Process for enriching enantiomers from an enantiomer mixture

Patent metadata

Field	Value
Publication number	US-10669222-B2
Application number	US-201716338633-A
Country	US
Kind code	B2
Filing date	Oct 5, 2017
Priority date	Oct 6, 2016
Publication date	Jun 2, 2020
Grant date	Jun 2, 2020

Abstract

The present invention relates to a process for enriching enantiomers from an enantiomer mixture by a fractionating melt crystallization in a melt crystallization apparatus. The invention specifically relates to a process for producing an enantiomer-enriched chiral terpene, in particular of D/L-Isopulegol. The process comprises:
i) a crystallization step to obtain a crystallizate and a mother melt and removal of the mother melt from the crystallizate to afford a mother melt fraction; ii) sweating of the crystallizate obtained in step i) to afford a molten sweating fraction and iii) subsequent melting of the sweated crystallizate to afford a molten crystallizate fraction,

wherein the optical rotation at least of the sweating fraction is determined online using a polarimeter and the changeover from step ii) to step iii) is controlled online by means of at least one control unit.

First claim

The invention claimed is:

1. A process for enriching an enantiomer from an enantiomer mixture by a fractionating melt crystallization in a melt crystallization apparatus, comprising
i) a crystallization step to obtain a crystallizate and a mother melt and removal of the mother melt from the crystallizate to afford a mother melt fraction,
ii) sweating of the crystallizate obtained in step i) to afford a molten sweating fraction and a sweated crystallizate, and
iii) subsequent melting of the sweated crystallizate to afford a molten crystallizate fraction, wherein the optical rotation at least of the sweating fraction is determined online using a polarimeter and the changeover from step ii) to step iii) is controlled online by means of at least one control unit.

2. The process according to claim 1 , wherein in order to control the changeover from step ii) to step iii)
(a) a target value for the optical rotation of the sweating fraction is specified;
(b) a maximum permitted control difference of the actual value from the target value for the optical rotation of the sweating fraction is specified;
(c) the actual value for the optical rotation of the sweating fraction is determined;
(d) the control unit effects the changeover from step ii) to step iii) not earlier than upon reaching the target value and not later than upon reaching the maximum permitted control difference of the actual value from the target value.

3. The process according to claim 2 , wherein the maximum permitted control difference of the actual value from the target value is not more than 0.3° for a length of the measuring cell of the polarimeter of 1 dm, a temperature of 25° C. and an employed wavelength of 589 nm.

4. The process according to claim 1 , wherein the melt crystallization apparatus comprises a discharge conduit for the melts generated in steps i) to iii) in which the polarimeter is located directly or with which the polarimeter is connected via a bypass conduit.

5. The process according to claim 4 , wherein the control unit controls a valve block that is located in the discharge conduit and is connected to the discharge conduit and to at least two vessels for receiving the generated melts.

6. The process according to claim 1 , wherein the melt crystallization apparatus has
a crystallization space having a feed for introduction of the molten enantiomer mixture to be fractionated into the crystallization space, a temperature sensor for measuring the temperature of the melt(s) in the crystallization space and a temperature-control device for varying the temperature of the introduced molten enantiomer mixture and/or of the crystallizate partly formed therefrom;
a discharge conduit which is closable with a valve and connected to the crystallization space and in which the polarimeter is located or with which the polarimeter is connected via a bypass conduit;
optionally a temperature sensor located in the discharge conduit for measuring the temperature of the melt(s) in the discharge conduit,
a valve block that is located in the discharge conduit and is connected to the discharge conduit and to at least two vessels for receiving the generated melts, and
a control unit which is data-coupled to the temperature sensor, the polarimeter, the temperature-control device and a valve block and with which the temperature of the solid and liquid phases in the crystallization space and/or the valve block is controllable.

7. The process according to claim 1 , having at least one of the features x 1 ) to x 6 ):
x 1 ) at least one control unit is preferably data-coupled to the polarimeter;
x 2 ) the melt crystallization is performed as a layer crystallization;
x 3 ) the melt crystallization is performed as a static layer crystallization on cooled surfaces;
x 4 ) the melt crystallization is performed as a falling film crystallization;
x 5 ) the enantiomer mixture to be fractionated does not have a racemic composition;
x 6 ) the enantiomer mixture to be fractionated may form a racemic conglomerate.

8. The process according to claim 1 , wherein the enantiomer mixture to be fractionated is a mixture of the enantiomers of a chiral terpene.

9. The process according to claim 8 , wherein the chiral terpene is isopulegol.

10. The process according to claim 9 , wherein a mixture of D-isopulegol and L-isopulegol having an enantiomeric excess of one of the enantiomers of at least 10% EE, is employed as the enantiomer mixture to be fractionated.

11. A melt crystallization apparatus having a crystallization space ( 1 ) having
a feed ( 7 ) for the molten enantiomer mixture to be fractionated into the crystallization space ( 1 ),
a temperature sensor ( 11 ) for measuring the temperature of the molten enantiomer mixture in the crystallization space ( 1 ),
and a temperature-control device ( 10 ) for varying the temperature of the introduced molten enantiomer mixture and of the crystallizate partly formed therefrom,
wherein the melt crystallization apparatus further comprises
a discharge conduit ( 2 ) which is closable with a valve ( 13 ) and connected to the crystallization space and in which a polarimeter ( 9 ) is located or with which the polarimeter ( 9 ) is connected via a bypass conduit,
optionally a temperature sensor ( 8 ) located in the discharge conduit ( 2 ), for measuring the temperature of the melt in the discharge conduit;
a valve block ( 3 ) that is located in the discharge conduit ( 2 ), and is connected to the discharge conduit ( 2 ) and to at least two buffer vessels ( 4 ), ( 6 ) for receiving the generated melts
and has a control unit ( 12 ) which is data-coupled to the temperature sensors ( 8 ), ( 11 ), the polarimeter ( 9 ), the temperature-control device ( 10 ) and the valve block ( 3 ) and with which the temperature of the solid and liquid phases in the crystallization space and/or the valve block is controllable.

12. The melt crystallization apparatus according to claim 11 which is configured as a falling film crystallizer or as a static layer crystallizer.

13. A process for producing an isopulegol enriched in terms of the L- or D-enantiomer, comprising a fractionating melt crystallization of a non-racemic mixture of the D- and L-enantiomers of isopulegol according to claim 1 .

14. The process according to claim 13 , wherein a mixture of D-isopulegol and L-isopulegol having an enantiomeric excess of one of the enantiomers of at least 10% EE is employed.

15. A process for producing menthol, comprising
I) providing an isopulegol enriched in terms of the L- or D-enantiomer by a process according to claim 13 and
II) hydrogenating the isopulegol enriched in terms of the L- or D-enantiomer obtained in step I).

16. The process according to claim 13 , wherein a mixture of D-isopulegol and L-isopulegol having an enantiomeric excess of one of the enantiomers in the range of 12.5% EE to 99% EE, is employed.

17. The process according to claim 1 , wherein the enantiomer mixture to be fractionated is a mixture of the enantiomers of a chiral monoterpene.

18. The process according to claim 17 , wherein the chiral monoterpene is D/L-isopulegol.

19. The process according to claim 9 , wherein a mixture of D-isopulegol and L-isopulegol having an enantiomeric excess of one of the enantiomers is in the range from 12.5% EE to 99% EE, is employed as the enantiomer mixture to be fractionated.

20. A melt crystallization apparatus having a crystallization space ( 1 ) having
a feed ( 7 ) for the molten enantiomer mixture to be fractionated into the

Assignees

• Basf Se

Inventors

• Wloch Sebastian
• Heydrich Gunnar
• Rauls Matthias

Classifications

• C07C35/08

  containing a six-membered rings · CPC title

• C07C29/78 Primary

  by condensation or crystallisation · CPC title

• B01D9/004

  Fractional crystallisation; Fractionating or rectifying columns · CPC title

• C07C29/172

  with the obtention of a fully saturated alcohol · CPC title

• B01D9/0013

  by indirect heat exchange · CPC title