【摘要】 [目的]合成新型杀菌剂联苯吡菌胺及对相关杂质进行分离、鉴定。[方法]以3,4-二氯苯胺为起始原料,经重氮化反应、Gomberg-Bachmann反应制得中间体3′,4′-二氯-5-氟-2-联苯胺,再与1-甲基-3-二氟甲基-1H-吡唑-4-甲酰氯发生酰化反应制得目标化合物联苯吡菌胺。[结果]目标化合物的结构经~1H NMR确证,收率为62.87%(以3,4-二氯苯胺为基准)。反应过程中分离得到2个相关杂质,结构经~1H NMR及HRMS进行确证。[结论]重氮化反应的最佳反应条件:反应时间30 min,NaOH质量浓度8 mol/L;Gomberg-Bachmann反应的最佳反应条件:反应时间45 min,4-氟苯胺预热及反应温度90℃,4-氟苯胺用量为重氮盐的10 eq;相关杂质分别为1,3-二(3,4-二氯苯基)-1-三氮烯和3-(二氟甲基)-N-(4-氟苯基)-1-甲基-1H-吡唑-4-甲酰胺。更多还原

【Abstract】 [Aims]The study aims to synthesis of a new fungicide bixafen and separation of related impurities was conducted. [Methods]The intermediate of 3′,4′-dichloro-5-fluoro-2-diphenylamine was synthesized from 3,4-dichloroaniline via diazotization and Gomberg-Bachmann reaction. Then the intermediate underwent acylation reaction with3-difluoromethyl-1H-pyrazole-4-carbonyl chloride to obtain the bixafen. [Results]Target compound was confirmed by ~1H NMR. The yield of bixafen was 62.87%(based on 3,4-dichloroaniline). Two important impurities were separated and their structure were confirmed by ~1H NMR and H RMS. [Conclusions]Optimal condition for diazo-reaction was determined as the reaction time of 30 min and concentration of NaOH with 8 mol/L. Optimal condition for Gomberg-Bachmann reaction was determined as preheating 4-fluoro aniline to 90 ℃ and reacting for 45 min at 90 ℃with 10 eq of 4-fluoroaniline to the dosage of diazonium salt. The characterized two relevant impurities in the manufacture process were 1,3-bis(3,4-dichlorophenyl)-1-triazene and 3-(difluoromethyl)-N-(4-fluorophenyl)-1-methyl-1 H-pyrazole-4-carboxamide.更多还原