Study on Some Heterocyclic Compounds of Expected Biological Activity

Abstract

Heterocyclic compounds, in particular oxygen-containing molecules, represent an indispensable class due to their physicochemical properties. The literature reveals that chromene and benzochromene derivatives are important pharmacophores associated with a broad range of pharmacological activities. Benzochromene nucleus has been emerged as a promising and attractive scaffold in the development of potent antitumor agents. Based on these considerations, the interest of the author was focused on synthesizing new heterocycles including benzochromene moieties with suitable substituents. In summary, this thesis comprises the following: Introduction: It covers a brief survey on the benzochromene derivatives including structure, nomenclature, methods of preparation, chemical reactions, and their biological activities. Results and Discussion: In this section, the reactions utilized for synthesis of novel 1H-benzo[f]chromene, benzo[f]chromeno[2,3-d]pyrimidine and 14H-benzo[f]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives are discussed with references to the knowledge available in the literature.

Mechanistic pathways are proposed to the synthesis of some compounds. Thus, treatment of naphthalene-2,7-diol (24) with a mixture of 4-chlorobenzaldehde (10) and malononitrile (11a) or with α-cyano-4-chlorocinnamonitrile (36) in ethanolic piperidine solution under reflux for 1 h afforded 1:1 adduct, 3-amino-1-(4-chlorophenyl)-9-hydroxy-1H-benzo[f]chromene-2-carbo-nitrile (25).

In a similar manner, the reaction of naphthalene-2,7-diol (24) with a mixture of 4-chlorobenzaldehyde (10) and ethyl cyanoacetate (11b) in ethanolic piperidine solution under reflux for 2 h afforded 1:1 adduct, ethyl 3-amino-1-(4-chlorophenyl)-9-hydroxy-1H-benzo[f]chromene-2-carboxylate (91), while reaction of (24) with ethyl α-cyano-4-chlorocinnamate (37) in ethanolic piperidine solution under reflux for 2 h afforded the ethyl 3-amino-1-(4-chlorophenyl)-9-hydroxy-1H-benzo[f]chromene-2-carboxylate-ethyl α-cyano-4-chlorocinnamate complex (92) instead of the β-enaminoester (91). The structure of (92) was confirmed by spectral data and X-ray single crystal data.

Interaction of 3-amino-1-(4-chlorophenyl)-9-hydroxy-1H-benzo[f]chromene-2-carbonitrile (25) with acetic anhydride for 0.5 h afforded the open chain product 9-acetoxy-3-acetylamino-1-(4-chlorophenyl)-1H-benzo[f]chromene-2-carbonitrile (93), while heating of the compound (25) with acetic anhydride for 3 h afforded the cycloaddition product 2-acetoxy-12-(4-chloro-phenyl)-10,11-dihydro-9-methyl-12H-benzo[f]chromeno[2,3-d]-pyrimidin-11-one (94) with acylation of the hydroxyl group at 9-position into the acetoxy group. Besides, condensation of compound (25) with formamide under reflux for 6 h afforded the cycloaddition product 11-amino-12-(4-chlorophenyl)-2-hydroxy-12H-benzo[f]chromeno[2,3-d]pyrimidine (95), while benzoylation of the compound (25) with benzoyl chloride under reflux gave the cycloaddition product 2-benzoxy-12-(4-chloro-phenyl)-10,11-dihydro-9-phenyl-12H-benzo[f]chromeno