Method for decarboxylation of amino acids via imine formation

Patent metadata

Field	Value
Publication number	US-10118898-B2
Application number	US-201615249719-A
Country	US
Kind code	B2
Filing date	Aug 29, 2016
Priority date	Mar 14, 2013
Publication date	Nov 6, 2018
Grant date	Nov 6, 2018

Abstract

The present application provides methods for decarboxylation of amino acids via imine formation with a catalyst under pressurized, heated, conditions in either a microwave or oil bath, with optional recovery of the catalyst and/or catalyst byproduct.

First claim

The invention claimed is:

1. A method for decarboxylation of amino acids to produce an amine via an imine intermediate, the method comprising:
(a) combining, in a pressurized reaction vessel, a mixture of an amino acid, a solvent, and a catalyst, the catalyst comprising a ketone, enone, enal, aldehyde, or combination thereof;
(b) heating the mixture at about 180° C., or more, for about 5 minutes, or more, wherein the amino acid is converted to its imine;
(c) cooling the reaction mixture from step (b) in the reaction vessel to a temperature below the boiling point of the solvent;
(d) adding an acid to the cooled reaction mixture from step (c) in the vessel; and
(e) heating the acid reaction mixture from step (d) to about 50° C., or more, to hydrolyze the imine to form an amine.

2. The method of claim 1 , wherein the solvent is a short chain alcohol or water.

3. The method of claim 1 , wherein the solvent is selected from the group consisting of: water, n-butanol, n-pentanol, isopropanol, ethanol, methanol, and n-propanol.

4. The method of claim 1 , wherein the catalyst is selected from the group of ketones, enones, and enals consisting of: R-carvone, S-carvone, cyclohex-2-ene-1-one, acetophenone, 3-penten-2-one, butanone, dihydrocarvone, citral, β-ionone, R-pulegone, carvenone, cinnamaldehyde, 3-methylcyclohex-2-enone, pentadione, acetone, piperitone, poperitenone, isopiperitenone, methyl vinyl ketone, butenones, 2-phenylpropenal, and other R-ene-aldehydes.

5. The method of claim 1 , wherein the catalyst is R-carvone, S-carvone, or mixture thereof.

6. The method of claim 1 , wherein the catalyst is dihydrocarvone or carvenone.

7. The method of claim 1 when the amount of catalyst is from about 0.1 to about 2 mole equivalents.

8. The method of claim 1 , wherein, in step (b), the mixture is heated in a microwave to a temperature of about 180° C. to about 190° C. and maintained at a temperature of about 180° C. to about 190° C. for about 5 min to about 10 min.

9. The method of claim 8 , wherein the mixture is heated in a microwave to a temperature of about 190° C. for about 5 min, and if the reaction mixture is not clear after the 5 minutes of heating, the mixture is heated in the microwave to about 190° C. for about 5 to about 25 min longer.

10. The method of claim 1 , wherein, in step (b), the mixture is heated in an oil bath at a temperature of about 180° C. to about 190° C. for about 5 min to about 20 min.

11. The method of claim 10 , wherein, mixture is heated in an oil bath at a temperature of about 180° C. to about 190° C. for about 5 min, and wherein, if the reaction mixture is not clear after the 5 minutes of heating, the mixture is heated at about 180° C. to about 190° C. for an additional time of about 5 to about 20 min.

12. The method of claim 1 , wherein the catalyst is a ketone, enone or enal capable of isomerization at temperatures of about 120° C., or more, to yield a byproduct selected from the group consisting of: enals, enones, phenolic terpenes, phenolic terpenoids, xylenols, and ethylmethylphenols.

13. The method of claim 12 , wherein the acid reaction mixture during step (e) is heated to about 120° C., or more, to hydrolyze the imine to form an amine and to isomerize any unreacted catalyst.

14. The method of claim 12 , wherein the catalyst byproduct is selected from the group consisting of: carvacrol, carvenone, thymol, xylenols, ethylmethylphenols, 2-pentenal, hex-3-en-2-one, piperitone, and 3-ehtyl-6-methylcyclohex-2-en-1-one, 3-ethylcyclopent-2-ene-1-one.

15. The method of claim 1 , wherein the catalyst is S-carvone, R-carvone, or dihydrocarvone and wherein the acid reaction mixture during step (e) is heated to about 180° C., or more, to hydrolyze the imine to form an amine and to isomerize any unreacted catalyst.

16. The method of claim 15 , wherein the catalyst is S- or R-carvone, or a mixture thereof, and wherein the S- or R-carvone is isomerized to produce carvacrol, and further comprising recovering the carvacrol.

17. The method of claim 15 , wherein the catalyst is dihydrocarvone and wherein the dihydrocarvone is isomerized to produce carvenone, and further comprising recovering the carvenone.

18. The method of claim 15 , wherein the acid reaction mixture is heated to about 185° C. to about 190° C. for about 5 min., or more.

19. The method of claim 12 , wherein the acid reaction mixture during step (e) is heated to about 50 to 80° C., or more, to hydrolyze the imine in equilibrium to form an amine, and further comprising:
(f) recovering the catalyst via extraction from the reaction mixture from step (e), and
(g) performing an additional reflux on the acid reaction mixture at a temperature of about 120° C., or more, for about 5 min., or more, to isomerize any unreacted catalyst.

20. The method of claim 1 , wherein the acid is a strong acid.

21. The method of claim 1 , wherein the acid is any of HCl, H 2 SO 4 , H 3 PO 4 , and HBr.

22. The method of claim 1 , further comprising:
(f) removing unreacted solvent and catalyst; and
(g) recovering the amine.

23. The method of claim 22 , wherein removing unreacted solvent and catalyst comprises washing the reaction mixture with ether and water solvent and distilling off the water, ether, solvent, and recovering an amine salt.

Assignees

• Univ Georgia

Inventors

• Morrison Richard W
• Jackson Douglas Michael
• Morrison Daniel Richard

Classifications

• C07D209/16

  Tryptamines · CPC title

• C07C209/68

  from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton · CPC title

• C07B37/06

  Decomposition, e.g. elimination of carbon dioxide · CPC title

• C07C209/52

  by reduction of imines or imino-ethers (C07C209/24 takes precedence) · CPC title

• C07C211/03

  Monoamines · CPC title