阅读说明：本技术 通过不对称氢化连续制备光学活性羰基化合物 (Continuous production of optically active carbonyl compounds by asymmetric hydrogenation ) 是由 P·策纳 O·贝 于 2019-09-03 设计创作，主要内容包括：通过在具有至少一个手性配体的均相铑催化剂存在下用氢气将前手性α,β-不饱和羰基化合物不对称氢化而连续生产光学活性羰基化合物的方法,其中在第一返混式反应器中对包含前手性α,β-不饱和羰基化合物的液体反应混合物施以气/液两相氢化,和液体反应混合物随后在第二反应器中进一步氢化,其中所述前手性α,β-不饱和羰基化合物在第一反应器中以3重量％至20重量％的浓度使用。所述方法能够实现前手性α,β-不饱和羰基化合物的高总转化率。(A process for the continuous production of optically active carbonyl compounds by asymmetric hydrogenation of prochiral alpha, beta-unsaturated carbonyl compounds with hydrogen in the presence of a homogeneous rhodium catalyst having at least one chiral ligand, wherein a liquid reaction mixture comprising the prochiral alpha, beta-unsaturated carbonyl compounds is subjected to a gas/liquid two-phase hydrogenation in a first back-mixed reactor, and the liquid reaction mixture is subsequently further hydrogenated in a second reactor, wherein the prochiral alpha, beta-unsaturated carbonyl compounds are used in a concentration of from 3% to 20% by weight in the first reactor. The process enables high overall conversion of prochiral alpha, beta-unsaturated carbonyl compounds.)

1. A process for the continuous production of optically active carbonyl compounds by asymmetric hydrogenation of prochiral alpha, beta-unsaturated carbonyl compounds with hydrogen in the presence of a homogeneous rhodium catalyst having at least one chiral ligand, wherein

Subjecting a liquid reaction mixture comprising a prochiral alpha, beta-unsaturated carbonyl compound to a gas/liquid two-phase hydrogenation in a first back-mixed reactor, and

the liquid reaction mixture is subsequently further hydrogenated in a second reactor,

wherein the prochiral α, β -unsaturated carbonyl compound is used in the first reactor at a concentration of 3 to 20 wt.%.

2. The process according to claim 1, wherein hydrogen is dispersed in the liquid reaction mixture in a second reactor section located at the inlet of the second reactor.

3. The method according to claim 1 or 2, which comprisesIn the first reactor so that the reaction rate is at least 0.8 times V_maxUse of concentration of V_maxIs the maximum of the reaction rate in the curve of the reaction rate against the concentration of prochiral alpha, beta-unsaturated carbonyl compounds.

4. The process according to any one of the preceding claims, wherein the liquid reaction mixture is reacted in the second reactor until the concentration of prochiral α, β -unsaturated carbonyl compound is less than 5 wt.%.

5. The process according to any one of the preceding claims, wherein the ratio of the reaction volume of the first reactor to the reaction volume of the second reactor is from 1:1 to 1: 5.

6. The process according to any of the preceding claims, wherein the first reactor is characterized by a reactor number N in the range of 1 to 3.

7. The process according to any of the preceding claims, wherein the first reactor has a volumetric specific power input of 0.5 to 5kW/m³。

8. The process according to any one of the preceding claims, wherein the first reactor is configured as a loop reactor.

9. The process according to any of the preceding claims, wherein back-mixing in the second reactor is limited and wherein, at least in the section of the second reactor located at the outlet of the second reactor, the hydrogenation is carried out in a single liquid phase.

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

11. The process according to any of the preceding claims, wherein the second reactor is characterized by a reactor number N greater than 4.

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

Wherein

R¹、R²Are different from each other and are each an unbranched, branched OR cyclic hydrocarbon radical having from 1 to 25 carbon atoms, which is saturated OR has one OR more nonconjugated olefinic double bonds, and which is unsubstituted OR carries one OR more identical OR different substituents selected from OR⁴、NR^5aR^5bHalogen, C₆-C₁₀Aryl and heteroaryl having 5 to 10 ring atoms,

R³is hydrogen OR an unbranched, branched OR cyclic hydrocarbon radical having from 1 to 25 carbon atoms, which is saturated OR has one OR more nonconjugated olefinic double bonds and which is unsubstituted OR carries one OR more identical OR different substituents selected from OR⁴、NR^5aR^5bHalogen, C₆-C₁₀Aryl and heteroaryl having 5 to 10 ring atoms,

or

R³With the radical R¹Or R²Together may also represent a 3-to 25-membered alkylene group in which 1, 2, 3 or 4 non-adjacent CH groups₂The radicals being substituted by O or N-R^5cAlternatively, wherein the alkylene is saturated OR has one OR more nonconjugated olefinic double bonds, and wherein the alkylene is unsubstituted OR bears one OR more identical OR different substituents selected from OR⁴、NR^5aR^5bHalogen, C₁-C₄Alkyl radical, C₆-C₁₀Aryl and heteroaryl having 5 to 10 ring atoms, where two substituents may also together represent a 2-to 10-membered alkylene group, where the 2-to 10-membered alkylene group is saturated or has one or more non-substituted groupsConjugated olefinic double bonds, and wherein the 2-to 10-membered alkylene is unsubstituted OR bears one OR more identical OR different substituents selected from OR⁴、NR^5aR^5bHalogen, C₆-C₁₀-aryl and heteroaryl having 5 to 10 ring atoms;

wherein

R⁴Is hydrogen, C₁-C₆Alkyl radical, C₆-C₁₀Aryl radical, C₆-C₁₄aryl-C₁-C₁₀Alkyl or C₁-C₁₀alkyl-C₆-C₁₄An aryl group;

R^5a、R^5beach independently is hydrogen, C₁-C₆Alkyl radical, C₆-C₁₀Aryl radical, C₆-C₁₄aryl-C₁-C₁₀Alkyl or C₁-C₁₀alkyl-C₆-C₁₄Aryl or

R^5aAnd R^5bTogether also represent an alkylene chain having 2 to 5 carbon atoms, which may be interrupted by N or O; and is

R^5cIs hydrogen, C₁-C₆Alkyl radical, C₆-C₁₀Aryl radical, C₆-C₁₄aryl-C₁-C₁₀Alkyl or C₁-C₁₀alkyl-C₆-C₁₄And (4) an aryl group.

13. The process according to claim 12 for the production of optically active citronellal of formula (III) by asymmetric hydrogenation of geranial of formula (Ia-1) or neral of formula (Ib-1) or a mixture comprising neral and geranial

Wherein denotes an asymmetric center.

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

15. The process according to any of the preceding claims, wherein the chiral ligand is a chiral bidentate diphosphine ligand, more particularly chiralphos.

16. A process according to any one of the preceding claims, wherein the process is carried out in the presence of a compound of formula (II),

wherein Z in formula (II) is CHR³R⁴And wherein the variable R¹、R²、R³、R⁴Independently, in particular collectively, the following:

R¹、R²identical or different and are unsubstituted or phenyl which carries 1, 2 or 3 substituents selected from the group consisting of methyl and methoxy, where R¹And R²Each being in particular unsubstituted phenyl;

R³is C₁To C₄Alkyl, especially methyl;

R¹⁴is with P (═ O) R^4aR^4bC of a radical₁To C₄Alkyl, especially CH₂-P(＝O)R^4aR^4bOr CH (CH)₃)-P(＝O)R^4aR^4bA group;

wherein

R^4a、R^4bIdentical or different and are unsubstituted or phenyl which carries 1, 2 or 3 substituents selected from the group consisting of methyl and methoxy, where R^4aAnd R^4bParticular preference is given to phenyl which is each unsubstituted.

17. A process for producing optically active menthol, wherein optically active citronellal of formula (III) is produced in a process according to claims 13 to 16, wherein the optically active citronellal of formula (III) is subjected to cyclization to provide optically active isopulegol, and the optically active isopulegol is hydrogenated to provide optically active menthol.

Examples

1500kg/h of citral and 1500kg/h of the catalyst mixture were fed to a reactor having a height of 12m³The liquid volume of (a) is injected into the loop reactor. The catalyst mixture is a mixture prepared in a similar manner to the procedures described in US 2018/057437A 1, WO 2006/040096 and WO 2008/132057A 1, wherein Rh (CO)₂acac, chiralphos and tri-dodecylamine with CO and H in citronellal in a molar ratio of 1:1.4:10₂And (4) reacting. The concentration of the catalyst mixture in the injection loop reactor is from 300 to 1000ppm by weight,based on the amount of rhodium in the catalyst. The ratio of external recycle to feed was 380: 130. The ratio of internal recycle to feed was 3000: 1000.

The power input is 2kW/m³. The pressure in the reactor was adjusted to 80 bar by feeding hydrogen (containing 1000ppm of carbon monoxide). The temperature in the reactor was adjusted to 22 ℃. The conversion of citral was 88%. A citral concentration of about 7 wt.% was present in the effluent of the first reactor.

The effluent from the reactor was fed to a reactor having a height of 9.7m³A liquid volume of the second reactor. The pressure in the second reactor was adjusted to 80 bar by feeding hydrogen (containing 1000ppm of carbon monoxide). The temperature in the reactor was adjusted to 22 ℃. The total conversion after the second reactor was between 93 and 99.9%.

The reaction rate in the first reactor was found to decrease at higher citral concentrations. It has therefore proved advantageous to operate the first reactor at low citral concentrations and to carry out the reaction in the second reactor.