Preparation method of 4,6-dichloropyrimidine

Abstract

The invention discloses a preparation method of 4,6-dichloropyrimidine, which comprises the following steps: mixing 4,6-dihydroxypyrimidine and phosphorus oxychloride, dropwise adding triethylamine under the temperature of 40-65 DEG C, then heating up to 110-120 DEG C, carrying out heat preservation reaction, stopping the reaction until the content of 4,6-dihydroxypyrimidine is less than 1%, cooling reaction mixture to below 30 DEG C, dropwise adding sodium hydroxide solution while controlling the temperature not more than 30 DEG C until the pH is in the range of 6-6.5, conducting steam distillation, collecting distillate, separating solid and liquid, and drying solid to obtain the 4,6-dichloropyrimidine; The invention uses stoichiometric or slight excess of phosphorus oxychloride. There is no need to recover phosphorus oxychloride after the reaction. Material and energy consumption and loss of product are reduced. Separation methods such as organic solvent extraction, drying and dehydration, organic solvent recovering and the like are not used. There is no need to use and recover organic solvent. The preparation method provided by the invention is environment friendly, avoids loss of product, produces no extra solid waste, and is conducive to industrial scale production. The product has high yield and purity, and can reach the commercial requirement without being subjected to secondary purification. The production cycle is short and the production cost is low.

Description

technical field [0001] The invention belongs to the field of organic chemistry and relates to a preparation method of a class of organic compounds. Background technique [0002] 4,6-Dichloropyrimidine is an important intermediate in the synthesis of sulfa drugs and fungicide azoxystrobin. There are many reports in the literature about its preparation method. One of the preparation methods is to react 4,6-dihydroxypyrimidine with triethylamine and excess phosphorus oxychloride at a certain temperature, and the resulting reaction mixture is distilled under reduced pressure to recover the excess phosphorus oxychloride, and poured into ice water. Extract with an organic solvent, dry and dehydrate, and recover the organic solvent to obtain 4,6-dichloropyrimidine. But above-mentioned method has the following problems in actual production: 1) reclaim excessive phosphorus oxychloride to carry out under higher vacuum degree, and recovery rate is low (sometimes less than 35%), not o...

AI Technical Summary

Problems solved by technology

But above-mentioned method has the following problems in actual production: 1) reclaim excessive phosphorus oxychloride to carry out under higher vacuum degree, and recovery rate is low (sometimes less than 35%), not only expends a large amount of energy, but also increases Material consumption; 2) The operations of organic solvent extraction, drying and dehydration, and recovery of organic solvents are cumbersome and time-consuming. Organic solvents are toxic to a certain extent, causing environmental pollution, and the recovery rate is not high, which increases production costs. In addition, drying and dehydration also produces a large amount of desiccant Solid waste; 3) Since 4,6-dichloropyrimidine has a certain sublimation property, partial loss of the product will be caused when excessive phosphorus oxychloride and organic solvents are recovered; 4) The obtained product is usually brown or yellow, and further purification is required to meet Commercial requirements