4-甲氧基-3-(3-吗啉-4-基丙氧基)苯甲腈的合成工艺

Synthesis of 4-methoxy-3-(3-morpholinopropoxy)benzonitrile

摘要:

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6h，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6h，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。

Abstract:

3-Hydroxy-4-methoxybenzonitrile was synthesized by dehydration of isovanillin and hydroxylamine hydrochloride with the yield of 96%.And 4-methoxy-3-(3-morpholinopropoxy)benzonitrile was synthesized by alkylation of 3-hydroxy-4-methoxybenzonitrile with N-(3-chloropropyl) morpholine. The structures of product were characterized by IR and NMR．The optimum reaction conditions for synthesis of 3-hydroxy-4-methoxybenzonitrile were as follows: n(isovanillin): n(hydroxylamine- hy-drochloride)=1:2, reaction temperature 72℃, reaction for 6 hours with the yield of 96%.The optimum reaction conditions for synthesis of 4-methoxy-3-(3-morpholinopropoxy)benzonitrile were as follows: n(3-hydroxy-4-methoxybenzonitrile): n(4-(3-chloropropyl)morpholine)=1.0:1.1, reaction for 6 hours at reflux temperature with the yield of 96%.After two steps of optimization, we can obtain the target compound that was high yield as well as more suitable for industrial production.