Tautomerism of Aza heterocycles: V. Structure of the spontaneous transformation products of 5-methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo-[4,3-c]pyridin-3-one in crystal and solution

5-Methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-3-one exists as zwitterion with a proton localized on the nitrogen atom of the piperidine ring and negative charge delocalized over the pyrazololate fragment. The compound is stable in crystal but ustable in solution. Its chromatographic purification and attempts to recrystallize or synthesize by condensation of phenylhydrazine with alkyl 1-methyl-4-oxopiperidin-3-carboxylate on heating in alcohols or benzene lead to the formation of a complex mixture of products. Among these products, we isolated and identified 3a,3a′-methylenebis(5-methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-3-one), 1-methyl-3-(2-phenylhydrazinylidene)pyrrolidin-2-one, and 5-methyl-2-phenyl-3,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine. The structure of methyl 3-(2-phenylhydrazinylidene)-4,5-dihydro-3H-pyrrole-2-carboxylate and 3a,5-dimethyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-3-one was proved by NMR spectroscopy. 3a,5-Dimethyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-3-one was isolated as hydrochloride hydrate whose structure was determined by X-ray analysis.     

Reaction of 2,3-dioxo-4-(N,N-dimethylaminomethylene)hexahydroazepine with hydrazine and its derivatives

8-Oxo-8H-4,5,6,7-tetrahydropyrazolo[5,4-c]azepine and a mixture of 2-phenyl-8-oxo-8H-4,5,6,7-tetrahydro [3,4-c]azepine and 2,3-dioxo-4-formylhexahydroazepine 4-phenylhydrazone were obtained in the reactions of 2,3-dioxo-4-(N,N-dimethylaminomethylene)-hexahydroazepine with hydrazine and phenylhydrazine, respectively. Cyclization of 2,3-dioxo-4-formylhexahydroazepine 4-phenylhydrazone gave 1-phenyl-8-oxo-8H-4,5,6,7-tetrahydropyrazolo [5,4-c]azepine. The reaction of 2,3-dioxo-4-(N,N-dimethylaminomethylene)hexahydroazepine with semicarbazide and thiosemicarbazide gives 2,3-dioxo-4-formylhexahydroazepine 4-semicarbazone and 4-thiosemicarbazone.Communication XXX from the series Research on Lactams. See [1] for communication XXIX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1248–1251, September, 1978.     

New 1H-1-alkyl-6-methyl-3-phenyl-7-phenylazo-pyrazolo[5,1-c][1,2,4]triazoles through regioselective alkylation of 1H-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles

1H-1-Alkyl-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles (2aa-ad) were obtained by regioselective alkylation of 1H-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles (2a). 1H-1-Alkyl-6-methyl-3-phenyl-7-phenylazopyrazolo[5,1-c][1,2,4]triazoles 2aa and 2ab were also prepared by coupling phenyldiazonium chloride with 1H-1-alkyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazoles 1aa and 1ab. The new compounds were characterized by IR, UV-VIS, ¹H-NMR, ¹³C-NMR, and ¹⁵N-NMR spectroscopy and their structures and actual tautomeric forms were established unequivocally.      

A comparative study on the synthesis of pyrazolo-[4,3-c]quinoline oxides by reductive cyclisations

Alternate routes for the reductive cyclisation of 4-acetyl-3-methyl-5-(2-nitrophenyl)-1-phenylpyrazole under different conditions are described. Whereas 3,4-dimethyl-1-phenylpyrazolo[4,3-c]quinoline 5-oxide is formed by mild noncatalytic reductions, catalytic and transfer hydrogenation processes cause the diastereoselective formation of cis-4,11-dihydro-3,5-dimethyl-1-phenylpyrazolo[4,3-c]quinoline 6-oxide.     

Synthèse et propriétés biologiques des pyrazolo〚4,3-c〛triazolo〚4,3-a〛〚1,5〛benzodiazépines

The addition of carbon disulfide to 3(5)-N-〚methyl (ethyl)-2-aminophenyl amino-5(3)-phenylpyrazole 3 (4) afforded 10-methyl (ethyl)-3-phenylpyrazolo〚4,3-c〛 〚1,5〛 benzodiazepine-4-thione 7 (8). These compounds reacted with alkyl halides and acetylhydrazide or benzoylhydrazide, to afford new heterocyclic systems: pyrazolo 〚4,3-c〛 triazolo〚4,3-a〛-1,5-benzodiazepines 15–18. Biological properties of compounds 8, 9, 16 and 17 have been evaluated.     

Studies on the synthesis of heterocyclic compounds. Part IV. Further investigation of the pschorr reaction with some pyrazole derivatives

Thermal decomposition of the diazonium sulfate derived from N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-aminobenzamide afforded products formulated as 1-phenyl-3-methyl[2]benzopyrano[4,3-c]pyrazol-5-one (yield 10%), 1,4-dimethyl-3-phenylpyrazolo[3,4-c]isoquinolin-5-one (yield 10%), N-methyl-(1-phenyl-3-methylpyrazol-5-yl)-2-hydroxybenzamide (yield 8%) and 4′-hydroxy-2,3′-dimethyl-1′-phenylspiro[isoindoline-1,5′-[2]-pyrazolin]-3-one (yield 20%). Decomposition of the diazonium sulfate derived from N-methyl-(1,3-diphenylpyrazol-5-yl)-2-aminobenzamide gave products formulated as 7,9-dimethyldibenzo[e,g]pyrazolo[1,5-a][1,3]-diazocin-10-(9H)one (yield 8%), 4-methyl-1,3-diphenylpyrazolo[3,4-c]isoquinolin-5-one (yield 7%) and 4′-hydroxy-2-methyl-1′,3′-diphenylspiro[isoindoline-1,5′-[2]pyrazolin]3-one (yield 10%). The spiro compounds 6a,b underwent thermal and acid-catalysed conversion into the hitherto unknown 2-benzopyrano[4,3-c]pyrazole ring system 7a,b in good yield. Analytical and spectral data are presented which supported the structures proposed.     

A Convenient Synthetic Approach to Newly Condensed Pyrazoloazines Based on Pyrazolo[3,4-b]pyridine

The reaction of 6-amino-5-cyano-3-methyl-1H-1-phenylpyrazolo[3,4-b]pyridine ( 2 ) and 6,7-dihydro-3-methyl-6-oxo-1H-1-phenylpyrazolo[3,4-b)]pyridine-5-carbonitrile ( 3 ) and 5-amino-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]-1H-pyrazolo[4′,3′-e]pyridine ( 12 ) with different reagents have been conducted to give newly condensed pyrazoloazines.     

Synthesis,structural characterization and biological activities of metal(II) complexes with Schiff bases derived from 5-bromosalicylaldehyde: Ru(II) complexes transfer hydrogenation

In this study, two novel Schiff base ligands (L¹ and L²) derived from condensation of methyl 2-amino-6-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate and methyl 2-amino-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate, both starting matter with 5-bromo-salicylaldehyde, and their Zn(II) and Ni(II) metal complexes have been prepared using a molar ratio of ligand:metal as 1:1 except the Ru(II) complexes 1:0.5. The structures of the obtained ligands and their metal complexes were characterized by elemental analysis, FT-IR, ¹H NMR, ¹³C NMR, UV–vis, thermal analysis methods, mass spectrometry, and magnetic susceptibility measurements. Antioxidant and antiradical activity of Schiff base ligands and their metal complexes were been evaluated in vitro tests. Antioxidant activities of metal complexes generally were more effectives than free Schiff bases. 1c and 2c were used as catalysts for the transfer hydrogenation (TH) of ketones. 1c, 2c complexes were found to be efficient catalyst for transfer hydrogenation reactions.     

Reactions with heterocyclic amidines,VII: Synthesis of some new pyrazolo[1,5-c]-1,2,4-triazines,pyrazolo[1,5-a]-1,3,5-triazines and pyrazolo[1,5-a]pyrimidines

Diazotised 5-amino-3-methyl-4-phenyloyrazole (1) reacted with active methylene reagents and with -naphthol to yield the pyrazolo[1,5-c)-1,2,4-triazine derivatives2a-e and5. Compound1 reacted with benzoyl isothiocyanate and with phenyl isothiocyanate to yield the corresponding pyrazol-5-ylthiourea derivatives6a, b. 5a was converted into the thiourea derivative8 by the action of acids or alkalies. A synthesis of 2-methyl-3-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrimidin-5-one from the reaction of -phenylacetoactonitrile (3-oxo-2-phenyl-butyric nitrile) and -cyanoethylhydrazine is reported.

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Reaktionen mit heterocyclischen Amidinen, VII: Synthese einiger neuer Pyrazolo[1,5-c]-1,2,4-triazine, Pyrazolo[1,5-a]-1,3,5-triazine und Pyrazolo[1,5-a]pyrimidine

Zusammenfassung Diazotiertes 5-Amino-3-methyl-4-phenylpyrazol (1) reagiert mit einer aktiven Methylenkomponente und -Naphthol zu den Pyrazolo[1,5-c]-1,2,4-triazin-Derivaten2a-e und5. 1 ergibt mit Benzoylisothiocyanat und Phenylisothiocyanat die entsprechenden Pyrazol-5-yl-thioharnstoffe6a, b. 5a wurde mittels Säure oder Base in das Thioharnstoffderivat8 umgewandelt. Es wird über eine Synthese von 2-Methyl-3-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrimidin-5-on aus -Phenylacetoacetonitril (3-Oxo-2-phenyl-butyronitril) und -Cyanoethylhydrazin berichtet.

     

Synthesis of condensed structures from 3-cyano-2-pyridylacrylic acids

Ammonolysis of the methyl esters of trans--(3-cyano-2-pyridyl)acrylic (I) and trans--(6-methyl-3-cyano-2-pyridyl)acrylic (II) acids gave the amides of these acids. The addition of bromine, diazomethane, and hydrogen to the double bond of cis- and trans-acids I and II is described. Hydrogenation of the methyl esters of trans-acids I and II over Raneynickel at room temperature and atmospheric pressure occurs with intramolecular cyclization to two-ring lactams — 7-oxo-5, 6,8,9-tetrahydropyrid[3,2-c]azepine and 2-methyl-7-oxo-5,6,8,9-tetrahydropyrid[3,2-c]azepine. Under the conditons of acid hydrolysis of acids I and II the elements of water add to the nitrile group with intramolecular cyclization to give, respectively, 3-carboxymethyl-1-oxo-2,3-dihydrofuro [4,3-b]pyridine and 5-methyl-3-carboxymethyl-1-oxo-2,3-dihydrofuro[4,3-b]pyridine, whereas refluxing these acids with aqueous sodium hydroxide gives two-ring lactams — 3-carboxymethyl-1-oxo-2, 3-dihydropyrrolo[4,3-b]pyridine and its 5-methyl homolog. The structures of the compounds were confirmed by the UV, IR, PMR, and mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 63–69, January, 1978.     

Etude cinétique comparée de la substitution nucléophile de quelques chloro-2 pyridines condensées

A comparatie kinetic study of nucleophilic substitution of some condensted 2-chloropyridines by piperidine was carried out and an “autocatalytic effect” was observed in the case of 1-methyl-4-chloro-5-azaindole. The rate constants of such substitutions were determined for 1-methyl-4-chloro-5-azaindole, 4-chlorofuro[3,2-c]pyridine, 1-phenyl- and 1-benzy;(1H)pyrazolo[4,3-c]pyridines, 4-chloro-6,7-dimethylpyrrolo[2,3-d]pyrimidine, and a classification of reactivity of these compounds, as compared to 2-chloropyridine, was established.     

Synthesis of 4-unsubstituted dihydropyrimidines. Nucleophilic substitution at position-2 of dihydropyrimidines

Synthesis of novel 4-unsubstituted dihydropyrimidines (DPs) was performed. Subsequently, a variety of 4-unsubstituted 1,4(3,4)-DPs with amino moieties at position-2 were obtained in excellent yields by activation of position-2 owing to regioselective alkoxycarbonylation at position-3 of the DP skeleton. 3-Oxo-2-phenyl-2,3,5,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrimidine was obtained using phenylhydrazine instead of amines. Individual tautomers of 1,4(3,4)-DP were observed in the ¹H NMR spectra of one derivative depending on temperature and concentration. On the other hand, only 1,4-DP was found in the solid state by single-crystal X-ray crystallography.     

α-aminoazoles in synthesis of heterocycles: IV. Regiodirection of 3(5)-amino-5(3)-methylpyrazole reaction with hexafluoroacetylacetone

The reaction of 3(5)-amino-5(3)-methylpyrazole with hexafluoroacetylacetone depending on the process conditions led to the formation either of pyrazolo[1,5-a]pyrimidine or pyrazolo[3,4-b]-pyridine. By means of 2D NMR spectroscopy the structure was established of a stable intermediate product, 2-methyl-5,7-bis(trifluoromethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrimidine-5,7-diol, whose dehydration yielded the above compounds.     

金属氯化物对硼氢化钠还原α-氯代苯乙酮的影响

以芳醛、麦氏酸和3-甲基-1-苯基-5-氨基吡唑为原料, 经微波辐射一步得到4-芳基-3-甲基-6-氧代-1-苯基-4,5,6,7-四氢吡啶并[2,3-c]吡唑衍生物, 反应2～6 min完成, 产率高. 产物结构通过红外、核磁共振、元素分析及单晶X射线分析确证.     

Palladium(II) and platinum(II) complexes of bidentate 2-pyridyl-1,2,3-triazole “click” ligands: Synthesis,properties and X-ray structures

The synthesis and characterization of palladium(II) and platinum(II) complexes of isomeric bidentate 2-pyridyl-1,2,3-triazole “click” ligands is reported. The complexes have been fully characterized by elemental analysis, HRESI-MS, IR, UV–Vis, ¹H and ¹³C NMR spectroscopy. Additionally, the molecular structures of the Pd(II) and Pt(II) complexes of the 2-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]pyridine ligand are confirmed by X-ray crystallography. Solution studies indicate the 2-(1-benzyl-1H-1,2,3-triazol-4-yl)pyridine ligand forms more stable complexes with Pd(II) and Pt(II) than the isomeric 2-[(4-phenyl-1H-1,2,3-triazol-1-yl)methyl]pyridine ligand.     

Reactions with diazoazoles. Part VI. Unequivocal synthesis of 3-methyl-3h-azolotetrazoles. Correction of the formerly described 3-methylazolotetrazoles in favour of mesoionic 2-methylazolotetrazoles

3-Methyl-3H-pyrazolo[1,5-d]tetrazoles 2 and 3-methyl-6-phenyl-3H-1,2,4-triazolo[1,5-d]tetrazole (4) have been unequivocally synthesized by annulation of the tetrazole moiety to the pyrazole resp. 1,2,4-triazole system. The constitution of some N-methyl substituted azolotetrazoles, formerly described as 3-methyl-3H-pyrazolo[1,5-d]tetrazoles 2, 3-methyl-6-phenyl-3H-1,2,4-triazolo[1,5-d]tetrazole (4) and 1-methyl-6-phenyl-1H-1,2,4-triazolo[4,3-d]tetrazole (5), has to be revised in favour of the corresponding mesoionic 2-methyl derivatives 2′, 4′, 5′. The structures of 3-methyl-3H- as well as of 2-methyl-2H-pyrazolo[1,5-d]tetrazole derivatives 2a, 2c, 2′a have been determined by X-ray analyses. The azapentalenic system is aromatic in all three measured compounds and mesoionic in the case of the 2-methyl-2H- substitution pattern. The phenyl and ester substituents are coplanar with the azapentalene system. 3-, 2-, and 1-Methylpyrazolo[1,5-d]tetrazoles exhibit different behaviour when allowed to react with stannous chloride or sodium ethoxide. Azolotetrazoles with a methyl substituent at N-1, N-2 or N-3 of the tetrazole moiety can be distinguished by a combination of ¹H and ¹³C nmr with respect to the chemical shifts of the N-methyl group and the bridgehead carbon. Results of semiempirical calculations of the pyrazolo[1,5-d]tetrazole anion and of its N-methyl derivatives are discussed.     

Electron Ionization Mass Spectra of Organophosphorus Compounds Part I: The Mass Fragmentation Pathways of Cyclic α-Aminophosphonates Monoester Containing 1,2,4-Triazinone Moiety

Abstract

The electron impact induced fragmentation reactions of 3-(4-chlorophenyl)-3,4- dihydro-2-ethoxy-2-oxido-7-methyl-2H,6H-[1,2,4]triazino[4,3-e][1,4,5,2]thiadiazaphosphin in-6-one (1), 3,7-dimethyl-2-ethoxy-2-oxido-1,2,3,4-tetrahydro-6H-[1,2,4]triazino[4,3-b][1,2,4,5]triazaphosphinin-6-one (2), and 9-amino-3,7-dimethyl-4-ethoxy-4-oxido-2,3,4,9-tetrahydro-8H-[1,2,4]triazino[3,2-c][1,2,4,5]triazaphosphinin-8-one (3) are presented and compared. The 1,2,4-triazine rings have almost identical fragmentation routes. The 1,2,4-triazine rings are rather stable relative to the phosphorus rings. Therefore, fragmentation of the phosphorus rings is more favorable for the compounds than the stable 1,2,4-triazine rings.     

Synthesis and thermal behaviour of new benzo-1,2-thiazine long-chain aryl-piperazine derivatives

A series of potential biologically active 2-[3-(4-phenyl-1-piperazinyl)propyl]-3-(4-substituted-benzoyl)-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides was synthesized in a straightforward manner by condensation of respective 3-substituted-4-hydroxy-1,2-benzothiazine 1,1-dioxides with 1-(1-chloropropyl)-4-phenylpiperazine. The structures of all of the newly formed compounds were identified by elemental analysis, FTIR and ¹H NMR. The synthesized compounds were subjected to preliminary evaluation using differential scanning calorimetry (DSC) to determine the existence of multiple crystal forms. The DSC scans for all compounds show more than one endothermic effect, which might suggest dynamic proton transfer between two or three possible tautomeric forms: O-keto/O-enol, O-enol/O-keto and O-keto/O-keto/CH₂ in crystals 2-[3-(4-phenyl-1-piperazinyl)propyl]-3-(4-substituted-benzoyl)-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides.     

The reaction of β-dicarbonyl compounds with trifluoromethyl-sulphenyl chloride Part II. The synthesis of 3-SCF3 substituted 2- and 4-quinolinones

3-SCF₃ substituted 4-methyl-2(1H)-, 4-phenyl-2(1H)-, 2-methyl-4(1H), and 2-phenyl-4(1H)-quinolinones were obtained by cyclization of the respective -SCF₃ submitted acetoacetanilides or benzoylacetanilides or their β-phenylimino analogues in concentrated sulphuric acid upon heating. The structures of the compounds obtained were elucidated by elemental analysis and their IR, ¹H and ¹⁹F NMR, and mass spectra.     

Structural tautomerism of 4-acylpyrazolone schiff bases and crystal structure of 5-methyl-2-phenyl-4-{1-[(pyridin-2-ylmethyl)-amino]-ethylidene}-2,4-dihydro-pyrazol-3-one

The Schiff base derivatives prepared from 4-acetyl-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one and alkyl amines are shown to remain exclusively in the amine-one(I) tautomeric form in chloroform solutions at room temperature using a combination of ¹H, ¹³C, APT, COSY, HMQC, and HMBC NMR spectroscopic methods. The crystal structure of 5-methyl-2-phenyl-4-{1-[(pyridin-2-ylmethyl)-amino]-ethylidene}-2,4-dihydro-pyrazol-3-one showed that this 4-acylpyrazolone Schiff base stays in the amine-one(I) form in the solid state as well, and the solid state structure supports the fact that strong hydrogen bonding between amine hydrogen and the pyrazolone C₃ carbonyl oxygen helps to stabilize the amine-one(I) tautomer.