Method for decarboxylation of amino acids via imine formation

Patent metadata

Field	Value
Publication number	US-9452954-B2
Application number	US-201414210655-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 14, 2013
Publication date	Sep 27, 2016
Grant date	Sep 27, 2016

Abstract

The present application provides methods for decarboxylation of amino acids via imine formation with a catalyst under pressurized and superheated conditions in either a microwave or oil bath.

First claim

The invention claimed is:

1. A method for decarboxylation of amino acids, the method comprising:
combining, in a pressurized reaction vessel, a mixture of an amino acid, a solvent, and a catalyst, wherein the solvent has a lower boiling point than cyclohexanol and does not produce a maximum vapor pressure exceeding the vessel limit;
heating the mixture at about 180° C., or more, for about 5 minutes, or more, wherein the amino acid is converted to its imine;
cooling the reaction vessel to a temperature below the boiling point of the solvent;
adding an acid to the reaction mixture in the vessel; and
heating the acid reaction mixture 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 solvent is n-propanol.

5. The method of claim 1 , wherein the catalyst is selected from the group consisting of: ceyclohex-2-ene-1-one, acetophenone, R-carvone, S-carvone, and acetone.

6. The method of claim 1 , wherein the catalyst is R-carvone.

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 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 minutes to about 10 minutes.

9. The method of claim 8 , wherein the mixture is heated in a microwave to a temperature of about 190° C. for about 5 minutes, 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 minutes longer.

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

11. The method of claim 10 , wherein, the mixture is heated in an oil bath at a temperature of about 180° C. to about 190° C. for about 5 minutes, 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 minutes.

12. The method of claim 10 , wherein the oil bath is heated to a temperature of about 210° C. prior to addition of the reaction vessel and brought back to a temperature between about 185° C. to about 190° C. after addition of the reaction vessel.

13. The method of claim 1 , wherein the catalyst is carvone and the acid reaction mixture is heated to about 80° C., or more, with gentle reflux to hydrolyze the imine in equilibrium.

14. The method of claim 13 , further comprising recovering the catalyst via extraction and performing an additional reflux at a temperature of about 180° C., or more, for about 5 minutes, or more, to isomerize any unreacted catalyst.

15. The method of claim 1 , wherein the acid reaction mixture is heated to about 180° C., or more, for about 5 minutes, or more, to hydrolyze the imine to form an amine and to isomerize any unreacted catalyst.

16. The method of claim 1 , wherein the acid reaction mixture is heated to about 185° C. to about 190° C. for about 5 minutes, or more, to hydrolyze the imine to form an amine and to isomerize any unreacted catalyst.

17. The method of claim 1 , wherein the acid is HCl.

18. The method of claim 1 , wherein the amino acid is selected from the group consisting of: histidine, isoleucine, lysine, phenylalanine, tryptophan, and tyrosine.

19. A method for decarboxylation of amino acids, the method comprising:
combining, in a pressurized reaction vessel, a mixture of an amino acid, n-propanol as solvent, and from about 0.1 to about 2 mol equivalents of R-carvone or S-carvone as catalyst; and
heating the mixture in a microwave to a temperature of about 180° C. to about 195° C. for about 5 minutes, or more, to convert the amino acid to an imine;
optionally heating the mixture in the microwave to a temperature of about 180° C. to about 195° C. for up to an additional 25 minutes;
cooling the reaction vessel to a temperature below the boiling point of n-propanol;
adding an acid to the reaction mixture in the vessel; and
re-heating the acid reaction mixture in the microwave to a temperature of about 180° C. to about 195° C. to hydrolyze the imine to form an amine and to convert unreacted carvone to carvacrol.

20. The method of claim 19 , further comprising:
removing unreacted solvent and carvacrol; and
recovering the amine.

21. The method of claim 20 , wherein removing unreacted solvent and carvacrol comprises washing the reaction mixture with ether and water solvent and distilling off the water, ether, solvent, and recovering an amine salt.

22. A method for decarboxylation of amino acids comprising:
Combining, in a pressurized reaction vessel, a mixture of an amino acid, n-propanol as solvent, and from about 0.1 to about 2 mol equivalents of R-carvone or S-carvone as catalyst; and
heating the mixture in an oil bath at a temperature of about 180° C. to about 195° C. for about 5 minutes to convert the amino acid to an imine;
optionally heating the mixture in the oil bath at a temperature of about 180° C. to about 195° C. for up to an additional 25 minutes;
cooling the reaction vessel to a temperature below the boiling point of n-propanol;
adding an acid to the reaction mixture in the vessel;
and re-heating the acid reaction mixture in the oil bath at a temperature of about 180° C. to about 195° C. to hydrolyze the imine to form an amine and to convert unreacted carvone to carvacrol.

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

24. A method for decarboxylation of amino acids, the method comprising:
combining, in a pressurized reaction vessel, a mixture of an amino acid, a solvent, and a catalyst;
heating the mixture at about 180° C., or more, at a pressure of greater than 1 atm for about 5 minutes, or more, wherein the amino acid is converted to its imine;
cooling the reaction vessel to a temperature below the boiling point of the solvent;
adding an acid to the reaction mixture in the vessel; and
heating the acid reaction mixture to about 50° C., or more, to hydrolyze the imine to form an amine.

Assignees

• Univ Georgia

Inventors

• Morrison Richard W
• Jackson Douglas Michael

Classifications

• C07B37/06 Primary

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

• C07C211/03

  Monoamines · CPC title

• C07C211/08

  containing alkyl groups having a different number of carbon atoms · CPC title

• C07D233/64

  with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine · CPC title

• C07C251/20

  having carbon atoms of imino groups being part of rings other than six-membered aromatic rings · CPC title