Synthesis, molecular structure and reactivity of 5-methylidene-1,2,3,5- tetrahydroimidazo[2,1-b]quinazolines

Abstract

Synthesis of novel 5-methylidene-1,2,3,5-tetrahydro[2,1-b]-quinazoline derivatives 2-4 with potential biological activities mediated by α-adrenergic and/or imidazoline receptors was performed by reacting 2-chloro-4,5-dihydroimidazole (1) with the corresponding 2-aminoacetophenones. Compound 2, which incorporates an enamine moiety, underwent a 1,3-dipolar cycloaddition reaction with the appropriate nitrones 5-9 to give 1,2,3,5-tetrahydro-imidazo[2,1-b]quinazolin-5,5′-spiro-2′, 3′-diphenylisoxazolidines 10-14. Reactions of the title compounds 2 and 4 with dimethyl acetylenedicarboxylate (DMAD) afforded dimethyl 2-(2,3-dihydroimidazo[2,1-b]quinazolin-5(1H)-ylidenemethyl)but-2-enedioates 15, 16. Imidazo[2,1-b]quinazoline 2 was further treated with acetyl chloride, benzoyl chloride and mesyl chloride to give the 1-substituted derivatives 17, 18 and 19, respectively. The structures of all new compounds obtained were confirmed by elemental analysis and spectral data (IR, 1H- and 13C-NMR) as well as X-ray crystallographic analysis of 3 and 18.