CN110845305B - Method for preparing L-menthol by adopting modified homogeneous catalyst - Google Patents
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Abstract
A method for preparing L-menthol by using a modified homogeneous catalyst comprises the steps of preparing the modified homogeneous catalyst, preparing isopulegol, preparing D, L-menthol and preparing the L-menthol, wherein the modified homogeneous catalyst is prepared by preparing a ligand from 2, 6-dimethylpyridine and a ketone compound, and reacting the ligand with alkyl aluminum to obtain an organic aluminum compound, and the preparation of the L-menthol is to obtain the L-menthol by carrying out chemical induction chiral resolution on the D, L-menthol. The invention uses the organic aluminum compound as the ring-closed catalyst of citronellal, so that the yield of isopulegol is improved, the selectivity to the product isopulegol is high, the used organic aluminum catalyst is easy to synthesize, the stereoselectivity to the reaction is high, and the crystallization recovery is easy; the D, L-menthol is resolved by a chemical induction method, the method is simple to operate, the reaction yield of each step is high, the reaction condition is stable, the product cannot be subjected to partial racemization, and the product loss is small.
Description
Technical Field
The invention relates to the technical field of L-menthol synthesis, in particular to a method for preparing L-menthol by using a modified homogeneous catalyst.
Background
L-menthol, commonly known as menthol, is a natural chiral compound extracted from mint and has wide application in the fields of medicine, health, essence and spice, food industry, fine chemicals for daily use and the like. In 2018, the total consumption of L-menthol worldwide exceeds 6 million tons, and in recent 5 years, the supply of natural menthol is increasing at a rate of not less than 15% every year, so that the demand for L-menthol is far from being met. However, menthol has 3 chiral centers, 8 isomers and 4 pairs of racemic compounds, so that the chiral separation difficulty is high, the cost is high, and the production of L-menthol is limited.
The synthesis of the L-menthol at present relates to an asymmetric synthesis technology, and the synthesis modes at present mainly comprise two modes: one method is to use myrcene or citral and other raw materials, use rhodium catalyst to carry out asymmetric hydrogenation to obtain dextro citronellal, and carry out ring-closing and hydrogenation on the dextro citronellal to obtain L-menthol.
The other method is that citronellal is used as a raw material, isopulegol is generated through selective ring closure of a catalyst, L-menthol is obtained through manual separation after isopulegol is hydrogenated, Lewis acid is mostly used as the catalyst in the ring closure reaction of the method, D, L-menthol is obtained after hydrogenation, and the development of the route is limited all the time by the chiral separation of the D, L-menthol. The use of ZnBr has been disclosed 2The method for producing isopulegol by catalyzing citronellal to close the loop is industrialized, but the loop closing process has only 87% of yield and 91% of corresponding selectivity. Chinese patent CN2011101374215 discloses an organic aluminum compoundThe catalyst prepared by the isopulegol has higher yield and better selectivity, but the used organic aluminum catalyst needs to be added with an ester auxiliary agent and requires low-temperature reaction, so that the catalytic flow is complicated, the catalyst needs to be quenched during recovery, the ligand is separately recovered, the catalyst structure is damaged, and the catalyst is not beneficial to recovery and reuse. Chinese patent CN2018103192285 discloses an organic aluminum catalyst, which effectively overcomes the defects of the organic aluminum catalyst, does not need to add ester auxiliary agents, simplifies the catalyst recovery process, does not need to destroy the ligand and the catalyst structure in the recovery process, but has complex ligand structure, high synthesis difficulty and high cost.
Disclosure of Invention
The invention aims to provide a method for preparing L-menthol by using a modified homogeneous catalyst, which solves the problems of low yield and low selectivity in the ring closure process of citronellal, the problems of high difficulty and low yield in the synthesis of a catalyst ligand, the problem of difficult recovery of the catalyst and the problems of high cost and serious loss of an organic chiral compound in the resolution process aiming at the problems in the background technology.
In order to achieve the purpose, the invention provides the following technical scheme:
a method for preparing L-menthol by adopting a modified homogeneous catalyst comprises the following reaction steps:
s1, preparing isopulegol: adding a first solvent, citronellal and a modified homogeneous catalyst into a dry reaction bottle, introducing nitrogen for protection, reacting at-10-50 ℃ for 2-16 h, stopping the reaction, and separating the reaction liquid into isopulegol by reduced pressure distillation;
s2, preparing D, L-menthol: adding a solvent II, isopulegol and a Pd/C catalyst into a dry hydrogenation reactor, replacing air in the reactor with hydrogen, sealing the reactor, pressurizing the hydrogen to 1-15atm, reacting at 0-110 ℃ for 2-16 h, stopping the reaction, filtering the reaction solution, and distilling the filtrate under reduced pressure to obtain D, L-menthol;
s3, preparing L-menthol: and carrying out chiral resolution on the D, L-menthol to obtain the L-menthol.
As a further scheme of the invention: the preparation method of the modified homogeneous catalyst comprises the following steps:
firstly, dissolving 2, 6-dimethylpyridine in a tetrahydrofuran solution under the protection of nitrogen and under the ice bath condition of-10 ℃, adding n-butyllithium, after 1-2 h, slowly dropwise adding the n-butyllithium to ensure that the temperature of a reaction system is stable, reacting at 15-40 ℃ for 2-6 h, cooling the reaction liquid to-10 ℃, dissolving a compound A in tetrahydrofuran, adding a tetrahydrofuran solution of the compound A into the reaction solution, heating to 15-40 ℃ after 1-2 h of addition, continuing to react for 2-6 h, then adding deionized water to quench the reaction solution, extracting the reaction solution for 3 times by using ethyl acetate, combining organic phases, drying the organic phases by using anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure, drying to obtain a ligand compound crude product, and recrystallizing the ligand compound crude product by using dichloromethane to obtain a ligand compound; in the reaction, in the 2, 6-dimethylpyridine molecule as the raw material, the electron cloud density on the molecule ring is reduced under the action of a nitrogen atom, the property is stable, the substituted methyl is arranged on the ortho position, and the carbon-hydrogen bond on the methyl is more active than the carbon-hydrogen bond on the pyridine ring through the electron effect, so that the hydrogen-lithium exchange reaction on the methyl is easy to realize after the n-butyl lithium is added, the carbonyl of the ketone is an electron-withdrawing group, and the carbonyl is negatively charged and is easy to react with the 2, 6-dimethylpyridine from which the hydrogen is extracted, so that the reaction is easy to carry out and the yield is high;
Secondly, dissolving the ligand compound in tetrahydrofuran, introducing nitrogen for protection, cooling the solution to below-40 ℃, and carrying out AlR3Adding the n-hexane solution within 1-2 h, naturally heating to 20 ℃, continuing to react for 2-8 h, filtering the reaction solution, and carrying out condensation by using tetrahydrofuran and the n-hexane solution in a volume ratio of 1: 0.1-10Crystal, namely placing the crystal in a freezer at the temperature of-25-0 ℃ for freezing for 10-20 h to obtain colorless crystal, wherein the colorless crystal is the modified homogeneous catalyst; two hydroxyl groups obtained by ketone addition in the ligand compound enable the ligand compound to have a more compact structure, and the hydroxyl groups can be combined with aluminum alkyl AlR3Reacting to connect ligand with Al to form Al compound containing ligand skeleton, and generating Van der Waals force between N element on pyridine and Al to form a certain space structure of organic aluminium compound, R1、R2The group can lead the ligand framework to form certain steric hindrance, the combined action of the factors is beneficial to the catalytic action of stereo selection, and in addition, the catalyst obtained by crystallization is easy to crystallize and separate out when being recovered, thereby reducing the loss of the catalyst and reducing the reaction cost.
As a further scheme of the invention: the 2, 6-lutidine: n-butyl lithium: compound 1: AlR 3In a molar ratio of 1: 0.5-2.5: 1-2: 0.5 to 1.5; the volume of tetrahydrofuran used per gram of 2, 6-lutidine is 2-10 mL; in the compound 1, R1Selected from substituted benzene or substituted naphthalene containing C1-C6 alkyl, methoxy, halogen, trihalomethyl and trihalomethoxy, R2Selected from C1-C6 alkyl, phenyl, methoxy, halogen, trihalomethyl and trihalomethoxy; the AlR3R in (1) is methyl or ethyl.
As a further scheme of the invention: the first solvent is one or more selected from n-hexane, toluene, ethylbenzene, xylene, diethylbenzene, tetrahydrofuran, dichloromethane and dichloroethane, and the second solvent is one or more selected from methanol, ethanol, isopropanol and n-butanol.
As a further scheme of the invention: the absolute pressure of the reduced pressure distillation is-1 to-0.01 MPa, and the temperature of the reduced pressure distillation is 40-80 ℃.
As a further scheme of the invention: the chiral resolution steps are as follows:
1) adding 0.1mol of D, L-menthol, 0.1-0.15mol of phthalic anhydride and 0.05-0.15mol of pyridine into a dry three-neck flask, heating to 80-120 ℃, reacting for 0.5-3h, cooling, adjusting the pH to 2-3 by using 1mol/L hydrochloric acid solution, extracting for 2-3 times by using dichloromethane, washing an organic phase by using water and saturated saline solution, drying by using anhydrous sodium sulfate, filtering, concentrating the filtrate under reduced pressure to obtain colorless oily liquid to obtain a white crystal compound B, reacting alcohol and acid anhydride to prepare ester so as to reduce the solubility of the compound, easily separating out the compound from the solvent for crystallization, and preparing the formed acid anhydride monoester for subsequent chiral induction;
2) Dissolving 0.1mol of compound B in 100mL of ether, adding 0.02-0.06mol of (S) -alpha-phenylethylamine into the solution, stirring at-10-5 ℃ for reaction until flocculent precipitate appears, continuing to react for 1-3h, freezing at-20-0 ℃ for 1-8h, filtering to obtain a crude product of chiral phenylethylamine salt, washing with 3mL of ether for 2-5 times to obtain a compound C, by adding chiral (S) -alpha-phenylethylamine, menthol with a levorotatory structure can be induced to react with the chiral (S) -alpha-phenylethylamine, the menthol with the dextrorotation structure cannot be combined with (S) -alpha-phenylethylamine due to the steric hindrance, the compound B is converted into chiral salt, the compound with the required optical activity is easily separated out by utilizing the principle that the salt is poor in solubility in an organic solvent, and the ee% value of the obtained compound is high;
3) adding 0.1mol of the compound C into 100mL of ether, adding 30-80mL of 2mol/L hydrochloric acid at 0-10 ℃, stirring for reacting for 1h, separating liquid, drying an ether layer by anhydrous sodium sulfate, filtering, and concentrating the filtrate under reduced pressure to obtain a compound D;
4) adding 0.1mol of compound D into 100mL of 25% potassium hydroxide solution, stirring and reacting for 5-10h at 15-25 ℃, extracting with diethyl ether for 2 times, combining diethyl ether layers, washing with water for 1-3 times, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain L-menthol. The compound C is subjected to common acid hydrolysis and alkali hydrolysis reaction in sequence, the chirality of the compound C is not affected, the price of the used reagent is low, and the reaction yield is high.
Compared with the prior art, the invention has the beneficial effects that:
by using modified homogeneous catalysts as ring-closure catalysts for citronellalTwo hydroxyl groups obtained by ketone addition in the ligand compound enable the ligand compound to have a more compact structure, and the hydroxyl groups can be reacted with alkyl aluminum AlR3The ligand is connected with Al through reaction to form an Al compound containing a ligand framework, and the N element on the pyridine can generate Van der Waals force with the Al, so that the modified homogeneous catalyst forms a certain spatial structure, the ligand framework forms a certain steric hindrance, the factors act together to facilitate the stereoselectivity in the citronellal ring closing process, and the problems of low yield and low selectivity in the citronellal ring closing process are solved;
by using 2, 6-lutidine as a raw material for synthesizing a ligand compound, the electron cloud density on a molecular ring is reduced and the property is stable under the action of a nitrogen atom in a 2, 6-lutidine molecule, and a substituted methyl group is arranged on an ortho position, and a carbon-hydrogen bond on the methyl group is more active than that on the pyridine ring under the electronic effect, so that after n-butyl lithium is added, the hydrogen-lithium exchange reaction on the methyl group is very easy to realize, while the carbonyl group of ketone is an electron-withdrawing group and is negatively charged and is easy to react with the 2, 6-lutidine from which hydrogen is extracted, so that the reaction is easy to carry out and the yield is high, and the problems of high difficulty and low yield in synthesizing a catalyst ligand are solved;
The modified homogeneous catalyst is obtained by recrystallization purification, and is easy to crystallize and separate out during recovery, so that the problem of difficult catalyst recovery is solved;
the D, L-menthol is resolved by a chemical induction method, the menthol with a levorotatory structure can be induced to react with the (S) -alpha-phenylethylamine by adding the (S) -alpha-phenylethylamine with chirality, the menthol with a dextrorotatory structure cannot be combined with the (S) -alpha-phenylethylamine due to the steric hindrance, the compound B is converted into chiral salt, the compound with the required activity is easily separated out by utilizing the principle that the salt has poor solubility in an organic solvent, the ee% value of the obtained compound is high, and the problems of high cost and serious product loss of the organic chiral compound in the resolution process are solved;
therefore, the method for preparing the L-menthol from the citronellal is a high-efficiency and industrially valuable preparation method.
Detailed Description
The technical solutions of the present invention will be described clearly and completely below with reference to embodiments of the present invention, and it should be apparent that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, belong to the protection scope of the present invention.
Example 1
Preparation of modified homogeneous catalyst:
firstly, under the conditions of nitrogen protection and ice bath at 0 ℃, dissolving 2, 6-lutidine (0.1mol) in 60mL of tetrahydrofuran solution, adding n-hexane solution of n-butyllithium (0.12mol), reacting for 3 hours at 20 ℃, cooling the reaction solution to 0 ℃ again, dissolving benzophenone (0.1mol) in 30mL of tetrahydrofuran, adding the tetrahydrofuran solution of benzophenone into the reaction solution, reacting for 3 hours after 1 hour of addition, heating to 20 ℃, continuing to react for 3 hours, adding 30mL of deionized water to quench the reaction solution, extracting the reaction solution for 3 times by using ethyl acetate, combining organic phases, drying the organic phases by anhydrous sodium sulfate, filtering, concentrating and drying the filtrate under reduced pressure to obtain a ligand compound crude product, recrystallizing the ligand compound crude product by using dichloromethane to obtain the ligand compound, wherein the yield is 72%;
secondly, dissolving the ligand compound (0.05mol) in 50mL tetrahydrofuran, introducing nitrogen for protection, cooling the solution to below-40 ℃, and adding AlMe3Adding (0.06mol) n-hexane solution within 1h, naturally heating to 20 ℃ to continue reacting for 5h, filtering the reaction solution, crystallizing by using tetrahydrofuran and the n-hexane solution in a volume ratio of 1:1, and freezing in a freezer at the temperature of-15 ℃ for 16h to obtain colorless crystals, wherein the colorless crystals are the modified homogeneous catalyst, and the yield is 87%.
Example 2
S1, preparing isopulegol:
adding 1L of dichloromethane, 100g of citronellal and 5g of modified homogeneous catalyst into a dry reaction bottle, introducing nitrogen for protection, reacting for 3 hours at 10 ℃, stopping the reaction, distilling the reaction solution under reduced pressure of-0.1 MPa and 60 ℃ to separate 96g of colorless oily product, wherein the yield of isopulegol is 94.2%, and the corresponding selectivity is 98.2% (GC area%: isopulegol is 98.2%, neo-isopulegol is 1.1%, neo-isopulegol is 0.7%, the gas chromatography model is Shimadzu 2010, the chromatography model is 50m long, and the column inner diameter is 0.25 mm);
s2, preparing D, L-menthol:
adding the isopulegol and 1L of methanol into a dry hydrogenation reactor, adding 10g of Pd/C catalyst, replacing air in the reactor with hydrogen, sealing the reactor, pressurizing to 3atm with hydrogen, reacting at 25 ℃ for 8 hours, stopping the reaction, filtering the reaction liquid to remove the catalyst, distilling the filtrate under reduced pressure to remove the methanol, and purifying by column chromatography to obtain a colorless solid product D, L-menthol 93g, wherein the yield is 95.6%;
s3, preparing L-menthol:
l-menthol is obtained by chiral resolution of D, L-menthol, and the specific steps are as follows,
1) adding 0.1mol of D, L-menthol, 0.1mol of phthalic anhydride and 0.05mol of pyridine into a dry three-neck flask, heating to 80 ℃ for reaction for 1h, cooling, adjusting the pH to 2-3 by using 1mol/L hydrochloric acid solution, extracting for 3 times by using dichloromethane, washing an organic phase by using water and saturated saline solution, drying by using anhydrous sodium sulfate, filtering, and concentrating the filtrate under reduced pressure to obtain a compound B of colorless oily liquid with the yield of 99%;
2) Dissolving the compound B in 100mL of diethyl ether, adding 0.03mol of (S) -alpha-phenylethylamine into the solution, stirring at 5 ℃ for reaction until flocculent precipitates appear, continuing to react for 3h, then freezing at-20 ℃ for 8h, filtering to obtain a crude product of chiral phenylethylamine salt, and washing with 3mL of diethyl ether for 2 times to obtain a compound C with the yield of 48%;
3) adding the compound C into 100mL of diethyl ether, adding 30mL of 2mol/L hydrochloric acid at 0-10 ℃, stirring for reacting for 1h, separating liquid, drying an diethyl ether layer by anhydrous sodium sulfate, filtering, and concentrating the filtrate under reduced pressure to obtain a compound D with the yield of 99%;
4) adding the compound D into 100mL of 25% potassium hydroxide solution, stirring and reacting at 15 ℃ for 5h, extracting with diethyl ether for 2 times, combining diethyl ether layers, washing with water for 3 times, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain the L-menthol, wherein the yield is 96%, and ee% ═ 98%.
Example 3
Preparation of modified homogeneous catalyst:
firstly, under the conditions of nitrogen protection and ice bath at 0 ℃, dissolving 2, 6-lutidine (0.1mol) in 60mL of tetrahydrofuran solution, adding n-hexane solution of n-butyllithium (0.12mol), completing 1.5h addition, reacting at 20 ℃ for 3h, cooling the reaction solution to 0 ℃ again, dissolving p-methylacetophenone (0.1mol) in 30mL of tetrahydrofuran, adding the tetrahydrofuran solution of p-methylacetophenone into the reaction solution, continuing to react for 3h after 1h addition, then adding 30mL of deionized water to quench the reaction solution, extracting the reaction solution for 3 times by using ethyl acetate, combining organic phases, drying the organic phases by anhydrous sodium sulfate, filtering, decompressing and concentrating the filtrate to dryness to obtain a ligand compound crude product, recrystallizing the ligand compound crude product by dichloromethane to obtain the ligand compound with a yield of 69%;
Secondly, dissolving the ligand compound (0.05mol) in 50mL tetrahydrofuran, introducing nitrogen for protection, cooling the solution to below-40 ℃, and adding AlMe3Adding (0.06mol) n-hexane solution within 1h, naturally heating to 20 ℃ to continue reacting for 5h, filtering the reaction solution, crystallizing by using tetrahydrofuran and the n-hexane solution in a volume ratio of 1:1, and freezing in a freezer at the temperature of-15 ℃ for 16h to obtain colorless crystals, wherein the colorless crystals are the modified homogeneous catalyst, and the yield is 83%.
Example 4
Preparation of isopulegol: adding 1L of dichloromethane, 100g of citronellal and 5g of the modified homogeneous catalyst obtained in example 3 into a dry reaction bottle, introducing nitrogen for protection, reacting at 10 ℃ for 3 hours, stopping the reaction, distilling the reaction solution at-0.1 MPa and 60 ℃ under reduced pressure to separate 97g of colorless oily product, wherein the yield of isopulegol is 95.6%, and the corresponding selectivity is 98.6% (GC area%: 98.6% for isopulegol, 0.9% for neo-isopulegol, 0.5% for neo-isopulegol, Shimadzu 2010, 50m long for chromatographic column, and 0.25mm for inner diameter of chromatographic column).
Comparative example 1
Preparation of isopulegol: adding 1L of dichloromethane, 100g of citronellal and 5g of ZnBr2 into a dry reaction bottle, introducing nitrogen for protection, reacting for 3 hours at 10 ℃, stopping the reaction, distilling the reaction solution under reduced pressure of-0.1 MPa and 60 ℃ to separate 89g of colorless oily product, wherein the yield of isopulegol is 81 percent, and the corresponding selectivity is 91 percent (GC area percent: isopulegol 91 percent, neo-isopulegol 5.3 percent, neo-isopulegol 3.7 percent, gas chromatography type Shimadzu 2010, chromatographic type of chromatographic column 50m long and column inner diameter 0.25 mm).
Comparative example 2
Preparation of isopulegol: adding 1L of dichloromethane, 100g of citronellal and 5g of binaphthol-based organoaluminum compound catalyst into a dry reaction bottle, introducing nitrogen for protection, reacting at 10 ℃ for 3 hours, stopping the reaction, distilling the reaction liquid under reduced pressure of-0.1 MPa and 60 ℃ to separate 91g of colorless oily product, wherein the yield of isopulegol is 88.2%, and the selectivity is 97% (GC area%: isopulegol 97%, neo-isopulegol 1.9%, neo-isopulegol 1.1%, and gas chromatography type Shimadzu 2010, chromatography type column with length of 50m and column inner diameter of 0.25 mm).
| Yield of isopulegol% | Corresponding selectivity% | |
| Example 2 | 94.2 | 98.2 |
| Example 4 | 95.6 | 98.6 |
| Comparative example 1 | 81 | 91 |
| Comparative example 2 | 88.2 | 97 |
TABLE 1
As can be seen from Table 1, the modified homogeneous catalysts prepared according to the present invention in examples 2 and 4 gave isopulegol with a corresponding selectivity of 98% or more and a yield of 94% or more, according to comparative example 1, using ZnBr2The catalytic reaction has lower enantioselectivity and yield of isopulegol, and the catalytic reaction has higher enantioselectivity by using the binaphthol-based organic aluminum compound as a catalyst in comparative example 2, but the yield is still lower than that in examples 2 and 4. Therefore, the yield and the corresponding selectivity of the isopulegol are greatly improved by adopting the modified homogeneous catalyst prepared by the invention.
Although the present specification describes embodiments, not every embodiment includes only a single embodiment, and such descriptions are provided for clarity, and it is understood that the specification is incorporated herein by reference, and the embodiments described in each embodiment may be combined as appropriate to form other embodiments, which will be apparent to those skilled in the art.
Therefore, the above description is only for the preferred embodiment of the present application and is not intended to limit the scope of the present application; all the equivalent changes made within the scope of the claims of the present application are the protection scope of the claims of the present application.
Claims (1)
1. A method for preparing L-menthol by adopting a modified homogeneous catalyst is characterized by comprising the following steps: the method comprises the following reaction steps:
s1, adding a first solvent, citronellal and a modified homogeneous catalyst into a dry reaction bottle, introducing nitrogen for protection, reacting at-10-50 ℃ for 2-16 h, stopping reaction, and separating isopulegol from a reaction solution through reduced pressure distillation;
s2, adding a second solvent, the isopulegol and a Pd/C catalyst into a dry hydrogenation reactor, replacing air in the reactor with hydrogen, sealing the reactor, pressurizing the hydrogen to 1-15atm, reacting at 0-110 ℃ for 2-16 h, stopping the reaction, filtering the reaction liquid, and distilling the filtrate under reduced pressure to obtain D, L-menthol;
S3, carrying out chiral resolution on the D, L-menthol to obtain L-menthol;
the preparation method of the modified homogeneous catalyst comprises the following steps:
the preparation process of the modified homogeneous catalyst comprises the following steps:
firstly, under the conditions of nitrogen protection and ice bath at the temperature of-10 ℃, dissolving 2, 6-dimethyl pyridine in a tetrahydrofuran solution, adding n-butyl lithium, reacting for 2-2 hours after the addition is finished, reacting for 2-6 hours at the temperature of 15-40 ℃, cooling the reaction solution again to-10 ℃, dissolving a compound A in tetrahydrofuran, adding the tetrahydrofuran solution of the compound A into the reaction solution, heating to 15-40 ℃ after the addition is finished for 1-2 hours, continuing to react for 2-6 hours, adding deionized water to quench the reaction solution, extracting the reaction solution for 3 times by using ethyl acetate, combining organic phases, drying and filtering the organic phases through anhydrous sodium sulfate, concentrating and drying the filtrate under reduced pressure to obtain a ligand compound crude product, and recrystallizing the ligand compound crude product through dichloromethane to obtain a ligand compound;
secondly, dissolving the ligand compound in tetrahydrofuran, introducing nitrogen for protection, cooling the solution to below-40 ℃, and carrying out AlR3Adding the n-hexane solution for 1-2 h, heating to 20 ℃, continuing to react for 2-8 h, filtering the reaction solution, crystallizing by using tetrahydrofuran and the n-hexane solution in a volume ratio of 1: 0.1-10, and freezing in a freezer at-25-0 ℃ for 10-20 h to obtain colorless crystals, wherein the colorless crystals are the modified homogeneous catalyst;
The ratio of the 2, 6-lutidine: n-butyl lithium: a compound A: AlR3In a molar ratio of 1: 0.5-2.5: 1-2: 0.5 to 1.5; the volume of tetrahydrofuran used per gram of 2, 6-lutidine is 2-10mL；
The compound A, the ligand compound and R in the modified homogeneous catalyst1Selected from substituted benzene or substituted naphthalene containing C1-C6 alkyl, methoxy, halogen, trihalomethyl and trihalomethoxy, R2Selected from C1-C6 alkyl, phenyl, methoxy, halogen, trihalomethyl and trihalomethoxy; the AlR3R in (1) is methyl or ethyl;
the solvent I is one or a mixture of more of n-hexane, toluene, ethylbenzene, xylene, diethylbenzene, tetrahydrofuran, dichloromethane and dichloroethane, and the solvent II is one or a mixture of more of methanol, ethanol, isopropanol and n-butanol;
the citronellal: modified homogeneous catalyst: the mass ratio of the Pd/C catalyst is 1: 0.01-0.1: 0.01 to 0.1;
the absolute pressure of the reduced pressure distillation is-1 to-0.01 MPa, and the temperature of the reduced pressure distillation is 40 to 80 ℃;
the chiral resolution comprises the following steps:
1) adding 0.1mol of D, L-menthol, 0.1-0.15 mol of phthalic anhydride and 0.05-0.15 mol of pyridine into a dry three-neck flask, heating to 80-120 ℃, reacting for 0.5-3 h, cooling, adjusting the pH to 2-3 by using 1mol/L hydrochloric acid solution, extracting for 2-3 times by using dichloromethane, washing an organic phase by using water and saturated saline solution, drying by using anhydrous sodium sulfate, filtering, and concentrating the filtrate under reduced pressure to obtain a colorless oily liquid to obtain a white crystalline compound B;
2) Dissolving 0.1mol of the compound B in 100mL of diethyl ether, adding 0.02-0.06 mol of (S) -alpha-phenylethylamine into the solution, stirring at-10-5 ℃ for reaction until flocculent precipitate appears, continuously reacting for 1-3 h, freezing at-20-0 ℃ for 1-8 h, filtering to obtain a crude product of chiral phenylethylamine salt, and washing with 3mL of diethyl ether for 2-5 times to obtain a compound C;
3) adding 0.1mol of the compound C into 100mL of diethyl ether, adding 30-80 mL of 2mol/L hydrochloric acid at 0-10 ℃, stirring and reacting for 1h, separating liquid, drying an diethyl ether layer by anhydrous sodium sulfate, filtering, and concentrating the filtrate under reduced pressure to obtain a compound D;
4) adding 0.1mol of the compound D into 100mL of 25% potassium hydroxide solution, stirring and reacting for 5-10 h at 15-25 ℃, extracting with diethyl ether for 2 times, combining diethyl ether layers, washing with water for 1-3 times, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain the L-menthol.
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