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Method for preparing p-hydroxythiobenzamide

A technology for hydroxythiobenzamide and p-hydroxybenzonitrile, which is applied in the field of preparing p-hydroxythiobenzamide, can solve the problems of unstable product quality, high water content, difficult absorption and processing, etc. High toxicity, simple reaction steps, cheap and easy to obtain effects

Active Publication Date: 2013-10-23
苏州诚和医药化学有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] The first and second methods have a large amount of foul-smelling toxic gas hydrogen sulfide in the reaction process, which requires high sealing of the equipment, is not easy to absorb and treat, and produces a large amount of wastewater containing DMF in the post-treatment process, and the water content Higher, unable to be processed and reused, and the quality and yield of p-hydroxythiobenzamide are low, and subsequent reactions can only be carried out after multiple purifications
[0010] In the third method, diethyl dithiophosphate, a material with high toxicity, strong corrosiveness and hydrogen sulfide stench, is used, and the cost of treating the phosphorus-containing and sulfur-containing wastewater produced by it is extremely high, and the product obtained by this synthesis method is The quality is extremely unstable, and it is difficult to meet the needs of large-scale industrial production
But about the method that the present invention obtains p-hydroxyl thiobenzamide, there is no report yet

Method used

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  • Method for preparing p-hydroxythiobenzamide
  • Method for preparing p-hydroxythiobenzamide
  • Method for preparing p-hydroxythiobenzamide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Add 400mL of 95% ethanol, 143g (1.2mol) of p-hydroxybenzonitrile and 100.5g (1.32mol) of thiourea into a 1000mL four-necked reaction flask, and keep the temperature at 45-50°C under stirring for 11 hours. During the reaction process, TLC tracking detection (developer is petroleum ether: ethyl acetate = 3:1, V / V, Rf = 0.8), no raw material p-hydroxybenzonitrile spots, and the incubation is over. The final reaction product was cooled to 0-5°C with conventional ice-salt water to crystallize, then separated by suction filtration, and vacuum-dried at 60°C to obtain 164.6 g (1.07 mol) of p-hydroxythiobenzamide, which was quantified by HPLC normalization method, mole The yield is 89.17%, and the product purity is 98.28%. After the separated mother liquor was distilled, 348 mL of ethanol and 4.88% of water were recovered. HPLC detection conditions: Waters high performance liquid chromatography, UV detector; C18 chromatographic column, 250mm×4.6mm; mobile phase is acetonitrile:...

Embodiment 2

[0033] Add 348mL of ethanol (4.88% moisture) recovered in Example 1, 252mL of unused 95% ethanol, 286g (2.4mol) of p-hydroxybenzonitrile and 237.5g (3.12mol) of thiourea into a 2000mL four-necked reaction flask , under stirring conditions, the temperature was controlled at 60-65° C. and the reaction was maintained for 8 hours. During the reaction process, TLC tracking detection, no raw material p-hydroxybenzonitrile spots, the end of the incubation. The final reaction product was cooled to 0-5°C with conventional ice-salt water to crystallize, then separated by suction filtration, and vacuum-dried at 60°C to obtain 337.8 g (2.2 mol) of p-hydroxythiobenzamide, which was quantified by HPLC normalization method, mole The yield is 91.67%, and the product purity is 98.77%. After the separated mother liquor was distilled, 521 mL of ethanol and 5.13% of water were recovered. TLC and HPLC detection conditions are the same as in Example 1.

Embodiment 3

[0035] Add 500mL of ethanol (moisture content: 5.13%) recovered in Example 2, 155g (1.3mol) of p-hydroxybenzonitrile and 118.7g (1.56mol) of thiourea into a 1000mL four-necked reaction flask. 80 ° C heat preservation reaction for 6 hours. During the reaction process, TLC tracking detection, no raw material p-hydroxybenzonitrile spots, the end of the incubation. The final reaction product was cooled to 0-5°C with conventional ice-salt water to crystallize, then separated by suction filtration, and vacuum-dried at 60°C to obtain 183.8 g (1.2 mol) of p-hydroxythiobenzamide, which was quantified by HPLC normalization method, mole The yield is 92.31%, and the product purity is 98.46%. After the separated mother liquor was distilled, 431 mL of ethanol and 4.42% of water were recovered. TLC and HPLC detection conditions are the same as in Example 1.

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Abstract

The invention discloses a method for preparing p-hydroxythiobenzamide. The method comprises the steps of adding p-cyanophenol and thiourea to a 94%-96% ethanol solvent according to a molar ratio of p-cyanophenol to thiourea being 1: 1.1-1.5; reacting for 6-11 hours at a temperature of 40-80 DEG C, then cooling, crystallizing, separating and drying to obtain p-hydroxythiobenzamide. A separated mother liquid is distilled to recycle ethanol. The method is mild in reaction, safe in operations, cheap and easily available in raw materials, simple in reaction steps and relatively high in product purity and mole yield. The solvent ethanol can be reused by recycle, and a small amount of waste residues can be treated by incineration, with relatively low treatment cost. A novel method for obtaining p-hydroxythiobenzamide is provided. The method provided by the invention can be used for large-scale production.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical intermediates, in particular to a method for preparing p-hydroxythiobenzamide. Background technique [0002] p-Hydroxythiobenzamide, also known as 4-hydroxythiobenzamide, molecular formula: C 7 h 7 NOS, molecular weight: 153.2, it is an important intermediate of febuxostat, a new anti-gout drug. The synthetic method report of p-hydroxythiobenzamide is a lot, mainly contains following several synthetic routes: [0003] 1. p-Hydroxybenzonitrile, sodium bisulfate, ammonium chloride method, the reaction equation is: [0004] ; [0005] Two, p-hydroxybenzonitrile, hydrogen sulfide, alkali sulfide method, the reaction equation is: [0006] ; [0007] Three, p-hydroxybenzonitrile, diethyl phosphorodithioate method, the reaction equation is: [0008] , wherein ACOEt is ethyl acetate. [0009] The first and second methods have a large amount of foul-smelling toxic gas hydrogen sulfide...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C327/48
Inventor 王利明夏秋景陈洁
Owner 苏州诚和医药化学有限公司