Interaction of benzimidazole-2-thione with propargyl bromide and 1,3-dibromopropyne

Interaction of benzimidazole-2-thione with propargyl bromide under found conditions permitted the direct synthesis of 2-(2-propynylsulfanyl)-3H-1,3-benzimidazolium bromide, the base 2-(2-propynylsulfanyl)-1H-1,3-benzimidazole, stable crystalline 2-(1,2-propadienylsulfanyl)-1H-1,3-benzimidazole, and 3-methyl[1,3]thiazolo[3,2-a][1,3]benzimidazole. The reaction of benzimidazole-2-thione with 1,3-dibromopropyne in chloroform or absolute methanol gave 2-(3-bromo-2-propynylsulfanyl)-3H-1,3-benzimidazolium bromide, and in absolute methanole in the presence of a twofold excess of sodium methoxide the reaction proceeded stereo-and regioselectively to give 3-[(Z)-bromomethylidene][1,3]thiazolo[3,2-a][1,3]benzimidazole. Presented to Academician B. A. Trofimov on his 70^th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, 1399–1405, September, 2008.     

An efficient synthesis of novel pyridothieno-fused thiazolo[3,2-a]pyrimidinones via Pictet–Spengler reaction

An efficient method for the synthesis of novel pyrido[3',2':4',5']thieno[3',2':2,3]pyrido [4,5:d][1,3]thiazolo[3,2-a]pyrimidine-4-one derivatives (5) has been developed using a Pictet-Spengler reaction between 2-(3-aminothieno[2,3-b]pyridin-2-yl)thiazolo[3,2-a] pyrimidin-5-one (3), which could be obtained from the condensation of 7-(chloromethyl)-5H-thiazolo[3,2-a]pyrimidin-5-one (1) with 3-cyanopyridine-2-thione (2) via Thorpe-Ziegler isomerization, and aromatic aldehydes under NH₂SO₃H as catalysis in good yields.     

New data on the alkylation of cyclic thioureas with á-halocarboxylic acids and their esters. 2. Alkylation of tetrahydropyrimidine-2(1h)-thione and 5,5-dimethyltetrahydropyrimidine-2(1h)-thione

In the absence of bases all the attempted variations for the alkylation of tetrahydropyrimidine-2(1H)-thione with á-halocarboxylic acids gave only the bicyclic product-2-R-6,7-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-3(2H)-one hydrohalide. However the hydrohalide of the “ open” S-ethoxycarbonyl derivative of propyleneisothiourea can be obtained by treatment of tetrahydropyrimidine-2(1H)-thione with ethyl chloro-or bromoacetate in anhydrous acetone at room temperature. Alkylation of 5,5-dimethyltetrahydro-2(1H)-pyrimidinethione with chloro-or bromoacetic acid in anhydrous acetone at room temperature gave the hydrohalide of the “open” S-carboxymethyl derivative of dimethylpropyleneisothiourea. All remaining variations for the alkylation of this substrate with á-halocarboxylic acids or their esters gave only the corresponding bicyclic compounds-the hydrohalide of 2-R-6,6-dimethyl-6,7-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-3(2H)-one-independently of the reaction conditions. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 593–604, April, 2006.     

One-Pot Synthesis of Novel Spiro Pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine Derivatives

In a one-pot synthesis, 1′-methyl-2,3″-dioxo-5″-aryl-1,2,5a″,7″,8″,9a″-hexahydro-5″H,6″H-dispiro[indole-3,2′-pyrrolidine-3′,2″-pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine]-4′-carboxylic acid methyl ester was prepared via the sequential reaction of 4-aryl-octahydro-pyrano[2,3-d]pyrimidine-2-thione, dimethyl acetylenedicarboxylate (DMAD), and a mixture of isatin and sarcosine. All the novel spiro compounds, in moderate yields, were characterized thoroughly by infrared, NMR, mass spectromentry, and elemental analysis together with x-ray crystallographic analysis.     

Some chemical properties of 2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-one and 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones

We have studied the reaction of 2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-one and 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones with amines, alkylating reagents, and hydrogen peroxide. We have shown that the presence of an aryl substituent at the 2 position of [1,3-thiazino[3,2-a]benzimidazol-4-ones has a substantial effect on the direction of the reactions. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 445–452, March, 2006.     

Cyclocondensation of n-(prop-2-yn-1-yl)- and n-(penta-2,4-diyn-1-yl)- <Emphasis Type="Italic">o</Emphasis>-phenylenediamines with phenyl isothiocyanate and carbon disulfide

The cyclocondensation of N-(prop-2-yn-1-yl)-o-phenylenediamines with phenyl isothiocyanate leads to the formation of 1-(prop-2-yn-1-yl)-1,3-dihydro-2H-benzimidazole-2-thiones irrespective of the substituent nature at the triple bond. Reactions of both mono- and diacetylenic derivatives of o-phenylenediamine with carbon disulfide in the presence of KOH proceed with the formation of two heterocyclic nuclei simultaneously. From N-(prop-2-yn-1-yl)-o-phenylenediamines containing an aryl substituent at the triple bond, and N-(penta-2,4-diyn-1-yl)-o-phenylenediamines 2-methylidene-2,3-dihydro[1,3]thiazolo[3,2-a]benzimidazoles are formed. The latter are readily isomerized under the action of base giving thiazolo[3,2-a]benzimidazoles. The cyclocondensation of N-(alk-2-yn-1-yl)-o-phenylenediamines with CS₂ leads to [1,3]thiazino[3,2-a]benzimidazoles.     

Reaction of <Emphasis Type="Italic">N</Emphasis>-aryl-3-oxobutanethioamides with 2-amino-1,3-thiazole and 2-amino-1,3-benzothiazole

N-Aryl-3-oxobutanethioamides react with 2-amino-1,3-thiazole (2-amino-1,3-benzothiazole) in acetic acid to give mixtures of 7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidine-5-thione (2-methyl-4H-pyrimido-[2,1-b][1,3]benzothiazole-4-thione) and 5-arylimino-7-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidines (4-arylimino-2-methyl-4H-pyrimido[2,1-b][1,3]benzothiazoles), whose ratio depends on the nature of the aryl substituent in the initial butanethioamide.     

Novel alkylations of cyclic thioureas by α-halocarboxylic acids and their esters. 4. Alkylation of 1-methyltetrahydropyrimidine-2(1H)-thione

Alkylation of 1-methyltetrahydropyrimidine-2(1H)-thione (N-methylpropylenethiourea) with chloro-and bromoacetic acids and their esters have given the 8-methyl-3-oxo-2,3,6,7-tetrahydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-8-ium chloride or bromide. The former is readily hydrolyzed in 95% ethanol to 3-[(3-methylamino)propyl]-1,3-thiazolidine-2,4-dione hydrochloride while the second is more stable towards hydrolysis such that the corresponding hydrobromide is not separated. A paradoxical trend in the extent of the hydrolysis decreasing with the content of the water in the alcoholic solution comes to a complete stop in water. A possible explanation of this phenomenon is given. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1242–1251, August, 2006.     

Utility of a Pyrimidin-2-Thione Derivative in Synthesis of New Fused Thiazolo[3,2-a]pyrimidines

A pyrimidin-2-thione derivative 2 was prepared and treated with 1,2-dibromoethane, chloroacetic acid and ethyl chloroacetate to give the alkylation products 3,4,9,5, respectively. Furthermore, the reaction of 2 with acrylonitrile and hydrazine hydrate yielded the pyrimidino[2,1-b]thiazine derivative 7, and [1,2,4]-triazolo[4,3-a]pyrimidine 8. Compound 9 was used as the key starting material for synthesis of thiazolo[3,2-a]pyrimidine and pyrano[2′,3′ :4,5]thiazolo[3,2-a]pyrimidine derivatives 10–13, through the reaction with ethyl acetate, malononitrile, hydrazine hydrate, β-aroylacrylic acid, and chalcone, respectively. Treatment of compound 5 with 3,5-dibromo-2-aminobenzoic acid in refluxing butanol gave the 3,1-benzoxazinone derivative 6. The structure assignment of the new compounds is based on chemical and spectroscopic evidence.     

Preparation of bicyclic β-lactam and bicyclic 1,3-oxazinone scaffolds using combined cycloaddition and metathesis processes

A simple, efficient two-step method for the preparation of heterobicyclic compounds was developed. Starting from 5-acyl or 5-carbamoyl-2,2-dimethyl-1,3-dioxa-4,5-dione bicyclic scaffolds of 1-azabicyclo[5.2.0]non-3-en-9-one, 6,9,10,10a-tetrahydro-4H-[1,3]oxazino[3,2-a]azepin-4-one, and 6,9,10,10a-tetrahydro-2H-[1,3]oxazino[3,2-a]azepine-2,4(3H)-dione were prepared using cycloaddition of thermally generated ketenes to aldimines with unsaturated side chains, followed by metathesis. The method was applied to ring closing metathesis (RCM) of different heterocyclic substrates to demonstrate its versatility.     

Simple construction of fused and spiro nitrogen/sulfur containing heterocycles by addition of thioamides or thioureas on cycloalkenyl-diazenes: examples of click chemistry

New 1-cycloalkenyl-1-diazenes have been obtained in good yields from cyclic β-ketoesters and hydrazine derivatives. They furnished new cycloalkyl[d][1,3]thiazolines with thioamides or new spirocycloalkyl-thiazolinones with thioureas. Moreover they gave, with imidazolidine-2-thione and tetrahydropyrimidine-2-thione, new and interesting spiro[cycloalkyl-1,2′-imidazo[2,1-b][1,3]thiazole] or spiro[cycloalkyl-1,2′-[1,3]thiazolo[3,2-a]pyrimidine] derivatives, respectively. Cycloalkyl[d][1,3]thiazolines were useful for the further preparation of unknown thia-triaza-tricyclo derivatives. Novel hexahydro-1,3-benzothiazoles have been achieved by reaction of N,N′-dialkylthioureas on N-1-phenyl-2-(1-cyclohexenyl)-1-diazene-1-carboxyamide. The acidic hydrolysis of spirocycloalkyl-thiazolinones produced 2-imino-5-(ω-carboxyalkyl)-4-thiazolidinones.     

Rearrangement of thiazolo[3,2-a]pyrimidines into triazolo[4,3-a]pyrimidines induced by C=N bond reduction

Chemistry of Heterocyclic Compounds - Triazolo[4,3-a]pyrimidines were prepared by the reduction of 5,6,7-trisubstituted 2-(arylhydrazinylidene)-5H-[1,3]thiazolo[3,2-a]- pyrimidin-3(2H)-ones with...     

Synthesis of Substituted 1,3-Cyclohexadienes,Pyridine-2(1H)-thiones,and Thieno[2,3-d]pyrimidine- 4(3H)-thiones by the Michael Reaction

Cyclopentylidene- and cyclohexylidene(cyano)acetamides reacted with malononitrile and cyano-(thioacetamide) according to the Michael pattern with exchange of the methylene components to give substituted 1-amino-2,6,6-tricyano-1,3-cyclohexadienes and thieno[2,3-d]pyrimidine-4(3H)-thiones. Condensation of cyclopentylidene- and cyclohexylidene(cyano)acetamide with 1,3-dicarbonyl compounds afforded 4,6-di-methyl-3-cyanopyridine-2(1H)-thione and morpholinium 4-methyl-6-oxo-3-cyano-1,6-dihydropyridine-2-thiolate which were converted into substituted 2-alkylsulfanylpyridines, thieno[2,3-b]pyridines, thiazolo[3,2-a]pyridine, and 2H-[1,3]thiazino[3,2-a]pyridine.     

Synthesis of 3-Substituted Pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidines and Related Fused Thiazolo Derivatives

New ethyl 3-(substituted)-4-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydropyrido[4',3':4,5]thieno-[2,3-d]pyrimidine-7-carboxylates ( 3a , b ), ( 6 ),( 11-13 ), ethyl 3-methyl-5-oxo-2,3,6,9-tetrahydro 5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-8(7H)-carboxylate ( 4 ), and ethyl 2-methyl-5-oxo-2,3,6,9-tetrahydro-5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]-pyrimidine-8(7H)-carboxylate ( 8 ) have been synthesized from diethyl 2-isothiocyanato-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate 1. The structure of these compounds as well as their intermediates have been established by their spectral data.     

Synthesis of diarylazolo[<Emphasis Type="Italic">a</Emphasis>]pyridines from [(<Emphasis Type="Italic">Z</Emphasis>)-2,4-diaryl-4-oxo-2-butenyl]azolium salts

A method for the synthesis of derivatives of [1, 3]thiazolo[3,2-a]pyridines, pyrido[2,1-b][1, 3]benzo-thiazole, [1, 3, 4]thiadiazolo[3,2-a]pyridine, and [1, 2, 4]triazolo[4,3-a]pyridine, which includes base initiated cyclization of quaternary azolium salts, formed by the interaction of (Z)-1,3-diaryl-4-bromo-2-buten-1-ones with 1-alkyl-1H-1,2,4-triazoles, 4-methyl-1,3-thiazole, 1,3-benzothiazole, and N-phenyl-1,3,4-thiadiazole-2-amine. Derivatives of 2-chloroimidazo[1,2-a]pyridine were obtained when 5-chloro-1-methyl-1H-imidazole was used.     

Cyclocondensation of 5-benzoyl-3-ethoxycarbonyl-6-methylthio-1-R-1,2-dihydropyrid-2-ones with heterocyclic N,N-and N,C-1,3-dinucleophiles

[3+3] Cyclocondensation of 5-benzoyl-3-ethoxycarbonyl-6-methylthio-1-R-1,2-dihydropyrid-2-ones with heterocyclic N,N-and N,C-1,3-dinucleophiles proceeds regioselectively to give a series of new tri-and tetracyclic heterosystems, viz. derivatives of 5,6-dihydropyrazolo[1,5-a]pyrido[2,3-d]pyrimidin-6-one, 1,2-dihydropyrido[2,3-d]pyrido[2′,3′: 3,4]pyrazolo[1,5-a]pyrimidin-2-one, 8,9-dihydro-5H-pyrido-[2,3-d]thiazolo[3,2-a]pyrimidin-8-one, 1,2-dihydrobenzo[4,5]imidazo[1,2-a]pyrido[2,3-d]pyrimidin-2-one, and 1,2-dihydrobenzo[4,5]imidazo[1,2-g][1,6]naphthyridin-2-one.     

Pyrimidinthiones (Part I): Utility of 2-Thioxopyrimidin-6-(1H)ones as Ring Transformer in the Synthesis of Fused Bi- and Tri-Cyclic Heterocyclic Compounds and Their Potential Biological Activities

The pyrimidinethiones have wide biological and pharmaceutical activities, that have attracted considerable interest in recent years especially as antiviral inhibiting production of hepatitis B virus (HBV), and in vitro insulin-mimetic. Activity of the complexes of pyrimidinone derivatives evaluated from 50% inhibitory concentration promoted us to study the transformation of the 2-thioxopyrimidin-6(1H) ones to fused bi- and tri-cyclic heterocyclic compounds having the pyrimidine moieties and screening their biological activity.

The reactivity of 2-mercapto-4-aryl-5-cyanopyrimidin-6(1H)ones (1) towards alkylation by different mono and bifunctional halo-organic compounds has been investigated to give S-monoalkylated products 2, 7 and 9; S- and N-dialkylated products 3, 13 and 14. Treatment of 1 and/or 2 with hydrazine hydrate as a nitrogen nucleophile have been investigated to give 4, treatment of 4 with CS₂ and sodium nitrite in the presence of acetic acid (0°C) produced 1,2,4-triazolopyrimidin-5(1H)one derivatives (5)and tetrazolo[1,5-a]pyrimidin-5(1H)ones (6), respectively. Also cyclization of 7 and 9 gave [1,3]thiazolo[3,2-a]pyrimidin-5(1H)one and [1,3]thiazolo[3,2-a]pyrimidin-3,5-dione derivatives 8 and 10 respectively, treatment of 10 with aromatic aldehyde produces 11 which reacted with guanidine HCl to give pyrimido[4,5-d]thiazolo[3,2-a]pyrimidin-6(1H)one derivative 12. Reaction of 14 with o-phenylenediamine was investigated and gave [1,4]quinoxalino[2,3-b][1,3]thiazolo[3,2-a]pyrimidin-9(1H)one derivative 15.     

Research in the field of unsaturated derivatives of azoles. 11. Reaction of benzimh)azole-2-thione with 1,2,3-tribromopropane

In the interaction of benzimidazole-2-thione with 1, 2, 3-tribromopropane under conditions of interfacial catalysis in an alkaline medium, 2-(2-bromo-2-propenylthio)benzimidazole is formed; debromination of this compound affords 3-methylthiazolo[3,2-a]benzimidazole, which is subsequently converted as a result of thermolysis to 2-propadienylthio)benzimidazole.For communication 10, see [1].Rostov State University, Rostov-on-Dan 344090. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 567–570, April, 1995. Original article submitted March 11, 1995.     

Metathetic sulfur transfer mediated by N-(2-aminophenyl)-4-methyl-thiazolin-2-thione derivatives: a route to diversely substituted S-alkylcarbamothioates

A new route to S-alkylcarbamothioates is disclosed. In a first step, N-(2-aminophenyl)-4-methyl-thiazolin-2-thione is transformed into a mono- or disubstituted urea at nitrogen, and then in a second step, alkylated at sulfur. The resulting salts, after treatment with a base, gave S-alkylcarbamothioates in high isolated yields together with 3-methyl[1,3]thiazolo[3,2-a]benzimidazole under very mild conditions.     

Condensation of 5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with haloacetic acids

Reactions of triazolethiones with haloacetic acids were studied with 5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione as an example. It was proved for the first time by X-ray diffraction that the cyclocondensation of these compounds proceeds regiospecifically to give 2-(4-methylphenyl)[1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)-one rather than its isomer 3-(4-methylphenyl)[1,3]thiazolo[2,3-c][1,2,4]triazol-5(6H)-one.