Reaction of 2-(2-oxoethylidene)furan-3(2H)-ones with isopropylidenehydrazides of aromatic carboxylic acids: Synthesis of 3-hydroxy-3-(2-oxoethyl)-2,3-dihydropyridazin-4(1H)-ones

Abstract

Keywords: 3-hydroxy-3-(2-oxoethyl)-2,3-dihydropyridazin-4(1H)-ones, 2-(2-oxoethylidene)furan-3-(2H)-ones, reactions with benzoic and p-nitrobenzoic isopropylidenehydrazides.The reactions of 2-ylidenefuran-3(2H)-ones with hydrazine or arylhydrazines lead to the formation of hydrazino derivatives of 3-oxofuran [1], 3-acylpyrazoles [2-4], or 3-alkyl(ylidene)-substituted pyridazine-4(1H)-ones [4]. It is known that the action of aroylhydrazines on 3-oxofuran-2(3H)-ylideneacetates leads to the formation of 1-aroylamino-2-hydroxy-3-oxo-2,3-dihydro-1H-pyrrol-2-ylacetic esters [5]. Other reactions of acyl or ylidene derivatives of hydrazine with five-membered 2-ylidene-2,3-dihydro-3-oxo heterocycles had not been studied before our investigations.As a result of the reaction of methyl 3-oxo-5-phenylfuran-2(3H)-ylideneacetate (1a) or 2-[2-(4-chlorophenyl)-2-oxoethylidene]-5-phenylfuran-3(2H)-one (1b) with benzoic or p-nitrobenzoic isopropylidenehydrazides we unexpectedly obtained preparative yields of the previously unknown stable cyclic O,N-acetals -3-hydroxy-3-(2-oxoethyl)-6-phenyl-2,3-dihydropyridazin-4(1H)-ones 2a-d. Equilibrium tautomeric forms C (5) H (A) and C (5) H 2 (B) were detected in solutions of compounds 2c,d in DMSO-d 6 .When the isopropylidenehydrazides of carboxylic acids are brought into reaction with 2-(2-oxoethylidene)furan-3(2H)-ones 1 nucleophilic attack by the NH group of the equilibrium enamino form NH-CMe=CH 2 of the reagent probably occurs at the C (5) atom of the ring in the substrate 1 with subsequent intramolecular heterocyclization of the enehydrazinocarbonyl intermediate, hydrolytic elimination of a molecule of acetone, and the formation of 3-hydroxy-3-(2-oxoethyl)-6-phenyl-2,3-dihydropyridazin-4(1H)-ones 2. The regioselectivity of NH-nucleophilic attack by the hydrazides at the electron-deficient center C (5) of compounds 1 during the theoretically possible attack also at the C (2) , C (2') , or C (3) atoms confirms the probable orbital control of the reaction [6]. __________________________________________________________________________________________