This document discusses amidocarbonylation, a transition metal catalyzed reaction that constructs amino acid frameworks from simple starting materials like aldehydes and nitriles. It describes the discovery of cobalt-catalyzed and palladium-catalyzed amidocarbonylation, and their applications in producing amino acid derivatives, N-acetyl-D,L-phenylalanine precursors, and sarcosinates. The document also outlines developments in substrate scope and reaction conditions that provide access to functionalized amino acids and N-substituted glycines.

1. WELCOME

2. Amidocarb
onylation
An Efficient Route to Amino acid Derivatives
UNDER THE SUPERVISION OF- NASHRA SALEEM
Dr. S. MASHHOOD Ali 12-0CHM-17
GH1792

3. CONTENTS
 INTRODUCTION
 DISCOVERY OF AMIDOCARBONYLATION
 WAKAMATSU REACTION
 COBALT CATALYSED REACTION
 APPLICATIONS
 PALLADIUM CATALYSED REACTION
 APPLICATIONS
 CONCLUSION
 REFERENCES

4.  Amidocarbonylation is the transition metal catalysed
multicomponent reaction that constructs the
aminoacid framework directly from simple,
inexpensive starting materials.
 The structure of N-acyl-a-amino acids are found in
many compounds. e.g - CAPTOPRIL , FLAMPROP-
ISOPROPYL, ASPARTAME etc.
INTRODUCTION

5. STRUCTURES-

6. HISTORICAL BACKGROUND
WAKAMATSU et al. FIRST
DISCOVERED
COBALT-CATALYZED
AMIDOCARBONYLATION
IN 1970
WITTE AND SEELIGER
DEVELOPED A
CORRESPONDING
KOCH
CARBONYLATION IN
SULPHURIC ACID

7. THE DISCOVERY OF
AMIDOCARBONYLATION

8. THE WAKAMATSU REACTION
 THE DEVELOPMENT OF THE OXO PROCESS FOR THE
PREPARATION OF 3-CYANOPROPIONALDEHYDE FROM
ACRYLONITRILE WAS ESSENTIAL STEP IN THE
DISCOVERY OF TODAY’S WELL KNOWN
AMIDOCARBONYLATION REACTION.
AS EARLY AS 1962 THE HYROFORMYLATION OF
ACRYLONITRILE WITH METHANOL AS THE SOLVENT
HAD BEEN USED SUCCESSFULLY ON THE COMMERCIAL
SCALE.

9. REACTION

10. COBALT CATALYSED REACTIONS

11. REACTION CONDITIONS
70-160◦C
50-200 bar
Solvents-dioxane ,THF,DME,ethyl acetate
acetone, or benzene.
Concentration of starting material in
solutions is usually 0.1-3 M and amide
may be used in excess.

12. MECHANISM

13. METHOD DEVELOPMENT IN COBALT
CATALYSED REACTION
IN ADDITION TO ALDEHYDES , OLEFINS ,
ACETALS, EPOXIDE, ALLYL ALCOHOLS AND
BENZYLCHLORIDE CAN ALSO BE USE AS
STARTING MATERIAL.

14. ALDEHYDES

15. INTRAMOLECULAR
AMIDOCARBONYLATION

16. ACETALS,EPOXIDE AND ALLYL
ALCOHOLS
 ACETALS AS SIMPLE PROTECTED ALDEHYDE
EQUIVALENTS ARE EITHER HYDROLYED IN SITU
UNDER THE REACTION CONDITIONS AND REACT IN
AN ANALOGOUS MANNER TO THE ALDEHYDES,OR
THEY LEADS TO THE CORRESPONDING
N-ACYLAMINOACID ESTERS BY WATER REMOVAL.
 ADVANTAGE
 IF OTHER FUNCTIONAL GROUPS ARE PRESENT IN
THE STARTING MATERIAL THEN IT ACTS AS
PROTECTING GROUP AND HELPS TO GET DESIRED
PRODUCT

17. EPOXIDE
 EPOXIDE SUCH AS STYRENE OXIDE OR PROPENE
OXIDE, MAY BE REARRANGED INTO ALDEHYDES BY
LEWIS ACID CATALYSIS AND THEN
AMINOCARBONYLATED.
 TRANSITION METAL COMPLEXES SUCH AS
[Fe2(CO)9],[PdCL2(PPh3)] etc. HAVE PROVED TO BE
SUITABLE FOR THE IN SITU ISOMERIZATION OF
ALLYL ALCOHOLS TO ENOLS,WHICH THEN
TAUTOMERIZE TO ALDEHYDES.

18. ALCOHOLS AND BENZYLCHLORIDE
 ALCOHOLS THAT FORMS STABLE CARBENIUM
IONS MAY BE HYDROFORMYLATED TO
CORRESPONDING ALDEHYDE.
 1-CYCLOPROPYLMETHANOL WAS CONVERTED
INTO N-ACETYL-3-CYCLOPROPYLALANINE BY
CARONYLATION-AMIDOCARBONYLATION.

19. APPLICATIONS
 N-ACETYL-D,L-PHENYLALANINE
 IT IS A PRECURSOR OF
L-PHENYLALANINE,THE KEY INTERMEDIATE
IN THE SYNTHESIS OF ASPARTAME(THE
METHYL ESTER OF L-ASPARTYL-L-
PHENYLALANINE),AN ARTIFICIAL SWEETENER.

20. REACTION

21. SARCOSINATES
 THE LONG–CHAIN N-ACYL DERIVATIVES OF
SARCOSINE (N-METHYL-GLYCINE)BELONGS
TO THE GROUP OF ANIONIC TENSIDES THAT
ARE USED AS COMPONENTS OF
SURFACTANTS, SOAPS AND EMULSIFIERS
BECAUSE OF THEIR LOW HARDENING
SENSITIVITY AND GOOD DERMATOLOGICAL
COMPATIBILITY .

22. PALLADIUM CATALYSED
AMIDOCARBONYLATION
 MILDER CONDITIONS.
 PRESENCE OF HALIDE IONS AS CO-CATALYST.
 SYNERGISTIC EFFECT IS SEEN.
 BOTH PALLADIUM(O) AND PALLADIUM(II) CAN
BE USE.
 PALLADIUM CATALYST HAVE AN ACTIVITY
GREATER THAN THE COBALT SYSTEM BY A
FACTOR OF 10 -100.

23. MECHANISM

25. DEVELOPMENT IN THE METHODOLOGY OF
PALLADIUM CATALYSED AMIDOCARBONYLATION
 DEPENDING ON THE NATURE OF THE STARTING
MATERIAL, THE USE OF UREA DERIVATIVES AS
AMIDE COMPONENTS HAS MADE IT POSSIBLE TO
ISOLATE THE ACTUAL AMIDOCARBONYLATION
PRODUCTS, THE N-UREIDOAMINO ACIDS.
HOWEVER, THE SUBSTITUTED HYDANTOIN IS
USUALLY OBTAINED WITH HIGH SELECTIVITY.
 HYDANTOIN ARE VERY IMPORTANT IN BOTH
PRODUCTION OF AMINO ACIDS AND IN
RESEARCH OF PHARMACEUTICALLY ACTIVE ,LOW
MW HETEROCYCLES.

27. AMIDOCARBONYLATION OF NITRILES
 AMIDOCARBONYLATION OF NITRILES WAS
DEVELOPED IN WHICH THE AMIDE IS
GENERATED INSITU.
 AMIDE IS USEFUL IN THE PRODUCTION OF N
ACETYL-D,L-VALINE OR METHIONINE.

28. SYNTHETIC APPLICATIONS OF PALLADIUM-
CATALYSED AMIDOCARBONYLATION
FUNCTIONALYSED ARYLGLYCINES
 THE PRODUCTS OF AMIDOCARBONYLATION OF
BENZALDEHYDES,N-ACYL-ARYLGLYSINE OCCURS AS
SUBSTRUCTURES IN MANY DIFFERENT
PHARMACOLOGICALLY ACTIVE COMPOUNDS.

29. N-SUBSTITUTED GLYCINES
THE AMIDOCARBONYLATION OF SECONDARY
AMIDES ARE MORE DIFFICULT TO CARRY OUT
THAN THE CORRESPONDING REACTIONS
PRIMARY AMIDES.HOWEVER ,IT HAS BEEN
POSSIBLE TO PREPARE A SERIES OF N-
SUBSTITUTED N-GLYCINES BY REACTION WITH
FORMALDEHYDE .

30. REACTION

31. CONCLUSION
 WITH THE ESTABLISHMENT OF TRANSITION
METAL CATALYSED
AMIDOCARBONYLATION,CRITICAL ADVANCES
HAVE BEEN MADE IN THE RECENT YEARS WITH
THE ATTAINMENT OF HIGHER CATALYST
ACTIVITIES UNDER MILDER CONDITION.
 IT WILL LEADS TO THE FORMATION OF
INTERESTING PRODUCTS FROM SIMPLE
STARTING MATERIALS.

32. REFERENCES
 Angewandte Chemie. International Ed.2000,39,1010-
1027
 K.Kuhlein, H.Geissler in Transition metals for
Organic synthesis.1998 p.79
 A.P.Mikhalin, Russ. Chem. Rev. 1995,64,259.