I. V. Krylova

Synthesis, properties, and biological activity of β-aroylpyruvoyl hydrazides oF N-methyl- and N-phenylanthranilic acid

Anthranilic acid hydrazides exhibit antistaphylococcus [ I ] and antiaggregation activity with respect to blood plasma thrombocytes [2]. They also can be used for the syntheses of nitrogen-containing heterocycles exhibiting various pharmacological effects [3]. Aroylpyruvic acid hydrazides exhibit a bacteriostatic effect against Staphylococcus aureus and Escherichia coli [4], inhibit the growth of A and B influenza viruses, and exhibit an antiinflammatory effect [5]. In searching for novel biologically active compounds we synthesized 13-aroylpyruvoyl hydrazides of N-methyland Nphenylanthranilic acids ( IVXVI) and studied their antiinflammatory and antimicrobial activity. The target products were obtained by the reaction of 5aryl-2,3-dihydrofuran-2,3-diones (I) with hydrazides of Nmethyland N-phenylanthranilic acids (I1 and III) in an inert solvent at room temperature. Compounds I1 and III qualify as binucleohilic reagents. The nucleophilic centers are the !3amino group ofhydrazide moiety and the aromatic N-methyland N-phenyl amino groups. The nucleophilic properties of the hydrazide 13-amino group are most pronounced, because nucleophilicity of the aromatic amino group is reduced due to the positive mesomeric effect. In addition, the steric effects can also affect the reactivity of this group [6]. It is well known that in the case of nonequivalent nucleophilic centers the furandione ring is opened under the action of the strongest nucleophilic agent [7]. The synthesized compounds are yellow solids, almost insoluble in water, and give like other ariylpyruvic acid derivatives a cherry color when reacted with an ethanol solution of FeCI3. This indicates that the compounds exist in the enol. The previous studies have established that cc-carbonyl of aroylpyruvic moiety undergoes enolization in any case [8].

Five-membered 2,3-dioxoheterocycles

The reaction of 5-aryl-2,3-dihydrofuran-2,3-diones with benzamide oxime, diaminoglyoxime, and hydroxyurea gave 3-phenyl-5-aroylacetyl-1,2,4-oxadiazoles, 5,6-dihydroxyimino-3-phenacylidenepiperazin-2-ones, and 3-hydroxy-5-phenacylideneimidazolidine-2,4-diones, respectively. 6-Phenacylidene-5-oxo-4,5,6,7-tetrahydrofurazano [3,4-b]pyrazines are formed in the reaction of 5-aryl-2,3-dihydrofuran-2,3-diones with diaminofurazan.

Five-membered 2,3-dioxoheterocycles. 28. Reaction of 5-aryl-2,3-dihydrofuran-2,3-diones with thioamides and thiosemicarbazides

The reaction of 5-aryl-2,3-dihydrofuran-2,3-diones (I) with thiocarbonyl compounds has been described only for thiourea. The products of this reaction are 3-aryl-5-phenacylidene-4-oxoimidazolidine-2-thiones [2]. It seemed of interest to study the conversion of the furandiones (I) with a wider range of thiocarbonyl compounds such as thioamides and thiosemicarbazides.