水介质中合成吗啉基N-杂环芳胺化合物

SYNTHESIS OF MORPHOLIN-4-YL N-HETEROAROMATIC AMINES IN WATER

研究了水介质中氯代N-杂环芳胺与吗啉的芳香亲核取代反应(SNAr),探讨了不同的催化剂和溶剂等对SNAr反应的影响及底物适用性。实验结果表明:在盐酸作用下,不同的氯代N-杂环芳胺底物与吗啉在水介质中能顺利发生SNAr反应,在底物与吗啉、盐酸的物质的量比为1∶3∶0.3、水的用量为1 mL/mmol底物、130℃反应2~8 h的条件下,不需要进一步纯化,可得到一系列高纯度的吗啉基N-杂环芳胺化合物,收率75.0%~97.6%。在给定反应条件下,2,4-二氯代底物有较好的区域选择性,以较高的收率得到4-位吗啉基单取代产物。

Nucleophilic aromatic substitution reaction(SNAr)of chloro N-heteroaromatic amines with morpholine to morpholin-4-yl N-heteroaromatic amines in water was studied.The effects of different catalysts and solvents on SNAr,and the scope of the substrates were investigated.The results show that the SNAr of different chloro N-heteroaromatic amines with morpholine can proceed well in water with catalytic amount of hydrochloric acid.A series of morpholin-4-yl N-heteroaromatic amines were synthesized in 75.0%97.6%yields under the conditions of molar ratio of substrate to morpholine and hydrochloric acid of 1∶3∶0.3,water dosage of 1mL/mmol substrate,react temperature of 130℃,react time of 28 h.The target products with high purity can be obtained without purification.Under the given reaction conditions,the 2,4-dichloro substituents have good regioselectivity,and the 4-morpholino monosubstituted products are obtained in high yield.