Preparation methods of glyoxylic acid L-menthyl alcohol ester and monohydrate of glyoxylic acid L-menthyl alcohol ester

A technology of menthol esters and glyoxylic acid, applied in the preparation of carboxylic acid halides, organic chemistry, etc., can solve the problems of explosion safety hazards, high prices, and ineffectiveness, and achieve mild reaction conditions, less reaction side reactions, and excellent operating techniques easy effect

Active Publication Date: 2012-06-27
ZHEJIANG XIANFENG TECH +1
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AI Technical Summary

Problems solved by technology

[0005] (1) After esterification of L-menthol with bromoacetyl bromide, bromoacetyl L-menthol ester was obtained, and then reacted with AgNO 3 The reaction generates nitrate, and finally reacts with sodium acetate to obtain the product L-menthyl glyoxylate (J. Org. Chem., 1986, 51, 4479; Tetrohedron, 1986, 42, 2993.), but the technical route reagent is expensive , low product yield, not suitable for industrial production
[0006] (2) Reaction of fumaric acid with thionyl chloride to convert it into acid chloride, and then synthesize dimenthyl fumarate with L-menthol under the action of alkali, and then oxidize with potassium permanganate to obtain dimenthyl tartrate , and then oxidized with periodic acid to generate L-menthyl glyoxylate; or directly react tartaric acid with L-menthol to synthesize dimenthyl tartrate, and then oxidize with periodic acid to generate L-menthyl glyoxylate Menthyl esters (Synthetic Commun., 1990, 20, 2837), but the reagents used in this technical route are also expensive and the product yield is low
The disadvantage of this method is that the preparation of monomenthyl maleate sodium salt is difficult and the ozonolysis operation is complicated, and both ozone and peroxide-containing ozonolysis products have potential safety hazards of explosion.
[0008] (4) Reaction of L-menthol with oxalyl chloride to form monomenthyl oxalyl chloride, and then reducing the acid chloride to aldehyde with tributyltin hydrogen to obtain L-menthyl glyoxylate (J. Org. Chem. 1970, 35, 3691; Synthesis, 1998, 11:1590-1592); the disadvantage of this method is that the reducing agent tributyltin hydrogen is highly toxic and expensive
(2) DMSO converts gem-dihalogenated benzyl compounds into corresponding aromatic aldehydes under high temperature conditions (Tetrahedron Lett., 2004, 45, 1071; Russ. J. Org. Chem. 2010, 46, 706), the same method Essentially ineffective against halogenated non-benzyl aliphatics

Method used

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  • Preparation methods of glyoxylic acid L-menthyl alcohol ester and monohydrate of glyoxylic acid L-menthyl alcohol ester
  • Preparation methods of glyoxylic acid L-menthyl alcohol ester and monohydrate of glyoxylic acid L-menthyl alcohol ester
  • Preparation methods of glyoxylic acid L-menthyl alcohol ester and monohydrate of glyoxylic acid L-menthyl alcohol ester

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Experimental program
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Effect test

Embodiment 1

[0035] Embodiment 1: Preparation of L-menthyl monochloroacetate (Ⅲ)

[0036] Add L-menthol (15.6g, 0.1mol), pyridine (8.6g, 0.11mol) and dichloromethane (200mL) to the reaction flask equipped with a stirrer, start stirring and cool with ice-salt bath, and add to the reaction flask A solution of chloroacetyl chloride (12.4g, 0.11mol) in dichloromethane (50mL) was slowly added dropwise to the bottle, and the drop was completed within 2 hours. The menthol disappeared, and the obtained white suspension was filtered, and the filtrate was washed with dilute hydrochloric acid (80mL, 2N), saturated aqueous sodium bicarbonate solution (80mL) and saturated brine (100mL), then dried over anhydrous sodium sulfate, and finally evaporated. The solvent dichloromethane was removed to obtain 22.3 g of L-menthyl chloroacetate as a colorless transparent liquid, with a yield of 95%.

Embodiment 2

[0037] Embodiment 2: Preparation of L-menthyl monobromoacetate (Ⅲ)

[0038] Add L-menthol (15.6g, 0.1mol), pyridine (8.2g, 0.105mol) and dichloromethane (200mL) into the reaction flask equipped with a stirrer, start stirring and cool the reaction system in an ice-salt bath to 0 o C. Slowly add a solution of bromoacetyl bromide (22g, 0.11mol) in dichloromethane (50mL) dropwise to the reaction flask, drop it over within 2 hours, then place the reaction system at room temperature for 1.5 hours, monitor with TLC until The raw material L-menthol disappeared, and the obtained white suspension was filtered, and the filtrate was washed with dilute hydrochloric acid (80mL, 2N), saturated aqueous sodium bicarbonate solution (80mL) and saturated brine (100mL), and then dried over anhydrous sodium sulfate , Distilled off the solvent methylene chloride to obtain 26.7 g of L-menthyl bromoacetate as a colorless transparent liquid, with a yield of 96%.

Embodiment 3

[0039] Example 3: Preparation of L-menthyl chloroacetate (Ⅲ) from chloroacetic anhydride

[0040] Add L-menthol (15.6g, 0.1mol), pyridine (8.6g, 0.11mol) and dichloromethane (200mL) to the reaction flask equipped with a stirrer, and then add chloroacetic anhydride (25.7g, 0.15 mol) was slowly added, stirred at room temperature until the raw material L-menthol disappeared, then the solvent was removed, dichloromethane was added to the obtained oil, washed with saturated aqueous sodium bicarbonate (80mL) and saturated brine (100mL), organic The phase was dried by adding anhydrous sodium sulfate, the desiccant was filtered off, and the solvent was evaporated to obtain 21.0 g of L-menthyl chloroacetate with a yield of 92%.

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Abstract

The invention relates to preparation methods of glyoxylic acid L-menthyl alcohol ester and a monohydrate of the glyoxylic acid L-menthyl alcohol ester, and belongs to the technical field of fine chemical industry. The glyoxylic acid L-menthyl alcohol ester is prepared by the following steps: reacting L-menthol with monohalogen or dihalogen acetyl halide or anhydride to generate monohalogen or dihalogen acetic acid L-menthyl alcohol ester; and reacting in the presence of a pro-oxidant to obtain the glyoxylic acid L-menthyl alcohol ester. The monohydrate of the glyoxylic acid L-menthyl alcohol ester is prepared by the following steps: cooling and diluting a reaction solution using monohalogen acetic acid L-menthyl alcohol ester as a raw material; treating by using a dimethylsulfoxide (DMSO) solution of P2O5 and triethylamine to obtain the glyoxylic acid L-menthyl alcohol ester; washing, extracting and concentrating a reaction solution using dihalogen acetic acid L-menthyl alcohol ester as a raw material to obtain the glyoxylic acid L-menthyl alcohol ester; and treating by using sodium hydrogen sulfite and formaldehyde to obtain the monohydrate of the glyoxylic acid L-menthyl alcohol ester. The total yield of the glyoxylic acid L-menthyl alcohol ester synthesized by the technology can reach over 72 percent; the total yield of the monohydrate of the glyoxylic acid L-menthyl alcohol ester can reach over 80 percent; the purity can reach over 99.5 percent; the technical process is simple and convenient; the raw materials are available; the yield is high; the product purity is high; and the process is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of fine chemicals, and in particular relates to a preparation method of L-menthyl glyoxylate and its monohydrate suitable for industrial production. Background technique [0002] L-menthyl glyoxylate and its hydrate (structural formula IV) are important chiral compounds, which are important for the industrial production of chiral drugs lamivudine (structural formula V) and emtricitabine (structural formula VI). Intermediates are also an important chiral source compound in chiral synthesis. [0003] [0004] The synthetic technology method of the glyoxylate L-menthyl ester and its monohydrate reported in the literature mainly includes: [0005] (1) After esterification of L-menthol with bromoacetyl bromide, bromoacetyl L-menthol ester was obtained, and then reacted with AgNO 3 The reaction generates nitrate, and finally reacts with sodium acetate to obtain the product L-menthyl glyoxylate (J. Org. Chem.,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C69/67C07C69/675C07C67/14
Inventor 李凤军邹刚高飞飞吴世刚刘文高王荣华
Owner ZHEJIANG XIANFENG TECH
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