Chemistry of iminofurans: IX. Synthesis and cyclization of (2<Emphasis Type="Italic">Z</Emphasis>)-2-{(2<Emphasis Type="Italic">Z</Emphasis>)-2-[2-(3-R-adamantan-1-yl)-2-oxoethylidene]hydrazinyl}-4-(het)aryl-4-oxobut-2-enoic acids

1-(3-R-adamantan-1-yl)-2-[(triphenyl-λ⁵-phosphanylidene)hydrazinylidene]ethanone reacted with 4-aryl(hetaryl)-2,4-dioxobutanoic acids to give 2-{2-[2-(3-R-adamantan-1-yl)-2-oxoethylidene]hydrazinyl}-4-aryl(hetaryl)-4-oxobut-2-enoic acids which were shown to exist in solution as mixtures of Z- and E-isomeric enehydrazine tautomers. The products underwent cyclization to 3-{[2-(3-R-adamantan-1-yl)-2-oxoethylidene]- hydrazinylidene}-5-aryl(hetaryl)furan-2(3H)-ones.     

Synthesis of 5-aryl(hetaryl)-4-methyl-2-(furan-2-yl)-1<Emphasis Type="Italic">H</Emphasis>-imidazol-1-oles

Reaction of 2-(hydroxyamino)-1-R-propan-1-one oximes with furfural in methanol afforded the corresponding α-furylnitrones. The cyclization of α-furylnitrones in alkaline medium results in the formation of 5-aryl(hetaryl)-2-(furan-2-yl)-1H-imidazol-1-oles.     

Synthesis of substituted 2-(thiophen-2-yl)-1<Emphasis Type="Italic">H</Emphasis>-imidazol-1-ols

Substituted 2-(thiophen-2-yl)-1H-imidazol-1-ols were synthesized by cyclization of the corresponding α-thienyl nitrones in alkaline medium. α-Thienyl nitrones were obtained by reaction of N-(1-hydroxyimine-1-R-propan-2-yl)hydroxylamines with thiophene-2-carbaldehyde in methanol. At boiling α-thienyl nitrones in methanol in the presence of sodium methylate 5-aryl(hetaryl)-2-(thiophen-2-yl)-1H-imidazol-1-ols are formed chemoselectively.     

Chemistry of Iminofurans: XV. Decyclization of Ethyl 2-[5-Aryl-2-oxofuran-3(2<Emphasis Type="Italic">H</Emphasis>)-ylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylates by the Action of Secondary Amines

Ethyl 2-[5-aryl-2-oxofuran-3(2H)-ylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylates reacted with secondary amines to give 4-aryl-2-(thiophen-2-yl)-4-oxobutanamides, whereas their reaction with piperazine afforded N,N′-disubstituted piperazine derivatives regardless of the reactant ratio.     

Synthesis and reactions of 3-(3-ethoxycarbonyl-1-phenyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-4-yl)propenic acid

The reaction of ethyl 4-formyl-1-phenyl-1H-pyrazole-3-carboxylate with the malonic acid led to the formation (2E)-3-(3-ethoxycarbonyl-1-phenyl-1H-pyrazol-4-yl)propenic acid. In reactions of this acid chloride with 4-amino-5-aryl(hetaryl)-4H-1,2,4-triazole-3-thiols were obtained ethyl 4-[(E)-2-{3-aryl(hetaryl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl}ethenyl]-1-phenyl-1H-pyrazoe-3-carboxylates, with 5-aryltetrazoles, ethyl 4-[(E)-2-(5-aryl-1,3,4-oxadiazol-2-yl)-ethenyl]-1-phenyl-1H-pyrazole-3-carboxylates, with 1-(2-hydroxy-3,5-dimethylphenyl) followed by the Baker-Venkataraman rearrangement and the cyclization, ethyl 4-[(E)-2-(6,8-dimethyl-4-oxo-4Hchromen-2-yl)ethenyl]-1-phenyl-1H-pyrazole-3-carboxylate.     

Dehydrogenation of 1-aryl(hetaryl)-1,2,3,4-tetrahydro-9<Emphasis Type="Italic">H</Emphasis>-β-carboline-3-carboxylic acids and their esters with dimethyl sulfoxide

Oxidative dehydrogenation of 1-aryl(hetaryl)-1,2,3,4-tetrahydro-9Н-β-carboline-3-carboxylic acids derivatives with dimethyl sulfoxide leads to the formation of 1-aryl(hetaryl)-9Н-β-carbolines. Simultaneously with the dehydrogenation decarboxylation occurs. At the oxidation with dimethyl sulfoxide of methyl 1-aryl (hetaryl)-1,2,3,4-tetrahydro-9Н-β-carboline-3-carboxylicates methyl 1-aryl(hetaryl)-9Н-β-carboline-3-carboxylates formed whose hydrolysis afforded the corresponding 1-aryl(hetaryl)-9Н-β-carboline-3-carboxylic acids.     

Fusion of 2-(furan-2-yl)thiazole to 1-methyl-1<Emphasis Type="Italic">H</Emphasis>-benzimidazole

Methylation of 5(6)-nitro-1H-benzimidazole with methyl iodide in the presence of potassium hydroxide and N-methylpyrrolidin-2-one gave a mixture of isomeric 1-methyl-5-nitro- and 1-methyl-6-nitro-1H-benzimidazoles which were reduced with tin in concentrated aqueous HCl on heating. The resulting amines reacted with furan-2-carbonyl chloride in N-methylpyrrolidin-2-one to give furan-2-carboxamides which were treated with excess P₂S₅ in pyridine. Oxidation of isomeric furan-2-carbothioamides with K₃[Fe(CN)₆] in alkaline medium afforded a mixture of intramolecular cyclization products, 2-(furan-2-yl)-6-methyl-6H-imidazo[4,5-g][1,3]benzothiazole and 2-(furan-2-yl)-8-methyl-8H-imidazo[4,5-g][1,3]benzothiazole which were separated by column chromatography and identified.     

Synthesis,Structure, and Reactivity of Naphtho-Fused 2-(Furan-2-yl)-1,3-thiazole

The condensation of naphthalen-2-amine with furan-2-carbonyl chloride in propan-2-ol gave N-(naphthalen-2-yl)furan-2-carboxamide which was treated with excess P₂S₅ in anhydrous toluene to obtain the corresponding thioamide. The oxidation of the latter with potassium hexacyanoferrate(III) in alkaline medium afforded 2-(furan-2-yl)naphtho[2,1-d][1,3]thiazole. A probable mechanism of its formation was proposed, and the ring closure involving C¹ of the naphthalene fragment was substantiated by quantum chemical calculations. Electrophilic substitution reactions of 2-(furan-2-yl)naphtho[2,1-d][1,3]thiazole (nitration, bromination, formylation, and acylation) involved exclusively the 5-position of the furan ring.     

Synthesis and Reactivity of Fusion Product of 2-Methylthiazole Fragment to 2-(Furan-2-yl)benzimidazole

Reaction of 1,2-diamino-4-nitrobenzene with furan-2-carbaldehyde in the presence of copper sulfate afforded 2-(furan-2-yl)-5(6)-nitro-1H-benzimidazole. Its N-methylation provided 1-methyl-5(6)-nitro isomers. After reduction of isomers with tin in conc. HCl a pure 3-methyl-2-(furan-2-yl)benzimidazol-5-amine was obtained. The condensation of this amine with acetic anhydride led to the formation of N-[3-methyl-2-(furan-2-yl)benzimidazol-5-yl]acetamide whose treatment with excess P₂S₅ in anhydrous pyridine resulted in the corresponding thioamide. The latter was oxidized with K₃[Fe(CN)₆] in alkaline environment to obtain 2,8-dimethyl-7-(furan-2-yl)-8H-imidazo[4,5-g][1,3]benzothiazole. Its reactions of electrophilic substitution were studied: nitration, bromination, sulfonation, formylation, acylation. The substituent is introduced exclusively in the position 5 of the furan ring.     

2-amino-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidines: Synthesis and reactions with electrophilic reagents

The hydrogenation of 2-amino-5-R-7-R′-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines with NaBH₄ led to the formation of 2-amino-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]pyrimidines. Acylation, sulfonylation, and alkylation of these compounds depending on conditions and the reagent character occur at the amino group, atoms N³ or N⁴. The treatment with alkali of 2-amino-3-benzyl-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo-[1,5-a]pyrimidinium bromide resulted in 2-amino-3-benzyl-5-R-7-R′-3,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]-pyrimidine, similar reaction of 2-acetamido-3-benzyl-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]-pyrimidinium bromide gave a mesoionic product of a hydrogen elimination from the amide nitrogen atom.     

Synthesis and properties of 2-(furan-2-yl)thiazolo[5,4-<Emphasis Type="Italic">f</Emphasis>]quinoline

N-(Quinolin-6-yl)furan-2-carboxamide was prepared by the coupling of quinoline-6-amine with furan-2-carbonyl chloride in propan-2-ol. Treatment of the product with excess Р2S₅ in anhydrous pyridine gave N-(quinolin-6-yl)furan-2-carbothioamide which was oxidized with potassium ferricyanide in an alkaline medium by the Jakobson procedure to obtain 2-(furan-2-yl)thiazolo[5,4-f]quinoline. The latter was subjected to electrophilic substitution reactions (nitration, bromination, formylation, and acylation), as well as characteristic nucleophilic substitution involving the quinoline ring and quaternization with methyl iodide in benzene.     

Synthesis and properties of 2,5-bis(furan-2-yl)-1<Emphasis Type="Italic">H</Emphasis>-imidazole

2,5-Bis(furan-2-yl)-1H-imidazole was synthesized by the Weidenhagen reaction of [2-(furan-2-yl)-2-oxoethyl]acetate with furfural. Alkylation of the title compound with methyl iodide in acetone in the presence of potassium hydroxide gave a mixture of isomeric N-methyl derivatives, 2,5-bis(furan-2-yl)-1-methyl-1H-imidazole being the major one. Electrophilic substitution reactions of the latter (nitration, bromination, sulfonation, hydroxymethylation, and acylation) were studied.     

Synthesis and Some Transformations of 7-(Fur-2-yl)-1-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazolo[4,3-<Emphasis Type="Italic">g</Emphasis>][1,3]benzothiazole

N-Methylation of 5-nitro-1H-indazole in a KOH–DMSO system resulted in a mixture of 1-methyl-5(6)-nitroindazoles in a ratio of 1: 2. Reduction of the isomers with tin in concentrated hydrochloric acid afforded pure 1-methyl-1H-indazole-6-amine. Condensation of the latter with furoyl chloride in 2-propanol yielded N-(1-methylindazol-6-yl)furan-2-carboxamide, treatment of which with an excess of P2S5 in anhydrous pyridine gave the corresponding carbothioamide. 7-(Fur-2-yl)-1-methyl-1H-pyrazolo[4,3-g][1,3]benzothiazole was synthesized by Jacobson oxidation of N-(1-methylindazol-6-yl) furan-2-carbothioamide with potassium ferricyanide in an alkaline medium. Some transformations of 7-(fur-2-yl)-1-methyl-1H-pyrazolo[4,3-g][1,3]- benzothiazole such as formylation and acylation were performed.     

Electrophilic intramolecular cyclization of functional derivatives of unsaturated compounds: VIII. Cyclization of 4-aryl-<Emphasis Type="Italic">N</Emphasis>-(thiophen-3-yl)but-3-enamides by the action of polyphosphoric acid and chlorosulfanylarenes

Intramolecular cyclization of 4-aryl-N-(thiophen-3-yl)but-3-enamides on heating in polyphosphoric acid afforded 8-aryl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-ones and 5-aryl-1-(thiophen-3-yl)pyrrolidin-2-ones. Cyclofunctionalization of the title compounds with (chlorosulfanyl)benzene and 4-(chlorosulfanyl)-toluene led to the formation of 8-aryl-7-arylsulfanyl-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-ones or their mixtures with 5-aryl-4-arylsulfanyltetrahydrofuran-2-ones. 1-(Chlorosulfanyl)-4-nitrobenzene reacted with 4-(4-methylphenyl)-N-(thiophen-3-yl)but-3-enamide and 4-(4-fluorophenyl)-N-(thiophen-3-yl)but-3-enamide to give 5-(4-methylphenyl)-4-(4-nitrophenylsulfanyl)-1-(thiophen-3-yl)pyrrolidin-2-one and 5-(4-fluorophenyl)-4-(4-nitrophenylsulfanyl)tetrahydrofuran-2-one, respectively.     

Cyclization of trifluoro-<Emphasis Type="Italic">N</Emphasis>-(prop-2-yn-1-yl)methanesulfonamides to <Emphasis Type="Italic">N</Emphasis>-(hydroxymethyl)-1,2,3-triazoles

Three-component heterocyclizations of trifluoro-N-(prop-2-yn-1-yl)methanesulfonamide, trifluoro-N-pheny-N-(prop-2-yn-1-yl)methanesulfonamide, and trifluoro-N,N-di(prop-2-yn-1-yl)methanesulfonamide with formaldehyde and sodium azide afforded N-{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}-, N-{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}-N-phenyl-, and N,N-bis{[2-(hydroxymethyl)-2H-1,2,3-triazol-4-yl]methyl}trifluoromethanesulfonamides as the major products together with minor 1-(hydroxymethyl)-1H-1,2,3-triazole isomers.     

Synthesis and reactivity of 2-(furan-2-yl)benzo[<Emphasis Type="Italic">e</Emphasis>][1,3]benzothiazole

N-(1-Naphthyl)furan-2-carboxamide was synthesized by the coupling of naphthalen-1-amine with furan-2-carbonyl chloride in propan-2-ol and then treated with excess P2S5 in anhydrous toluene to obtain the corresponding thioamide. The latter was oxidized with potassium ferricyanide in an alkaline medium by the Jakobson procedure to synthesize 2-(furan-2-yl)benzo[e][1,3]benzothiazole which was subjected to electrophilic substitution reactions: nitration, bromination, formylation, and acylation.     

Synthesis of new aryl(hetaryl)vinyl-substituted benzo[<Emphasis Type="Italic">f</Emphasis>]quinolines and 4,7-phenanthrolines

Previously unknown 1-[2-aryl(quinolin-2-yl)ethenyl]-3-[aryl(quinolin-2-yl)]benzo[f]quinolines and 3-aryl-1-(2-arylethenyl)-4,7-phenanthrolines were synthesized by reactions of 1-methylbenzo[f]quinolines and 1-methyl-4,7-phenanthrolines with substituted N-benzylideneanilines and N-(quinolin-2-ylmethylidene)aniline on heating in dimethylformamide in the presence of potassium hydroxide.     

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.     

Synthesis and characterization of novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and dihydro-alkylthio-benzyloxopyrimidine (S-DABO) analogs containing a benzo[<Emphasis Type="Italic">d</Emphasis>]thiazol moiety

A series of novel dihydro-alkylthio-benzyloxopyrimidine (S-DABO) and 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)thymine (HEPT) analogs bearing a (benzo[d]thiazol-2-yl)methyl moiety at the C⁶ position of the pyrimidine core have been synthesized. 5-Allyl-6-{(benzo[d]thiazol-2-yl)methyl}-2-thiouracil and 5-allyl-6-{(benzo-[d]thiazol-2-yl)methyl}uracil were alkylated to give, respectively, S²- and N¹- ethoxymethyl and -methylthiomethyl uracil derivatives. 5-Allyl-6-[(benzo[d]thiazol-2-yl)methyl]-2-thiouracil was also alkylated by S² with methyl bromoacetate and hydrolyzed to the corresponding acid.     

Features of Reaction of 2-(5-Methyl-2-phenyl-2<Emphasis Type="Italic">H</Emphasis>-1,2,3-diazaphosphol-4-yl)-4<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">e</Emphasis>]-1,3,2-dioxaphosphorin-4-one with 1,2-Dicarbonyl Compounds

2-(5-Methyl-2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-4H-benzo[e]-1,3,2-dioxaphosphorin-4-one reacts with perfluorodiacetyl, 3,6-di(tert-butyl)-1,2-benzoquinone and phenanthrenequinone only with the participation of a three-coordinated phosphorus atom to form spirophosphoranes containing acyclic 5-methyl-2- phenyl-2H-1,2,3-diazaphosphol-4-yl substituent, whereas the interaction with tetrachloro-1,2-benzoquinone proceeds via expanding the six-membered heterocycle to the nine-membered one to form 2-(2-phenyl-2H-1,2,3-diazaphosphol-4-yl)-2,9-dioxo-4,5,6,7-tetrachlorodibenzo[d,h]-1,3,8-trioxaphosphonine.