一种毒死蜱半抗原衍生物的合成

Synthesis of A Hapten Derivative of Chlorpyrifos

毒死蜱衍生物的羧基基团能够与蛋白质分子发生酰化或重氮化反应,能够对农药残留快速进行分析检测,在食品安全领域具有潜在应用价值。以三氯硫磷和乙醇为原料,通过醇解,酚羟基、醇羟基亲核取代和三氟乙酸水解4步反应设计并合成了毒死蜱半抗原衍生物,其结构经^(1)H NMR,^(13)C NMR和MS(ESI)表征,并对关键步骤的合成工艺进行优化。结果表明:二氯硫代磷酸乙酯与3,5,6-三氯-2-吡啶酚的物质的量之比为1.5∶1.0时,酚羟基亲核取代反应的收率最佳,可达39%。反应中引入4-羟基丁酸叔丁酯后,以4-二甲氨基吡啶为碱,当4-二甲氨基吡啶与O-乙基O-(3,5,6-三氯-2-吡啶基)硫代磷酸的物质的量之比为1.5∶1.0时,醇羟基亲核取代反应的收率最高,可达22%。当水解底物与三氟乙酸的体积比为3.0∶1.0时,水解收率最好,可达63%。

The carboxyl groups of chlorpyrifos derivatives can acylation or diazotization with protein molecules,which can quickly analyze and detect pesticide residues,and has potential application value in the field of food safety.Chlorpyrifos hapten derivatives were synthesized from thiophosphorus trichloride and ethanol by a 4-step reaction of alcoholysis,nucleophilic substitution of phenol hydroxyl and alcohol hydroxyl,and hydrolysis of trifluoroacetic acid.Its structure was characterized by^(1)H NMR,^(13)C NMR and MS(ESI),and the key synthetic process was optimized.The results showed that the yield of phenol hydroxyl nucleophilic substitution was up to 39%when the ratio of ethyl dichlorothiophosphate to 3,5,6-trichloro-2-pyridinol was 1.5∶1.0.After tert-butyl 4-hydroxybutyrate was introduced into the reaction,4-dimethylaminopyridine was used as the base,and the yield of the alcohol hydroxyl nucleophilic substitution reaction was up to 22%when the ratio of the substance amount of 4-dimethylaminopyridine to O-ethyl O-(3,5,6-trichloro-2-pyridinyl)phosphorothioate was 1.5∶1.0.When the volume ratio of hydrolyzed substrate to trifluoroacetic acid was 3.0∶1.0,the hydrolysis yield is preferably up to 63%.