Reaction of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>][1,3]thiazin-7-ones with Aryl Bromomethyl Ketones and Benzyl Bromide

The products of the reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with aryl bromomethyl ketones are 2-aryl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones and aryl methyl ketones or 2,5-diaryl[1,3]thiazolo[3,2-b][1,2,4]triazoles and 3-phenyl-2-propenoic acid, depending on the structure of R. The reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with benzyl bromide yields 5-aryl-3-benzylthio-4H-1,2,4-triazoles and 3-aryl-2-propenoyl bromide. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 905–909, June, 2005.     

Heterophase N-aminomethylation of 5-arylidenepseudothiohydantoins by arylamines and aqueous formaldehyde in aromatic solvents: Effect of substituents in the heterocyclic substrate and the aryl amine on the efficiency of the process

We have obtained a series of 3-aryl-7-arylidene-3,4-dihydro-2H-[1,3]thiazolo[3,2-a][1,3,5]triazin-6(7H)-ones by means of heterophase aminomethylation of 2-amino-5-arylidene-1,3-thiazol-4(5H)-ones with aqueous formaldehyde and aromatic amines in benzene or toluene. We explain the effect of substituents in the heterocyclic substrate and the aryl amine on the efficiency of the process within a detailed scheme for one of the possible aminomethylation reaction routes. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1095–1104, July, 2006.     

Unexpected Direction of Iodocyclization of 3-Allylthio-5-phenyl-4H-1,2,4-triazole

The reaction of 3-allylthio-5-phenyl-4H-1,2,4-triazole with iodine to give a mixture of 5,6-dihydro-5-iodomethyl-3-phenyl[1,3]thiazolo[2,3-c][1,2,4]triazole, 6,7-dihydro-6-iodo-3-phenyl-5H-[1,2,4]triazolo[3,4-b][1,3]thiazine, 5,6-dihydro-6-iodomethyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole, and 6,7-dihydro-6-iodo-2-phenyl-5H-[1,2,4]triazolo[5,1-b][1,3]thiazine has been studied. The structure of the products obtained was established using ¹H NMR spectroscopy of their dehydriodination products.     

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.     

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.     

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.     

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.     

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.     

Pyridyl-substituted [1,3]Dithiolo-[4,5-<Emphasis Type="Italic">b</Emphasis>][1,4]dithiine-2-thiones

We have obtained 5-(2-pyridyl)[1,3]dithiolo[4,5-b][1,4]dithiine-2-thione for the first time by cycloaddition of 2-ethynylpyridine to 4,5-dihydro-1,3-dithioltrithione (isotrithionedithiol). We have studied this thione, 5-(2-pyridyl)- and 5-(4-pyridyl)-5,6-dihydro[1,3]dithiolo[4,5-b][1,4]dithiine-2-thiones by mass spectroscopy and also IR, UV, ¹H and ¹³C NMR spectra. We have determined the crystal and molecular structure of 5-(2-pyridyl)-5,6-dihydro[1,3]dithiolo[4,5-b][1,4]dithiine-2-thione.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 429–434, March, 2005.     

Condensed Imidazo-1,2,4-azines. 31. Synthesis and Chemical Transformations of Substituted 1,2,4-Triazepino[2,3-a]benzimidazoles

By reaction of 1,2-diaminobenzimidazole with 1,3-diketones, acetoacetic ester and its derivatives, we have synthesized substituted 1,2,4-triazepino[2,3-a]benzimidazole and 5H-1,2,4-triazepino[2,3-a]benzimidazol-4-one. By reaction of 5H-2-methyl-1,2,4-triazepino[2,3-a]benzimidazol-4-one with aromatic aldehydes or phenyldiazonium chloride, we have obtained 3-arylidene(phenylazo) derivatives of this compound, and by reaction with P₂S₅ we have obtained 5H-2-methyl-1,2,4-triazepino[2,3-a]benzimidazole-4-thione. We have shown that when reacted with ammonia, primary or secondary amines, the latter forms 4-amino-substituted 2-methyl-1,2,4-triazepino[2,3-a]benzimidazole.     

Aminolysis of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>]1,3]thiazin-7-ones

We have established that the products of aminolysis of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo-[5,1-b][1,3]thiazin-7-ones in boiling ethanol are 3-R-3-(5-aryl-4H-1,2,4-triazol-3-ylsulfanyl)-propanamides, and at 180°C–210°C (depending on the structure of the substituent R): 3-phenyl-4,5-dihydro-1H-1,2,4-triazoline-5-thione and 3-arylacrylamides or 3-(3-aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)propanamides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1587–1592, October, 2005.     

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.     

2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones

A novel method for synthesis of 2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of 3-R-4,5-dihydro-1H-1,2,4-triazole-5-thiones with 3-aryl(heteryl)-2-propenoyl chlorides is proposed.     

Synthesis of Novel Spiro Thiazolo[3,2-a][1,3,5]triazines via 1,3-Dipolar Cycloaddition of Azomethine Ylide

The 1,3‐dipolar cycloaddition of an azomethine ylide generated by a decarboxylative route from sarcosine and acenaphthenequinone to 7‐arylmethylidene‐3‐aryl‐3,4‐dihydro‐2H‐thiazolo[3,2‐a][1,3,5]triazin‐6(7H)‐ones afforded novel dispiro[acenaphthylene‐1,2′‐pyrrolidine]‐3′,7′ ′‐[1,3]thiazolo[3,2‐a][1,3,5]triazines in moderate yields. The structures of the products were determined and characterized thoroughly by NMR, MS, IR, elemental analysis and X‐ray crystallographic analysis. The results of experiment indicated that this 1,3‐dipolar cycloaddition proceeded with high stereoselectivity and regioselectivity.     

Synthesis and halocyclization of 2-alkenylthioquinolines

Bromination of 2-vinylthioquinoline and cis-2-styrylthioquinoline with molecular bromine leads to the formation of 2-bromo(3-phenyl)-2,3-dihydrothiazolo[3,2-a]quinolinium bromides, and of 2-allyl-thioquinoline to a mixture of 2-and 3-bromomethyl-2,3-dihydrothiazolo[3,2-a]quinolinium bromides. Iodine reacts with allylthioquinoline with the formation of 3-iodomethyl-2,3-dihydrothiazolo-[3,2-a]quinolinium triiodide. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1664–1668, November, 2008.     

Condensed isoquinolines 28*. Synthesis and properties of 10a,15b-diazadibenzo[a,e]-pleiaden-11-ones

The reaction of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones with o-xylidene dibromide leads to 11-oxo-4bH,5H,10H,11H,16H-10a-aza-15b-azoniadibenzo[a,e]pleiadene bromides, which are converted to 11-oxo-10H,11H,16H-10a-aza-15b-azoniadibenzo[a,e]pleiadene salts upon oxidation using nitrobenzene. The reaction of these salts with benzylamine leads to 6-{2-[(benzylimino)methyl]phenyl}-7,12-dihydroisoquino[3,2-b][2]benzazepin-14(6H)-ones, which recyclize to 11-oxo-5H,10H,11H-10a-aza-15b-azoniadibenzo[a,e]pleiadene perchlorates upon the action of perchloric acid. The reactions of the 10a,15b-diazadibenzo[a,e]pleiadene salts obtained with NaBH₄ were studied and the structures of the reduction products were determined by spectral methods. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 280–292, February, 2008.     

Synthesis and halogenation of propargyl pyrazolo-[3,4-d]pyrimidine thioether

The reaction of 4-imino-1-methyl-5-phenyl-6-propargylthio-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine with halogens leads to the formation of (Z)-8-halomethylene-4-imino-1-methyl-5-phenyl-4,5,7,8-tetrahydro-1H-pyrazolo[4,3-e][1,3]thiazolo[3,2-a]pyrimidinium trihalide. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1085–1088, July, 2008.     

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.     

Synthesis of 2-Aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-Aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones

The reaction of 2-mercaptobenzimidazole, 5-ethoxy-2-mercaptobenzimidazole, and 2-mercaptoimidazoline with cinnamoyl chloride, its derivatives, and heteroanalogs was studied. Convenient methods were found for the synthesis of 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones.     

Synthesis of substituted [1,3]thiazolo[4,5-b]pyridines and [1,3]thiazolo[4,5-d][1,2,3]triazines

In this work, we described an easy preparation of substituted 4-amino-5-cyano-1,3-thiazoles. These compounds have been used as starting materials to obtain two classes of compounds. New substituted [1,3]thiazolo[4,5-e]pyridines were synthesized in one step via Friedländer reaction. Diazotation of 4-amino-5-cyano-1,3-thiazoles afforded 4-chloro[1,3]thiazolo[4,5-d][1,2,3]triazines in one step. The later was substituted by a secondary amine to obtain substituted 4-amino[1,3]thiazolo[4,5-d][1,2,3]triazines.