Synthesis and Structure of 5-Indolyl-6-thienyl-1,2,4-triazines

Acylation of indole and 2,5-dimethylthiophene with 2-(3-indolyl)-2-oxoacetyl chloride afforded the corresponding diketones. 1-(2,5-Dimethyl-3-thienyl)-2-(3-indolyl)ethanedione reacted with thiosemicarbazide under atmosperic and elevated pressure to give 6-(2,5-dimethyl-3-thienyl)-5-(3-indolyl)-2,3-dihydro-1,2,4-triazine-3-thione whose structure was studied in detail by the X-ray diffraction method. Reactions of 6-(2,5-dimethyl-3-thienyl)-5-(3-indolyl)-2,3-dihydro-1,2,4-triazine-3-thione with amines and hydrazine resulted in formation of fused triazolo- and tetrazolotriazines.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 6, 2005, pp. 895–902.Original Russian Text Copyright © 2005 by Krayushkin, Yarovenko, Sedishev, Zavarzin, Vorontsova, Starikova.Dedicated to Full Member of the Russian Academy of Sciences V.I. Minkin on his Jubilee     

Synthesis of 2-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-carbonyl)-6,6-dimethyl-3-phenyl-3,5,6,7-tetrahydro-2H-benzofuran-4-one Derivatives via Multicomponent Reaction

A sequential one-pot, two-step reaction for an efficient preparation of 2-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-carbonyl)-6,6-dimethyl-3-phenyl-3,5,6,7-tetrahydro-2H-benzofuran-4-one derivatives has been described. One-pot reaction of in situ–formed benzopyran-substituted pyridinium ylides with aromatic aldehydes and dimedone gives corresponding 2,3-dihydrofurans in good yields. The structures of all the newly synthesized compounds were confirmed from their analytical and spectral data.     

Synthesis and Crystal Structure of 5-[（1H-1,2,4-Triazol-1- yl）methyl]-4-（2,3-dimethoxybenzylideneamino）-2- 2H-1,2,4-triazole-3（4H）-thione Monohydrate

1 INTRODUCTION Heterocyclic compounds bearing the 1,2,4-tri- azole moiety have attracted considerable attention over the past few decades since they exhibit some fungicidal activities against Puccinia recondite and applications in the field of root-growth regu- lation[1~3]. Meanwhile, 4-amino-5-mercapto-1,2, 4-triazole moiety has great versatility in fusing tovarious ring systems and possesses a broad spec- trum of biological activities[4, 5]. In our con- tinuous work directed towards the…     

Unprecedented Multicomponent Reaction of Indoles,CS2 and Nitroarenes: Stereoselective Synthesis of (Z)-3-((Arylamino)methylene)indoline-2-thiones

An efficient method for the stereoselective synthesis of (Z)-3-((arylamino)methylene)indoline-2-thiones have been developed via a novel multicomponent reaction of indoles, CS₂ and nitroarenes. A range of functionalized indoline-2-thiones were prepared in moderate to good yields from easily available starting materials. The indoline-2-thione products can be easily derivatized to give biologically active thieno[2,3-b]indole and thiopyrano[2,3-b]indole skeletons in high yields.     

Reactions of 1,5-π-cyclization of gem-difluoro-substituted azomethine ylides involving an aromatic ring

Reactions of N-(5-R-furan-2-ylmethylidene)anilines with difluorocarbene proceeds through intermediate azomethine ylides suffering 1,5-π-cyclization to yield 6,6-difluorocyclopropa[b]furo[2,3-c]pyrrole and/or 4,4,6,6-tetrafluorocyclopropa[b]furo[2,3-c]pyrrole. The heating of these compounds without solvent resulted in high yields of 2,5-disubstituted 7-fluoro-4,5-dihydrofuro[3,2-c]pyridin-4(5H)-ones.     

4-Oxa(thia)-9-oxa-2-azabicyclo[4.2.1]nonane-3-on(thion) derivatives

The synthesis of 7,8-dihydroxy-2-(2-methoxycarbonylethyl)-4,9-dioxa-2-azabicyclo[4.2.1]nonane- 3-thione ( 16 ) and of its parents 9-oxa-4-thia-3-thione 17 , and 9-oxa-4-thia-3-one 18 is described. The conversion of 5′-deoxy-5′-iodo-2′,3′-O, O-isopropylidene-5,6-dihydrouridin ( 1 ) into the 2-O-methyl-5,6-dihydrouridine 5 , the 5′-O-acetyl-5,6-dihydrouridine 4 , and into the N-(5-O-acetyl-2,3-O, O-isopropylidene-β-D -ribofuranosyl)-N-(2-methoxycarbonyl thyl)-urea ( 6 ) invoked 2′,3′-O, O-isopropylidene-2,5′-anhydro-5,6-dihydrouridine ( 2 ) as the common intermediate.     

Synthesis of (2E)-2-(tetrafluoroethylidene)-3,3-bis(trifluoromethyl)-2,3-dihydrothiazolo[3,2-a]benzimidazole

The reaction of benzimidazoline-2-thione with perfluoro-2-methylpent-2-ene in the presence of triethylamine afforded (2E)-2-(tetrafluoroethylidene)-3,3-bis(trifluoromethyl)-2,3-dihydrothiazolo[3,2-a]benzimidazole whose structure was confirmed by X-ray diffraction analysis. The reaction pathways are discussed.     

Short and efficient synthesis of 2H-pyrroles from 7-oxanorbornadiene derivatives

A microwave-assisted tandem [3+2] cycloaddition/retro-Diels-Alder reaction of azomethine ylides derived from imines of α-amino esters to dimethyl 7-oxabicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylate derivatives is described. The procedure delivers, in a short reaction time, pyrrolines in high yields. In a such sequence, the oxanorbornadiene derivatives behave as masked forms of dimethyl acetylenedicarboxylate. Subsequent oxidation of the synthesized 3-pyrrolines with DDQ affords 2H-pyrroles with yields in the 76-88% range. If this three-step sequence is run on the non-substituted 7-oxabicycloheptadienedicarboxylate, purification of the intermediate 3-pyrrolines is avoided to afford 2H-pyrroles in less than 2 h.     

4a,6,7,8a-Tetrahydro-1,3-dithiolo[4',5':5,6]-1,4-dithiino [2,3-b]-1,4-dithiine-2-thione as a precursor for synthesis of new organic π-donors

[2+4[-Cycloaddition of 2,3-dihydro-1,4-dithiine and oligomeric 1,3-dithiol-2,4,5-trithione results in the formation of 4a,6,7,8a-tetrahydro-1,3-dithiolo[4',5':5,61-[1,4[dithiino[2,3-b[1,4-dithiine-2-thione, which is a precursor for synthesis of new organic rz-donors.Translated fromIzvestiya Akademi Nauk Seriya Khimicheskaya No. 3, pp. 775–776, March, 1996.     

Preparation of 2,3- and 2,5-dihydropyrazine 1,4-dioxides from 2-hydroxyamino-2-methylpropanal oxime and some of their properties

3-Hydroxy-2,3-dihydropyrazine 1,4-dioxide derivatives were obtained by condensation of 2-hydroxyamino-2-methylpropanal oxime with glyoxal, diacetyl, and 1,2-cyclohexanedione in water, and 3-methoxy-2,3-dihydropyrazine 1,4-dioxide was obtained by condensation with diacetyl in methanol. 2,5-Dihydropyrazine 1,4-dioxide is formed when 2-hydroxyamino-2-methylpropanal oxime is heated in a solution of acetone and dilute hydrochloridic acid. The reduction of 3-hydroxy- and 3-methoxy-2,3-dihydropyrazine 1,4-dioxides and 2,5-dihydropyrazine 1,4-dioxide leads to 1,4-dihydroxypiperazines, and the bromination of 3-methoxy-2,3-dihydropyrazine 1,4-dioxide gives 5,6-bis(bromomethyl)-3-methoxy-2,3-dihydropyrazine 1,4-dioxide. 1,4-Dihydroxy-2,5-piperazinedione was obtained by oxidation of 2,5-dihydropyrazine 1,4-dioxide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1414–1418, October, 1983.     

PdI2-catalyzed coupling-cyclization reactions involving two different 2,3-allenols: an efficient synthesis of 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives

Transition-metal-catalyzed dimeric coupling-cyclization reactions of two different 2,3-allenols afforded 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives 3. 2-Substituted 2,3-allenols 1 cyclized to form the 2,5-dihydrofuran ring, whereas the 2-unsubstituted 2,3-allenols 2 provided the 1,3-diene unit at the 4-position. The reaction is proposed to proceed through an oxypalladation, insertion, and beta-hydroxide elimination process. The C=C double bond was formed with high E stereoselectivity by beta-hydroxide elimination.     

Saturated heterocycles, 75. Preparation of tetracyclic thiophene derivatives with bridgehead nitrogen. Synthesis of polymethylenethieno[2,3—d]dihydropyrrolo-, tetrahydropyrido- and tetrahydroazepino[1,2—a]pyrimidin-4-ones and -4-thiones

The following tetracyclic ring systems and their derivatives have been synthesized for pharmacological investigations: Trimethylenethieno[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-one and -4-thione (1 a, 5 a); Tetramethylenethieno[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-one and -4-thione (1 b, 1 j, 5 b); Pentamethylenethieno[2,3—d]dihydropyrrolo[1,2—a]pyrimidin-4-one and-4-thione (1 c, 5 c); Trimethylenethieno[2,3—d]tetrahydropyrido[1,2—a]pyrimidin-4-one and -4-thione (1 d, 5 d); Tetramethylenethieno[2,3—d]tetrahydropyrido[1,2,—a]pyrimidin-4-one and -4-thione (1 e, 5 e); Pentamethylenethieno[2,3—d]tetrahydropyrido[1,2—a]pyrimidin-4-one and -4-thione (1 f, 5 f); Trimethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-one and -4-thione (1 g, 5 g); Tetramethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-on and -4-thione (1 h, 5 h); Pentamethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-one and -4-thione (1 i, 5 i); Tentamethylenethieno[2,3—d]tetrahydroazepino[1,2—a]pyrimidin-4-one (7 b); Pentamethylenethieno-[2,3—d]tetrahydropyrido[1,2—a]pyrimidin-4-one (7 c).Compounds1 a–i were synthesized from 2-amino-3-ethoxycarbonyl-4,5-polymethylenethiophene2 a–c with the corresponding lactim ethers (3 a–c) in chlorobenzene in the presence of polyphosphoric acid (PPA). Compounds7 b and7 c were obtained in the reaction of -amino acid esters2 b and2 c with 2-bromopyridine (6). The thione derivatives (5 a–i) were prepared from compounds1 a–i with phosphorus(V) sulphide.Part 74:Szabó J, Fodor L, Szcs E, Bernáth G, Sohár P (1984) Pharmazie 39: 347.     

2,3-Dihydro-5,6-tetramethylenespiro(cyclohexane-2-thieno[2,3-d]pyrimidine)-4(1H)-thione. A Novel Synthetic Route and Crystalline Structure

Self-condensation of cyclohexylidenecyanothioacetamide gave 2,3-dihydro-5,6-tetramethylenespiro(cyclohexane-2-thieno[2,3-d]pyrimidine)-4(1H)-thione, the structure of which was proved by X-ray analysis. A mechanism is proposed for its formation and its alkylation has been studied.     

4-(3-Cyanopyridin-2-ylthio)acetoacetates in synthesis of heterocycles

Substituted 2-amino-4-aryl-3-cyano-5-oxo-5,6-dihydro-4H-pyrano[2,3-d]pyrido[3",2":4,5]thieno[3,2-b]pyridines were synthesized by the reactions of 4-hydroxy-1H-thieno[2,3-b;4,5-b]dipyridin-2-ones with arylidenemalononitriles or by the three-component reactions of hydroxythienodipyridinones with aldehydes and malononitrile in DMF in the presence of triethylamine. Methods for syntheses of substituted 3-alkoxycarbonyl-6-amino-4-aryl-2-(3-cyanopyridin-2-ylthiomethyl)-4H-pyrans were developed on the basis of the reactions of 4-(3-cyanopyridin-2-ylthio)acetoacetates and arylidenemalononitriles or aldehydes and malononitrile. Ethyl 4-(3-cyanopyridin-2-ylthio)acetoacetate and 4-methoxybenzylidenecyanothioacetamide were used for the synthesis of 6-(pyridin-2-ylthiomethyl)-3-cyanopyridine-2(1H)-thione.     

Synthesis and conversions of 5-(3,5-6-trichloro-1,4-benzoquinon-2-yl)-2-isopropylidenehydrazinothiazole and 2-isopropylidenazinothiazolines

When 2,5-dihydroxy-3,4,6,7-tetrachloro-2,3-dihydrobenzo[b]furan interacts in acetone with thiosemicarbazide or its 4-methyl or 4-phenyl derivative, the respective products are 5-(2,5-dihydroxy-3,4,6-trichlorophenyl)-2-(isopropylidenehydrazino)thiazole and -3-R-2-(isopropylidenazino)thiazolines, respectively. It has been shown that hydrolysis of these compounds forms 3-amino-5-(2,5-dihydroxy-3,4,6-trichlorophenyl)-2-imino(or 2-R-imino)thiazolines. These products of hydrolysis and their predecessors are oxidized to the corresponding 2-hetaryl-substituted 3,5,6-trichloro-1,4-benzoquinones.Riga Technical University, Riga, LV-1048. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1424–1431, October, 1996. Original article submitted July 1, 1996.     

Synthesis of the precursors of bis(trichloro-1,4-benzoquinonyl)tetrathiafulvalenes

In reaction with potassium butylxanthate and sodium tert-butyltrithionate, 2,5-dihydroxy-3,4,6,7-tetrachloro-2,3-dihydrobenzo[b]furan forms the products from nucleophilic substitution of a chlorine atom, i.e., O-butyl S-(2,5-dihydroxy-4,6,7-trichloro-2,3-dihydrobenzo[b]furan-3-yl) xanthate and S-tert-butyl S-(2,5-dihydroxy-4,6,7-trichloro-2,3-dihydrobenzo[b]furan-3-yl) trithiocarbonate respectively. Recyclization of the xanthate in concentrated sulfuric acid gave 4-(2,5-dihydroxy-3,4,6-trichlorophenyl)-1,3-dithiol-2-one, which was oxidized by iron trichloride to the corresponding benzoquinone. Cyclization of the trithiocarbonate in the presence of trifluoroacetic and p-toluenesulfonic acid led to 7-hydroxy-5,6,8-trichloro-3a,8b-dithiolo[4,5-b]benzo[d]furan-2-thione.Dedicated to Prof. A. Katritzky in honor of his seventieth birthday.Riga Technical University, Riga LV-1048, Latvia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1055–1060, August, 1998.     

Three-Component Reaction for an Efficient Synthesis of Stable Phosphorus Ylides Using Mercapto Compounds

Stabilized phosphorus ylides were obtained from the three-component reaction between dialkyl acetylenedicarboxylate and sulfur compounds such as pyridine-2-thione, 2-furylmethanethiol, ethanedithioamide, and N-phenyl-1,2,4-triazole-3-thiol in the presence of triphenylphosphine in excellent yields.     

Synthesis of 3-N,N-Dialkylamino-5-(3,5,6-trichloro-1,4-benzoquinon-2-yl)thiazoline-2-thiones

N,N-Dialkylhydrazides of S-(4,6,7-trichloro-2,5-dihydroxy-2,3-dihydrobenzo[b]-3-furanyl)dithiocarbonic acids have been obtained by the reaction of 3,4,6,7-tetrachloro-2,5-dihydroxy-2,3-dihydrobenzo[b]furan with N,N-dialkylhydrazinium salts of N,N-dialkylhydrazides of dithiocarbonic acids. Recyclization in boiling ethanol in the presence of conc. HCl with subsequent oxidation leads to the formation of 3-N,N-dialkylamino-5-(3,5,6-trichloro-1,4-benzoquinon-2-yl)thiazoline-2-thiones. An attempt at recyclization in boiling trifluoroacetic acid led to the formation of 3-N,N-dialkylamino-5,6,8-trichloro-7-hydroxy-2,3,3a,8b-tetrahydrothiazolo[4,5-b]benzo[d]furane-2-thiones.     

Comparison of oxygen and sulfur effects on keto-enol chemistry in benzolactone systems: benzo[b]-2,3-dihydrofuran-2-one and -2-thione and benzo[b]-2,3-dihydrothiophene-2-one and -2-thione

Carbon-acid ionization constants, Q(K)(a)(concentration quotient at ionic strength = 0.10 M), were determined by spectrophotometric titration in aqueous solution for benzo[b]-2,3-dihydrofuran-2-one (3, pQ(K)(a) = 11.87), benzo[b]-2,3-dihydrothiophene-2-one (2, pQ(K)(a) = 8.85), and benzo[b]-2,3-dihydrofuran-2-thione (1, pQ(K)(a) = 2.81). Rates of approach to keto-enol equilibrium were also measured for the latter two substrates in perchloric acid, sodium hydroxide, and buffer solutions, and the rate profiles constructed from these data gave the ionization constants of the enols ionizing as oxygen or sulfur acids pQ(E)(a) = 5.23 for 2 and pQ(E)(a) = 2.69 for 1. Combination of these acidity constants with the carbon-acid ionization constants according to the relationship Q(K)(a)/Q(E)(a) = K(E) then gave the keto-enol equilibrium constants pK(E) = 3.62 for 2 and pK(E) = 0.12 for 1. The fourth, all-sulfur, member of this series, benzo[b]-2,3-dihydrothiophene-2-thione (4), proved to exist solely as the enol in aqueous solution, and only the enol ionization constant pQ(E)(a) = 3.44 could be determined for this substance; the limits pK(E) < 1.3 and pQ(K)(a) < 2.1, however, could be set. The unusually high acidities and enol contents of these substances are discussed, as are also the relative values of the ketonization and enolization rate constants measured; in the latter cases, Marcus rate theory is used to determine intrinsic kinetic reactivities, free of thermodynamic effects.     

Studies on Phosphonium Ylides-XXIII: The Behavior of Active and Stabilized Phosphonium Ylides Towards Thiohydantoins

Thiohydantoin 1 reacts with 2-oxovinylidenetriphenylphosphorane (2) to give 1-methyl-2-thioxo-6-(triphenyl-λ⁵-phosphoranylidene)-hexahydro-furo[2,3-d]imidazol-5-one (5). On the other hand, when 1 reacts with phosphorus ylides 3a–d, the respective olefinic adducts 6a, 6b, 8, and the dimeric product 7 were obtained together with triphenyl-phosphine oxide. Moreover, the application of reagent 4 on 1 renders the new product 4-methyl-2,3-diphenyl-2,3,4,6-tetrahydro-1-oxa-1,3,4,6-tetra-azapentalene-5-thione. Mechanisms accounting for the formation of the products are presented based on analytical and spectroscopic data.