Reaction of aroyl- and hetaroyltrifluoroacetones with acylhydrazines: Regioselectivity and tautomerism of the condensation products

Acylhydrazines react with 1,3-diketones of the general formula CF₃COCH₂COR (where R is an aryl or hetaryl group) at both carbonyl groups. The reaction at the trifluoroacetyl group is favored by donor substituents in the aromatic ring of the 1,3-diketone or by the 2-furyl and, especially, 2-thienyl group as a hetaryl substituent, as well as by elevated temperature. The condensation products at the carbonyl group contiguous to the aryl or hetaryl ring have the structure of 5-hydroxy-4,5-dihydropyrazoles and do not undergo tautomeric transformations in solution. The condensation products at the trifluoroacetyl group have either 5-hydroxy-4,5-dihydropyrazole or hydrazone structure and give rise to ring-chain tautomeric equilibrium in solution. Electron-withdrawing substituents in the aromatic ring of the 1,3-dicarbonyl fragment and CDCl₃ as solvent favor formation of the cyclic tautomer. The state of the tautomeric equilibrium is weakly sensitive to structural variations in the hydrazine component.     

1-(Pyrimidin-4-yl)pyrazol-5(4H)-one derivatives: I. Synthesis of 3-methyl-1-(6-methyl-2-methylsulfanylpyrimidin-4-yl)-pyrazol-5-ol and specificity of its Knoevenagel reaction

3-Methyl-1-(6-methyl-2-methylsulfanylpyrimidin-4-yl)-1H-pyrazol-5-ol available via cyclocondensation of 6-methyl-2-methylsulfanylpyrimidin-4-ylhydrazine with ethyl acetoacetate reacted with aromatic aldehydes to give two kinds of products, 4-arylmethylidene-5-oxo-4,5-dihydropyrazole and arylbis(5-hydroxypyrazol-4-yl)methane derivatives, depending on the substituent in the aromatic aldehyde.     

Regioselective 1,3-dipolar cycloaddition of nitrilimines to 2-methyl-2-vinyl oxirane

1,3-Dipolar cycloaddition of in situ generated C,N-diaryl nitrilimines to 2-methyl-2-vinyl oxirane gives rise to the regioselective formation of novel 5-(2-methyloxiranyl)-4,5-dihydropyrazole derivatives in moderate to good yields. The structures and stereochemistries of the new cycloadducts were confirmed by spectroscopic/physical methods including X-ray diffraction data.     

Reaction of 1,5-Diphenyl-1,4-pentadien-3-one and 1,5-Diphenyl- 1-penten-4-yn-3-one with Monosubstituted Hydrazines

Phenyl- and isopropylhydrazines react with 1,5-diphenyl-1,4-pentadien-3-one to give 4,5,6,7-tetrahydroindazole derivatives instead of the expected 4,5-dihydropyrazoles. The reaction of phenylhydrazine with 1,5-diphenyl-1-penten-4-yn-3-one leads to formation of 1,5-diphenyl-3-phenylethynyl-4,5-dihydropyrazole. 2,4-Dinitrophenylhydrazine reacts with 1,5-diphenyl-1-penten-4-yn-3-one, affording the corresponding unsaturated hydrazone rather than pyrazole derivative.     

A one-pot approach to 4,5-dihydropyrazoles from ketones,arylacetylenes, and hydrazines

An efficient and straightforward one-pot strategy for the synthesis of 4,5-dihydropyrazole derivatives from ketones, arylacetylenes, and hydrazines in the presence of KO^tBu/DMSO is described. This strategy provides a flexible and rapid route to polysubstituted 4,5-dihydropyrazoles.     

Addition of diprotic nucleophiles to a C60-tetrazine monoadduct: structural reassignment and correction of a novel rearrangement

C60-tetrazine Diels-Alder adducts bearing electron deficient dihydropyridazine groups undergo chemoselective amination and hydration reactions upon addition of primary aliphatic amines and water, respectively, to form new adducts with 4,5-dihydropyrazole groups nested atop the [60]fullerene skeleton.     

Reaction of monocyclic ferrocenyl-4,5-dihydropyrazoles with β-dicarbonyl compounds

Monocyclic 3- and 5-ferrocenyl-4,5-dihydropyrazoles with a free NH group in the molecule react with acetylacetone to form the corresponding enaminocarbonyl compounds. The latter were isolated as a single isomer, presumably E. 3-Ferrocenyldihydropyrazoles and 5-ferrocenyl-3-(p-methoxyphenyl)-4,5-dihydropyrazole analogously react with acetoacetic ester. 5-Ferrocenyl-3-phenyl-, 3-(p-bromophenyl)-5-ferrocenyl, and 3,5-diferrocenyl-4,5-dihydropyrazoles react with acetoacetic ester to form acetoacetylpyrazolides.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 12, 2004, pp. 1942–1947.Original Russian Text Copyright © 2004 by E. Klimova, Vazquez Lopez, T. Klimova, Martinez Garcia, Meleshonkova, Ruiz Ramirez.This revised version was published online in April 2005 with a corrected cover date.     

2-异（口恶）唑啉等氮杂环化合物在二铬酸氢四吡啶合镍（II）氧化下的脱氢芳构化反应

研究了3，5-二芳基-4，5-二氢异（口恶）唑化合物（1a～3c)和1，3，5-三苯 基-4，5-二氢吡唑化合物（5）分别在二铬酸氢四吡啶合镍（II）[（Py)_4Ni (HCrO_4)_2]氧化下脱氢反应的结果；研究了在[(Py)_4Ni(HCrO_4)_2]存在下，吡 啶叶立德、喹啉叶立德或异喹啉叶立德分别和缺电子烯烃反应，一步法合成中氮茚 衍生物 9a～9b，11a～11b，13的结果，发现金属配合物氧化剂二铬酸氢四吡啶合 镍（II）可用于多类杂环化合物的脱氢芳构化。     

Aromatic derivatives of 1H-2,3-dihydropyrazolo[4,5-b]-1,5-diazepine

Aromatic derivatives of 1H-2,3-dihydropyrazole[4,5-b]-1,5-diazepine were obtained by the reaction of 1-phenyl-3-methyl-4,5-diaminopyrazole with chalcones and acetylarenes, catalyzed by acetic or sulfuric acid. The seven-membered ring in these compounds has a conformation of the boat type. The IR, UV, PMR, and mass spectra of the compounds are discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 363–369, March, 1987.     

A Convenient Method to Obtain 4,5-Dihydro-1H-Methylpyrazoles by A Ring Transformation Reaction

A convenient method for the synthesis of alkyl[aryl]-substituted 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-methylpyrazole (2) from a new ring transformation reaction of alkyl[aryl]-substituted-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-pyrazolethiocarboxyamide (1) with methylhydrazine in THF, and the thermal dehydration of 2, are reported.     

Synthesis, structures and biological activity research of novel ferrocenyl-containing 1H-1,2,4-triazole derivatives

Novel ferrocene-containing propenones have been synthesized from acetylferrocene via a Mannich-type intermediate. Sequential condensation cyclization of these propenones with phenylhydrazine afforded highly substituted 4,5-dihydropyrazole derivatives, which structures have been characterized by spectra data and single crystal X-ray diffraction analysis. In addition, these new ferrocene-containing derivatives have been evaluated for in vitro fungicidal activities against five selected fungi.     

1,2,4-Triazines – products of reaction of thiocarbohydrazide and its alkyl(aryl)-substituted derivatives with 1,2-dicarbonyl compounds

The reaction of a series of 1,2-dicarbonyl compounds with thiocarbohydrazide and its 1- and 1,4-alkyl-(aryl)-substituted analogs has been studied. Treatment of diacetyl with the polynucleophiles indicated gives monohydrazones and/or 5-methylene-4,5-dihydro-2H-[1,2,4]triazine-3-thiones. Reaction of phenylglyoxal and benzil with thiocarbohydrazide yields 5-hydroxy- or 5-alkoxy-4,5-dihydro-2H-[1,2,4]triazine-3-thiones depending on the nature of the solvent. The products of condensation with 1,1-dimethylthiocarbohydrazide showed a thiocarbonohydrazone – 5-hydroxy-4,5-dihydro-2H-[1,2,4]tri-azine-3-thione ring-chain type equilibrium.     

Prenylisoflavone derivatives from the roots of Hedysarum scoparium

Four new prenylisoflavone derivatives, namely, 5-hydroxy-4'-methoxy-8-prenyl-2'-hydroxyisopropyldihydrofurano[4,5:6,7]-isoflavone (1), 5-hydroxy-4'-methoxy-6-prenyl-2'-hydroxyisopropyldihydrofurano[4,5:8,7]-isoflavone (2), 5-hydroxy-4'-methoxy-8-prenyl-1',2'-peroxyl-3',3'-dimethyldihydropyrano[5,6:6,7]-isoflavone (3), and 5-hydroxy-4'-methoxy-6-prenyl-1',2'-peroxyl-3',3'-dimethyldihydropyrano[5,6:8,7]-isoflavone (4), together with three known ones 5-7, were isolated from the roots of Hedysarum scoparium. Their structures were established by means of detailed spectroscopic analysis (IR, EI- or HR-ESI-MS as well as 1D- and 2D-NMR), and by comparison of their spectroscopic data with those reported for structurally related compounds.     

Solvolysis of (4,5)-anti-4-aryl-5-tosyloxy-2(E)-hexenoate derivatives

The solvolysis reaction of (4,5)-anti-4-aryl-5-tosyloxy-2(E)-hexenoates 4a-k gave (4,5)-anti-4-aryl-5-hydroxy-2(E)-hexenoates 2a-k and (4,5)-anti-5-aryl-4-hydroxy-2(E)-hexenoates 5a-k along with the complete inversion. This 1,2-aryl migration was induced by treatment with heating in water-saturated nitromethane. On the basis of the substituent effect on the aromatic ring, this 1,2-aryl migration is thought to proceed via the sigma-bridged phenonium ion. The product selectivity between 2a-k and 5a-k was found to be subtly governed by the substituent and substitution pattern in the aromatic ring of the substrates 4a-k.     

N NMR spectroscopy of partially saturated pyrazoles

Partially saturated pyrazoles, namely 1-(4-substituted)phenyl-3-methoxycarbonyl-5-ethoxycarbonyl-4,5-dihydropyrazoles, were submitted to extensive ¹⁵N NMR spectroscopic analyses, performed in natural abundance. Nitrogen chemical shifts were measured by means of INEPT and HMBC experiments, while long range proton-nitrogen scalar coupling values were taken through J-HMBC experiments. A linear plot between nitrogen chemical shifts and Hammett σ_p was observed, enabling us to relate quantitatively the observed chemical shifts to the electronic features of the substituent in the 1-position of the 4,5-dihydropyrazole ring.     

Haloacetylated enol ethers. 5 [5]. Heterocyclic ring closure reactions of β-alkoxyvinyl dichloromethyl ketones with hydroxylamine

The β-alkoxyvinyl dichloromethyl ketones 1a-d are cyclocondensed with hydroxylamine hydrochloride in pyridine to afford the 5-hydroxy-5-dichloromethyl-4,5-dihydroisoxazoles 2a-d in good yield. The cyclo-condensation of compound 1c gave, together with 2c , 3-cyano-2-hydroxy-2-dichloromethyltetrahydrofuran 5c. The dehydratation of compounds 2a,b , derived from acyclic enol ethers, with concentrated sulfuric acid at 30°, led the corresponding 5-dichloromethylisoxazoles 3a,b. The dehydratation of compounds 2c,d , derived from cyclic enol ethers, with concentrated sulfuric acid at 30°, led the bicyclic 4,5-dihydroisoxazoles 4c,d , and at 55°, a competitive rearrangement reaction gives the 3-cyano-2-hydroxy-2-dichloromethyl-2H-pyran 5d.     

Polyfluoro-2,3-epoxyalkanes in reactions with thiourea and thiosemicarbazide

Reactions of polyfluoro-2,3-epoxyalkanes with thiourea and thiosemicarbazide afforded 2-amino-4-hydroxy-4,5-di(polyfluoroalkyl)-5-fluoro-l,3-thiazolines and 2-hydrazino-4-hydroxy-4,5-di(polyfluoroalkyl)-5-fluoro-l,3-thiazolines respectively. Unsymmetrical oxiranes furnish mixtures of regioisomeric heterocyclic compounds, and the epoxy cycle is predominantly cleaved from the side of bulkier fluoroalkyl group. The reactions of E-oxiranes are stereospecific and provide 1,3-thiazolines in the E-form. The structure of compounds obtained was confirmed by IR,¹⁹F,¹H, and¹³C NMR spectroscopy, by mass spectra and chemical transformations. E-isomers of 2-amino-4-hydroxy-4,5-bis(trifluoromethyl)-5-fluoro-l,3-thiazoline and 2-amino-5-heptafluoropropyl-4-hydroxy-4-trifluoromethyl-5-fluoro-1,3-thiazoline were subjected to X-ray diffraction analysis. The study was carried out under financial support of the Russian Foundation for Basic Research (grant no. 00-03-332767), and the Foundation for Support of the Leading Scientific Schools (grant no. 00-15-97390).     

The reaction of (4R,5R)- and (4S,5S)-4,5-epoxy-2(E)-hexenoates and secondary amines.

A reaction of methyl (4R,5R)-4,5-epoxy-2(E)-hexenoate 1 with N-benzylmethylamine gave a diastereomerically pure methyl (4R,5R)-4,5-epoxy-(3S)-N-benzylmethylamino hexanoate 6 and methyl (4S,5R)-4-N-benzyl-methylamino-5-hydroxy-2(E)-hexenoate 7. The former was chemoenzymatically converted to (-)-osmundalactone 11, which is an aglycone of osmundalin. On the other hand, the directly conjugated addition of dimethylamine to methyl (4S,5S)-4,5-epoxy-2(E)-hexenoate 1 followed by treatment with MeOH at 40 degrees C exclusively provided methyl (4R,5S)-4-dimethylamino-5-hydroxy-2(E)-hexenoate 16, which was converted into L-(-)-forosamine 18.     

Synthesis of spiro[imidazole-2,2′-pyrroles] by reaction of 4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with urea

Substituted alkyl 4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with urea to give alkyl 2-(carbamoylamino)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates which underwent intramolecular cyclization to 8-hydroxy-1,3,6-triazaspiro[4.4]non-8-ene-2,4,7-triones by the action of sodium methoxide.     

Syntheses of “oxidized” hemopyrrole and kryptopyrrole: Porphyric monopyrroles

Straightforward, short synthetic procedures have been developed to produce gram quantities of 4,5-dimethyl-3-ethyl-5-hydroxy-3-pyrrolin-2-one ( 1 ) and 3,5-dimethyl-4-ethyl-5-hydroxy-3-pyrrolin-2-one ( 2 ), which are, respectively, the oxidized hemopyrrole and kryptopyrrole factors associated with psychiatric and prophyric disorders.