Continuous preparation of an optically active carbonyl compound by asymmetric hydrogenation

Patent metadata

Field	Value
Publication number	US-11242306-B2
Application number	US-201917274142-A
Country	US
Kind code	B2
Filing date	Sep 3, 2019
Priority date	Sep 5, 2018
Publication date	Feb 8, 2022
Grant date	Feb 8, 2022

Abstract

Process for the continuous production of an optically active carbonyl compound by asymmetric hydrogenation of a prochiral α,β-unsaturated carbonyl compound with hydrogen in the presence of a homogeneous rhodium catalyst that has at least one chiral ligand, wherein a liquid reaction mixture comprising the prochiral α,β-unsaturated carbonyl compound is subjected in a first, backmixed reactor to a gas/liquid two-phase hydrogenation, and the liquid reaction mixture is then further hydrogenated in a second reactor, wherein the prochiral α,β-unsaturated carbonyl compound is employed in the first reactor in a concentration from 3% to 20% by weight. The process allows a high total conversion to the prochiral α,β-unsaturated carbonyl compound.

First claim

The invention claimed is:

1. A process for the continuous production of an optically active carbonyl compound by asymmetric hydrogenation of a prochiral α,β-unsaturated carbonyl compound with hydrogen in the presence of a homogeneous rhodium catalyst that has at least one chiral ligand, wherein
a liquid reaction mixture comprising the prochiral α,β-unsaturated carbonyl compound is subjected in a first, backmixed reactor to a gas/liquid two-phase hydrogenation, and
the liquid reaction mixture is then further hydrogenated in a second reactor,
wherein the prochiral α,β-unsaturated carbonyl compound is employed in the first reactor in a concentration from 3% to 20% by weight.

2. The process according to claim 1 , wherein hydrogen gas undergoes dispersion in the liquid reaction mixture in a section of the second reactor located at the entrance to the second reactor.

3. The process according to claim 1 , wherein the prochiral α,β-unsaturated carbonyl compound is employed in the first reactor in a concentration at which the reaction rate is at least 0.8 times V max , V max being the maximum value for the reaction rate in a plot of the reaction rate against the concentration of the prochiral α,β-unsaturated carbonyl compound.

4. The process according to claim 1 , wherein the liquid reaction mixture undergoes reaction in the second reactor until the concentration of the prochiral α,β-unsaturated carbonyl compound is less than 5% by weight.

5. The process according to claim 1 , wherein the ratio of the reaction volume of the first reactor to the reaction volume of the second reactor is 1:1 to 1:5.

6. The process according to claim 1 , wherein the first reactor is characterized by a reactor number N within a range from 1 to 3.

7. The process according to claim 1 , wherein the volume-specific power input into the first reactor is 0.5 to 5 kW/m 3 .

8. The process according to claim 1 , wherein the first reactor is configured as a loop reactor.

9. The process according to claim 1 , wherein backmixing in the second reactor is limited and wherein, at least in a section of the second reactor located at the exit from the second reactor, the hydrogenation is carried out in liquid single-phase.

10. The process according to claim 9 , wherein backmixing in the second reactor is limited by internals.

11. The process according to claim 1 , wherein the second reactor is characterized by a reactor number N of more than 4.

12. The process according to claim 1 , wherein the prochiral α,β-unsaturated carbonyl compound is selected from compounds of the general formula (I)

where
R 1 , R 2 are different from one another and are each an unbranched, branched or cyclic hydrocarbon radical having 1 to 25 carbon atoms that is saturated or has one or more unconjugated ethylenic double bonds and that is unsubstituted or bears one or more identical or different substituents selected from OR 4 , NR 5a R 5b , halogen, C 6 -C 10 aryl and heteroaryl having 5 to 10 ring atoms,
R 3 is hydrogen or an unbranched, branched or cyclic hydrocarbon radical having 1 to 25 carbon atoms that is saturated or has one or more unconjugated ethylenic double bonds and that is unsubstituted or bears one or more identical or different substituents selected from OR 4 , NR 5a R 5b , halogen, C 6 -C 10 aryl and heteroaryl having 5 to 10 ring atoms,
or
R 3 jointly with either of the radicals R 1 or R 2 may also represent a 3- to 25-membered alkylene group wherein 1, 2, 3 or 4 nonadjacent CH 2 -groups may be replaced by O or N—R 5c , wherein the alkylene group is saturated or has one or more unconjugated ethylenic double bonds and wherein the alkylene group is unsubstituted or bears one or more identical or different substituents selected from OR 4 , NR 5a R 5b , halogen, C 1 -C 4 -alkyl, C 6 -C 10 -aryl and heteroaryl having 5 to 10 ring atoms, wherein two substituents may also jointly represent a 2- to 10-membered alkylene group, wherein the 2- to 10-membered alkylene group is saturated or has one or more unconjugated ethylenic double bonds and wherein the 2- to 10-membered alkylene group is unsubstituted or bears one or more identical or different substituents selected from OR 4 , NR 5a R 5b , halogen, C 6 -C 10 -aryl and heteroaryl having 5 to 10 ring atoms;
where
R 4 is hydrogen, C 1 -C 6 alkyl, C 6 -C 10 aryl, C 6 -C 14 aryl-C 1 -C 10 alkyl, or C 1 -C 10 alkyl-C 6 -C 14 aryl;
R 5a , R 5b are each independently hydrogen, C 1 -C 6 alkyl, C 6 -C 10 aryl, C 6 -C 14 aryl-C 1 -C 10 alkyl or C 1 -C 10 alkyl-C 6 -C 14 aryl or
R 5a and R 5b may also jointly represent an alkylene chain having 2 to 5 carbon atoms, which may be interrupted by N or O; and
R 5c is hydrogen, C 1 -C 6 alkyl, C 6 -C 10 aryl, C 6 -C 14 aryl-C 1 -C 10 alkyl, or C 1 -C 10 alkyl-C 6 -C 14 aryl.

13. The process according to claim 12 for producing optically active citronellal of the formula (III)

where * denotes the asymmetric center;
by asymmetric hydrogenation of geranial of the formula (Ia-1) or of neral of the formula (Ib-1)

or of a mixture comprising neral and geranial.

14. The process according to claim 1 , wherein the catalyst concentration is 0.001 to 1 mol % based on the amount of prochiral α,β-unsaturated carbonyl compound in the reaction mixture calculated as rhodium atoms present in the catalyst.

15. The process according to claim 1 , wherein the chiral ligand is a chiral bidentate bisphosphine ligand.

16. The process according to claim 1 , wherein the process is executed in the presence of a compound of the formula (II),

where Z in the formula (II) is a CHR 3 R 4 group and where the variables R 1 , R 2 , R 3 , R 4 are independently as follows:
R 1 , R 2 : are identical or different and are phenyl that is unsubstituted or bears 1, 2 or 3 substituents selected from methyl and methoxy;
R 3 is C 1 to C 4 alkyl;
R 4 is C 1 to C 4 alkyl bearing a P(═O)R 4a R 4b group;
where
R 4a , R 4b : are identical or different and are phenyl that is unsubstituted or bears 1, 2 or 3 substituents selected from methyl and methoxy.

17. A process for producing optically active menthol in which optically active citronellal of the formula (III) is produced in the process according to claim 13 in which the optically active citronellal of the formula (III) is subjected to a cyclization to afford optically active isopulegol and the optically active isopulegol is hydrogenated to afford optically active menthol.

18. The process according to claim 15 , wherein the chiral ligand is chiraphos.

19. The process according to claim 16 , wherein:
R 1 and R 2 are each unsubstituted phenyl;
R 3 is methyl;
R 4 is a CH 2 —P(═O)R 4a R 4b or CH(CH 3 )—P(═O)R 4a R 4b group; and
R 4a and R 4b are each unsubstituted phenyl.

Assignees

• Basf Se

Inventors

• Zehner Peter
• Bey Oliver

Classifications

• B01J19/0066

  Stirrers (mixing per se B01F) · CPC title

• B01J31/24

  Phosphines {, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands} · CPC title

• B01J2219/00033

  Continuous processes · CPC title

• B01J2531/822

  Rhodium · CPC title

• B01J19/1837

  Loop-type reactors · CPC title