2-氯甲基-3-甲基-4-(2,2,2-三氟乙氧基)-吡啶的合成研究

以2,3-二甲基吡啶为原料,经过氧化、硝化、取代、酰化以及氯化反应,合成目标产物2-氯甲基-3-甲基-4-(2,2,2-三氟乙氧基)-吡啶,5步总收率为35.6%。对中间体2,3-二甲基-4-(2,2,2-三氟乙氧基)-吡啶-N-氧化物的合成条件进行了优化选择,其较佳的合成条件:甲基异丁基甲酮作为溶剂,四丁基溴化铵为相转移催化剂,n(三氟乙醇)∶n(K2CO3)∶n(2,3-二甲基-4-硝基吡啶-N-氧化物)=4.5∶1.2∶1,反应时间12 h,反应温度95℃,所得中间体收率91.9%,所得中间体结构经1HNMR表征,确定为2,3-二甲基-4-(2,2,2-三氟乙氧基)-吡啶-N-氧化物。

Study on synthesis of 2-chloromethyl-3-methyl-4 -(2,2,2-trifluoroethyoxyl)- pyridine

Using 2,3-dimethyl-byridine as the material,the process involved the following five steps:oxidation,nitration,substitution,acylation and chlorination,the total yield was 35.6%.The optimal synthetic condition of intermediate 2,3-dimethyl-4-(2,2,2-trifluoroethoxy)nitro-pyridine-N-oxide was:methyl iso-butylketone as the solvent and tetrabutyl ammonium bromide as the phase transfer catalyst,n(CF3CH2OH)∶n(K2CO3)∶n(2,3-dimethyl-4-nitro-pyridine-N-oxide)=4.5 ∶1.2 ∶1,reaction time 12 h,temperature 95 ℃,the yield of intermediate was 91.9%.The structure of intermediate was characterized by 1H NMR spectra,the target compound was 2,3-dimethyl-4-(2,2,2-trifluoroethoxy) nitro-pyridine-N-oxide.