Bitler et al., US Patent 6,831,116 (December 14, 2004) 2. S.P. Bitler, US Patent 7,101,928 (September 5, 2006) US. Patent 6,989,417 (January 26, 2006) Notes 101
    • C. Fluorine Title: Multifunctional (Meth)Acrylate Compound, Photocurable Resin Composition and Article Author: Y. Yoshikawa et al., US Patent Application 2007-0116971 (May 24, 2007) Assignee: Shin-Etsu Chemical Co., Ltd. (Annaka-shi, JP) SIGNIFICANCE Trifunctional (meth)acrylate fluorine-containingcyclicandacyclicsilane compounds have been prepared that form photocurable resin compositions. Coatings from these resins are anti-fouling and resist organic stains from oil mist and fingerprints without detracting from surface mar resistance. REACTION Si O O O O H H H F2C CF2 F2C CF2 F2C CF2 F2C CF3 Si O O O O O O O F2C CF2 F2C CF2 F2C CF2 F2C CF3 O O O O O O i ii Resin i: 2-Hydroxyethyl acrylate, toluene, N,N-diethylhydroxylamine ii: g-Acryloxypropyltrimethoxysilane, trimethylolpropane triacrylate, 1,6-hexane- diol diacrylate, DarocureRTM , UV irradiation 102
    • EXPERIMENTAL 1. Preparation of tri(2-Hydroxyethyl Acrylate) 1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8- Perfluoro-11-Decyl Cyclotrimethylsilane A reactor was charged with 1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8-perfluoro-11-decyl cyclo- trimethyl-silane (0.1 mol), 2-hydroxyethyl acrylate (0.315 mol), and toluene (111.9 parts) and then treated with N,N-diethylhydroxylamine (0.0126 mol). Thereafter the reaction was heated for 8 hours at 70 C, cooled to ambient temperature, washed with water,andconcentrated.Theproductwasisolatedhavingaviscosityof93.0 mm2 /swith a refractive index of 1.4018. 2. Preparation of Photocurable Resin A mixture consisting of silica (40 parts) previously treated with g-acryloxypropyl- trimethoxysilane, trimethylolpropane triacrylate (40 parts), 1,6-hexanediol diacrylate (20 parts), the Step 1 product (0.5 parts), and DarocureRTM (5 parts) as the free radical initiator were spin-coated and irradiated with UV light to form a coating having a thickness of roughly 5 mm. DERIVATIVES O Si F2C CF2 F2C CF2 F2C CF2 F2C CF3 OO Si O O Si Si O O O O O O OSi O O O O O O O NH O O O O O O CF O CF2 CF O F2C CF2 O CF3 F3C F3C NOTES 1. A crosslinkable silicone rubber coating composition, (I), was prepared by Azechi [1] and used in preparing automotive airbags. Notes 103
    • O Si OSi O Si OSi H H OO O O (I) 2. Crosslinkable tetravinylsiloxane derivatives, (II), prepared by Hare [2] were used as low-viscosity materials in dental impressions. Si O O O O Si Si Si Si (II) 3. Morita [3] prepared silsesquioxane resins using crosslinkable vinyl monomers, (III), for use in semiconductor devices. OSiO Si O SiOSiO Si O Si O O Si O Si OSi O Si O Si O O O O O (III) Si References 1. S. Azechi et al., US Patent 7,153,583 (December 26, 2006) 2. R.V. Hare, US Patent 6,561,807 (May 13, 2003) 3. K. Morita et al., US Patent Application 20070054135 (March 8, 2007) 104 Multifunctional (Meth)Acrylate Compound, Photocurable Resin Composition and Article
    • D. Hydrophilic Title: Polyoxyalkylene Phosphonates and Improved Process for Their Synthesis Author: S. Wo et al., US Patent 7,208,554 (April 24, 2007) Assignee: Rhodia Inc. (Cranbury, NJ) SIGNIFICANCE Hydrophilic surface active agents containing C1–C4 phosphoric acid derivatives providelimited benefitsbecause of their short aliphatic chain. To address this concern, hydrophilic phosphonic acid derivative containing an oligomeric ethylene glycol component has been prepared. REACTION H O O O O O O O O P OCH3 O OCH3 H O O P OH O OH iii iii 10 10 1010 Note 1 i: Acetic anhydride ii: Di-t-butyl peroxide, dimethyl hydrogen phosphite iii: Water EXPERIMENTAL 1. Preparation of Acetyl Polyethylene Glycol Allyl Ether A two-neck flask equipped with a Snyder distilling column and distilling head was charged with polyethylene glycol allyl ether (1.0 mol; Mw ¼ 498 daltons) and then 105
    • treated with acetic anhydride (1.05 mol). The mixture was heated to 110 C for 3 hours during which time the acetic acid by-product was collected. At the end of the reaction excess acetic anhydride was removed under vacuum, and the product was isolated. 2. Preparation of Acetyl Polyethylene Glycol Dimethyl Phosphite The Step 1 product (1 mol) was mixed with di-t-butyl peroxide (0.1mol) and then added to a second flask containing dimethyl hydrogen phosphite (1.1 mol) and heated for 5.5 hours at between 130 C and 135 C. At the conclusion of the reaction excess dimethyl hydrogen phosphite was removed under vacuum, and the product was isolated. 3. Preparation of Polyethylene Glycol Phosphonopropyl Ether The entire Step 2 product was treated with excess water and hydrolyzed for 20 hours from 135 C to 150 C. During this time the volume ratio of the Step 1 product/water was kept at 1:1, and methanol and acetic acid by-products were continuously removed by distillation. Thereafter the product was isolated and was completely soluble in water. DERIVATIVES No additional derivatives were prepared. NOTES 1. Baker [1] determined that both polyethylene glycol phosphonopropyl ether, (I), with repeat units of 4 and 10 were effective as cerium oxide nanoparticle dispersants. aH O O P OH O OH a = 4, 10 (I) 2. Zeller [2] prepared anionic and nonionic surface-active agents, (II), consisting of fatty alcohols and ethylene oxide which were used as surfactants. a O O X 13-15 (II) X = OH, PO(OH)2, SO3H a = 3–11 106 Polyoxyalkylene Phosphonates and Improved Process for Their Synthesis
    • 3. In an earlier investigation by the author [3] sulfonated polyesters were prepared consisting of ethylene glycol and terephthalate acid capped with dimethyl-5- sulfoterephthalate. References 1. J.M. Baker et al., US Patent Application 2006-0241008 (October 26, 2006) 2. E. Zeller et al., US Patent 7,183,446 (February 27, 2007) and US Patent 6,963,014 (November 8, 2005) 3. S. Wo, US Patent 6,576,716 (June 10, 2003) Notes 107
    • E. Hydrophobic Title: Polymers and Polymer Coatings Author: C. Ober et al., US Patent Application 2007-0053867 (March 8, 2007) Assignee: Cornell Research Foundation, Inc. (Ithaca, NY) SIGNIFICANCE A limited number of marine paint additives exist that can provide antifouling coatings that are nontoxic and “fouling repellant.” Silicon-free polyacrylates containing a pendant semifluorinated alkyl substituent have been prepared to address this need. REACTION OO t-C4H9 Br OO t-C4H9 OO OO t-C4H9 OO Br OOO Br O C F2 F2 C 23 23 82 23 82 x y x = 0–15 y = 1–7 i ii iii OHOOO Br 23 82 iv i: Acetone, pentamethyldiethylene triamine, copper(I) bromide, copper(II) bro- mide, methyl 2-bromopropionate ii: Copper(I) bromide, styrene, pentamethyldiethylene triamine iii: Hydrochloric acid, dioxane iv: Pyridine, 1,3-dicyclohexylcarbodiimide, 4-dimethylaminopyridine, ZonylÒ FSO-100, THF 108
    • EXPERIMENTAL 1. Preparation of Poly(t-Butylacrylate) Macroinitiator A mixture containing 3 ml of acetone, t-butylacrylate (80 mmol), and pentamethyl- diethylene-triamine (0.8 mmol) were added to CuBr (0.8 mmol) and CuBr2 (0.04 mmol). This mixture was then treated with methyl 2-bromopropionate (1.6 mmol) and heated for 6 hours at 60 C. It was cooled to ambient temperature and treated with 50 ml of acetone and neutral alumina. The acetone solution was concentrated and the residue purified by dissolving in diethyl ether. The purified material was precipitated in a methanol/water mixture, 1:1, at 0 C, dried, and the product was isolated having a Mn of 3000 daltons with a polydispersity index of 1.1. 2. Preparation of Poly[(t-Butylacrylate)-block-Styrene] A mixture consisting of the Step 1 product (0.67mmol) and CuBr (0.95 mmol) mixed withstyrene(95 mmol)wasstirreduntilthepolymerdissolved.Pentamethyldiethylene triamine (0.95 mmol) was added, and the mixture was heated for 2 hours at 100 C. After cooling to ambient temperature the viscous polymer was dissolved in 150 ml of THF and then passed through a column of neutral alumina. The solution was concentrated, the residue precipitated in methanol, and the polymer isolated having polydispersity index of 1.1. 3. Preparation of poly(Acrylic Acid)-block-Polystyrene Twomillilitersofconcentratedhydrochloricacidsolutionwasaddedtoa10%solution of the Step 2 product dissolved in dioxane and refluxed for 6 hours. After cooling to ambient temperature the polymer was precipitated in water, and the product was isolated after recovering by filtration. 1 H NMR (DMSO-d6): d 2.2 and 1.6 (br s, –CH2, >CH–); 6.5 and 7.1 (br s, 5H, styrene); 12.0 (br s, COOH) FTIR (film; cmÀ1 ): 3600-2400 (O–H stretching, carboxylic acid); 3026 (C–H stretching, aromatic); 2926 (C–H stretching, backbone); 1716 (C¼O stretching, ester); 1492, 1452 (C¼C stretching, aromatic); 758 and 700 (C–H bending, aromatic) 1 H NMR (CDCl3): d 1.5 (s, 9H, –C(CH3)3); 1.85 and 2.35 (br s, –CH2, , >CH–); (s, 3H, –OCH3) 4.1 (m, 1H, >CH–Br) FTIR (film; cmÀ1 ): 2977 (C–H stretching, t-butyl); 2929 (C–H stretching, backbone); 1727 (C¼O stretching, ester); 1367 (C–H bending, t-butyl). 1 H NMR(CDCl3):d1.5(s,9H,–C(CH3)3);1.85and2.35(brs,–CH2,>CH–);6.5AND7.1(brs,5H,styrene) FTIR (film; cmÀ1 ): 3026 (C–H stretching, aromatic); 2976 (C–H stretching, t-butyl); 2926 (C–H stretching, backbone);1728(C¼Ostretching,ester);1493,1452(C¼Cstretching,aromatic);1367(C–Hbending,t- butyl); 758 and 700 (C–H bending, aromatic) Experimental 109
    • 4. Preparation of poly(Ethoxylated Fluoroalkyl Acrylate)-block-Polystyrene In the first vessel the Step 3 product (1 g) was dissolved in 5 ml of pyridine. In a second vessel 1,3-dicyclohexylcarbodiimide (6.57 mmol), 4-dimethylamino- pyridine (0.823 mmol), and Zonyl FSO-100 (6 g) were dissolved in THF and then added dropwise to the first vessel. The reaction was stirred for 2.5 days at ambient temperature and filtered to remove dicyclohexylurea. The solution was concentrated and then precipitated by pouring into methanol. It was re-dissolved in THF and re- precipitated into methanol; the product was isolated after filtration. DERIVATIVES No additional derivatives were prepared. TESTING Quantitative testing data on biofouling assays was not provided. NOTES 1. Semifluorinated block copolymers, (I), were previously prepared by the author [1] and then blended with styrene-ethylene/butylene-styrene thermoplastic elastomers to provide surface-active block copolymers. x y x = 500–1000 y = 200–1000 z = 100–1000 n = 4, 6 n CF2 F O CF2 F n 8 O z (I) 8 1 H NMR (300 MHz, CDCl3): d 6.5 and 7.1 (5H, styrene); 4.16 (br s, 2H, –COOCH.sub.2–); 3.77 (t, 2H,– COOCH.sub.2CH.sub.2–); 3.64 (br s, –OCH.sub.2CH.sub.2O–); 2.42 (m, 2H, –CH.sub.2CF. sub.2–); 1.86, 1.43 (backbone) 19 F NMR (CDCl3, CF3COOH reference) d: À126.65, À124.16, À123.38, À122.41, À113.95, À81.27 (3F, –CF3) FTIR (film; cmÀ1 ): 3026 (C–H stretching, aromatic); 2922 (C–H stretching, backbone); 1731 (C¼O stretching, ester); 1490, 1450 (C¼C stretching, aromatic); 1400–1000 (C–F stretching); 754 and 698 (C–H bending, aromatic) 110 Polymers and Polymer Coatings
    • 2. Biofouling-resistant surfactant compositions, (II), were prepared by Swedberg [2] that had a hydrophobic domain that promoted adsorption of the surfactant molecule to the surface of selected surface active materials. (PEO)129 (PPO)100 (PEO)129 O H N O SO3H (II) 3. Pendant quaternary amine salts prepared by Price [3] were effective as antifouling additives in marine paint. a N H O NH Palmitic (III) References 1. C. Ober et al., US Patent 6,750,296 (June 15, 2004) 2. S.A. Swedberg et al., US Patent 7,201,834 (April 10, 2007) 3. C. Price, US Patent Application 2007-0082972 (April 12, 2007) Notes 111
    • Title: Photochemical Crosslinkers for Polymer Coatings and Substrate Tie-Layer Author: P. Guire et al., US Patent Application 2007-0003707 (January 4, 2007) Assignee: SurModics, Inc. (Eden Prairie, MN) SIGNIFICANCE Two trifunctional benzophenone derivatives have been synthesized that are UV photoactive at 254 nm and photolytically incorporated into poly(e-caprolactone) and poly(vinylpyrrolidone). These agents are designed to be used in photopolymerization reactions. REACTION HO O O O NN OH N OH O O O O O OH O i Photochemical curing agent i: Glycerol triglycidyl ether, potassium carbonate, acetone EXPERIMENTAL Preparation of tri(N-2-Hydroxy-3-(4-Benzophenoxy)Propyl))-s-Triazine A round bottom flask was charged with 4-hydroxybenzophenone (2.26 g), 0.532 ml of glycerol triglycidyl ether, potassium carbonate (3.3 g), and 50 ml of acetone and then refluxed 24 hours and concentrated. The residue was dissolved in CCl3H and filtered. Thefiltratewaswashedthreetimeswith4 MNaOHaqueoussolution,oncewithwater, 112
    • twicewith1 M HCl, andre-washed threetimeswithwater.Thesolutionwasdriedover MgSO4, filtered, and concentrated. The residue was washed three times with diethyl ether and then re-dried, and the product was isolated. TESTING Wettable Testing A coating solution was prepared in isopropanol using the Step 1 product (0.5 mg/ml) and poly-vinylpyrrolidone (50 mg/ml). A 100 ml of the coating solution was applied to polyvinylchloride coverslips and then dried overnight. All pieces were illuminated at 254 nm light from 0 to 10 minutes and rinsed with 30 minutes in water with gentle agitating.Thestaticcontact anglewithwaterwastakenonagoniometerwiththree3 ml drops of water and measured three times. Contact angle testing results are provided in Table 1. Photoreactive Surface Preparation and Testing A photoreactive polymer solution was prepared by mixing poly(e-caprolactone) (50 mg/ml)filmwiththeStep1product(0.5 mg/ml)andthencastingthemixtureonto a glass slide. The film was treated with poly(vinylpyrrolidone) (10 ml 50 mg/ml, 30,000daltons),dissolvedinisopropanolsolution,andthemixturewasconcentrated. The film was illuminated for 20 minutes using 254 nm light and then incubated in water on a shaker for 3 hours to remove unbound PVP. After staining with 0.5% w/v aqueous solution of Congo Red the components of a film consisting of poly(vinyl- pyrrolidone) and poly(e-caprolactone) was determined to be homogeneously distributed. By contrast, films prepared without the triazine crosslinker showed no stainings, suggesting that the unbound poly(vinylpyrrolidone) was removed by the rinse. TABLE 1. Contact angles of PVC coated with the Step 1 product followed by UV activation at 254 nm. Illumination Time at 254 nm (min) Contact Angle (deg) 0 38.1 – 10.0 0.5 24.8 – 7.8 1 31.7 – 6.3 2 31.1 – 4.4 5 23.1 – 8.8 10 29.1 – 3.0 Uncoated 61.9 – 1.4 Testing 113
    • NOTES 1. Oxime derivatives were prepared by Kunimoto [1] containing both esteroxime and aryl ketone components, (I), were particularly effective in photopolymer- ization reactions. N O O S O (I) 2. Blood compatible surfaces were prepared by the author [2] by UV curing of benzophenone-containing polyethylene ether, (II). O O N H O CO2H4 13 (II) 3. Swan [3] prepared a benzene 1,3-disulfonic acid derivative, (III), as a surface coating agent for polyvinylpyrrolidone for subsequent use as a surface modifier on polyvinylchloride urinary catheters. O O O O SO3KKO3S (III) 4. Swan [4] prepared terpolymers, (IV), containing photoreactive groups that covalently bond to nucleic acids for use in preparing nucleic acids microarrays. 114 Photochemical Crosslinkers for Polymer Coatings and Substrate Tie-Layer
    • NHO O O 2 NH2O OO HN O O O 3 cba (IV) References 1. K. Kunimoto et al., US Patent 7,189,489 (March 13, 2007) 2. P. E. Guire et al., US Patent 7,144,573 (December 5, 2006) and US Patent 7,071,235 (July 4, 2006) 3. D. G. Swan, US Patent 7,138,541 (November 21, 2006) 4. D. G. Swan et al., US Patent 6,762,019 (July 13, 2004) Notes 115
    • Title: Use of Poly(Dimethyl Ketone) to Manufacture Articles in Direct Contact with a Humid or Aqueous Medium Author: B. Brule et al., US Patent 7,011,873 (March 24, 2006) Assignee: Arkema (Puteaux, FR) SIGNIFICANCE The low water permeability of polydimethyl ketone has been found to be effective in preparing hermetically sealed industrial food packaging that comes in direct contact with a humid or aqueous medium. REACTION O O O C O O O iii a bNotes 1, 2 a > b i: Pyrolysis ii: Aluminium tribromide, carbon tetrachloride EXPERIMENTAL 1. Preparation of Dimethylketene Isobutyric anhydride was pyrolysized between 550 C and 675 C under an absolute pressure of between 30 and 40 mmHg and while under a nitrogen stream of 1.5 ft3 /h. Gaseous products from the pyrolysis chamber passed through a water-jacketed copper condenser and then through two glass cylinder separators. The residue vapors were next passed though a cold trap at À50 C and conducted to a cold condenser and receiver to collect the dimethylketene, BP ¼ 34 C. 116
    • 2. Preparation of Poly(Dimethyl Ketone) Dimethylketene (15.2 g) enclosed in a tubular reactor was placed in an acetone Dewar flask at À30 C and treated with 38 ml of carbon tetrachloride and 2.5 ml of 0.86M aluminium tribromide solution. Thereafter the mixture was stirred for 5 hours at À30 C and at ambient temperature for 19 hours. The reaction was quenched by the addition of 20 ml of methanol, and the polymer was isolated after precipitation in 200 ml of methanol containing 4 ml of hydrochloric acid. DERIVATIVES Only the Step 2 product was prepared. TESTING Water Permeability Water permeability was determined at 38 C for 24 hours using a 50 mm thick film in accordance with the ASTM E96E standard. Testing results are provided in Table 1. NOTES 1. Linemann [1] prepared polydimethylketene by the Friedel-Craft cationic polymerization of dimethylketene using AlBr3. 2. The Step 2 product containing up to 30 mol% ether content was effective as an oxygen barrier under high relative humidity and used in pipes, bottles, and containers by Egret [2]. References 1. R. Linemann et al., US Patent 7,105,615 (September 12, 2006) 2. H. Egret et al., US Patent 6,793,995 (September 21, 2004), US Patent 6,528,135 (September 21, 2004), and US Patent 6,528,135 (March 4, 2003) TABLE 1. Water permeability testing results of selected polymers using the ASTM E96E standard. Material Water Permeability (g/m2 24 h) Step 2 product 6 High-density polyethylene 3 Polypropylene 5 Low-density polyethylene 5 Polyvinyl chloride 18 Poly(ethylene-co-vinyl alcohol) [32 mol% ethylene] 35 Polyaniline 50 Notes 117
    • F. Thermally Stable Title: Polyaryleneetherketone Phosphine Oxide Compositions Incorporating Cycloaliphatic Units for Use as Polymeric Binders in Thermal Control Coatings and Method for Synthesizing Same Author: T. D. Dang et al., US Patent 7,208,551 (April 24, 2007) Assignee: University of Dayton (Dayton, OH) SIGNIFICANCE The use of polymers as thermal control coatings in space environments is desirable, since they provide significant weight reduction, good mechanical strength, and exhibit thermal and thermooxidative stability. Therestillremains a need,however, for coatings that resist degradation by ultraviolet radiation and atomic oxygen. This investigation addresses that need using polyaryleneetherketone phosphine oxide materials. REACTION a HO O O OH Cl O O Cl O O H3CO OCH3 O O P O i ii O O HO OH iii Not isolated 118
    • i: 4,9-Diamantanedicarboxylic acid, thionyl chloride, aluminum chloride, anisole ii: Pyridine hydrogen chloride iii: 4,40 -Difluorotriphenylphosphine oxide, potassium carbonate, DMAc, toluene EXPERIMENTAL 1. Preparation of 4,9-bis(4-Methoxybenzoyl)Diamantane 4,9-Diamantanedicarboxylic acid and excess thionyl chloride were refluxed until a clear solution was obtained and then concentrated. The crude 4,9-diamantanedi- carboxylic acid chloride (0.0211 mole) was slowly added to a chilled solution of AlCl3 (6.75 g) and anisole (22.8 g), and the mixture was stirred overnight at ambient temperature. The product was precipitated by pouring into 0.1M aqueous HCl, then stirred, filtered, and the solid further stirred in methanol to remove unreacted anisole. The white solid was re-crystallized from a mixture of 700 ml toluene and 100 ml THF and the product was isolated in 72% yield, MP ¼ 213–214 C. 2. Preparation of 4,9-bis(4-Hydroxybenzoyl)Diamantane A round-bottomed flask was charged with the Step 1 product (0.0285 mol) and excess pyridinehydrochloride(0.2850 mol),thenheatedfor3 hoursat225 Candcooled.The reaction mixture was poured into 40 ml of concentrated HCl diluted with 200 ml of water, and a precipitate formed. The solid was isolated, dried, then dissolved in THF with hexane slowly added until the solution became slightly turbid. The solution was next slowly cooled, and the product was isolated in 57% yield, MP ¼ 313–315 C. 3. Preparation of 4,9-Diamantane-Based Polyaryleneetherketone Triphenylphosphine Oxide AreactionvesselequippedwithaDean–StarktrapwaschargedwiththeStep2product (1.3212 g), 4,40 -difluorotriphenylphosphine oxide (0.9689 g), potassium carbonate (1.022 g), 7.2 ml DMAc, and 15 ml of toluene and then refluxed for at least 4 hours. After removal of the azeotrope and toluene, the mixture was refluxed at 165 C for an additional 16 hours. The polymer was precipitated in water, shredded in a blender, filtered, dried, and the product was isolated in 92% yield. Experimental 119
    • DERIVATIVES NOTE Resins prepared by Timberlake [1] consisting of benzoguanamine-modified phenol- formaldehyde or melamine-phenol-formaldehyde resins were treated with tris(4- methoxy- phenyl)phosphine oxide to prepare coatings in printed circuit boards. Isomeric mixtures of tris(2-hydroxyphenyl)-phosphine oxide compounds were also converted into resins by Brennan [2] by reacting with tris(4-methoxy-phenyl)phos- phine oxide derivatives. References 1. L.D. Timberlake et al., US Patent 7,202,311 (April 10, 2007) and US Patent 7,201,957 (April 10, 2007) 2. D.J. Brennan et al., US Patent 6,740,732 (May 25, 2004) and US Patent 6,969,756 (November 29, 2005) TABLE 1. Selected polyaryleneetherketone phosphine oxide derivatives prepared according to the current invention and corresponding viscosities at 30 C. Entry Structure Polymer Concentration (g/25 ml CCl3H) [Z] (dl/g) Step 1 product O O P O n 0.0632 0.27 7 O O O O P O n 0.25 1.18 11 O O O O P O n 0.25 0.38 120 Polyaryleneetherketone Phosphine Oxide Compositions Incorporating Cycloaliphatic Units
    • G. Vapor Deposition of Polymers Title: Functionalization of Porous Materials by Vacuum Deposition of Polymers Author: M. G. Mikhael et al., US Patent 7,157,117 (January 2, 2007) Assignee: Sigma Laboratories of Arizona, LLC (Tucson, AZ) SIGNIFICANCE Vapor deposition has been used to prepare fibers such as woven and nonwoven synthetic and natural fibers having hydrophobic/oleophobic and biocide properties. Thisprocessentailsflashevaporationofaperfluoroacrylatemonomeranditsradiation curing in a vacuum chamber onto a selected fiber surface. REACTION ... O F2 C CF3 ... ... O F2C CF3 i aNote 1 b b b > 5 a ... i: Perfluoroacrylate 121
    • EXPERIMENTAL Preparation of Polypropylene-g-Perfluoroacrylate Nonwoven Fabric with a Hydrophobic/Oleophobic Repellent Surface A perfluoroacrylate monomer was flash evaporated at 100 millitorr and exposed to polypropylene fibers pretreated in a plasma field within one second while the fabric was traveling at 50 m/min. The condensed monomer layer was then cured in-line by electron beam radiation within 100 milliseconds resulting in a 0.1 mm perfluoroa- crylate coating on the material surface. The product had an adequate repellency for both water and oil and a surface energy of 27 dyne/cm. DERIVATIVES NOTES 1. Color changing sensing coatings were prepared in the current invention using a mixture of phenolphthaleine and perfluoroacrylate monomer; heat-sensing coatings were prepared by grafting 4-pentyl-4-cyanobiphenyl; and strawberry odor smelling coatings were prepared by coating a surface with 4-(2,6, 6-trimethyl-1-cyclohexen-1-yl)-3-buten-2-one. 2. In an earlier investigation by the author [1], 0.3 to 0.8 m coatings of polyethylene and poly(a-methylstyrene) solid oligomers having Mn’s of roughly 4000 and 1300 daltons, respectively, were vapor deposited onto a polyester surface at 1 Â 10À4 to 1 Â 10À5 torr at 300 C. 3. Affinito [2] vapor coated hexanediol diacrylate, trimethylolpropane triacrylate, and tripropyleneglycol diacrylate liquid monomers at roughly 80 C and 1 Â 10À4 torr onto polyethylene terephtholate and then radiation polymerized the surface using electron beam radiation. TABLE 1. Water/alcohol and oil repellency testing of fabrics modified with perfluoroacrylate monomer to confer a hydrophobic/oleophobic repellent surface. Water/Alcohol Repellency Test Oil Repellency Test Fabric Sample Unwashed 10 Wash Cycles Unwashed 10 Wash Cycles Cotton Control 1 1 1 1 Treated 6 4 5 3 Polyester*1 Control 3 3 1 1 Treated 6 5 6 4 Nylon*2 Control 3 3 1 1 Treated 6 5 6 4 Note: Higher testing values are preferred. Surface energies of fabrics were not provided by author. *1 Polyester not specified. *2 Nylon not specified. 122 Functionalization of Porous Materials by Vacuum Deposition of Polymers
    • 4. Cured coatings having dielectric dissipation factors < 0.05 at 24 C at 600 Hz on conductorswere prepared by Krongauz [3] by radiation curing a surface coating containing hydroxyl-terminated hydrogenated 1,2- and 1,4-polybutadiene, isophorone diisocyanate, and hydroxyethylacrylate. 5. Bilodeau [4] prepared barriers consisting of radiation cured N-vinyl-2-pyrro- lidone and N-vinylcaprolactam that were impervious to migratory components in autmotive tires. References 1. M.G. Mikhael et al., US Patent 7,005,161 (February 28, 2006) 2. J.D. Affinito, US Patent 7,112,351 (September 26, 2006) 3. V.V. Krongauz et al., US Patent 7,109,253 (September 19, 2006) 4. W.L. Bilodeau et al., US Patent 7,141,285 (November 28, 2006) Notes 123
    • H. Succinic Anhydride Derivatives Title: Light Absorbent Agent Polymer for Organic Anti-reflective Coating and Preparation Method and Organic Anti-reflective Coating Composition Comprising the Same Author: J.-c. Jung et al., US Patent 7,033,729 (April 25, 2006) Assignee: Hynix Semiconductor, Inc. (Kyungki-do, KR) SIGNIFICANCE In the fabrication process of ultra-fine patterns for photoresists using ArF light source (193 nm), few organic or inorganic anti-reflective coating currently exist. This art addresses this need using poly(maleic anhydride-co-4-dihydro-1,4-methano-naph- thalene-5,8-diol) diacetate crosslinked with poly(styrene-co-vinyl dimethylacetal). REACTION a b OO O OO O OO O O i Organic anti-reflective material ii Note 1 i: 4-Dihydro-1,4-methano-naphthalene-5,8-diol diacetate, propylene glycol methy- lether acetate, 2,20 -azobis isobutyronitrile ii: Poly(styrene-co-vinyl dimethylacetal), propylene glycol methylether acetate, methyl 3-methoxy propionate, 2-heptanone, THF, 2-hydroxycyclo-pentyl-1-tri- fluoromethylsulfonic acid 124
    • EXPERIMENTAL 1. Preparation of Light-Absorbing Polymer Agent A reaction vessel was charged with maleic anhydride (20 g), 1,4-dihydro-1,4-metha- no-naphthalene-5,8-diol diacetate (26 g), and propylene glycol methylether acetate (26 g), and then treated with 2,20 -azobissobutyronitrile (0.5 g). The mixture was reacted at 65 C for 7 hours, concentrated, precipitated in water, washed with diethyl ether, and the product was isolated in 40% yield, Mw of roughly 7000 daltons. 2. Preparation of Organic Anti-reflective Coating Composition The Step 1 product (1 g) and poly(styrene-co-vinyl dimethylacetal) (0.4 g) were dissolved in a mixture comprising propylene glycol methylether acetate (4 g), methyl 3-methoxy propionate, 2-heptanone (10 g), and THF (7 g). The solution was then treated with 2-hydroxycyclo-pentyl-1-trifluoromethylsulfonic acid (0.1 g), filtered, and the product was isolated. 3. Preparation of Organic Anti-reflective Coating and Photoresist Pattern The Step 2 product was spin-coated onto a silicone wafer and baked for 2 minutes at 215 C. Thereafter the anti-reflective mixture was coated with a Keum Ho petroleum photosensitive agent and baked for 90 seconds 110 C. After these processes the material was exposed to a light source by means of ASML/900 scanner apparatus and baked an additional 90 minutes at 130 C. The exposed wafer was developed using an aqueous solution of 2.38% tetramethyl-ammonium hydroxide. DERIVATIVES Only the Step 2 product was prepared. NOTES 1. The Step 2 crosslinking agent, poly(styrene-co-vinyl dimethylacetal), (I), is illustrated below. O O a b (I) Notes 125
    • 2. An additional Step 1 light absorbing polymer agent, (II), was prepared by the author [1] in a subsequent investigation and used as an organic anti-reflective coating. OO O OHHO O O a b (II) 3. Compositions for an anti-reflective light-absorbing layer using diazoquinones, (III), were prepared by Yoon [2] and used in forming patterns in semiconductor devices. a OO O N2 OO CO2H (III) 4. Lee [3] prepared organic anti-reflective polymer coatings consisting of poly- vinyl phosphoric acid and poly(vinyl acetate-co-ethylene). 126 Light Absorbent Agent Polymer for Organic Anti-reflective Coating and Preparation Method
    • 5. Anti-reflective polymer coatings, (IV), prepared by the author [4] were used in forming ultra-fine patterns of photoresist for photolithography. O NO O O O CH2 NO OO OO a b a b (IV) References 1. J.-c. Jung et al., US Patent Application, 2005-0084798 (April 21, 2005), US Patent 7,205,089 (April 17, 2007), and US Patent Application, 2006-0004161 (January 5, 2006) 2. S.-w. Yoon et al., US Patent 6,838,223 (January 4, 2005) 3. G.-s. Lee et al., US Patent 7,198,887 (April 3, 2007) 4. J.-c. Jung et al., US Patent 7,186,496 (March 6, 2007) Notes 127
    • V. COSMETICS Title: Water-Soluble or Water-Dispersible Graft Polymers, Their Preparation and Use Author: S. N. Kim et al., US Patent 6,992,161 (January 31, 2006) Assignee: BASF Aktiengesellschaft (Ludwigshafen, DE) SIGNIFICANCE Urethane and polyurea segments have been introduced into a polymer containing polyesters, polyethers, and casein. When blended into hair spray formulations containing upto 5 wt% solids, enhanced curl retention and flexural strength resulted. REACTION O O HN O O O O O O O O O 20 4 6 20 H N O NH HN Casein O HN O O CO2H CO2H i a i: Isophthalic acid, adipic acid, hexanediol, polyethylene glycol, dimethylolpropanoic acid, isophorone dissocyanate, triethanolamine, casein, 2-amino-2-methylpropanol EXPERIMENTAL 1. Preparation of Polyethylene Glycol Graft Copolymer A reaction kettle was charged with polyesterdiol (0.5 mol; Mw 1000 daltons; prepared from isophthalic acid, adipic acid and hexanediol), polyethylene glycol (0.05 mol; MW ¼ 1500 daltons), and dimethylolpropanoic acid (1.25 mol) dissolved in methyl ethyl ketone. The mixture was heated to 80 C. When the reaction was completed the Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 129
    • mixture temperature was lowered to 50 C and isophorone diisocyanate (1.9 mol) was added dropwise. At an internal temperature of 90 C the reaction mixture was stirred until the isocyanate group content remained constant. Thereafter the reaction mixture was cooled to ambient temperature and treated dropwise with 15% casein (116.5 g) dissolved in triethanolamine, and next stirred until isocyanate groups were no longer detectable. The mixture was then treated with water and the product was neutralized with 2-amino-2-methylpropanol. The solution was concentrated, and the product was obtained by spray drying under vacuum at À80 C. Hair Spray Formulation Flexural Strength and Curl Retention NOTES 1. Polyurethanes containing polytetrahydrofuran, diethylene glycol, stearyl alco- hol, and hexamethylene diisocyanate were prepared by Meffert [1] and used in hair compositions. 2. Alkali-swellable polymer compositions consisting of acrylic acid, methyl methacrylate, behenyl methacrylate, lauryl methacrylate, and sodium lauryl sulfate were prepared by Tamareselvy [2] and used as a hair rheology modifier and as a hair setting agent. TABLE 1. Hand pump spray formulation with a volatile organic compounds content of 55%. Component Charge (wt%) Step 1 product (Solids content) 5 Water 40 Ethanol 55 Fragrance/surfactant q.s TABLE 2. Hair spray formulations of selected casein-containing Step 1 products and their effect on curl retention and flexural strength. Entry Polyesterdiol (mol) PEG E1500 (mol) DMPA (mol) MDEA (mol) IPDI (mol) Casein (wt%) Curl Retention (%) Flexural Strength (cN) 3 1 0.1 — — — 50 51 312 4 1 0.1 2.5 — 3.8 10 65 356 6 0.9 0.1 2.5 0.1 3.8 5 73 452 130 Water-Soluble or Water-Dispersible Graft Polymers, Their Preparation and Use
    • 3. Rollat [3] prepared acrylate terpolymers consisting of 2-ethylhexyl acrylate, isobornyl acrylate, acrylic acid, and methacrylic acid, 55, 50, 2.5, 2.5 parts, respectively, that were useful in hair styling compositions. 4. Polymers consisting of t-butyl acrylate, methacrylic acid, sodium ether dodecyl sulfate, and n-dodecylthiol were prepared by Drohmann [4] and used in hairsprays. References 1. H. Meffert et al., US Patent 7,019,061 (March 28, 2006) 2. K. Tamareselvy et al., US Patent 7,153,496 (December 26, 2006) 3. I. Rollat et al., US Patent 7,122,175 (October 17, 2006) and US Patent 7,048,916 (May 23, 2006) 4. C. Drohmann et al., US Patent 7,147,842 (December 12, 2006) Notes 131
    • VI. DENTAL A. Cement Title: (Meth)Acrylate-Substituted Iminooxidiazine Dione Derivatives Author: N. Moszner et al., US Patent 7,078,446 (July 18, 2006) Assignee: Ivoclar Vivadent AG (Schaan, LI) SIGNIFICANCE UV-curable dental cement composites consisting of 20% asymmetrical 1,3,5- oxadiazine-2,4-dione trimethacrylate derivatives have been prepared that have lower shear viscosities than their symmetric triazole counterpart. This property is particu- larly needed for preparing “flowable” pre-cured cement paste. REACTION O O O N NCOOCN NCO O O O N N H N H O O O O O N H O O O O O O O 6 66 6 66 i Note 1 i: 2-Hydroxylethyl methacrylate, 2,2,6,6-tetramethyl-piperidine-1-oxyl, hydroqui- none monomethylether, dibutyltin dioctoate, CH2Cl2 Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 133
    • EXPERIMENTAL Preparation of 3,5-bis(6-(6-Hexyl Carbamate-Methacrylate)-6-[(6-Hexyl Carbamate-Methacrylate)Imino]-1,3,5-Oxadiazine-2,4-Dione 3,5-bis(6-Isocyanato-hexyl)-6-[(6-isocyanato-hexyl)imino]-1,3,5-oxadiazine-2,4- dione (0.1 mol) was added dropwise at ambient temperature to a solution containing 2-hydroxylethyl methacrylate (0.3 mol), 2,2,6,6-tetramethyl-piperidine-1-oxyl (12 mg), hydroquinone monomethylether (25 mg), and dibutyltin dioctoate (0.2 g) dissolved in 100 ml of CH2Cl2 and then stirred for 20 hours. Next the reaction mixture was washed twicewith 100 ml of 1.0M NaOH and three times with 100 ml of saturated brine.TheorganicphasewasdriedwithNa2SO4 andconcentrated,andtheproductwas isolated in 67% yield. DERIVATIVES TABLE 1. Viscosity of UV-curable dental composites containing 20% experimental assymmetric additives or a symmetric reference. Entry Structure Paste Shear Viscosity (Pas) 1 O O O N N H N H O O O O O N H O O O O O O O 6 66 2.21 Symmetrical Reference N N N O O N H N H O O O O O N H O O O O O O O 6 66 O 3.36 IR (ATR; cmÀ1 ): 3368 (w), 2930 (m), 2858 (w), 1785 (w), 1682 (s), 1522 (m), 1458 (s), and 1163 1 H-NMR (CDCl3): d 1.35 (br, 12 H, CH2), 1.51 (br, 6H, CH2), 1.63 (br, 6H, CH2), 1.94 (s, 9H, CH3), 3.17 and 3.34 (t, sat. 6H,CH2N), 3.84 (t, 6H, CH2N), 4.31 (br, 12H, CH2O), 5.02 5.03 (br, 3H, NH), 5.59 and 6.13 (2s, each 3H, .dbd.CH2) ppm 134 (Meth)Acrylate-Substituted Iminooxidiazine Dione Derivatives
    • Table 1. (Continued ) Entry Structure Paste Shear Viscosity (Pas) 2 O O O N N H N H O O O NH O O 6 66 O O O O O O O O OO O OO O 2.20 Symmetrical Reference N O O N H N H O O O NH O O 6 66 O O O O O O O O OO O OO O O 2.79 Note: The remainder of the composit consisted of 80 wt% filler consisting of barium- aluminum-boron silicate glass powder, silicon dioxide-zirconium dioxide, and ytterbium fluoride. For dental composites lower viscosities are preferred because of their flowability. Derivatives 135
    • NOTES 1. The preparation of the triisocyanate Step 1 reagent is described by Richter [1]. 2. In an earlier investigation by the author [2] di-amides, (I) and (II), were prepared and used in dental adhesive composites. Materials based on acryl- ic-ester phosphonic acids, (III) and (IV), and used in dental cements were also prepared by the author [3]. N N O O N H O O H N N H O O O H N O )II()I( O O O P OH O OH O O O O O P OH O OH O P HO O HO (III) (IV) 3. In a subsequent investigation by the author [4] photopolymerizable bis- acylphosphine oxides, (V), effective as Norrish type I cleavage agents at 400 to 500 nm, were prepared and used as self-conditioning dental fixing cements. Self-etching dental materials such as adhesives, coating materials, and composites consisting of (meth)acrylamide phosphates, (VI), were also prepared by the author [5] and used in restorative dentistry. P O O O O O (V) O N O N P OH O OH O(VI) 136 (Meth)Acrylate-Substituted Iminooxidiazine Dione Derivatives
    • 4. Polymerizable cyclopropyl acrylates, (VII), were prepared by the author [5] and used as components in dental cements and filling materials. O O O O CO2C2H5 C2H5O2CO O O O (VII) References 1. F.L. Richter et al., US Patent 5,914,383 (January 22, 1999) 2. N. Moszner et al., US Patent 6,953,832 (October 11, 2005) 3. N. Moszner et al., US Patent 6,953,832 (October 11, 2005) and US Patent 6,900,251 (May 31, 2005) 4. N. Moszner et al., US Patent Application 2007-0027229 (February 1, 2007) 5. N. Moszner et al., US Patent Application 2006-0178469 (August 10, 2006) Notes 137
    • B. Dental Composites Title: (Meth)Acrylic Ester Compound and Use Thereof Author: A. Otsuji et al., US Patent Application 2007-0078198 (April 5, 2007) Assignee: Mitsui Chemicals, Inc. (Tokyo, JP) SIGNIFICANCE Diacrylatemonomershavebeenpreparedthatarephotocurableinvisiblelightandthat have small polymerization shrinkage and high X-ray contrast properties. When polymerized with 0.01 to 0.04 mm glass powder, these dental composites were easily machined into artificial teeth. REACTION O O O O O OO O O OO O ClCl O OO O O OO O Note 1 i ii O OO O OH OH iii i: 4-Phenylphenol, sodium hydroxide, DMAc 138
    • ii: 3-Chloropropionic acid chloride, DMAc iii: Acetone, triethyl amine EXPERIMENTAL 1. Preparation of 1,3-di-[2-Hydroxyl-3-(4-Phenylphenoxy)-1-Propoxy] Benzene A reactor was charged with 4-phenylphenol (0.40 mol), NaOH (0.53 g), and DMAc (40 g) and then treated with the dropwise addition of a solution of resorcin diglycidyl ether (0.20 mol) in DMAc (40 g). The mixture was stirred for 6 hours at 100 C and diluted with 200 g of methanol/water, 1:1. Crystals that precipitated were collected, dried, and the product was isolated in 97% yield as a colorless powder. 2. Preparation of 1,3-di-[2-(Chloropropionic Acid Ester)-3- (4-Phenylphenoxy)-1-Propoxy]Benzene The Step 1 product (0.10 mol) was dissolved in DMAc (60 g) and treated with the dropwise addition of 3-chloropropionic acid chloride (0.36 mole) at 60 C for over 60 minutes. The mixture was stirred for 4 hours at 60 C and cooled to ambient temperature. It was poured into ice water, extracted with of toluene (250 g), and washed with 3% aqueous NaHCO3. The organic layer was repeatedly washed with water until it was neutral and concentrated, and the product was isolated in 95% yield as a colorless, transparent, and viscous liquid. 3. Preparation of 1,3-di-[2-(Acrylic Ester)-3-(4-Phenylphenoxy)-1- Propoxy]Benzene The Step 2 product (0.10 mol) was dissolved in acetone (100g) and treated with triethyl amine (0.36 mol) at 5 C for over 1 hour and then stirred for 2 hours. The mix-ture temperature was warmed to ambient temperature and extracted with 200 g apiece toluene and water. The organic portion was isolated and treated with 5% hydro- chloric acid, washed repeatedly with water until it was chloride free, and then concen- trated.Theresiduewaspurifiedbysilicagelcolumnchromatographyusingtoluene,and the product was isolated in 80% yield as a colorless and transparent liquid. 1 H-NMR (CDCl3) d 4.20–4.30 (m, 8H), 5.50–5.60 (m, 2H), 5.85 (d, 2H), 6.10–6.20 (m, 2H), 6.45 (d, 2H), 6.50–6.60 (m, 3H), 6.90–7.60 (m, 19H) FD-MS (m/z); 670 (Mþ) Experimental 139
    • DERIVATIVES O OO O O OO O O OO O O OO O O OO O O OO O NOTES 1. Experimental dental fillers were cured by irradiation with visible rays for 60 seconds using a visible ray irradiator. 2. Nakamura [1] prepared UV-curable acyclic esters of 1,3-dithiolane, (I), for use as dental composites. a S S O O O O (I) a = 2 – 4 3. Crosslinkable polyhedral oligomeric silsesquioxane, (II), prepared by Jin [2] were used as dental composites in restorative applications, especially in crown and bridge materials. 140 (Meth)Acrylic Ester Compound and Use Thereof
    • Si SI Si Si Si Si Si R R OY R R OY R OY R R O O O O O O O O (II) R = C1 – C9 Y= acrylate 4. Methacrylate-substituted asymmetric trimers consisting of iminooxidiazine dione derivatives, (III), were prepared by Moszner [3] that had excellent mechanical properties and were used as dental cements. N O N O N O N H N H O O O O O O O O N H O O O O 6 66 (III) 5. Heilmann [4] prepared a dental material from the co-oligomerization of i-octyl acrylate and methacryloyloxyethylcarbamoyl-ethylmethylketonoxime, (IV). The copolymer had a Mn of roughly 21,000 daltons and a shrinkage of less than 2% after thermal curing. O N H O N O O (IV) 6. Metathesis-curable compositions of polyethylene glycol monomers, (V), using ruthenium derivatives, (VI), were prepared by Angeletakis [5] and used as dental impression materials and orthodontic appliances. Notes 141
    • O O O O O O O O O O O O 8 Ru Cl Cl NNMesityl Mesityl (V) (VI) References 1. M. Nakamura et al., US Patent 6,835,844 (December 28, 2004) 2. S. Jin et al., US Patent 7,160,941 (January 9, 2007) 3. N. Moszner et al., US Patent 7,078,446 (July 18, 2006) 4. S.M. Heilmann et al., US Patent 7,074,858 (July 11, 2006) and US Patent 7,015,286 (March 21, 2006) 5. C. Angeletakis et al., US Patent 7,001,590 (February 21, 2006) 142 (Meth)Acrylic Ester Compound and Use Thereof
    • VII. ELECTROACTIVE A. Charge Transport Materials Title: Hole Transport Polymers and Devices Made with Such Polymers Author: G. D. Jaycox et al., US Patent 7,205,366 (April 17, 2007) Assignee: E.I. du Pont de Nemours and Company (Wilmington, DE) SIGNIFICANCE Manyelectroluminescentmaterialshavepoorcharge transport properties. Thepresent invention is directed to polymeric agents containing grafted naphthalene or pyrene, which makes then effective as both hole transport and electroluminescent agents. REACTION OCH3O OCH3 O O O OH i OCH3 O O O a b a bii O NH O i: 2-Hydroxyethyl methacrylate, VazoÒ 52, 2,20 -azobis(2,4-dimethyl pentane nitrile), acetone ii: 1,10 -Carbonyldiimidazole, 1-(1-naphthyl)ethylamine, THF Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 143
    • EXPERIMENTAL 1. Preparation of Poly(Methyl Methacrylate-co-2-Hydroxyethyl Methacrylate) A container was charged with a solution of VazoÒ 52 catalyst and 2,20 -azobis(2,4- dimethyl pentane nitrile) (4.5 g) dissolved in acetone (600 g); a second container was charged with methyl methacrylate (540 g) and 2-hydroxyethyl methacrylate (180 g). The first and second containers were uniformly fed into a reactor for 330 and 240 minutes, respectively, and then refluxed for 1 hour. After standard workup the product wasisolatedin100%yield,havingaMnof30,308daltons,Mw of93,195daltons,anda PDI of 3.07. 2. Preparation of Poly(Methyl Methacrylate-co-Ethyl-(Naphthyl Carbamate)- Methacrylate) A reactor was charged with the Step 1 product (20 g), THF (445 g), and 1,10 - carbonyldiimidazole (7.50 g) and then stirred for 1 hour at ambient temperature. The mixture was treated with the dropwise addition of 1-(1-naphthyl)ethylamine (7.9 g) dissolved in THF (67 g) over 20 minutes and then stirred for 48 hours at ambient temperature. The mixturewas concentrated to one-third its volume and precipitated in 200 ml water. The residue was extracted five times with 200 ml of water, ground in a blender and dried, and the product isolated was in 84% yield. DERIVATIVES A pyrene polyamide derivative, (I), was also prepared. a H N H N O O HN O (I) 1 H-NMR (DMSO-d6) d 6.7–8.1 (aromatic protons for pendant naphthylene group); ratio of aromatic H aliphatic H ¼ 0.20 (theoretical ¼ 0.19) UV-Vis (DMSO) lmax 305 nm 144 Hole Transport Polymers and Devices Made with Such Polymers
    • NOTES 1. By incorporating ethynyl functions into existing 1,3,4-oxadiazole-containing electroluminescent electron hole transport dyes, (II), Roberts [1] increased the device operating lifetime by inhibiting oxadiazole aggregation. Tokarski [2] prepared azine derivatives, (III), that were also effective as hole transport agents. C4H9 C4H9 N N O t-C4H9 O N N C4H9 C4H9 t-C4H9 (II) SS S HO O N N N OH O N (III) 2. Electroluminescent polymeric 1,3,4-oxadiazole-containing agents, (IV), pre- pared by Roberts [3] were also effective as electron hole transport agents. a N N O C8H17 C8H17 C8H17 C8H17 OC8H17 (IV) Notes 145
    • 3. Electron hole transport composites consisting of poly(aniline-co-2-acrylami- do-2-methyl-propanesulfonic acid), (V), and silicon nanoparticles were prepared by Hsu [4] and then used to prepare light-emitting diodes and electrodes for thin film field effect transistors. H N NHO SO3H (V) a b 4. Tamao [5] prepared a light-emitting material effective as a charge transport agent containing boron, (VI), which was used as a luminescent element. B C8H17O OC8H17 (VI) a References 1. R.R. Roberts et al., US Patent 7,192,657 (March 20, 2007) 2. Z. Tokarski et al., US Patent 7,189,482 (March 13, 2007) 3. R.R. Roberts et al., US Patent 7,094,902 (August 22, 2006) 4. C.-H. Hsu et al., US Patent 7,189,771 (March 13, 2007) 5. K. Tamao et al., US Patent 7,157,154 (January 2, 2007) 146 Hole Transport Polymers and Devices Made with Such Polymers
    • Title: Acrylic Polymer and Charge Transport Material Author: H. Ishizawa et al., US Patent 7,012,123 (March 14, 2006) Assignee: Sekisvi Chemical Co., Ltd. (Osaka, JP) SIGNIFICANCE Isotacticandsyndiotacticpoly(9-fluorenylmethacrylate)s havebeenpreparedthat are effective as hole mobility charge transport materials and as electrical conductors of charge transport materials. REACTION a OH O O OO iii Isotactic and syndiotactic prepared i: Benzene, triethylamine, methacryloyl chloride ii: THF, t-butyllithiun EXPERIMENTAL 1. Preparation of 9-Fluorenyl Methacrylate A 200 ml reaction flask charged with 9-fluorenol (11 mmol),180 ml of benzene, and triethylamine (13.75 mmol) was cooled to 6 C and then treated with the slow addition of methacryloyl chloride (13.75 mmol). Thereafter the mixture was stirred at ambient temperature for 24 hours.The solution was washed with water and saturated NaHCO3, and the organic layer was isolated, dried with MgSO4, and concentrated. The residue 147
    • was purified by column chromatography using benzene, and the product was isolated in 40% yield as white solid, MP ¼ 61 C. 2. Preparation of Syndiotactic Poly(9-Fluorenyl Methacrylate) A 25 ml reaction tube was charged with the Step 1 product (0.687 mmol), dissolved in 3.2 ml of THF, and then cooled to À78 C and treated with 0.07 ml of 1.36 M t-BuLi (0.095 mmol). The mixture reacted at À78 C and was quenched with 2 ml of methanol. The solution was precipitated in 30 ml of methanol and isolated. The precipitate was dissolved in 30 ml hexane, filtered, and concentrated, and 0.147 g product was isolated having a Mn of 2600 daltons with a PDI of 1.25. DERIVATIVES The isotactic derivative was also prepared TESTING 1. Measurement of Hole Mobility of Charge Transport Material (TOF Method) A CH2Cl2 solution consisting of 10 wt% of the Step 2 product and 1 wt% of 2,4,7- trinitrofluorene malononitrile as dopant was prepared and cast onto an ITO glass substrate, dried; a 1 mm film was isolated. Aluminum was thenvacuum deposited onto the film to a thickness of 1000 C forming a 5 Â 5 mm aluminum electrode. Hole transfer time was measured by applying a voltage of 5 V to the electrode while simultaneously exposing it to a pulse laser beam at 337 nm. Hole mobility testing results are provided in Table 1. 2. Electrical Conductivity of Charge Transport Material The film prepared above was evaluated for electrical conductivity at an interelectrode distance of 90 mm. Testing results are provided in Table 1. TABLE 1. Hole mobility and electrical conductivity for syndiotactic and isotactic poly(9-fluorenyl methacrylate). Entry Hole mobility (cm2 VÀ1 sÀ1 ) Electrical Conductivity (S/cm) Syndiotactic 1.02 Â 10À4 1.13 Â 10À5 Isotactic 8.02 Â 10À4 5.13 Â 10À5 1 H-NMR (CDCl3) d 7.696 (2H, d), 7.580 (2H, d), 7.427 (2H, t), 7.306 (2H, t), 6.868 (1H, s), 6.166 (1H, s), 5.621 (1H, s) and 2.015 (3H,s) 1 H-NMR (CDCl3) d 6.988 7.501 (8H, m), 6.322 (1H, s), 2.108 (1.79H, s), 1.127 (2.9H, s) 148 Acrylic Polymer and Charge Transport Material
    • NOTES 1. Electroactive fluorene copolymers, (I), were prepared by Uckert [1] using 2,7- diiodo-9,9-di-2-ethylhexyl fluorine. This product was used as a component in light-emitting diodes. aN C6H13 C8H17 C8H17 (I) 2. Chen [2] prepared electroluminescent conjugated polymers, (II), containing phosphorescent components that were used as light-emitting diodes. Boron analogues, (III), prepared by Tamao [3] were also used as light-emitting diode components. a a NN (II) B SS (III) References 1. F.P. Uckert et al., US Patent 7,220,820 (May 22, 2007), US Patent 7,214,763 (May 8, 2007), and US Patent 7,211,643 (May 1, 2007) 2. S.-A. Chen et al., US Patent 7,220,819 (May 22, 2007) 3. K. Tamao et al., US Patent 7,157,154 (January 2, 2007) Notes 149
    • B. Dielectric Materials Title: Thermosetting Aromatic Dielectric Material Author: J. Economy et al., US Patent 7,211,642 (May 1, 2007) Assignee: The Board of Trustees of the University of Illinois (Urbana, IL) SIGNIFICANCE Although minimization in integrated circuits allows for faster device operation, propagation delays increase with increasing numbers of interconnects. To address this problem, lower dielectric constant materials have been prepared. 150
    • REACTION OH O O O O O O O O O O O O a i ii i: Benzenetricarboxylic acid chloride, pyridine, CH2Cl2 ii: 3-Diethynyl benzene, phenylacetylene, copper(I) chloride, oxygen, acetone, pyridine EXPERIMENTAL 1. Preparation of tris-(3-Ethynyl-Phenyl)Trimesate A reaction flask was charged with 3-ethynyl phenol (0.017 mol), 5 ml of pyridine, and 20 ml of CH2Cl2 and treated with the dropwise addition of 1,3,5-benzenetricarboxylic acid chloride (0.0055 mol) dissolved in 10 ml of CH2Cl2 and refluxed for 6 hours at 45 C. The resulting yellow solution was washed 3 times apiecewith 20 ml of 1 M HCl, 1MNaOH,andwater.ThemixturewasthendriedwithNa2SO4,filtered, concentrated, and the product was isolated as a yellow powder in 58% yield. Experimental 151
    • 2. Preparation of Poly[3-Diethynyl Benzene-co-(tris-(3-Ethynyl-Phenyl) Trimesate)] A reactor was charged with CuCl (0.0135 mol) and 67 ml acetone and then slowly heated with stirring to 30 C and treated with 0.83 ml of acetone/pyridine, 1:1. The slurry was stirred for 10 minutes until oxygen bubbled through the mixture turning the light green slurry dark green. The flow of O2 was continued throughout the rest of the reaction. In a separatevessel, a mixture consisting of 3-diethynyl benzene (14.27 mmol), the Step 1 product (1.59 mmol), phenylacetylene (0.111 mol), and 0.83 ml of the acetone/ pyridine mixture in 40 ml of acetone was added to this vessel in a single portion. Heating was removed, an additional 5 ml of the acetone/pyridine was added over a period of 30 minutes, and the temperature was kept below 45 C via an ice bath. After the acetone/pyridine addition was completed, the reaction temperature was kept between30 Cand40 Cfor12hoursinthedark.Thereactionmixturewasprecipitated in 400 ml of methanol containing 11 ml of 12M HCl, filtered, and washed with methanol. The light yellow paste was dissolved in 50 ml of CCl3H, washed 3 times apiece with 10 ml 10% HCl and then water, dried with MgSO4, filtered, and concentrated. The residue was dissolved in 20 ml of CCl3H and then re-precipitated from 600 ml of methanol. The mixture was re-filtered, washed with methanol, and dried, and 1.19 g of product was isolated as a white powder. DERIVATIVES A second derivative was also prepared as shown below. a O O O O NOTES 1. Low dielectric constant compositions consisting of adamantyl, (I), and diada- mantyl derivatives with a porogen consisting of polyacenaphthylene homopoly- mer were prepared by Li [1] and used as substrate materials in microchips, 1 H-NMR d 9.2 (m, 3H), 7.2 7.5 (m, 12H) FTIR (cmÀ1 ) 3300 ethynyl C–H stretch, 1750 C¼O 152 Thermosetting Aromatic Dielectric Material
    • multichip modules, laminated circuit boards, and printed boards. Related adamantly and diadamantyl derivatives were prepared by Lau [2]. (I) 2. A low dielectric constant composition consisting of poly(divinylsiloxanebis- benzocyclobutene) having a Mw of roughly 50,000 daltons and poly(propylene glycol) biscinnamate having a Mw of roughly 2200 daltons, was prepared by Bruza [3] and used in electronic applications such as integrated circuits, multichip modules, and flat panel display devices. 3. You [4] prepared porous thermoset dielectric materials having low dielectric constants which were used in electronic component manufacture with cross- linked polymeric porogen particles as provided in Table 2. 4. Pore-generating materials, particularly b-cyclodextrins, were used by Lyu [5] with silsesquioxane derivatives to prepare low dielectric constant materials. TABLE 1. Components used in preparing porogen particles which were compatible with the B-staged benzocyclobutene dielectric materials after crosslinking with 10% trimethylol-propane triacrylate. Entry Monomer A Monomer B Ratio A/B A Styrene N-Vinylpyrrolidone 45/45 B N-Vinylpyrrolidone — — D Styrene Vinylanisole 45/45 G Styrene Vinylanisole 80/10 Notes 153
    • References 1. B. Li et al., US Patent 7,141,188 (November 28, 2006), US Patent 7,060,204 (July 13, 2006), and US Patent 6,740,685 (May 25, 2004) 2. K. Lau et al., US Patent 6,987,147 (January 17, 2006) 3. K.J. Bruza et al., US Patent 7,109,249 (September 19, 2006) 4. Y. You et al., US Patent 6,998,148 (February 14, 2006) 5. Y.Y. Lyu et al., US Patent 7,169,477 (January 30, 2007) 154 Thermosetting Aromatic Dielectric Material
    • C. Donor-Acceptor Complexes Title: Polyester Having p-Conjugated Group in Side Chain and Charge Transporting Material Using the Same Author: T. Nakano, US Patent 7,235,620 (June 26, 2007) Assignee: Japan Science and Technology Corporation (Saitama, JP) SIGNIFICANCE Beginning with 9-fluorene carboxylic acid, high molecular weight poly(9-hydroxy methyl-9-fluorene carboxylic acid) has been prepared by the homopolymerization of 9-hydroxymethyl-9-fluorene carboxylic acid using trifluoro methanesulfonate as the catalyst. This polymeric agent readily formed donor-acceptor complexes with 1,3-dinitrobenzene and is suitable as a charge transport material. REACTION a CO2H HO2C OH OO O i ii i: THF, paraformaldehyde, CH2Cl2, butyl lithium ii: THF, methanol, tin(II), trifluoromethanesulfonate, diazomethane 155
    • EXPERIMENTAL 1. Preparation of 9-Hydroxymethyl-9-Fluorene Carboxylic Acid A reactor was charged with 9-fluorene carboxylic acid (23.7 mmol) and 300 ml of THF and then cooled to À78 C and treated with 41.0 ml of 1.6 M butyl lithium solution in hexane. The mixture was stirred for 30 minutes, treated with parafor- maldehyde (75.0 mmol) dissolved in 100 ml of THF at À78 C, and stirred 13 hours at ambient temperature. Water was then added, the solution extracted with diethyl ether, and the pH of the aqueous layer lowered to 2 using 1M hydrochloric acid. The mixture was re-extracted with CCl3H, and the organic layer dried using anhydrous MgSO4. The low-boiling fraction was distilled under reduced pressure and 4.21 g of residue isolated. The CH2Cl2-insoluble fraction was collected, and the product isolated in 80.5% yield. 2. Preparation of Poly(9-Hydroxymethyl-9-Fluorene Carboxylic Acid) The Step 1 product (0.21 mmol) and (CF3SO3)2Sn (0.9 mg) were introduced into a reaction vessel; the mixture was shaken until uniform then heated for 3 hours at 180 C. The mixture was then separated by decantation into THF where 47.1 mg dissolved and 2.20 mg was insoluble. The THF-soluble portion was then re- dissolved in 3 ml THF and treated with diazomethane dissolved in 1 ml diethyl ether and stirred for 5 hours at ambient temperature. The mixture was concentrated and the residue divided into a methanol-soluble part (8.10 mg) and methanol- insoluble part (34.9 mg). The methanol-insoluble part was divided into a THF- soluble part (14.19 mg) and a THF-insoluble part (20.64 mg). The part that was insoluble in methanol but soluble in THF was identified as the product with a Mn of roughly 1.0 Â 105 daltons. DERIVATIVES 9-Hydroxy-9-fluorene carboxylic acid was also prepared. HO2C OH 1 H-NMR (CDCl3) d: 7.78 (d, J ¼ 7.5, 2H), 7.67 (d, J ¼ 7.5, 2H), 7.46 (dd, J ¼ 7.0, 2H), 7.54 (dd, J ¼ 8.0, 2H), 4.02(s, 4H). 156 Polyester Having p-Conjugated Group in Side Chain and Charge Transporting Material
    • TESTING Donor-Acceptor Testing The Step 2 product (2.98 mg) and 1,3-dinitrobenzene (1.80 mg) were dissolved in 10 ml of THF and then diluted 100 times. This stock solution was used for absorption spectrum measurements in a 10 mm quartz cell at ambient temperature. The intensity was 0.140 at 242 nm, which changed to 0.108 after the addition of 1,3-dinitrobenzene. By changing the 1,3-dinitrobenzene concentration from 2.5 Â 10À5 M and 5.0 Â 10À5 M at 242 nm, the absorption intensity changed from to 0.077 and 0.059, respectively. This hypochromic effect demonstrated that the fluorene ring of the polymer and 1,3- dinitrobenzene formed a stacked complex. NOTES 1. Donor-acceptor fluorene complexes were also prepared by Ishizawa [1] using the poly(9-fluorenyl methacrylate), (I), substrate. a OO (I) 2. Fluorene monomers, (II), previously prepared by the author [2] then polymer- ized and, had a light emission peak at 400 nm, which was different from the polymer light emission peak wave length of 305 nm. (II) References 1. H. Ishizawa et al., US Patent 7,012,123 (March 14, 2006) 2. T. Nakano et al., US Patent Application 2004-0132963 (July 8, 2004) Notes 157
    • D. Electroconductive Title: Halogenated Thiophene Monomer for the Preparation of Regioregular Polythiophenes Author: C. Werner et al., US Patent 7,262,264 (August 28, 2007) Assignee: Honeywell International, Inc. (Morristown, NJ) SIGNIFICANCE Poly(3-hexyl)thiophene has been prepared in 93.5% head-to-tail regioregularity by reacting 5-bromo-2-chloro-3-hexylthiophene with magnesium, t-butylmagnesium chloride, 1,2-bis(diphenylphosphino)ethane nickel(II) chloride, and triethylpho- sphite. Potential applications for these conducting polymers include field-effect transistors, sensors, capacitor coatings, battery electrodes, and light-emitting diodes. REACTION a S C6H13 Br Cl S C6H13 i Note 1 i: 2-Methyltetrahydrofuran, magnesium, t-butylmagnesium chloride, triethylpho- sphite, 1,2- bis(diphenylphosphino)ethane nickel(II) chloride 158
    • EXPERIMENTAL Preparation of Poly(3-Hexyl)Thiophene with a 93.5% 5-Bromo-2-chloro-3-hexylthiophene (0.0355 mol) was added over a period of 30 minutes to a mixture consisting of 75 ml of 2-methyltetrahydrofuran, magnesium (0.0355 mol),and0.15 mlof1Mt-butylmagnesiumchloridesolutioninTHFat60 C to 70 C. The mixture was stirred for 90 minutes at 70 C. It was then cooled to 60 C and treated with a suspension of 1,2-bis(diphenylphosphino)ethane nickel(II) chloride (0.177 mmol) in 12.5 ml of 2-methyltetrahydrofuran for over 30 minutes. The mixture was stirred an additional 3 hours at 80 C and further treated with triethylphosphite (3 mmol)andstirredfor30minutesat80 C.Themixturewasthenconcentratedandthe residue dissolved in 10 ml of toluene. This solution was poured into 100 ml of EtOAc, which created a suspension, and the suspension was stirred for 30 minutes at 80 C. The cooled suspension was filtered, the residue washed twice with 20 ml of EtOAc, and the product isolated in 81% yield having a Mn of 19,543 daltons with a Tm of 224 C. DERIVATIVES Only the Step 1 derivative was prepared. NOTES 1. Poly(3-dodecylthiophene) having an 99% regiospecificity was prepared in 80% yield by McCullough [1] using 2,5-dibromo-3-dodecylthiophene with catalytic amounts of 1,3-diphenylphosphinopropane nickel(II) chloride. In a subsequent investigation by Koller [2], regiospecificity exceeding 90% for poly(3-hexyl) thiophene was obtained using 2,5-di-bromo-3-hexylthiophene with catalytic amounts of 1,3-diphenylphosphinopropane nickel(II) chloride. 2. Leclerc [3] prepared regioregular and water soluble polythiophenes by oxidiz- ing thiophene derivatives with iron (III) chloride which were then used as optical and electrochemical detectors of double-stranded oligonucleotides. aS O N(C2H5)3 S O N(C2H5)3 i ++ i: Dimethyl ether, iron (III) Chloride UV (CHCl3): max ¼ 450.79 nm; film: 521, 550, 602 nm Notes 159
    • 3. Regioregular poly(5,50 -(4,40 -dihexyl-2,20 -bithiazole)), (I), was prepared by Curtis [4] and used in electronic applications such as LED’s, rechargeable batteries, and electrolytic capacitors. S N N S C6H13 C6H13(I) n References 1. R.D. McCullough et al., US Patent 6,166,172 (December 26, 2000) 2. G. Koller et al., US Patent Application 2005-0080219 (April 14, 2005) 3. M. Leclerc et al., US Patent 7,083,928 (August 1, 2006) 4. D.M. Curtis et al., US Patent 5,536,808 (July 16, 1996) 160 Halogenated Thiophene Monomer for the Preparation of Regioregular Polythiophenes
    • Title: Electrically Conductive Polymeric Biomaterials, the Process for Their Preparation and Use in Biomedical and Health Care Fields Author: S. Panero et al., US Patent 7,253,152 (August 7, 2007) Assignee: Fidia Advanced Biopolymers, s.r.l. (Abano Terme, IT) SIGNIFICANCE Polypyrrole composite biomaterials having electrically conductive properties have been prepared using hyaluronic acid or its sodium salt by galvanostatic and potentio- static methods. These agents are useful for preparing medical devices such as nerve and bone regeneration materials. REACTION a H N H N i Note 1 EXPERIMENTAL Preparation of Polypyrrole Using Hyaluronic Acid Conductive polymer films based on polypyrrole and hyaluronic acid were synthesized usingbothagalvanostaticmethod––byapplyingcurrentataconstantintensityranging between 0.5 and 10 mA for periods varying between 60 and 150 minutes––and a potentiostatic method with the constant potentials ranging between 0.3 and 0.75 V 161
    • versus SCE. The first method was the preferred method, however, because it produced films with even surfaces, thereby reducing reaction times. Polymer films were synthesized in aqueous solutions using concentrations of pyrrole varying from between 0.05M and 0.3M and concentrations of hyaluronic acid or sodium hyalur- onate varying from between 0.9M and 5M. POLYMERIZATION SCOPING NOTES 1. Oxidized polypyrrole, (I), was used by Shastri [1] to induce biological activities within stem cells by electromagnetic stimulation. H N N H H N N H ... ... (I) 2. Hyaluronic acid succinylate, (II), was prepared by Rivarossa [2] by reacting succinic anhydride with sodium hyaluronate and the material used in either venous and arterial vascular anastomoses. This included creating a physical hemostatic barrier to prevent scar tissue formation or to prevent post surgical adherence of the vessels to the surrounding tissues. Laredo [3] prepared TABLE 1. Effect of experimental conditions on the film thickness of polypyrrole. Entry Pyrrole (M) Hyaluronic Acid (mg/ml) Synthetic Method Film Thickness (mm) 1 0.1 2 Potentiostatic 0.33 V ¼ 720 mV vs. SCE, 0.19C 2 0.1 2 Galvanostatic 4.2 Total charge ! 1C 3 0.1 2 Galvanostatic 8.4 Total charge ! 5C 4 0.1 2 Galvanostatic 18 Total charge ! 6.24C 5 0.2 4 Galvanostatic 12 Total charge ! 6C 162 Electrically Conductive Polymeric Biomaterials
    • musculoskeletal tissue repair agents consisting of tetraalkylammonium bromide hyaluronic acid salts, (III). O O OHO NH O OH HO OH O (III) a O N(C4H9)4 O O OHO NH O OH HO O O OH (II) CO2H a O 3. Heteroatom biodegradable and electrically conducting polymers, (IV), effec- tive for tissue engineering applications were prepared by Schmidt [4] and used in spinal cord regeneration, wound healing, and bone repair. a H N S H N O O O O O O O O (IV) References 1. V. Shastri et al., US Patent 6,569,654 (May 27, 2003) 2. A. Rivarossa et al., US Patent 7,202,230 (April 10, 2007) 3. W.R. Laredo et al., US Patent 7,091,191 (August 15, 2006) 4. C.E. Schmidt et al., US Patent 6,696,575 (February 24, 2004) Notes 163
    • Title: Dibenzodiazocine Polymers Author: V. J. Lee et al., US Patent 7,238,771 (July 3, 2007) Assignee: Solvay Advanced Polymers, L.L.C. (Alpharetta, GA) SIGNIFICANCE Polydibenzodiazocine materials have been prepared by polymerization of dibenzoyl- benzidine derivatives using toluene sulfonic acid These agents are useful as electrically conducting artificial muscles. REACTION a NO2 Br O N NH2 Br O NH2 O NH2 O N N i iiiii iv Br i: THF, methanol, potassium hydroxide, phenylacetonitrile ii: Acetic acid, iron 164
    • iii: bis(1,5-Cyclooctadiene)nickel(0), DMF, hydrochloric acid iv: Toluene sulfonic acid monohydrate, 1,3-dichlorobenzene EXPERIMENTAL 1. Preparation of Heterocyclic Intermediate A glass reactor was charged with 4-bromonitrobenzene (0.126 mol) dissolved in 300 ml ofTHF/methanol,1:2,respectively,and thentreated withpotassiumhydroxide (2.64 mol), phenylacetonitrile (0.126 mol), and 300 ml of methanol at 0 C. The mixture was stirred for 4.5 hours at 0 C poured into 1 liter of water. The resulting precipitate was collected by filtration, and purified by re-crystallization using methanol, and the product was isolated in 59.4% yield. 2. Preparation of 5-Bromo-2-Aminobenzophenone The Step 1 product (0.10 mol) was dissolved in 200 ml of acetic acid at 80 C and then treated with 50 ml of water and iron powder (0.5 mol) in 10 portions over a two-hour period. The mixture was stirred at 80 C for an additional hour and then cooled to ambient temperature. It was diluted with 1 liter of diethyl ether and extracted with 1 liter of water. The organic layer was separated, dried, concen- trated, and re-crystallized from methanol, and the product was isolated in 81% yield. 3. Preparation of 3,30 -Dibenzoylbenzidine A slurry of bis(1,5-cyclooctadiene)nickel(0) (81.5 mmol) in 200 ml of DMF was added to the Step 2 product (54 mmol) in 150 ml of DMF. The mixture was stirred for 15 minutes at the ambient temperature, 90 minutes at 42 C, and then poured into 500 mlof2%aqueoushydrochloricacid.ItwasextractedwithCH2Cl2,andtheorganic layer was filtered, dried, and concentrated. The residue was purified by chromatogra- phy, and the product was isolated in 50% yield. 4. Preparation of Polydibenzodiazocine A round-bottomed flask fitted with a Dean–Stark trap was charged with the Step 3 product (5 mmol), toluene sulfonic acid monohydrate (1 mmol), and 20 ml of 1,3-dichlorobenzene and then refluxed 2 hours. The mixture was cooled to ambient temperature, neutralized with 0.5 ml of triethylamine, precipitated in 75 ml of methanol, dried, and 0.77 g of product was isolated having a Mn of 12,000 daltons. Experimental 165
    • DERIVATIVES NOTES 1. Mono- and dibendodiazocine analogues, (I) and (II), were previously prepared by Milkowski [1] and Johnson [2], respectively, and used in pharmaceutical applications. N H H N (II) N N N N Cl Cl (I) TABLE 1. Step 4 polydibenzodiazocine derivatives prepared according to the present invention and corresponding yields and number average molecular weights. Entry Structure Yield (%) Mn (daltons) 2 aN NO 10 29,000 and 5,000,000 (bimodal) 5 aN N O 91 90,000 16 a N N O 54 61,000 166 Dibenzodiazocine Polymers
    • 2. Electroactive polymer and rolled electroactive polymers having dielectric constants between 2.5 and about 12 were used by Kornbluh [3] and Rosenthal [4], respectively, to prepare artificial muscles. References 1. W. Milkowski et al., US Patent 4,243,585 (January 6, 1981) 2. R.A. Johnson et al., US Patent 4,447,607 (May 8, 1984) 3. R.D. Kornbluh et al., US Patent 7,211,937 (May 1, 2007) 4. M.A. Rosenthal et al., US Patent 7,233,097 (June 19, 2007) Notes 167
    • Title: Redox-Active Polymer and Electrode Comprising the Same Author: T. Mitani et al., US Patent 7,214,762 (May 8, 2007) Assignee: Japan Science and Technology Agency (Kawaguchi-shi, JP) SIGNIFICANCE A new high-energy density battery consisting of a redox-active polymer has been prepared that is effective at low temperatures. The polymer was prepared by the condensation of N,N0 -1,4-phenylene-bis-thiourea with phenylene-1,4-diisothiocya- nate and is suitable as a cathode for secondary lithium batteries. REACTION a a H2N N H S H N NH2 S H2N N S N NH2 S N H N S N H N S N H S H N S i ii iii N N S N N SN S N S N Note 1 i: NMP, ethanol, benzyl chloride ii: Phenylene-1,4-diisothiocyanate, THF, benzene iii: Oxidant (unspecified) 168
    • EXPERIMENTAL 1. Preparation of N,N0 -1,4-Phenylene-bis-Thiourea-S,S0 -Benzyl Ether A reaction flask charged with N,N0 -1,4-phenylene-bis-thiourea (230 mg) was dis- solved in a mixed solution of 4 ml apiece NMP and ethanol and then treated with benzylchloride(270 mg)andrefluxedfor30minutes.Thesolutionwascooled,treated withasolutionof10 mlwatercontainingNaOH(80 mg),andthenextractedwith40 ml of diethyl ether. The extract wasdried with MgSO4,filtered, concentrated, and 400 mg of product were isolated. 2. Preparation of S-Benzylized Poly(Phenyl-2,4-Dithiobiuret) The Step 1 product (406 mg) was dissolved in 10 ml apiece THF and benzene and then treated with phenylene-1,4-diisothiocyanate (200 mg) dissolved in 5 ml apiece THF and benzene. This mixture was refluxed for 3 days and filtered, the solid rinsed with acetone, and 100 mg of product isolated. 3. Preparation of Poly(1,2,4-Dithiazolium-Diaminobenzene) The Step 3 product was prepared by reacting the Step 2product with an with oxidant or electrochemically. DERIVATIVES Only the Step 3 product was prepared. NOTES 1. A sample electrode was prepared by grinding the polymeric Step 2 product in a mortar with acetylene black and then adding polyvinylidene fluoride and mixing with DMF. The mixture was next printed on a titanium foil and heated for 3 hours at 80 C. 2. High-energy density batteries having superior stability were prepared Morioka [1] using polynitroxyl radicals components, (I). Sulfur, (II), and boron, (III), free radical analogues prepared by Bannai [2] were also effective as secondary battery components. N N OO .. n (I) S S B .. (II) (III) Notes 169
    • 3. Kofinas [3] prepared a polymeric nanoscale solid-state battery system, (IV), consisting of electrochemical cells connected in series, that was used as a secondary battery. N Co N O O t-C4H9 t-C4H9 O O O OH O O Li(IV) a b c 4. Indole trimer, (V), prepared by Nabuto [4] was used as an electrode component in an electrochemical cell. N H NH NH (V) 5. Nakanishi [5] prepared siloxane-modified cyclic carbonates, (VI), that when combined with a nonaqueous solvent and an electrolyte salt formed a non- aqueous electrolytic solution that was used to construct a secondary battery having improved temperature and cycle properties. Si O Si O Si 10 (VI) O OO 170 Redox-Active Polymer and Electrode Comprising the Same
    • References 1. Y. Morioka et al., US Patent 7,122,277 (October 17, 2006) 2. Y. Bannai et al., US Patent 7,045,248 (May 16, 2006) 3. P. Kofinas et al., US Patent 7,063,918 (January 20, 2006) 4. T. Nobuta et al., US Patent Application 2007-0095656 (May 3, 2007) 5. T. Nakanishi et al., US Patent Application 2007-0059597 (March 15, 2007) Notes 171
    • Title: Use of Sulphonic, Phosphonic and Phosphoric Acids as Dopants for Polyaniline and for Conductive Polyaniline-Based Composite Materials Author: A. Pron et al., US Patent 7,101,495 (September 5, 2006) Assignee: Commissariat A L’Energie Atomique (Paris, FR) SIGNIFICANCE Polyaniline in the emeraldine base state doped with di(butoxyethoxyethyl) ester of sulphosuccinic acid had high film conductivity and an elongation at break of 195%. This high flexibility is particularly needed for elastomer coatings to impart elasticity on conductive materials. 172
    • REACTION NH2 HN N N OH OH O O HO3S O O O O HO3S O O O O Intermediate HN N N O O O O SO3HO O O O Dopant Polyaniline i ii iii a a i: Lithium chloride, hydrochloric acid, ethanol, ammonium persulfate, iron (II) chloride ii: 2-(2-Butoxy-ethoxy)ethanol, water iii: 2,2-Dichloroacetic acid EXPERIMENTAL 1. Preparation of Polyaniline (Emeraldine Base) A mixture at À27 C consisting of freshly distilled aniline (0.1097 mol), 85 ml of 3M HCl, 95 ml of ethanol, and LiCl (16 g) was treated with ammonium persulphate (0.0274 mol), 60 ml of 2M HCl,and LiCl (8 g) also at À27 C. The mixturewasreacted for roughly 2 hours while the potential of the reaction mixture was controlled by a standard calomel electrode. It was then treated with FeCl2 (0.0183 mol), LiCl (5 g), and 50 ml of 2M HCl. After an additional hour the reaction was terminated, and the polymer could be isolated by either filtration or by centrifuging. It was then washed withdistilledwater,dried,andconvertedtotheemeraldinesaltusing2MHCl.Thissalt was then converted to the emeraldine base by treatment with 2 liter of 0.3 M aqueous Experimental 173
    • ammonia solution for 48 hours. The product was washed with 5 liter of distilled water followed by 2 liter of methanol and then dried. The fractions with low molecular weights were removed by extracting the polymer with chloroform in a Soxhlet apparatus. The intrinsic viscosity of the emeraldine base as prepared was 2.5 dl/g in a 0.1 wt% solution in 96% sulphuric acid. 2. Preparation Di(Butoxyethoxyethyl) Ester of Sulphosuccinic Acid Dopant A 70 wt% aqueous solution of sulphosuccinic acid (50.5 mmol) was mixed with 2-(2- butoxy- ethoxy)ethanol (151.5 mmol) at 110 C under a constant stream of nitrogen. The material was dried under vacuum at 70 C, and the product was isolated. 3. Preparation of a Self-supported and Drawable Film of Doped Polyaniline The Step 1 product (111 mg) and the Step 2 product (302 mg) were mixed in 2,2- dichloroaceticacid(22.2 g)andstirreduntilnofurther changewasobservedintheUV- Vis-NIR spectrum. Self-supported films were prepared by pouring about 1 ml onto a polypropylene substrate and removing the solvent by evaporation at 45 C. The film was detached from its substrate and dried under vacuum; the film’s thickness was on the order of 20 to 30 mM. The film’s conductivity was measured at 90 S/cm by the 4-contact method at ambient temperature. The manually drawn film exhibited an elongation at break of 195% at ambient temperature. DERIVATIVES NOTES 1. Olinga [1] prepared and used the aromatic diester dopant, (I), with polyaniline and prepared flexible films having film conductivities between 100 to 200 S/cm. TABLE 1. Effect of selected dopants on the film conductivity and elongation at break for polyaniline (emeraldine base). Dopant Elongation at Break (%) Film Conductivity (S/cm) Sulphosuccinic acid, di(2-ethylhexyl) ester 36 115 Camphorsulphonic acid 2 230 2-Acrylamido-2-methyl-1-propanesulphonic acid, 115 90.5 Sulphosuccinic acid, di(butoxyethyl) ester 195 125 Note: All doping was conducted in 2,2-dichloroacetic acid with 20 to 30 mM films prepared on a polypropylene substrate. 174 Use of Sulphonic, Phosphonic and Phosphoric Acids as Dopants
    • Nanotubes using lignosulfonic acid-doped polyaniline were prepared by Vis- wanathan [2]. O O O O C2H5 C2H5 HO3S (I) 2. Wang [3] prepared chiral polyaniline by amidating with the chiral dopant acid, (1R)–[À]–camphor sulfonic acid, (II), which was used in nanomaterials having lengths of between 1 to 5 microns. When Wang [4] polymerized either aniline D- or L-tartrate, the corresponding water-soluble polyaniline derivative was isolated. The derivatives were readily doped with ammonium hydroxide (green) or hydrochloric acid (blue). Water-soluble polyaniline was also pre- pared by Angelopoulos [5] by polymerizing aniline in the presence of the polymeric dopant, polystyrene sulfonic acid. a O3S O NH HN NH (II) 3. Lee [6] observed that when polyaniline or polypyrrole were N-functionalized with N-t-butoxy carbonyl, these materials displayed enhanced physical and mechanical properties with higher solubility and electrical conductivity than the corresponding nonfunctionalized counterparts. Notes 175
    • References 1. T. Olinga et al., US Patent 7,014,794 (March 21, 2006) 2. T. Viswanathan et al., US Patent 7,063,808 (June 20, 2006) 3. H.-L. Wang et al., US Patent 7,074,887 (July 11, 2006) 4. H-L. Wang et al., US Patent 7,074,887 (July 11, 2006) 5. M. Angelopoulos et al., US Patent 7,166,241 (January 23, 2007) 6. S.-H. Lee et al., US Patent 7,067,229 (June 27, 2006) 176 Use of Sulphonic, Phosphonic and Phosphoric Acids as Dopants
    • Title: 3,4-Alkylenedioxy-Thiophene Copolymers Author: B. Groenendaal et al., US Patent 6,995,223 (February 7, 2006) Assignee: Agfa-Gevaert (Mortsel, BE) SIGNIFICANCE An aqueous dispersion consisting of polyethylene glycol containing a (2,3-dihydro- thieno[3,4-b][1,4]dioxin-2-yl)-methanol terminus has been prepared. This material exhibited electrical conductivities, visible light transmittances, and good processability. REACTION a S OO HO2C CO2H OH S OO OH S OO O O iii Note 1,2 Note 3 i: DMAc, copper (II) dichromate, quinoline ii: p-Toluenesulfonyl chloride, pyridine, polyethylene oxide, hydrochloric acid EXPERIMENTAL 1. Preparation of (2,3-Dihydro-Thieno[3,4-b][1,4]Dioxin-2-yl)-Methanol A reactionvessel was charged with 2-hydroxymethyl-2, 3-dihydro-thieno[3,4-b][1,4] dioxine-5,7-dicarboxylicacid(0.184 mol)dissolved in500 mlDMAcandthentreated with copper dichromate (8.6 g) and 15 drops of quinoline. This mixture was stirred for 2 hours at 150 C and cooled to the ambient temperature. It was poured into EtOAc, and the catalyst was removed by filtration. The filtrate was washed with acidic water and brine, then concentrated, and the product was isolated by distillation at 115 C to 120 C at 0.05 mmHg. 177
    • 2. Preparation of Polyethylene Oxide Substituted (2,3-Dihydro-Thieno[3,4-b] [1,4]Dioxin-2-yl)-Methanol p-Toluenesulfonyl chloride (44 mmol) was dissolved in 20 ml of pyridine and treated dropwise with mexthoypolyethylene oxide (Mw ¼ 750 daltons; 20 mmol) dissolved in 30 ml of pyridine. The mixture was stirred for 2 hours at 25 C to 30 C and poured into ice-watercontaininghydrochloricacid.ThisaqueousphasewasextractedwithCH2Cl2, after which the combined organic fractions werewashed with 1 M of sodiumhydrogen carbonate solution. Final purification was done by column chromatography using CH2Cl2/ethanol and polyethylene oxide tosylate isolated. The Step 1 product (5.8 mmol) was dissolved into 25 ml of THF and treated with sodium hydride (0.25 g) while stirring for 30 minutes and further treated with methoxypolyethylene oxide tosylate (5.3 g). The mixture refluxed for 2 hours, cooled to the ambient temperature, and poured into ice-water containing a few drops of concentrated hydrochloric acid. This mixture was extracted using CH2Cl2, and combined extracts were washed with a 1 M aqueous solution of sodium hydrogen carbonate and brine, dried, and concentrated. The residue was purified by column chromatography using CH2Cl2/methanol, 95:5, respectively, and the product was isolated. DERIVATIVES The following derivatives were prepared: S OO O O 3 S OO O CO2H S OO O SO3Na NOTES 1. Urethane derivatives, (I), of the Step 1 product were prepared by Reuter [1] and used in optical signal processing. S OO O NH O C4H9 (I) 178 3,4-Alkylenedioxy-Thiophene Copolymers
    • 2. Additional Step 1 decarboxylation transformation methods are provided by Reynolds [2]. 3. Poly(3,4-alkylenedioxythiophenedioxide), (II), derivatives were prepared by the author [3] and used as an electroconductive layer in a light-emitting diode. a S O2 OO O O (II) 4. Tahon [4] prepared poly(3,4-alkoxythiophene), (III), derivatives to enhance the conductivity in nonaqueous printing. The process for preparing aqueous and nonaqueous solution dispersions of this agent are described by Louwet [5]. aS OO (III) References 1. K. Reuter et al., US Patent 6,852,831 (February 8, 2005) 2. J.R. Reynolds et al., US Patent 6,425,966 (March 11, 2004) 3. B. Groenendaal et al., US Patent 6,927,298 (August 9, 2005) and US Patent 7,105,620 (September 12, 2006) 4. J.-P. Tahon et al., US Patent 7,223,357 (May 29, 2007) and US Patent 7,122,130 (October 17, 2006) 5. F. Louwet et al., US Patent 6,425,966 (May 23, 2006) Notes 179
    • E. Electroluminescence Title: Electroactive Polymer, Device Made Therefrom and Method Author: K. E. Litz et al., US Patent 7,217,774 (May 15, 2007) Assignee: General Electric Company (Niskayuna, NY) SIGNIFICANCE High and low molecular weight electroactive polymers containing pendant 2-(7- benzothiazolyl-9,90 -dioctylfluorene) units have been prepared. These materials dis- play electroluminescent properties that are useful in electronic devices. REACTION a C8H17 C8H17 S N Br Br C8H17 C8H17 OHC Br C8H17 C8H17 Br C8H17 C8H17 S N C8H17 C8H17 S N iii iiiiv Note 1 i: Butyl lithium, THF, dimethylformamide ii: 2-Aminothiophenol, dimethyl sulfoxide 180
    • iii: Cesium fluoride, tris(dibenzylideneacetone)dipalladium, tri-t-butylphosphine, tributyl(vinyl)-stannane, tetraglyme, toluene iv: Benzoyl peroxide, benzene EXPERIMENTAL 1. Preparation of 2-Bromo-7-Formyl-9,90 -Dioctylfluorene Butyl lithium (0.116 mol) was added dropwise to a solution of 2,7-dibromo-9,90 - dioctylfluorene (0.0918 mol) in 200 ml of THF at À78 C over 45 minutes and then stirred for an additional 30 minutes. The mixturewas treated with dimethylformamide (0.1539 mol) at À78 C, warmed to ambient temperature over 4 hours, and concen- trated. The yellow residue was dissolved in 130 ml of hexanes/xylenes, 10:3, respec- tively, and then quenched with 5 ml 20% hydrochloric acid. After separating from the aqueous fraction, the organic layer was neutralized with NaHCO3, filtered, dried over MgSO4, and decolorized with activated carbon (10 g). The final solution was filtered and concentrated, yielding a colorless solid with a faint greenish hue. The light greenishcolorwasremovedbysuspensioninmethanol,andtheproductwasisolatedin 83% yield as a colorless microcrystalline solid with MP ¼ 48–50 C. 2. Preparation of 2-Bromo-7-Benzothiazolyl-9,90 -Dioctylfluorene The Step 1 product (0.0603 mol) and 2-aminothiophenol (0.0693 mol) was dissolved in 80 ml of dimethyl sulfoxide and heated for 1 hour at 198 C and then quenched by pouring into 100 ml of cold water. The aqueous layer was decanted from the bright yellow oil and extracted twice with 25 ml of pentane. The organic layers were combined and quenched with 20 ml of 20% acetic acid. The layers were separated and the acidic solution extracted twice with 25 ml pentane. The organic fractions were combined and neutralized by washing twice with 100 ml of saturated NaHCO3 solution. The basic solution was extracted twice with 25 ml of pentane, and the organic fractions were combined and dried over MgSO4. The mixture was decolor- ized with activated carbon, leaving a bright yellow solution. The solution was then concentrated and a yellow residue purified by column chromatography using alumina with xylenes/cyclohexane, 4:1, respectively, followed by re-crystalliza- tion in methanol. The product was isolated in 53% yield as a colorless crystalline solid with MP ¼ 79–81 C. 3. Preparation of 2-Vinyl-7-Benzothiazolyl-9,90 -Dioctylfluorene A mixture consisting of the Step 2 product (0.0083 mol), cesium fluoride (0.0175 mol), tris(dibenzylideneacetone)dipalladium (0.041 mmol), tri-t-butylphosphine (0.123 mmol), and tributyl(vinyl)stannane (0.0087 mol) was dissolved in a mixture of tetraglyme (6 g) and 7 ml of toluene and then heated for 14 hours at 90 C in a sealed 30-ml vial. Once cooled to ambient temperature, a blue-green precipitate formed, Experimental 181
    • which was extracted with 20 ml of diethyl ether and filtered. The filtrate was decolorized with activated charcoal (2.0 g) and dried using 4 A  molecular sieves (2.0 g). The solution was then concentrated, and the residual oil was added dropwise intodryacetonitrileleavinga bright yellow solid. Thebright yellow solidwasextracted twice with 10 ml of diethyl ether leaving an insoluble white solid. The ether extract was concentrated, and the product was isolated in 61% yield in greater than 95% purity. 4. Preparation of Poly(2-Vinyl-7-Benzothiazolyl-9,90 -Dioctylfluorene) The Step 3 product (0.2 g) was combined with benzoyl peroxide (2.8 mg) in 1 ml of benzene, and the mixture was heated to 66 C overnight. The polymer was then precipitated by pouring into methanol, filtered, and vacuum dried. The product was isolated as a solid with a Mw of 8600 daltons, Mn of 5100 daltons, and a polydispersity index of 1.68. DERIVATIVES Poly(styrene-co-2-vinyl-7-benzothiazolyl-9,90 -dioctylfluorene) was also prepared. C8H17 C8H17 S N ba 1. Electrical Activity Testing Fluorescence quantum yields were determined using coumarin 540 in EtOAc as a reference. UV absorption maxima were determined in chloroform; HOMO and LUMO values were determined by cyclic voltammetry in acetonitrile/tetrabutylam- monium fluoroborate solution. Optical and electrical properties of each derivative are provided in Table 1. 182 Electroactive Polymer, Device Made Therefrom and Method
    • NOTES 1. Chen [1] prepared imidazole-fused phenanthroline derivatives, (I), that were effective as organic light-emitting devices. N N N N (I) 2. A highly efficient green light-emitting electroluminescent device was prepared by Brunner [2] using a carbazole trimer as the charge-transporting conjugated donor, (II). The corresponding electroactive polymeric carbazole, (III), was previously prepared by Leclerc [3]. NN N OCH3 OCH3 H3CO (II) TABLE 1. Summary of electroactive properties of poly(2-vinyl-7-benzothiazolyl-9, 90 -dioctylfluorene) and poly(styrene-co-2-vinyl-7-benzothiazoly-9,90 -dioctyl-fluorene). Polymer Homo Polymer Styrene Copolymer Lamda (abs), nm 362 422 Lamda (PL), nm 403 425 HOMO, eV 6.02 5.9 LUMO, ev 3.08 2.63 E gap, eV 2.94 3.27 Quantum yield, % 59 97 Mw (daltons) 8,600 114,600 PDI 2.01 2.3 Note: Although both derivatives exhibited good blue luminescence, quantum yield differences were observed. Notes 183
    • a N C8H17 (III) 3. Fryd [4] prepared organic emitting materials consisting of polymeric-metal complex salts, (IV). Their preparation is illustrated in below. 4N O O F3C F3C O Eu O F3C F3C NH+ Eu(NO3)3 (IV) ............ ............ 4. Electroluminescent polymers containing grafted 1,3,4-oxadiazoles, (V), were prepared by Roberts [5] and were significantly red-shifted from the corre- sponding monomer. These agents were used in making organic light-emitting diodes. O N N OC8H17 15 (V) References 1. J.P. Chen et al., US Patent 7,179,542 (February 20, 2007) 2. K. Brunner et al., US Patent Application 20060051611 (March 9, 2006) 3. M. Leclerc et al., US Patent 6,833,432 (December 21, 2004) 4. M. Fryd et al., US Patent 7,060,372 (June 13, 2006) and US Patent 6,869,693 (March 22, 2005) 5. R.R. Roberts et al., US Patent 7,094,902 (August 22, 2006) 184 Electroactive Polymer, Device Made Therefrom and Method
    • Title: Polymers and Oligomers, Their Synthesis, and Electronic Devices Incorporating the Same Author: A. J. Epstein et al., US Patent 7,071,290 (July 4, 2006) Assignee: The Ohio State University (Columbus, OH) SIGNIFICANCE Conjugated and nonconjugated block copolymers and oligomers have been prepared that have electroluminescing properties. The materials consist of polyaromatics and heteroaromatics and were prepared in a single synthetic step. REACTION O O OCH3 OHC OCH3 H3CO CHO H3CO O O OCH3 O OCH3 H3CO H3CO N OCH3 OCH3 66 i a i: 1,4-Pyridylylenebis(triphenylphosphonium), THF, potassium t-butoxide EXPERIMENTAL 1. Preparation of Polyaromatic Ether Containing a Conjugated Pyridine To a stirred solution containing the dialdehyde (1.12 mmol) and 1,4-pyridylylenebis (triphenyl-phosphonium)(1.12 mmol)dissolvedin150 mlofTHFwasaddeddropwise 10 ml of 2 M potassium t-butoxide dissolved in THF, and the mixture refluxed 2 hours. The solution was then concentrated and the residue dissolved in CCl3H. The polymer was precipitated in methanol and purified by Soxhlet extraction with methanol for 12 hours. The purified polymer was isolated in 92% yield as a light-yellow solid. 1 H-NMR (CDCl3) d 1.4 (m, 4H), 1.6 (t, 4H), 3.7 (s, 12H), 3.9 (t, 4H), 6.7 (s, 4H), 7.0 (t, 1H), 7.1 (d, 4H), 7.5 (d, 2H). 185
    • DERIVATIVES TABLE 1. Product conversions for selected electroluminescing polyaromatic and heteroaromatic polymer agents. Entry Structure Yield (%) 2 a 6 O O OCH3 O H3CO H3CO N OCH3 OCH3 H3CO 90 13 a OCH3 OCH3 OCH3 H3CO H3CO H3CO OO 6 88 14 a OCH3 OCH3 H3CO OO 6 90 15 a OCH3 H3CO OO 6 90 16 a OCH3 OCH3 H3CO H3CO OO 6 88 Note: H-NMR characterization data provided by the author. 186 Polymers and Oligomers, Their Synthesis, and Electronic Devices Incorporating the Same
    • NOTES 1. In an earlier investigation by the author [1] electroluminescing polymers were designed to remain in a de-aggregated state to prevent the redshifting. This was achieved by incorporating rotaxanes into experimental polymeric agents, (I). TABLE 2. Step 1 product yields for conjugated monomeric analogues effective as electroluminescing agents. Entry Structure Yield (%) 4 N N 59 5 N N OCH3 H3CO 49 6 N N 52 10 N N OCH3 H3CO 46 12 50 Note: H-NMR characterization data provided by author. Notes 187
    • (H2CCH2O)6 (I) Rotaxane 2. Biphenyl derivatives consisting of both carbazole, (II), and indolyl components were prepared by Takiguchi [2] and used as light-emitting agents; tricarbazole triphenylamine derivatives, (III), prepared by Iwakuma [3] were also effective as light-emitting agents. N N (II) N N N N (III) 3. Okada [4] determined that polymer materials having an arylamine repeating unit containing p-conjugation on its main chain, (IV), had excellent lumi- nous properties and were particularly useful as organic electroluminescence elements. N C6H13 S S (IV) a 188 Polymers and Oligomers, Their Synthesis, and Electronic Devices Incorporating the Same
    • 4. Polymers containing benzotriazole repeating units, (V), which had high glass transition temperatures and good thermal stability, were fabricated into coat- ings and films by Rogers [5] and used in electroluminescent devices. C8H17 C8H17 H3CO C8H17 C8H17 (V) a 5. Egawa [6] prepared light-emitting stilbene derivatives, (VI), having a large energy gap suitable for use as a host material in a light-emitting layer. a a (VI) References 1. A.J. Epstein et al., US Patent 6,962,757 (November 8, 2005) 2. T. Takiguchi et al., US Patent Application 2007-0057250 (March 15, 2007) 3. T. Iwakuma et al., US Patent Application 2007-0054151 (March 8, 2007) 4. T. Okada et al., US Patent Application 2007-0048637 (March 1, 2007) 5. J. Rogers et al., US Patent Application 2007-0043204 (February 22, 2007) and US Patent Application 2005-0175856 (August 11, 2005) 6. M. Egawa et al., US Patent Application 2007-0100180 (May 3, 2007) Notes 189
    • Title: Process for Preparing Poly(Arylene Ethers) with Pendant Crosslinkable Groups Author: B. Chen et al., US Patent 7,038,004 (May 2, 2006) Assignee: Lumera Corporation (Bothell, WA) SIGNIFICANCE Two crosslinkable perfluorinated bisphenol A polymeric derivatives having nonlinear optical chromophores containing thiophene have been prepared. Both crosslinked polymers had higher Tg’s and greater mechanical stability than their noncrosslinked analogues and were used as light-emitting diodes. 190
    • REACTION F5 F5 F5 F4 O O F4 F5 F5 F4 O O F4 F5 OH O a i F5 F4 O O F4 F5 O O a O O F3 Not isolated N O O O O F3 F3 S C4H9O OC4H9 S O NC NC CN ii iii Crosslinked polymer Chromophore C4H9O OC4H9 Note 1 i: 4,40 -(1-Phenyl ethylidene)-bisphenol A, potassium carbonate, DMAc, 3,5- dihydroxybenzylalcohol ii: N-Methylpyrrolidone, 4-trifluoro-vinyloxybenzoyl chloride, pyridine iii: Cyclopentanone Reaction 191
    • EXPERIMENTAL 1. Preparation of Poly(4,40 -(1-Phenyl Ethylidene-Bisphenol-4,40 - Di(perfluorobiphenyl)-co-3,5-Dihydroxy-Benzyl Alcohol) A glass reactor was charged with decafluorobiphenyl (0.3 mol), 4,40 -(1-phenyl ethylidene)-bisphenol (0.15 mol), K2CO3 (26 g), and 400 ml of DMAc and then heated to 120 C for 20 hours. The temperature was lowered to 105 C over 1 hour and the mixture treated with 3,5-dihydroxy-benzylalcohol (0.15 mol) and K2CO3 (20 g).Overa3-hourperiodthetemperaturewasincreasedto115 Cwhereitremained for 1 hour. The mixture was hot filtered through a frit and the frit washed with 50 ml of THF. The solution was cooled to ambient temperature and precipitated into a mixture of 750 ml of methanol and 200 ml of water in a blender. The solid was re-dissolved in 250 ml of THF where it formed aviscous solution that was re-precipitated in a solution of 500 ml of methanol and 200 ml of water. The solid was then collected and air-dried on the frit for over 5 hours. It was further dried at 80 C at 87 torr on a rotary evaporator for 5 hours and the product isolated as a fine white powder in 30% yield. 2. Preparation of Poly(4,40 -(1-Phenyl Ethylidene-Bisphenol-4,40 - Di(perfluorobiphenyl)-co-3,5-Dihydroxy-1-Benzyl (4-Trifluorovinyloxy Benzoate) A reaction vessel was charged with 350 ml of N-methylpyrrolidone, the Step 1 product (44.3 g), and 100 ml of pyridine and then stirred at ambient temperature for one hour and treated with of 4-trifluorovinyloxybenzoyl chloride (0.085 mol). This mixture was stirred for 20 hours when the solution color changed from light yellow to brown. The mixture was precipitated by pouring into 500 ml of methanol and 200 ml of water in a blender. The solid was isolated by filtering through a glass frit where a reasonable amount of emulsified polymer formed in the filtrate, suggesting a degree of polymer fractionation. The collected solid was washed with 2 liters of methanol and dried on a glass frit in air for 48 hours. The solid was dissolved in 250 ml of THF and precipitated in 750 ml of methanol and 200 ml of water in a blender. The solid was re-filtered and re-washed with 2 liters of methanol and air dried on the frit for 4 hours. It was re-dissolved in 250 ml of THF and re-precipitated in a solution of 750 ml of methanol and 200 ml of water in a blender, the process being repeated once; 40.0 g of product were isolated as a white powder. 3. Preparation of the Crosslinked Polymer Containing a Chromophore A 30 wt% solution of the chromophorewas mixed with the Step 2 product dissolved in cyclopentanone and then spin-coated onto 200 glass wafers coated with indium tin oxide; the wafer soft baked at 100 C. A corona voltage of 5 kV was applied to the film while it was heated to 220 C for 10 minutes. While at this temperature the voltage was 192 Process for Preparing Poly(Arylene Ethers) with Pendant Crosslinkable Groups
    • increased to 5.5 kV, 6.5 kV, and 7.5 kV for 15, 23, and 30 minutes, respectively. After 40 minutes the wafer was cooled to ambient temperature under the 7.5 kV field. The product was then isolated and had a r33 of 24 pm/V measured at 1310 nm using the Teng–Man method. DERIVATIVES One additional Step 2 crosslinkable polymer, (I), was prepared. F5 F4 O F3C CF3 O F4 F5 O O a O O F3 (I) NOTES 1. The preparation of the Step 3 crosslinking nonlinear optical chromophore co- reagent is described by Huang [1]. Additional crosslinkable luminescent agents, (I) are provided below, (I). N O O O O F3 F3 S C4H9O OC4H9 S R C4H9O OC4H9 H2C O NH CH2 NC CN NC CN NC CN CH2 R = (I) Notes 193
    • 2. Poly(acrylic acid-co-butylmethacrylate) functionalized with cyclometalated luminescent complexes, (II), were prepared by Fryd [2] and used as high efficiency organic light-emitting devices. F Ir CF3 O O O O OO n-C4H9 (II) a b 3. Tamao [3] prepared a polymeric light-emitting agent consisting of poly(3,7- dibromo-5-(2,4,6-triisopropylphenyl)-2,8-dioctyloxy-5H-dibenzo(b,d)borole), (III),which was used in electronicdevices or as a charge transport material. Poly (9,9-di-(4-t-butyldimethylsilyloxy-phenyl)fluorene-2,70 -diyl), (IV), was pre- pared by Woo [4] and used as a light-emitting diode having the potential for subsequent crosslinking. B C8H17O OC8H17 i-C3H8 i-C3H8 i-C3H8 (III) O O SISi t-C4H9 t-C4H9 aa (IV) 4. O’Neill [5] and Inbasekaran [6] prepared photopolymerizable and crosslink- able luminescent monomers, (V), and (VI), respectively, which were used as light emitters in displays, backlights, and electronic equipment. 194 Process for Preparing Poly(Arylene Ethers) with Pendant Crosslinkable Groups
    • C3H7 C3H7 S S O O OO O O (V) O O N N (VI) References 1. D. Huang et al., US Patent 6,995,884 (February 7, 2006) and, US Patent 7,019,453 (March 28, 2006) 2. M. Fryd et al., US Patent 7,060,372 (June 13, 2006) 3. K. Tamao et al., US Patent 7,157,154 (January 2, 2007) 4. E.P. Woo et al., US Patent 6,900,285 (May 31, 2005) and US Patent 6,605,373 (August 12, 2003) 5. M. O’Neill et al., US Patent 7,199,167 (April 3, 2007) 6. M. Inbasekaran et al., US Patent Application 2007-0063191 (March 22, 2007) Notes 195
    • F. Semiconductors Title: Mono-, Oligo-, and Polythieno[2,3-b]Thiophenes Author: M. Heeney et al., US Patent 7,183,418 (February 27, 2007) Assignee: Merck Patent Gesellschaft (Darmstadt, DE) SIGNIFICANCE Polymers having a central core consisting of [2,3-b]-thienothiophene were prepared having a Mn > 6000 daltons and Mw > 9000 daltons and used as semiconductors or charge transport materials in electronic devices. By varying the aromatic or aliphatic content of this material, a lmax between 380 and 462 nm was obtained. REACTION S S HO2C CO2H S S Br Br S S S SC8H17 C8H17 S S S SC8H17 C8H17 iii iii a i: NMP, N-bromosuccinimide ii: THF, Rieke zinc, 2,5-dibromo-3,4-dimethylthieno[2,3-b]thiophene, [1,10 -bis (diphenyl-phosphino)ferrocene]palladium(II) chloride iii: Ferric chloride, CCl3H 196
    • EXPERIMENTAL 1. Preparation of 2,5-Dibromo-3,4-Dimethylthieno[2,3-b]Thiophene A solution of 3,4-dimethylthieno[2,3-b]thiophene-2,5-dicarboxylic acid (0.11 mol) dissolved in 800 ml of NMP and 50 ml of water was treated with the portionwise addition of N-bromosuccinimide (0.25 mol) for over 30 minutes. The mixture was stirred for 16 hours at ambient temperature and then poured into 1 liter of water. The resultant precipitate was dried, the residue purified by flash chromatography over silica using petrol, and the product isolated in 77% yield. 2. Preparation of 2,5-bis(3-Octylthiophen-2-yl)-3,4-Dimethylthieno[2,3-b] Thiophene The Step 1 product (14.5 mmol) dissolved in 20 ml of THF was treated with Rieke zinc (17 mmol) at À78 C, stirred 16 hours at ambient temperature. With the stirring stopped, the solution was allowed to settle for 2 hours, whereupon the solution was transferred by cannula into a flask containing 2,5-dibromo-3,4-dimethylthieno[2,3- b]thiophene (3.9 mmol), 50 ml of THF, and [1,10 -bis(diphenylphosphino)ferrocene] palladium(II) chloride (64 mg) at 0 C. The mixture was warmed to ambient temperature for over 30 minutes and refluxed for 24 hours. The reaction was cooled and quenched with 5% hydrochloric acid and then extracted 3 times with 50 ml of EtOAc. Combined extracts were washed with brine, dried using Na2SO4, and concentrated. The residue was purified by flash chromatography over silica with petrol-followed by reverse, phase chromatography using CH3CN/THF, 2:1, respec- tively, and the product was isolated in 72% yield as a colorless oil. 3. Preparation of Poly(2,5-bis(3-Octylthiophen-2-Yl)-3,4-Dimethylthieno [2,3-B]thiophene) The Step 2 product (1.28 mmol) dissolved in 20 ml CCl3H was treated with the dropwise addition of ferric chloride (6. 2 mmol) dissolved in 100 ml CCl3H. A steady stream of nitrogen was passed through the solution to remove HCl formed during the reaction as it stirred 18 hours at ambient temperature. The mixture was then poured into 500 ml methanol and stirred for 30 minutes, filtered, and the precipitate washed with water and methanol. The yellow precipitate was stirred in 16 M of NH4OH for 60 minutes then filtered and dried. The solid was Soxhlet extracted with methanol, iso-hexane, and acetone. The material was then dissolved in CCl3H, re-precipitated in methanol, dried, and the product isolated. Mn (GPC) ¼ 17,000 daltons Mw (GPC) ¼ 20,000 daltons lmax ¼ 380 nm M/Z: 556 (Mþ ) Elemental analysis: Found C, 69.1%, H, 7.6% Calc. for C32H44S4C, 69.0; H 8.0 Experimental 197
    • DERIVATIVES NOTES 1. Methods for preparing polymeric selenophene analogues of the current invention using selenophene-2,5-diyl derivatives have been proposed Tierney [1]. 2. Copolymers of 9-H,H-fluorene and thiophene, (I), were prepared by the author [2] and used as charge transport materials in electronic devices. S S (I) a 3. Poly(3,30 -dialkyl-2,20 :50 2-terthiophene) derivatives, (II), prepared by McCul- loch [3] were also effective in electronic components as charge transport materials and semiconducters. TABLE 1. Selected poly(thieno[2,3-b]thiophene) derivatives and corresponding physical properties. Entry Structure Mn (daltons) Mw (daltons) lmax (nm) 2 S S S S C8H17 C8H17 a 9,000 22,000 380 4 aS S C8H17 SS C8H17 6,400 9,400 414 5 aS S C12H25 SS C12H25 14,000 22,000 414 6 aS S S C6H13 13,000 40,000 462 1 H- and 13 C-NMR for intermediates supplied by author. 198 Mono-, Oligo-, and Polythieno[2,3-b]Thiophenes
    • a S S S R R R = CH3 - C8H17 (II) 4. Crosslinkable mesogenic azulenes, (III) and (IV), prepared by Farrand [4], and anthracenyl, (V), and tetracenyl, (VI), thiophenes, prepared by Gerlach [5], were used as semiconductors and charge transport agents in electronic devices. S S S S S S S S O(CH2)6O2CCH=CH2H2C=HCCO2(H2C)6O (VI) O(CH2)6O2CCH=CH2 (III) H2C=HCCO2(H2C)6O (IV) (V) 5. Trimeric thiophenes attached to a core-shell structure, (VII), were prepared by Kirchmeyer [6] and used as semiconductors. T TT T T T T T T T S S S C10H21T = (VII) Notes 199
    • References 1. S. Tierney et al., US Patent Application 2007-0045592 (March 1, 2007) 2. M. Heeney et al., US Patent 7,126,013 (October 24, 2006) 3. I. McCulloch et al., US Patent 6,953,957 (October 11, 2005) 4. L.D. Farrand et al., US Patent 7,115,755 (October 3, 2006) 5. C.P. Gerlach,US Patent 6,998,068 (February 14, 2006) 6. S. Kirchmeyer et al., US Patent 7,078,724 (July 18, 2006) 200 Mono-, Oligo-, and Polythieno[2,3-b]Thiophenes
    • Title: Poly(Arylene Ether) Dielectrics Author: C. Lim et al., US Patent 7,166,250 (January 23, 2007) Assignee: Chartered Semiconductor Manufacturing Ltd. (Singapore, SG) SIGNIFICANCE Three polyarylene ethers having a Mn > 10,500 with dielectric constants ofaround 2.5 were prepared and used as low k dielectric layers in electronic applications. Polyarylene ethers were prepared using the Ullmann ether synthesis and had Td ‘s in air of at least 310 C. REACTION OHHO OO S S a i Note 1 i: Benzophenone, toluene, sodium hydroxide, 2,5-dibromo-thiophene, copper(I) chloride, acetic acid, methanol EXPERIMENTAL 1. Preparation of Poly(Arylene Ether) The Ullmann ether catalyst was prepared by charging a 50-ml flask with copper(l) chloride (0.61 mmol) and 0.6 ml of quinoline and then stirring at 25 C for 48 hours. A mixture consisting of 9,9-bis(4-hydroxyphenyl)fluorene (2.86 mmol), benzophenone (5 g), and about 3 ml of toluene was charged to a 50-ml three-necked round bottom flask fitted with a distillation apparatus and heated to 60 C. The mixture was treated 201
    • with aqueous sodium hydroxide (5.72 mmol) and water azeotroped by vacuum distillation at an elevated temperature and then cooled. After re-heating to 80 C the mixture was treated with 2,5-dibromo-thiophene (2.86 mmol) and further heated to 180 C and treated with 0.6 ml of the Ullmann ether catalyst. Heating was continued at 180 C for 17 to 24 hours, and the mixture was next treated with a single portion of 0.02 gdrycopper(I)chloridepowder.Themixturetemperaturewasincreasedto190 C for 24 hours, treated with 0.3 g of 2-bromothiophene, and stirred an additional hour. It was cooled to 100 C, treated with roughly 5.5 ml of toluene, and precipitated in a solution of acetic acid and methanol. The polymer was Soxhlet extracted for 24 hours using methanol, acetone, and chloroform. The polymer was dissolved in a minimum amount of chloroform, re-precipitated in 100 ml of methanol, and the product was isolated. DERIVATIVES NOTES 1. Additional derivatives of the current invention were prepared by the author [1] in a subsequent investigation. TABLE 1. Summary of physical and dielectric properties of selected poly(arylene ethers) prepared using the Ullmann ether catalyst. Entry Structure Mn (daltons) Td ( C) (air) Td ( C) (N2) Tg ( C) e (100 kHz) 1 OO S S a 25,000 310 355 312 2.43 2 OO aN N 11,000 345 325 214 2.65 3 OO aN N 32,000 450 450 227 2.35 202 Poly(Arylene Ether) Dielectrics
    • 2. Terahara [2] utilized the Ullmann ether catalyst of the current invention to prepare poly(arylene ethers), (I), for use as a component in fuel cells. OO n (I) 3. Bai [3] surface modified polymeric low dielectric constant gate insulator films consisting of polystyrene/polyacrylate block copolymers, (II), having an e  4.6. Perfluoroether acyl oligothiophenes, (III), prepared by Gerlach [4] were also effective as low dielectric constant gate insulators. OO N H O O ON NC CN a b c (II) S R1 O R1 O (III) R1 a a CF2(CF2CF2CF2O)3CF3 5 CF(CF3)CF2OCF(CF3)OCF3 6 4. Low dielectric constant gate insulators were prepared by Kelley [5] consisting of poly(stryene-co-vinyl phosphonic acid) and having termini consisting of either trimethyloxysilyl- or phosphinic acid. 5. Weber [6] devised a method for repairing porous low k dielectric films by sealing with polydentate ligands, such as ethylene diamine tetraacetic. 6. Burgoyne [7] prepared polyarylene ethers containing grafted furfuryl, (IV), that crosslinked at low temperatures and were useful as dielectric or super high Notes 203
    • aperture enhancing materials with high glass transition temperatures and low moisture uptake. O O O O HO O a b a:b =2:1 (IV) References 1. C. Lim et al., US. Patent 7,179,879 (February 20, 2007) 2. A. Terahara et al., US. Patent 7,081,497 (July 25, 2006) 3. F. Bai et al., US. Patent 7,098,525 (August 29, 2006) 4. C.P. Gerlach et al., US. Patent 7,151,276 (December 19, 2006) 5. T.W. Kelley et al., US. Patent 6,946,676 (September 20, 2005) 6. F. Weber et al., US. Patent 7,163,900 (January 16, 2007) 7. W.F. BurgoyneJr. et al., US Patent 7,179,878 (February 20, 2007) 204 Poly(Arylene Ether) Dielectrics
    • Title: Polythiophenes and Devices Author: B. S. Ong et al., US Patent 7,141,644 (November 28, 2006) Assignee: Xerox Corporation (Stamford, CT) SIGNIFICANCE Mechanically durable and structurally flexible polythiophene derivatives have been prepared that are useful as semiconducters in thin film field effect transistors and are soluble in chlorobenzene. Materials prepared from these agents have a bandgap between 1.5 and 3.0 eV that enhance their function as film transistors. REACTION S Br S S S S S S S S a i ii i: THF, magnesium, 1,3-bis(diphenylphosphino]dichloronickel(II), 5,50 -dibromo- 2,20 -dithiophene, hydrochloric acid ii: Ferric chloride, CCl3H 205
    • EXPERIMENTAL 1. Preparation 5,50 -Bis(3-Dodecyl-2-Thienyl)-2,20 -Dithiophene A solution of 2-bromo-3-dodecylthiophene (34.92 mmol) dissolved in 40 ml of anhydrous THF was slowly added over a period of 20 minutes to a mechanically stirred suspension of magnesium turnings (51.83 mmol) in 10 ml of THF under an inert argon atmosphere. The mixture was stirred at ambient temperature for 2 hours and then at 50 C for 20 minutes before cooling down to ambient temperature. This mixture was added by cannula to 5,50 -dibromo-2,20 -dithiophene (13.88 mmol) and 1,3-bis(diphenylphosphino)dichloronickel (II) (0.35 mmol) in 80 ml of THF and refluxed for 48 hours. The reaction mixture was then diluted with 200 ml of EtOAc, washed twice with water and 5% HCl, dried with Na2SO4, and concentrated. The dark brown syrupy residue was purified by column chromatography on silica gel, and the product was isolated in 55% yield as a yellow crystalline solid, MP ¼ 58.9 C. 2. Preparation of Poly[5,50 -bis(3-Dodecyl-2-Thienyl)-2,20 -Dithiophene] A solution of the Step 1 product (0.75 mmol) in 7 ml of CCl3H was slowly added to a stirred mixture of FeCl3 (2.47 mmol) in 3 ml of CCl3H and heated to 50 C for 1 hour and then to 40 C for 24 hours. After the polymerization, the mixture was diluted with 20 ml of toluene and washed three times with water. The separated organic phase was stirred with 200 ml of 7.5% NH4OH, washed three times with water, and poured into methanol to precipitate the crude polythiophene. The residue was purified by Soxhlet extraction with methanol, hexane, and chlorobenzene, and the product was isolated with a Mw ¼ 27,300 daltons and Mn ¼ 16,900 daltons. DERIVATIVES Only poly[5,50 -bis(3-dodecyl-2-thienyl)-2,20 -dithiophene] in varying molecular weights was prepared. Testing Results Thin film transistor devices were fabricated by spin coating using a 1% solution of the selected polythiophene dissolved in chlorobenzene and drying in vacuo at 80 C for 20 hours. No precautions were taken to exclude oxygen, moisture, or light during device fabrication. From transistors with dimensions of 5000 Â 60 m, electrical properties were determined as summarized in Table 1. 1 H NMR (CDCl3) d 7.18 (d, J ¼ 5.4 Hz, 2H), 7.13 (d, J ¼ 3.6 Hz, 2H), 7.02 (d, J ¼ 3.6 Hz, 2H), 6.94 (d, J ¼ 5.4 Hz, 2H), 2.78 (t, 4H), 1.65 (q, 1.65, 4H), 1.28 (bs, 36H), 0.88 (m, 6H) 206 Polythiophenes and Devices
    • TABLE1.Effectofpoly[5,50 -bis(3-dodecyl-2-thienyl)-2,20 -dithiophene]ofvaryingmolecularweightsofthecurrentinventiononmobility andcurrenton/offratiowhenspincastedontothinfilmtransistordevices. Step2Product Mw(Mn) (daltons)Reactions/PurificationsConditionsMobility(cm2 /V. s) InitialCurrent On/OffRatio CurrentOn/Off after5Days 3890(3800)25 C(24hours);precipitatedfrom CH3OH 0.9–2.0Â10À4 1.2Â103 –– 14,900(9000)40 C(1hour);25 (48hours);extracted withtoluene 2.0–3.1Â10À4 2.2–4.7Â103 –– 14,900(9000) Thendevice annealedat 135 C10 minutes 14,000(11,400) 40 C(1hour);25 C(24hours); extractedwithCH3OH,hexane,and chlorobenzene50 C(1hour);then 40 C. 1.1–3.4Â10À3 4.5–9.0Â104 0.7–1.1Â104 1.9–8.7Â10À3 5.0–8.5Â105 1.1–2.5Â105 27,300(16,900)50 C(1hour)then40 C(24hours); extractedwithCH3OH,hexane,and chlorobenzene 0.9–2.0Â10À2 1.0–5.1Â106 1.9–3.2Â105 207
    • NOTES 1. In earlier investigations by the author [1] polythiophene analogues containing phenylene, (I), were prepared and used as semiconducters in thin film field effect transistors. S S S S Br Br S S S S a i (I) i: 1,4-Benzenebis(pinacolboronate), toluene, Aliquot 336, tetrakis(triphenyl- phosphine)-palladium 2. Sotzing [2] prepared intrinsically conducting water-borne dispersions of poly (thieno[3,4-b]thiophene) homopolymer, (II), and copolymers of thieno[3,4-b] thiophene and 3,4-ethylenedioxythiophene, (III), for electroactive applications including electrochromic displays, optically transparent electrodes, and anti- static coatings. S S S S S S S S S S S OO S S S O O a b a b (II) (III) 208 Polythiophenes and Devices
    • 3. Groenendaal [3] prepared water soluble 4-(2,3-dihydro thieno[3,4-b)][1,4] dioxin-2-yl-methoxy)-butane-1-sulfonic acid sodium salt, (IV), and copoly- mers with poly(styrenesulphonic acid) having a Mw of 290,000 daltons that were used in electroconductive devices. S OO O SO3Na (IV) 4. Additional polythiophene p-conjugated polymer precursors were prepared by Reuter [4], (V), and Groenendaal [5], (VI), and used in electroconductive devices as semiconductors. S S OO OO HO OH (V) S OO (VI) R R = C8H17 C10, H21 C12, H25 5. Kirchmeyer [6] prepared linear organic thiophenephenylene oligomers, (VII), that were effective as semiconductor coatings. S S S S S S C10H21 C10H21 (VII) Notes 209
    • 6. Regioregular intriniscally conducting mono-, di-, and triblock moderate mo- lecular weight polythiophenes containing a well-defined terminus, (VIII), were prepared by McCullough [7] and used in thin field-effect transitor applications. S S OH H 46 (VIII) References 1. B.S. Ong et al., US Patent 7,132,500 (November 7, 2006) and US Patent 7,132,682 (November 7, 2006) 2. G.A. Sotzing,US Patent 7,125,479 (October 24, 2006), US Patent Application 2005-0124784 (June 9, 2005), and US Patent Application 2004-0010115 (January 15, 2004) 3. B. Groenendaal et al., US Patent 7,105,620 (September 12, 2006) 4. K. Reuter, US Patent 7,102,016 (September 5, 2006) 5. B. Groenendaal et al., US Patent 7,094,865 (August 22, 2006) 6. S. Kirchmeyer et al., US Patent 7,199,251 (April 3, 2007) 7. R.D. McCullough et al., US Patent 7,098,294 (August 29, 2006) 210 Polythiophenes and Devices
    • Title: Mono-, Oligo- and Polymers Comprising Fluorene and Aryl Groups Author: M. Heeney et al., US Patent 7,126,013 (October 24, 2006) Assignee: Merck Patent GmbH (Darmstadt, DE) SIGNIFICANCE Polymers and elastomers comprising at least one 9-H,H-fluorene group and at least one arylene group have been prepared. These materials are suitable for use as semiconductors or charge transport materials in optical, electrooptical, or electronic devices, including field-effect transistors, electroluminescent, photovoltaic, and sensor devices. REACTION Br Br B B O O O O S C12H25 S S C12H25 C12H25 S S C12H25 C12H25 Br Br S S C12H25 C12H25 Intermediate a i ii iii iv Intermediate i: Bis(pinacolato)diboron, potassium acetate, dichlorobis(tricyclohexylphosphine) palladium(II), 4-dioxane ii: BuLi, tetramethylethylenediamine, copper(II) chloride iii: N-Bromosuccinimide, CCl3H, acetic acid iv: Tetrakis(triphenylphosphine)palladium, Aliquat 336, toluene, sodium carbonate 211
    • EXPERIMENTAL 1. Preparation of 2,7-Bis(4,4,5,5-Tetramethyl-1,3,2-Dioxaborolan-2-yl)- Fluorene A flask was charged with 2,7-dibromofluorene (17.73 mmol), bis(pinacolato)dibor- on (44.33 mmol), potassium acetate (5.22 g, 53.20 mmol), dichlorobis(tricyclohex- ylphosphine)-palladium(II) (0.61 mmol), and 150 ml of 1,4-dioxane and stirred at 100 C for 24 hours. The reaction mixture was quenched with 100 ml of water and extracted twice with 200 ml of CCl3H. Combined extracts were washed with 100 ml of water, dried with Na2SO4, and concentrated. The residue was purified by column chromatography using CH2Cl2, and the product was isolated as a white solid in 76% yield. 2. Preparation of 4,40 -Didodecyl-2,20 -Bithiophene A solution of 3-dodecylthiophene (39.61 mmol) in 40 ml of THF at ambient temperature was treated dropwise with 18 ml of 2.5 M BuLi in hexanes (45.00 mmol) and 6.8 ml of tetramethylethylenediamine (45.06 mmol) and refluxed 1 hour. The mixture was cooled to À78 C and treated with copper(II) chloride (47.53 mmol) in a single portion. It was then stirred at ambient temperature for 18 hours and refluxed for 6 hours. The mixture was acidified with dilute hydrochloric acid and extracted twice with 200 ml of diethyl ether. Combined extracts were washed with 100 ml of water and dried with Na2SO4 and concentrated. The residue was purified by column chromatography using petroleum ether 40 60, re-crystal- lized from diethyl ether at À78 C, and the product was isolated as a yellow solid in 38% yield. 3. Preparation of 5,50 -Dibromo-4,40 -Didodecyl-2,20 -Bithiophene Avessel containing the Step 2 product (1.49 mmol) dissolved in 5 ml apiece of CCl3H andglacialaceticacidwastreatedportionwisewithN-bromosuccinimide(2.98 mmol) andstirredovernightbeforebeingpouredintowaterandextractedtwicewith250 mlof CH2Cl2.Combinedextractswerewashedtwicewith100 mlofwaterandconcentrated. The residue was purified by column chromatography using petroleum ether, and the product was isolated as a yellow solid in 100% yield. 1 H-NMR (CDCl3, 300 MHz) d 6.97 (2H, s), 6.76 (2H, s), 2.56 (4H, t,3J.sub.HH ¼ 8.0 Hz), 1.61 (4H, m), 1.20 1.40 (36H, br), 0.88 (6H, t, .sup.3J.sub.HH ¼ 7.0 Hz) 13 C-NMR (CDCl3, 75 MHz) d 44.0, 137.4, 124.8, 118.7, 32.0, 30.6, 30.4, 29.7, 29.6, 29.5, 29.4, 29.3, 22.7, 14.2 1 H-NMR (CDCl3, 300 MHz) d 6.77 (2H, s), 2.51 (4H, t, .sup.3J.sub.HH ¼ 8.0 Hz), 1.57 (4H, m), 1.20 1.40 (36H, br), 0.88 (6H, t, sup.3J.sub.HH ¼ 7.0 Hz) 13 C-NMR (CDCl3, 75 MHz) d 142.8, 136.0, 124.3, 107.0, 31.8, 29.5, 29.4, 29.2, 29.0, 22.6 212 Mono-, Oligo- and Polymers Comprising Fluorene and Aryl Groups
    • 4. Preparation of Poly(4,40 -Didodecyl-2,20 -Bithiophene-alt-Fluorene) A flask was charged with the Step 1 (1.44 mmol) and Step 3 (1.44 mmol) products, tetrakis-(triphenylphosphine)palladium(0) 0.03 mmol), Aliquat 336 (0.25 g), and 20 ml toluene and then treated with 2.5 ml of 2 M aqueous Na2CO3. The mixture was refluxed for 48 hours and precipitated by pouring into 400 ml of methanol. The polymer was collected and washed with water followed by methanol and then dried. The dried polymer was Soxhlet extracted for 16 hours with methanol and six hours by iso-hexane. The polymer was re-dissolved in hot CCl3H and precipitated in 400 ml methanol and dried; the product was isolated as a green solid in 78% yield. DERIVATIVES TABLE 1. Selected bisthiophene-fluorene copolymers and monomer prepared according to the current invention. Entry Structure Tm ( C) Tg ( C) MS (m/e) 1 S S C6H13 C6H13 a 122 199 — 3 a C6H13 C6H13 >300 — — 4 S O O O S O O O — — 768 (M þ OH) Note: Extensive 1 H- and 13 C-NMR for all entries provided by author. Tm ¼ 130 C Tg ¼ 160 C Td ¼ 360 C Mn ¼ 32,000 daltons (bimodal) Mw ¼ 137,000 daltons Absorbance (lmax CDCl3) ¼ 405 nm 1 H-NMR (CDCl3, 300 MHz) d 7.84 (2H, d, .sup.3J.sub.HH ¼ 8.0 Hz), 7.66 (2H, s), 7.51 (2H, d, .sup.3J.sub. HH ¼ 8.0 Hz), 7.11 (2H, s), 4.02 (2H, s), 2.71 (4H, br), 1.67 (4H, br), 0.95 1.40 (36H, br), 0.87 (6H, br) Derivatives 213
    • NOTES 1. Conjugated polyazulene derivatives, (I) and (II), prepared by Farrand [1] were useful as components in optical, electro-optical, and electronic devices. a a (I) (II) 2. Jubran [2] and Tokarski [3] prepared photoreceptors comprising an electrically conductive substrate and a photoconductive element consisting of phenothia- zines, (III) and (IV), and carbazole, (V), derivatives, respectively. N S R N N OH S S S N OH N N S R (III) N S N N OH S S N OH N N S (IV) N S N R = CH3, C2H5 N OH N N O (V) 214 Mono-, Oligo- and Polymers Comprising Fluorene and Aryl Groups
    • 3. Perfluoroacyl oligomeric thiophene derivatives, (VI), prepared by Gerlach [4] were effective as n-channel semiconductor thin film layers in electronic devices. S O O O CF3 O CF3 C F2 C3F7O C F2 OC3F7 CF3 CF3 (VI) 5 References 1. L.D. Farrand et al., US Patent 7,034,174 (April 25, 2006) 2. N. Jubran et al., US Patent 7,169,520 (January 30, 2007) 3. Z. Tokarski et al., US Patent 7,166,400 (January 23, 2007) 4. C.P. Gerlach et al., US Patent 7,211,679 (May 1, 2007) Notes 215
    • VIII. ENERGETIC POLYMERS Title: Glycidyl Dinitropropyl Formal, Poly(Glycidyl Dinitropropyl Formal), and Preparation Method Thereof Author: J. S. Kim et al., US Patent 7,208,637 (April 24, 2007) Assignee: Agency for Defense of Korea (Daejeon, KR) SIGNIFICANCE An energetic polyether containing grafted gem-nitro’s has been prepared having a decomposition temperature of 200  C or higher. This polymeric agent is useful as a stable energetic binder for insensitive and high-performance explosives. REACTION a OH NO2O2N O O NO2O2N O O NO2O2N O O OO O O NO2 NO2 iiiiii i: Formaldehyde, allyl alcohol, CH2Cl2, boron trifluoride etherate ii: CCl3H, 3-chloroperbenzoic acid iii: 1,4-Butandiol, boron trifluoride etherate, CH2Cl2 Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 217
    • EXPERIMENTAL 1. Preparation Allyl Dinitropropyl Formal A reactor was charged with 2,2-dinitropropanol (0.1 mol), formaldehyde (0.11 mol), allyl alcohol (0.3 mol), and CH2Cl2 (40 g) and treated with the slow addition of boron trifluoride etherate (0.3 mol) at 5 C. After the addition the mixture was stirred at 5 C for40minutes.Thereafter 100 mlofwaterwasslowlyaddedtothemixture,whichwas then stirred and the aqueous component discarded. The organic layer was washed 3 times with NaOH, oncewith water, oncewith brine, and again with water. The organic phase was then dried, concentrated, and the product was isolated in 73% yield. 2. Preparation of Glycidyl Dinitropropyl Formal TheStep1product(0.15 mol)andCCl3H(400 g)werechargedintoaflaskthentreated with 3-chloroperbenzoic acid (0.18 mol) over 30 minutes. After the addition was complete, the mixture was refluxed for 3 hours, cooled to ambient temperature, and stirredanadditional 12hours.Themixturewascooled to0 C,filtered, andthesolution was washed twice with 5% sodium sulfite and with 5% sodium hydroxide. The solution was nextwashed with brine, dried, concentrated, and the product was isolated in 92% yield. 3. Preparation of Poly(Glycidyl Dinitropropyl Formal) 1,4-Butandiol (2 mmol) was added to boron trifluoride etherate (1 mmol) and vacuum purified for 2 hours to remove diethyl ether. This mixture was then treated with CH2Cl2 (12 g) and the slow addition of the Step 2 product (50 mmol) dissolved in CH2Cl2 over 3 hours. The mixture was reacted an additional 30 minutes and washed with 50 ml of water, 30 ml of CH2Cl2, and three times with 50 ml of brine. It was dried using MgSO4 and then precipitated in 20 ml ethanol. The polymer was next heated to 80 C at 1 mmHg for 5 hours to purify, and the product isolated in 90% yield. The product had a Mw of 2,200 daltons, a polydispersity index of 1.12, a hydroxyl group of 0.621 eq/kg, a Tg of À23 C, and a decomposition temperature greater than 200 C. DERIVATIVES No additional derivatives were prepared. 1 HNMR(CDCl3) d 2.17(s, 3H), 2.60(t, 1H), 2.78(t, 1H), 3.1(m, 1H), 3.8(m, 1H), 4.3(s, 2H), 4.7(s, 2H) 218 Glycidyl Dinitropropyl Formal, Poly(Glycidyl Dinitropropyl Formal), and Preparation
    • NOTES 1. In an earlier investigation by the author [1] poly(glycidyl dinitropropyl carbonate), (I), was prepared and used as an energetic binder for insensitive and high-performance explosives. O O O NO2 O NO2 (I) a 2. Sanderson [2] prepared the energetic thermoplastic elastomer poly(3,3-bis (azidomethyl)-oxetane), (II), for use as a binder for a propellant, explosive, or gas generant for a supplemental restraint system in automobiles. Random block copolymers of poly(azidomethyloxirane) and poly(3,3-bis(azidomethyl)oxe- tane), (III), were also prepared by Sanderson [3] using toluene diisocyanate as the coupling agent. a O N3 N3 (II) O H N O N H O O N3N3 N3 (III) a b 3. Adams [4] prepared energetic fullerenes of the generic formula, C60(NO2)n, where n ¼ 1–60, and where at least 10% of the molecule consisted of nitrogen. References 1. J.S. Kim et al., US Patent 6,706,849 (March 16, 2004) 2. A.J. Sanderson et al., US Patent 7,101,955 (September 5, 2006) 3. A.J. Sanderson et al., US Patent Application 2006-0157173 (July 20, 2006) 4. C. Adams, US Patent 7,025,840 (April 11, 2006) Notes 219
    • Title: Synthesis of Energetic Thermoplastic Elastomers Containing Both Polyoxirane and Polyoxetane Blocks Author: A. J. Sanderson et al., US Patent 7,101,955 (September 5, 2006) Assignee: Alliant Techsystems, Inc. (Edina, MN) SIGNIFICANCE An energetic thermoplastic elastomer consisting of poly(azidomethyloxirane)-b- (3,3- bis(azidomethyl)-oxetane) has been prepared that is suitable for use as a binder for a propellant, explosive, and/or gas generator. Block seqments were prepared using 2,4-diisocyanate toluene. REACTION OH Br Br Br O N3 N3 O N3 N3O H N NH O O N3 a b i ii i: Tribromoneopentylalcohol, toluene, tetrabutylammonium bromide, sodium hydr- oxide sodium azide ii: Poly(azidomethyloxirane), dibutyltin dilaurate, toluene-2,4-diisocyanate, CH2Cl2 EXPERIMENTAL 1. Preparation of 3,3-bis(Azidomethyl)Oxetane A reactor was charged with tribromoneopentylalcohol (600 g), 1200 ml of toluene and tetrabutylammonium bromide (6 g) then cooled to 12 C and slowly treated with a 40 wt% solution of sodium hydroxide (193 g). After 36 hours crude bis(bromomethyl) oxetane was washed with water until the pH was less than 9 and then distilled; the product was isolated in 65% yield. 220
    • 2. Preparation of Poly[(Azidomethyloxirane)-b-(3,3-bis(Azidomethyl)- Oxetane)] In a 250 ml round bottom flask poly(azidomethyloxirane) (19.62 g) and the Step 1 product (6.63 g) were dissolved in 80 ml of CH2Cl2; the solution concentrated sufficiently for the solution to become cloudy. This cloudy solution was then treated with 0.12 ml of dibutyltin dilaurate and toluene-2,4-diisocyanate (3.11 g). After 4 hours, butane-1,4-diol (0.805 g) was added, causing the solution to become steadily more viscous; after another 18 hours, the solution was too viscous to stir. The mixture was then diluted with 50 ml of CH2Cl2, precipitated, and the product was isolated having a Mn of 28,440 daltons, Mw of 219,500, and a polydispersity index of 7.7. DERIVATIVES Poly(nitromethyloxirane)-b-(3,3-bis(azidomethyl)-oxetane) was also prepared. O N3 N3O H N NH O O O2 N a b NOTES 1. Sanderson [1] and Highsmith [2] prepared glycidyl nitrate and subsequently converted it into polyglycidyl nitrate (I) using calcium hydride and boron trifluoride. a O ONO2 (I) Derivatives 221
    • 2. Poly(glycidyl dinitropropyl formal), (II), was prepared by Kim [3] and used as a performance insensitive explosive. a O OO O O NO2 NO2 (II) 3. The energetic plasticizer, 2,2-dinitro-1,3-propanediol-diformate, (III), pre- pared by Highsmith [4] was used in explosive and propellant compositions. NO2O2 N O O H O H O (III) References 1. A.J. Sanderson et al., US Patent 6,861,501 (March 1, 2005) and US Patent 6,861,501 (May 4, 2004) 2. T.K. Highsmith et al., US Patent 6,362,311 (March 26, 2002) 3. J.S. Kim et al., US Patent 7,208,637 (April 24, 2007) 4. T.K. Highsmith et al., US Patent 6,425,966 (July 30, 2002) 222 Synthesis of Energetic Thermoplastic Elastomers Containing Both Polyoxirane
    • IX. FIBERS Title: Rigid-Rod Benzobisazole Polymers Incorporating Naphthalene-1,5-Diyl Structure Units Author: T. D. Dang et al., US Patent 7,041,779 (May 9, 2006) Assignee: United States of America as Represented by the Secretary of the Air Force (Washington, DC) SIGNIFICANCE Aromatic heterocyclic rigid-rod polymers that have exceptional thermal oxidative stability have been prepared using 1,5-naphthylene dicarboxylic acid and 2,5-diami- no-1,4-benzenedithiol. These heterocyclic rigid-rod polymers materials are useful as protective garments in ballistic vests and abrasion- and flame-resistant fabrics. REACTION CO2H HO2 C S N N a S i Notes 1,2 i: 2,5-Diamino-1,4-benzenedithiol dihydrochloride, polyphosphoric acid, phospho- rous pentoxide Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 223
    • EXPERIMENTAL Preparation of Benzobisthiazole-Naphthalic Fibers A resin flask was charged with naphthalene-1,5-dicarboxylic acid (0.0116 mole), 2,5- diamino-1,4-benzenedithiol dihydrochloride (0.0116 moles), and 77% polyphospho- ric acid (20.8 g). The mixture was then dehydrochlorinated over a period of 24 hours under a nitrogen flow while slowly raising the temperature to 105 C. The mixture was then cooled and treated with P2O5 (11.37 g) and heated to 165 C and the polymeriza- tion reaction proceeded overnight. During this process, stir opalescence characteristic of the anisotropic phase was observed. The mixture was further heated to 180 C for a fewhours,androughly3 gofthepolymerdopeweretakenoutforfiberspinning.Using polarizing optical microscopy a sample of the dope was sealed between two glass slides and found to exhibit optical birefringence; the persistence of the observed optical textureseveraldayslater wasindicativeof lyotropicliquid crystallinebehavior of the material. The remaining dope was precipitated in water and the fibrous polymer shredded in a blender. The polymer was filtered off, Soxhlet extracted with hot water and dried, and the product was isolated as a dark yellow solid having an intrinsic viscosity of 13.2 dl/g measured in methanesulfonic acid at 30 C. DERIVATIVES No additional derivatives were prepared. NOTES 1. The preparation of naphthalene-1,5-dicarboxylic acid is illustrated below. NH2 NH2 CN CN CO2H CO2H iii I I iii i: Hydrochloric acid, sodium nitrite, potassium iodide ii: Copper(I) cyanide, sodium cyanide, water iii: Hydrobromic acid, acetic acid, water 2. The Step 1 product was fabricated into fibers using the continuous dry jet–wet spinning method. 224 Rigid-Rod Benzobisazole Polymers Incorporating Naphthalene-1,5-Diyl Structure Units
    • 3. Kumar [1] demonstrated that the fiber strength of polyphenylenebenzobisthia- zole, (I), increased by using compositions containing carbon nanotubes. S N N S (I) a 4. Rigid-rod compositions consisting of polyphenylene derivatives were used by Goldberg [2] as advanced thermoplastics in preparing orthodontic wire. 5. Bazan [3] prepared conformationally flexible rigid rod cationic conjugated polymers, (II), comprising monomers that perturbed the polymer’s ability to form rigid-rod structures, thereby allowing them to form a greater range of three-dimensional structures. c (H3C)3N N(CH3)3 (H3C)3N N(CH3)3 BrBrBr BrBr a b (II) 6. Petschek [4] used heterocyclic rigid-rod polyionomers, including poly(pyr- idinium) salt, (III), and poly(benzimidazole-sulfonate), (IV), for coating directionally onto charged surfaces to impart planar alignment and pre-tilt to the surfaces. aa N N (III) N N H N H N SO3 (IV) Notes 225
    • References 1. S. Kumar et al., US Patent 6,900,264 (May 31, 2005) 2. A.J. Goldberg et al., US Patent 7,186,115 (March 6, 2007) 3. G.C. Bazan et al., US Patent 7,144,950 (December 5, 2006) and US Patent Application 2007-0088130 (April 19, 2007) 4. R.G. Petschek et al., US Patent 6,942,905 (September 13, 2005) 226 Rigid-Rod Benzobisazole Polymers Incorporating Naphthalene-1,5-Diyl Structure Units
    • Title: Polybenzazole Fiber and Use Thereof Author: Y. Abe et al., US Patent Application 2006-0083923 (April 20, 2006) Assignee: Canon Kabushiki Kaisha (Tokyo, JP) SIGNIFICANCE Polybenzazolefibershavebeenpreparedcontainingblendedorganicpigmentsthatare heat,moisture,andlightresistantwiththermaldecompositiontemperaturesexceeding 200 C.These materialsare usefulas fibersfor high-strengthrope, cement/concretere- inforcers, and bullet proof vests. REACTION a H2N NH2 OHHO N O O N i i: Terephthalic acid, polyphosphoric acid EXPERIMENTAL Preparation of Poly(p-Phenylenebenzobisoxazole) Under a stream of nitrogen gas, 4,6-diamino-resorcinol dihydrochloride (334.5 g), terephthalic acid (260.8 g), and polyphosphoric acid (2,078.2 g) were mixed and stirred at 60 C for 30 minutes. The temperature was gradually increased to 135 C for 20 hours, 150 C for 5 hours, 170 C for 20 hours, and then the material isolated. The producthadanintrinsicviscosityof30 dL/gat30 Cmeasuredinmethanesulfonicacid. DERIVATIVES Only the single derivative was prepared. 227
    • TESTING Filaments were subjected to storage testing at elevated temperatures and high humidity as well as light exposure testing. Testing results are provided in Table 1. NOTES 1. Saitoh [1] prepared oriented polybenzazole, (I), films having high strength and high elastic modulus and heat and flame resistance. a O N O N (I) 2. Kodama [2] prepared high molecular weight polybenzazoles, (I), using iron, (II), phosphate octahydrate as a reaction catalyst. TABLE 1. Effect of high temperature and humidity and light exposure on poly (p-phenylene-benzobisoxazole) film strength retention containing various dopants. Entry Dopant Initial Strength (GPa) Exposure to 80% Humidity at 80 C for 700 hours Exposure to Light from Xenon Lamp for 100 hours Final Strength (GPa) Retention (%) Final Strength (GPa) Retention (%) 1 29H,31H- Phthalocyaninate(2-)- N29,N30,N31,N32 copper 5.6 5.0 90 4.9 83 4 9,19-Dichloro-5,15- diethyl-5,15- dihydrodiindlo[2,3- c:20 ,30 -n]triphenodiox- azine 5.5 4.8 88 4.5 81 12 Bisbenzimidazo[2,1- b:20 ,10 -I]benzo[1mn][3,8]- phenathroline- 8,17-dione 5.8 5.0 87 4.8 82 15 29H,31H-Phthalocyaninate(2-)- N29, N30,N31,N32 copper 4.7 4.3 92 4.2 89 228 Polybenzazole Fiber and Use Thereof
    • 3. Polybenzazole block copolymer, (II), prepared by Kodama [3] and containing light-resisting m- or p-phenylenediamine had a 30% reflectance in the wave- length region of from 450 to 700 nm. c O N O N O N a b (II) 4. Polybenzazole fibers, (I), prepared by Kitagawa [4] had a compression strength of not less than 0.5 GPawhen blended with 1% to 15% carbon nanotubes having a length of more than 20 nm and width of between 0.5 mm–10 mm. The resulting fibers had high strength, high elastic modulus, and fine fiber structure. 5. Adamantyl benzoxazole pre-polymers, (III) and (IV), were prepared by Takaragi [5] and Nagano [6], respectively, and used to prepare high molecular weight polymers with porous structures that were used in dielectric films associated with semiconductors. a OH O H2N OH O N (IV) O OH OH O H2N OH O N (III) a References 1. F. Saitoh et al., US Patent 7,122,617 (October 17, 2006) 2. F. Kodama et al., US Patent 6,169,165 (January 2, 2001) 3. T. Kodama et al., US Patent 6,818,734 (November 16, 2004) 4. T. Kitagawa, US Patent 6,884,506 (April 26, 2005) 5. A. Takaragi et al., US Patent Application 2007-0078256 (April 5, 2007) 6. S. Nagano et al., US Patent Application 2007-0032556 (February 8, 2007) Notes 229
    • X. FLUORINE A. Critical Polymerization Title: Process for Producing Fluoropolymer Author: M. Tsukamoto et al., US Patent 7,173,098 (February 6, 2007) Assignee: Daikin Industries, Ltd. (Osaka, JP) SIGNIFICANCE An efficient method for preparing polyvinylidene fluoride by reacting above the monomer critical density and temperature is described. When polyvinylidene fluoride was prepared in this manner, molecular weights were at least four times greater than those noncritically prepared. REACTION F F F2 C i Notes 1,2 i: Di-n-propyl peroxydicarbonate EXPERIMENTAL Preparation of Polyvinylidene Fluoride A stainless steel autoclave with an internal volume of 1083 ml was charged with vinylidene fluoride (542 g) using a high-pressure plunger pump to establish a monomer density of 0.50 g/ml. Using a band heater the reaction temperature was raised to 40 C, which provided a reaction pressure of 5.72 MPa. The reaction Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 231
    • was then initiated with 6.1 g of 50% di-n-propyl peroxydicarbonate solution in methanol; the polymerization continued for 1 hour. After venting, unreacted monomer, 29.5 g of a white-colored product was isolated with Mn ¼ 36,080 daltons and Mw ¼ 78,050 daltons. SCOPING STUDIES NOTES 1. In subsequent investigations by the author [1] when the Step 1 reaction of the current invention was continued for 120 to 150 minutes, the corresponding polymer had a Mn of 81,000 daltons and a Mw of 203,000 daltons. Additional critical polymerization reaction scoping studies using vinylidene fluoride are described by the author [2]. 2. Lee [3] polymerized vinylidene fluoride in supercritical water, namely TH2O > 374 C and PH2O > 218:2 atm, using either t-butyl peroxyacetate or t-butyl peroxy-2-ethylhexanoate and obtained Mn’s exceeding 1 million daltons with a crystalline content >50%. In an earlier investigation by Lee [4] showed TABLE 1. The effects of polymerization of vinylidene fluoride for one hour at 318 K at varying reaction pressures. Entry Monomer (g) Monomer Reaction Density (g/ml) Reaction Pressure (MPa) Mn (daltons) Mw (daltons) 1 542 0.50 5.72 36, 080 78,050 2 639 0.59 6.62 54,900 118,500 Noncritical Comparison 314 0.29 5.13 8,560 14,700 Note: Critical parameters for vinylidene fluoride are 4.430 MPa as a critical density and 303.30 K as a critical temperature. TABLE 2. Critical parameters for selected perfluoro monomers. Monomer Critical Density (g/ml) Critical Temperature (K) Vinylidene floride 4.430 303.30 Hexafluoropropene 2.900 367.10 Tetrafluoroethylene 3.940 306.00 Chlorotrifluoroethylene 3.960 379.00 Note: Critical parameters for perfluoro solvents were also provided by the author. 232 Process for Producing Fluoropolymer
    • that when methyl methacrylate and glycidal methacrylate were copolymerized in supercritical water, a low polydispersed product was obtained. References 1. M. Tsukamoto et al., US Patent Application 2006-0122347 (June 8, 2006) 2. M. Tsukamoto et al., US Patent Application 2005-0043498 (February 24, 2005) 3. S. Lee et al., US Patent 7,091,288 (April 15, 2006) Notes 233
    • B. High Strength Title: Fluorinated Terpolymer Author: S. Kurihara et al., US Patent 7,009,017 (March 7, 2007) Assignee: Unimatec Co., Ltd. (Tokyo, JP) SIGNIFICANCE Perfluoro terpolymers consisting of tetrafluoroethylene, perfluoro(ethyl vinyl ether), and perfluoro(propyl vinyl ether) have been free radically prepared to have distin- guished transparency and good mechanical strength at both ambient temperature and 372 C. These materials are particularly useful as high-strength moldings. REACTION F2C CF2 C F2 F2 C C F2 CF C F2 CF O C2F5 O C3F7 i a i: Isobutyryl peroxide, perfluoro-n-heptane, perfluoro(ethyl vinyl ether), perfluoro (propyl vinyl ether EXPERIMENTAL Preparation of Poly[Tetrafluoroethylene-co-Perfluoro(Ethyl Vinyl Ether)-co- Perfluoro-(Propyl Vinyl Ether)] Ahigh-pressurereactorwaschargedwithwater(1200 g),perfluoro-n-heptane(690 g), perfluoro(ethyl vinyl ether) (22 g), perfluoro(propyl vinyl ether)(26 g), and methanol (0.1 g). After the temperature was increased to 30 C, tetrafluoroethylene (160 g) was added until a pressure of 0.85 MPa was obtained. The overall monomer ratio 234
    • of tetrafluoroethylene/perfluoro(ethyl vinyl ether)/perfluoro(propyl vinyl ether) was 77/10/13, respectively. The polymerization was initiated with 25 wt% isobutyryl peroxide (4.0 g) dissolved in CClF2CF2CHClF. Since the reaction pressure decreased with the reactions progress, additional reagent mixture was added to maintain a pressure of 0.85 MPa. Following the addition of these monomers, the mixture continued to react until the reaction pressure remained constant and the mixture aged. Unreacted gases were purged from the reactor at 0.5 MPa, and 231 g of product was isolated. REACTION SCOPING NOTES 1. Functionalized terpolymers, (I), consisting of vinylidene fluoride, hexafluor- opropene, and silyl-modified tetrafluoroethylene were prepared by Chung [1] to increase the reactivity of perfluoropolymers to subsequent chemical modi- fication. a F2 C C F2 CF C F2 CF CF3 H Si (I) TABLE 1. Physical properties of perfluoro terpolymers as a function of composition. Item Sample 1 Sample 3 Sample 5 Sample 9 Composition (wt%) Tetrafluoroethylene 95 72 46 46 Perfluoro(ethyl vinyl ether) 2 13 25 39 Perfluoro(propyl vinyl ether) 3 15 29 15 Tensile strength at break (372 C; Â 103 Pa.s) 11 22 1.4 1.1 Light transittance 250 nm (%) 62 95 96 95 650 nm (%) 92 96 97 97 Glass transition temperature ( C) 102 43 21 21 Notes 235
    • 2. Perfluoro terpolymerss consisting of tetrafluoroethylene, hexfluoropropylene, and vinylidene fluoride were prepared by Park [2] using electron beam radiation. Perfluoro terpolymers were also prepared by Park [3] using 2,5-dimethyl-2,5-di(t-butylperoxy)-hexane. 3. Liquid vulcanizable fluoroelastomers consisting of vinylidene fluoride, per- fluoro(methyl vinyl ether), and tetrafluoroethylene were prepared by Kojima [4] and Park [5] and used for molding materials of low hardness. 4. Elastomers consisting of vinylidene difluoride/hexafluoropropylene or vinyli- dene difluoride/hexafluoropropylene/tetrafluoroethylene elastomers were pre- pared by Hochgesang [6] and cured using 4,40 -hexafluoroisopropylidene diphenol. References 1. T.Z. Chung et al., US Patent 7,045,248 (May 22, 2007) 2. E.H. Park et al., US Patent 7,230,038 (June 12, 2007) 3. E.H. Park et al., US Patent 7,153,908 (December 26, 2006) 4. Y. Kojima et al., US Patent 7,202,299 (April 10, 2007) 5. E.H. Park et al., US Patent 7,230,038 (June 12, 2007) 6. P.J. Hochgesang et al., US Patent 7,098,270 (August 29, 2006) 236 Fluorinated Terpolymer
    • C. Low Molecular Weight Title: Directly Polymerized Low Molecular Weight Granular Polytetrafluoroethylene Author: R. A. Morgan, US Patent 7,176,265 (February 13, 2007) Assignee: E.I. du Pont de Nemours and Company (Wilmington, DE) SIGNIFICANCE Tetrafluoroethylenepolymerizedinthepresenceofthechaintransferagentethanewas used to prepare elastomeric grandular polytetrafluoroethylene. The average reaction time was roughly 90 minutes and occurred in the absence of the surfactant perfluoro- octanoic acid. REACTION F F F F F F FFi a i: Ethane, ammonium persulfate, water EXPERIMENTAL Preparation of Low Molecular Weight Polytetrafluoroethylene Specific concentrations and reaction parameters are provided in Table 1. All poly- merizations were carried out in a stainless steel autoclave equipped with a two-bladed, 45 angled flat downdraft agitator mounted on a vertical shaft. An autoclave was charged with water (21.4 kg) and ammonium persulfate dissolved in water (0.3 to 0.6 kg). The vessel was then purged of air by alternately pressuring it with tetrafluoroethylene and evacuating. The chain transfer agent was 237
    • added, and the autoclave heated to 65 C and then pressurized to 1.83 MPa with tetrafluoroethylene with an agitator speed at 600 rpm for the reaction. The initiator solution was next pumped into the autoclave and sufficient tetrafluoroethylene added to maintain a 1.83 MPa reaction pressure. The reaction was completed once the amount of tetrafluoroethyleneadded was between 6.4 and 8 kg. The autoclave was dismantled and the product was isolated. REACTION SCOPING REACTION SCOPING TABLE 1. Single-step experimental parameters used in preparing low molecular weight granular polytetrafluoroethylene using either ethane or chloroform as chain transfer agents. Entry Chain Transfer Agent*1 (mol%) Ammonium Persulface Initiator (lb) Perfluorooctanoic Acid Surfactant (lb) TFE Added (lbs) Reaction Time (min) 1 CHCl3 (2.0) 0.013 None 14.3 128 2 CHCl3 (3.5) 0.019 None 15.9 132 3 C2H6 (2.2) 0.033 None 14.1 82 4 C2H6 (5.4) 0.053 None 14.1 73 5 C2H6 (5.3) 0.066 0.0048 15.9 117 8 C2H6 (3.1) 0.033 None 14.1 98 10 C2H6 (0.33) 0.010 None 14.1 63 11 C2H6 (0.55) 0.013 None 14.1 74 *1 Mol% of gas at the beginning of polymerization TABLE 2. Physical properties of polytetrafluoroethylene formed in the presence of chain transfer agents ethane and chloroform. Particle Size DSC Melting Point ( C)Entry Viscosity Polymer Melt (Pa.S) Specific Surface Area (m2 /g) Average Size (mm) 1 7.1 Â 103 3.58 24.9 125 2 3.8 Â 104 4.24 21.7 148 3 1.3 Â 105 4.35 36.7 296 4 7.9 Â 103 — 25.0 148 5 2.0 Â 103 4.99 12.7 105 8 2.4 Â 104 — 32.8 176 10 NA 4.49 830 1535 11 NA 4.40 649 1535 238 Directly Polymerized Low Molecular Weight Granular Polytetrafluoroethylene
    • NOTES 1. Albano [1] prepared oligomers consisting of 40% perfluoromethylvinylether and 60% tetrafluoroethylene using the surfactant CF2ClO(CF2CF(CF3) O)n(CF2O)mCF2COOH where n/m ¼ 10 with a Mn $ 600 daltons using 1,6-diiodoperfluorohexane as the chain transfer agent. In a subsequent investi- gation by Comino [2] perfluoro oligomers were prepared using 1,10-perfluor- odecadiene, (I), as the crosslinking agent. C F2 (I) 6 2. Perfluoroelastomers prepared by Bish [3] and Hung [4] containing roughly 3 wt% of the termonomer perfluoro(8-cyano-5-methyl-3,6-dioxa-1-octene), (II), or N,N0 -bis(2-propenyl)-4,40 -(hexafluoro-isopropylidene)diphthalimide, (III), respectively, were thermally cured and used as seals in high temperature automotive applications. F2C F C O F2 C CF O C F2 F2 C CF3 CN (II) N CF3 N O O O O (III) CF3 3. Navarrini [5] prepared tetrafluoroethylene/fluorovinyl ether co- and terpo- lymers, (IV), and (V), respectively, that behaved as both plastomers having good thermal and mechanical properties at high temperatures and elastomers with improved properties at low temperatures. Tetrafluoroethylene and non- fluorinated vinyl ether co- and terpolymers were also prepared in the investigation. F2 C C F2 F2 C CF O F2C O C F2 CF3 CF F2 C C F2 F2 C CF O F2C O C F2 CF3 O F2 C CF O CF2 O F3C F3C (IV) (V) a b a b c Notes 239
    • References 1. M. Albano et al., US Patent 7,022,773 (April 4, 2006) 2. C. Comino et al., US Patent Application 2005-0282969 (December 22, 2005) 3. C.J. Bish et al., US Patent 6,638,999 (October 28, 2003) 4. M.H. Hung et al., US Patent 6,794,455 (September 21, 2004) 5. W. Navarrini, US Patent 6,963,013 (November 8, 2005) 240 Directly Polymerized Low Molecular Weight Granular Polytetrafluoroethylene
    • Title: Fluoroelastomers Containing Copolymerized Units of Vinyl Esters Author: M.-H. Hung et al., US Patent Application 2007-0100101 (May 3, 2007) Assignee: Dupont Performance Elastomers, L.L.C. (Wilmington, Del) SIGNIFICANCE In order to fully develop physical properties such as tensile strength, elongation, and compression set, perfluoro elastomers must be cured. Perfluoro elastomers containing vinyl acetate units were prepared that, when saponified with sodium hydroxide, provide hydroxyl cure sites. REACTION F2C CF OCF3 F2 C CF OCF3 F2 C C F2 O O a b c i i: Ammonium perfluorononante, disodium phosphate heptahydrate, ammonium persulfate, vinyl acetate, tetrafluoroethylene EXPERIMENTAL 1. Preparation of Poly(Tetrafluorene-co-Perfluoro(Methylvinyl Ether)-co- Vinyl Acetate) A 1-liter stainless reactor was charged with 450 ml of water, ammonium perfluor- ononante (3.0 g), disodium phosphate heptahydrate (2.0 g), ammonium persulfate (0.4 g), and vinyl acetate (5.0 g). The reactor was sealed, treated with tetrafluoroethy- lene (45 g) and perfluoro(methylvinyl ether) (40 g), and heated to 70 C for 8 hours 241
    • with an agitation speed of 900 rpm. Thereafter the latex was coagulated with saturated MgSO4 solution, and the precipitate was collected by filtration. The solid was washed with warm water, dried, and 29.4 g of product were isolated as a white polymer. The product had a Tg of 0.2 C and a composition consisting of TFE/PMVE/ VAc, 60.0:32.0:8.0 mol%, respectively. DERIVATIVES TABLE 1. Summary of random co-vinyl acetate derivatives prepared by emulsion polymerization using ammonium persulfate as the free radical initiator. Entry Polymer*1 Composition Tg ( C) 2 PMVE-VAc 31.7 68.3 23 3 TFE-TFP-PVAc 63.0:30.4:5.0 — TFE-TFP-VA 63.0:30.4:1.6 — 4 TFE-P-VAc-TFP 63.3:31.8:3.2:1.7 6.9 5 TFE-PMVE-E-VAc 46.7:27.3:25.2:10.8 À11.1 Note: Vinyl acetate derivatives was saponified using sodium hydroxide. *1 E, Ethylene P, Propylene VA, Polyvinyl alcohol VAc, Vinyl acetate PMVE, Perfluoromethylvinyl ether TFE, Tetrafluoroethylene TFP, 3,3,3-Trifluoropropene NOTES 1. In an earlier investigation by the author [1] a random polymer consisting of TFE-VF2-PVME-VAc, 30.4:41.9:27.0:0.7 mol%, respectively, was prepared having a Tg of À28.1 C. 2. A copolymer consisting of TFE and 24 mol% of perfluoro-3,5-dioxa-1-hep- tene, (I), with a Tg of À21.4 C was prepared by Navarrini [2] that had good high-temperature properties and elastomers with improved low-temperature properties when using perfluoropropenylperoxide as the free radical initiator. Arrigoni [3] used perfluoro-3,5-dioxa-1-heptene with vinylidene fluoride and 3,3,4,4,5,5,6,6,7,7,8,8-dodecylfluoro-1,10 decadiene, (II), to prepare perfluor- oelastomers with enhanced low-temperature properties. F3C F2 C O F2 C O F C CF2 (I) F2 C 6 (II) 242 Fluoroelastomers Containing Copolymerized Units of Vinyl Esters
    • 3. Perfluoro elastomers having improved low-temperature properties were pre- pared by Grootaert [4] and consisted of TFE-HFP-perfluorocyanopropyl perfluorovinyl ether, (III), 65.0:34.2:0.8, respectively, NC F2 C C F2 F2 C O F C CF2 (III) References 1. M.-H. Hung et al., US Patent Application 2007-0100099 (May 3, 2007) 2. W. Navarrini, US Patent Application 2007-0100100 (May 3, 2007) 3. S. Arrigoni et al., US Patent Application 2007-0093625 (April 26, 2007) 4. W.M.A. Grootaert et al., US Patent 7,094,839 (April 22, 2006) Notes 243
    • D. Low Surface Energy Title: Amorphous Polyether Glycols Based on bis- Substituted Oxetane and Tetrahydrofuran Monomers Author: A. A. Malik et al., US Patent 6,998,460 (February 14, 2006) Assignee: Aerojet-General Corporation (Sacramento, CA) SIGNIFICANCE Mono- and di-substituted oxetane monomers containing 2,2,2-trifluoroethoxy methyl substituents have been prepared. These agents were then used to prepare elastomers, thermoset plastics, and related articles where a very low surface energy was required. REACTION O OO F3CH2C CH2CF3 O O O F3CH2C CH2CF3 ii O OO Tosylate Tosylate i a i: DMF, sodium hydride, trifluoroethanol ii: Trifluoroethanol, boron trifluoride etherate, CH2Cl2 EXPERIMENTAL 1. Preparation of 3,3-bis-(2,2,2-Trifluoroethoxymethyl)Oxetane Sodium hydride (0.383 mol) was suspended in 200 ml of DMF, treated with the dropwise addition of trifluoroethanol (0.383 mol), and stirred for 30 minutes. This mixture was further treated with a solution of 3,3-bis-(hydroxymethyl)oxetane di-p- toluenesulfonate (0.073 mol) in 50 ml of DMF. The mixture was then heated to 75 C for 64 hours, poured into water, and extracted twice with CH2Cl2. The combined extracts were washed with brine, 2% aqueous HCl, water, dried using MgSO4, and 244
    • concentrated. The residue was purified by bulb-to-bulb distillation at 42 C to 48 C at 0.1 mm, and the product was isolated in 79% yield as a colorless oil. 2. Preparation of Poly[3,3-bis-(2,2,2-Trifluoroethoxymethyl)Oxetane] A reaction vessel was charged with a solution of trifluoroethanol (0.058 mol) and boron trifluoride etherate (0.81 mol) dissolved in 900 ml of CH2Cl2 and treated with a solution of the Step 1 product (4.1 mol) dissolved in 485 ml of CH2Cl2 over 2.5 hours. The mixture was stirred at ambient temperature for 16 hours and then quenched with water. The organic layer was washed with brine and 2% aqueous HCl, concentrated, and the product was isolated in 91% yield having a DSC mp of 71.7 C, decomposition temperature >210 C, and a Mn of 27,000 daltons with a PDI of 2.2. DERIVATIVES O O CH2CF3 O O CH2C6F13 O O CH2C10F21 NOTES 1. In an earlier investigation by the author [1] the Step 2 product was converted into urethanes by reacting with toluene diisocyanate, (I). a O O O F3CH2C CH2CF3 HN O NH O O F3CH2C F3CH2C (I) 1 H NMR d 3.87 (s 4H), 3.87 (q, J ¼ 8.8 Hz, 4H), 4.46 (s, 4H) 13 CNMR d 43.69, 68.62 (q, J ¼ 35 Hz), 73.15, 75.59, 123.87 (q, J ¼ 275 Hz); 19 F NMR d À74.6(s) FTIR (KBr, cmÀ1 ) 2960 2880, 1360 1080, 995, 840 Notes 245
    • 2. Thermoplastic polyurethane resins were also prepared by the author [2] from 4,40 -methylene diphenylisocyanate with poly(3,3-bis-(2,2,3,3,4,4,4-hepta- fluorobutoxymethyl)-co-3-(2,2,3,3,4,4,4-heptafluorobutoxymethyl)-3-methy- loxetane) using dibutyltin dilaurate as catalyst and used in low surface energy coating applications 3. Yamamoto [3] prepared perfluoroalkoxy methacrylate, (II), by reacting poly(2- hydroxyethyl methacrylate), (III), with boron trifluoride-diethyl ether com- plex, which was then used to reduce water repellency on surfaces. O O O C8F17 (II) a O C8F17 (III) 4. Kaplan [4] prepared fluorochemical release agents, (IV), for use as fluoroe- lastomer fuser component in electrostatographic reproducing equipment. O Si O CF2 F2C F2C CF2 CF2 F2C CF3 Si a b (IV) References 1. A.A. Malik et al., US Patent 6,417,314 (June 9, 2002) 2. A.A. Malik et al., US Patent Application 2006-0135729 (June 22, 2006) 3. I. Yamamoto et al., US Patent 7,176,267 (February 13, 2007) 4. S. Kaplan et al., US Patent 6,830,819 (December 14, 2004) 246 Amorphous Polyether Glycols Based on bis-Substituted Oxetane and Tetrahydrofuran Monomers
    • E. Silicon Fluids Title: Cyclic Siloxane Compounds and Making Method Author: K. Uehara et al., US Patent 7,189,868 (March 13, 2007) Assignee: Shin-Etsu Chemical Co., Ltd. (Tokyo, JP) SIGNIFICANCE Cyclic siloxane compounds containing an aliphatic unsaturation component and fluorinatedalkylgroupswerepreparedinatwo-stepprocesswithoverallyields >53%. These polymerizable agents are characterized as having water and oil repellency in addition to weather, solvent, and chemical resistance. REACTION Si O Si O Si O F3C CF3 F3C Si O Si O Si O F3C CF3 F3C Si Cl Cl Si O Si O Si O SiO CF3 CF3 F3C iii Notes 1,2 i: Vinylmethyldichlorosilane, hexamethylphosphoric triamide ii: Water, isooctane EXPERIMENTAL 1. Preparation of 1-Chloro-1-Methyl-1-Vinylsiloxy-3,5,7-Tris(30 ,30 ,30 - Trifluoropropyl)-7-Chloro-7-Methylsiloxy-3,5,7-Hexamethylcyclotrisiloxane A flask was charged with 1,3,5-tris(30 ,30 ,30 -trifluoropropyl)-1,3,5-hexamethylcyclo- trisiloxane(0.3 mol)thathadbeenmeltedbyheatingthesolidto40 Cto50 Candthen treated with vinylmethyldichlorosilane (0.3 mol). The mixture was further treated with the dropwise addition of hexamethylphosphoric triamide (0.0015 mol) and the 247
    • temperature kept at roughly 50 C for 2 hours. An analysis of the contents by gas chromatography indicated that the product yield was 91%. 2. Preparation of 1-Vinyl-3,5,7-Tris(30 ,30 ,30 -Trifluoropropyl)-1,3,5,7- Tetramethylcyclotetra-Siloxane A flask was charged with 162 ml of water and slowly treated with the dropwise addition of the Step 1 product while the mixture stirred at À10 C. After the addition, themixturewasstirred30minutesatambienttemperaturewithIRmonitoringuntilthe reaction was complete. The mixture was extracted with 180 g of isooctane and then washed with water and concentrated under reduced pressure. The residue was purified by distillation at 101 C to 105 C under reduced pressure, and 114 g ofa liquid fraction product was isolated in 68% yield. DERIVATIVES Si O Si O Si O SiOR CF3 CF3 F3C NOTES 1. Additional polymerizable cyclic siloxane derivatives, (I), were prepared by the author [1] in a subsequent investigation. Si O Si O Si O SiO CF3 CF3 F3C O O (I) TABLE 1. Step 1 and 2 product yields of tetramethylcyclotetrasiloxane derivatives. Entry R Step 1 Yield (%) Step 2 Yield (%) 2 CH2¼C(CH3)CO2CH2CH2CH2 84 64 3 CF2¼CH2CH2 85 98 1 H-NMR (CDCl3) d 0.16 0.17, d, 9H; 0.20, s, 3H; 0.74 0.84, m, 6H; 1.96 2.16, m, 6H; 5.74 6.10, m, 3H MS ¼ 554 248 Cyclic Siloxane Compounds and Making Method
    • 2. Cyclic oligosiloxanes were prepared by Shinbo [2] through a disproportion- ation reaction using tri(i-propoxy)aluminum as the catalyst as illustrated below. (H3C)3SiO OSi Si(CH3)3 H O Si O Si O Si OSiH H H H 45 i i: Tri(i-propoxy)aluminum 3. Kiyomori [3] prepared a monofunctional polymerizable oligosiloxane cage, (II), which improved compatibility with solvents and was also polymerizable with other monomers. O Si O O (II)Oligosiloxane cage 4. Fluorosilane monomers, (III), prepared by Kinsho [4] were converted into the corresponding terpolymer, (IV), by reacting with water and acetic acid then used in resist compositions. SiC2H5O OC2H5 OC2H5 O O O CF2 CF3 OH O Si O O O CF2 CF3 OH O Si O O t-C4H9 O Si O O (III) 20 30 503/23/23/2 (IV) 5. Through the polymerization of pentamethylcyclopentasiloxane, (V), Kennedy [5] prepared new compositions of matter consisting of poly(cyclosiloxane) network derivatives, (VI), as illustrated below. Notes 249
    • O HSi O H Si O SiH OSi H O Si O Si O Si OSi O Si O SiH O Si OSi O Si O Si O Si OSi O Si O Si O Si OSi O O O O ..... ..... ..... ..... ..... ..... ..... (V) (VI) ..... i i: Platinum divinyl complex, toluene (Karstedt’s system) 6. Molding compositions were prepared by Fehn [6] by curing vinyldimethylsiloxy-terminated polydimethylsiloxane with rhodium(III) acetylacetonate. References 1. K. Uehara et al., US Patent Application 2006-0264649 (November 23, 2006) 2. K. Shinbo et al., US Patent Application 2006-0223963 (October 5, 2006) 3. A. Kiyomori et al., US Patent Application 2006-0074213 (April 6, 2006) 4. T. Kinsho et al., US Patent Application 2007-0009832 (January 11, 2007) 5. J. Kennedy et al., US Patent 7,071,277 (July 4, 2006) 6. A. Fehn et al., US Patent Application 2006-0058484 (March 16, 2006) 250 Cyclic Siloxane Compounds and Making Method
    • F. Surfactants Title: Fluorinated Organosilicon Compounds and Fluorochemical Surfactants Author: H. Yamaguchi et al., US Patent Application 2006-0264596 (November 23, 2006) Assignee: Shin-Etsu Chemical Co., Ltd. (Tokyo, JP) SIGNIFICANCE Although fluorochemical surfactants containing perfluoroalkyl carbonyl fluorides currently exist in the art, it is difficult to obtain perfluoroalkyl derivatives containing sixormorecarbons.Amethodtoaddressthisproblemusingorganosiliconcompounds is described. REACTION O Si (CH2)3 CH3 CH3 OCH2CF CF3 (OCF2CF) CF3 F Si O(H2C)2 Si CH3 (CH2)3 CH3 (CH2CHO)3CH3 Si((H3C)2HSiO) 3 CH2CH2 Si (OSiH(CH3)2)3 i Note 1 0.75 2.25 2 2 i: Di(perfluoroethylene oxide) allyl ether, toluene, platinum(0) 1,3-divinyl-1,1,3, 3-tetramethyldisiloxane, tri(ethylene oxide) allyl ether EXPERIMENTAL Preparation of Polysiloxane Aflaskwaschargedwithasiloxane(85.7 g)andtoluene (105.6 g)containingplatinum (0) 1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex (0.18 g; 0.9 mg Pt) and heated 251
    • to 80 C. This mixture was treated with the dropwise addition of di(perfluoroethylene oxide)allylether(125.4 g)andtri(ethyleneoxide)allylether(147.1g)forover2 hours. The mixture was then concentrated, and 320.0 g of product were isolated as a pale brown oil. DERIVATIVES Derivatives corresponding to the Step 1 product with varying polyether/fluorine content are provided in Table 1. NOTES 1. Structures of the Step 1 co-reagents perfluoropolyether allyl ether, (I), and allyl polyether, (II), are provided below. F (CFCF2OCF)2 CF3 CF3 CH2OCH2CH=CH2 CH3(CH2CH2O)3OCH2CH=CH2 (I) (II) 2. The surface treatment agent perfluoropolyether-modified silane, (III), was prepared by the author [1] and had improved water/oil repellency, chemical resistance, and antifouling properties. Si OC2H5 (CH2)3OC2H5O OC2H5 CH2CF2 (OC2F4)21(OCF2)24OCF2CH2 O(CH2)3 Si OC2H5 OC2H5 OC2H5 (III) TABLE 1. Correlation of surface tension and HLB for Step 1 products containing varying amounts of polyether and fluorine contents. Entry Fluorine Content (%) Polyether Content (%) HLB Surface Tension (dynes-cmÀ1 ) 1 21.6 26.6 5.3 24.5 2 24.7 37.3 7.5 23.3 3 11.5 49.4 9.9 25.1 4 5.9 56.0 11.2 26.3 5 27.1 22.2 4.4 23.5 1 H-NMR d 0–0.1 (36H, Si–CH3), 0.1-0.2 (16H, Si–CH2–),1.3–1.5 (12H, –CH2–), 3.1 (27H, CH3O–), 3.2– 3.5 (72H, –CH2O–) 252 Fluorinated Organosilicon Compounds and Fluorochemical Surfactants
    • 3. Copolymers consisting of N-methyl perfluorooctyl sulfonamidoethylacrylate and 3-trimethyl-silylpropyl methacrylate, (IV), were prepared by Dams [2] and used as oil and water repellents. O ONHO SO2 C8F17 (H3CO)3Si (IV) a b 4. The polycondensate of FomblinÒ and 3-(trimethoxysilyl)propyl amine pre- pared by Moore [3] was used to provide resistance to water, oil, and stain repellency to a substrate or fabric. De Dominicis [4] used mono and difunc- tional perfluoropolyether phosphates and amidosilane derivatives as anti- staining agents for ceramic materials. 5. A three-component, (V), (VI), and (VII), curable fluoropolyether useful in rubber compositions and rubber fabrics was prepared by Osowa [5]. The material exhibited solvent resistance, chemical resistance, weather resistance, water and oil repellency, and heat resistance. Si N CF O F2 C CF O C F2 F2 C O CF O CF3 CF3 C F2 O CF CF3 CF3 N O Si (V) C8F17 Si H Si Si O Si a b 3 )IIV()IV( a + b = 130 References 1. H. Yamaguchi et al., US Patent 7,196,212 (March 27, 2007) 2. R.J. Dams, US Patent 7,166,329 (January 23, 2007) 3. G.G.I. Moore et al., US Patent 7,097,910 (August 29, 2006) 4. M. De Dominicis et al., US Patent 7,045,016 (May 16, 2006) 5. Y. Osawa et al., US Patent 6,979,710 (December 27, 2005) Notes 253
    • XI. GELS A. Gelling Agent Title: Ferrocene-Containing, Organic Gelling Compound, and Gel and Cast Film Using the Same Author: N. Kimizuka et al., US Patent 7,041,842 (May 9, 2006) Assignee: Honda Giken Kogyo Kabushiki Kaisha (Tokyo, JP) SIGNIFICANCE Ferrocene compounds and polymers have been used as micelle-forming agents in electrochemical processes for producing organic films usable in electronic materials such as color filters. To increase the concentration of ferrocene in these processes, an ferrocene oligomer having gelling properties has been prepared. REACTION O NH2 O N H O H N O O t-C4H9 O H NO O N H O NH3 Cl O H NO O N H O NH O H NO O Fe Gel i iiiii iv 11 11 11 11 11 11 11 i: Butyloxycarbonyl-l-glutamic acid, triethylamine, THF, diethyl phospho- rocyanidate ii: Trifluoroacetic acid Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 255
    • iii: CCl3H, triethylamine, ferrocene carboxylic acid, 2-oxo-3-oxazolidinyl)-phos- phinic chloride iv: Acetonitrile, N-methyl-N0 -methoxymethyl-imidazolium bromide EXPERIMENTAL 1. Preparation of BOC Intermediate A reaction vessel was charged with 3-lauryloxypropyl-1-amine (17.8 mmol), buty- loxycarbonyl-l-glutamic acid (8.1 mmol), and triethylamine (17.8 mmol) dissolved in 150 ml of THF, and then ice-cooled. This mixture was slowly treated with diethyl phosphorocyanidate(17.8mmol)andthenstirredundericecoolingfor30minutesand at ambient temperature for 3 days. It was concentrated and a pale-yellow oily residue isolated. The residue was dissolved in CCl3H, washed twice apiece with 5% aqueous NaHCO3 and water, and dried using Na2SO4. The solution was filtered, concentrated as apale-yellowsolid after recrystallizationinacetone, and the product wasisolated as a colorless powder in 60.2% yield. 2. Preparation of Ammonium Chloride Intermediate The Step 1 product (4.9 mmol) was dissolved in 100 ml of CH2Cl2, treated with 20% trifluoroacetic acid, and stirred overnight at ambient temperature. The mixture was concentrated, and an oily residue was isolated. The residue was dissolved in 50 ml of acetone and then treated with 1 ml concentrated hydrochloric acid with cooling until a precipitate was formed. The solid was re-crystallized twice from EtOAc, and the product was isolated as a colorless powder in 40.9% yield. 3. Preparation of Ferrocene-Containing Gelling Compound The Step 2 product (1.58 mmol) and triethylamine (1.8 mmol) were dissolved in CCl3H and treated with water, and then the mixture shaken. The CCl3H phase was isolated, dried with Na2SO4 and concentrated. The residue was dissolved in CH2Cl2 andtreatedwithtriethylamine(1.8mmol),ferrocenecarboxylicacid(1.73mmol),and N,N-bis(2-oxo-3-oxazolidinyl)-phosphinic chloride (1.73 mmol). This mixture was stirred under ice-cooling for 30 minutes, stirred at ambient temperature 3 days, and then concentrated. The residue was dissolved in CCl3H, washed with 5% aqueous NaHCO3 and dilute with hydrochloric acid. The mixture was filtered and concentrat- ed, and the residue was purified by chromatography with silica gel using CCl3H. Four componentswere identified.The first twocomponents were discarded. The remaining two components were separated by silica gel column chromatography using CCl3H/ CH3OH, 10/1, respectively, to isolate the gel-forming third component. This compo- nent was then re-crystallized from hexane, and the product was isolated as a pale- yellow solid in 31% yield, MP ¼ 82.1  C to 83.5  C. 256 Ferrocene-Containing, Organic Gelling Compound, and Gel and Cast Film Using the Same
    • 4. Preparation of Gel A 20 mM solution of the Step 3 product in acetonitrile and N-methyl-N0 -methoxy- methyl-imidazolium bromide was prepared. The mixture was heated and left to stand at ambient temperature for 30 minutes. An organogel and ionogel formed that were observed using a dark-field optical microscope. The organogel indicated the presence of microcrystals suggesting that they have an associated fibrous structure or that crystals were formed by the slide cover glass; the micron-level fibrous structures were not observed in the ionogel. DERIVATIVES Only the Step 3 product was prepared. NOTES 1. A supramolecular hydrogel underwent a reversible gel-sol transformation that was formed by adding 9,10-dimethoxy-2-anthracenesulfonic acid to an aque- ous dispersion of a cationic amphiphile, (I), as was previously prepared by the author [1]. The gel had a network with a bilayer-membrane and a nanofiber structure. N H O H N O H N O N OH 11 11 (I) 2. Sugar-derived gelatinizers, (II), having gel-forming capability in both organic solvents and water were prepared by Jung [2], and agglomerates were system- atically designed by altering the hydrocarbon tail. OHO HO OH OH O NH (II) 3. Eagland [3] demonstrated that in the presence of acid, polyvinylalcohol and poly(4-(4-formylphenylethenyl)-1-methyl)-pyridinium methosulphonate, Notes 257
    • (III), formed a hydrogel that could be used to encapsulate water-insoluble materials. Soybean-based materials prerpared by Liu [4] were also effective as hydrogels and used as drug delivery agents. O OOH OH N a b (III) References 1. N. Kimizuka et al., US Patent 6,576,679 (June 10, 2003) 2. J.H. Jung et al., US Patent 7,196,178 (March 27, 2007) 3. D. Eagland et al., US Patent 7,202,300 (April 10, 2007) 4. Z. Liu et al., US Patent Application 2007-0077298 (April 5, 2007) 258 Ferrocene-Containing, Organic Gelling Compound, and Gel and Cast Film Using the Same
    • B. Hydrogels Title: Random Block Copolymers Author: N.B. Graham et al., US Patent 7,241,845 (July 10, 2007) Assignee: Ocutec Limited (Glasgow, GB) SIGNIFICANCE A linear urea-urethane block copolymer containing polyethylene oxide and polypro- pylene oxide was prepared by reacting polyethylene glycol and polypropylene glycol withdicyclohexylmethane4,40 -diisocyanateand4,40 -diaminodiphenylmethane.These materialsareparticularlyadvantageousbecauseoftheirhighmechanicalstrengthinthe swollenstate.Mechanicalpropertytestingindicatedthattheenergyneededtobreakthe copolymer hydrogel was at least 40% of that of the copolymer in the dry state. REACTION O O O OO O N H O N H NH O N H O N H O N H O O 75 5 n HO O OH 75 i i: Polyethylene glycol, polypropylene glycol, 4,40 -diaminodiphenylmethane, dicy- clohexylmethane 4,40 -di-isocyanate, ferric chloride EXPERIMENTAL Random Urea-Urethane Copolymer of Polyether Glycol, Polypropylene Glycol, Dicyclohexylmethane 4,40 -Diisocyanate, and 4,40 -Diaminodiphenylmethane A reactor was charged with polyethylene glycol having a Mn 5830 daltons and polypropylene glycol with a Mn 425 daltons and then heated until melted and 259
    • thoroughly mixed. The mixture was next heated to 95 C to 100 C and treated with anhydrous ferric chloride and stirred until the catalyst dissolved. This mixture was treatedwith4,40 -diaminodiphenylmethane(0.726 g)andagainthoroughlymixeduntil the solution was homogeneouse; the solution was then posttreated with 12.67 ml dicyclohexylmethane 4,40 -diisocyanateand heated for2minutes at90 C.The mixture was poured into preheated polypropylene test tube molds and placed into an oven at 95 C for 20 hours, and the product was isolated. DERIVATIVES TABLE 1. Reagent variations in preparing poly(urea-urethane) derivatives using polyethylene glycol and polypropylene glycol. Entry PEG-5380 (wt%) PPG-425 (mol) Diamine (mol) Diisocyanate (mol) 1 10.01 72.0 3.554 80.320 4 27.19 21.0 1.310 24.476 7 48.34 8.0 0.736 10.223 9 63.55 4.0 0.560 5.838 TABLE 2. Equilibrium swelling for selected poly(urea-urethane) derivatives in water at 37 C. Entry PEG-5380 (wt%) Equilibrium Water Uptake (pph) Equilibrium Water Content (%) Equilibrium PPG/Water 1 10.01 21.0 17.36 25.63 4 27.19 82.0 45.05 59.99 7 48.34 183.0 64.66 81.74 9 63.55 298.0 74.87 90.84 TABLE 3. Mechanical properties for water-swollen poly(urea-urethane) derivatives at 37 C. Entry PEG-5380 (wt%) Water Content (%) Young’s Modulus (MNmÀ2 ) Energy to Break Dry Film (MNmÀ2 ) Energy to Break Swollen Film (MNmÀ2 ) 1 10.01 17.36 0.764 48.719 8.529 4 27.19 45.05 0.830 57.626 67.313 7 48.34 64.66 1.500 172.934 76.203 9 63.55 74.87 0.507 299.697 52.047 260 Random Block Copolymers
    • NOTES 1. Degradable difunctional poly(ethylene glycol) acrylates, (I), were prepared by Harris [1] and then photolytically converted into hydrogels and used in drug delivery systems. CH2=CHCO2-PEO2-O-CH2CO2CH(CH3)CH2CONH-PEO2CCH=CH2 (I) 2. Muller [2] prepared hydrogels that were used in contact lenses with difunc- tional siliconecontaining crosslinkers, (II), with amphiphilic block prepoly- mers. Tetrafunctional crosslinkers, (III), prepared by Lewis [3] were used as biocompatible coating applications. N O Si O Si N N H OOCN N H O NCO H N O Si O Si H N O 3 354 (II) (III) 3 3 b b a 3. Swellable hydrogels, (IV), used for sensor coatings were prepared by Van Antwerp [4] and were capable of water uptake of at least 200% by weight. N H H N H N O N HO N H O N H O O O N H O a b c (IV) References 1. J.M. Harris et al., US Patent 7,214,388 (May 8, 2007), US Patent 7,166,304 (January 23, 2007), and US Patent 7,018,624 (March 28, 2006) 2. B. Muller et al., US Patent 7,091,283 (August 16, 2006) 3. A.L. Lecvis et al., US Patent 7,064,174 (June 20, 2006) 4. W.P. Van Antwerp et al., US Patent 6,784,274 (August 31, 2004) Notes 261
    • Title: (Meth)Acrylic Esters of Polyalkoxylated Trimethylolpropane Author: A. Popp et al., US Patent 7,199,211 (April 3, 2007) Assignee: BASF Aktiengesellschaft (Ludwigshafen, DE) SIGNIFICANCE Oligomeric agents were prepared by condensing trimethylolpropane with ethylene and/or propylene oxides and capping with acrylic acid. These materials were subsequently crosslinked using 2,20 -azobisamidinopropane dihydrochloride, which formed superabsorbent swellable hydrogel addition polymers and were useful as components in diapers or in feminine hygiene products. REACTION HO OH OH O O O OO O H O H O O H O O O OO OO O O O O O 5 30 5 30 5305 30 5 305 30 Notes 1,2 i ii Superabsorbant hydrogel i: Potassium hydroxide, ethylene oxide, propylene oxide ii: Acrylic acid, sulfuric acid, methylcyclohexane, hydroquinone monomethyl ether, triphenyl phosphate, hypophosphorous acid 262
    • EXPERIMENTAL 1. Preparation of Trimethylolpropane Ethoxylated/propoxylated (TMP-30EO-5PO) An autoclave was charged with trimethylolpropane (77 g) and 45% aqueous KOH (0.5 g) and then azeotroped at 80 C and 20 mbar. The mixture was next treated with ethylene oxide (759 g) at, 45 C to 155 C and reacted at elevated pressure until no further change in pressure was observed. The mixture was stirred an additional 30 minutes at 150 C and then treated with propylene oxide (167 g) at 120 C to 130 C. The reactor was purged, the contents cooled to 60 C, and the catalyst removed by filtration. The product was isolated and consisted of 30-tuply ethoxylated and 5- tuply propoxylated trimethylolpropane. 2. Preparation of Trimethylolpropane Ethoxylated/propoxylated Triacrylate The Step 1 product (1427 parts) was converted into the corresponding acrylate ester by treating with acrylic acid (216 parts), sulfuric acid (5 parts) in methyl- cyclohexane (345 parts), hydroquinone monomethyl ether (3 parts), triphenyl phosphite (1 part), and hypophosphorous acid (1 part). The reaction continued until 44 parts of water were removed before beginning the vacuum distillation. The residue was purified by filtering through a K300 filter, and the acid number was determined. The product viscosity was adjusted to 330 mPas by the addition of 96 parts of acrylic acid, and a colorless product was isolated. DERIVATIVES NOTES 1. Step 2 products were subsequently converted into crosslinked superabsorbent hydrogels and used as components in diapers or in feminine hygiene products. The preparation of these superabsorbant hydrogels is described below. TABLE 1. Properties of hydrogels prepared by free radically polymerizing the corresponding triacrylate with 2,20 -azobisamidinopropane dihydrochloride. Entry Hydrogel Saponification Index CRC-1*1 (g/g) 1b TMP-15E0 11.6 29.7 1d TMP-30EO-5PO 4.7 30.1 1f TMP-5PO-30EO 7.0 29.5 1g TMP-10PO-50EO 4.1 30.1 *1 Centrifuge retention capacity test Notes 263
    • Preparation of a Superabsorbent Hydrogel Using Internal Crosslinkers A reactor containing acrylic acid (305 g), 37.3wt % aqueous sodium acrylate (3204 g), and water (1465 g) was treated with ethoxylated (15 EO) trimethylolpropane tria- crylate (12.2 g), 2,20 -azobisamidinopropane dihydrochloride (0.61 g), and sodium persulfate (3.05 g). The mixture was purged for 30 minutes and further treated with hydrogen peroxide (0.244 g) dissolved in water (5 g) and ascorbic acid (0.244 g) also dissolved in water (5g). The mixture was then heated in a thermally insulated tub for about 30 minutes; the temperature at the start of the reaction was 113  C. The reaction started after a few minutes and proceeded under adiabatic conditions until the product was isolated and comminuted through a meat grinder equipped with a 6 mm breaker plate. The residue was dried at 80 C under reduced pressure and the produce, was isolated having a sieve fraction of 300 to 600 mm. 2. Additional superabsorbent hydrogel derivatives containing EO/PO ratios other than those of the current invention were prepared by the author [1] in a subsequent invention. 3. Smith [2] prepared a series of superabsorbent polymers with high permeability consisting of the reaction product of NaOH, water, acrylic acid, methoxypo- lyethyleneglycol (750), monomethacrylate of trimethylolpropanetriacrylate, TMP-3EO, and hydroxymonoallyl ether-10EO. These materials were useful in the transportation of liquids in the swollen state. 4. Funk [3] prepared hydrogels with different pH values by reacting 90 parts of hydrophilic polymeric agents with glacial acrylic acid, water, and penta- erythritol triallyl with 10 parts of acrylic acid, sorbitan monococoate, and allyl methacrylate. 5. Water absorbing polymers consisting of acrylic acid, polyethylene glycol monoallyl ether acrylate, and polyethylene glycol diacrylate were prepared by Brehm [4] containing interstitial agents such as zeolites high in silicon. References 1. A. Popp et al., US Patent 7,259,212 (August 21, 2007) 2. S.J. Smith et al., US Patent 7,173,086 (February 6, 2007) and US Patent 7,169,843 (January 30, 2007) 3. R. Funk et al., US Patent 7,144,957 (December 5, 2006) 4. H.G. Brehm et al., US Patent 7,101,946 (September 5, 2006) 264 (Meth)Acrylic Esters of Polyalkoxylated Trimethylolpropane
    • Title: Prepolymers for Improved Surface Modification of Contact Lenses Author: Y.-C. Lai, et al., US Patent 7,176,268 (February 13, 2007) Assignee: Bausch & Lomb, Inc. (Rochester, NY) SIGNIFICANCE Fumarate- and fumaramide-containing hydrogels have been prepared with silicone as a co-component that are highly oxygen permeable. These agents are biocompatible and useful as biomedical devices, particularly as contact lenses. REACTION Si O Si O Si H OO HO OH Si O Si O Si OO I O O O O HO O O OH Si O Si O Si OO O O O O O O O OH2N 22 22 22 Si O Si O Si OO O O O O O O O O 22a dc b ON O N Not Isolated i ii NH2 3 H N NH 33 OO Note 1 e 3 i: Fumaryl chloride, water 265
    • ii: Hexanol, N,N-dimethylacrlyamide, DaracureÒ , tris(hydroxymethyl)aminome- thane, water EXPERIMENTAL 1. Preparation of Polydimethylsiloxane with Fumaric Acid Termini A dried 500-ml round bottom flask was charged with bis(a,o-hydroxybutyl poly- dimethylsiloxane)(Mn 1624daltons;0.0185 mol)andfumarylchloride(0.0418 mol) andthenheatedto60 Cfor2hoursandconcentrated.Theresiduewastreatedwith3 mg of water and 30 ml of THF and refluxed until noIR evidence of acid chloride absorption waspresent.Themixturewasnextconcentrated,theresiduedissolvedin200 mldiethyl ether, extracted three times with 50 ml, dried with MgSO4, re-concentrated, and the product was isolated. 2. Preparation of Hydrogel Films A mixture consisting of the Step 1 product (32 parts), N,N-dimethylacrylamide (32 parts),tris(hydroxymethyl)aminomethane(36parts),hexanol(27parts),andDarocurÒ (0.3parts)werecastbetweentwosilane-treatedglassplatesandcuredfor1hourat70 C. The cured films were then released, extracted in isopropanol, and boiled for 4 hours in water. Hydrogel films were stored in borate buffered saline solution until needed. DERIVATIVES TABLE 1. Selected Step 1 hydrogel pre-polymers converted into hydrogels by curing with tris(hydroxymethyl) aminomethane, hexanol, and DarocurR for 1 hour at 70 C. Entry Monomer(s) N,N-Dimethylacrylamide: Monomer Ratio (mol) 8 Glycidyl methacrylate 6:1 9 Octafluoropentyl methacrylate/glycidyl methacrylate 5.7:1.07:1 10 Octafluoropentyl methacrylate/glycidyl methacrylate 2.85:1.07:1 13 Methacrylic acid 3.60:1 Source: Very limited characterization data supplied by author. Mn ¼ 2001 daltons Mw ¼ 3141 daltons Pd ¼ 1.57 Water content ¼ 39%, Modulus ¼ 36 g/mm2 Tear strength ¼ 13 g/mm Oxygen permeability ¼ 93 Dk unit 266 Prepolymers for Improved Surface Modification of Contact Lenses
    • NOTES 1. Additional Step 2 polymer analogues containing hydrophilic arylsiloxy-con- taining macro-monomers, (I), were prepared by Salamone [1]. O O Si O Si O O Si O O N O 3 a b a (I) 2. Schmitt [2] prepared high-transparency lens materials by free radical polymer- ization of methacrylate monomers containing carbamate, (II), and ether, (III), segments. Free radical polymerization of 3-thietanyl derivatives, (IV)–(VI), using UV radiation was prepared by Kobayashi [3] and used in the manufacture of high-transparency lens. O O H N O O H N O O O O O X O X O O aa (II) (III) a = 2 – 20 X = O, S S S S S S S S S RS S n n = 1,2 (IV) (V) (VI) R = CH2NCO CH=CH2 S Notes 267
    • 3. Polyisocyanates bicyclo[2.2.1]heptane-2,5(6)-diisocyanate, (VII), and tricyclo [5.2.1.0.2,6 ]-decane-3(4),8(9)-diisocyanate were used by Haseyama [4] to prepare high-transparency polythiourethane, (VIII), lens materials. HN NH CO S S S S S CO OCN NCO n = 1,2 n n )IIIV()IIV( 4. Thioamino, (IX), and siloxy, (X), crosslinkable prepolymers were prepared by Muller [5] and used in the manufacture of contact lenses. N H H N H N OO SHHS N H O Si O Si N H O (IX) (X) n References 1. J.C. Salamone et al., US Patent Application 2006-0287455 (December 21, 2006), US Patent Application 2006-0286147 (December 21, 2006), and US Patent Application 2006-0270749 (November 30, 2006) 2. B. Schmitt et al., US Patent 7,144,954 (December 5, 2006) 3. S. Kobayashi et al., US Patent Application 2005-0215757 (September 29, 2005) and US Patent 7,132,501 (November 7, 2006) 4. K. Haseyama et al., US Patent Application 2005-0049430 (March 3, 2005) 5. B. Muller et al., US Patent 7,091,283 (August 15, 2006) 268 Prepolymers for Improved Surface Modification of Contact Lenses
    • Title: Preparation of High Molecular Weight Polysuccinimides Author: C. S. Sikes, US Patent 7,053,170 (May 30, 2006) Assignee: Aquero Company (Eugene, OR) SIGNIFICANCE L-Aspartic acid solubilized with hydrochloric was polymerized with 30% polypho- sphoric acid at 180 C to prepare linear polysuccinimides having a Mw of 180,000 daltons. When the polysuccinimide was hydrolyzed with dilute sodium hydroxide an a,b-polysodium aspartate hydrogel was generated. REACTION H2N O OH HO O N O O i H N H N O O O O OO Na Na ii Notes 1,2a a i: Hydrochloric acid, polyphosphoric acid ii: Sodium hydroxide, water EXPERIMENTAL 1. Preparation of Polysuccinimide Eleven50-mlbeakerswaschargedwithL-asparticacid(0.01 mol)andsolubilizedwith 13.3 ml of 1M hydrochloric acid (0.013 mol) at ambient temperature. The first three beakerswere treatedwith0.066 ml ofpolyphosphoric acid (specificgravity 2.0)and then warmed to 80 C acid. The second three beakers was treated with 0.266 ml polyphosphoricacid;thelastfourbeakersweretreatedwith0.399 gofpolyphosphoric acid. Each solution was dried at 120 C, resulting in clear glassy pucks of intimate mixtures of aspartic acid and the polyphosphoric acid catalyst. The dried materials 269
    • were then thermally polymerized at 180 C, and aliquots were intermittently removed from between 1 to 7 hours. Aliquots were washed with water and centrifuged, the process being repeated 3 times, and the products isolated as light powders. Analytical results are provided in Table 1. 2. Preparation of a,b-Poly Aspartate Sodium The Step 1 product was ring-opened by mild alkaline hydrolysis using 1 equivalent of 0.1M of NaOH per equivalent of succinimide. The alkaline conditions were held at pH 10 by auto-titration at 80 C in water bath. Under these mild conditions polysucci- nimides were converted to polyaspartates within 1 hour. REACTION SCOPING NOTES 1. The procedure for preparingsodium polyaspartate bythe basic hydrolysis of the Step 1 product using 0.1M, NaOH in this investigation was too vague to be experimentally useful. Instead the procedure was obtained from a subsequent publication by the author [1]. 2. In a subsequent investigation by the author [1] polysuccinimdes were prepared using phosphoric, metaphosphoric, and diphosphoric acids. TABLE 1. Summary of weight average molecular weights from the preparation of polysuccinimides using L-aspartic acid using polyphosphoric acid. L-Aspartic Acid Catalyst Reaction Time@ 180 C (h) Mw (dalton) None 2 7,400 Hydrochloric acid 4 12,000 Polyphosphoric acid 7 178,000 Hydrochloric acid þ 10% polyphosphoric acid 7 12,000 Hydrochloric acid þ 20% polyphosphoric acid 7 38,000 Hydrochloric acid þ 30% polyphosphoric acid 3 136,000 Hydrochloric acid þ 30% polyphosphoric acid 4 172,000 Hydrochloric acid þ 30% polyphosphoric acid 6 178,000 270 Preparation of High Molecular Weight Polysuccinimides
    • 3. Poly(succinimide-co-sodium aspartate), (I), was previously prepared [2] by the author and used in biodegradable and personal product applications. a N H N O O ONa O O (I) b 4. Poly(sodium aspartate-co-asparagine-co-succinimide), (II), was prepared by the author [3] by hydrolysis of polysuccinimide with ammonium and sodium hydroxides. A method for preparing branched polysuccinimide derivatives of the current investigation was also provided. a b H N H N N O OO OH2N O O ONa (II) c 5. Swift [4,5] prepared poly(succinimide-co-sodium aspartate) by copolymeriz- ing aspartic acid with monosodium aspartate and polysuccinimide using L-aspartic acid in supercritical CO2. 6. By initiating the polymerization of aspartic acid with a malimide end capping initiator, (III), Swift [6] prepared a functionalized polysuccinimide derivative. N O O O O O (III) References 1. C.S. Sikes, US Patent Application 2006-0205918 (September 14, 2006) 2. C.S. Sikes et al., US Patent 6,495,658 (December 7, 2002) 3. C.S. Sikes, US Patent 7,091,305 (August 15, 2007) 4. G. Swift et al., US Patent 6,903,181 (June 7, 2005) 5. G. Swift et al., US Patent 6,919,421 (July 19, 2005) and US Patent 6,887,971 (May 3, 2005) 6. G. Swift et al., US Patent Application 2006-0211843 (September 21, 2006) Notes 271
    • Title: Degradable Crosslinkers and Degradable Crosslinked Hydrogels Comprising Them Author: H. Zhang et al., US Patent 7,135,593 (November 14, 2006) Assignee: Biosphere Medical, Inc. (Rockland, MA) SIGNIFICANCE Base-labile crosslinkering agents consisting of N,N0 -(dimethacryloyloxy)alkylamide derivatives were prepared and used in synthesizing degradable crosslinked polymers and hydrogels. The degradation rates of these hydrogels was controlled by co-reacting the crosslinking agent with selected acrylamides. REACTION Crosslinker Component H3CO O OCH3 O H N O H N O HO OH H N O H N O O O O O i ii Intermediate 272
    • Hydrogel Crosslinking Intermediate HN O HN O O O O O O O OH O O OH O O OH a b c iii i: Dimethyl glutarate, hydroxylamine, methanol, ethanol ii: Pyridine, DMF, methacryloyl chloride, DMF, chloroform, water iii: DMF, glycerol, ammonium persulfate, N,N,N,N-tetramethylethylenediamine, ethanol EXPERIMENTAL 1. Preparation of Glutaroyl Dihydroxamic Acid Dimethyl glutarate (0.6 mol) was added to 400 ml of methanol and treated with an aqueous solution of hydroxylamine (50 wt% in water; 1.34 mol). The reaction stirred for 85 hours at ambient temperature, and the product was precipitated by introducing 400 ml of ethanol. The precipitate was isolated, and washed three times with ethanol, and vacuum-dried at 40 C for 48 hours; the product was isolated in 66% yield as a white powder. 2. Preparation of N,N0 -Dimethacryloyloxy)glutarylamide A reactor was charged with the Step 1 product (0.20 mol), 50 of ml pyridine, and 260 mlofDMFandthentreateddropwisewithmethacryloylchloride(0.4 mol)diluted with 40 ml of DMF and stirred 3 hours at ambient temperature. The mixture was next treatedwith300 mlofCCl3Handpouredinto1000 mlofvigorouslystirringwater.The organic phase was washed three times with water, dried overnight using MgSO4, and concentrated. The residue was re-crystallized in diethyl ether/hexane, and the product was isolated in 34% yield. Experimental 273
    • 3. Preparation of 2-Hydroxyethyl Acrylate Crosslinked Hydrogel Ina100-mlround-bottomflasktheStep2productwasdissolvedinDMFandtreatedwith 2-hydroxyethyl acrylate (2.0 g) followed by glycerol and water (20 g), 1:1. The reactor was placed in an oil bath kept at 55 C and the polymerization was initiated using ammonium persulfate (50 mg) and accelerated with 0.1ml N,N,N,N-tetramethylethy- lenediamine. The hydrogel formed immediately and was immersed in ethanol over- night, washed with ethanol, vacuum-dried for 20 hours, and the product was isolated. DERIVATIVES Asummaryofbase-labilecrosslinkingagentsisprovidedinTable1.Hydrolyticstability of homopolymer and copolymer hydrogels are provided in Tables 2 and3, respectively. N H O O N H OO O O n TABLE 1. Summary of N,N0 -(dimethacryloyloxy)alkylamide derivatives effective as hydrogel crosslinking agents. Name n N,N0 -Dimethacryloyloxy)malonamide 1 N,N0 -Dimethacryloyloxy)succinamide 2 N,N0 -Dimethacryloyloxy)glutarylamide 3 N,N0 -Dimethacryloyloxy)adipamide 4 N,N0 -Dimethacryloyloxy)suberoylamide 6 Source: Limited 1 H-NMR data supplied by author. TABLE 2. Degradation times forcrosslinked homopolymer hydrogels hydrolyzed in a buffer solution at pH 7.4 at 37 C. Monomer*1 Crosslinker Degration Time TS N,N0 -Dimethacryloyloxy)glutarylamide 22 days HEA N,N0 -Dimethacryloyloxy)glutarylamide 26 days PEG-macromer N,N0 -Dimethacryloyloxy)adipamide 31 days AA N,N0 -Dimethacryloyloxy)glutarylamide 8 hours NaAA N,N0 -Dimethacryloyloxy)adipamide 6 hours DMA N,N0 -Dimethacryloyloxy)adipamide 32 hours AAm N,N0 -Dimethacryloyloxy)adipamide 7 hours *1 TS ¼ N-[Tris(hydroxymethyl)methyl]acrylamide HEA ¼ N-(Hydroxymethyl)methacrylamide PEG-macromer ¼ Poly(ethylene glycol)-methacrylate, MW  526 daltons AA ¼ Acrylic acid NaAA ¼ Sodium acrylate DMA ¼ N,N-Dimethylacrylamide AAm ¼ Acrylamide 274 Degradable Crosslinkers and Degradable Crosslinked Hydrogels Comprising Them
    • NOTES 1. Goupil [1] prepared biomedical articles consisting of biodegradable poly(vinyl alcohol) hydrogels crosslinked with N-methacrylamidoacetaldehyde dimethyl acetal, (I), N-acrylamido-acetaldehyde dimethyl acetal, (II), and 1-(2,2-di- methoxyethyl)-3,4-dimethylpyrrole-2,5-dione, (III). HN O H3CO OCH3 HN O H3CO OCH3 N O O OCH3 H3CO (I) (II) (III) 2. Hubbell [2]preparedbiocompatiblehydrogelsconsistingofpoly(acrylicacid-b- ethylene oxide) crosslinked with hydrolytically susceptible carbonates, (IV), urethanes, (V), ureas, (VI), ester amides, (VII), and diamides, (VIII). O X O Y O O O YXCrosslinker IV OO V NO VI NN TABLE 3. Degradation times for copolymer hydrogels crosslinked with N,N0 - dimethacryloyloxy)glutarylamide hydrolyzed in a buffer solution at pH 7.4 at 37 C. Monomer 1*1 Comonomer*2 Degration Time HEA, 90% DMA 13 days HEA 80% DMA 9.5 days HEA 90% AA 4 days TS, 90% DMA 7 days TS, 80% DMA 4 days TS, 90% AA 23 hours TS, 80% AA 15 hours *1 HEA ¼ N-(Hydroxymethyl)methacrylamide TS ¼ N-[Tris(hydroxymethyl)methyl]acrylamide *2 AA ¼ Acrylic acid DMA ¼ N,N-Dimethylacrylamide Notes 275
    • X Y O O YXCrosslinker VII NO VIII NN 3. Frechet [3] prepared bioactive microgels by free radical polymerization of acrylamide with acid-labile crosslinkers such as bisacrylamide 4-methox- ybenzaldehyde acetal, (IX), and bistrifluoroacetamide 4-(3-azidopropylether) benzaldehyde acetal, (X). H N O O O H N OCH3 O F3C H N O O O H N O CF3 O (IX) (X) N3 4. Hydrolytically unstable polyethylene was prepared by Wilson [4] by copo- lymerizing ethylene with acid-labile crosslinkers 1-allyloxy-penta-1,4-diene, (XI), tetraallyloxysilane, (XII), or 3,9-divinyl-2,4,8,10-tetraoxaspiro [5,5] undecane, (XIII). O Si OO O O OO O O (XI) (XII) (XIII) 5. Loomis [5] prepared poly(lactide-co-(ethylene oxide-co-propylene oxide-co- lactide) bioresorbable compositions for use in implantable prosthesis. 276 Degradable Crosslinkers and Degradable Crosslinked Hydrogels Comprising Them
    • References 1. D.W. Goupil et al., US Patent 7,070,809 (July 4, 2006) 2. J.A. Hubbell et al., US Patent 6,943,211 (September 13, 2005) 3. J.M.J. Frechet et al., US Patent 7,056,901211 (June 6, 2006) 4. R.B. Wilson Jr. et al., US Patent 7,037,992 (May 2, 2006) 5. G.L. Loomis et al., US Patent Application 2007-0015844 (January 18, 2007) and US Patent 7,109,255 (September 19, 2006) Notes 277
    • C. Sol-gel Title: Thermosensitive Poly(Organophosphazenes), Preparation Method Thereof and Injectable Thermosensitive Polyphosphazene Hydrogels Using the Same Author: S.-C. Song et al., US Patent 7,259,225 (August 21, 2007) Assignee: Korea Institute of Science and Technology (Seoul, KR) SIGNIFICANCE Thermosensitive polyphosphazene polymers have been prepared by reacting poly- dichlorophosphazene with methoxypolyethylene glycol and isoleucineethyl ester. These materials are suitable for use as injectable thermosensitive biodegradable drug delivering system that have sol-gel behavior near human body temperature. REACTION N P Cl Cl N P N P HN HN HN HN O O CH(CH3)CHC2H5 O CO-lactose O O 15 a i O Note 1 a i: THF, triethylamine, isoleucineethyl ester hydrogen chloride, ethyl-2-(O-glycyl) lactate ammonium oxalate, poly(aminomethoxyethylene glycol 278
    • EXPERIMENTAL 1. Preparation of Poly[(Aminomethoxyethyleneglycol)(Isoleucineethylester)- (Ethyl-2-(O-Glycyl)Lactate)] (NP(AMPEG550)0.78(IleOEt)1.18(GlyLacOEt)0.04) Poly(dichlorophosphazene) (17.26 mmol) was dissolved in THF and then put into a dry ice-acetone bath and treated with triethylamine (82.84 mmol) and isoleucineethyl esterhydrogenchloridesalt(20.71mmol).Afterthemixturewasstirredfor48hoursat ambient temperature, it was treated with a solution of ethyl-2-(O-glycyl)lactate ammonium oxalate(0.69 mmol) and triethylamine (3.45 mmol) in 50 ml acetonitrile, and reacted a further 19 hours in an ice bath. Finally poly(aminomethoxy-ethylene glycol) (25.89 mmol, Mw $500 daltons) and triethylamine (51.78 mmol) were added and the mixture was reacted for 48 hours at 50 C. The reaction mixture was filtered, concentrated until a small quantity of solvent remained, and dissolved in THF. The mixture was precipitated by adding excessive hexane and filtered, the process being repeated 3 times. The solid was dissolved in a small amount of methanol and dialyzed usingmethanoland distilled waterfor5daysapiece.Theproductisolated in58%yield had a Mw of roughly 27,000 daltons, maximum viscosity of roughly 312.8 Pa-s, and a maximum gel temperature of 43 C. DERIVATIVES NOTES 1. Additional biodegradable and thermosensitive polyphosphazenes derivatives, (I), were prepared by the author [1] in an earlier investigation. Thermosensitive cyclotriphosphazene analogues were also prepared by Sohn [2]. TABLE 1. Physical properties of selected polyphosphazenes prepared according to the current invention. Entry Formula Mw (daltons) Maxium Viscisity (PaÁ s) Maxium Gel Temperature ( C) 1 NP(AMPEG550)0.78(IleOEt)1.18 (GlyLacOEt)0.04 27,000 312.8 43 2 NP(AMPEG550)0.70(IleOEt)1.20 (GlyLacOEt)0.10 41,000 550.0 39 3 NP(AMPEG550)0.08(IleOEt)1.20 42,000 400.0 40 4 NP(AMPEG750)0.65(IleOEt)1.35 22,000 680.0 47 Notes 279
    • N P N P HN O N HN O O R' O 7 g 7 Pa b O O 7 R R" c N P N P HN NHR N HN NHR R" Pd e NHR' R' R" f R R' R" Gly-Gly-OEt LeuOEt AlaOEt (I) 2. Multisubsituted linear polyphosphazene polymers, (II), having high ion con- ductivity at ambient temperature were prepared by Allcock [3] and used as gel polymer electrolytes. aN P N P O O N O O P O O CF3 CF3 CF3 O O O O O O (II) 3. Copolymers consisting of polyphosphazene norbornene derivatives, (III), were prepared by Allcock [4] and used as electrically conductive materials, biomed- ical materials, and as compatibilizing agents. aO PH N P O O N O O P O O O CF3 CF3 CF3 CF3 CF3 (III) CF3 CF3 280 Thermosensitive Poly(Organophosphazenes)
    • References 1. S.-C. Song et al., US Patent 6,319,984 (November 20, 2001) 2. Y.S. Sohn et al., US Patent 6,417,383 (July 9, 2002) 3. H.R. Blankenship et al., US Patent 6,605,237 (August 12, 2003) 4. H.R. Allcock et al., US Patent 6,392,008 (May 21, 2002) Notes 281
    • XII. IMAGING AGENT Title: Polymerization Method for the Synthesis of Polypeptide Imaging Agents Author: B. J. Grimmond et al., US Patent 7,205,385 (April 17, 2007) Assignee: General Electric Company (Niskayuna, NY) SIGNIFICANCE Low molecular weight magnetic resonance imaging contrast-enhancing agents are widely used because they rapidly diffuse into plaques, but they disperse too rapidly fromthebodybecauseoftheirlowmolecularweights.Thecompoundgadolinium(III) diethylenetriaminepentaacetic acid is a typical example. To address this concern, moderate molecular weight polyamino acids have been prepared containing gadolin- ium (III) diethylenetriamine pentaacetic acid that are as effective as imaging agents which diffuse at much slower rates through the body. Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 283
    • REACTION O OH NH2 B OHN O NH2 B OHN O HN 4N(C2H5)3DTPA O OH NH2 NH 4N(C2H5)3DTPA NH2 O OH NH2 NH DTPA Gd(III)Na NH NH DTPA Gd(III)Na O O O H H N N H OH O NH DTPA. Gd(III). Na O 0.8 0.2 i ii iii ivv vi i: Methanol, 9-borobicyclononane (9-BBN), THF ii: Diethylenetriaminepentaacetic acid (DTPA), triethylamine, isobutylchloro- fomate iii: Ethylene diamine (EDA) iv: Gadolinium (III) chloride (Gd), trisodium citrate v: CH2Cl2, triethylamine, triphosgene vi: N-Carboxy anhydride (NCA)-valine, acetone, CH2Cl2 EXPERIMENTAL 1. Preparation of 9-Borobicyclononanelysine Complex A sample of lysine (1 eq) was stirred in methanol at ambient temperature, slowly treated with 9-borobicyclononane (9-BBN) (1 eq) in THF, and refluxed for 1 hour at 50 C. The clear and colorless mixture was concentrated to give a solid that was re- dissolved in THF at 40 C and then filtered and re-concentrated. The product was isolated as an off-white solid and used without further purification. 284 Polymerization Method for the Synthesis of Polypeptide Imaging Agents
    • 2. Preparation of 9-BBN-Lysine-Diethylenetriaminepentaacetic Acid A sample of 0.1M solution diethylenetriaminepentaacetic acid (DTPA) (1 eq) in acetonitrile was treated with triethylamine (5 eq) and degassed for 20 minutes before heating for 1 hour at 50  C. The solution was then cooled to À45 C, treated with the dropwise addition of isobutylchloro-fomate (1.1 eq), and stirred for 1 hour. This mixture was next treated with the Step 1 product (1 eq) dissolved in acetonitrile and stirred 12 hours at ambient temperature. The solution was concentrated, the residue re-crystallized from THF and diethyl ether, and the product isolated as a white solid. 3. Preparation of Lysine-N-å-DTPA AmixtureoftheStep2product(1eq)inTHFandethylenediamine(1.1eq)washeated for 10 minutes at 60 C. The solution was then concentrated and the residue washed with pentanes, re-crystallized from warm THF and diethyl ether, and the product isolated. 4. Preparation of Lysine-N-å-DTPA Gadolinium (III) Sodium (Gd.Na) A 0.1M aqueous solution of the Step 3 product (1 eq) was added to a pH 6 buffer solution of GdCl3 (1.2 eq) and trisodium citrate (2.4 eq). The mixture was then stirred for 12 hours and the volume reduced; next it was filtered twice through a Sephadex plug. The volume was further reduced and poured into acetone. A white precipitate formed, and the product was isolated after filtration. 5. Preparation of N-Carboxy Anhydride (NCA)-Lysine-N-å-DTPA.Gd.Na A 0.1M CH2Cl2 solution of the Step 4 product (1 eq) and triethylamine (2 eq) was treated with triphosgene (0.3 eq) at 0 C. The mixture was stirred for 1 hour at ambient temperature and concentrated; the residue was extracted with EtOAc. The extract was filtered was re-concentrated, the residue re-crystallized in CH2Cl2/pentanes, and the product was isolated as a white solid. 6. Preparation of Poly(Lysine-N-å-DTPAGd.Na)-(Valine) Random Copolymer The Step 5 product (1 eq) and NCA-valine (0.25 eq) were dissolved in CH2Cl2 and acetone, 5:1, respectively, and the mixture was heated to 60  C. The mixture was then treated with triethylamine (0.01 eq) dissolved in CH2Cl2 and heated for 24 hours at 60 C. Thereafter the mixture was treated with 0.01M aqueous hydrochloric acid, and a white solid formed. The solid was washed with acetone, and the product was isolated. Experimental 285
    • DERIVATIVES Gadolinium-containing poly(lysine) homopolymer, (I), and biotin terpolymer, (II), were also prepared. H H N N H H N NH-DTPA. Gd. Na O O OH NH-Biotin O 0.66 0.170.17 (II) HO H N H O NH-DTPA. Gd. Na (I) NOTES 1. Compositions containing complexed gadolinium for enhancing transmem- brane transport, (III), were prepared by Wedeking [1] and used as diagnostic or therapeutic treatment agents. N N NN CO2 O2C CO2 Gd O N H NO CO2H O H N N N HN N O H2N 3 (III) N H O H N O N N NN O2C O2C CO2 3 Gd 2. Lauffer [2] prepared gadolinium-containing contrast-enhancing imaging agents, (IV), containing an image-enhancing component and to monitor e chemoembolization by magnetic resonance imaging therapy. 286 Polymerization Method for the Synthesis of Polypeptide Imaging Agents
    • N N N CO2 CO2 CO2 O2C O2C O P OO O Gd 3 (IV) 3. Giovenzana [3] prepared a novel class of multidentate aza ligands, (V), that formed complexes with gadolinium having particularly favorable stability and relaxation times. N N CO2H CO2H CO2HHO2C HO2C (V) 4. Ranganathan [4] enhanced the stability of MRI contrast imaging agents by incorporating ascorbic acid, (VI), to diminish oxidation of substituents from free radical reactions induced by radionuclide decay. N N NN CO2O2C CO2 N H O H N O OH O HO HO O Gd 3 (VI) Notes 287
    • References 1. S. Wedeking et al., US Patent 7,175,829 (February 13, 2007) and US Patent 7,147,837 (December 12, 2006) 2. R.B. Lauffer et al., US Patent 7,182,934 (February 27, 2007) and US Patent 7,198,776 (April 3, 2007) 3. G.B. Giovenzana et al., US Patent 7,186,400 (March 6, 2007) 4. R.S. Ranganathan et al., US Patent 7,160,535 (January 9, 2007) 288 Polymerization Method for the Synthesis of Polypeptide Imaging Agents
    • XIII. INK Title: Process for Preparing Chain Extended Thermoplastic Guanidinium Polymers Author: D. Hall et al., US Patent 7,172,274 (February 6, 2007) Assignee: Fujifilm Imaging Colorants Limited (Manchester, GB) SIGNIFICANCE A method for preparing guanidinium or biguanidinium pre-polymers and then chain extending them with tetraethyleneglycol diepoxide or isophorone diisocyanate is described. These agents are effective as fixing agents to reduce highlighter smear of prints prepared by ink jet printing. REACTION H2N NH . HCl NH2 N H NH N H NH N H NH N H H N a bH2N NH H N NH2 i N H NH N H NH N H NH N H H N a bHN NH H N NH OH HO O O O O 4 4 ii Note 1 Note 2 i: Hexamethylene diamine ii: Water, tetraethyleneglycol diepoxide Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 289
    • EXPERIMENTAL 1. Preparation of Polyhexamethyleneguanidine Pre-Polymer A vessel was charged with guanidine and hydrochloride (200 parts) and hexamethy- lene diamine (292 parts) and heated 4 hours at 120 C and an additional 5 hours at 150 C to 170 C. The mixture was cooled and treated with water (400 parts) and then stirred at 80 C until dissolution occurred. When further cooled to ambient tempera- ture, the solid remain dissolved in water. 2. Preparation of Polyhexamethyleneguanidine with Epoxy Termini The Step 1 product (51.2 g) was mixed with water (78.83 g) and tetraethyleneglycol diepoxide (9.8 g) and reacted for 2 hours at 25 C. The prepolymer isolated had a Mn of 1520 daltons and Mw of 3190 daltons. SCOPING REACTIONS NOTE Polyhexamethyleneguanidine pre-polymers were also chain extended with isophor- one diisocyanate and physical properties provided in Table 2. TABLE 1. Physical properties of polyhexamethyleneguanidine with epoxy termini prepared by reacting the Step 1 pre-polymer with tetraethyleneglycol diepoxide. Entry Epoxide : Prepolymer Ratio Mn Mw 2 0.80 1,970 9,420 3 0.95*1 2,330 26,440 4 0.60 1,250 2,160 *1 Reaction performed in 1,5-pentanediol TABLE 2. Physical properties of polyhexamethyleneguanidine derivatives prepared by reacting the Step 1 pre-polymer with isophorone diisocyanate. Entry Isocyanate : Prepolymer Ratio Mn Mw 13 0.60 1,650 82,490 14 0.80 1,770 96,120 14 0.95 1,800 310,930 Mn ¼ 710 daltons Mw ¼ 1010 daltons NH2 termini content ¼ 4.7% Amine content ¼ 71.5 wt Triple substitution ¼ 12% 290 Process for Preparing Chain Extended Thermoplastic Guanidinium Polymers
    • NOTES 1. Ammonolysis of poly(hexamethylene urea), (I), was used by Miyamoto [1] to prepare guanidine polyhexamethyleneguanidine, (II), as illustrated below. Fitzpatrick [2] subsequently converted this material into a polyguanidine ethers, (III), by reacting with 1,2-dibromoethane and 1,4-butanediol. H2N NH2 OCN NCO N H N H O + 666 N H N H NH 6 NH3 (I) (II) H2N NH2 OCN NCO N H N H O + 666 N H N H NH 6 NH3 (I) (II) N H N H NH 6 N H N H NH 6 (III) BrCH2CH2Br HOCH2CH2CH2CH2OH OO 4 a aa 2. Imashiro [3] converted p-diphenylmethane diisocyanate, (IV), into the corre- sponding polycarbodiimide, (V), and then postreacted with dibutyl amine forming the corresponding polyguanidine derivative, (VI). H2 COCN NCO H2 CNCN H2 CNC H N a a N (IV) (V) (VI) i ii i: THF, 3-methyl-1-phenyl-2-phosphorene-1-oxide ii: THF, dibutyl amine 3. Although selected polyamines, (VII), functionalized with guanidine, (VIII), were prepared by Dhal [4] for use in the treatment of gastrointestional disorders; their application as a crosslinkable resin was also suggested by the author. a NH2 NHHN NH2 HCl N N NH2 HClHN + a (VIII)(VII) Notes 291
    • 4. Polyamide resin components containing pendant guanidine, (IX), were pre- pared by Rothbard [5] to aid in the delivery of selected biological agents. 3 N H H N R HO O NH NHH2N O NH NH2HN O NH NHH2N (IX) R = Therapeutic agent References 1. K. Miyamoto et al., US Patent 7,157,534 (September 22, 2002) 2. R.J. Fitzpatrick, US Patent 6,955,806 (October 18, 2005) 3. Y. Imashiro et al., US Patent 6,225,417 (May 1, 2001) 4. P.K. Dhal et al., US Patent 6,294,163 (September 25, 2001) 5. J.B. Rothbard et al., US Patent 7,157,534 (July 6, 2004) 292 Process for Preparing Chain Extended Thermoplastic Guanidinium Polymers
    • XIV. LIQUID CRYSTALS A. Liquid Crystal Aligner Title: Diamines, Polyimide Precursors, and Polyimides Produced by Using the Diamines and Liquid Crystal Aligning Agents Author: K. Hosaka et al., US Patent 7,169,878 (January 30, 2007) Assignee: Nissan Chemical Industries, Ltd. (Tokyo, JP) SIGNIFICANCE Poly(amic acids) were prepared by the ambient temperature condensation of 1,2,3,4- cyclobutane tetracarboxylic dianhydride with selected aromatic diamines. When the poly(amic acids) and liquid crystal alignment agents g-butyrolactone and N-methyl- pyrrolidone were spin-coated and cured onto an inert surface, the polyimide was effective as a liquid crystal aligner. Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 293
    • REACTION H2N O O NH2 H2N O ONH2 H2N O2C CO2 NH2 O C12H25O C12H25O .... .... HNNH2 O2C i N O ON O C12H25O C12H25O ....NN O O O O O O O2C CO2 CO2ii N N a b a b O O O O O O OO O O O N O O OO ....c c i: N-Methylpyrrolidone, 3,5-di-dodecyloxybenzyl-3,5-diamino-benzoatediamine, 1,2,3,4-cyclobutane tetracarboxylic dianhydride ii: N-methylpyrrolidone, g-butyrolactone EXPERIMENTAL 1. Preparation of Poly(Amic Acid) Intermediate A reaction flask was charged with 3,5-di-dodecyloxybenzyl-3,5-diamino-benzoate- diamine (0.75 mmol), 1, 2, 2’-bis[4-(4-aminophenoxy)phenyl]propane (4.25 mmol), 1,2,3,4-cyclobutane tetracarboxylic dianhydride (5.00 mmol), and N-methylpyrrol- idone (17.69 g) and then stirred at ambient temperature until a 15 wt% solid content polyimide precursor solution was obtained. Viscosity (25 C): 5184 MPas MW (GPC): 413,000 daltons 294 Diamines, Polyimide Precursors, and Polyimides
    • 2. Preparation of Mixed Polyimides as Liquid Crystal Aligning Films The Step 1 product was diluted with N-methylpyrrolidone and g-butyrolactone then spin-coated on glass substrates having transparent electrodes. The mixturewas heated at 80 C for 10 minutes and at 180 C or 250 C for 60 minutes to form a uniform polyimide coating film. DERIVATIVES O O NH2 O C12H25O C12H25O NH2 H2NH2N Amine 2Amine 1 H2N NH2 O OC12H25 OC12H25 Amine 3 TESTING Viscosity and contact angle testing results are provided in Tables 2 and 3, respectively. TABLE 1. Three amine co-reagents used in reacting with 5.00 mmol cyclobutane tetracarboxylic dianhydride. Entry Amine 1 (mmol) Amine 2 (mmol) Amine 3 (mmol) NMP/c butyrolactone Aligning Agents, 8:2 (g) Viscosity*1 (MPas) Mw (daltons) 4 4.75 0.25 5.00 17.17 7,600 624,000 5 2.50 — 2.50 19.35 172*2 41,200 6 3.75 1.25 — 18.13 344*3 78,000 Note: Poly(amic acids) were prepared by mixing and stirring reagents at 25 C. *1 Measured at 25 C *2 16% solids *3 15% solids TABLE 2. Physical properties of polyimides as liquid crystal aligning films prepared by heating N-methyl-pyrrolidone and c-butyrolactone, 8:2, respectively, with polyamic acids described in Table 1. Entry Viscosity (MPas) Solid Content (%) 4 24.3 4.10 5 24.9 3.98 6 28.2 2.80 Testing 295
    • TABLE 3. Results of water and methylene/iodine repellency testing of polyimide films obtained by reacting 1,2,3,4-cyclobutane tetracarboxylic dianhydride with amines described in Table 1. Amine 3 Contact Angle Surface Energy Entry Content (%) Water ( ) Methylene/iodine ( ) (dyn/cm) 4 50 97.7 56.1 30.8 50 93.6 52.7 32.8 5 25 93.3 54.5 31.8 25 91.8 51.5 33.5 6 15 87.9 51.7 33.8 15 90.756.1 50.9 33.9 NOTES 1. Polyimides containing polyaromatic amines, (I) and (II), were previously prepared by the author [1] and used as electronic insulating agents. H2N O H N OC12H25O H N O NH2 O O H2N NH2 C12H25O O (I) (II) In a subsequent investigation by the author [2] four additional amines, (III)–(VI), were prepared and used to prepared polyimides for coating applica- tions. H2N NH2 O OC8H17 A B BAAmine III CyclohexylCyclohexyl IV PhenylCyclohexyl V CyclohexylPhenyl VI PhenylPhenyl 296 Diamines, Polyimide Precursors, and Polyimides
    • 2. Photo-crosslinkable malimide (VII) and styryl (VIII) derivatives were prepared by Nakata [3] and used as liquid crystal aligning agents and liquid crystal display elements. O O O O O 6 2R R N O O VII CHCHC6H5VIII Entry References 1. K. Hosaka et al., US Patent 6,740,371 (May 25, 2004) 2. K. Hosaka et al., US Patent Application 2006-0246230 (November 2, 2006) 3. S. Nakata et al., US Patent 7,074,344 (July 11, 2006) and US Patent Application 2004-0009310 (January 15, 2004) Notes 297
    • Title: Photosensitive Polyimides for Optical Alignment of Liquid Crystals Author: W. M. Gibbons et al., US Patent 7,005,165 (February 28, 2006) Assignee: Elsicon, Inc. (Newark, DE) SIGNIFICANCE Polyimides derived from 1,2,3,4-cyclobutanetetracarboxylic dianhydride and sele- cted aromatic diamines have been found effective as photosensitive materials. These materials have applications as liquid crystals aligners, liquid crystal displays, and related liquid crystal optical elements. The film preparation uses a noncontact method that can reduce dust and static charge buildup and improve resolution. REACTION a Br H N N H2N NO2 N H2N NH2 N H2N O CO2 NH2 CO2 O N N O O O O N i ii viiii v i: Methyl amine, methanol, diethyl ether ii: 3-Fluoro-4-nitroaniline, triethyl amine, N-methylpyrrolidinone iii: Tin (II) chloride dihydrate, ethanol, hydrochloric acid, potassium hydroxide iv: 1,2,3,4-Cyclobutanetetracarboxylic dianhydride, N-methylpyrrolidinone) 298
    • EXPERIMENTAL 1. Preparation of N-(3-Methyl-2-Butenyl)-N-Methyl Amine A reactor was charged with 4-bromo-2-methyl-2-butene (15.0 g) and then treated with 110 ml of 40% of aqueous methyl amine, 110 ml of diethyl ether, and 50 ml of methanol. The mixture was extracted, and the extracts were dried over potassium carbonate and distilled; 5.25 g of product were isolated, BP ¼ 80–89 C. 2. Preparation of 3 [N-(3-Methyl-2-Butenyl)-N-Methyl]Amino- 4-Nitroaniline The Step 1 product was stirred with 3-fluoro-4-nitroaniline (3.12 g), 6.2 ml of triethyl amine, and 30 ml of N-methylpyrrolidinone at 80 C to 85 C for 10 hours and then extracted with water and diethyl ether. The extract was purified by chromatography on silica gel; and the product was isolated. 3. Preparation of 1-(3-[N-(3-Methyl-2-Butenyl)-N-Methyl)-2,5- Benzenediamine The Step 2 product (4.55 g) was treated with tin (II) chloride dihydrate (18.0 g) dissolved in 100 ml of ethanol and 16 ml of 10M hydrochloric acid and then stirred at ambient temperature for 9 hours. The mixture was basified with chilled 20 wt% potassium hydroxide (160 g), extracted with diethyl ether, and purified by chromatography on silica gel; the product was isolated as a light amber oil. 4. Preparation Polyamic Acids: General Procedure A mixture of 1,2,3,4-cyclobutanetetracarboxylic dianhydride (0.58 mmol), a selected diamine (0.58 mmol), and 1.25 ml of N-methylpyrrolidinonewere stirred at 18 C for 3 hours and then diluted to 5 wt% with c-butyrolactone (3.49 g). The product was used for spinning thin films. 5. Preparation of Films: General Procedure Two 0.9" Â 1.2" Â 1 mm thick soda lime glass substrates containing transparent indium-tin-oxide were spin-coated and cured with the Step 4 product by heating thin films in air for 15 minutes at 80 C and for 60 minutes at 200 C. Experimental 299
    • DERIVATIVES NOTES 1. In a subsequent investigation by the author [1] additional Step 5 products, (I) and (II), were prepared and used in liquid crystal alignment layers. a N N O O O O (I) O O O OCH3 O (II) TABLE 1. Optical alignment of polyimide compositions derived from 1,2,3,4- cyclobutane-tetracarboxylic dianhydride and selected diamines. Entry Diamine Lamp Exposure (J/cm2 ) Alignment Quality Holding Ratio (75 C) Contrast 4 H2N NH2 N 10 fair 0.911 10:1 8 H2N NH2 N 20 good 0.835 179:1 9 H2N N NH2 20 fair 0.823 316:1 12 H2N NH2 N 10 excellent 0.806 82:1 300 Photosensitive Polyimides for Optical Alignment of Liquid Crystals
    • 2. The preparation of other aromatic diamines, (III), useful in preparing photo- sensitive polyimides effective as liquid crystal alignment agents is provided by the author [2]. N O C8H17 NH2 H2N (III) 3. Polyimide esters, (IV), prepared Buchecker [3], containing a photoactive side chain were used as orientation layers for liquid crystals and in the construction of both unstructured and structured optical elements. a N N O O O O O O O O H3CO n-C4H9-O (IV) 4. Polyimides derived from diamines containing a steroid component, (V), were prepared by Hiraoka [4] and used as method for producing liquid crystal alignment layers. O OH2N NH2 (V) Notes 301
    • References 1. W.M. Gibbons et al., US Patent Application 2006-0051524 (March 9, 2006) 2. W.M. Gibbons et al., US Patent 6,713,135 (March 30, 2004) and US Patent 6,380,432 (April 30, 2002) 3. R. Buchecker et al., US Patent 6,831,148 (December 14, 2004) 4. H. Hiraoka et al., US Patent 6,312,769 (November 6, 2001) 302 Photosensitive Polyimides for Optical Alignment of Liquid Crystals
    • B. Liquid Crystal Materials Title: Homopolymers That Exhibit a High Level of Photo-inducable Birefringence Author: H. Berneth et al., US Patent 7,214,752 (May 8, 2007) Assignee: Bayer MaterialScience AG (Leverkusen, DE) SIGNIFICANCE Homopolymers that are capable of absorbing visible light and that are structured so that in their thermodynamically stable state they are distended and strongly aniso- metric have been prepared. After absorbing electromagnetic radiation, the side group formsanangleofatleast30 withthelongitudinalaxis.Thesematerialsaresuitablefor storage of optically provided information. 303
    • REACTION a NH2 CN CN NH2 N N NC CN HN N N NC CN O O O O HN N N NC CN O O O O i iiiii Note 1 i: Nitrosylsulphuric acid, sulfuric acid, aniline ii: Dioxane, 4-(2-methacryloyloxy)-ethoxy-benzoic acid chloride iii: DMF, azobis(isobutyronitrile) EXPERIMENTAL 1. Preparation of 4-Amino-20 ,40 -Dicyano-Azobenzene 2,4-Dicyanoaniline (31.4 g) was treated with nitrosylsulfuric acid (72 g) at 0 C to 5 C in 300 ml of 50% aqueous sulfuric acid, and the batch was stirred for 1 hour. This mixture was then slowly poured into a solution of aniline (20.4 g) and urea (4.5 g) dissolvedin300 mlof50%aqueoussulfuricacidandthenstirredforanadditionalhour at 0 C to 5 C. Thereafter the reaction mixture pH was raised to 5.5 with sodium carbonate. A precipitate formed that was filtered off under suction,washedwith water, anddried;34 gofproductwereisolated.Thismaterialwasusedinthenextstepwithout further purification. 2. Preparation of Liquid Crystal Monomer The Step 1 product (27.6 g) was dissolved in 500 ml dioxane and added to a solution of 4-(2-methacryloyloxy)-ethoxy-benzoic acid chloride (33 g) in 100 ml dioxane and then stirred for 2 hours. The product was precipitated by pouring the solution into 2 liters of water, purified by crystallization twice from dioxane, and 30.4 g of orange- red crystals isolated with kmax ¼ 404.5 nm (DMF) and a mp ¼ 215–217 C. 304 Homopolymers That Exhibit a High Level of Photo-inducable Birefringence
    • 3. Preparation of the Liquid Crystal Homopolymer The Step 2 product (7.9 g) was polymerized at 70 C in 75 ml DMF under argon using 2,20 -azobis(isobutyronitrile) (0.39 g) for 24 hours. The mixture was filtered, concen- trated, and the residue boiled with methanol to remove unreacted monomer. The material was dried, and 7.18 g amorphous polymer were isolated having a glass transition temperature of 150 C. DERIVATIVES TABLE 1. Selected azo monomers and corresponding melting points and lmax. Entry Monomer Structure MP ( C) lmax (DMF) (nm) 11 HN N N O OO O S N NO2 207-208 392 12 N N N NC CN NNO 164 521 13 HN N N N(CH3)2 O OO O 218–220 428 TABLE 2. Light-induced birefringence, Dn, at 250 mV at a wavelength of 514 nm using 0.9 lm thick polymer films. Entry na Dn l (nm) 11 26,000 0.244 820 12 20,800 0.233 633 13 27,855; 19380 0.194 820 Derivatives 305
    • NOTES 1. Additional azoderivatives were previously prepared by the author [1] 2. Partially hydrogenated polymers derived from norbornene derivatives, [I], prepared by Miyaki [2] were low in birefringence, high in wavelength dependency birefringence, and excellent in transparency and heat resistance. Additional functionalized norbornene derivatives were prepared by Liaw [3]. N O O CO2CH3 (I) References 1. H. Berneth et al., US Patent 6,875,833 (April 5, 2005) and US Patent 6,441,113 (August 22, 2002) 2. N. Miyaki et al., US Patent 7,230,058 (June 12, 2007) and US Patent 6,846,890 (January 25, 2005) 3. D.-J. Liaw et al., US Patent 7,045,248 (April 17, 2007) 306 Homopolymers That Exhibit a High Level of Photo-inducable Birefringence
    • Title: Liquid Crystalline Compound, Liquid Crystalline Composition, and Retardation Film Author: H. Nishikawa et al., US Patent 7,169,325 (January 30, 2007) Assignee: Fuji Photo Film Co., Ltd. (Minami-Ashigara, JP) SIGNIFICANCE Oligomeric phenylacetylene liquid crystalline derivatives capable of exhibiting a biaxial liquid crystal phase have been prepared. When these agents were functiona- lized with the polymerizable group 4-(4-acryloyloxybutyloxy)benzoic acid and then coated onto an alignment film and polymerized. An optically anisotropic retardation film was produced. 307
    • REACTION O O O O O O O O Br O O O O TMS O O O O TMS O O O O O O O O O O O O OH OH OH OH OH OH OR1 OR1 OR1 OR1 OR1 OR1 OR2 OR2 OR2 OR2 OR2 OR2 i ii iii ivv vi vii O O O O O O O 7 4R1 = R2 = i: 1,3-Dibromobenzene, triphenylphosphine, bis(triphenylphosphine)palladium (II) dichloride, copper(I) iodide, triethylamine ii: Trimethylsilyl acetylene, triphenylphosphine, bis(triphenylphosphine)palladi- um(II) dichloride, copper(I) iodide, triethylamine iii: THF, tetrabutylammonium fluoride iv: 2,6-Dibromo-1,4-diacetoxybenzene, triphenylphosphine, bis(triphenylphosphine)- palladium(II) dichloride, copper(I) iodide v: THF, methanol, sodium methoxide vi: 4-Octyloxybenzoic acid chloride, THF, diisopropylethylamine, 4-dimethyl- aminopyridine vii: 4-(4-Acryloyloxybutyloxy)benzoic acid, THF, diisopropylethylamine, 4-dimethyl- aminopyridine EXPERIMENTAL 1. Preparation of 1-(2,5 Diacetoxyphenyl)-2-(3-Bromophenyl)Acetylene A mixture consisting of 2,5 diacetoxyphenylacetylene (3 g), 1,3-dibromobenzene (10 g), triphenylphosphine (58 mg), bis(triphenylphosphine)palladium(II) dichloride 308 Liquid Crystalline Compound, Liquid Crystalline Composition, and Retardation Film
    • (29 mg), and copper(I) iodide (10 mg) were dissolved in 50 ml of triethylamine and then refluxed for 10 hours under a nitrogen atmosphere. After cooling, water was added, and the reaction solution was extracted with EtOAc, washed with saturated brine, and concentrated. The residue was purified by column chromatography, and 2.8 g of product were isolated. 2. Preparation of 1-(2,5 Diacetoxyphenyl)-2-(3-Trimethylsilylethynylphenyl) Acetylene A mixture consisting of the Step 1 product (2.1 g), trimethylsilyl acetylene (0.83 g), triphenyl-phosphine (24 mg), bis(triphenylphosphine)palladium(II) dichloride (12 mg), and copper(I) iodide (4 mg) dissolved in 20 ml of triethylamine was refluxed for 10 hours under a nitrogen atmosphere. After cooling, water was added, and the reaction solution was extracted with EtOAc, washed with saturated brine, and concentrated. The residue was purified by column chromatography, and 1.5 g of product was isolated. 3. Preparation of 1-(2,5 Diacetoxyphenyl)-2-(3-Ethynylphenyl)Acetylene The Step 2 product (1.5 g) was dissolved in 200 ml of THF, treated with 5 ml of 1.0 M THF solution of tetrabutylammonium fluoride, and stirred at ambient temperature for 30 minutes. The solution was treated with water, extracted with EtOAc, and washed with saturated brine. The organic layer was concentrated under reduced pressure and then purified by column chromatography; 0.9 g of product was isolated. 4. Preparation of 1-[(2,5-Diacetoxyphenyl)-2-[3-(2,5- Diacetoxyphenylethynylphenyl)] Acetylene (Product 4A) and 1-[(2,5- Diacetoxyphenyl)-3-(2,5-Diacetoxyphenylethynylphenyl)]-2-[(2,5-Diacetoxy- phenyl)-3-2,5-Diacetoxyphenylethynylphenyl)] Acetylene (Product 4B) AmixtureconsistingoftheStep3product(0.7 g), 2,6-dibromo-1,4-diacetoxybenzene (0.37 g), triphenylphosphine (10 mg), 5 mg of bis(triphenylphosphine)-palladium(II) dichloride, and copper(I) iodide (2 mg) dissolved in 20 ml of triethylamine was refluxed for 10 hours under a nitrogen atmosphere. The mixture was cooled and then treated with water. The solution was extracted with EtOAc, washed with saturated brine, and concentrated. The residue was purified by column chromatography, and 0.21 g and 0.18 g of products 4A and 4B, respectively, were isolated. 5. Preparation of 1-[(2,5-Dihydroxyphenyl)-3-[2,5- Dihydroxyphenylethynylphenyl)]-2-[(2,5-Dihydroxyphenyl)-3-(2,5- Dihydroxyphenylethynylphenyl)]Acetylene The Step 4B product (0.18 g) was dissolved in 20 ml of THF, treated with 5 ml of methanol and 0.4 ml of sodium methoxide dissolved in 28% methanol, stirred for 1 hour at ambient temperature, and neutralized with dilute hydrochloric acid. Experimental 309
    • Themixturewasextracted withEtOAc,concentrated,and0.12 gofcrystallineproduct was isolated. 6. Preparation of 1-[(2,5-(4-Octyloxybenzoxy))-3-(2,5-(4-Octyloxybenzoxy) Ethynylphenyl)]-2-[(2,5-(4-Octyloxybenzoxy)-3-(2,5-(4-Octyloxybenzoxy))] Acetylene The Step 5 product (0.06 g) and 4-octyloxybenzoic acid chloride (0.4 g) were dissolved in 10 ml of THF, treated with diisopropylethylamine (0.2 g) and 4-dimethy- laminopyridine(0.01 g),andstirred12hoursatambienttemperature.Waterwasadded to the reaction mixture, and the mixture was extracted with EtOAc. The mixture was concentrated and then purified by column chromatography; 0.2 g of the crystalline product was isolated. 7. Preparation of 1-[(2,5-(4-(4-Acryloyloxybutyloxy)Benzoxy)-3-(2,5-(4- Acryloyloxybutyl-oxy)-Benzoxy)Ethynylphenyl)]-2-[(2,5-(4- Acryloyloxybutyloxy)Benzoxy)-3-(2,5-(4-Acryloyloxybutyloxy)Benzoxy)] Acetylene The Step 6 procedurewas repeated using 4-(4-acryloyloxybutyloxy)benzoic acid, and the product was isolated. DERIVATIVES Two additional derivatives, (I), were prepared. OR OR OR OR O O O O4 R = H; (I) BIAXIAL LIQUID CRYSTAL TESTING RESULTS Step 6 Product The phase transition temperature of the Step 6 product was examined by observing its texture through a polarizing microscope. When the temperature was elevated, the 1 H-NMR (CDCl3) d (ppm): 1.70 1.90 (12H, m) 1.90 2.00 (12H, m) 3.95 4.30 (24H, m) 5.75 5.80 (6H, m) 6.056.20 (6H, m) 6.35 6.50 (6H, m) 6.90 7.00 (12H, m) 7.00 7.50 (16H, m) 8.10 8.25 (12H, m) 1 H-NMR (CDCl3) d (ppm): 0.85 0.95 (18H, m) 1.20 1.60 (60H, m) 1.70 1.90 (12H, m) 3.95 4.10 (12H, m) 6.90 7.00 (12H, m) 7.00 7.50 (16H, m) 8.10 8.25 (12H, m) 310 Liquid Crystalline Compound, Liquid Crystalline Composition, and Retardation Film
    • phase changed from crystal phase to isotropic liquid phase in the vicinity of 140 C. When the temperature was gradually lowered from 150 C, the phase changed to the N phase in the vicinity of 120 C. Finally, when the temperature was further lowered to ambient temperature, the material reverted to crystal phase. As a result this agent was judged to be a biaxial liquid crystal. Step 7 Product The phase transition temperature of the Step 7 product was also examined using a polarizing microscope. When the temperature was initially elevated, the crystal phase reverted to isotropic liquid phase in the vicinity of 80 C. Gradually lowering the temperature from 90 C resulted in an N phase at approximately 60 C. When the temperature was finally lowered to ambient temperature, the formation of a crystal phase was observed. As a result this agent was judged to be a biaxial liquid crystal. PREPARATION OF RETARDATION FILM 8A. Formation of Alignment Film A polyvinyl alcohol containing 5% glutaraldehyde was dissolved in sufficient methanol/water, 20/80, respectively, to prepare a 5% solution. This solution was coated onto a cellulose triacetate film having a thickness of 100 mm and a size of 270 Â 100 mm and then dried with hot air for 2 minutes at 100 C. The film was rubbed to form an alignment film having a thickness of 0.5 mm. 8B. Formation of Optically Anisotropic Layer On the alignment film obtained in Step 8A, a coating was evaluated for optically anisotropic properties by coating a #4 wire bar with the following components. Step 7 product, 100 parts Air interface orientation controlling agent, (II), 0.2 parts (unspecified) Photopolymerization initiator HJ-1, (III), 2.0 parts by mass Lucirin TPO-L, 2.0 parts Methyl ethyl ketone, 300 parts N N N HN NHN H OC12H25 OC12H25 C12H25O C12H25O OC12H25 OC12H25 HO HN O N N N CCl3 CCl3 (II) (III) Preparation of Retardation Film? 311
    • 8C. Formation of Retardation Film The Step 8B film was coated onto the optically anisotropic layer, placed in a thermostatic chamber at 80 C, and heated for 5 minutes 60 . Thereafter the film was cooled at 40 C for 30 seconds in a thermostatic chamber that had an oxygen content of 2%andthenirradiatedwithultravioletradiationat600 nm.Thefilmwasnextcooledto ambient temperature, and the retardation film was isolated having an optically anisotropic layer thickness of 1.55 mm. The retardation in the direction perpendicular to the face of the retardation film was 150 nm parallel to the rubbing direction. NOTES 1. Cinnamic acid liquid crystalline derivatives, (IV), capable of exhibiting a biaxial liquid crystal phase were also prepared by the author [1] and used as a component in retardation films. O O OR OR RO O O RO OR OR (IV) R=CH2(CH2)3-OCO-CH=CH2 2. Phenylacetylene derivatives, (V), were prepared by Tang [2] and converted into the corresponding polyacetylenes, (VI), as illustrated below, containing a side- chain liquid crystal molecular architecture of backbone þ spacer þ mesogenic group. These products were subsequently used in electronic and mechanical applications. 312 Liquid Crystalline Compound, Liquid Crystalline Composition, and Retardation Film
    • O OO O O OO O 3 5 3 5 (V) (VI) i a i: Rhodium(nitrobenzofuranzan chloride)dimer, THF, triethylamine 3. Coates [3] prepared liquid crystal films with a homeotropic alignment that was induced by an aligning perfluoropolymer substrate after UV irradiation of the three component phenylacetylene mixture, (VII)–(IX). Other cyano-analogues, (X), were prepared by Radcliffe [4]. OO O OR O O O O O CN C5H11 Component a (VII) (VIII) (IX) 3 6 6 3 CN(X) 2 or 6 a R Notes 313
    • 4. Tanaka [4] prepared 30 mm-thick retardation films consisting of mixedesters of hydroxypropyl cellulose and acryloyl and n-butyryl chlorides, (XI), having a retardation value of 180 nm at a wavelength of 550 nm after photo polymeri- zation. O O O O O O O O O O O a (XI) References 1. H. Nishikawa et al., US Patent 7,153,548 (December 26, 2006) 2. B.Z. Tang et al., US Patent 7,070,712 (July 4, 2006) 3. D. Coates et al., US Patent 7,170,575 (January 30, 2007) 4. M.D. Radcliffe et al., US Patent 7,160,586 (January 9, 2007) 5. K. Tanaka et al., US Patent 7,163,723 (January 16, 2007) 314 Liquid Crystalline Compound, Liquid Crystalline Composition, and Retardation Film
    • Title: Perfluoroallyloxy Compound and Liquid Crystal Composition Containing the Same Author: H. Shinano et al., US Patent 7,001,647 (September 22, 2006) Assignee: Asahi Denka Co., Ltd. (Tokyo, JP) SIGNIFICANCE Perfluoroalloxy liquid crystals were prepared by the Williamson ether synthesis using perfluoro iodopropene. These materials can be mixed with nematic liquid crystal materials to provide liquid crystal compositions having low viscosity, low refractive index anisotropy, high dielectric anisotropy, and broad nematic phase ranges. REACTION OH O F2C F F FiC3H7 C3H7 i: Dimethylimidazolidinone, 3-iodoperfluoropropene, triethylamine EXPERIMENTAL Preparation of Pentafluoro-3-(4-[4-(4-n-Propylcyclohexyl)Cyclohexyl] Phenoxy)-Propene A reactor was charged with 4-[4-(4-n-propylcyclohexyl)cyclohexyl]phenol (4 mmol) dissolved in dimethylimidazolidinone (7 g) and then treated with 3-iodoperfluoro- propene (4 mmol) and triethylamine (4.8 mmol). The mixture was reacted for 2 hours, treated with EtOAc and hydrochloric acid, washed with water until neutral, and dried using MgSO4. The solvent was then exchange with toluene, treated with silica, and concentrated. The residue was purified by repeated kugel-rohr distillations followed by 315
    • re-crystallization in EtOAc/methanol, 1/18, respectively, and then acetone; the product was isolated as white crystals in 47% yield. DERIVATIVES TABLE 1. Phase transition temperatures for perfluorooalloyloxy compounds and corresponding optical anisotropy (Dn) and dielectric anisotropy (Dee). Entry Structure Phase Transition*1 Temperatures ( C) Dn De 1 O F2C F F F C3H7 Sm ¼ 157.3 N ¼ 174.2 ! I 0.0926 4.3 14 O F2C F F F F F C5H11 C ¼ 67.1 Sm ¼ 84.9 N ¼ 114.1 ! I 0.126 8.47 18 O F2C F F F F F C3H7 Sm ¼ 41.2 N ¼ 166.6 ! I 0.1006 7.3 19 O F2C F F F F C5H11 Sm ¼ 44.4 N ¼ 170.8 ! I 0.101 6.0 Note: All experimental agents were prepared using the Williamson ether synthesis *1 Sm: smectic phase N: nematic phase I: isotropic phase 1 H-NMR d 7.3 7.0 (m, 4H), 2.6 2.3 (m, 1H), 2.2 0.4 (m, 26H) FTIR (cmÀ1 ) 2920, 2850, 1794, 1609, 1508, 1447, 1389, 1319, 1223, 1196 316 Perfluoroallyloxy Compound and Liquid Crystal Composition Containing the Same
    • NOTES 1. Katoh [1] prepared a liquid crystal composition for use as electronic paper consisting of one dual-frequency switchable smectic liquid crystal, (I), and at least one dichroic dye. C6H13 O O Cl O O C5H11 (I) 2. Liquid-crystalline phenol esters, (II), having a nematic phase of À30 C and a clearing point above 90 C were prepared by Reiffenrath [2] and used in thin- film transistors. Naphthyl derivatives, (III), prepared by Takehara [3] were also effective in thin film transistor applications. C3H7 F F O O F (II) C3H7 F OCHF2 F (III) 3. Perfluoropropenylcyclohexane-containing liquid crystals, (IV), prepared by Kato [4] were used as components in liquid crystal display elements. C3H7 F F CF3 (IV) References 1. T. Katoh et al., US Patent 7,220,466 (May 22, 2007) 2. V. Reiffenrath et al., US Patent 7,179,511 (February 20, 2007) 3. S. Takehara et al., US Patent 7,145,047 (December 5, 2006) 4. T. Kato et al., US Patent 7,074,464 (July 11, 2006) Notes 317
    • Title: Liquid Crystal Polymers Author: B. Benicewicz et al., US Patent 7,148,311 (December 12, 2006) Assignee: Rensselaer Polytechnic Institute (Troy, NY) SIGNIFICANCE Liquid crystal copolyesters were prepared using 4-phenylnaphthalene derivatives with 4-hydroxybenzoic acid, 6-hydroxy-2-naphthoic acid, or other aromatic diacids. These materials display an improved balance of low melt viscosity, fast cycle time in molding, high tensile, low thermal expansion coefficient, and thermostability. REACTION Br H3CO H3CO COOH O COOH i ii iii O O O O O O a i: 4-Carboxyoxybenzene boronic acid, 1-propanol, palladium acetate, triphenyl- phosphine, sodium carbonate, acetic acid ii: Hydrobromic acid, acetic anhydride, sulfuric acid iii: 4-Hydroxybenzoic acid, tin (II) trifluoromethane sulfonate EXPERIMENTAL 1. Preparation of 2-(40 -Carboxyphenyl)-6-Methoxynaphthalene A mixture consisting of 2-bromo-6-methoxynaphthalene (20 mmol), 4-carboxyox- ybenzene boronic acid (20 mmol), and 40 ml of 1-propanol were mixed at ambient 318
    • temperature and then treated with palladium acetate (0.06 mmol), triphenylphosphine (0.009 mmol), 18 ml of 2M Na2CO3 solution, and 8 ml of water. The mixture was refluxed for 90 minutes then, with 25 ml of water while it was still hot, and refluxed with 50 ml of acetic acid for 45 minutes. It was then cooled to ambient temperature whereupon crystals formed. The crystals were filtered, washed with water, and re-crystallized from acetone; the product was isolated 83% yield as white crystals. 2. Preparation of 2-(40 -Carboxyphenyl)-6-Acetoxynaphthalene A mixture of the Step 1 pro[duct (10 mmol), 80 ml of 48% aqueous hydrobromic acid, and 150 ml of acetic acid were refluxed overnight and then poured into 400 ml water. The residue was mixed with 40 ml acetic anhydride with 1 to 2 drops of H2SO4 for 2 hours, and a pink solid was isolated. This material was re-crystallized from acetone or pentanone, and the product was isolated in 66% yield as light yellow crystals. 3. Preparation of Polyesters by Bulk Polymerization A mixture consisting of the Step 2 product and 4-hydroxybenzoic acid with approxi- mately 500 ppm of potassium acetate or Sn(CF3S03)2 was charged into a polymeriza- tion tube with a side branch and then degassed and purged with nitrogen. While the mixturewaspurgedwithnitrogen,thereactiontemperaturewasincreased to250 Cfor about 1.5 hours, 280 C for 30 minutes, 300 C for 30 minutes, and 320 C for 30 minutes. During the temperature gradient, acetic acid was collected in a testtube at the end of the side branch. At the final stage the temperature was kept at 320 C to 330 C, and a vacuum was applied for 60 minutes to remove residual acetic acid. DERIVATIVES Monomers X Y MP ¼ 254–256 C DSC MP ¼ 262 C IR (KBr) (cmÀ1 )[nujol] COOÀH (2800 3100, broad, m), 1685 (C¼O, s), 1225 (CÀOÀC, vs), 1365 (CH3CO, s) 1 H NMR (500 MHz, CDCl3) d 2.34 (s, 3H), 7.3 8.4 (m, 10H), 13.02 (s, 1H) MP ¼ 288–289 C IR (KBr) (cmÀ1 ))[nujol] 2500 3000 (COOÀH, very broad, m), 1030 (OCH3, s), 1678 (C¼O, s). 1 H NMR (500 MHz, CDCl3) d 3.90 (s, 3H), 7.2 8.3 (m, 10H), 12.99 (s, 1H) Derivatives 319
    • Polyesters O O OO O b a TABLE 2. Thermal properties of copolyesters derived from 6-hydroxy-2-naphthoic acid and 6-(40 -acetoxyphenyl)-2-naphthoic acid. Monomer Ratio (a:b) 5% Weight Loss ( C) 10% Weight Loss ( C) Crystal Mp ( C) 75:25 378 394 352 67.5:32.5 373 385 270 60:40 426 440 260 50:50 420 436 276 40:60 425 438 401 Note: Copolymers had limited solubility in perfluorophenol. Endothermic peaks for all materials corresponding to Tg’s were weak and ambiguous. TABLE 1. Transition temperatures for selected 4-phenylnaphthalene monomers of the current invention. Entry X Y Crystal Mp ( C) Neumatic Mp ( C) Isotropic Mp ( C) 1 OCH3 OCH3 196 187 142 2 OH COOH 296 322 –– 3 COOH OCH3 269 339 –– 4 OCOCH3 OCOCH3 182 207 –– 5 OCOCH3 COOH 263 Polymerizes –– 6 COOH COOH >350 –– –– Note: Evidence for liquid crystal formation for meta- and ortho-phenylnaphthalene monomers was not detected. 320 Liquid Crystal Polymers
    • O O OO O a b NOTES 1. Multireactive mesogenic triester derivatives, (I), containing at least two poly- merizable components were prepared by Farrand [1] and used as synthetic resins with anisotropic mechanical properties. C8H17 O O O O O O (I) 2. Mesogen-containing acetylene monomers, (II), were prepared by Tang [2] and polymerized into polyacetylenes, (III). These monomers had excellent tracta- bility typically associated with polymers having flexible backbones. TABLE 3. Thermal properties of copolyesters derived from 4-hydroxybenzoic acid and 6-(40 -acetoxyphenyl)-2-naphthoic acid. Monomer Ratio (a:b) 5% Weight Loss ( C) 10% Weight Loss ( C) Tg ( C) Crystal Mp ( C) 80:20 405 425 242 435 65:35 426 430 189 430 55:45 409 424 163 417 50:50 450 460 160 420 40:60 423 435 –– 408 Note: Although Tg’s provided by the author were reproducible, peaks were weak and ambiguous. Notes 321
    • O O O O O6 6 O O O O O6 6 n i (II) (III) i: Rhodium(2,5-norbornadiene)chloride dimer, THF, triethylamine 3. Liquid crystal polymers prepared by Wellinghoff [3] by UV-curing of meso- genic dimers such as methacrylate carboxylic acid esters, (IV), and diacrylate dimethylsiloxanes, (V), had good fracture toughness, limited shrinkage, me- chanical strength, and four-point bending strength and were used in dental applications. Liquid crystal monomers, (VI), with ultra–low cure shrinkage were prepared by Norling [4] and were used in dental resin composites. O O O t-C4H9 O O O O O O O t-C4H9 O 8 (IV) O O O t-C4H9 O O SiO O t-C4H9O O Si O Si O (V) 6 O O O O O O O O O O 6 (VI) 322 Liquid Crystal Polymers
    • 4. Vaughn-Spickers [5] prepared chiral photoisomerizable mesogenic com- pounds, (VII), that retained their chirality upon photoinitation and were used in optical and electrooptical devices. O O O O O O O O O C5H11 3 (VII) References 1. L. Farrand et al., US Patent 7,125,500 (October 24, 2006) 2. B.Z. Tang et al., US Patent 7,070,712 (July 4, 2006) 3. S.T. Wellinghoff et al., US Patent 7,098,359 (August 29, 2006) and US Patent 7,094,360 (August 22, 2006) 4. B.K. Norling et al., US Patent 7,135,589 (November 14, 2006) 5. J. Vaughn-Spickers et al., US Patent 7,122,227 (October 17, 2006) Notes 323
    • XV. NANOPARTICLES A. Carbon Nanotubes Title: Method of Coating a Substrate with a Polymer Having a Combination of Crown Ether and Carbon Nanotubes Having Guanidine Groups Author: H. S. Lee, US Patent 7,261,924 (August 28, 2007) Assignee: Samsung Electro-Mechanics Co., Ltd. (Suwon, KR) SIGNIFICANCE A functionalized carbon multi-walled nanotube, MWNT, was prepared in 2 steps by initially oxidizing the unfunctionalized nanotubewith mixed acids followed by amida- tion with guanidine. When reacted with polystyrene-g-dibenzo-18-crown-6-ether, the polymer, polystyrene-g-dibenzo-18-crown-6-ether-g-(nanotube-g-guanidine), was formed having the nanotube component aligned perpendicular to the polystyrene backbone. Advances in Polymer Chemistry and Methods Reported in Recent US Patents, by Thomas F. DeRosa Copyright Ó 2008 by John Wiley & Sons, Inc. 325
    • REACTION c aa COOH CO2H O O O O OO O O H NO NH2 NH Nanotube Intermediate i ii Intermediate iii iv O O O O OO O O HN O NH NH O a b i: Sulfuric acid, nitric acid ii: Guanidine, CH2Cl2 iii: Polystyrene-g-carboxylic acid, hydroxylmethyl dibenzo-18-crown-6-ether, pyr- idine, water iv: Ethanol EXPERIMENTAL 1. Preparation of Multi-walled Carbon Nanotube-g-Carboxylic Acid MWNTs (40 mg) were added to a mixture of 60 ml of H2SO4 and 20 ml of HNO3 and then reacted for 24 hours at 50 C with ultra-sonication at about 30 kHz. The strongly acidic reaction solution was diluted with water to a pH of roughly 7, filtered through of 0.5 to 1-mm filter paper, dried at 80 C for 6 hours, and the product was isolated. FTIR (cmÀ1 ) 1700, C¼O, 3300, OÀH 326 Method of Coating a Substrate with a Polymer Having a Combination of Crown Ether
    • 2. Preparation of Nanotube-g-Guanidine A mixture consisting of the Step 1 product (10 mg), guanidine (20 mg), and 5 ml of 2M oxalic acid were dissolved in CH2Cl2 and heated for 6 hours at 50 C. The mixture was then filtered, and the product was isolated. 3. Preparation of Polystyrene-g-Dibenzo-18-Crown-6-Ether Polystyrene-g-carboxylic acid (5 g) and hydroxylmethyl dibenzo-18-crown-6-ether (1g) were dissolved in 500 ml of pyridine and reacted at ambient temperature for 5 hours. The mixture was then treated with water, and the layers were separated. The organic phase was concentrated, and the product was isolated. 4. Preparation of Polystyrene-g-Dibenzo-18-Crown-6-Ether-g- (Nanotube-g-Guanidine) A 1-mm thick copper substrate was coated with a 200 -mm thick film consisting of the Step 3 product and then dried at 50 C. The film was coated with 200 mm of the Step 2 product (10 mg) dispersed in 100 ml of ethanol. Thereafter the coating was dried at 70 C, and the product was isolated having MWNTs aligned perpendicularly to the copper substrate at regular intervals. DERIVATIVES No additional derivatives were prepared. NOTES 1. Hwang [1] prepared polymers, (I), of polyphenylenebisbenzothizaole and SWNT-g-carboxylic acid as a method of improving the solubility of nanotubes in organic solvents. a N X X N H N O (I) Nanotube X = O,S Notes 327
    • 2. Chen [2] enhanced the solubility of nanotubes in organic solvents by a noncovalent, nonwrapping approach using p-stacking with rigid-rod conjugat- ed polymers, (II). a OC10H21 C10H11O OC10H21 C10H21O S (II) S O 3. Nanotube patterned films were prepared by Park [3] using surface-modified carbon nanotubes with polyoxetanes. References 1. W.-F. Hwang et al., US Patent 7,262,266 (August 28, 2007) 2. J. Chen et al., US Patent 7,244,407 (July 17, 2007) and US Patent 7,241,496 (July 10, 2007) 3. J.J. Park et al., US Patent 7,229,747 (June 12, 2007) 328 Method of Coating a Substrate with a Polymer Having a Combination of Crown Ether
    • Title: Process for Derivatizing Carbon Nanotubes with Diazonium Species Author: J. M. Tour et al., US Patent 7,250,147 (July 31, 2007) Assignee: William Marsh Rice University (Houston, TX) SIGNIFICANCE Single-walled carbon nanotubes, SWNT, having a diameter of 0.7 nm were electro- chemically derivatized on the sides and ends with diazonium tetrafluoroborate derivatives. In this process the estimated degree of functionality was about 1 out of every 20 to 30 carbons in the nanotube. These chemically modified nanotubes have applications in polymer composite materials, molecular electronic applications, and sensor devices. REACTION C14H29 NH2 C14H29 N2BF4 C14H29 C14H29 C14H29 iii Nanotube + _ i: 4-Tetradecylaniline, acetonitrile, CH2Cl2, tetrafluoroborate ii: Bucky paper, 1,2-dichlorobenzene, acetonitrile, tetra-n-butylammonium tetra- fluoroborate 329
    • EXPERIMENTAL 1. Preparation of 4-Tetradecylbenzenediazonium Tetrafluoroborate 4-Tetradecylaniline (1 eq) was dissolved in a 1:1 mixture of acetonitrile and CH2Cl2 and then added to tetrafluoroborate (1.2 eq) at À30 C. Stirring was continued for 30 minutes, and the cooling bath was removed. After stirring for an additional 30 minutes, the solution was diluted with two times its volume with diethyl ether product. The precipitated that formed was filtered and isolated in 69% yield, MP ¼ 82 C. 2. General Procedure for Electrochemical Derivatization of SWNT A three-electrode cell with an Ag/AgNO3 reference electrode and platinum wire counterelectrode was used in the electrochemical derivatization experiments where bucky paper (1–2 mg) served as the working electrode. The bucky paper was prepared by filtering a 1,2-dichlorobenzene suspension of the bucky paper over a 0.2-mM Teflon 47 mm membrane. After drying under vacuum, the paper was peeled off the membrane and a piece was excised for use in the derivatization process. The paper was held with an alligator clip previously treated with colloidal silver paste and immersed in an acetonitrile solution of 0.5 mM diazonium salt and 0.05 M tetra-n-butylammonium tetrafluoroborate. A potential of À1.0 V was applied for a period of 30 minutes while nitrogen was bubbled through the solution. Thereafter the portion of the bucky paper that was not immersed in the solution was excised while the remainder was soaked in acetonitrile for 24 hours, washed with acetonitrile, chloroform, and ethanol. After drying, this material was sonicated in acetonitrile for 20 minutes, filtered, re-washed with acetonitrile, 2-propanol, and chloroform. The residue was dried under vacuum at ambient temperature, and the product was isolated. DIAZONIUM TETRAFLUOROBORATE DERIVATIVES R N2BF4 + _ 1 H