Reaction of acetylenedicarboxylic acids esters with 4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-1-carbothioamides and 3,4,5,6-tetrahydro-2<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazepine-3-thiones

The reactions of dimethyl acetylenecarboxylate with 3,4,5,6-tetrahydro-2H-1,2,4-triazepine-3-thiones and 4,5-dihydro-1H-pyrazole-1-carbothioamides are convenient methods for the synthesis of 7,8-dihydrothiazolo[3,2-b][1,2,4]triazepin-3-ones derivatives and methyl esters of (2Z)-[2-(4,5-dihydro-1H-pyrazol-1-yl)-4-oxo-1,3-thiazol-5(4H)-ylidene]acetic acids, respectively. The reaction of methyl propynoates with 4,5-dihydro-1H-pyrazole-1-carbothioamides or with 5,5,7-trimethyl-2,4,5,6-tetrahydro-3H-1,2,4-triazepine-3-thione gives 2-(4,5-dihydro-1H-pyrazol-1-yl)-4H-1,3-thiazin-4-ones.     

An unexpected aromatization during the N-alkylation reaction of 3,4-dihydro-1H-pyrazole derivatives: insight into the reaction mechanism

In this letter we describe the unexpected aromatization that takes place during the N-alkylation reaction performed on several 3-(2-nitrobenzoyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid methyl esters, giving rise to a mixture of 1-alkyl-3-(2-nitrobenzoyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid methyl esters and 1-alkyl-3-(2-nitrobenzoyl)-1H-pyrazole-5-carboxylic acid methyl esters.     

Reactions of Aliphatic Diazo Compounds: III. Reaction of Ethyl Diazoacetate with 1,3-Diarylpropenones

Ethyl diazoacetate adds to 1,3-diarylpropenones in a regioselective fashion to give intermediate 4,5-dihydro-3H-pyrazole derivative; 1,3-hydride shift in the latter leads to formation of isomeric ethyl 4-aryl- 5-aroyl-4,5-dihydro-1H-pyrazole-3-carboxylate and ethyl 4-aryl-3-aroyl-4,5-dihydro-1H-pyrazole-5-carboxylate at a ratio of 5:1. Thermolysis of these products is not stereospecific; as a result, three isomeric substituted ethyl cyclopropanecarboxylates and 2-pyranone derivative are formed.     

Synthesis of 1-Aryl-1H-pyrazolecarbonitriles and related derivatives

The synthesis of 1-aryl-5-cyano-1H-pyrazole-4-carboxylic acid, ethyl esters 1 is described. Subsequent chemistry led to relatively simple and unique pyrazole derivatives. Most important of these are 1-aryl-5-(aminocarbonyl)-1H-pyrazole-4-carboxylic acids 2, which are chemical hybridizing agents in wheat and barley. The regioselective hydrolysis of 1-(3-chlorophenyl)-1H-pyrazole-4,5-dicarboxylic acid, dimethyl ester (7b) and subsequent chemistry is also described.     

Polycondensed nitrogen heterocycles. XXII. A new synthesis of 5,6-dihydro-7H-pyrazolo[1,5-d][1,4]benzodiazepin-6-ones

A new synthesis of 2-methyl-9-R'-10-R-5,6-dihydro-7H-pyrazolo[1,5-d][1,4]benzodiazepin-6-ones ( 4a-c ) is deserved. Reaction of ethyl hydrazinoacetate hydrochloride with 1,3-diketones 1a-c gave both 3-methyl-5-(4R'-5-R-2-nitrophenyl)pyrazol-1-yl-acetate acids ( 2a-c ) and the corresponding ethyl esters 3a-c . Reduction with the appropiate reducing agent of compounds 2a-c and 3a-c directly gave the title compounds. Compound 4a showed insecticidal properties against the house fly.     

Synthesis of New 2-Aminopyrrole Derivatives by Reaction of Furan-2,3-diones 3-Acylhydrazones with CH-Nucleophiles

Recyclization of furan-2,3-diones acylhydrazones under the action of esters, amides and nitriles of cyanoacetic acids gave the corresponding esters, amides and nitriles of 2-amino-1-R-4-oxo-5- (2-oxo-2-aryl/tert-butylethylidene)-4,5-dihydro-1H-pyrrole-3-carboxylic acids.     

Reaction of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with arylhydrazines. synthesis of isomeric 5-arylcarbamoyl-4-aroyl- and 5-aryl-4-aryloxamoyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazoles

Methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with arylhydrazines to give methyl 3-aroyl-1-aryl-2-(2-arylhydrazinyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates which underwent thermal recyclization into isomeric methyl 1-aryl-5-(arylcarbamoyl)-4-aroyl-1H-pyrazole- 3-carboxylates and methyl 1,5-diaryl-4-[2-oxo-2-(arylamino)acetyl]-1H-pyrazole-3-carboxylates.     

Synthesis of 4,10-dihydro-4,10-dioxo-1H-[1]-benzopyrano[3,2-b]pyridine, 4,5-Dihydro-4,5-dioxo-1H-[1]-benzopyrano[2,3–6]pyridine and 1,5-Dihydro-1,5-dioxo-4H-[1]-benzopyrano[3,4-b]pyridine derivatives from aminobenzopyrones

3-Aminochromone and 3-aminocoumarin were condensed with diethyl ethoxymethylenemalonate and with dimethyl acetylenedicarboxylate to give intermediates, which were thermally cyclized to give 4,10-dihydro-4,10-dioxo-lH-[1]-benzopyrano[3,2-b]pyridinecarboxylates and 1,5-dihydro-1,5-dioxo-4H-[1]-benzopyrano-[3,4-b]pyridinecarboxylates. 2-Aminochromone was converted to 4,5-dihydro-4,5-dioxo-1H-[1]-benzopyrano-[2,3-b]pyridinecarboxylate via an intermediate condensation product with diethyl ethoxymethylenemalonate. These esters were hydrolyzed to the corresponding carboxylic acids (21, 30, 36, 50, and 60). Attempts to prepare 4,5-dihydro-4,5-dioxo-1H-[1]-benzopyrano[4,3-b]pyridinecarboxylates from 4-aminocoumarin were unsuccessful.     

Thermolysis of hexasubstituted-4,5-dihydro-3H-pyrazoles: Synthesis of 1-alkoxy- and 1-acetoxy-1,2,2,3,3-pentasubstituted-cyclopropanes

A series of 5-alkoxy- and 5-acetoxy-4,4-dimethyl-3,3,5-trisubstituted-4,5-dihydro-3H-pyrazoles 2a-f (hexasubstituted pyrazolines) was synthesized by oxidation of the corresponding 3,4-dihydro-2H-pyrazoles with lead tetraacetate in the appropriate solvents. The 5-acetoxy compounds were produced when the oxidations were carried out in methylene chloride. Oxidation with lead tetraacetate in dry alcoholic solvents resulted in the formation of the 5-alkoxy derivatives as the major products. Thermolysis of the hexasubstituted-4,5-dihydro-3H-pyrazoles 2a-f in cyclohexane or as the melt at high temperature yielded the 1-alkoxy- and 1-acetoxy-1,2,2,3,3-pentasubstituted cyclopropanes 3a-f in good yields. Trace amounts of alkene products were formed in several reactions. No products attributable to cycloreversion pathways were detected. The product distributions were consistent with extrusion of nitrogen gas from 2a-f to yield the singlet 1,3-diradical, closure of which resulted in cyclopropane formation with partial retention of stereochemistry.     

Electrophilic cyclization of <Emphasis Type="Italic">N</Emphasis>-allyl(propargyl)-5-amino-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-4-carboxamides. Synthesis of 4-[(dihydro)oxazol-2-yl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-5-amines

N-Allyl-5-amino-1H-pyrazole-4-carboxamides in reactions with polyphosphoric acid, with N-halosuccinimides in chloroform, and with (chlorosulfanyl)benzenes in nitromethane in the presence of lithium perchlorate underwent cyclization involving the N-allylamide fragment to give 4-[5-methyl(halomethyl)-4,5-dihydrooxazol-2-yl]-1H-pyrazol-5-amines and 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methyl]-4,5-dihydro-1,3-oxazolium perchlorates, respectively. Analogous reactions of N-propargyl-5-amino-1H-pyrazole-4-carboxamides with polyphosphoric acid afforded 4-(5-methyloxazol-2-yl)-1H-pyrazol-5-amines, and with (chlorosulfanyl) benzenes, 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methylidene]-4,5-dihydro-1,3-oxazolium perchlorates.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. VI. Synthesis of ethyl or methyl 1,5-disubstituted 1H-pyrazole-4-carboxylates

Reaction of ethyl or methyl 3-oxoalkanoates with N,N-dimethylformamide dimethyl acetal gave, generally in excellent yields, a series of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates II which reacted with phenylhydrazine to afford the esters of 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids III in high yields. Esters III were hydrolyzed to the relative 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids which were converted by heating to 5-substituted 1-phenyl-1H-pyrazoles in excellent yields. Reaction of II with methylhydrazine afforded in general a mixture of 3- and 5-substituted ethyl 1-methyl-1H-pyrazole-4-carboxylates with the exception of IIg , which gave in high yield methyl 5-benzyl-1-methyl-1H-pyrazole-4-carboxylate, which was hydrolyzed to the relative pyrazolecarboxylic acid. This afforded by heating 5-benzyl-1-methyl-1H-pyrazole in quantitative yield.     

Transformations of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one under various conditions of cyclopropyldiazonium generation

Cyclopropyldiazonium generated by basic decomposition of N-cyclopropyl-N-nitrosourea easily entered into an azo coupling reaction with 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one (2) to give the corresponding cyclopropylhydrazone in up to 90% yield. Competitive processes occurring under the conditions of cyclopropyldiazonium generation by nitrosation of cyclopropylamine with butyl nitrite mainly include nitrosation of the starting pyrazolone 2. Subsequent transformations of the resulting heterocyclic 3-methyl-1-phenyl-1H-pyrazole-4,5-dione 4-oxime yield 4-[cyclopropyl(oxido)imino]-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2151–2155, December, 2006.     

Synthesis of Azaheterocyclic Cymantrene Derivatives

The reduction of acetylcymantrene with sodium tetrahydridoborate gave cymantrenylethanol which was acylated with 4,5-dichloroisothiazole- and 5-(4-methylphenyl)isoxazole-3-carbonyl chlorides to obtain esters containing a 1,2-thia(oxa)zole fragment. The condensation of acetylcymantrene with 5-arylisoxazole-3- carbaldehydes, (5-arylisoxazol-3-yl)methoxybenzaldehydes (Ar = Ph, 4-Tol), and 4,5-dichloroisothiazole-3- carbaldehyde afforded the corresponding (E)-3-(azol-3-yl)-1-cymantrenylprop-2-en-1-ones. The resulting α,β- unsaturated ketones reacted with semicarbazide hydrochloride and thiosemicarbazide to produce substituted 4,5-dihydro-1H-pyrazole-1-carboxamides and -1-carbothioamides, and their reaction with hydroxylamine hydrochloride led to the formation of 4,5-dihydroisoxazoles containing cymantrene and 1,2-azole fragments. Heterocyclization of azolylcymantrenylpropenones with guanidine gave 2-aminopyrimidine derivatives, and dihydropyrimidine-2-thiones were obtained by their reaction with thiourea.     

5-Oxo-1H-4,5-dihydro-1,2,4-benzotriazepines. Chemical behavior towards alkylating,acidic and alkaline agents

The chemical behavior of 4-methyl and 4-phenyl-5-oxo-1H-4,5-dihydro-1,2,4-benzotriazepines towards methylating and acidic agents has been investigated. The 4-methyl derivative, when treated with methyl fluorosulfonate furnished, after crystallization from water, a quaternary salt (2,4-dimethyl-5-oxo-1H-4,5-dihydro-1,2,4-benzotriazepinium fluorosulfonate), whereas from the 4-phenyl derivative, a complex mixture was obtained, which, after boiling with water, afforded 2-methylindazolone, aniline fluorosulfonate and formic acid. In acidic medium the 4-methyl derivative underwent an isomerization reaction yielding 1-imino-3-methylquinazolin-4-one, but the 4-phenyl derivative exclusively yielded products resulting from ring opening. In alkaline medium, both compounds gave hydrolytic cleavage products.     

Synthesis of 4,5-Dialkyl 1-Isopropyl 3-Isopropoxy1 H -Pyrazole-1,4,5-tricarboxylate by Using Mitsunobu Chemistry

4,5-dialkyl 1-isopropyl 3-isopropoxy-1H-pyrazole-1,4,5-tricarboxylate was obtained in an excellent yield from the reaction of dialkyl acetylenedicarboxylates and diisopropyl azodicarboxylate in the presence of triphenylphosphine in dry dichloromethane. This reaction provides a useful synthetic route to highly functionalized pyrazoles.     

α,α-Dibromoketone precursors in the synthesis of some new thiazole derivatives: Thiazol-2-yl hydrazonobutanoates,thiazol-2-yl pyrazole-4-carboxylates and acids

In the present study, α,α-dibromoacetophenones are used as efficient precursors for the facile synthesis of several new hydrazonothiazoles, ethyl 3-((4-arylthiazol-2-yl)hydrazono)butanoates, which undergo Vilsmeier-Haack cyclization to obtain thiazolylpyrazole esters, ethyl 3-methyl-1-(4-arylthiazol-2-yl)-1H-pyrazole-4-carbxylates, basic hydrolysis of which gives the corresponding acids, 3-methyl-1-(4-arylthiazol-2-yl)-1H-pyrazole-4-carbxylic acids. All these compounds are tested for antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis; Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa and antifungal activity against Saccharomyces cerevisiae and Candida albicans.     

Five-membered 2,3-dioxo heterocycles: LXXXII. Recyclization of dimethyl 4,5-Dioxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates in reaction with monosubstituted hydrazines. crystalline and molecular structure of dimethyl 1-benzyl-5-(4-methylphenylcarbamoyl)-1H-pyrazole-3,4-dicarboxylate

Dimethyl 1-aryl(benzyl)-4,5-dioxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates reacted with phenylhydrazine and benzylhydrazine to give dimethyl 1-aryl(benzyl)-5-[(aryl or benzyl)carbamoyl]-1H-pyrazole-3,4-dicarboxylates.     

Furan derivatives. Part 8 On substituent effects in the synthesis of 4,5-dihydro-3H-naphtho[1,8-bc]furans

4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 6 which have various substituents (R¹ and R²) have been synthesized from 8-oxo-5,6,7,8-tetrahydro-1-naphthyloxyacetic acids 1 and 3 or their ethyl esters 2 . The reaction of acids 1 and 3 with sodium acetate in acetic anhydride gave a mixture of furans 4 and 6 and lactones 5 and 7 . The ratios of the products were varied according to the types of substituents (R¹ and R²) in acids 1 and 3 . As the substituent R¹ (R² = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, production of furans 4 became more difficult. However, when a phenyl group was used as the substituent, furan 4 was obtained in good yield. Similarly, as the substituent R² (R¹ = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, furan formation was more difficult. In contrast, acids 3 which had electron-withdrawing substituents such as chlorine, bromine or a nitro group at the 4-position afforded furans 6 in good yield. 4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 4,5-dihydro-3H-naphtho[1,8-bc]furan-2-carbocylic acids 8 were synthesized from the reaction of esters 2 and potassium hydroxide in dioxane. When the substituents R¹ or R² in esters 2 were varied from hydrogen to a methyl, ethyl or isopropyl group the total yields of furans 4 and furancarboxylic acids 8 were reduced.     

Synthesis of polyfunctionalized alkenes and α,β-unsaturated γ-lactams from the reaction of alkyl propiolates and CH-acids such as diethyl acetamidomalonate and ethyl acetamidocyanoacetate in the presence of triphenylphosphine

Dialkyl 1-(Z)-2-(acetylamino)-2-butenedioates, 1,1-diethyl-3-alkyl (E)-(1-acetylamino)-2-propene-1,1,3-tricarboxylate, 5-ethyl-1-methyl (E)-4-(acetylamino)-4-cyano-2-pentenedioate and ethyl 1-acetyl-2-cyano-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylate were obtained from the three-component reactions between alkyl propiolates and CH-acids such as diethyl acetamidomalonate and ethyl acetamidocyanoacetate in the presence of triphenylphosphine at room temperature in dry dichloromethane. Correspondence: Sakineh Asghari, Chemistry Department, Mazandaran University, P. O. Box 453, Babolsar, Iran.     

A novel rearrangement of 2(5H)-furanones

A novel rearrangement of 2(5H)-furanones is described. When refluxed in aq. Ethanolic solution in the presence of excess KOH, the 2,5-dihydro-2-oxofuran-3-carboxamides 6 underwent a novel rearrangement to the corresponding 4,5-dihydro-4-oxo-2-(phenylamino)-3-furancarboxylic acids 1 in moderate-to-excellent yields.