I. V. Mashevskaya

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).

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.

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: LIX. Reaction of 3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with Acyclic β-Enaminoesters. Crystal and Molecular Structure of Ethyl 3-Benzoyl-4-hydroxy-1-o-hydroxyphenyl-5-oxo-2,3-dihydro-1H-pyrrolo-2-spiro-3′-(5-methyl-2-oxo-2,3-dihydro-1H-pyrrolo-4-carboxylate)

Abstract3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones react with substituted alkyl 3-amino-2-propenoates to form substituted alkyl 3-aroyl-4-hydroxy-1-o-hydroxyphenyl-5-oxo-2,5-dihydro-1H-pyrrole-2-spiro-3′-(2-oxo-2,3-dihydro-1H-pyrrole-4-carboxylates). Crystal and molecular structure of ethyl 3-benzoyl-4-hydroxy-1-o-hydroxyphenyl-5-oxo-2,5-dihydro-1H-pyrrole-2-spiro-3′-(5-methyl-2-oxo-2,3-dihydro-1H-pyrrole-4-carboxylate) was investigated.

Synthesis and Study of the Antibacterial and Analgesic Activity of 3-Acyl-1,2,4,5-tetrahydro-[1,2-a]quinoxaline-1,2,4-triones

As is known, derivatives of 1,2,3,4-tetrahydro-2-quinoxalones possess pronounced anticonvulsant and analgesic properties [1]. It was of interest to broaden the spectrum of pharmacological activity of compounds belonging to this class by modifying the base structure by annelation with a pyrrole cycle via the 1 – 2 bond of quinoxalone. For this purpose, we synthesized a series of 3-acyl-1,2,3,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones (X – XVIII) using reactions of 3-alkoxycarbonylmethyleneand 3-phenacylidene-1,2,3,5-tetrahydro-2-quinoxalones (I – IX) with oxalyl chloride in anhydrous chloroform conducted by the method developed in [2].

Synthesis and analgesic activity of the products of the interaction between 3-aroylpyrrolo[1,2-a]-quinoxaline-1,2,4(5H)-triones with benzoic acid hydrazides

The synthesis, properties, structure, and analgesic activities of the products of the interaction of 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones with benzoic acid hydrazides are described. The significance of the structure-function relationship is discussed.

Five-membered 2,3-dioxoheterocycles: LXXIII. Synthesis and thermolysis of 3-acylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones

Reactions of (Z)-3-(phenacylidene-2-oxo)-3,4-dihydroquinoxalin-2(1H)-ones and (Z)-3-(3,3-dimethyl-2-oxobutylidene)-3,4-dihydroquinoxalin-2(1H)-one with oxalyl chloride led to the formation of 3-acyl-1Hpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones that at the thermal decarbonylation generated acyl(3-oxoquinoxalin-2-yl)ketenes which underwent the intramolecular stabilization giving 3-acylfuro[3,2-b]quinoxalin-2(4H)-ones.

Five-Membered 2,3-Dioxo Heterocycles: XLIV. Reaction of 3-Aroyl-1,2,4,5-tetrahydropyrrolo[1,2-a]- quinoxaline-1,2,4-triones with o-Phenylenediamines

The reaction of (Z)-3-phenacylidene-1,2,3,4-tetrahydroquinoxalin-2-ones with oxalyl chloride gives 3-aroyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones which react with o-phenylenediamine to afford 8-aryl-6,7,9,14,15,16-hexahydroquinoxalino[1,2-a]pyrrolo[2,3-b][1,5]benzodiazepine-6,7,15-triones.

New pathway of the reaction of hetareno[a]pyrrole-2,3-diones with NH nucleophiles

By reactions of 3-benzoylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-trione (Ia) with phenylhydrazine and of 3-benzoyl-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine1,2,4-trione (Ib) with 2-hydrazinobenzoic acid (reactant molar ratio 1 : 1, anhydrous acetonitrile, 1–3 min under reflux; TLC monitoring), we obtained products resulting from nucleophilic attack at the C carbon atom, (Z)-3-benzoyl-2-(2-phenylhydrazono)pyrrolo[1,2-a]quinoxaline-1,4(2H,5H)-dione (IIa) and (Z)-2-{2-(3-benzoyl)-1,4-dioxo-1H-benzo[b]pyrrolo[1,2-d][1,4]-oxazin-2(4H)-ylidenehydrazino}benzoic acid (IIb). The product structure was proved by X-ray analysis of compound IIb. Although the possibility for other (than those indicated above [1]) direction of nucleophilic attack on 4-acyl-1H-pyrrole-2,3-diones fused at the N–C bond to various heterocycles was theoretically predicted about 20 years ago [2], products of such reactions were isolated for the first time.

Five-membered 2,3-dioxo heterocycles: LXXIV. Recyclization of 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones by the action of benzohydrazides. Crystalline and molecular structure of N-[2,4-dihydroxy-5-oxo-3-(3-oxo-3,4-dihydroquinoxalin-2-yl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]benzamide

Recyclization of 3-aroyl-1H-pyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones by the action of benzoic acid hydrazides gave N-[2,4-dihydroxy-5-oxo-3-(3-oxo-3,4-dihydroquinoxalin-2-yl)-2-aryl-2,5-dihydro-1H-pyrrol-1-yl]benzamides whose structure was proved by X-ray analysis.