Method for producing indanone derivatives

Patent metadata

Field	Value
Publication number	US-9676691-B2
Application number	US-201214241964-A
Country	US
Kind code	B2
Filing date	Aug 24, 2012
Priority date	Sep 1, 2011
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

A method is described for producing a compound having the formula (I)

or an admixture comprising a compound having the formula (I),

having the following steps:
dissolving an indanone having the formula (II) in a solvent or in an admixture which contains a solvent, the solvent being selected from the group of solvents which form an azeotrope with water, converting the indanone having the formula (II) with an aromatic aldehyde having the formula (III) in the presence of at least one organic base, according to the drawing:

where R 1 and R 2 independently of each other signify hydrogen or a branched or unbranched alkyl group having from 1 to 12 carbon atoms and

where R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 independently of each other signify hydrogen, hydroxy or a branched or unbranched alkyl or alkoxy group having from 1 to 12 carbon atoms and
removing water formed from the reaction admixture during the conversion.

An admixture comprising a compound of the formula (I) and other components is further described.

First claim

The invention claimed is:

1. Method for the manufacture of a compound of formula (I) having a purity of at least 99.9% comprising:

dissolving an indanone of formula (II) in a solvent or in a mixture containing a solvent that forms an azeotrope with water and has a solubility that is less than 20 g of solvent per liter of water at 20° C.,
conversion of the indanone of formula (II) with an aromatic aldehyde of formula (III) in the presence of at least one organic base that is an alkali metal or alkaline earth metal alcoholate with a branched alcoholate anion, according to the scheme

wherein R 1 and R 2 represent, independently of each other, hydrogen or a branched or unbranched alkyl group with 1 to 12 carbon atoms, respectively,
R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 represent, independently of each other, hydrogen, hydroxy or a branched or unbranched alkyl or alkoxy group with 1 to 12 carbon atoms, respectively, and
the molar ratio of the used amount of organic base to the used amount of indanone of formula (II) is smaller than 0.05, and

removal of the generated water from the reaction mixture during the conversion.

2. Method according to claim 1 , wherein
R 1 and R 2 represent, independently of each other, methyl, ethyl, n-propyl or iso-propyl, respectively, and R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 represent, independently of each other, hydrogen, methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, propoxy or butoxy, respectively.

3. Method according to claim 1 , wherein the molar ratio of the used amount of indanone of formula (II) to the used amount of aldehyde of formula (III) is in the range of 0.6 to 1.4.

4. Method according to claim 1 , further comprising:
removal of the water that is generated during the conversion from the reaction mixture by means of azeotropic distillation and/or
removal of the water that is generated during the conversion from the reaction mixture by means of adsorption to a water adsorber.

5. Method according to claim 1 , wherein the solvent that forms an azeotrope with water is selected from the group consisting of benzene, toluene, xylene, n-hexane, n-heptane, cyclohexane, methylcyclohexane and carbon tetrachloride.

6. Method according to claim 1 , comprising the following additional steps for treatment of an existing product mixture once conversion has taken place:
neutralisation of the product mixture,
removal of the solvent by distillation from the neutralised product mixture, and
subsequently, recrystallisation of the product.

7. Method according to claim 1 with the following step before the conversion of the indanone of formula (II) with the aromatic aldehyde of formula (III):
washing of the solution that is present after dissolving of the indanone of formula (II) with an aqueous, alkaline solution and separation of the aqueous phase after washing.

8. Method according to claim 1 with the following steps:
provision or production of an indanone of formula (II) and of an aldehyde of formula (III),
dissolving of the indanone in the solvent or in a mixture containing the solvent so as to achieve a solution of the indanone,
washing of the solution that is present after dissolving of the indanone of formula (II) with an aqueous, alkaline solution and separation of the aqueous phase after washing,
addition of the organic base and of the aldehyde to the solution of the indanone, so that a reaction mixture is formed in which the indanone of formula (II) reacts with the aromatic aldehyde of formula (III),
removal of the water that is generated during the conversion from the reaction mixture by means of azeotropic distillation,
neutralisation of the product mixture that is present once the conversion has taken place,
removal of the solvent by distillation from the neutralised product mixture, and
recrystallisation of the product.

9. Method according to claim 1 , wherein the process conditions are adjusted such that the molar ratio of the
produced amount of the compound of formula (I) to
the amount of the compound of formula (IV) that has been produced as side-product, where appropriate,

in which the denotation of the groups R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and R 12 is the same as the denotation of the groups termed equally in the compound of formula (I),

is larger than 50.

10. Method for the manufacture of a compound of formula (I) having a purity of at least 99.9% comprising:

dissolving an indanone of formula (II) in a solvent that forms an azeotrope with water and has a solubility of less than 20 g of solvent per liter of water at 20° C.,
converting the indanone of formula (II) with an aromatic aldehyde of formula (III) in the presence of at least one organic base selected from the group consisting of potassium tert-butylate, sodium tert-butylate, lithium tert-butylate, barium tert-butylate, magnesium tert-butylate, potassium tert-pentylate, sodium tert-pentylate and lithium tert-pentylate, according to the scheme

wherein R 1 and R 2 represent, independently of each other, hydrogen or a branched or unbranched alkyl group with 1 to 12 carbon atoms,
R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 represent, independently of each other, hydrogen, hydroxy or a branched or unbranched alkyl or alkoxy group with 1 to 12 carbon atoms, and
the molar ratio of the used amount of organic base to the used amount of indanone of formula (II) is smaller than 0.05, and

removing the water generated during the conversion.

11. Method according to claim 10 , wherein
R 1 and R 2 represent, independently of each other, methyl, ethyl, n-propyl or iso-propyl, and
R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 represent, independently of each other, hydrogen, methyl, ethyl, n-propyl, iso-propyl, methoxy, ethoxy, propoxy or butoxy.

12. Method according to claim 10 , wherein the molar ratio of the indanone of formula (II) to the aldehyde of formula (III) is in the range of 0.6 to 1.4.

13. Method according to claim 10 , wherein the water is removed by azeotropic distillation and/or by adsorption to a water absorber.

14. Method according to claim 10 , wherein the solvent that forms an azeotrope with water is selected from the group consisting of benzene, toluene, xylene, n-hexane, n-heptane, cyclohexane, methylcyclohexane and carbon tetrachloride.

15. Method according to claim 10 , wherein the solvent that forms an azeotrope with water is toluene and/or xylene.

16. Method for the manufacture of a compound of formula (I) having a purity of at least 99.9% comprising:

dissolving an indanone of formula (II) in a solvent that forms an azeotrope with water and has a solubility less than 20 g of solvent per liter of water at 20° C., wherein the solvent is selected from the group consisting

Assignees

• Koch Oskar
• Schatkowski Dietmar
• Johncock William
• Jahnke Christel
• Fahlbusch Karl-Georg
• Symrise Ag

Inventors

• Koch Oskar
• Schatkowski Dietmar
• Johncock William
• Jahnke Christel
• Fahlbusch Karl-Georg

Classifications

• C07C49/755

  a keto group being part of a condensed ring system with two or three rings, at least one ring being a six-membered aromatic ring · CPC title

• C07C45/65 Primary

  by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups · CPC title

• C07C45/74

  combined with dehydration · CPC title

• C07C45/72

  by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups · CPC title

• A61Q19/00

  Preparations for care of the skin · CPC title