Continuous preparation of an optically active carbonyl compound by asymmetric hydrogenation

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.

Claims

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.sub.max, V.sub.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.sup.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) ##STR00008## where R.sup.1, R.sup.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.sup.4, NR.sup.5aR.sup.5b, halogen, C.sub.6-C.sub.10 aryl and heteroaryl having 5 to 10 ring atoms, R.sup.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.sup.4, NR.sup.5aR.sup.5b, halogen, C.sub.6-C.sub.10 aryl and heteroaryl having 5 to 10 ring atoms, or R.sup.3 jointly with either of the radicals R.sup.1 or R.sup.2 may also represent a 3- to 25-membered alkylene group wherein 1, 2, 3 or 4 nonadjacent CH.sub.2-groups may be replaced by O or N—R.sup.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.sup.4, NR.sup.5aR.sup.5b, halogen, C.sub.1-C.sub.4-alkyl, C.sub.6-C.sub.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.sup.4, NR.sup.5aR.sup.5b, halogen, C.sub.6-C.sub.10-aryl and heteroaryl having 5 to 10 ring atoms; where R.sup.4 is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.6-C.sub.10 aryl, C.sub.6-C.sub.14 aryl-C.sub.1-C.sub.10 alkyl, or C.sub.1-C.sub.10 alkyl-C.sub.6-C.sub.14 aryl; R.sup.5a, R.sup.5b are each independently hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.6-C.sub.10 aryl, C.sub.6-C.sub.14 aryl-C.sub.1-C.sub.10 alkyl or C.sub.1-C.sub.10 alkyl-C.sub.6-C.sub.14 aryl or R.sup.5a and R.sup.5b may also jointly represent an alkylene chain having 2 to 5 carbon atoms, which may be interrupted by N or O; and R.sup.5c is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.6-C.sub.10 aryl, C.sub.6-C.sub.14 aryl-C.sub.1-C.sub.10 alkyl, or C.sub.1-C.sub.10 alkyl-C.sub.6-C.sub.14 aryl.

13. The process according to claim 12 for producing optically active citronellal of the formula (III) ##STR00009## where * denotes the asymmetric center; by asymmetric hydrogenation of geranial of the formula (Ia-1) or of neral of the formula (Ib-1) ##STR00010## 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), ##STR00011## where Z in the formula (II) is a CHR.sup.3R.sup.4 group and where the variables R.sup.1, R.sup.2, R.sup.3, R.sup.4 are independently as follows: R.sup.1, R.sup.2: are identical or different and are phenyl that is unsubstituted or bears 1, 2 or 3 substituents selected from methyl and methoxy; R.sup.3 is C.sub.1 to C.sub.4 alkyl; R.sup.4 is C.sub.1 to C.sub.4 alkyl bearing a P(═O)R.sup.4aR.sup.4b group; where R.sup.4a, R.sup.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.sup.1 and R.sup.2 are each unsubstituted phenyl; R.sup.3 is methyl; R.sup.4 is a CH.sub.2—P(═O)R.sup.4aR.sup.4b or CH(CH.sub.3)—P(═O)R.sup.4aR.sup.4b group; and R.sup.4a and R.sup.4b are each unsubstituted phenyl.

Description

(1) The invention is more particularly elucidated by the accompanying figures and by the example that follows.

(2) FIG. 1 shows a plot of the reaction rate (relative to the maximum reaction rate) of the hydrogenation of citral in the presence of a chiraphos rhodium catalyst as a function of the citral concentration.

(3) FIG. 2 shows a schematic representation of a system suitable for executing the process of the invention.

(4) FIG. 3 shows a schematic representation of a system suitable for executing the process of the invention.

(5) The data shown in FIG. 1 were obtained in a jet loop reactor in which different conversions were achieved through different catalyst loads. The difference between the amount of citral entering and exiting the reactor was related here to the mass of rhodium in the reactor and plotted via the citral concentration in the outflow from the reactor. This reaction rate thus determined was normalized with the maximum reaction rate.

(6) It can be seen from FIG. 1 that the reaction rate of the citral hydrogenation increases hyperbolically with the citral concentration at low citral concentrations, but then decreases sharply at higher citral concentrations. The maximum reaction rate V.sub.max is attained at a citral concentration of about 9% by weight. Reaction rates equal to or greater than 0.8 times V.sub.max are attained in the concentration range from about 5% to 20% by weight of citral.

(7) According to FIG. 2, a system suitable for executing the process of the invention comprises a first hydrogenation reactor 201 and a second hydrogenation reactor 202.

(8) The hydrogenation reactor 201 comprises a stirrer 203. A liquid comprising a reactant to be hydrogenated is supplied to the hydrogenation reactor 201 via line 204. Hydrogen gas is supplied to the hydrogenation reactor 201 via line 205. The offgas from the hydrogenation reactor 201 is conducted out of the hydrogenation reactor 1 via line 206.

(9) The outflow stream 207 conducted out at the bottom of the hydrogenation reactor 201 is supplied to the hydrogenation reactor 202. The hydrogenation reactor 202 comprises a stirrer 208. Hydrogen gas is supplied to the hydrogenation reactor 202 via line 209. The offgas from the hydrogenation reactor 202 is conducted out of the hydrogenation reactor 202 via line 210.

(10) The hydrogenation reactor 202 comprises fitted trays 211 that limit backmixing in the hydrogenation reactor 202. The trays are preferably perforated sheets. Dispersed hydrogen gas is at least partially retained by the trays, with the result that the proportion of dispersed gas in the liquid reaction mixture in the section located at the exit from the second reactor decreases. At the exit at least, the hydrogenation takes place in liquid single-phase.

(11) A liquid comprising the hydrogenated reaction product is conducted out of the hydrogenation reactor 202 via line 212.

(12) A liquid comprising a homogeneous rhodium catalyst that has at least one chiral ligand is metered into the liquid stream 204 (not shown).

(13) According to FIG. 3, a system suitable for executing the process of the invention comprises a first hydrogenation reactor 301 and a second hydrogenation reactor 302.

(14) The hydrogenation reactors 301 and 302 are mixed by injection and each has a pumped-circulation circuit.

(15) The hydrogenation reactor 301 comprises a jet nozzle 303. A liquid is supplied from line 304 to the hydrogenation reactor 301 via the jet nozzle 303. The liquid stream from line 304 comprises the reactant stream 305 and the pumped-circulation stream 306. The reactant stream 305 comprises a liquid comprising a reactant to be hydrogenated. The pumped-circulation stream 306 is a substream of the outflow stream 307 conducted out at the bottom of the hydrogenation reactor 1. Hydrogen gas is supplied to the hydrogenation reactor 301 via line 308. The hydrogenation reactor 301 comprises a guide tube 309, the jet nozzle 303 being arranged above the level of the liquid and the gas/liquid jet generated by the jet nozzle 303 being directed into the guide tube 309. The offgas from the hydrogenation reactor 301 is conducted out of the hydrogenation reactor 301 via line 310.

(16) A substream of the outflow stream 307 is combined with the liquid pumped-circulation stream 311 withdrawn from the backmixed zone of the hydrogenation reactor 302 to form liquid stream 312 and supplied to the hydrogenation reactor 302 via the jet nozzle 313. Hydrogen gas is supplied to the hydrogenation reactor 302 via line 314. The hydrogenation reactor 302 comprises a guide tube 315, the jet nozzle 313 being arranged above the level of the liquid and the gas/liquid jet generated by the jet nozzle 313 being directed into the guide tube 315. The offgas from the hydrogenation reactor 302 is conducted out of the hydrogenation reactor 302 via line 316.

(17) The hydrogenation reactor 302 comprises fitted trays 317 that limit backmixing in the hydrogenation reactor 302. The trays are preferably perforated sheets. Dispersed hydrogen gas is at least partially retained by the trays, with the result that the proportion of dispersed gas in the liquid reaction mixture in the section located at the exit from the second reactor decreases. At the exit at least, the hydrogenation takes place in liquid single-phase.

(18) A liquid comprising the hydrogenated reaction product is conducted out of the hydrogenation reactor 302 via line 318.

(19) A liquid comprising a homogeneous rhodium catalyst that has at least one chiral ligand is metered into the pumped-circulation circuit of the hydrogenation reactor 301, for example into the liquid stream 304 (not shown). The pumped-circulation circuit of the hydrogenation reactor 301 and of the hydrogenation reactor 302 comprises an external heat exchanger (not shown) that for example cools the outflow stream 307 and the pumped-circulation stream 311.

EXAMPLE

(20) 1500 kg/h of citral and 1500 kg/h of a catalyst mixture were fed into a jet loop reactor having a liquid volume of 12 m.sup.3. The catalyst mixture was a mixture prepared in analogous manner to the procedures described in US 2018/057437 A1, WO 2006/040096, and WO 2008/132057 A1, in which Rh(CO).sub.2acac, chiraphos, and tridodecylamine in a molar ratio of 1:1.4:10 were reacted with CO and H.sub.2 in citronellal. The concentration of the catalyst mixture in the jet loop reactor was 300 to 1000 ppm by weight based on the amount of rhodium in the catalyst. The ratio of external circulation to feed was 380:130. The ratio of internal circulation to feed was 3000:1000.

(21) The power input was 2 kW/m.sup.3. The pressure in the reactor was regulated to 80 bar by feeding in hydrogen gas (containing 1000 ppm of carbon monoxide). The temperature in the reactor was regulated to 22° C. Conversion of the citral was 88%. A citral concentration of about 7% by weight was present in the outflow from the first reactor.

(22) The outflow from the reactor was fed into a second reactor having a liquid volume of 9.7 m.sup.3. The pressure in the second reactor was regulated to 80 bar by feeding in hydrogen gas (containing 1000 ppm of carbon monoxide). The temperature in the reactor was regulated to 22° C. The total conversion after the second reactor was between 93 and 99.9%.

(23) It was found that the reaction rate in the first reactor decreased at higher citral concentrations. It thus proved advantageous to operate the first reactor at low citral concentrations and to complete the reaction in the second reactor.