b-(4-Chlorobenzoyl)acrylic acid (1) proved to be a convenient precursor for the synthesis of a variety of heterocyclic systems through the reaction with compounds containing active methylene groups under Michael reaction conditions. Also, the reactivity of Michael adduct towards nitrogen nucleophiles was investigated to afford diazepine, indazole, isoxazole and quinazoline derivatives. Some of the synthesized compounds were screened for their biological activity.
Keywords: Indazole; Isoxazole; Michael adduct; Diazepine and quinazoline derivatives.Recently, significant progress has been made in the development of antiviral chemotherapy due to pyrazole and diazepine derivatives. [13][14][15][16] Accordingly, the condensation of Michael adducts 2a and 2b-h with hydrazines (viz. hydrazine hydrate and phenyl hydrazine) in refluxing ethanol afforded 4-(4-chlorophenyl)-2-(3-methyl-5-oxo-1H/phenyl-4,5-dihydro-1H-pyrazol-4-yl)-4-oxobutyric acid (3a,b) and diazepine derivatives (4a,b to 10a, b), respectively (Scheme I).An even more convenient access to the synthesis of heterocyclic compounds of biological interest was established by fusion of b-(4-chlorobenzoyl)acrylic acid with acetyl acetone in the presence of sodium methoxide to give a mixture of 6-acetyl-3-(4-chlorophenyl)-5-oxo-cyclohex-3ene carboxylic acid (11) and 3,3-diacetyl-2,4-bis[2-(4-chlorophenyl)-2-oxoethyl]pentanedioic acid (12).
Scheme II
General procedure of the reaction of b-(4-chlorobenzoyl)acrylic acid (1) with active methylene compounds: Formation of 2a-hA mixture of 1 (2.25 g, 0.01 mol), the active methylene compound, namely ethyl acetoacetate, acetyl acetone, ethyl-cyanoacetate, camphor, cyclohexanone, ethyl phenyl acetate, diethylmalonate and malononitrile (0.02 mol) in ethanol (30 mL), was treated with sodium hydroxide (3g, 6 mL). The reaction mixture was heated at 40°C for 24 h and then left overnight at room temperature (in the case of ethyl acetoacetate or 1208
