2,6-二甲基3,5-二氯-4-羟基吡啶合成工艺研究

Study on the Synthetic Conditions of 2,6-Dimethyl-3,5-dichloro-4-hydroxypyridine

以脱氢醋酸为原料经两步反应合成 2 ,6 二甲基 3,5 二氯 4 羟基吡啶 ,第一步是 2 ,6 二甲基 4 羟基吡啶的制备 ,第二步是 2 ,6 二甲基 4 羟基吡啶的氯化反应。对于 2 ,6 二甲基 4 羟基吡啶的制备 ,投料比为n (脱氢醋酸 )∶n (氨 ) =1∶2 ,反应溶剂的体积组成为V(N ,N 二甲基甲酰胺 )∶ V(反应中蒸出液 )∶ V(前次反应抽滤母液 ) =1∶1∶2 5 ,投料的顺序为先将脱氢醋酸溶于溶剂中 ,再加氨水 ,而不能先加氨水后加溶剂。氯代反应制备 2 ,6 二甲基 3,5 二氯 4 羟基吡啶 ,2 ,6 二甲基 4 羟基吡啶水溶液的质量浓度为 0 0 5g/mL ,操作顺序为通氯气一定时间后 ,先调节反应液pH到 3,然后将固体滤出。

Dimethyl 3,5 dichloro 4 hydroxypyridine(Ⅶ) was synthesized by two step reaction.Dehydroacetic acid(Ⅰ) reacted on aqueous ammonia giving an intermadiate product,2,6 dimethyl 4 hydroxypyridine(Ⅵ),and Ⅵ was then chlorinated.A study of the influencing factors on the synthesis gave the optimum reaction conditions.For first step reaction,the molar ratio of dehydroacetic acid(Ⅰ) to ammonia was 1∶2 and the solvent used was composed of three parts,i.e.DMF,distillate of reaction process and mother liquor after filtering solid Ⅵ,the volume ratio of which was 1∶1∶2.5.The sequence of adding materials should be that 25% ammonia liquor was added after dehydroacetic acid was dissolved in solvent DMF.For the chlorination,the concentration of Ⅵ in water was 0 05 g/mL and the filtration of title compound Ⅶ was done after adjusting pH to 3.