Method for obtaining 1S, 5R-pinanol through chiral carboxylic acid mediated dynamic kinetic resolution of trans-pinanol

Abstract

The invention belongs to the technical field of chiral resolution of organic compounds, and particularly discloses a method for obtaining 1S, 5R-pinanol by chiral carboxylic acid-mediated dynamic kinetic resolution of trans-pinanol, which comprises the following steps: dissolving trans-pinanol, chiral carboxylic acid and a solid acid catalyst in a solvent, stirring at a proper temperature, and reacting to obtain the 1S, 5R-pinanol. The method comprises the following steps: carrying out selective esterification reaction on trans-pinyl hydrate to generate a chiral ester intermediate, carrying out rapid racemization on unreacted trans-pinyl hydrate, after the reaction is finished, filtering and recovering a solid acid catalyst, carrying out reduced pressure rectification on filtrate, separating a product chiral ester and recovering a solvent, and further hydrolyzing the chiral ester in an alkaline system to obtain optically pure 1S, 5R-pinyl hydrate, and recovering the chiral carboxylic acid. The optically pure 1S, 5R-pinyl hydrate is prepared in a green and efficient manner by utilizing the catalytic synergistic effect of chiral carboxylic acid and solid acid, and the method has the advantages of high enantioselectivity, high raw material utilization rate, good process adaptability and good industrial application prospect.

Description

Technical Field

[0001] This invention belongs to the field of chiral resolution technology of organic compounds, and relates to the chiral resolution of trans-hydrated pinol, specifically to a method for obtaining 1S,5R-hydrated pinol by chiral carboxylic acid-mediated dynamic kinetic resolution of trans-hydrated pinol. Background Technology

[0002] 1S,5R-hydrated pinol (English name: trans-Sobrerol, chemical name: trans-p-menthol-6-ene-2,8-diol), molecular formula is C 10 H 18 O2 is a bichiral diol compound with two chiral centers and two hydroxyl groups, belonging to the p-menthene class of terpene derivatives. Its unique molecular configuration endows it with good pharmacological activity and broad industrial application value.

[0003] In the pharmaceutical field, studies have shown that 1S,5R-hydrated pinol exhibits good expectorant and anti-inflammatory activities in the treatment of respiratory diseases and has been used as an intermediate or active ingredient in antitussive and expectorant drugs [Children 2023,10, 1210]. Furthermore, this compound can enhance hippocampal cholinergic signaling function and possesses anti-tau protein and Aβ synthesis activity, and is considered promising for the treatment of neurodegenerative diseases such as Alzheimer's disease [Int. J. Mol. Sci.2025, 26, 4613]. Simultaneously, related studies have also found that its binding with pharmaceutically acceptable salts can promote myoblast differentiation, potentially for the treatment of muscle degeneration diseases related to myasthenia gravis [CN108601755A]. In the fine chemical industry, 1S,5R-hydrated pinol is widely used in the synthesis of natural products, chiral drugs, and high-value-added fragrances (such as L-carvone and chiral terpenoids). With the increasing demand for its applications, developing efficient, green, and industrially scalable synthesis methods has become a research hotspot.

[0004] Currently, methods for preparing optically pure 1S,5R-hydrated pinol mainly fall into the following categories: First, enzyme-catalyzed kinetic resolution, such as the selective esterification of racemic trans-hydrated pinol catalyzed by lipase PS. However, this method requires a large amount of catalyst and the yield is limited to the theoretical upper limit of 50%, making it unsuitable for industrial scale-up [Tetrahedron: Asymmetry 1991, 2, 931]; Second, asymmetric synthesis strategies, such as using methyl 3,5-dihydroxy-4-methylbenzoate as a starting material to synthesize the enantiomer of the target chiral product through 8 steps [Synth. Commun. 2003, 33, 2125]. However, this method is cumbersome, uses precious metal catalysts, and produces complex byproducts, resulting in high overall process costs and a heavy environmental burden, limiting its practical application; Third, metal-catalyzed kinetic resolution, such as palladium-catalyzed selective oxidation of racemic trans-hydrated pinol to achieve resolution [J. Org. Chem. 2003, [68,7535] Although these methods exhibit good enantioselectivity, the raw material utilization rate is still limited to 50%, leading to resource waste. In summary, these methods suffer from problems such as complex steps, harsh reaction conditions, and limited yield and purity. In particular, obtaining high optical purity 1S,5R-hydrated pinol under industrial scale-up conditions still faces significant challenges.

[0005] Dynamic kinetic resolution (DKR) is a strategy that combines in-situ dynamic racemization of racemic substrates with selective conversion by chiral catalysts, selectively converting two enantiomers into a single configuration product. Theoretically, it can achieve 100% yield and 100% ee, demonstrating significant advantages in chiral synthesis. However, for diol substrates with bichiral centers and complex spatial configurations (such as trans-hydrated pinol), there is still a lack of efficient and universal resolution systems, necessitating the development of novel, green, and efficient dynamic kinetic resolution methods. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide a method for the dynamic kinetic resolution of trans-hydrated pinol mediated by chiral carboxylic acids to obtain 1S,5R-hydrated pinol. This invention utilizes the synergistic effect of chiral carboxylic acids and solid acid catalysis to efficiently prepare optically pure 1S,5R-hydrated pinol from racemic or low enantioselective trans-hydrated pinol. The method of this invention exhibits high enantioselectivity, high feed utilization, and good process adaptability, making it suitable for the green and efficient preparation of 1S,5R-hydrated pinol, and possessing promising prospects for industrial application.

[0007] This invention is achieved through the following technical solution: A method for the dynamic kinetic resolution of trans-hydrated pinol mediated by chiral carboxylic acid to obtain 1S,5R-hydrated pinol includes the following steps: dissolving trans-hydrated pinol, chiral carboxylic acid, and a solid acid catalyst in a solvent, and stirring at a suitable temperature to allow trans-hydrated pinol to undergo selective esterification to generate a chiral ester intermediate; unreacted trans-hydrated pinol undergoes rapid racemization; the reaction process is monitored by chiral gas chromatography; after the reaction is completed, the solid acid catalyst is recovered by filtration; the filtrate is subjected to vacuum distillation to separate the product chiral ester and recover the solvent; the chiral ester is further hydrolyzed in an alkaline system to obtain optically pure 1S,5R-hydrated pinol, and the chiral carboxylic acid is recovered.

[0008] The reaction equation is as follows:

[0009] In this invention, chiral carboxylic acids serve simultaneously as enantiomeric resolving agents and esterification substrates, achieving the enrichment of target enantiomeric compounds by constructing chiral esters. Simultaneously, under acidic conditions, the racemization of unreacted 1R,5S-hydrated pinol is promoted to generate 1S,5R-hydrated pinol, which then participates in the selective esterification reaction, thereby achieving highly efficient dynamic kinetic resolving.

[0010] A further improvement to the present invention is as follows: The trans-hydrated pinol is a racemic or low-enantioselective trans-hydrated pinol with an ee value of 0-60%.

[0011] Furthermore, the chiral carboxylic acid is an organic carboxylic acid with central chirality, including (S)-2-phenylpropionic acid, (S)-2-phenylbutyric acid, (S)-1,2,3,4-tetrahydro-1-naphthoic acid, (S)-ibuprofen, (S)-naproxen, (S)-ketoprofen, (S)-2-methylbutyric acid, (S)-3-cyclohexene-1-carboxylic acid, (1R,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxylic acid, pinone acid, etc.

[0012] Furthermore, the solid acid catalyst is used to activate carboxylic acids to promote esterification, including Amberlyst-15 (sulfonated resin) and H3PW. 12 O 40 / SiO2 (phosphotungstic acid-supported), sulfonated graphene, H-ZSM-5 (proton zeolite), ZrO2-SO4 2- Zirconium oxide sulfate, WO3 / ZrO2 solid acid, Fe3O4@SiO2-SO3H (magnetic solid acid), sulfonated biochar, etc.

[0013] Furthermore, the solvent is an organic solvent that can form an azeotropic reaction with water, which facilitates the removal of the generated water through a water separator during the reaction process. Examples include cyclopentyl methyl ether, isopropyl ether, methyl tert-butyl ether, benzene, toluene, xylene, cyclohexane, n-hexane, ethyl acetate, etc.

[0014] Furthermore, the mass ratio of the solid acid catalyst to trans-hydrated pinol is 1:50-100; the molar ratio of the chiral carboxylic acid to trans-hydrated pinol is 1-2:1.

[0015] Furthermore, the reaction temperature is 40-120 °C.

[0016] Furthermore, the alkaline system is an aqueous solution of potassium hydroxide, sodium hydroxide, or lithium hydroxide.

[0017] Furthermore, the recovered solid acid catalyst and chiral carboxylic acid can be reused. The solid acid catalyst can be recycled at least ten times after filtration and the chiral carboxylic acid can be recycled an unlimited number of times after hydrolysis.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention utilizes the synergistic effect of chiral carboxylic acids and solid acid catalysis to efficiently prepare 1S,5R-hydrated pinol with an optical purity greater than 99% from racemic or low enantioselective trans-hydrated pinol. The chiral carboxylic acid also serves as an enantiomeric resolving agent and an esterification substrate to form chiral esters and enrich the target enantiomeric compounds.

[0019] This invention features a mild reaction, simple operation, and excellent enantioselectivity. The chiral carboxylic acid and solid acid catalytic system can be reused, making it suitable for the green and efficient synthesis of chiral flavor intermediates such as L-carvone, and it has good prospects for industrial application.

[0020] This invention not only provides a novel dynamic kinetic separation strategy for the efficient preparation of optically pure 1S,5R-hydrated pinol, but also allows for the recycling of both the solid acid catalyst and the chiral carboxylic acid used, aligning with green chemistry principles and significantly reducing the production cost of trans-hydrated pinol, thus laying a solid foundation for its industrial application. Detailed Implementation

[0021] The present invention will now be described in detail with reference to specific embodiments. Example 1

[0022] Select a 100 mL reaction flask and add 10.0 g of trans-pinene hydrate (20% ee), dissolved in 20 mL of toluene. Then add 0.1 g of Amberlyst-15 and 10.6 g of ( S1.2 phenylpropionic acid (1.2 equiv.). The reaction system was stirred at 120 °C, and a water separator was installed to remove the generated water. Samples were taken periodically, and the reaction progress was monitored by chiral gas chromatography (GC). After 8 hours of reaction, the content of hydrated pinol in the reaction solution was detected to be <3%, and the reaction was stopped.

[0023] Post-reaction processing: The reaction solution was cooled to room temperature, and 0.096 g of Amberlyst-15 was separated by filtration. The filtrate was subjected to vacuum distillation to recover toluene, yielding 16.0 g of pinene hydrate. Subsequently, 1N sodium hydroxide solution (120 mL) was added to the ester, and hydrolysis was carried out with stirring at room temperature. A large amount of white solid precipitated, which was filtered and dried to give 8.9 g of 1 S 5 R - Hydrated pinol (88.9% yield, 99.2% ee). The resulting ( S Sodium 2-phenylpropionate was acidified with 1N hydrochloric acid (160 mL) to give 7.9 g ( S )-2-Phenylacetic acid. Amberlyst-15 and ( S 2-Phenylacetic acid can be repeatedly recycled. Example 2

[0024] Select a 100 mL reaction flask and add 10.0 g of trans-hydrated pinene (20% ee), dissolved in 20 mL of xylene. Then add 0.1 g of H3PW. 12 O 40 / SiO2 and 11.6 g ( S 2-Phenylacetic acid (1.2 equiv.). The reaction system was stirred at 120 °C, and a water separator was installed to remove the generated water. Samples were taken periodically, and the reaction progress was monitored by chiral gas chromatography (GC). After 8 hours of reaction, the content of hydrated pinol in the reaction solution was detected to be <3%, and the reaction was stopped.

[0025] Post-reaction processing: The reaction solution was cooled to room temperature, and 0.09 g of H3PW was separated by filtration. 12 O 40 / SiO2. The filtrate was subjected to vacuum distillation to recover xylene and obtain 17.0 g of pinene hydrate. Then, 1N sodium hydroxide solution (120 mL) was added to the ester, and hydrolysis was carried out with stirring at room temperature. A large amount of white solid precipitated, which was filtered and dried to obtain 9.0 g of 1 S 5 R - Hydrated pinol (89.8% yield, 99.4% ee). The resulting ( S Sodium 2-phenylbutyrate was acidified with 1N hydrochloric acid (160 mL) to give 8.8 g (S 2-Phenylacetic acid. The recovered H3PW 12 O 40 / SiO2 and ( S 2-Phenylacetic acid can be repeatedly recycled. Example 3

[0026] Select a 100 mL reaction flask and add 10.0 g of trans-hydrated pinene (20% ee), dissolved in 20 mL of benzene. Then add 0.1 g of sulfonated graphene and 7.2 g ( S 2-Methylbutyric acid (1.2 equiv.). The reaction system was stirred at 100 °C, and a water separator was installed to remove the generated water. Samples were taken periodically, and the reaction progress was monitored by chiral gas chromatography (GC). After 9 hours of reaction, the content of hydrated pinol in the reaction solution was detected to be <3%, and the reaction was stopped.

[0027] Post-reaction processing: The reaction solution was cooled to room temperature, and 0.098 g of sulfonated graphene was separated by filtration. The filtrate was subjected to vacuum distillation to recover benzene and obtain 14.2 g of hydrated pinene ester. Then, 1N sodium hydroxide solution (120 mL) was added to the ester, and hydrolysis was carried out by stirring at room temperature. A large amount of white solid precipitated, which was filtered and dried to obtain 9.4 g of 1 S 5 R - Hydrated pinol (93.9% yield, 99.8% ee). The resulting ( S Sodium 2-methylbutyrate was acidified with 1N hydrochloric acid (160 mL) to give 5.6 g ( S )-2-methylbutyric acid. The recovered sulfonated graphene and ( S 2-Methylbutyric acid can be repeatedly recycled. Example 4

[0028] Select a 100 mL reaction flask and add 10.0 g of trans-hydrated pineneol (20% ee), dissolved in 20 mL of cyclohexane. Then add 0.1 g of H-ZSM-5 and 12.4 g (… S 1,2,3,4-Tetrahydro-1-naphthoic acid (1.2 equiv.). The reaction system was stirred at 80 °C, and a water separator was installed to remove the generated water. Samples were taken periodically, and the reaction progress was monitored by chiral gas chromatography (GC). After 7 hours of reaction, the content of hydrated pinol in the reaction solution was detected to be <3%, and the reaction was stopped.

[0029] Post-reaction processing: The reaction solution was cooled to room temperature, and 0.099 g of H-ZSM-5 was separated by filtration. The filtrate was subjected to vacuum distillation to recover cyclohexane and obtain 17.2 g of pinene hydrate. Then, 1N sodium hydroxide solution (120 mL) was added to the ester, and hydrolysis was carried out with stirring at room temperature. A large amount of white solid precipitated, which was filtered and dried to obtain 8.8 g of 1 S 5 R - Hydrated pinol (87.9% yield, 98.2% ee). The resulting ( S Sodium 1,2,3,4-tetrahydro-1-naphthoate was acidified with 1N hydrochloric acid (160 mL) to give 9.0 g ( S )-1,2,3,4-Tetrahydro-1-naphthoic acid. The recovered H-ZSM-5 and ( S 1,2,3,4-Tetrahydro-1-naphthoic acid can be repeatedly recycled. Example 5

[0030] Select a 100 mL reaction flask and add 10.0 g of trans-hydrated pineneol (20% ee), dissolved in 20 mL of n-hexane. Then add 0.1 g of ZrO₂-SO₄. 2- and 8.9 g ( S 1.2 equiv. of 3-cyclohexene-1-carboxylic acid was used. The reaction system was stirred at 70 °C, and a water separator was installed to remove the generated water. Samples were taken periodically, and the reaction progress was monitored by chiral gas chromatography (GC). After 6 hours of reaction, the content of hydrated pinol in the reaction solution was detected to be <3%, and the reaction was stopped.

[0031] Post-reaction processing: The reaction solution was cooled to room temperature, and 0.095 g of ZrO2-SO4 was separated by filtration. 2- The filtrate was subjected to vacuum distillation to recover n-hexane and yield 16.0 g of pinene hydrate. Subsequently, 1N sodium hydroxide solution (120 mL) was added to the ester, and hydrolysis was carried out with stirring at room temperature. A large amount of white solid precipitated, which was filtered and dried to give 9.5 g of 1 S 5 R - Hydrated pinol (94.9% yield, 98.9% ee). The resulting ( S Sodium 3-cyclohexene-1-carboxylate was acidified with 1N hydrochloric acid (160 mL) to give 7.1 g ( S 3-Cyclohexene-1-carboxylic acid. ZrO₂-SO₄ recovered. 2- and( S 3-Cyclohexene-1-carboxylic acid can be repeatedly recycled. Example 6

[0032] Select a 100 mL reaction flask and add 10.0 g of trans-hydrated pinene alcohol (20% ee), dissolved in 20 mL of methyl tert-butyl ether. Then add 0.1 g of Fe3O4@SiO2-SO3H and 14.6 g ( S Ibuprofen (1.2 equiv.). The reaction system was stirred at 58 °C, and a water separator was installed to remove the generated water. Samples were taken periodically, and the reaction progress was monitored by chiral gas chromatography (GC). After 10 hours of reaction, the content of hydrated pinol in the reaction solution was detected to be <3%, and the reaction was stopped.

[0033] Post-reaction processing: The reaction solution was cooled to room temperature, and 0.096 g of Fe3O4@SiO2-SO3H was recovered by magnetic separation. The filtrate was subjected to vacuum distillation to recover methyl tert-butyl ether and obtain 18.5 g of hydrated pinene ester. Then, 1N sodium hydroxide solution (120 mL) was added to the ester, and hydrolysis was carried out with stirring at room temperature. A large amount of white solid precipitated, which was filtered and dried to obtain 8.7 g of 1 S 5 R - Hydrated pinol (86.9% yield, 99.1% ee). The resulting ( S Ibuprofen sodium salt was acidified with 1N hydrochloric acid (160 mL) to give 10.4 g ( S )-Ibuprofen. The recovered Fe3O4@SiO2-SO3H and ( S Ibuprofen is recyclable. Example 7

[0034] Select a 100 mL reaction flask and add 10.0 g of trans-hydrated pineneol (20% ee), dissolved in 20 mL of ethyl acetate. Then add 0.1 g of WO3 / ZrO2 solid acid and 13.0 g (1 R ,2 S 5 R 2-Isopropyl-5-methylcyclohexanecarboxylic acid (1.2 equiv.). The reaction system was stirred at 78 °C, and a water separator was installed to remove the generated water. Samples were taken periodically, and the reaction progress was monitored by chiral gas chromatography (GC). After 9 hours of reaction, the content of hydrated pinol in the reaction solution was detected to be <3%, and the reaction was stopped.

[0035] Post-reaction processing: The reaction solution was cooled to room temperature, and 0.093 g of WO3 / ZrO2 solid acid was separated by filtration. The filtrate was subjected to vacuum distillation to recover ethyl acetate and obtain 18.6 g of pinene hydrate. Subsequently, 1N sodium hydroxide solution (120 mL) was added to the ester, and hydrolysis was carried out with stirring at room temperature. A large amount of white solid precipitated, which was filtered and dried to obtain 9.2 g of 1 S 5R - Hydrated pinol (91.9% yield, 85% ee). The resulting (1) R ,2 S 5 R Sodium 2-isopropyl-5-methylcyclohexanecarboxylate was acidified with 1N hydrochloric acid (160 mL) to give 10.0 g (1 R ,2 S 5 R )-2-isopropyl-5-methylcyclohexanecarboxylic acid. The recovered WO3 / ZrO2 solid acid and (1 R ,2 S 5 R 2-Isopropyl-5-methylcyclohexanecarboxylic acid can be repeatedly recycled. Example 8

[0036] A 100 mL reaction flask was selected, and 10.0 g of trans-hydrated pinene alcohol (20% ee) was added, dissolved in 20 mL of cyclopentyl methyl ether. Subsequently, 0.1 g of sulfonated biochar and 13.0 g of pinone acid (1.2 equiv.) were added. The reaction system was stirred at 110 °C, and a water separator was installed to remove the generated water. Samples were taken periodically, and the reaction progress was monitored by chiral gas chromatography (GC). After 8 hours of reaction, the content of hydrated pinene alcohol in the reaction solution was detected to be <3%, and the reaction was stopped.

[0037] Post-reaction processing: The reaction solution was cooled to room temperature, and 0.098 g of sulfonated biochar was separated by filtration. The filtrate was subjected to vacuum distillation to recover cyclopentyl methyl ether and obtain 19.1 g of hydrated pinene ester. Then, 1N sodium hydroxide solution (120 mL) was added to the ester, and hydrolysis was carried out with stirring at room temperature. A large amount of white solid precipitated out, which was filtered and dried to obtain 9.5 g of 1 S 5 R - Hydrated pinene alcohol (94.9% yield, 98.0% ee). The resulting sodium pinone was acidified with 1N hydrochloric acid (160 mL) to give 10.1 g of pinene acid. The recovered sulfonated biochar and pinene acid can be recycled. Example 9

[0038] A 100 mL reaction flask was selected, and 20 mL of cyclopentyl methyl ether (distilled under reduced pressure in Example 8), 10.0 g of trans-hydrated pineneol (20% ee) were added. Then, 0.1 g of sulfonated biochar (filtered in Example 8) and 13.0 g of recovered pinone acid (1.2 equiv.) were added. The reaction system was stirred at 110 °C, and a water separator was installed to remove the generated water. Samples were taken periodically, and the reaction progress was monitored by chiral gas chromatography (GC). After 8 hours of reaction, the content of hydrated pineneol in the reaction solution was detected to be <3%, and the reaction was stopped.

[0039] Post-reaction processing: The reaction solution was cooled to room temperature, and 0.097 g of sulfonated biochar was separated by filtration. The filtrate was subjected to vacuum distillation to recover cyclopentyl methyl ether and obtain 19.0 g of hydrated pinene ester. Then, 1N sodium hydroxide solution (120 mL) was added to the ester, and hydrolysis was carried out with stirring at room temperature. A large amount of white solid precipitated, which was filtered and dried to obtain 9.5 g of 1 S 5 R - Hydrated pinene alcohol (94.9% yield, 98.0% ee). The resulting sodium pinone was acidified with 1N hydrochloric acid (160 mL) to give 10.2 g of pinone acid. The recovered sulfonated biochar and pinone acid can be recycled.

[0040] Comparative Example 1 In this comparative example, conventional non-chiral carboxylic acid-phenylpropionic acid (10.6 g, 1.2 equiv.) was used instead of the one used in Example 1. S 2-Phenylacetic acid was used, and other operations were the same as in Example 1, which will not be repeated here. The reaction progress was monitored by chiral gas chromatography (GC). After 8 hours of reaction, the content of hydrated pinol in the reaction solution was detected to be <3%, and the reaction was stopped. After the same post-processing as in Example 1, 8.5 g of hydrated pinol was finally obtained, with a yield of 85.0% and an ee value of only 2%, which did not show dynamic kinetic separation effect.

[0041] Comparative Example 2 In this comparative example, the conventional acid catalyst H3PW was used. 12 O 40 Instead of the solid acid catalyst H3PW in Example 2 12 O 40 The reaction proceeded using SiO2, and other operations were the same as in Example 2, and will not be repeated here. The reaction progress was monitored by chiral gas chromatography (GC). After 8 hours of reaction, the hydrated pinol content in the reaction solution was detected to be 15%. After the same post-processing as in Example 2, 8.6 g of hydrated pinol was finally obtained, with an ee value of 81%. Compared with solid acid catalysts, the conversion rate was lower, but it still showed a certain dynamic kinetic resolution effect; meanwhile, the conventional acid catalyst H3PW... 12 O 40 Effective recycling is difficult to achieve.

[0042] The above description of the embodiments is only for illustrating the technical concept and features of the present invention. Its purpose is to enable those skilled in the art to understand the content of the present invention and implement it accordingly. Those skilled in the art can obviously easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative effort. Therefore, the above embodiments should not be used to limit the scope of protection of the present invention. All improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A method for obtaining 1S,5R-hydrated pinol from trans-hydrated pinol via chiral carboxylic acid-mediated dynamic kinetic resolution, characterized in that, Includes the following steps: Trans-hydrated pinol, chiral carboxylic acid, and a solid acid catalyst were dissolved in a solvent and stirred at a suitable temperature to allow the trans-hydrated pinol to undergo selective esterification, generating a chiral ester intermediate. Unreacted trans-hydrated pinol underwent rapid racemization. The reaction process was monitored by chiral gas chromatography. After the reaction was completed, the solid acid catalyst was recovered by filtration. The filtrate was then subjected to vacuum distillation to separate the chiral ester product and recover the solvent. The chiral ester was further hydrolyzed in an alkaline system to obtain optically pure 1S,5R-hydrated pinol, and the chiral carboxylic acid was recovered.

2. The method for obtaining 1S,5R-hydrated pinol by chiral carboxylic acid-mediated dynamic kinetic resolution of trans-hydrated pinol according to claim 1, characterized in that: The trans-hydrated pinol is a racemic or low-enantioselective trans-hydrated pinol with 0-60% ee.

3. The method for obtaining 1S,5R-hydrated pinol by chiral carboxylic acid-mediated dynamic kinetic resolution of trans-hydrated pinol according to claim 1, characterized in that: The chiral carboxylic acid is one or a mixture of two or more of the following: (S)-2-phenylpropionic acid, (S)-2-phenylbutyric acid, (S)-1,2,3,4-tetrahydro-1-naphthoic acid, (S)-ibuprofen, (S)-naproxen, (S)-ketoprofen, (S)-2-methylbutyric acid, (S)-3-cyclohexene-1-carboxylic acid, (1R,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxylic acid, or pinone acid.

4. The method for obtaining 1S,5R-hydrated pinol by chiral carboxylic acid-mediated dynamic kinetic resolution of trans-hydrated pinol according to claim 1, characterized in that: The solid acid catalyst is Amberlyst-15 or H3PW. 12 O 40 One or more of the following: SiO2, sulfonated graphene, H-ZSM-5, sulfated zirconium oxide, WO3 / ZrO2 solid acid, Fe3O4@SiO2-SO3H, or sulfonated biochar.

5. The method for obtaining 1S,5R-hydrated pinol by chiral carboxylic acid-mediated dynamic kinetic resolution of trans-hydrated pinol according to claim 1, characterized in that: The solvent is one or a mixture of two or more of the following: cyclopentyl methyl ether, isopropyl ether, methyl tert-butyl ether, benzene, toluene, xylene, cyclohexane, n-hexane, or ethyl acetate.

6. The method for obtaining 1S,5R-hydrated pinol by chiral carboxylic acid-mediated dynamic kinetic resolution of trans-hydrated pinol according to claim 1, characterized in that: The mass ratio of the solid acid catalyst to trans-hydrated pinol is 1:50-100; the molar ratio of the chiral carboxylic acid to trans-hydrated pinol is 1-2:

1.

7. The method for obtaining 1S,5R-hydrated pinol by chiral carboxylic acid-mediated dynamic kinetic resolution of trans-hydrated pinol according to claim 1, characterized in that: The reaction temperature is 40-120 ℃.

8. The method for obtaining 1S,5R-hydrated pinol by chiral carboxylic acid-mediated dynamic kinetic resolution of trans-hydrated pinol according to claim 1, characterized in that: The alkaline system is an aqueous solution of potassium hydroxide, sodium hydroxide, or lithium hydroxide.

9. The method for obtaining 1S,5R-hydrated pinol by chiral carboxylic acid-mediated dynamic kinetic resolution of trans-hydrated pinol according to claim 1, characterized in that: The recovered solid acid catalysts and chiral carboxylic acids can be reused.

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