Synthesis and Antidepressant Activity of Some New Coumarin Derivatives

The coumarin-3-cinnamoyl derivatives 2a-d were prepared via Claisen-Schmidt condensation of 3-acetylcoumarin 1 with different aromatic aldehydes. Cycloaddition reaction of 2b,e with guanidine and thiourea yielded the corresponding aminopyrmimidine 3a,b and thioxypyrimidine derivatives 4a,b, respectively. Compounds 4a, b were condensed with chloroacetic acid or 3-bromopropionic acid to yield coumarin 3-thiazolo-pyrimidine 5a,b and thiazinopyrimidine 6a,b derivatives, respectively. Compounds 4a, b were condensed with chloroacetic acid and aromatic aldehyde to yield the aryl methylene derivatives 7a,b which could be prepared directly by condensation of compounds 5a, b with aromatic aldehydes. Compounds 2a-e were condensed with malononitrile or ethyl cyano acetate in presence of ammonium acetate to yield cyanopyridine 8a,b and cyanopyridone 9a-d derivatives, respectively, which were prepared by condensation of 3-acetylcoumarin 1, malononitrile or ethylcyanoacetate and aromatic aldehydes in presence of ammonium acetate. Condensation of compounds 2a,b,e with o-phenylenediamine in refluxing ethanol led to the formation of 10a-c as intermediate, followed by cleavage by thermolysis to benzimidazole derivative 11 along with compounds 12a-c as mixture, which were obtained directly by fusion of alpha,beta-unsaturated ketones 2 with o-phenylene diamine at 200-220 degrees C, while compound 11 could be prepared in pure form by fusion of 1 with o-phenylene diamine at the same temperature. The pharmacological screening showed that many of these obtained compounds have good antidepressant activity comparable to Tranylcypromine (R) as reference drugs.