Method for preparing menthol glucoside
Through the dehydration and condensation of tetrabenzyl-protected glucose and menthol under Lewis acid catalysis, combined with the Pd catalyst and H2 hydrogenation steps, the preparation process of menthol glucoside is simplified, the defects in the volatility and chemical synthesis methods of menthol in the prior art are solved, and efficient and economical preparation effects are achieved.
Patent Information
- Application Number
- CN202510024260.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-07
- Publication Date
- 2025-04-15
AI Technical Summary
In the prior art, menthol is volatile and has poor water solubility, which hinders its larger-scale application. In addition, chemical synthesis methods have problems such as poor stability of bromine sugar, toxic or expensive catalysts, and long reaction steps, making it difficult to develop a green, safe and low-cost synthesis route.
Tetrabenzyl-protected glucose and menthol were dehydrated and condensed under Lewis acid catalysis to form tetrabenzyl-protected menthol glucoside, and the tetrabenzyl protecting group was detached by Pd catalyst and H2 hydrogenation, simplifying the preparation process.
It realizes simple preparation of menthol glucoside, short reaction route, high efficiency, good economic benefits, simple and cheap raw materials and reagents, suitable for large-scale production.
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Abstract
Description
Technical Field
[0001] The present invention relates to the field of menthol preparation, and more particularly to a method for preparing menthol glucoside. Background Art
[0002] Menthol is in great demand and is widely used in tobacco, medicine, food, cosmetics and other fields. However, L-menthol is volatile and poorly water-soluble, which hinders its larger-scale application. Glycosylation can effectively make up for the above defects. Plants contain menthol glucoside, but its content is very low and the cost of natural extraction is expensive. In the chemical synthesis method, brominated sugars have poor stability, toxic mercury salts or expensive silver salts, or sulfhydryl groups (smell) need to be introduced, the yield is not high, and the reaction steps are too long. Therefore, a green, safe and low-cost synthesis route needs to be developed. Summary of the invention
[0003] In order to overcome the deficiencies of the prior art, the present invention provides a method for preparing menthol glucoside.
[0004] To achieve the above object, the present invention provides the following technical solution: a method for preparing menthol glucoside, characterized in that the method comprises the following steps: using tetrabenzyl-protected glucose and menthol as starting materials, undergoing dehydration condensation under the catalysis of Lewis acid to form tetrabenzyl-protected menthol glucoside, and driving the reaction by benzene or toluene, catalyzing the tetrabenzyl-protected menthol glucoside with a Pd catalyst and H 2 Hydrogenation removes the tetrabenzyl protecting group to produce menthol glucoside. The specific chemical reaction formula is as follows:
[0005]
[0006] As a preferred technical solution of the present invention, the usage ratio of tetrabenzyl-protected glucose and menthol is 1:(0.5-1), and the usage ratio of menthol and Lewis acid is (5-1000):1.
[0007] As a preferred technical solution of the present invention, the Lewis acid is one or more of Sc(OTf)3, Zn(OTf)2, and In(OTf)3.
[0008] As a preferred technical solution of the present invention, the reaction temperature of benzene in the dehydration condensation step is (100-120)°C, and the reaction temperature of toluene in the dehydration condensation step is (110-140)°C.
[0009] As a preferred technical solution of the present invention, the Pd catalyst is one of supported Pd, Pd metal powder, ligand-coordinated Pd complex, and Pd salt, and the ratio of the Pd catalyst to the tetrabenzyl-protected menthol glucoside is 1:(10-100000).
[0010] As a preferred technical solution of the present invention, H 2 During hydrogenation, H 2 The pressure is (1~100)atm.
[0011] As a preferred technical solution of the present invention, the tetrabenzyl protecting group is catalyzed by Pd catalyst and H 2 The temperature during hydrogenation is (0~100)℃.
[0012] Compared with the prior art, the present invention has the following beneficial effects: tetrabenzyl-protected glucose is condensed with menthol to construct tetrabenzyl-protected menthol glucoside, and the menthol glucoside is synthesized by Pd / C and H 2 Menthol glucoside can be easily prepared by removing the tetrabenzyl protecting group in two steps under mild hydrogenation conditions. The reaction route is short, the efficiency is high, and the economic benefit is good. The raw materials and reagents are simple, cheap and easy to obtain. The reaction steps are short, the yield is high, and the separation is easy, which is suitable for large-scale production. DETAILED DESCRIPTION
[0013] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.
[0014] Example 1
[0015] A method for preparing menthol glucoside, characterized in that tetrabenzyl-protected glucose and menthol are used as starting materials, dehydration condensation is carried out under the catalysis of Lewis acid to form tetrabenzyl-protected menthol glucoside, and the reaction is driven by benzene or toluene, and the tetrabenzyl-protected menthol glucoside is catalyzed by Pd catalyst and H 2 Hydrogenation removes the tetrabenzyl protecting group to produce menthol glucoside. The specific chemical reaction formula is as follows:
[0016]
[0017] Furthermore, the ratio of the tetrabenzyl-protected glucose to menthol is 1:(0.5-1), and the ratio of menthol to Lewis acid is (5-1000):1.
[0018] Furthermore, the Lewis acid is one or more of Sc(OTf)3, Zn(OTf)2, and In(OTf)3, preferably Sc(OTf)3.
[0019] Furthermore, the reaction temperature of benzene in the dehydration condensation step is (100-120)°C, and the reaction temperature of toluene in the dehydration condensation step is (110-140)°C.
[0020] Furthermore, the Pd catalyst is one of supported Pd, Pd metal powder, ligand-coordinated Pd complex, and Pd salt, preferably supported Pd, and Pd / C is selected. Pd / C is a common palladium catalyst, and the C in its abbreviation represents activated carbon as a carrier. Pd / C has high catalytic activity and fine particle size, and is widely used in reduction reactions and carbonylation reactions in the field of organic synthesis.
[0021] The dosage ratio of the Pd catalyst to the tetrabenzyl protected menthol glucoside is 1:(10-100000).
[0022] Furthermore, H 2 During hydrogenation, H 2 The pressure is (1~100)atm.
[0023] Furthermore, the tetrabenzyl protecting group was catalyzed by Pd and H 2 The temperature during hydrogenation is (0~100)℃.
[0024] Tetrabenzyl-protected menthol glucoside was constructed by condensation of tetrabenzyl-protected glucose and menthol. 2 Menthol glucoside can be simply prepared by removing the tetrabenzyl protecting group in two steps under mild hydrogenation conditions. The reaction route is short, the efficiency is high, and the economic benefit is good. The raw materials and reagents are simple, cheap and easy to obtain. The reaction steps are short, the yield is high, and the separation is easy, which is suitable for large-scale production.
[0025] Example 2
[0026] Tetrabenzyl-protected glucose and menthol were used as starting materials. Dehydration condensation occurred under the catalysis of Sc(OTf)3 to form tetrabenzyl-protected menthol glucoside. The reaction was driven by benzene or toluene. Tetrabenzyl-protected menthol glucoside was catalyzed by Pd / C and H 2 Hydrogenation removes the tetrabenzyl protecting group to produce menthol glucoside. The specific chemical reaction formula is as follows:
[0027]
[0028] Furthermore, the ratio of the tetrabenzyl-protected glucose to menthol is 1:(0.5-1), and the ratio of menthol to Sc(OTf)3 is (5-1000):1.
[0029] Furthermore, the reaction temperature of benzene in the dehydration condensation step is (100-120)°C, and the reaction temperature of toluene in the dehydration condensation step is (110-140)°C.
[0030] Furthermore, the ratio of Pd / C to tetrabenzyl protected menthol glucoside is 1:(10-100000).
[0031] Furthermore, H 2 During hydrogenation, H 2 The pressure is (1~100)atm.
[0032] Furthermore, the tetrabenzyl protecting group was catalyzed by Pd / C and H 2 The temperature during hydrogenation is (0~100)℃.
[0033] Preparation of Tetrabenzyl-Protected Menthol Glucoside
[0034] 20 mmol of tetrabenzyl protected glucose and 20 mmol of menthol were dissolved in 150 mL of benzene, 1 mmol of Sc(OTf)3 was added, and the mixture was heated, stirred, refluxed and water was separated. After 15 h, about 3.5 mL of water was collected and the reaction was stopped. The solvent was removed by rotation, and the mixture was separated by PE / EA column chromatography to obtain 86% of tetrabenzyl protected menthol glucoside, specifically 11.677 g. The specific reaction formula is as follows:
[0035]
[0036] Preparation by removal of tetrabenzyl protecting group
[0037] Select a 200 mL reactor, dissolve 10 mmol of tetrabenzyl protected menthol glucoside in 50 mL of methanol and 50 mL of ethyl acetate, add 0.5 mmol of 10 w% Pd / C, and pass 10 atm of H 2 Replace three times and fill with 30atm H 2 , control the temperature at 50 °C and stir overnight, carefully releasing excess H 2 , filter to remove Pd / C, spin off the solvent, and recrystallize in ethyl acetate to obtain 90% menthol glucoside, specifically 2.866 g.
[0038]
[0039] It should be noted that: 10w% means the mass fraction is 10%, that is, the mass of the solute accounts for 10% of the total mass of the solution;
[0040] PE / EA column chromatography separation is a commonly used chemical separation technology, mainly used to separate and purify organic compounds. PE (petroleum ether) and EA (ethyl acetate) are two commonly used solvents with different polarities. The polarity of the mixed solvent can be changed by adjusting their ratio to meet the separation requirements of different compounds.
[0041] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.
[0042] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.
Claims
1. A method for preparing menthol glucoside, characterized in that: The method comprises the following steps: using tetrabenzyl-protected glucose and menthol as starting materials, performing dehydration condensation under the catalysis of Lewis acid to form tetrabenzyl-protected menthol glucoside, and driving the reaction by benzene or toluene, and removing the tetrabenzyl protecting group from the tetrabenzyl-protected menthol glucoside by catalysis of Pd catalyst and H2 hydrogenation to prepare menthol glucoside. The specific chemical reaction formula is as follows:
2. A method for preparing menthol glucoside according to claim 1, characterized in that: The usage ratio of tetrabenzyl protected glucose and menthol is 1:(0.5-1), and the usage ratio of menthol and Lewis acid is (5-1000):
1.
3. A method for preparing menthol glucoside according to claim 1, characterized in that: The Lewis acid is one or more of Sc(OTf)3, Zn(OTf)2, and In(OTf)3.
4. A method for preparing menthol glucoside according to claim 1, characterized in that: The reaction temperature of benzene in the dehydration condensation step is (100-120)°C, and the reaction temperature of toluene in the dehydration condensation step is (110-140)°C.
5. A method for preparing menthol glucoside according to claim 1, characterized in that: The Pd catalyst is one of supported Pd, Pd metal powder, ligand-coordinated Pd complex and Pd salt. The dosage ratio of the Pd catalyst to the tetrabenzyl-protected menthol glucoside is 1:(10-100000).
6. A method for preparing menthol glucoside according to claim 1, characterized in that: The pressure of H2 during H2 hydrogenation is (1~100)atm. A method for preparing menthol glucoside according to claim 1, characterized in that: The temperature for removing the tetrabenzyl protecting group by Pd catalyst and H2 hydrogenation is (0-100)°C.