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Preparation method of 2-alkyl thioisonicotinamide

A technology of alkyl thioisonicotinamide and thioisonicotinamide is applied in the direction of organic chemistry, etc., can solve the problems of expensive catalyst silver nitrate, low selectivity of alkylation reaction, no practical value, etc., and achieves improved reaction The effect of high conversion, high selectivity, and easy to scale production

Active Publication Date: 2010-06-09
SUZHOU KAIYUAN MINSHENG SCI & TECH CORP
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0003] Can show from above-mentioned existing preparation method, take methyl ethyl ketone and acetic anhydride as its process steps of raw material method, and yield is low, does not have practical value
Using 4-cyanopyridine as raw material, the method of preparing 2-alkylthioisonicotinamide through alkylation and thioammoniation reaction has the disadvantages of low selectivity of the alkylation reaction and isomer products, which need to be extracted , rectification and other steps of purification; the catalyst silver nitrate is expensive and cannot be recycled; the whole step is cumbersome to operate and the cost is high

Method used

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  • Preparation method of 2-alkyl thioisonicotinamide
  • Preparation method of 2-alkyl thioisonicotinamide
  • Preparation method of 2-alkyl thioisonicotinamide

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[0020] The preparation method of 2-alkylthioisonicotinamide of the present invention uses 4-cyanopyridine as a raw material, and 4-cyanopyridine and ammonium sulfide react under the catalysis of sulfur to obtain thioisonicotinamide; Niacinamide and fatty acid undergo an alkylation reaction under the catalysis of lead tetraacetate (LTA) to obtain the crude product of 2-alkylthioisonicotinamide, which is refined with ethanol to obtain the fine product. The selectivity of the alkylation reaction can be effectively improved, the purity of the product can be significantly improved, and the step of rectification is not required, so it is better suitable for industrial application.

[0021] The specific process is: first, add sulfur to 20% ammonium sulfide aqueous solution, heat and stir until dissolved, then add 4-cyanopyridine to react, wherein the molar ratio of 4-cyanopyridine to ammonium sulfide and sulfur is 1 : (2~4): (0.3~1), the temperature of reaction is 40~60 ℃, and the ti...

Embodiment 1

[0023] Synthesis of thioisonicotinamide: Put 294g of 20% ammonium sulfide aqueous solution into a four-neck flask, add 4.2g of sulfur under stirring, heat and stir until completely dissolved, add 45g of 4-cyanopyridine, heat up to 40°C, keep warm 4 hours; the reaction formula is as follows figure 1 shown.

[0024] After the reaction, the temperature was lowered to 25°C, suction filtered, and the filter cake was washed with distilled water at 70°C until neutral to obtain thioisonicotinamide, which was dried to obtain 47.3g.

[0025] Synthesis of 2-ethylthioisonicotinamide: 56.8g ammonium persulfate was dissolved in 113.6g water to make ammonium persulfate solution, set aside. Add 47.3g of thioisonicotinamide, 23.6g of concentrated sulfuric acid, and 1.42g of lead tetraacetate to 240g of water, add 50.7g of propionic acid and ammonium persulfate solution under stirring, and react at 60°C for 2 hours; the reaction formula is as follows: figure 2 shown.

[0026] After the reac...

Embodiment 2

[0028] Synthesis of thioisonicotinamide: Put 441.6g of 20% ammonium sulfide aqueous solution into a four-neck flask, add 6.9g of sulfur under stirring, heat and stir until completely dissolved, add 45g of 4-cyanopyridine, heat up to 50°C, Keep warm for 5 hours; after the reaction, cool down to 25°C, filter with suction, wash the filter cake with distilled water at 70°C until neutral to obtain thioisonicotinamide, and dry to obtain 49.8g.

[0029] Synthesis of 2-propylthioisonicotinamide: 74.7g of ammonium persulfate was dissolved in 149.4g of water to make an ammonium persulfate solution for subsequent use. Add 49.8g of thioisonicotinamide, 29.9g of concentrated sulfuric acid, and 1.6g of lead tetraacetate to 350g of water, add 63.5g of butyric acid and ammonium persulfate solution under stirring, and react at 70°C for 2 hours; the reaction formula is as follows: image 3 shown.

[0030] After the reaction, the temperature was lowered to 25°C, ammonia water was slowly added t...

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Abstract

The invention provides a preparation method of 2-alkyl thioisonicotinamide, comprising the following steps of: preparing thioisonicotinamide through the reaction between 4-cyanopyridine as raw material and ammonium sulfide under the catalysis of sulphur; preparing crude 2-alkyl thioisonicotinamide through the hydrocarbonylation reaction between the thioisonicotinamide and fatty acid under the catalysis of lead tetraacetate (LTA), and refining to obtain the fine product by adopting ethanol. By adopting the reaction route of first sulfuric ammonization and then hydrocarbonylation, the positioning effect of the hydrocarbonylation reaction is improved, the generation of isomerized products in the reaction is reduced, and the operation is simplified; by adopting lead tetraacetate to substitute high-price silver nitrate, not only the cost is reduced, but also the reaction conversion ratio is improved, the two-step yield reaches up to 64 percent, the product purity reaches up to more than 98.5 percent, and the scale production is easy to realize.

Description

technical field [0001] The invention relates to a method for preparing 2-alkylthioisonicotinamide, which belongs to the technical field of fine chemicals. Background technique [0002] 2-alkyl-thioisonicotinamide (2-alkyl-thioisonicotinamide), which can be used to treat tuberculosis, such as ethionamide and prothionamide. At present, the synthetic methods of 2-alkyl-thioisonicotinamide are as follows: 1. take methyl ethyl ketone and acetic anhydride as raw materials, and obtain the target product through eight-step synthetic reactions, and the total yield is 3%; 2. use 4-cyanopyridine as The raw material is obtained through a two-step reaction. The first step is the alkylation reaction, 4-cyanopyridine reacts with fatty acid and ammonium persulfate, silver nitrate is used as a catalyst, and the generated alkyl-4-cyanopyridine has many isomers, not only 2-substituted products, There are also 2-, 6-disubstituted products, which need to be extracted and rectified to obtain 2-...

Claims

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Application Information

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IPC IPC(8): C07D213/83
Inventor 王中喜徐剑锋李伟信张俭
Owner SUZHOU KAIYUAN MINSHENG SCI & TECH CORP
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