Study On The Synthesis Of 2-Amino-3-heterocyclic Substituted Chromene Derivatives

2-Amino chromene derivatives play important roles in heterocyclic compounds which are widely distributed in natural products. Because of their unique biological and pharmacological activities, including anti-cancer, anti-proliferative, anti-tumor, anti-viral, and anti-microbial activities, 2-amino chromene and its derivatives have also been regarded as one type of ‘privileged medicinal scaffolds'. Their synthesis has also attracted considerable attention for the significant application of the 2-amino-4H-chromene framework. Although there are many reports referred to the synthesis of 2-amino-4H chromene derivatives, rarely reports about the facile synthesis of 2-amino-3-heterocyclic chromene derivatives have been appeared.This paper adopts the following ideas to study the synthesis of 2-amino-3-heterocyclic chromene derivatives. In the beginning,(E)-2-(benzothiazol-2-yl)-3-(2-hydroxyphenyl) acrylonitrile as an electron acceptor of Michael addition reaction reacted with different electron donors by the catalysis of a series of catalysts. The experimental result indicated that(E)-2-(benzothiazol-2-yl)-3-(2-hydroxyphenyl) acrylonitrile and diphenyl phosphate can occur tandem Michael addition under the catalysis of K2CO3, to afford(2-amino-3-(benzothiazol-2-yl)-4H-chromen-4-yl) phosphonate derivatives. The reaction condition was optimized as using 20 mol% catalysts, CH2Cl2 as solvent and at room temperature. Then the substrate scope was investigated and the corresponding products could be obtained with excellent yields(up to >99%).In addition, one-pot three component reaction of salicylaldehyde, 2-(benzothiazol-2-yl) acetonitrile and diphenyl phosphate was also developed using Et3 N as catalyst to afford the corresponding(2-amino-3-(benzothiazol-2-yl)-4H-chromen-4-yl) phosphonate derivatives. The reaction condition was also optimized as using 20 mol% catalysts, CH2Cl2 as solvent and at room temperature. Then the substrate scope was also investigated and the corresponding products could be obtained with moderate yields(up to 59%). Meanwhile, we proposed a plausible mechanism for this one-pot three component reaction.Finally,(E)-2-(benzothiazol-2-yl)-3-(2-hydroxyphenyl) acrylonitrile as an electron acceptor of Michael addition reaction reacted with different Michael donors(such as dimethyl phosphite, diethyl phosphate, etc.) were also explored, but did not reach the desired effect as we expected.