Preparation of pantolactone

Patent metadata

Field	Value
Publication number	US-10150746-B2
Application number	US-201615737551-A
Country	US
Kind code	B2
Filing date	Jun 17, 2016
Priority date	Jun 19, 2015
Publication date	Dec 11, 2018
Grant date	Dec 11, 2018

Abstract

The present invention relates to a novel process for the preparation of pantolactone by reaction of hydroxypivalaldehyde cyanohydrin in a phase separation process.

First claim

The invention claimed is:

1. A process for the preparation of pantolactone (I)

comprising:
a) providing an aqueous composition which comprises hydroxypivalaldehyde cyanohydrin (II)

as starting material,
b) subjecting the starting material provided in step a) to a reaction with H 2 SO 4 as acid at a pH of less than 1.1 in a homogeneous liquid phase,
c) adding NH 3 in gaseous or aqueous form as base to the reaction product from step b) until the pH is in a range from 3 to 7 and where the water content of the reaction mixture in step c) following the addition of the base is in a range from 40 to 60% by weight, based on the total weight of the reaction mixture, with an organic phase being formed which comprises the pantolactone (I), and an aqueous phase which comprises the base salt of the strong acid,
d) leaving the phases to separate and separating off the organic phase from the aqueous phase.

2. The process according to claim 1 , where, for the provision of the starting material in step a):
a1) formaldehyde is subjected with isobutyraldehyde to an aldol addition, giving hydroxypivalaldehyde, and
a2) the hydroxypivalaldehyde is reacted with a cyanide source, giving hydroxypivalaldehyde cyanohydrin (II).

3. The process according to claim 1 , where the acid used in step b) is at least 90% strength H 2 SO 4 .

4. The process according to claim 1 , where, during the reaction in step b), the pH of the reaction mixture is kept in a range from 0 to 1.2.

5. The process according to claim 1 , where, in step b), the molar ratio of the acid used to hydroxypivalaldehyde cyanohydrin (II) is in a range from 0.5:1 to 2:1.

6. The process according to claim 1 , where the reaction in step b) takes place at a temperature from 50 to 110° C.

7. The process according to claim 1 , where the reaction in step b) takes place at a pressure in the range from 850 to 1150 mbar.

8. The process according to claim 1 , where the reaction in step b) takes place at a pressure in the range from 100 to 800 mbar.

9. The process according to claim 8 , where, during the reaction in step b), water is removed distillatively from the reaction mixture.

10. The process according to claim 1 , where, in step c), at least one base is added to the reaction product from step b) until the pH is in a range from 4 to 6.

11. The process according to claim 1 , where the reaction in step b) takes place at a pressure in the range from 200 to 700 mbar, and during the reaction in step b) water is removed distillatively from the reaction mixture and, in step c), aqueous NH 3 is added as base to the reaction product from step b).

12. The process according to claim 1 , where the water content of the reaction mixture in step c) following the addition of the base is in a range from 45 to 50% by weight, based on the total weight of the reaction mixture.

13. The process according to claim 1 , where, in step d), the phases are left to separate at a temperature in the range from 50 to 100° C.

14. The process according to claim 1 , further comprising
e) subjecting the organic phase which comprises the pantolactone (I) to a work-up.

15. The process according to claim 14 , where the organic phase is subjected to a distillative separation, giving at least one fraction enriched in pantolactone (I) and at least one fraction depleted in pantolactone (I).

16. The process according to claim 14 , where the organic phase or at least one fraction enriched in pantolactone (I) is subjected to a racemate cleavage, giving at least one fraction enriched in D-pantolactone.

17. The process according to claim 1 , where, during the reaction in step b), the pH of the reaction mixture is kept in a range from 0.2 to 1.

18. The process according to claim 1 , where, in step b), the molar ratio of the acid used to hydroxypivalaldehyde cyanohydrin (II) is in a range from 0.7:1 to 1.5:1.

19. The process according to claim 1 , where the reaction in step b) takes place at a temperature from 75 to 100° C.

20. The process according to claim 1 , where the reaction in step b) takes place at a pressure in the range from 900 to 1100 mbar.

Assignees

• Basf Se

Inventors

• Fischer Klaus
• Nehls Benjamin
• Deschler Jürgen
• Dobler Walter
• Lauterbach Arnulf
• Schlautmann Sabine

Classifications

• C07B55/00

  Racemisation; Complete or partial inversion · CPC title

• A61Q19/00

  Preparations for care of the skin · CPC title

• C07B63/04

  Use of additives {(anti-oxidant compositions or compositions inhibiting chemical change in general C09K15/00)} · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• C07D307/33 Primary

  in position 2, the oxygen atom being in its keto or unsubstituted enol form · CPC title