Process for the manufacture of dibenzoylmethane derivatives

Patent metadata

Field	Value
Publication number	US-9561993-B2
Application number	US-201113996042-A
Country	US
Kind code	B2
Filing date	Dec 19, 2011
Priority date	Dec 20, 2010
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

Abstract

The invention relates to a process for the manufacture of substituted dibenzoylmethane derivatives. This economical process provides products in high purity and yields and results in shorter reaction times.

First claim

The invention claimed is:

1. A process for the preparation of substituted dibenzoylmethane derivatives of formula (I):

wherein R1 and R2 are independently selected from the group consisting of hydrogen, C 1 to C 12 alkyl, C 1 to C12 alkoxy, C 3 to C 12 alkenyloxy and C2 to C 12 alkenyl; and wherein
the process comprises the step of forming the potassium salt of formula (I) with a yield of 85% or greater by condensing in a condensation step a homogenous reaction mixture of a ketone of formula (II) with an ester of formula (III) in the presence of a potassium alcoholate of formula (IV):

wherein R 1 and R 2 are as defined above; R 3 is hydrogen; R 4 is C 1 to C 12 alkyl and R 5 is C 1 to C 8 alkyl;
with the proviso that at least one of R 1 and R 2 is not hydrogen and with the proviso that the potassium alkoxide is of an alcohol R 5 —OH having a boiling point below 100° C.

2. The process according to claim 1 wherein R 1 and R2 are independently selected from the group consisting of hydrogen, C1 to C 12 alkyl and C1 to C12 alkoxy.

3. The process according to claim 1 wherein R 3 is hydrogen and R 4 is methyl, ethyl or 1,1 dimethylethyl.

4. The process according to claim 1 wherein the condensation step is carried out in an inert solvent.

5. The process according to claim 4 wherein the inert solvent is toluene and/or xylene, preferably toluene.

6. The process according to claim 1 wherein the potassium alcoholate is at least one selected from the group consisting of potassium methylate and potassium tert-butylate.

7. The process according to claim 1 wherein the process comprises continuously removing the alcohols R 4 OH and R 5 OH as the alcohols are formed.

8. The process according to claim 1 wherein R 1 is methoxy, R 2 is 1,1 dimethylethyl and R 4 is methyl, ethyl or 1,1 dimethylethyl.

9. The process according to claim 1 wherein the molar ratio of the ketone of formula (II) to the ester of formula (III) is in a range of 0.5 to 1.25.

10. The process according to claim 1 wherein the molar ratio of the ketone of formula (II) to the potassium alcoholate is in a range of 0.5 to 1.1.

11. The process according to claim 1 , wherein the solvent is toluene, and wherein the process is conducted at a reaction temperature which is in a range of 80° to 120° C.

12. The process according to claim 1 , wherein following the condensation step the process comprises a step of hydrolysis using an organic or mineral acid.

13. The process according to claim 12 wherein the mineral acid is sulfuric acid.

14. A composition comprising substituted dibenzoylmethane derivatives of formula (V), formula (VI) and formula (VII):

wherein the molar ratio of formula (V) to the sum of formula (VI) and formula (VII) is in a range of 75:1 to 55:1.

15. A topical composition comprising the composition according to claim 14 , and a topical carrier.

16. The process according to claim 6 , wherein the potassium alcoholate is potassium methylate.

17. The process according to claim 9 , wherein the molar ratio of the ketone of formula (II) to the ester of formula (III) is in a range of 0.9 to 1.

18. The process according to claim 10 , wherein the molar ratio of the ketone of formula (II) to the potassium alcoholate is in a range of 0.8 to 1.

19. The process according to claim 12 wherein the hydrolysis is conducted using a mineral acid.

Assignees

• Wehrli Christof
• Dsm Ip Assets Bv

Inventors

• Wehrli Christof

Classifications

• C07C45/455 Primary

  with carboxylic acids or their derivatives · CPC title

• C07C49/84 Primary

  containing ether groups, [IMAGE cpc-sch-C07C-0958.gif] groups,[IMAGE cpc-sch-C07C-0959.gif] groups, or[IMAGE cpc-sch-C07C-0960.gif] groups · CPC title

• C07C45/45 Primary

  by condensation · CPC title