阅读说明：本技术 一种2,2’-二硫代二乙胺二盐酸盐的合成方法 (Synthesis method of 2, 2' -dithiodiethylamine dihydrochloride ) 是由 贺斌 于 2021-09-15 设计创作，主要内容包括：本发明属于医药化工技术领域,具体涉及一种2,2’-二硫代二乙胺二盐酸盐的合成方法,将2-氨基乙硫醇盐酸盐、氧化剂和催化剂加入至反应溶剂中；在催化剂作用下并升温至40～90℃进行氧化反应；随着氧化反应的进行,底物逐渐减少,产物逐渐增多,产物在反应溶剂中逐渐析晶,反应4-10h后,冷却至室温,继续析晶2～3h,经过滤、洗涤和干燥得2,2’-二硫代二乙胺二盐酸盐；对环境污染小,母液可多次进行套用,三废量少,适用于大规模生产。反应条件温和,氧化剂安全性高,环境友好,经济易处理。生产效率高,产品质量高,后处理简单,一个单元操作即可结束。(The invention belongs to the technical field of pharmaceutical chemicals, and particularly relates to a synthesis method of 2, 2' -dithiodiethylamine dihydrochloride, which comprises the steps of adding 2-aminoethanethiol hydrochloride, an oxidant and a catalyst into a reaction solvent; under the action of a catalyst, heating to 40-90 ℃ for oxidation reaction; with the progress of the oxidation reaction, gradually reducing the substrate, gradually increasing the product, gradually crystallizing the product in a reaction solvent, reacting for 4-10h, cooling to room temperature, continuously crystallizing for 2-3 h, filtering, washing and drying to obtain 2, 2' -dithiodiethylamine dihydrochloride; has little environmental pollution, can reuse the mother liquor for many times, has little three wastes and is suitable for large-scale production. The reaction condition is mild, the oxidant safety is high, the environment is friendly, and the method is economical and easy to treat. High production efficiency, high product quality, simple post-treatment and one unit operation.)

1. A method for synthesizing 2, 2' -dithiodiethylamine dihydrochloride is characterized in that:

adding 2-aminoethanethiol hydrochloride, an oxidant and a catalyst into a reaction solvent; under the action of a catalyst, heating to 40-90 ℃ for oxidation reaction; with the progress of the oxidation reaction, gradually reducing the substrate, gradually increasing the product, gradually crystallizing the product in a reaction solvent, reacting for 4-10h, cooling to room temperature, continuously crystallizing for 2-3 h, filtering, washing and drying to obtain 2, 2' -dithiodiethylamine dihydrochloride; the reaction equation is:

2. the method for synthesizing 2, 2' -dithiodiethylamine dihydrochloride according to claim 1, characterized in that: adding 2-aminoethanethiol hydrochloride into a reaction solvent, and stirring for dissolving; and then adding a catalyst, heating to raise the temperature, adding an oxidant when the temperature is raised to 30-45 ℃, and preserving the heat to carry out an oxidation reaction when the temperature is raised to above 55 ℃.

3. The method for synthesizing 2, 2' -dithiodiethylamine dihydrochloride according to claim 1, characterized in that: the drying is vacuum drying, the drying temperature is 55-65 ℃, and the drying time is 6 hours.

4. The method for synthesizing 2, 2' -dithiodiethylamine dihydrochloride according to claim 1, characterized in that: the oxidant is dimethyl sulfoxide or other organic sulfur oxides.

5. The method for synthesizing 2, 2' -dithiodiethylamine dihydrochloride according to claim 1, characterized in that: the reaction solvent is one or more of methanol, ethanol, acetone, acetonitrile and chloroform.

6. The method for synthesizing 2, 2' -dithiodiethylamine dihydrochloride according to claim 1, characterized in that: the catalyst is one or more of formic acid, glacial acetic acid and hydrochloric acid.

7. The method for synthesizing 2, 2' -dithiodiethylamine dihydrochloride according to claim 1, characterized in that: after reacting for 5-6h, cooling to room temperature.

8. The method for synthesizing 2, 2' -dithiodiethylamine dihydrochloride according to claim 1, characterized in that: the mass ratio of the reaction solvent to the 2-aminoethanethiol hydrochloride is 2.5-3.5: 1; the mass ratio of the oxidant to the 2-aminoethanethiol hydrochloride is 0.8-1.2: 1, and the mass ratio of the catalyst to the 2-aminoethanethiol hydrochloride is 0.25-0.30: 1.

9. The method for synthesizing 2, 2' -dithiodiethylamine dihydrochloride according to claim 1, characterized in that: r in the reaction equation comprises amino, alkali metal, halogen and phenyl.

Technical Field

The invention belongs to the technical field of pharmaceutical chemicals, and particularly relates to a synthetic method of 2, 2' -dithiodiethylamine dihydrochloride.

Background

From a synthetic and biological point of view, symmetrical disulfides are one of the most important compounds, besides being industrially useful as vulcanizing agents for rubbers and elastomers, important starting materials for the synthesis of sulfinylated intermediates, sulfenyl intermediates, vinyl sulfides, disulfides.

In recent years, symmetrical disulfides have been studied more and more extensively, for example as photoinitiators for initiating photopolymerization of unsaturated olefins; the catalyst is used for catalyzing the isomerization reaction of the alpha, beta-unsaturated carbonyl compound; the selective deprotection reaction of aromatic acetate and aromatic benzoate formed by phenolic hydroxyl is combined with NMP.

Disulfide bond-containing compounds exist widely in nature and often show high biological activity, and therefore, how to effectively form disulfide becomes important.

The existing synthetic route of the symmetrical disulfide mainly comprises 8 methods of air direct oxidation coupling method, hydrogen peroxide oxidation coupling method, ammonium persulfate oxidation coupling method, halogen-containing oxidant oxidation coupling method, transition metal compound oxidation coupling method, nitrogen-containing compound oxidation coupling method, electrolytic oxidation coupling method and enzyme catalysis coupling method, wherein some methods need expensive reagents, some methods have great safety risk, some methods have troublesome treatment and are not suitable for industrial operation.

Disclosure of Invention

Aiming at the technical problems, the invention provides a synthesis method of 2, 2' -dithiodiethylamine dihydrochloride, which is simple and safe, has mild reaction conditions, is easy to operate, has high yield and good quality, and is suitable for industrial production.

In order to solve the technical problems, the invention adopts the technical scheme that:

a method for synthesizing 2, 2' -dithiodiethylamine dihydrochloride,

adding 2-aminoethanethiol hydrochloride, an oxidant and a catalyst into a reaction solvent; under the action of a catalyst, heating to 40-90 ℃ for oxidation reaction; with the progress of the oxidation reaction, gradually reducing the substrate, gradually increasing the product, gradually crystallizing the product in a reaction solvent, reacting for 4-10h, cooling to room temperature, continuously crystallizing for 2-3 h, filtering, washing and drying to obtain 2, 2' -dithiodiethylamine dihydrochloride; the reaction equation is:

adding 2-aminoethanethiol hydrochloride into a reaction solvent, and stirring for dissolving; and then adding a catalyst, heating to raise the temperature, adding an oxidant when the temperature is raised to 30-45 ℃, and preserving the heat to carry out an oxidation reaction when the temperature is raised to above 55 ℃.

The drying is vacuum drying, the drying temperature is 55-65 ℃, and the drying time is 6 hours.

The oxidant is dimethyl sulfoxide or other organic sulfur oxides.

The reaction solvent is one or more of methanol, ethanol, acetone, acetonitrile and chloroform.

The catalyst is one or more of formic acid, glacial acetic acid and hydrochloric acid.

After reacting for 5-6h, cooling to room temperature.

The mass ratio of the reaction solvent to the 2-aminoethanethiol hydrochloride is 2.5-3.5: 1; the mass ratio of the oxidant to the 2-aminoethanethiol hydrochloride is 0.8-1.2: 1, and the mass ratio of the catalyst to the 2-aminoethanethiol hydrochloride is 0.25-0.30: 1.

In the reaction formula, R is amino, alkali metal, halogen and phenyl.

Compared with the prior art, the invention has the following beneficial effects:

1. has little environmental pollution, can reuse the mother liquor for many times, has little three wastes and is suitable for large-scale production.

2. The reaction condition is mild, the oxidant safety is high, the environment is friendly, and the method is economical and easy to treat.

3. High production efficiency, high product quality, simple post-treatment and one unit operation.

Detailed Description

The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

Adding 50g of cysteamine hydrochloride and 125g of methanol into a 500ml four-neck flask, stirring to completely dissolve, then adding 1.2g of glacial acetic acid, starting heating, raising the temperature to 40 ℃, keeping the temperature at 40-45 ℃, slowly adding 50g of dimethyl sulfoxide into the system, continuing raising the temperature to 60 ℃, keeping the temperature to react for 5 hours, and separating out solids after reacting for 1 hour. And (3) cooling to about 25 ℃ for crystal growth for 2h after the reaction time is up, filtering, washing a filter cake with 20g of methanol, carrying out vacuum drying at 55-65 ℃ for 6h, and collecting to obtain 44.8g of cystamine dihydrochloride, wherein the mass yield is 89.6%, the liquid phase purity is 99.25%, and the content is 99.9%.

Example 2

Adding 500g of cysteamine hydrochloride and 1000g of methanol into a 2000ml four-neck flask, stirring to completely dissolve, then adding 15g of glacial acetic acid, starting heating, raising the temperature to 30 ℃, keeping the temperature at 30-35 ℃, slowly adding 450g of dimethyl sulfoxide into the system, continuing raising the temperature to 55 ℃, keeping the temperature to react for 6 hours, and separating out solids after reacting for 1.5 hours. And (3) cooling to room temperature for crystal growth for 2h after the reaction time is up, filtering, washing a filter cake with 180g of methanol (mother liquor is reserved for use) at 55-65 ℃, vacuum-drying for 6h, and collecting to obtain 455g of cystamine dihydrochloride, wherein the yield is 91%, the liquid phase purity is 99.55%, and the content is 99.7%.

Example 3

Adding 500g of cysteamine hydrochloride into a 2000ml four-neck flask, adding the filtered mother liquor of the embodiment 2 at room temperature, heating to 30 ℃, keeping the temperature at 30-35 ℃, slowly adding 45g of dimethyl sulfoxide and 0.75g of glacial acetic acid into the system, continuously heating to 55 ℃, keeping the temperature for reaction for 6 hours, and separating out solids after the reaction is carried out for 0.5 hour. And (3) when the reaction time is up, cooling to room temperature for crystal growth for 2h, filtering, washing a filter cake with 180g of methanol (mother liquor is reserved for use), carrying out vacuum drying for 6h at 55-65 ℃, and collecting to obtain 468g of cystamine dihydrochloride, wherein the yield is 93.6%, the liquid phase purity is 99.05%, and the content is 100%.

Example 4

Adding 500g of cysteamine hydrochloride into a 2000ml four-neck flask, adding the filtered mother liquor of the embodiment 3 at room temperature, heating to 30 ℃, keeping the temperature at 30-35 ℃, slowly adding 45g of dimethyl sulfoxide and 0.75g of glacial acetic acid into the system, continuously heating to 65 ℃, keeping the temperature for reaction for 6 hours, and separating out solids after the reaction is carried out for 0.5 hour. And (3) when the reaction time is up, cooling to room temperature for crystal growth for 2h, filtering, washing a filter cake with 180g of methanol, carrying out vacuum drying for 6h at 55-65 ℃, and collecting to obtain 463g of cystamine dihydrochloride, wherein the yield is 92.6%, the liquid phase purity is 98.95%, and the content is 99.4%.

Although only the preferred embodiments of the present invention have been described in detail, the present invention is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present invention within the knowledge of those skilled in the art, and all changes are encompassed in the scope of the present invention.