A. N. Maslivets

Synthesis and Antimicrobial Activity of the Products of Interaction of 3-Aroyl-2,4-dihydro-1h-pyrrolobenzoxazine-1,2,4-triones with Urea and Thiourea

The products of interaction of 3-aroyl-2,4-dihydro-1Hpyrrolo[2,1-c]benzoxazine-1,2,4-triones (I – IV) with water exhibited antimicrobial activity. In this context, it was of interest to study the antimicrobial properties of the products of interaction of pyrrolobenzoxazinetriones I – IV with some other nucleophilic reagents, in particular with urea and thiourea, taking into account the role of these fragments in various biologically active compounds [2]. Boiling 3-aroyl-2,4-dihydro-1H-pyrrolo[2,1-c]benzoxazine-1,2,4-triones (I – IV) with urea or thiourea in acetonitrile or dioxane for 3 – 5 min led to a high yield of 3-[ -(2,5dioxoand 5-oxo-2-thioxo-Z-4-imidazolidinylidene)phenacyl]-2H-1,4-benzoxazin-2-ones (V – XII) (Table 1).

Five-membered 2,3-dioxo heterocycles: LI. Reaction of 3-aroyl-2,4-dihydro-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with 3-amino-5,5-dimethylcyclohex-2-en-1-ones

Abstract3-Aroyl-2,4-dihydro-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones react with N-unsubstituted and N-substituted 3-amino-5,5-dimethylcyclohex-2-en-1-ones to give 3′-aroyl-4′-hydroxy-1′-(o-hydroxy-phenyl)-6,6-dimethyl-6,7-dihydrospiro[indole-3,2′-pyrrole]-2,4,5′(1H,1′H,5H)-triones. The molecular and crystalline structure of the 1-cyclohexyl-substituted derivative was studied by X-ray analysis.

Synthesis and chemical transformations of 2,3-dihydropyrrole-2,3-diones annelated on the [a] side by azaheterocycles. (Review)

Data on methods for the synthesis of 2,3-dihydro-2,3-pyrrolediones condensed with azaheterocycles on the [a] side are reviewed. Their reactions with nucleophilic reagents, allylboronation, reduction, and thermal transformations are discussed.

Five-membered 2,3-dioxo heterocycles: XLV. Thermolysis of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones in the absence of other partners and in the presence of carbonyl compounds

Aroyl(phenyl)ketenes generated by thermolysis of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones undergo [4+2]-cyclodimerization to 3-aroyl-6-aryl-3,5-diphenyl-3,4-dihydro-2H-pyran-2,4-diones. Heating of the latter leads to rearrangement with formation of 4-aroyloxy-6-aryl-3,5-diphenyl-2H-pyran-2-ones. Thermolysis of 5-aryl-4-phenyl-2,3-dihydrofuran-2,3-diones in the presence of carbonyl compounds yields 6-aryl-5-phenyl-4H-1,3-dioxin-4-ones.

Five-membered 2,3-dioxoheterocycles: LXXXIV. [4+2]-Cycloaddition of styrene to 4,5-diaroyl-1H-pyrrole-2,3-diones. Crystal and molecular structures of 7a-(2,5-dimethylbenzoyl)-4-(2,5-dimethylphenyl)-1-(4-methoxyphenyl)-6-phenyl-7,7a-dihydropyrano[4,3-b]-pyrrole-2,3(1H,6H)-dione

Abstract1-Aryl-4,5-diaroyl-1H-pyrrole-2,3-diones react with styrene to form substituted 7,7a-dihydropyrano[4,3-b] pyrrole-2,3(1H,6H)-diones whose structure was confirmed by XRD analysis. The crystal and molecular structure of 7a-(2,5-dimethylbenzoyl)-4-(2,5-dimethyl-phenyl)-1-(4-methoxyphenyl)-6-phenyl-7,7a-dihydropyrano[4,3-b] pyrrole-2,3(1H,6H)dione was examined.

A Comparative Study of the Antimicrobial Activity of Some Quinoxalines, 1,4-Benzoxazines, and Aza-Analogs

It was reported that (Z )-3-phenacylidene-1,2,3,4tetrahydro-2-quinoxalones and (Z )-3-phenacylidene-3,4dihydro-2H-1,4-benzoxazin-2-ones [1, 2] possess antiinflamatory [2, 3], antitumor, and bacteriostatic properties [4]. The purpose of our study was to modify the structure of these compounds by substituting the heteroyl fragment for the aroyl fragment and introducing a heteroatom into the benzene ring of quinoxaline or 1,4-benzoxazine, so as to trace the possible change in activity (in particular, antimicrobial) in the series of such derivatives. For this purpose, we have synthesized a series of compounds including (Z )-3-aroyl(heteroyl)methylene-1,2,3,4-tetrahydro-2-quinoxalones (I, II) [5], (Z )-3-aroyl(heteroyl)-methylene-3,4-dihydro-2H-1,4-benzoxazin-2-ones (III – V) [5], (Z )-2-heteroylmethylene-1,2,3,4-tetrahydropyrido[2, 3-b]pyrazin-2-ones (VI, VII) [6], and (Z )-3-aroyl(heteroyl)methylene-3,4-dihydro2H-pyrido[2, 3-b]-1,4-oxa-zin-2-ones (VIII – IX). The synthesized compounds were tested for antimicrobial activity. Aroyl(heteroyl)pyridooxazinones (VIII – X) were obtained via the interaction of equimolar amounts of the corresponding 4-aryl(heteryl)2,4-dioxobutanoic acids and 2-amino-3-hydroxypyridine. Compounds VIII – X appear as bright-yellow crystalline substances, soluble in ethanol, dioxane, and acetonitrile and insoluble in water (Table 1). The spectroscopic characteristics of the new products agree well with those of the previously reported aroyl(heteroyl)-1,4-banzoxazinones [2, 5]. Indeed, the IR spectra of compounds VIII – X (Table 2) exhibit absorption bands due to the stretching vibrations of ketone carbonyl groups in the region of 1630 – 1640 cm – 1 and ester carbonyl groups at 1770 cm – . The H NMR spectra of com-

Five-membered 2,3-dioxoheterocycles: LXIV. Reactions of 1-methyl-3,4-dihydroisoquinolines with 5-arylfuran-2,3-diones and (Z)-alkyl 4-aryl-2-hydroxy-4-oxobut-2-enoates. Crystal and molecular structure of (2Z,5Z)-3-hydroxy-5-{8,8-dimethyl-2,3,8,9-tetrahydro[1,4]dioxino[2,3-g]isoquinolin-6(7H)-ylidene}-1-phenylpent-2-ene-1,4-dione

Abstract5-Arylfuran-2,3-diones and (Z)-alkyl 4-aryl-2-hydroxy-4-oxobut-2-enoates react with 3,3-dialkyl-1-methyl-3,4-dihydroisoquinolines to give (2Z,5Z)-1-aryl-3-hydroxy-5-[3,3-dialkyl-3,4-dihydroisoquinolin-1(2H)-ylidene]pent-2-ene-1,4-diones whose structure has been proved by XRD analysis.

Five-membered 2,3-dioxo heterocycles: LII. Reactions of 5-aryl-4-(quinoxalin-2-yl)-2,3-dihydrofuran-2,3-diones with Schiff bases and dicyclohexylcarbodiimide. Crystalline and molecular structure of substituted 2-(4-oxo-3,4-dihydro-2H1,3-oxazin-5-yl)quinoxalines

Aroyl(quinoxalinyl)ketenes generated by thermolysis of 5-aryl-4-(quinoxalin-2-yl)-2,3-dihydrofuran-2,3-diones react with N-benzylideneanilines and N,N’-dicyclohexylcarbodiimide according to the [4+2]-cycloaddition pattern where the aroylketene acts as diene, and C=N component, as dienophile, to give 3-aryl-2-(2,3,6-triaryl- and 6-aryl-3-cyclohexyl-2-cyclohexylimino-4-oxo-3,4-dihydro-2H-1,3-oxazin-5-yl)quinoxalines. The structure of two cycloaddition products was proved by X-ray analysis.

Five-membered 2,3-dioxo heterocycles: LXXXVIII. Reaction of 3-aroylpyrrolo[1,2-d][1,4]benzoxazine-1,2,4(4H)-triones with N,N′-dicyclohexylcarbodiimide under thermolysis conditions

Thermolysis of 3-aroylpyrrolo[1,2-d][1,4]benzoxazine-1,2,4(4H)-triones generates aroyl(2-oxo-1,4-benzoxazin-3-yl)ketenes which react as dienes at the aroylketene fragment in [4 + 2]-cycloaddition at the C=N bond of N,N′-dicyclohexylcarbodiimide with formation of 3-[6-aryl-4-oxo-3-cyclohexyl-2-cyclohexylimino-3,4-dihydro-2H-1,3-oxazin-5-yl]-2H-1,4-benzoxazin-2-ones. Thermolysis of the latter is accompanied by elimination of N,N′-dicyclohexylcarbodiimide, and aroyl(2-oxo-1,4-benzoxazin-3-yl)ketenes thus generated undergo cyclodimerization to produce 7-aroyl-6,10-dioxo-9-(2-oxo-2H-1,4-benzoxazin-3-yl)-6,10-dihydrobenzo[b]pyrido[1,2-d][1,4]oxazin-8-yl benzoates.

Five-membered 2,3-dioxo heterocycles: LXXV. Reaction of methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with 1,3-diphenylguanidine. Crystalline and molecular structure of 9-Benzoyl-8-hydroxy-2-imino-6-(4-methylphenyl)-1,3-diphenyl-1,3,6-triazaspiro-[4.4]non-8-ene-4,7-dione

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 1,3-diphenylguanidine to give the corresponding 6-aryl-9-aroyl-8-hydroxy-2-imino-1,3-diphenyl-1,3,6-triazaspiro[4.4]non-8-ene-4,7-diones. The molecular and crystalline structures of 9-benzoyl-8-hydroxy-2-imino-6-(4-methylphenyl)-1,3-diphenyl-1,3,6-triazaspiro[4.4]non-8-ene-4,7-dione were determined by X-ray analysis.