Reaction of 5-arylfuran-2(3H)-ones with amines

Abstract

5-(4-Chlorophenyl)-and 5-phenylfuran-2(3H)-ones reacted with guanidine carbonate at the methylene group in the unsaturated lactone molecule, leading to the formation of 4-(2-aryl-5-oxo-2,5-dihydrofuran-2-yl)-5-aryltetrahydrofuran-2-ones, while 5-(4-methylphenyl)furan-2(3H)-one under analogous conditions gave rise to N, N′-bis[4-(4-methylphenyl)-4-oxobutanoyl]guanidine. The reactions of 5-arylfuran-2(3H)-ones with thioacetamide afforded 4-aryl-N-{1-[5-aryl-2-oxo-2,3-dihydrofuran-3-ylidene]ethyl}-4-oxobutanamides. The corresponding N-(4-aryl-4-oxobutanoyl)thioureas were obtained by heating 5-arylfuran-2(3H)-ones with thiourea.Various nitrogen-containing heterocyclic systems are often synthesized following an approach based on the reaction of equimolar amounts of difunctional electrophiles with amines. 5-Arylfuran-2(3H)-ones I are synthetic equivalents of 1,4-bielectrophiles. Although studies on the properties of these compounds have been initiated long ago by Biedermann [1] and Fittig [2] in the end of the XIXth century, known reactions of 5-arylfuran-2(3H)-ones I with amines are strongly limited; examples of their reactions with hydrazine derivatives and primary and secondary alkyl-and arylamines have been reported; in some cases, these reactions led to the formation of pyrrole [3-5] and pyridazine derivatives [6]. We now report on the reactions of 5-arylfuran-2(3H)-ones Ia-Ic with 1,3-binucleophiles, namely guanidine, thiourea, and thioacetamide, which were expected to produce nitrogen-and sulfur-andnitrogen-containing heterocycles.It is known that heating of 5-arylfuran-2(3H)-ones I with amines results in opening of the lactone ring and formation of the corresponding 4-aryl-4-oxobutanoic acid amides [2,3,5]. 5-(4-Methylphenyl)furan-2(3H)-one (Ic) reacted with guanidine carbonate according to a similar scheme: fusion of a mixture of the reactants at 120-130°C gave a 4-(4-methylphenyl)-4-oxobutanamide derivative. The product structure followed from its 1 H NMR spectrum which contained signals from methylene protons as two triplets at δ 2.70 and 3.22 ppm ( 3 J = 6.5 Hz) and NH proton signal at δ 9.33 ppm, br.s. This pattern is typical of 4-aryl-4-oxobutanoic acid derivatives [7]. In the IR spectrum of the product we observed ν NH bands at 3350 and 3289 cm -1 . In keeping with the mass-spectral data, the product was diacyl-substituted guanidine (m/z 408 [M + 1] + ). The above spectral data are consistent with three isomeric structures: