【摘要】 以4-氯吡啶-2-甲酸甲酯为原料,经氨解、酰胺脱水、卤素交换反应得到目标化合物4-氟吡啶-2-甲腈。通过对反应所需的溶剂、催化剂、温度、时间和物料比等条件进行筛选,确定最佳反应条件为:以甲醇为溶剂,氨解反应温度为20～30℃,物料比为n(氨水,w=25%～28%)∶n(4-氯吡啶-2-甲酸甲酯)=1.2～1.34∶1;酰胺脱水反应溶剂为四氢呋喃,温度为30～35℃,物料比为n(三氟乙酸酐)∶n(4-氯吡啶-2-甲酰胺)=1.1∶1;卤素交换反应溶剂为N,N-二甲基甲酰胺,温度为130～140℃,催化剂为四丁基溴化铵,反应时间3 h。合成方法简单,反应条件温和,产物收率及纯度高,总收率达66.2%,GC纯度达到99.0%以上,适合工业化生产。产物结构经~1H NMR和GC-MS确证。更多还原

【Abstract】 The target compound was obtained by the reaction of ammonolysis, dehydration, halogen exchange, using Methyl 4-chloropicolinate as starting material. Through the screening of solvent, catalyst, temperature, time and material ratio for the reaction, the optimum reaction conditions were as follows: methanol as solvent, ammonolysis reaction temperature of 20-30 ℃, material ratio of n(ammonia water, w=25%-28%)∶n(methyl 4-chloropicolinate)=1.2-1.34∶1; amide dehydration reaction; The solvent of amide dehydration reaction is tetrahydrofuran, the temperature is 30-35 ℃, the material ratio is n(trifluoroacetic anhydride)∶n(4-Chloropyridine-2-carboxamide)=1.1∶1; The halogen exchange reaction was conducted with N, N-dimethylformamide as solvent, temperature 130-140 ℃, catalyst tetrabutylammonium bromide for 3 h. The synthesis route adopted had the advantages of simple synthesis method, mild reaction conditions, high product yield and purity. The total yield was up to 66.2%, GC purity was over 99.0%. This program is suitable for large-scale industrial production. The structure of product was confirmed by ~1H NMR and GC-MS.更多还原