The Use of 3-Benzylidene Phthalide as Precursor to Synthesize New 1,3,4-Oxadiazole Derivatives

A series of new 2,5-disubstituted 1,3,4-oxadiazoles represented by compounds 2-phenyl-1(2-(5-(5-aryl-1,3,4-oxadiazol-2-yl amino)-4H-1,2,4-triazol-3-yl)phenyl)ethanone (5a-f) have been synthesized from(Z)-3-benzylidene phthalide as useful precursor. 3-Benzylidene phthalide was reacted, firstly with urea under microwave irradiation and dry conditions to afford the corresponding 1-(2-(α-phenylacetyl)benzoyl)urea (1). The later compound underwent cycloaddition reaction with hydrazine hydrate (80%) to give 1-(2-(5-amino-4H-1,2,4-triazol-3yl)phenyl)-2-phenylethanone (2), which upon reaction with ethyl chloroformate provided the corresponding ethyl- 5-(2-(α-phenylacetyl)phenyl)-4H-1,2,4-triazol-3-yl carbamate (3). 4-(5-(2-(α-Phenylacetyl)phenyl)-4H-1,2,4-triazol-3-yl) semicarbazide (4) was also prepared from the reaction of compound (3) with hydrazine hydrate (80%) under mild conditions. Finally, 2-phenyl-1-(2-(5-(5-aryl-1,3,4-oxadiazol-2-yl amino)-4H-1,2,4-triazole-3-yl)phenyl) ethanone (5a-f) were obtained via the reaction of compound (4) with various substituted benzoic acid by the action of phosphorous oxychloride. The structure of the prepared compounds were confirmed by the available physical and spectral methods.