Catalytic hydrogenation for producing amines from carboxylic acid amides, carboxylic acid diamides, di-, tri-, or polypeptides, or peptide amides

Patent metadata

Field	Value
Publication number	US-9878975-B2
Application number	US-201415034120-A
Country	US
Kind code	B2
Filing date	Oct 16, 2014
Priority date	Nov 5, 2013
Publication date	Jan 30, 2018
Grant date	Jan 30, 2018

Abstract

The present invention relates to a process for the preparation of amines, comprising the following steps: a. reaction of a (i) carboxylic acid amide of the general formula (I), or (ii) carboxylic acid diamide of the general formula (II), or (iii) di-, tri- or polypeptide, or (iv) peptide amide with carboxy-terminal amide function with an alkylating agent, b. addition of a hydrogenation catalyst to the reaction mixture in a molar ratio of from 1:10 to 1:100 000, based on carboxylic acid amide, carboxylic acid diamide, di-, tri- or polypeptide or peptide amide, c. reaction of the reaction mixture with hydrogen, where a hydrogen pressure of from 0.1 bar to 200 bar is established and where a temperature in a range of from 0° C. to 250° C. is established.

First claim

The invention claimed is:

1. A process for the preparation of amines, comprising the steps:
a) performing an O-alkylation of one or more compounds by reacting said compounds with an alkylating agent in a reaction mixture, wherein said alkylating agent is selected from the group consisting of: alkyl halides; esters of sulphonic acid; esters of fluorosulphonic acid; esters of trifluoromethanesulphonic acid; esters of chloroformic acid; oxonium salts; dialkyl sulphates; and diazomethane and said compounds are selected from the group consisting of:
i) a carboxylic acid amide of the general formula (I):

wherein:
R is selected from the group consisting of: H, (C 1 -C 24 )-alkyl, (C 3 -C 20 )-cycloalkyl, (C 2 -C 13 )-heterocycloalkyl, (C 6 -C 14 )-aryl, (C 3 -C 13 )-heteroaryl and the acid radical of an amino acid selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine; and
R 1 and R 2 , independently of one another, are selected from the group consisting of: H, (C 1 -C 24 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 2 -C 7 )-heterocycloalkyl, (C 6 -C 14 )-aryl or (C 3 -C 13 )-heteroaryl, where both the radicals R with R 1 , R with R 2 and also R 1 with R 2 may, independently of one another, form a saturated or mono- or polyunsaturated (C 2 -C 18 )-alkylene or (C 2 -C 18 )-heteroalkylene bridge, such that an aliphatic or aromatic ring having in total 3-20 ring atoms is formed;

ii) a carboxylic acid diamide of the general formula (II):

wherein:
R′″ is selected from the group consisting of divalent (C 1 -C 24 )-alkyl radicals, (C 3 -C 20 )-cycloalkyl radicals, (C 2 -C 13 )-heterocycloalkyl radicals, (C 6 -C 14 )-aryl radicals, (C 3 -C 13 )-heteroaryl radicals; and
R′ and R″, independently of one another, are selected from the group consisting of H, (C 1 -C 24 )-alkyl, (C 1 -C 24 )-heteroalkyl, (C 3 -C 8 )-cycloalkyl, (C 2 -C 7 )-heterocycloalkyl, (C 6 -C 14 )-aryl or (C 3 -C 13 )-heteroaryl, where the radicals R′ with R″ may together form a saturated or mono- or polyunsaturated (C 2 -C 18 )-alkylene or (C 2 -C 18 )-heteroalkylene bridge, such that an aliphatic or aromatic ring having in total 3-20 ring atoms is formed;

iii) a di-, tri- or polypeptide, and
iv) a peptide amide with a carboxy-terminal amide function;

b) adding a hydrogenation catalyst to the reaction mixture, wherein the molar ratio of hydrogenation catalyst to carboxylic acid amide, or carboxylic acid diamide, or di-, tri- or polypeptide or peptide amide, is in a range of from 1:10 to 1:100 000;
c) reacting the reaction mixture with hydrogen, at a hydrogen pressure of from 0.1 bar to 200 bar and at a temperature of from 0° C. to 250° C.

2. The process of claim 1 , wherein the hydrogenation catalyst comprises at least one active metal.

3. The process of claim 2 , wherein the active metal is a metal of group VII B and/or VIII B of the Periodic Table of the Elements.

4. The process of claim 1 , wherein, after step a), a base is added to the reaction mixture and wherein a molar ratio of base to alkylating agent of from 1:1 to 1:3 is produced.

5. The process of claim 1 , wherein the reaction is carried out in a solvent.

6. The process of claim 5 , wherein the solvent is selected from the group consisting of: hydrocarbons; chlorinated hydrocarbons; ethers; esters; and alcohols.

7. The process of claim 1 , wherein the reaction is carried out without solvents.

8. The process of claim 5 , wherein said alkylating agent is anhydrous and wherein an anhydrous solvent is used.

9. The process of claim 1 , wherein said compounds are carboxylic acid amides of the general formula (I):

wherein:
R is selected from the group consisting of: H, (C 1 -C 24 )-alkyl, (C 3 -C 20 )-cycloalkyl, (C 2 -C 13 )-heterocycloalkyl, (C 6 -C 14 )-aryl, (C 3 -C 13 )-heteroaryl and the acid radical of an amino acid selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine; and
R 1 and R 2 , independently of one another, are selected from the group consisting of: H, (C 1 -C 24 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 2 -C 7 )-heterocycloalkyl, (C 6 -C 14 )-aryl or (C 3 -C 13 )-heteroaryl, where both the radicals R with R 1 , R with R 2 and also R 1 with R 2 may, independently of one another, form a saturated or mono- or polyunsaturated (C 2 -C 18 )-alkylene or (C 2 -C 18 )-heteroalkylene bridge, such that an aliphatic or aromatic ring having in total 3-20 ring atoms is formed.

10. The process of claim 9 , wherein: R is H or a C 1 -C 6 alkyl; and R 1 and R 2 are independently: H, a (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 2 -C 7 )-heterocycloalkyl, a (C 6 -C 14 )-aryl or a (C 3 -C 13 )-heteroaryl.

11. The process of claim 1 , wherein said compounds are carboxylic acid diamides of the general formula (II):

wherein:
R′″ is selected from the group consisting of divalent (C 1 -C 24 )-alkyl radicals, (C 3 -C 20 )-cycloalkyl radicals, (C 2 -C 13 )-heterocycloalkyl radicals, (C 6 -C 14 )-aryl radicals, (C 3 -C 13 )-heteroaryl radicals; and
R′ and R″, independently of one another, are selected from the group consisting of H, (C 1 -C 24 )-alkyl, (C 1 -C 24 )-heteroalkyl, (C 3 -C 8 )-cycloalkyl, (C 2 -C 7 )-heterocycloalkyl, (C 6 -C 14 )-aryl or (C 3 -C 13 )-heteroaryl, where the radicals R′ with R″ may together form a saturated or mono- or polyunsaturated (C 2 -C 18 )-alkylene or (C 2 -C 18 )-heteroalkylene bridge, such that an aliphatic or aromatic ring having in total 3-20 ring atoms is formed.

12. The process of claim 1 , wherein said compounds are one or more of the following: N,N,N′,N′-tetramethylsuccinic acid diamide; N,N,N′,N′-tetramethyladipic acid diamide; N,N,N′,N′-tetramethylsuberic acid diamide, N,N,N′,N′-tetramethylterephthalic acid diamide and sarcosine anhydride.

13. The process of claim 1 , wherein said compounds are di-, tri- or polypeptides.

14. The process of claim 1 , wherein said compounds are peptide amides with a carboxy-terminal amide function.

15. The process of claim 1 , wherein said alkylating agent is an alkyl halide.

16. The process of claim 1 , wherein said alkylating agent is an ester of sulphonic acid; an ester of fluorosulphonic acid; or and ester of trifluoromethanesulphonic acid.

17. The process of claim 1 , wherein said alkylating agent is an ester of chloroformic acid.

18. The process of claim 1 , wherein said alkylating agent is an oxonium salts.

19. The process of claim 1 , wherein said alkylating agent is a dialkyl sulphate.

20. The process of claim 1 , wherein said alkylating agent is diazomethane.

Assignees

• Evonik Degussa Gmbh

Inventors

• Kadyrov Renat

Classifications

• C07F9/4006

  Esters of acyclic acids which can have further substituents on alkyl · CPC title

• C07D295/03

  with the ring nitrogen atoms directly attached to acyclic carbon atoms · CPC title

• C07D295/027

  containing only one hetero ring · CPC title

• C07K5/06078

  and aromatic or cycloaliphatic · CPC title

• C07K5/06026

  the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala · CPC title