Synthesis of novel 3-(α-arylhydrazono-1,3,4-oxadiazol-2-ylmethyl)-2-oxo-1,2-dihydroquinoxalines and their characteristic tautomerism between the hydrazone imine and diazenyl enamine forms

The reactions of 3-(α-arylhydrazono)hydrazinocarbonylmethyl-2-oxo-1,2-dihydroquinoxalines 1a,b with triethyl orthoesters resulted in the intramolecular cyclization to give the 3-(α-arylhydrazono-1,3,4-oxadiazol-2-ylmethyl)-2-oxo-1,2-dihydroquinoxalines 4a–d , but not the 1,2,4,5-tetrazepinylquinoxalines 5a–d . The cyclization mode into the 1,3,4-oxadiazole ring was confirmed by the alternate syntheses of 4a,c from the reactions of 3-(1,3,4-oxadiazol-2-ylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxalines 6a,b with o-chlorophenyl diazonium salts, respectively. Moreover, 4a–d exhibited an interesting tautomerism between the hydrazone imine form A and diazenyl enamine form B.     

Synthesis of 3-(α-chlorophenylhydrazono)heteroarylmethyl-2-oxo-1,2-dihydroquinoxalines with antimicrobial activity

The reactions of 3-(α-chlorophenylhydrazono)hydrazinocarbonylmethyl-2-oxo-1,2-dihydroquinoxalines 4a,c with triethyl orthoesters resulted in the intramolecular cyclization to give the 3-(α-chlorophenylhydrazono-1,3,4-oxadiazol-2-ylmethyl)-2-oxo-1,2-dihydroquinoxalines 5a-d , but not the 1,2,4,5-tetrazepinylquinoxalines 6a-d . The cyclization mode into the 1,3,4-oxadiazole ring was confirmed by the alternate syntheses of 5a,c from the reactions of the 3-(1,3,4-oxadiazol-2-ylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxalines 7a,b with o-chlorobenzenediazonium chloride. Moreover, the reactions of 3-(benzimidazol-2-ylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxaline hydrochloride 8 with o-, m- and p-chlorobenzenediazonium chlorides afforded the 3-(α-chlorophenylhydrazonobenzimidazol-2-ylmethy])-2-oxo-1,2-dihydroquinoxa]ine hydrochlorides 9a-c , respectively. Compounds 5a-d and 9a-c were found to exhibit antimicrobial activities.     

Reaction of 3-phenyl-3-chloro-2-oxopropionic acid derivatives with ortho-phenylenediamine

Conclusions The reaction of dialkylamides of 3-phenyl-3-chloro-2-oxopropionic acid with orthophenylenediamine gave 2-(N,N-dialkylcarbamoyl)-1,4-dihydroquinoxalines, while esters of this acid react with ortho-phenylenediamine to give 3-(-chlorobenzyl)-2-oxo-1,2-dihydro-quinoxalines, which react with phosphites to yield the corresponding 3-(O,O-dialkylphos-phonobenzyl)-2-oxo-1,2-dihydroquinoxalines.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1412–1414, June, 1989.     

1H-NMR study on the tautomer ratios between the hydrazone imine and diazenylenamine forms in 3-(arylhydrazono)-methyl-2-oxo-1,2-dihydroquinoxalines

The o-substituted 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines 1a-c and 2a , c were synthesized to investigate the tautomeric behavior between the hydrazone imine A and diazenylenamine B forms in a series of mixed dimethyl sulfoxide/trifluoroacetic acid media. The chemical shifts of the hydrazone NH, N₄-H, hydrazone CH, and diazenyl CH protons for o-, m-, and p-substituted 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines 1 and 2 synthesized so far are summarized in Tables 3 and 4, respectively, which are found to be useful for the specification of the proton signals due to the hydrazone imine form A (hydrazone NH, hydrazone CH) and diazenylenamine form B (N₄-H, diazenyl CH).     

3-(α-azidoalkyl)quinoxalin-2(1H)-ones and related alkylquinoxalinyl ketones

A convenient method has been developed for the synthesis of 3-alkanoyl-and 3-benzoyl-2-oxo-1,2-dihydroquinoxalines from the corresponding 3-(α-azidoalkyl)quinoxalines using acetic acid. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 574–577, 2007.     

Substituent effects on the tautomer ratios between the hydrazone imine and diazenyl enamine forms in side-chained quinoxalines

The 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines 9–11 were synthesized by the reaction of the quinoxalines 6–8 with various p-substituted benzenediazonium salts. Compounds 9–11 showed the tautomeric equilibria between the hydrazone imine A and diazenyl enamine B forms in dimethyl sulfoxide media. The substituent effect on the tautomer ratios of A to B was studied by the nmr spectroscopy to clarify that the presence of the ester group R² on the hydrazone carbon and electron-donating p-substituent R¹ on the side chain benzene ring exhibited a tendency to increase the ratios of the tautomer A .     

Synthesis and conversions of 3-(4-amino-5-methyl-4H-1,2,4-triazol-3-ylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxaline

The reaction of the hydrazone 3a with hydrazine hydrate in DBU/ethanol conveniently gave 3-(4-amino-5-methyl-4H-1,2,4-triazol-3-ylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxaline 6 . The reactions of 6 with an equimolar and 2-fold molar amount of nitrous acid afforded 3-(α-hydroxyimino-4-amino-5-methyl-4H-1,2,4-triazol-3-ylmethyl)-2-oxo-1,2-dihydroquinoxaline 9 and 3-(α-hydroxyimino-5-methyl-2H-1,2,4-triazol-3-ylmethyl)-2-oxo-1,2-dihydroquinoxaline 10 , respectively, which were converted into the 3-heteroarylisoxazolo[4,5-b]quin-oxalines 13a,b and 11 , respectively. Compound 9 was also cyclized into the 8-quinoxalinyl-1,2,4-triazolo-[3,4-f][1,2,4]triazines 14a,b .     

Chemistry of acyl(imidoyl)ketenes. 7. Synthesis and thermolysis of 5-aryl-4-quinoxalinyl-2,3-dihydrofuran-2,3-diones

3-Aryl-Z-2-aroylmethylidene-1,2-dihydroquinoxalines react with oxalyl chloride to form 3-aryl-2-(2-aryl-4,5-dioxo-4,5-dihydro-3-furyl)quinoxalines, whose thermal decarbonylation generate 5-aryl-2-3(arylquinoxalin-2-yl)-4-aroyl-3-aroyloxy-1H-pyrido[1,2-a]quinoxalin-1-ones. The crystal and molecular structures of one of them (Ar = Ph) were established by X-ray diffraction analysis.     

Cyclopropanation of 2-arylmethylidenemalononitriles,alkyl 3-aryl-2-cyanoprop-2-enoates,and N-substituted 3-aryl-2-cyanoprop-2-enamides with bromine-containing zinc enolates

Zinc enolates derived from 2,2-dibromoindan-1-one and 2,2-dibromo-1,2,3,4-tetrahydronaphthalen-1-one reacted with 2-arylmethylidenemalononitriles, alkyl 3-aryl-2-cyanoprop-2-enoates, and N-substituted 3-aryl-2-cyanoprop-2-enamides to give, respectively, 3-aryl-1′-oxo-1′,3′-dihydrospiro[cyclopropane-1,2′-indene]-2-2-dicarbonitriles, 3-aryl-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2,2-dicarbonitriles, alkyl 3-aryl-2-cyano-1′-oxo-1′,3′-dihydrospiro[cyclopropane-1,2′-indene]-2-carboxylates, alkyl 3-aryl-2-cyano-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2-carboxylates, and N-substituted 3-aryl-2-cyanol-1′-oxo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalene]-2-carboxamides as a single diastereoisomer. The stereoconfiguration of the products was determined by ¹H and ¹³C NMR spectroscopy.     

Zur addition von nucleophilen an C(2) heterocyclischer 2-methylsubstituierter quartärsalze

1-(4-Chlorophenyl)-2-methyl-3-phenylquinoxalinium perchlorate ( 5 ) obtained by two different routes, on treating with nucleophiles HX or X⁻ yielded 1,3-diaryl-2-methyl-2X-1,2-dihydroquinoxalines 10 . Alkylation of 10e yielded 4-(4-chlorophenyl)-1,3-dimethyl-3-nitromethyl-2-phenyl-3,4-dihydroquinoxalinium perchlorate ( 11e ). The ¹H-nmr and mass spectra are presented. Diastereoisomerism of the products is discussed.     

Synthesis of Some 3-Substituted 1,2-Dihydroindoles

The reaction of 4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6-methyl carboxylate 2 with hydrazine hydrate in methanol gave 4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6-carbonylhydrazine 3. Furthermore, the reaction of 3 with carbon disulfide and then hydrazine hydrate afforded 3-[6-(4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4-oxo-1,3-thiazin-2-yl] hydrazone-1,3-dihydroindol-2-one 5. the latest reacted with DMAD to give {6-hydroxy-3-[4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6yl]-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-7-ylidene}methoxycarbonylmethylene 6.     

Reaction of N-substituted 2-oxochromen-3-carboxamides with bromoderivatives of zinc enolates prepared from alkyl 2,2-dialkyl-4,4-dibromo-3-oxoalkanoates and zinc

Zinc enolates obtained from ethyl 2,2-dialkyl-4,4-dibromo-3-oxobutanoates and zinc react with N-substituted 2-oxochromen-3-carboxamides forming ethyl 3-{1a-(R³-carbamoyl)-2-oxo-1a,7b-dihydrocyclopropa[c]chromen-1-yl}-2,2-dialkyl-3-oxopropanoate isomer with a Z-position of methine hydrogens. Zinc enolates prepared from alkyl 2,2-dialkyl-4,4-dibromo-3-oxopentanoates and-hexanoates and zinc react with N-substituted 2-oxochromen-3-carboxamides to give rise to esters of 3-{1-alkyl-1a-(R³-carbamoyl)-2-oxo-1a,7b-dihydrocyclopropa-[c]chromen-1-yl}-2,2-dialkyl-3-oxopropanoic acid as isomers with the E-position of the methine proton and the alkyl substituent. The reaction carried out in the presence of small quantities of THF and HMPA leads to the formation of 9c-alkyl-2-R³-9b,9c-dihydro-5-oxa-2-azacyclopenta[2,3]-cyclopropa[1,2-a]naphthalene-1,3,4-triones. Zinc enolates from alkyl 2,2-dialkyl-4,4-dibromo-3-oxopentanoates and-hexanoates and zinc with the secondary amides of 2-oxochromen-3-carboxylic acid form alkyl 3-{2-oxo-1a-(piperidinocarbonyl)-and 3-{6-R¹-1a-(morpholinocarbonyl)-2-oxo-1a,7b-dihydrocyclopropa[c]chromen-1-yl}-2,2-R²,R²-3-oxopropanoates as single geometrical isomers.     

Substituent effects on the tautomer ratios between the hydra-zone imine and diazenyl enamine forms in 3-(arylhydra-zono)methyl-2-oxo-1,2-dihydroquinoxalines. Correlation of the hammett constants σp with the tautomeric equilibrium constants KT

The 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines 1a-e and 2a-i showed tautomeric equilibria between the hydrazone imine A and diazenyl enamine B forms in dimethyl sulfoxide media. The sub-stituent effects on the tautomer ratios of A to B in compounds 1a-e and 2a-i were studied by the nmr spec-troscopy. The electron-donating or electron-withdrawing p-substituents R¹ in compounds 2a-i represented a tendency to increase the ratios of the tautomer A or the tautomer B , respectively, exhibiting the linear correlation of the Hammett constants σ_p (-0.17 to +0.78) with the tautomer ratios of A to B or the tautomeric equilibrium constants K_T. However, the presence of the ester group R² in compounds 1a-e induced the exclusive existence of the tautomer A regardless of the nature of the p-substituents R¹. In the tautomeric thermodynamic study, the elevating temperature increased the ratios of the hydrazone imine tautomer A in compounds 2a-i . The tautomeric thermodynamic parameters ΔG°, ΔH° and ΔS° were derived from the van't Hoff plots for compounds 2a , b , h , i , wherein the entropy term dominated the free-energy difference between the A and B tautomers.     

Synthesis and tautomeric behavior of 3-(pyrazolylhydrazonomethyl)-2-oxo-1, 2-dihydroquinoxalines. Specification of hydrazone imine and diazenyl enamine forms

3-(Pyrazolylhydrazonomethyl)-2-oxo-1, 2-dihydroquinoxalines were synthesized, and their tautomer ratios between hydrazone imine and diazenyl enamine forms were specified by pmr spectral data.     

A new method for the synthesis of novel 1-aryl-3-heteroaryl-1H-pyrazolo[3,4-b]quinoxalines

The reaction of 3-(2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-ylmethylene)-2-oxo-1,2,3,4-tetrahydroquinoxaline 4 with o-chlorobenzenediazonium chloride gave 3-[α-(o-chlorophenylhydrazono)-2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-ylmethyl]-2-oxo-1,2-dihydroquinoxaline 6 , whose refluxing in phosphoryl chloride/pyridine afforded 1-(o-chlorophenyl)-3-(2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-yl)-1H-pyrazolo[3,4-b]quinoxaline 7. The reactions of 6 and 7 with nitrous acid resulted in sulfur extrusion to provide 1-(o-chlorophenyl)-3-(4-methyl-4H-1,2,4-triazol-5-yl)1H-pyrazolo[3,4-b]quinoxaline 8 and 3-[α-(o-chlorophenylhydrazono)-4-methyl-4H-1,2,4-triazol-5-ylraethyl]-2-oxo-1,2-dihydroquinoxaline 9 , respectively.     

Conformational Behaviour of Substituted 2-Methoxy-2-Oxo-1,2-Oxaphospholan-3-Ols

Abstract

Conformational behaviour of about 30 2-methoxy-2-oxo-1,2- oxaphospho l an-3-0 1 s containing various substituents was examined by ¹H and ¹³C NMR. Vicinal coupling constants J(HCCH), J(HCCP), J(HCOP), J(CCOP) and J(CCCP) were employed in this study. Conformation of the 1,2-oxaphospholane ring is governed almost exclusively by substituents at C-3, C-4 and C-5, as we l l as by their orientation. The configuration of the P atom has little or no influence on conformation of the ring in diastsreomeric pairs. Strong preference of phenyl, methyl and substituted methyl groups to occupy the equatorial or pseudoequatoria l positions was observed for all but one compounds studied. In the cis-fused bicyclic syst ems conformat ionally rigid 6-membered rings forced the 1,2-oxaphospholane rings to adopt an enve l ope-l ike (E₄) conformation. No influence of the p=o……HO-C-3 hydrogen bond on conformation of the 1,2-oxaphospholane ring was found. Preferred conformations for (2R, 3R, 4R)-3-(hydroxymethyI)-2-methoxy-2-oxo-1,2-oxaphospho lane-3,4-diol and its triacetate are shown below.     

New chiral metal complexes based on 2-ethoxymethylidene-3-oxo-3-polyfluoroalkylpropionates

Ethyl 2-ethoxymethylidene-3-oxo-3-polyfluoroalkylpropionates reacted with (1S,2S)-1,2-diphenylethane-1,2-diamine to give diethyl 2,2′-{[(1S,2S)-diphenylethane-1,2-diyl]bis[iminomethylidene]}bis(3-oxo-3-polyfluoroalkyl)alkanoates which were used as ligands to obtain chiral complexes with transition metals.     

3-Aryl-2-benzyl -1,2-dihydroquinoxalines

The reaction of 1,2-phenylenediamine with 2-bromo-1,3-diaryl-1-propanones led to stable and crystalline 3-(4-R-phenyl)-2-(4-R-benzyl)-1,2-dihydroquinoxalines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 830–832, June, 1987.     

Synthese von imidazo[1,5-a]- und pyrazino[1,2-a]benzimidazolen

1,2-Dihydro-3H-imidazo[1,5-a]benzimidazoles (6), 1-oxo-1,2-dihydro-3H-imidazo[ 1,5-a] benzimidazoles (8), 3H-imidazo[1,5-a]benzimidazoles (7), 3-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a] benzimidazoles (12), and 3,4-dioxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]benzinudazoles (13) were synthesized from 2-α-aminobenzyl (benzhydryl)-benzimidazoles (2).     

Reaction of 3-Benzoyl-2,3-dibromopropionic Acid with Substituted ortho-Phenylenediamines

3-Benzoyl-2,3-dibromopropionic acid reacts with 4-substituted o-phenylenediamines to give 3-aryl-2-carboxymethylene-1,2-dihydroquinoxalines.