Synthesis and biological evaluation of novel polysubstituted chromene, chromenopyrimidine and chromenotriazolopyrimlidine derivatives

2-Amino-4H-chromene-3-carbonitrile derivatives 3a-e were synthesized by treatment of resorcinol or phloroglucinol with alpha-cyanocinnamonitriles or ethyl alpha-cyanocinnamates. Cyclization of compound 3a with formamide furnished chromeno[2,3-d]pyrimidine derivative 4. Acetylation of 3b,c,d with acetic anhydride produced 2-acetamido-7-acetoxy-3-cyanochromene derivatives 5ac. 2-Ethoxymethyleneamino derivative 6 was obtained through the reaction of 3a with triethyl orthoformate. While, using triethyl orthoformate/acetic anhydride mixture, 7-acetoxy-2-ethoxymethyleneamino derivative 7 was obtained. Cyclocondiensation of 6 with p-chloroaniline afforded the corresponding chromeno[2,3-d]pyrimidine S. Furthermore, interaction of 6 with hydrazine hydrate gave 3-amino-4-imino derivative 10 which was subjected to cyclocondensation with formic acid, acetic anhydride and benzoyl chloride, where the corresponding triazolopyrimidine derivatives 11, 12 and 13 were obtained, respectively. Selected compounds are screened in vitro for antimicrobial activity.