戊唑醇中主要杂质异戊唑醇的分离、结构鉴定与转化

利用1,2,4-三唑两种异构体1H-1,2,4-三唑(Ⅳ)和4H-1,2,4-三唑(Ⅴ)的热力学稳定性差异,选择N,N-二甲基-4-氨基吡啶为催化剂,在强碱性条件下与1-(4-氯苯乙基)-1-叔丁基环氧乙烷(Ⅰ)发生开环反应,将在不使用催化剂时生成的异戊唑醇(Ⅲ)转化为戊唑醇(Ⅱ)。n(Ⅰ)∶n(氢氧化钾)∶n(1,2,4-三唑)∶n(催化剂)=1.0∶0.125∶1.38∶0.02,正丁醇为溶剂,回流反应6 h,收率≥85.0%(以Ⅰ计),不需重结晶产品w(Ⅱ)≥98.0%。MS、1HNMR、13CNMR和碳氢相关谱确认了Ⅲ和Ⅱ的结构。该工艺避免了产品的精制,该技术已在300 t/a生产装置上得到应用。

Separation of the Main Impurity Isotebuconazole from Tebuconazole and Its Identification and Transformation

Based on the different thermodynamic stability of two isomers of 1,2,4-triazole,4H-1,2,4-triazole(Ⅴ) was converted into 1H-1,2,4-triazole(Ⅳ) by N,N-dimethyl-4-aminopyridine as the catalyzer in the presence of strong base and reacted with 2-(4-chlorophenylethyl)-2-tert-butyloxirane(Ⅰ).Isotebuconazole(Ⅲ) as the main byproduct could be transformed into tebuconazole(Ⅱ) completely.The reaction conditions were n(Ⅰ)∶n(KOH)∶n(1,2,4-triazole)∶n(catalyzer) =(1.0∶0.125∶)1.38∶0.02,n-BuOH as the solvent and refluxing for 6 h.Purity of the product Ⅱ was over 98.0% without recrystallization and the yield was over 85.0%.Structures of Ⅱ and Ⅲ were identified by MS,~1HNMR,~(13)CNMR and HMQC.This synthetic technology is better than other reports and has been industrialized successfully in 300 t/a plant.