CN107602476B

CN107602476B - Preparation method of 2-mercapto-1-methylimidazole

Info

Publication number: CN107602476B
Application number: CN201710939304.8A
Authority: CN
Inventors: 漆伟君; 李静; 肖海旺
Original assignee: Plus Science & Technology (shanghai) Co ltd
Current assignee: Plus Science & Technology (shanghai) Co ltd
Priority date: 2017-10-10
Filing date: 2017-10-10
Publication date: 2020-06-26
Anticipated expiration: 2037-10-10
Also published as: CN107602476A

Abstract

The invention discloses a preparation method of electronic grade 2-mercapto-1-methylimidazole, which comprises the following steps: 1) performing a tank-closing reaction on chloral dimethyl acetal and methylamine aqueous solution at the temperature of 80-85 ℃ for 16 hours, cooling, releasing pressure, extracting by using a solvent, concentrating the solvent, and performing reduced pressure rectification to obtain an intermediate methylamino acetaldehyde dimethyl acetal; 2) reacting methylamino acetaldehyde dimethyl acetal and tert-butyl thionitrile under the catalysis of boron trifluoride at 50-70 ℃ to perform condensation reaction to obtain 2-tert-butylthio-1-methylimidazole; 3) adding a solvent into 2-tert-butylthio-1-methylimidazole, adding a catalyst and an organic solvent, reacting at normal temperature, filtering, concentrating filtrate, and crystallizing by using electronic grade water to obtain the product 2-mercapto-1-methylimidazole. The raw materials adopted by the invention are low in price and environment-friendly, the synthetic method is simple and convenient to operate, and the product quality meets the application standard of electronic chemicals.

Description

Preparation method of 2-mercapto-1-methylimidazole

The technical field is as follows:

the invention belongs to the field of organic chemistry, and particularly relates to a preparation method of 2-mercapto-1-methylimidazole.

Background art:

2-mercapto-1-methylimidazole is an antithyroid agent and is commonly used in medicine. In recent years, the liquid crystal material has been found to play an important role in liquid crystal materials, and is attracted attention and researched by a great number of electronic chemical manufacturers.

At present, the literature reports methods for synthesizing 2-mercapto-1-methylimidazole, which mainly include two methods:

1) first Synthesis method

The method comprises the steps of taking bromoacetaldehyde dimethyl acetal and methylamine water solution as raw materials, carrying out ammonolysis reaction to obtain an intermediate methylamino acetaldehyde dimethyl acetal, and then reacting with potassium thiocyanate to obtain a target product

The synthetic route is as follows:

however, the synthesis method has the defects of high cost of the bromoacetaldehyde dimethyl acetal and the like.

2) Second Synthesis method

Guziec et al (J.Org.chem.1994, 59, 4691-4692) in the prior art disclose a preparation method of methimazole, which takes N-methylimidazole as a raw material to react with N-butyl lithium, and then sulfur powder is added for reflux reaction, and finally the yield of the crude methimazole is 42%.

The synthetic route is as follows:

the method has harsh reaction conditions, and the dropwise addition of the n-butyl lithium is carried out at-78 ℃, so that the industrial scale-up production is difficult.

The invention content is as follows:

in order to overcome the defects, the invention aims to provide the preparation method of the 2-mercapto-1-methylimidazole, which has the advantages of simple process and mild conditions and is completely suitable for industrial production.

The preparation method of the 2-mercapto-1-methylimidazole is technically characterized by comprising the following steps of:

step one, performing tank closing reaction on chloroacetaldehyde dimethyl acetal and methylamine water solution at the temperature of 80-85 ℃, and performing reduced pressure rectification to obtain methylamino acetaldehyde dimethyl acetal;

secondly, methylamino acetaldehyde dimethyl acetal and tert-butyl thionitrile react under the catalysis of boron trifluoride at 50-70 ℃ to perform condensation reaction to obtain 2-tert-butylthio-1-methylimidazole;

adding a solvent into 2-tert-butylthio-1-methylimidazole, adding a catalyst and an organic solvent, reacting at normal temperature, filtering, concentrating the filtrate, and recrystallizing with water to obtain 2-mercapto-1-methylimidazole;

the reaction route is as follows:

further, in the first step, a 50-65% concentration of methylamine water solution is adopted.

Further, in the first step, the ratio of chloroacetaldehyde dimethyl acetal to methylamine is 1: 2.5-3.5.

Further, in the second step, boron trifluoride is boron trifluoride-diethyl ether, boron trifluoride-tetrahydrofuran or boron trifluoride-acetonitrile.

Further, in the second step, the molar ratio of methylamino acetaldehyde dimethyl acetal, tert-butyl sulfur nitrile and boron trifluoride is 1: 0.95-1.05: 0.05-0.15.

Further, in the third step, the organic solvent is toluene, xylene or anisole.

Further, in the third step, the catalyst is selected from aluminum trichloride or boron trichloride, and the adding amount is 0.10-0.15 equivalent of 2-tert-butylthio-1-methylimidazole.

The invention has the beneficial effects that:

1. the chloroacetaldehyde acetal has relatively low price, and the reaction speed is equivalent to the reaction speed of bromide by adjusting the concentration of methylamine solution.

2. Avoids the generation of byproduct HSCN inevitably during post-treatment when KSCN is adopted in the prior method, and the substance can be rapidly decomposed at normal temperature to generate highly toxic substance HCN, thereby being beneficial to the labor protection of workers.

DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION

Example 1:

firstly, adding 249g of chloroacetaldehyde dimethyl acetal and 218g of water into a 1L high-pressure reaction kettle, then introducing 218g of monomethylamine gas, starting stirring, heating to 80-85 ℃, reacting for 16 hours, wherein the GC detection raw material content is less than or equal to 0.5%, cooling, releasing pressure, reducing the temperature to about 20 ℃, adding 100g of dichloromethane each time, extracting for 3 times, combining organic phases, evaporating the solvent, then carrying out vacuum rectification to obtain 202g of a product, wherein the GC content is 96%, and the yield is 85%.

Secondly, 202g of the product, 186g of tert-butyl sulfonitrile and 600mL of toluene are added into a 1L three-necked flask, the mixture is stirred, the temperature is reduced to about 15 ℃, and 12g of boron trifluoride diethyl etherate solution is added dropwise, and the temperature is controlled to be not more than 25 ℃. After the dripping is finished, the temperature is raised to 50-55 ℃ for reaction for 3 hours, the temperature is raised while the reaction is carried out, the solvent is evaporated out under normal pressure until the GC detection raw material disappears, the temperature is reduced to 20 ℃, 20 percent sodium hydroxide is used for adjusting the pH value to 7, 3 x 300g dichloromethane is used for extraction, the organic phases are combined, 100g electronic grade ultrapure water is used for washing for 1 time, the solvent is concentrated, and then the product 240g is distilled out through decompression and distillation, the GC content is 94 percent, and the yield is 83 percent.

And thirdly, adding 240g of the product and 1.2L of toluene into a 2L three-necked bottle under the protection of nitrogen, adding 19g of aluminum trichloride in batches under stirring, stirring at room temperature until the GC controlled raw material completely reacts, filtering out insoluble substances, concentrating the filtrate under reduced pressure until solid is separated out, adding 500g of ethyl acetate, heating to 50 ℃, stirring for 30 minutes, cooling to 10 ℃, centrifuging to obtain a crude product, crystallizing the crude product by using electronic grade ultrapure water to obtain 146g of product, wherein the yield is 91%.

Example 2:

firstly, adding 249g of chloroacetaldehyde dimethyl acetal and 84g of water into a 1L high-pressure reaction kettle, then introducing 156g of monomethylamine gas, starting stirring, heating to 80-85 ℃, reacting for 16 hours, wherein the content of GC detection raw materials is less than or equal to 0.5%, cooling, releasing pressure, reducing the temperature to about 20 ℃, adding 100g of dichloromethane each time, extracting for 3 times, combining organic phases, evaporating a solvent, then carrying out vacuum rectification to obtain 198g of a product, wherein the content of GC is 95%, and the yield is 83%.

Secondly, 198g of the product, 201g of tert-butyl sulfonitrile and 600mL of toluene are added into a 1L three-necked flask, stirring is started, the temperature is reduced to about 15 ℃, 36g of boron trifluoride tetrahydrofuran solution is dropwise added, and the temperature is controlled to be not more than 25 ℃. After the dripping is finished, the temperature is raised to 60-70 ℃ for reaction for 3 hours, the temperature is raised, the reaction is carried out while the solvent is distilled off at normal pressure until the raw material is disappeared by GC detection, the temperature is reduced to 20 ℃, 20% sodium hydroxide is used for adjusting the pH value to 7, 3 x 300g dichloromethane is used for extraction, the organic phases are combined, 100g electronic-grade ultrapure water is used for washing for 1 time, the solvent is concentrated, and then the product 238g is distilled out by decompression and distillation, the GC content is 94%, and the yield is 84%.

And thirdly, adding 238g of the product and 1.2L of dimethylbenzene into a 2L three-neck bottle under the protection of nitrogen, introducing 25g of boron trichloride while stirring, stirring at room temperature until the GC-controlled raw material completely reacts, filtering out insoluble substances, concentrating the filtrate under reduced pressure until solid is separated out, adding 500g of ethyl acetate, heating to 50 ℃, stirring for 30 minutes, cooling to 10 ℃, centrifuging to obtain a crude product, crystallizing the crude product by using electronic grade ultrapure water to obtain 142g of the product, wherein the yield is 89%.

Example 3:

firstly, adding 249g of chloroacetaldehyde dimethyl acetal and 117g of water into a 1L high-pressure reaction kettle, then introducing 218g of monomethylamine gas, starting stirring, heating to 80-85 ℃, reacting for 16 hours, wherein the content of a raw material detected by GC is less than or equal to 0.5%, cooling, releasing pressure, reducing the temperature to about 20 ℃, adding 100g of dichloromethane each time, extracting for 3 times, combining organic phases, evaporating a solvent, then carrying out vacuum rectification to obtain 207g of a product, wherein the content of GC is 96%, and the yield is 87%.

And secondly, adding 207g of the product, 200g of tert-butyl sulfonitrile and 600mL of toluene into a 1L three-necked flask, starting stirring, cooling to about 15 ℃, and dropwise adding 29g of boron trifluoride acetonitrile solution, wherein the temperature is controlled to be not more than 25 ℃. After dripping, the temperature is raised to 60-70 ℃ for reaction for 3 hours, the temperature is raised, the reaction is carried out while the solvent is distilled off at normal pressure until the GC detection raw material disappears, the temperature is reduced to 20 ℃, 20 percent sodium hydroxide is used for adjusting the pH value to 7, 3 x 300g dichloromethane is used for extraction, the organic phases are combined, 100g electronic grade ultrapure water is used for washing for 1 time, the solvent is concentrated, then the product 246g is distilled out by decompression and distillation, the GC content is 94 percent, and the yield is 83 percent.

And thirdly, adding 246g of the product and 1.2L of anisole into a 2L three-necked bottle under the protection of nitrogen, adding 29g of aluminum trichloride in batches under stirring, stirring at room temperature until the GC controlled raw material completely reacts, filtering out insoluble substances, concentrating the filtrate under reduced pressure until solid is separated out, adding 500g of ethyl acetate, heating to 50 ℃, stirring for 30 minutes, cooling to 10 ℃, centrifuging to obtain a crude product, crystallizing the crude product by using electronic grade ultrapure water to obtain 150g of the product, wherein the yield is 91%.

The foregoing shows and describes the general principles and broad features of the present invention and advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.

Claims

1. A preparation method of 2-mercapto-1-methylimidazole is characterized by comprising the following steps: step one, performing tank closing reaction on chloroacetaldehyde dimethyl acetal and methylamine water solution at the temperature of 80-85 ℃, and performing reduced pressure rectification to obtain methylamino acetaldehyde dimethyl acetal; in the first step, the ratio of chloroacetaldehyde dimethyl acetal to methylamine is 1: 2.5-3.5;

secondly, performing condensation reaction on methylamino acetaldehyde dimethyl acetal and tert-butyl thionitrile at 50-70 ℃ under the catalysis of boron trifluoride to obtain 2-tert-butylthio-1-methylimidazole; in the second step, the molar ratio of methylamino acetaldehyde dimethyl acetal, tert-butyl sulfur nitrile and boron trifluoride is 1: 0.95-1.05: 0.05-0.15;

adding a catalyst and an organic solvent into 2-tert-butylthio-1-methylimidazole, reacting at normal temperature, filtering, concentrating the filtrate, and recrystallizing with water to obtain 2-mercapto-1-methylimidazole; in the third step, the catalyst is selected from aluminum trichloride or boron trichloride; the addition amount of the catalyst is 0.10-0.15 equivalent of 2-tert-butylthio-1-methylimidazole.

2. The process according to claim 1 for preparing 2-mercapto-1-methylimidazole, which comprises: in the first step, 50-65% concentration methylamine water solution is adopted.

3. The process according to claim 1 for preparing 2-mercapto-1-methylimidazole, which comprises: in the second step, boron trifluoride is boron trifluoride-diethyl ether, boron trifluoride-tetrahydrofuran or boron trifluoride-acetonitrile.

4. The process according to claim 1 for preparing 2-mercapto-1-methylimidazole, which comprises: in the third step, the organic solvent is toluene, xylene or anisole.