Reductive alkylation of amines with orthocarboxylic acid esters

Abstract

The present invention relates to a process for the N-alkylation of amines by reacting an amine with an orthocarboxylic acid ester and with hydrogen in the presence of a hydrogenation catalyst.

Claims

1. A process for the N-alkylation of amines or of ammonia, comprising reacting an orthocarboxylic acid ester with an amine or with ammonia and with hydrogen in the presence of a hydrogenation catalyst.

2. The process of claim 1, wherein the reaction takes place in the presence of an acid.

3. The process of claim 2, wherein the reaction takes place at a molar ratio of acid to amine in a range from 0.01:100 to 10:100.

4. The process of claim 1, wherein the reaction takes place at a molar ratio of hydrogenation catalyst to the amine used in a range from 1:10 to 1:100 000.

5. The process of claim 1, wherein the reaction takes place at a hydrogen partial pressure in a range from 0.1 bar to 200 bar.

6. The process of claim 1, wherein the reaction is carried out in a temperature range from 20 C. to 200 C.

7. The process of claim 1, wherein the hydrogenation catalyst is a heterogeneous hydrogenation catalyst.

8. The process of claim 7, wherein the heterogeneous hydrogenation catalyst comprises at least one active metal.

9. The process of claim 8, wherein the active metal is a metal of group VII B and/or VIII B of the Periodic Table of the Elements.

10. The process of claim 1, wherein the reaction takes place in a solvent.

11. The process of claim 10, wherein the solvent is selected from the group consisting of hydrocarbons, chlorohydrocarbons, ethers, esters and alcohols.

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

13. The process of claim 4, wherein the reaction takes place at a hydrogen partial pressure in a range from 0.1 bar to 200 bar.

14. The process of claim 13, wherein the reaction is carried out in a temperature range from 20 C. to 200 C.

15. The process of claim 4, wherein the hydrogenation catalyst is a heterogeneous hydrogenation catalyst.

16. The process of claim 15, wherein the heterogeneous hydrogenation catalyst comprises at least one active metal.

17. The process of claim 16, wherein the active metal is a metal of group VII B and/or VIII B of the Periodic Table of the Elements.

18. The process of claim 17, wherein the reaction takes place in a solvent.

19. The process of claim 18, wherein the solvent is selected from the group consisting of hydrocarbons, chlorohydrocarbons, ethers, esters and alcohols.

20. The process of claim 17, wherein the reaction is carried out without solvents.

Description

EXAMPLES

(1) General Procedure for the Reductive Alkylation of Amines with Orthocarboxylic Acid Esters

(2) An autoclave was filled with catalyst (1 mol % based on the molar amount of amine), flushed with argon and topped up with a solution of amine (0.1 mol) and orthocarboxylic acid ester (0.11-0.3 mol) in 10 ml of methanol (or ethanol) and 0.5 ml of a 0.2 M solution of anhydrous p-toluenesulphonic acid in methanol (or ethanol). The mixture was heated to 120 C. and hydrogen was injected to 40 bar and then the mixture was stirred at a constant pressure until hydrogen absorption could no longer be detected (0.2-6 h). After being filtered off from the catalyst, the filtrate was distilled.

(3) The yields can be found in Table 1.

(4) TABLE-US-00001 TABLE 1 Yields in the reductive alkylation of amines with orthocarboxylic acid esters. Ortho- carboxylic Ex- Ortho- acid ample carboxylic ester/ Hydrogenation Time, Yield No. acid ester Amine Product amine catalyst [h] [%] 1 HC(OMe).sub.3 2.5 3% Pt/C 3 99 2 HC(OMe).sub.3 2.5 5% Ru/Al.sub.2O.sub.3 5 98 3 HC(OMe).sub.3 2.5 [(dppb)Rh(COD)]BF.sub.4 6 83 4 HC(OMe).sub.3 2.5 5%Pd/C 1 92 5 HC(OMe).sub.3 0 2.5 5% Pt/C 0.2 97 6 HC(OMe).sub.3 2.5 5% Ru/C 0.3 96 7 HC(OMe).sub.3 2.5 5% Rh/C 0.3 98 8 EtC(OMe).sub.3 PhNH.sub.2 1.1 3% Pt/C 1 66 9 n-Buc(OEt).sub.3 1.3 5% Pt/C 1 81 10 n-Buc(OEt).sub.3 0 1.3 5% Pt/C 0.2 95 11 n-Buc(OEt).sub.3 1.3 5% Ru/C 0.2 90 12 n-Buc(OEt).sub.3 1.3 5% Rh/C 0.2 86 13 PhC(OEt).sub.3 1.1 3% Pt/C 1 93 14 PhC(OEt).sub.3 1.1 5% Rh/C 1 81 15 HC(OMe).sub.3 0 3 5% Pd/C 1 99 16 HC(OMe).sub.3 3 5% Pt/C 0.5 99 17 EtC(OMe).sub.3 1.2 5% Pd/C 2 64 18 EtC(OMe).sub.3 1.2 5% Pt/C 1 69 19 EtC(OMe).sub.3 1.2 5% Pd/C 1 82 20 EtC(OMe).sub.3 0 1.2 5% Pt/C 0.1 75 21 EtC(OMe).sub.3 1.2 5% Ru/C 0.5 71 22 EtC(OMe).sub.3 1.2 5% Rh/C 0.1 85 23 EtC(OMe).sub.3 1.2 5% Pt/C 0.1 83 24 EtC(OMe).sub.3 1.2 5% Ru/C 0.2 84 25 EtC(OMe).sub.3 0 1.2 5% Rh/C 0.2 90 26 EtC(OMe).sub.3 1.2 5% Ru/C 0.5 93 27 EtC(OMe).sub.3 1.2 5% Rh/C 0.1 95 28 HC(OMe).sub.3 3 5% Pd/C 0.5 98 29 HC(OMe).sub.3 3 5% Pt/C 0.1 99 30 HC(OMe).sub.3 0 3 5% Ru/C 0.3 98 31 HC(OMe).sub.3 3 5% Rh/C 0.3 97 32 EtC(OMe).sub.3 2 5% Pt/C 0.3 90 33 HC(OEt).sub.3 2 5% Pd/C 0.5 82 34 HC(OEt).sub.3 2 5% Pt/C 0.2 90 35 HC(OEt).sub.3 0 2 5% Ru/C 0.3 88 36 HC(OEt).sub.3 2 5% RhC 0.3 87