4-甲氧基-3-(3-吗啉-4-基丙氧基)苯甲腈的合成工艺

Synthetic Process of 4-Methoxy-3-(3-morpholinopropoxy) benzonitrile

以异香兰素和盐酸羟胺为起始原料,脱水得到3-羟基-4-甲氧基苯腈;再与N-（3-氯丙基）吗啉经烷基化反应制得4-甲氧基-3-（3-吗啉-4-基丙氧基）苯甲腈。产物结构经IR和NMR表征。经单因素实验,确定合成3-羟基-4-甲氧基苯腈的最优条件为n（异香兰素）∶n（盐酸羟胺）=1∶2,乙腈为溶剂,反应温度为72℃,反应时间6 h,收率为96%;确定合成4-甲氧基-3-（3-吗啉-4-基丙氧基）苯甲腈的最优条件为n（3-羟基-4-甲氧基苯腈）∶n[N-（3-氯丙基）吗啉]=1.0∶1.1,乙腈为溶剂,回流反应6 h,收率为96%。经过两步优化,高产率获得目标化合物,后处理简单,更适合工业化生产。

3-Hydroxy-4-methoxybenzonitrile was synthesized from isovanillin and hydroxylamine hydrochloride by dehydration. And then 4-methoxy-3-（ 3-morpholinopropoxy） benzonitrile was synthesized by alkylation of 3-hydroxy-4-methoxybenzonitrile with 4-（ 3-chloropropyl） morpholine. The structures of product were characterized by IR and nuclear magnetic resonance（ NMR）. The optimum reaction conditions for the synthesis of 3-hydroxy-4-methoxybenzonitrile were as follows： n（ isovanillin） ∶ n（ hydroxylamine hydrochloride） =1∶2,acetonitrile as solvent,reaction temperature 72 ℃,reaction time 6 hours. Under these conditions,the yield of 3-hydroxy-4-methoxybenzonitrile reached 96%. The yield of 4-methoxy-3-（ 3-morpholinopropoxy） benzonitrile reached 96% under the optimum reaction conditions of n（ 3-hydroxy-4-methoxybenzonitrile） ∶n[N-（ 3-chloropropyl） morpholine]=1. 0∶1. 1,acetonitrile as solvent,reaction time 6 hours at reflux temperature. After two steps of optimization,the target compound with high yield was obtained. The post-treatment is simple and more suitable for industrial production.