Method for producing optically active, racemic menthol

Patent metadata

Field	Value
Publication number	US-9988331-B2
Application number	US-201213658003-A
Country	US
Kind code	B2
Filing date	Oct 23, 2012
Priority date	Nov 30, 2007
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

The present invention relates to a particularly economic overall method for producing menthol, specifically for producing optically active, essentially enantiomerically and diastereomerically pure L-menthol and racemic menthol, starting from the starting material citral which is available inexpensively on an industrial scale. The method has the following steps
a.1) catalytic hydrogenation of neral and/or geranial to give citronellal, b.1) cyclization of citronellal to isopulegol in the presence of an acidic catalyst, c.1) purification of isopulegol by crystallization and d.1) catalytic hydrogenation of isopulegol to give menthol.

First claim

The invention claimed is:

1. A method for producing optically active menthol, comprising the steps
a2) pretreating an asymmetric rhodium complex with carbon monoxide to provide an asymmetric, hydrogenation rhodium catalyst that is soluble in a reaction mixture,
b2) including neral and/or geranial in the reaction mixture, and in the presence of the catalyst of step a2), hydrogen, and 100 to 1200 ppm carbon monoxide, the hydrogenation of the neral and/or geranial provides optically active citronellal,
c2) cyclization of optically active citronellal to give optically active isopulegol in the presence of an acidic catalyst,
d2) purification of the optically active isopulegol by crystallization, and
e2) contacting the optically active isopulegol from step d2) with a hydrogenation catalyst to provide the optically active menthol.

2. A method for producing optically active menthol, comprising the steps
a1) forming an asymmetric rhodium catalyst that includes chiral diphos ligands and carbon monoxide,
b1) catalytic hydrogenation of a mixture of neral and geranial to provide optically active citronellal in the presence of the catalyst formed from step a1) and 100 to 1200 ppm carbon monoxide,
c1) cyclization of the optically active citronellal to give provide optically active isopulegol in the presence of an acidic catalyst,
d1) purification of optically active isopulegol of step c1) by melt crystallization, and
e1) catalytic hydrogenation of the purified isopulegol of step d1) to give optically active menthol, and purifying the optically active menthol by distillation, where the purification is conducted in a dividing wall column having 50 to 200 theoretical plates and one or more side take-off points at an absolute operating pressure of from 5 to 500 mbar.

3. The method of claim 2 , wherein the cyclization according to step c1) is carried out in the presence of a Lewis-acidic aluminum-containing catalyst.

4. The method of claim 1 , wherein in step e2), the hydrogenation catalyst is pretreated with a gas mixture comprising carbon monoxide and hydrogen.

5. The method of claim 2 , wherein the dividing wall column has 100 to 200 theoretical plates.

6. A method for producing enantiomerically enriched L-(−)-menthol and racemic or enantiomerically depleted menthol, comprising the steps
a) asymmetrically catalytically hydrogenating neral to give D-(+)-citronellal with an enantiomer excess of from 70 to 99%, the asymmetric hydrogenation conducted in the presence of an asymmetric rhodium catalyst that includes chiral diphos ligands,
b) cyclizing the D-(+)-citronellal of a) in the presence of an acidic catalyst to give L-(−)-isopulegol,
c) purifying L-(−)-isopulegol of b) by crystallization to give enantiomerically enriched L-(−)-isopulegol and racemic or enantiomerically depleted isopulegol,
d) catalytically hydrogenating the L-(−)-isopulegol of c) to give L-(−)-methanol,
e) catalytically hydrogenating the racemic or enantiomerically depleted isopulegol of c) to give racemic or enantiomerically depleted menthol.

7. The method of claim 1 , wherein the crystallization is conducted in a static layer crystallizer comprising an internal heat exchanger surface.

8. The method of claim 1 , wherein the acidic catalyst is an aluminum-containing Lewis-acid catalyst.

9. The method of claim 1 , wherein step c2) provides enriched isopulegol with a chemical purity of at least about 95% by weight.

10. The method of claim 2 , wherein the acidic catalyst is a diarylphenoxyaluminum compound.

11. A method for producing optically active menthol comprising:
providing a hydrogenation rhodium catalyst with the asymmetric ligand (R,R)-chiraphos;
providing a mixture of neral and geranial, wherein the mixture comprises 0.5 to 20% by weight geranial and 99.5 to 80% by weight neral, or the mixture is citral;
contacting the mixture of neral and geranial with the (R,R)-chiraphos, rhodium catalyst in the presence of hydrogen and 100 to 1200 ppm carbon monoxide, the hydrogenation of the neral and geranial provides optically active D-(+)-citronellal;
contacting the optically active D-(+)-citronellal in the presence of a Lewis-acidic aluminum-containing catalyst to provide optically active L-(−)-isopulegol;
purification of the L-(−)-isopulegol by distillation or crystallization and separating the L-(−)-isopulegol from the Lewis-acidic catalyst; and
contacting the purified L-(−)-isopulegol with a hydrogenation catalyst to give L-(−)-menthol.

12. The method of claim 11 , wherein the purification of the L-(−)-isopulegol is carried out by vacuum distillation in the presence of a solvent having a boiling point that is at least 20° C. greater than the boiling point of the L-(−)-isopulegol.

13. The method of claim 11 , wherein the purification of the L-(−)-isopulegol is carried out by melt crystallization to provide L-(−)-isopulegol with a purity of 95 to 99.5% by weight.

14. The method of claim 1 , wherein the asymmetric, hydrogenation rhodium catalyst includes diphos ligands selected from the group consisting of formulae (VIII), (IX), and (X)

wherein:
R 31 , R 32 in each case independently of one another are an unbranched, branched or cyclic alkyl radical having 1 to 20 carbon atoms, which can optionally carry one or more, ethylenic double bonds and/or one or more substituents selected from OR 39 , NR 40 R 41 , halogen, C 6 -C 10 -aryl and C 3 -C 9 -hetaryl, and R 31 and R 32 together can form a 4 to 20-membered ring which can include one or more O atoms;
R 33 , R 34 in each case independently of one another are hydrogen or straight-chain or branched C 1 - to C 4 -alkyl;
R 35 , R 36 , R 37 , R 38 are in each case C 6 - to C 10 -aryl, which can optionally carry 1 to 4, substituents selected from C 1 - to C 4 -alkyl, C 6 - to C 10 -aryl, C 1 - to C 4 -alkoxy and amino; and
R 39 , R 40 , R 41 in each case independently of one another are hydrogen, C 1 -C 4 -alkyl, C 6 -C 10 -aryl, C 7 -C 12 -aralkyl or C 7 -C 12 -alkylaryl, where R 40 , R 41 together can form an alkylene chain having 2 to 5 carbon atoms, which may be interrupted by N or O.

15. The method of claim 6 , wherein the chiral diphos ligands are selected from the group consisting of formulae (VIII), (IX), and (X)

wherein
R 31 , R 32 in each case independently of one another are an unbranched, branched or cyclic alkyl radical having 1 to 20 carbon atoms, which can optionally carry one or more,
ethylenic double bonds and/or one or more substituents selected from OR 39 , NR 40 R 41 , halogen, C 6 -C 10 -aryl and C 3 -C 9 -hetaryl, and R 31 and R 32 together can form a 4 to 20-membered ring which can include one or more O atoms;
R 33 , R 34 in each case independently of one another are hydrogen or straight-chain or branched C 1 - to C 4 -alkyl;
R 35 , R 36 , R 37 , R 38 are in each case C 6 - to C 10 -aryl, which can optionally carry 1 to 4, substituents selected from C 1 - to C 4 -alkyl, C 6 - to C 10 -aryl, C 1 - to C 4 -alkoxy and amino; and
R 39 , R 40 , R 41 in each case independently of one another are hydrogen, C 1 -C 4 -alkyl, C 6 -C 10 -aryl, C 7 -C 12 -aralkyl or C 7 -C 12 -alkylaryl, where R 40 , R 41 together can form an alkylene chain having 2 to 5 carbon atoms, which may be interrupted by N or O.

Assignees

• Basf Se

Inventors

• Heydrich Gunnar
• Gralla Gabriele
• Rauls Matthias
• Schmidt-Leithoff Joachim
• Ebel Klaus
• Krause Wolfgang
• Oehlenschläger Steffen
• JÄKEL Christoph
• Friedrich Marko
• Bergner Eike Johannes
• Kashani-Shirazi Nawid
• Paciello Rocco

Classifications

• C07C2601/14

  The ring being saturated · CPC title

• C07C2601/16

  the ring being unsaturated · CPC title

• C07C29/78

  by condensation or crystallisation · CPC title

• C07C29/172

  with the obtention of a fully saturated alcohol · CPC title

• C07C45/62

  by hydrogenation of carbon-to-carbon double or triple bonds · CPC title