The document discusses using ReactIR technology to provide insights into chemical reactions and processes. It presents three case studies where ReactIR was used: (1) monitoring an unstable acid chloride intermediate in a Vilsmeier reaction, (2) studying mixed anhydride formation with unstable intermediates, and (3) gaining understanding of a chiral resolution process. ReactIR allowed observing reaction components in real-time, identifying side reactions, and gaining mechanistic insights in all three cases.
Application of Aqsens Technology: Case studies presented at SPE Oilfield Chem...Aqsens Oy
Aqsens novel method for testing polymeric scale inhibitor was presented with two case studies at SPE International Symposium on Oilfield Chemistry 13th-15th April 2015 in Texas.
Polymeric scale inhibitors can be difficult to detect at MED levels even with sophisticated analytical procedures. The necessary equipment is located in remote laboratories causing delays in obtaining results. It can take weeks to know the effectiveness of the scale control program.
Novel Aqsens technology is based on time-resolved-fluorescence method. It opens the possibility to control scale program efficiency infield with portable field lab unit. The results are ready for use in 10-15 minutes depending on the concentration.
The case studies presented at SPE symposium tested how well Aqsens technology performs compared to current testing possibilities such as HPLC. Aqsens effectiveness was demonstrated on more than 90 produced water samples collected from offshore and onshore wells.
See the full case studies on onshore mature heavy oil field and North Sea fields from attached SPE presentation.
Intercomparison of Different Technologies for the Analysisof Total Mercury in...gurleyuk
Multiple methods promulgated by the EPA for compliance monitoring of mercury in wastewater were investigated and compared to cold vapor inductively coupled plasma mass spectrometry. This study was performed to identify the limitations and benefits associated with each analytical method and to identify how varying waste streams can induce method failures.
Determination of Carbohydrates in Various Matrices by Capillary High-Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection (HPAE-PAD)
This presentation describes the combined advantages of a reagent-free capillary format Ion Chromatography (IC) to determine monosaccharides and disaccharides in various applications, from low concentrations in synthetic urine samples to high concentrations in beverage samples. In a reagent-free IC system, the hydroxide eluent is electrolytically generated inline to deliver accurate and precise concentrations for isocratic or gradient separations by only adding deionized water. Eluent generation eliminates carbonate contamination and errors from manual preparation. A capillary scale system with µL/min flow rates can run 24/7, always on and always ready for samples.
Application of Aqsens Technology: Case studies presented at SPE Oilfield Chem...Aqsens Oy
Aqsens novel method for testing polymeric scale inhibitor was presented with two case studies at SPE International Symposium on Oilfield Chemistry 13th-15th April 2015 in Texas.
Polymeric scale inhibitors can be difficult to detect at MED levels even with sophisticated analytical procedures. The necessary equipment is located in remote laboratories causing delays in obtaining results. It can take weeks to know the effectiveness of the scale control program.
Novel Aqsens technology is based on time-resolved-fluorescence method. It opens the possibility to control scale program efficiency infield with portable field lab unit. The results are ready for use in 10-15 minutes depending on the concentration.
The case studies presented at SPE symposium tested how well Aqsens technology performs compared to current testing possibilities such as HPLC. Aqsens effectiveness was demonstrated on more than 90 produced water samples collected from offshore and onshore wells.
See the full case studies on onshore mature heavy oil field and North Sea fields from attached SPE presentation.
Intercomparison of Different Technologies for the Analysisof Total Mercury in...gurleyuk
Multiple methods promulgated by the EPA for compliance monitoring of mercury in wastewater were investigated and compared to cold vapor inductively coupled plasma mass spectrometry. This study was performed to identify the limitations and benefits associated with each analytical method and to identify how varying waste streams can induce method failures.
Determination of Carbohydrates in Various Matrices by Capillary High-Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection (HPAE-PAD)
This presentation describes the combined advantages of a reagent-free capillary format Ion Chromatography (IC) to determine monosaccharides and disaccharides in various applications, from low concentrations in synthetic urine samples to high concentrations in beverage samples. In a reagent-free IC system, the hydroxide eluent is electrolytically generated inline to deliver accurate and precise concentrations for isocratic or gradient separations by only adding deionized water. Eluent generation eliminates carbonate contamination and errors from manual preparation. A capillary scale system with µL/min flow rates can run 24/7, always on and always ready for samples.
No single liquid chromatography (LC) detector delivers ideal results. Often with LC detectors one analyte responds more strongly than another, or may not respond at all. What is most desired is the ability to accurately measure a wide range of analytes with consistent response simultaneously.
Charged Aerosol detection (CAD) is a mass sensitive technique for determining levels of any non-volatile and many semi-volatile analytes after separation by liquid chromatography. This technique provides consistent analyte response independent of chemical characteristics and gives greater sensitivity over a wider dynamic range. An analytes response does not depend on optical properties, like with UV-vis absorbance, or the ability to ionize, as with mass spectrometry (MS). The presence of chromophoric groups, radiolabels, ionizable moieties, or chemical derivatization is needed for detection.
The Claus process is the industry standard and so the most
significant gas desulfurizing process, recovering elemental sulfur
from gaseous hydrogen sulfide.
The process is commonly referred to as a sulfur recovery unit
(SRU) and is very widely used to produce sulfur from the
hydrogen sulfide found in raw natural gas and from the by-product
sour gases containing hydrogen sulfide derived from refining
petroleum crude oil and other industrial facilities.
There are many hundreds of Claus sulfur recovery units in
operation worldwide.
In fact, the vast majority of the 68,000,000 metric tons of sulfur
produced worldwide in one year is by-product sulfur from
petroleum refining and natural gas processing plants.
Presentation Outline for Expanding Your High Performance Liquid Chromatography and Ultra High Performance Liquid Chromatography Capabilities with Universal Detection-Shedding Light on Non-Chromophore Compounds:
• Introduction to Charged Aerosol Detection
• How Charged Aerosol Technology Works
• Comparison with Evaporative Light Scattering Detectors
(ELSD)
• Examples of Applications
• Inverse Gradient Solution for Uniform Response
High-performance anion-exchange chromatography with pulsed amperometric detection is valuable for oligosaccharide analysis with the value derived from the high-resolution separation followed by sensitive detection of native oligosaccharides. In this presentation the application of HPAE-PAD to oligosaccharides released from glycoproteins is demonstrated.
The slickwater stimulation of unconventional gas and oil shale plays creates flowback water with a composition that is unique to particular shale formations. Characteristically, these fluids contain high concentrations of salts (e.g., chloride, bromide) which are routinely determined using ion chromatography. This analysis typically requires sample preparation, including manual dilution, which can significantly increase the cost of analysis. Results presented will show highly reproducible determination of anions and cations from Marcellus Shale flowback water using inline conductivity to identify high salt samples and then automatically diluting them prior to injection, saving time and column life.
Calibration , Commissioning & Testing of Bently Novada Vibration Analyzer , Emerson Vibration CSIC 2140, Hydrogen Sulphide , Crude Oil in Water, Water in Hydrocarbon Flue Gas HF Laser Gas Analyzers, MSA 4X, Ventis, Detector, Machine Analyzer, IR Temperature, Pressure Recorder, Infra Red Temperature Recorders, Thermocouples testing Humidity Meter, Temperature Calibrators , Laser Level , Carbon Monoxide, LEL detector , Oil & Water Meter , Fluke Thermocouple source meter calibration & CEMS Analyzers. Laboratory Chillers. Planning execution testing training and covering standard documentation at client site .
Plants concentrate metals by absorbing them from the soil in which they are grown. Some metals are beneficial and essential for life whereas other metals are highly toxic and have negative effects with even the lowest of levels. Because of their toxicity, quantification of these elements is needed. This application will investigate the preparation and analysis for heavy metals in Cascade Hops using Shimadzu AA-7000 with Graphite Furnace Atomic Absorption and Cold Vapor techniques.
Determination of Common Counterions and Impurity Anions in Pharmaceuticals Using a Capillary HPIC System with Suppressed Conductivity and Charge Detection
Recently, identification and quantification of ions in early stage drug development has gained increasing attention, because the APIs maybe contaminated with different counter ions from synthesis steps, and because selecting the counter ion to enhance APIs’ solubility and stability is becoming a key step in formulation development. This presentation demonstrates the identification and quantification of 22 commonly found anions in pharmaceuticals in a single run using a high-pressure capillary IC system (HPIC) with 4-μm particle ion –exchange column, and CD-QD dual detectors.
Understanding the Issues Affecting the Accuracy of Measuring Oxygen Consumpti...InsideScientific
LIVE WEBINAR: Thursday, December 7, 2017
Sponsor: http://www.aeitehcnologies.com/
During this webinar Phil Loeb introduces the measurements, variables and factors in determining VO2. He examines common sources of error and challenges that influence accuracy and reproducibility, and reviews validation methods commonly used by the research community. Following, Danny Rutar, Managing Director of Redback Biotek, presents best-practices, as embodied by the MOXUS Metabolic Cart, that are proven to minimize data error.
Background information:
Metabolic Carts have been used for decades as a means of measuring Oxygen Consumption, VO2, via indirect calorimetry. However, the accuracy of these systems is generally not well known nor well understood -- there is no universally accepted standard for determining the accuracy, or the validity, of Metabolic Cart measurements. In addition, scientists often do not have access or an appreciation for the specific calculations that are being used by these systems to calculate VO2 and other metabolic data. Collectively, this makes it challenging for researchers and physicians to understand if their data is valid.
Overview of webinar:
Rechargeable, manganese-based, lithium-ion batteries (LiBs) are environmentally friendly, have a good safety record, and can be made at a lower cost than other metal-based LiBs. However, they have a shorter lifetime. Much research has been spent on improving product safety, cycle life, and product performance, yet understanding fundamental processes and degradation mechanism in LiBs remains a challenge. Identifying breakdown products and understanding degradation processes can lead to enhancing battery performance, improvements in product safety, and insight into component failure mechanisms.
The impact of additive manufacturing on micro reactor technology (slideshare ...Raf Reintjens
The continuous tubular reactor is a well-known concept which is applied broadly and has proven its value to the chemical industry. In essence the micro reactor is nothing else than a tubular reactor with an unusual small diameter. Its excellent performance originates from the fact that the characteristic time for heat and mass transfer scales quadratic with the length scale. Ten times smaller diameter results in a hundred times faster transfer.
But, the very principles that lead to high performance seem to disable economical viable applications. Even at ‘micro reactor level’ productivity an astronomically large number of parallel channels is required to reach plant scale production capacities. The negative influence on manufacturability and cost can be countered by influencing the fluid dynamics inside the channel. Making use of secondary flow phenomena we succeed to maintain the ‘micro reactor level’ productivity at mm sized channel diameters. The desired secondary flow effect originates from influencing the shape, geometry and lay-out of the channel.
Selective laser melting (3D metal printing) is a new fast developing manufacturing technology that delivers excellent freedom of design combined with a promising cost level. Those properties match very well with the needs within micro reactor technology, and act as a strong enabler for applications in process development as well as industrial production.
No single liquid chromatography (LC) detector delivers ideal results. Often with LC detectors one analyte responds more strongly than another, or may not respond at all. What is most desired is the ability to accurately measure a wide range of analytes with consistent response simultaneously.
Charged Aerosol detection (CAD) is a mass sensitive technique for determining levels of any non-volatile and many semi-volatile analytes after separation by liquid chromatography. This technique provides consistent analyte response independent of chemical characteristics and gives greater sensitivity over a wider dynamic range. An analytes response does not depend on optical properties, like with UV-vis absorbance, or the ability to ionize, as with mass spectrometry (MS). The presence of chromophoric groups, radiolabels, ionizable moieties, or chemical derivatization is needed for detection.
The Claus process is the industry standard and so the most
significant gas desulfurizing process, recovering elemental sulfur
from gaseous hydrogen sulfide.
The process is commonly referred to as a sulfur recovery unit
(SRU) and is very widely used to produce sulfur from the
hydrogen sulfide found in raw natural gas and from the by-product
sour gases containing hydrogen sulfide derived from refining
petroleum crude oil and other industrial facilities.
There are many hundreds of Claus sulfur recovery units in
operation worldwide.
In fact, the vast majority of the 68,000,000 metric tons of sulfur
produced worldwide in one year is by-product sulfur from
petroleum refining and natural gas processing plants.
Presentation Outline for Expanding Your High Performance Liquid Chromatography and Ultra High Performance Liquid Chromatography Capabilities with Universal Detection-Shedding Light on Non-Chromophore Compounds:
• Introduction to Charged Aerosol Detection
• How Charged Aerosol Technology Works
• Comparison with Evaporative Light Scattering Detectors
(ELSD)
• Examples of Applications
• Inverse Gradient Solution for Uniform Response
High-performance anion-exchange chromatography with pulsed amperometric detection is valuable for oligosaccharide analysis with the value derived from the high-resolution separation followed by sensitive detection of native oligosaccharides. In this presentation the application of HPAE-PAD to oligosaccharides released from glycoproteins is demonstrated.
The slickwater stimulation of unconventional gas and oil shale plays creates flowback water with a composition that is unique to particular shale formations. Characteristically, these fluids contain high concentrations of salts (e.g., chloride, bromide) which are routinely determined using ion chromatography. This analysis typically requires sample preparation, including manual dilution, which can significantly increase the cost of analysis. Results presented will show highly reproducible determination of anions and cations from Marcellus Shale flowback water using inline conductivity to identify high salt samples and then automatically diluting them prior to injection, saving time and column life.
Calibration , Commissioning & Testing of Bently Novada Vibration Analyzer , Emerson Vibration CSIC 2140, Hydrogen Sulphide , Crude Oil in Water, Water in Hydrocarbon Flue Gas HF Laser Gas Analyzers, MSA 4X, Ventis, Detector, Machine Analyzer, IR Temperature, Pressure Recorder, Infra Red Temperature Recorders, Thermocouples testing Humidity Meter, Temperature Calibrators , Laser Level , Carbon Monoxide, LEL detector , Oil & Water Meter , Fluke Thermocouple source meter calibration & CEMS Analyzers. Laboratory Chillers. Planning execution testing training and covering standard documentation at client site .
Plants concentrate metals by absorbing them from the soil in which they are grown. Some metals are beneficial and essential for life whereas other metals are highly toxic and have negative effects with even the lowest of levels. Because of their toxicity, quantification of these elements is needed. This application will investigate the preparation and analysis for heavy metals in Cascade Hops using Shimadzu AA-7000 with Graphite Furnace Atomic Absorption and Cold Vapor techniques.
Determination of Common Counterions and Impurity Anions in Pharmaceuticals Using a Capillary HPIC System with Suppressed Conductivity and Charge Detection
Recently, identification and quantification of ions in early stage drug development has gained increasing attention, because the APIs maybe contaminated with different counter ions from synthesis steps, and because selecting the counter ion to enhance APIs’ solubility and stability is becoming a key step in formulation development. This presentation demonstrates the identification and quantification of 22 commonly found anions in pharmaceuticals in a single run using a high-pressure capillary IC system (HPIC) with 4-μm particle ion –exchange column, and CD-QD dual detectors.
Understanding the Issues Affecting the Accuracy of Measuring Oxygen Consumpti...InsideScientific
LIVE WEBINAR: Thursday, December 7, 2017
Sponsor: http://www.aeitehcnologies.com/
During this webinar Phil Loeb introduces the measurements, variables and factors in determining VO2. He examines common sources of error and challenges that influence accuracy and reproducibility, and reviews validation methods commonly used by the research community. Following, Danny Rutar, Managing Director of Redback Biotek, presents best-practices, as embodied by the MOXUS Metabolic Cart, that are proven to minimize data error.
Background information:
Metabolic Carts have been used for decades as a means of measuring Oxygen Consumption, VO2, via indirect calorimetry. However, the accuracy of these systems is generally not well known nor well understood -- there is no universally accepted standard for determining the accuracy, or the validity, of Metabolic Cart measurements. In addition, scientists often do not have access or an appreciation for the specific calculations that are being used by these systems to calculate VO2 and other metabolic data. Collectively, this makes it challenging for researchers and physicians to understand if their data is valid.
Overview of webinar:
Rechargeable, manganese-based, lithium-ion batteries (LiBs) are environmentally friendly, have a good safety record, and can be made at a lower cost than other metal-based LiBs. However, they have a shorter lifetime. Much research has been spent on improving product safety, cycle life, and product performance, yet understanding fundamental processes and degradation mechanism in LiBs remains a challenge. Identifying breakdown products and understanding degradation processes can lead to enhancing battery performance, improvements in product safety, and insight into component failure mechanisms.
The impact of additive manufacturing on micro reactor technology (slideshare ...Raf Reintjens
The continuous tubular reactor is a well-known concept which is applied broadly and has proven its value to the chemical industry. In essence the micro reactor is nothing else than a tubular reactor with an unusual small diameter. Its excellent performance originates from the fact that the characteristic time for heat and mass transfer scales quadratic with the length scale. Ten times smaller diameter results in a hundred times faster transfer.
But, the very principles that lead to high performance seem to disable economical viable applications. Even at ‘micro reactor level’ productivity an astronomically large number of parallel channels is required to reach plant scale production capacities. The negative influence on manufacturability and cost can be countered by influencing the fluid dynamics inside the channel. Making use of secondary flow phenomena we succeed to maintain the ‘micro reactor level’ productivity at mm sized channel diameters. The desired secondary flow effect originates from influencing the shape, geometry and lay-out of the channel.
Selective laser melting (3D metal printing) is a new fast developing manufacturing technology that delivers excellent freedom of design combined with a promising cost level. Those properties match very well with the needs within micro reactor technology, and act as a strong enabler for applications in process development as well as industrial production.
Micro Reaction Technology - Explains Design, Process and Applications of Micr...rita martin
Micro reaction technology, gaining its importance in various sectors of chemistry business, molecular biology and pharmaceutical chemistry. This technology increases the performance of chemical reaction process increasing in faster product development and safe production of chemicals
Gas Chromatography Thermo Fisher ScientificYuniarHasani
What is Chromatography?
Separation process that is achieved by distributing the analytes to be separated
between a mobile phase and a stationary phase.
Sample transported by mobile phase
Some components in sample interact more strongly with stationary phase
and are more strongly retained
Effect of Operating Conditions on CSTR performance: an Experimental StudyIJERA Editor
In this work, Saponification reaction of ethyl acetate by sodium hydroxide is studied experimentally in a continuous stirred tank reactor at 1 atmospheric pressure. The aim of this study is to investigate the influence of operating conditions on the conversion and specific rate constant. The parameters considered for analysis are temperature, feed flow rate, residence time, volume of reactor and stirrer rate. The steady state conversion of 0.45 achieved after a period of 30 minutes. Conversion decreases with increase of reactant flow rate due to decrease of residence time. The stirrer rate has a positive effect on the conversion and rate constant. Specific rate constant and conversion increase with temperature within the studied temperature range. Within the range of reactor volume selected for analysis, conversion increases with increase in reactor volume. The results obtained in this study may be helpful in maximizing the conversion of ethyl acetate saponification reaction at industrial scale in a CSTR.
Residence Time Distribution Data
0 INTRODUCTION/PURPOSE
1 SCOPE
2 FIELD OF APPLICATION
3 DEFINITIONS
4 BASICS OF RESIDENCE TIME DISTRIBUTION DATA
5 USE OF RESIDENCE TIME DISTRIBUTION DATA
5.1 Micromixing and Macromixing
5.2 Example 1 - Reaction is First Order
5.3 Example 2 - Reaction is Second Order
5.4 Complex Reactions and Residence Time Distribution
5.5 Examples
6 RESIDENCE TIME MEASUREMENTS WITH
RADIOISOTOPES
6.1 General
6.2 Types of Reactors
6.3 Models Based on Method of Moments
6.4 Non-impulse Input
6.5 Diagnosis of Problems
6.6 Commercial Radioisotope Service
7 BIBLIOGRAPHY
Gas - Liquid Reactors
0 INTRODUCTION/PURPOSE
1 SCOPE
2 FIELD OF APPLICATION
3 DEFINITIONS
4 PRELIMINARY CONSIDERATIONS
4.1 Preliminary Equipment Selection
4.2 Equipment for Low Viscosity Liquids
4.3 Equipment for High Viscosity Liquids
5 REACTOR DESIGN
6 ESSENTIAL THEORY
6.1 Rate and Yield Determining Steps
6.2 Chemical and Physical Rates
6.3 Modification for Exothermic and Complex Reactions
6.4 Preliminary Selection of Reactor Type
7 EXPERIMENTAL DETERMINATION OF REGIME
7.1 Direct Measurement of Reaction Kinetics
7.2 Laboratory Gas-Liquid Reactor Experiments
8 EQUILIBRIUM AND DIFFUSIVITY DATA SOURCES
9 OVERALL EFFECTS
9.1 Liquid Flow Patterns
9.2 Scale of Mixing
9.3 Gas Flow Pattern : Mean Driving Force for Mass Transfer
9.4 Gas-Liquid Reactor Modeling
9.5 Heat Transfer
9.6 Materials of Construction
9.7 Foaming
10 FINAL CHOICE OF REACTOR TYPE
11 SCALE-UP AND SPECIFICATION OF GAS-LIQUID
REACTORS
11.1 Bubble Columns
11.2 Packed Columns
11.3 Trickle Beds
11.4 Plate or Tray Columns
11.5 Spray Columns
11.6 Wiped Film
11.7 Spinning Film Reactors
11.8 Stirred Vessels
11.9 Plunging Jet
11.10 Surface Aerator
11.11 Static Mixers
11.12 Ejectors, Venturis and Orifice Plates
11.13 3-Phase Fluidized Bed
12 BIBLIOGRAPHY
TABLES
1 REGIMES OF GAS-LIQUID MASS TRANSFER WITH ISOTHERMAL CHEMICAL REACTION
2 REGIMES OF GAS-LIQUID MASS TRANSFER IGNORING LARGE EXOTHERMS OR OTHER COMPLICATIONS
3 COMPARATIVE MASS TRANSFER PERFORMANCE OF CONTACTING DEVICES
4 COMPARATIVE MASS TRANSFER DATA
5 CHOICE OF GAS-LIQUID REACTOR TYPE
FIGURES
1 RATE AND YIELD DETERMINING STEPS
2 ENHANCEMENT FACTOR vs HATTA NUMBER
3 ENHANCEMENT FACTOR vs HATTA NUMBER : EFFECT OF THERMAL & OTHER FACTORS
4 REACTORS FOR LIQUID-PHASE KINETICS
MEASUREMENT
5 EXPERIMENTS TO DETERMINE THE OPERATING
REGIME
6 EXPERIMENTS DETERMINE THE OPERATING REGIME WHERE A SOLID CATALYST IS INVOLVED
7 THE MIXED ZONES IN LOOPS' MODEL FOR STIRRED REACTORS
Outline of presentation:
Overview — Plating Baths and High Pressure Liquid Chromatography (HPLC)
Determination of Accelerator and Suppressor by HPLC and Charged Aerosol Detection
Sample Preparation, Calibration, Measurements
Comparisons to CVS data
Determination of Accelerator and Leveller by HPLC and Electrochemical Detection (ECD)
Coulometric Detection Mechanism and Design
Calibration and Measurements
Nickel Additives, Saccharin and Sodium Alkylsulfate
Gage Study Results
The purpose of this webinar is to highlight GSK's approach to:
- create a simple, mechanistically descriptive model
- verify its utility with clarity of objectives, and
- communicate understanding via creative but aligned metrics
... for a challenging chemical reaction.
ReactIR as a Diagnostic Tool for Developing Robust, Scalable Synthetic Processes
1. David W. Place Scientific Update Basel, Switzerland ReactIR as a Diagnostic Tool for Developing Robust, Scalable Synthetic Processes 29-OCT-2007 InPACT
24. Vilsmeier Catalytic Cycle Me 2 NH 2 + Cl - + CO + HCl H 2 O H 2 O CO + CO 2 + 2HCl H 2 O H 2 O Thermal Barrier? Degradents Thermal Barrier? Solubility Solubility
25.
26.
27.
28.
29. LC/MS Data for Major Impurity = 193 amu Degradation via cyclic intermediate Acid Catalyzed cyclization Trace Impurity Detected in ReactIR Impurity identity Confirmed by NMR
30. Acid Catalyzed isomerization Isomers can be detected with the SiCOMP ConcIRT Component Spectra: IR “Footprint region” Cis- C=C-H 744, 667 cm -1
31.
32. David Place Case Study #2: Unstable In-Situ Intermediates 10-APR-2007
33.
34.
35.
36.
37.
38. Scaleup: Mixed anhydride Formation Stressed 3h (0.04 mole/h, 0.6 equiv/h) addition to avoid exotherm on scaleup (a) (b) (e) (f) (g) (d) (c) (a) To (b) IBCF Addition over 10 min (c) To (e) NMM addition over 3 h (f) To (g) RNH 2 addition over 3 h HPLC assay @ 220 nm Inflection at ~1 equiv NMM Incomplete reaction?
39. 3-D Contour Reveals More Info NMM.HCl is evident in solution R 3 N + -H Str. Vibrations Consumption Of IBCF Mixed anhydride Dissolved NMM.HCl was not observed with NMM Addition over 30 minutes
40.
41.
42.
43. David Place Case Study #3: A Peek into Chiral Resolution 10-APR-2007
44.
45.
46.
47.
48.
49.
50.
51.
52.
Editor's Notes
Any spectra at any given point in time is a composite of all IR active components. Due to this, monitoring of a specific species in solution at a set wavenumber gives a kinetic profile that is a composite of all kinetic profiles of all species absorbing at that wavenumber. Best case scenario is when there is an isolated IR band to monitor. Then the kinetic profile obtained from monitoring that band is simply achieved by subtraction of a baseline in the system (usually solvent). In many cases however this scenario does not exist for all components of interest in a reaction mixture. Depending on the severity of spectral overlap certain information, such as endpoint determination and or establishing functional group assignments to specific components, may be skewed or difficult to pinpoint. As an analogy, the IR spectrum is the same as drawing the structures of all the components one on top of the other. You can see from the garbled mass that there are amine and carbonyl functional groups but you cannot with certainty assign them to any spectific component of the reaction. This is where deconvolution software is useful. By using statistics to analyze the changes in the IR spectrum over time, establishing component spectra that better describe the components and relating them to specific kinetic profiles eliminate some (but not all) of the uncertainty and make the technique more powerful and useful for mapping out reaction relationships and interdependencies.
*ATR Raw intensity data correlation to GC is limited by Thermal Background and Baseline Absorption by EtOAc *Detection Limit for Ethanol in Ethyl Acetate is 1.36 wt% at room temperature. *Detection limits will depend on spectral overlap and band absorbativity
Can we use ReactIR to help define the dependencies of the Vilsmeier catalytic cycle. First start with what is known: the suspected catalytic cycle. *Is there and operational window of temperatures that enables the control of the catalytic cycle and eliminates decomposition? How do we monitor this though? Conventional HPLC or GC techniques will give you almost no useful information. NMR techniques may provide useful information but we will have to operate in either special solvents or in a system that really does not simulate the reaction environment as it will be run. Can you really bring an NMR to the reactor? Some very distinct functional groups exist in all the anticipated components of the catalytic cycle, this gives us a hand hold onto following the fate of each species and defining the interconversions between reactive species. *Water contamination: We can infer certain decay pathways by derivatizing the acid chloride to its ester or amide, but this tells us limited information about what is actually happening in the reactor. Can use ReactIR to confirm or identify the most critical step that is responsible for inefficient conversions due to this parameter. *Solubility: Is a concern for using ReactIR. We need to understand the conversion process to acid chloride, but the starting material HCl salt is not soluable in the reaction solvent. Also solubility of acid chloride is not known.
Example shows that there is a thermal operational window for this process. If heat ramp control is inadequate or uncontrolled could lead to less acid chloride. May be a reason why lab scale reactions work consistently and large batch reactions show variability.
From Report on 07/13/2006. Initial temp was set to 0C during oxalyl chloride addition.
Reaction mixture is a slurry at the start of the experiment. Almost no Product acid chloride is soluable at the point of quenching with water. The “sinusoidal” waves in the data are due to the partial immiscibility od water in THF. As a globual of water passes by the IR sensor the acid and acid chloride component concentrations increase indicating a higher conc of these components dissolved in the water phase. Eventually the mixture homogenized.
Simplified display of ConcIRT deconvolution showing only major components: (a) Charge 10.53mL Isobutyl chloroformate (IBCF) over 10 minutes at Tr = -11.5C; (b) End IBCF charge; (c) Charge NMM over 3 h at Tr = -11.5C; (d) Sampled L34669-183-1#5; (e) End NMM charge sampled L34669-183-1#6; (f) Start FluoroPhenylDMPA Addition over 3 h at Tr = -8.5C; (g) End FluoroPhenylDMPA charge, Julabo Setpoint changed to –5C. NMM addition set to 1.8 equiv not enough when addition times are long. ~10% more NMM is required.
Establishing the components in a reaction is the most important first step when using ConcIRT algorythm to analyze your data. This will usually require processing that data in multiple ways (all spectra collected vs. broken into logical unit operations, processing with and without solvent subtraction from the entire data set, using 1 of 4 baselining techniques, changing the spectral range to incorporate key vibrational bands or exclude large bands due to solvents) By doing this, certain characteristic Component spectra become evident and inefficiencies in the deconvolution of known and unknown components can be evaluated.
Salt form A is produced immediately after mandelic acid is introduced (reaction <2 minutes) having featureless absorption at 1616 cm-1 and broad absorption at 2200-2800 cm-1 (indicative of a COO- NH+ salt). Salt form A converts to Salt Form B upon cooling to 50C or Form A crystallizes out and the rise in Form B is due to effective concentration in solution (the former is the more likely explanation). After point (e) the disappearance of form A can be attributed to crystallization out of solution.
Critical observables should typically be kinetic profiles of reaction components like the product, starting material impurities of interest, solvents or any combination of those.