CN112239421A

CN112239421A - Method for synthesizing L-homocystine

Info

Publication number: CN112239421A
Application number: CN202011231604.9A
Authority: CN
Inventors: 姚胜宇; 陈荣; 徐慧; 丁海宏
Original assignee: Jiangsu Baozong & Baoda Pharmachem Co ltd
Current assignee: Jiangsu Baozong & Baoda Pharmachem Co ltd
Priority date: 2020-11-06
Filing date: 2020-11-06
Publication date: 2021-01-19

Abstract

The invention relates to a synthetic method of L-homocystine; the synthesis method comprises the following steps: 1) adding L-methionine into a reaction bottle, directly adding 40% hydrobromic acid into the reaction bottle, heating to 90-100 ℃, dropwise adding acetic acid into the reaction bottle, and keeping the temperature for 20 hours at the temperature after dropwise adding; the mol ratio of the L-methionine, the 40% hydrobromic acid and the acetic acid is as follows: 1:3-5: 2.5-4; the reaction equation is as follows:

Description

Method for synthesizing L-homocystine

Technical Field

The invention relates to the field of medicines, in particular to a method for synthesizing L-homocystine.

Background

The common production mode is that L-methionine is heated in mixed acid (sulfuric acid and hydrobromic acid) to remove two molecules of methyl to form L-homocystine. In the production process, in addition to the absorption and control of the tail gas, the salts such as sodium sulfate, sodium bromide and the like generated by the tail gas are also removed.

Disclosure of Invention

The invention provides a synthetic method of L-homocystine.

Technical scheme of the invention

A method for synthesizing L-homocystine; the synthesis method comprises the following steps:

1) adding L-methionine into a reaction bottle, directly adding 40% hydrobromic acid into the reaction bottle, heating to 90-100 ℃, dropwise adding acetic acid into the reaction bottle, and keeping the temperature for 20 hours at the temperature after dropwise adding; the mol ratio of the L-methionine, the 40% hydrobromic acid and the acetic acid is as follows: 1:3-5: 2.5-4; the reaction equation is as follows:

。

2) after reduced pressure distillation, firstly adding a proper amount of water into a reaction bottle, then adding liquid caustic soda into the reaction bottle, and carrying out pH adjustment to generate sodium acetate and separate out a crude product of L-homocystine.

3) And pulping the crude L-homocystine twice by using hot water to obtain the high-purity L-homocystine.

The reaction bottle is a three-necked bottle, a thermometer, a condenser pipe and a constant-pressure dropping funnel are arranged on the reaction bottle, and the condenser pipe is sequentially connected with a buffer bottle and a two-stage alkali liquor absorption device through a hose; the alkali liquor absorption device is an absorption bottle filled with alkali liquor; in the step 2), the distilled methyl acetate, the excessive hydrobromic acid and the acetic acid are absorbed by an alkali liquor absorption device.

Sampling and detecting after the step 1) and before the step 2), and judging the reaction progress.

The invention has the advantages of reasonable design and simple structure, and the conversion rate of the L-homocystine is about 81.6-90.1% by adopting the synthesis method, and the conversion rate is high; and reduced pressure distillation is adopted in cooperation, so that methyl acetate, excessive hydrobromic acid and acetic acid can be easily removed.

Detailed Description

Example 1:

A1L three-necked bottle (containing a thermometer, a condenser tube and a constant pressure dropping funnel) is prepared, a buffer bottle and a two-stage alkali liquor absorption device are connected above the condenser tube. Adding L-methionine (100 g, 0.67 mol) into a reaction bottle, directly adding 40% hydrobromic acid (340 g, 1.68 mol) into the reaction bottle, heating to 90 ℃, dropwise adding acetic acid (201 g, 3.35 mol) into the reaction solution, keeping the temperature for 20 hours at the temperature after dropwise adding, sampling and controlling, wherein the conversion rate of L-homocystine is about 81.6% on a liquid phase HPLC (high performance liquid chromatography) chart, the residual 8.4% of raw material L-methionine and the impurity (desulfhydryl methyl) accounts for about 5.6%. About 31.2g of L-homocystine was obtained by the post-treatment.

Example 2:

A1L three-necked bottle (containing a thermometer, a condenser tube and a constant pressure dropping funnel) is prepared, a buffer bottle and a two-stage alkali liquor absorption device are connected above the condenser tube. Adding L-methionine (100 g, 0.67 mol) into a reaction bottle, directly adding 40% hydrobromic acid (340 g, 1.68 mol) into the reaction bottle, heating to 100 ℃, dropwise adding acetic acid (201 g, 3.35 mol) into the reaction solution, keeping the temperature for 20 hours at the temperature after dropwise adding, sampling and controlling, wherein the conversion rate of L-homocystine is about 86.6% on a liquid phase HPLC (high performance liquid chromatography) chart, the residual 2.4% of raw material L-methionine and the impurity (desulfhydryl methyl) accounts for about 4.6%. About 41.5g of L-homocystine was obtained by the post-treatment.

Example 3:

A1L three-necked bottle (containing a thermometer, a condenser tube and a constant pressure dropping funnel) is prepared, a buffer bottle and a two-stage alkali liquor absorption device are connected above the condenser tube. Adding L-methionine (100 g, 0.67 mol) into a reaction bottle, directly adding 40% hydrobromic acid (340 g, 1.68 mol) into the reaction bottle, heating to 100 ℃, dropwise adding acetic acid (120.6 g, 2.01 mol) into the reaction solution, after dropwise adding, keeping the temperature for 20 hours at the temperature, sampling and controlling, wherein the conversion rate of L-homocystine is about 83.1% on a liquid phase HPLC (high performance liquid chromatography) chart, the residual 3.6% of raw material L-methionine and the impurity (desulfhydrylmethyl) accounts for about 5.3%. About 38.5g of L-homocystine was obtained by the post-treatment.

Example 4:

A1L three-necked bottle (containing a thermometer, a condenser tube and a constant pressure dropping funnel) is prepared, a buffer bottle and a two-stage alkali liquor absorption device are connected above the condenser tube. Adding L-methionine (100 g, 0.67 mol) into a reaction bottle, directly adding 40% hydrobromic acid (542.7 g, 2.68 mol) into the reaction bottle, heating to 100 ℃, dropwise adding acetic acid (120.6 g, 2.01 mol) into the reaction solution, after dropwise adding, keeping the temperature for 20 hours at the temperature, sampling and controlling, wherein the conversion rate of L-homocystine is about 90.1% on a liquid phase HPLC (high performance liquid chromatography) chart, the raw material L-methionine is remained for 2.6%, and impurities (desulfomethyl) account for about 4.1%. About 37.5g of L-homocystine was obtained by the post-treatment.

Because of the limited character expression, there exist practically unlimited specific structures, and it will be apparent to those skilled in the art that a number of improvements, decorations, or changes may be made without departing from the principles of the present invention, or the above technical features may be combined in a suitable manner; such modifications, variations, combinations, or adaptations of the invention using its spirit and scope, as defined by the claims, may be directed to other uses and embodiments.

Claims

1. A method for synthesizing L-homocystine; the synthesis method is characterized by comprising the following steps:

adding L-methionine into a reaction bottle, directly adding 40% hydrobromic acid into the reaction bottle, heating to 90-100 ℃, dropwise adding acetic acid into the reaction bottle, and keeping the temperature for 20 hours at the temperature after dropwise adding; the mol ratio of the L-methionine, the 40% hydrobromic acid and the acetic acid is as follows: 1:3-5: 2.5-4; the reaction equation is as follows:

；

after reduced pressure distillation, firstly adding a proper amount of water into a reaction bottle, then adding liquid caustic soda into the reaction bottle, and carrying out pH adjustment to generate sodium acetate and precipitate crude L-homocystine;

and pulping the crude L-homocystine twice by using hot water to obtain the high-purity L-homocystine.

2. The method for synthesizing L-homocystine according to claim 1, characterized in that the reaction flask is a three-necked flask, on which a thermometer, a condenser tube and a constant pressure dropping funnel are mounted, the condenser tube is connected with a buffer flask and a two-stage alkali liquor absorption device in sequence through a hose; the alkali liquor absorption device is an absorption bottle filled with alkali liquor; in the step 2), the distilled methyl acetate, the excessive hydrobromic acid and the acetic acid are absorbed by an alkali liquor absorption device.

3. The method for synthesizing L-homocystine according to claim 1, characterized in that after step 1) and before step 2), a sample is taken for detection to determine the progress of the reaction.