Synthesis of 6-hydroxytetrahydro-1,3-thiazine-2-thiones and methyl esters of 3-oxoalkyldithiocarbamic acids from 1,3-isothiocyanato ketones

Sodium salts of 3-oxoalkyldithiocarbamic acids were obtained by the reaction of 1,3-isothiocyanato ketones with sodum hydrosulfide. These salts were converted by reaction with methyl iodide into the corresponding dithiocarbamates, and with a mineral acid into the 6-hydroxytetrahydro-1,3-thiazine-2-thiones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 416–419, March, 1991.     

Synthesis of 2-aryl-2-trifluoromethyl-1,3-thiazolidin-4-ones and 2-aryl-2-trifluoromethyltetrahydro-4<Emphasis Type="Italic">H</Emphasis>-1,3-thiazin-4-ones and their oxidation with hydrogen peroxide

Reactions of aryl trifluoromethyl ketone imines with 2-sulfanylacetic and 3-sulfanylpropanoic acids afforded 2-aryl-2-trifluoromethyl-1,3-thiazolidin-4-ones and 2-aryl-2-trifluoromethyltetrahydro-4H-1,3-thiazin-4-ones, respectively. Their subsequent oxidation with hydrogen peroxide gave the corresponding 2-aryl-2-trifluoromethyl-1,3-thiazolidin-4-one 1-oxides and 2-aryl-2-trifluoromethyltetrahydro-4H-1,3-thiazin-4-one 1-oxides and 1,1-dioxides.     

Synthesis of 2-aryl-4-hydroxy-5-thio substituted 1,3-thiazin-6-ones via sulfenylation of 2-aryl-4-hydroxy-[1,3]thiazin-6-ones with sulfenyl chlorides

A series of 2-aryl-4-hydroxy-5-thio substituted 1,3-thiazin-6-ones were synthesized for human immunodeficiency virus-1 protease inhibition. These compounds were synthesized by the treatment of 4-hydroxy-5-thio substituted-1,3-thiazin-6-ones with the corresponding sulfenyl chlorides. The products were obtained in good isolated yields, inspite of the presence of bulkyl substitutents at the ortho position of phenyl sulfenyl chloride portion.     

New method for the synthesis of the 1,3-thiazine system. 2-phenylamino-5,6-dihydro-4H-1,3-thiazin-5-ones

Treatment of N-phenylthioureidoalkyl--diazo ketones with acids leads to 2-phenyl-amino-5,6-dihydro-4H-1,3-thiazin-5-ones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1327–1330, October, 1980.     

Azines and azoles: CXXIX. Synthesis,structure, and some reactions of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-ones

Reactions of 2-aryl-4-chloro-6H-1,3-thiazin-6-ones with sodium sulfide in aqueous alcohol at 18–20°C led to the formation of a readily separable mixture of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-one sodium salts (yield >70%) and bis(2-aryl-6-oxo-6H-1,3-thiazin-4-yl) sulfides (<10%). The latter can also be obtained in more than 50% yield by treatment of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-one sodium salts with 2-aryl-4-chloro-6H-1,3-thiazin-6-ones. Methylation of 2-aryl-4-sulfanyl-6H-1,3-thiazin-6-ones afforded the corresponding methylsulfanyl derivatives (yield >90%) regardless of the alkylating agent, solvent, temperature, reactant concentration, and their ratio. 2-Aryl-4-sulfanyl-6H-1,3-thiazin-6-ones in the crystalline state and in solutions in polar and nonpolar protic and aprotic solvents exist preferentially as 4-sulfanyl-6-oxo tautomers, and they undergo almost complete ionization in neutral aqueous, alcoholic, and aqueous-alcoholic media (pK _a = 4.3). Reactions of 4-sulfanyl-2-phenyl-6H-1,3-thiazin-6-one with ammonia, amines, and difunctional N-centered nucleophiles involve cleavage of the C⁶-S bond in the thiazine ring and subsequent recyclization of linear intermediates to pyrimidines and diazole derivatives. The structure of the isolated compounds was confiirmed by ¹H and ¹³C NMR, IR, and UV spectra.     

New Approach to the Synthesis of 1,3-Chloroisothiocyanatoalkanes. Synthesis of Tetrahydro-1,3-thiazine-2-thiones and 2-Alkylamino-5,6-dihydro-1,3-thiazines

A method was developed to prepare 1,3-chloroisothiocyanatoalkanes by reducing 1,3-isothiocyanato ketones using sodium borohydride at pH ~7 and subsequent treatment of the resultant 1,3-isothiocyanato alcohols with thionyl chloride. The reaction of 1,3-chloroisothiocyanatoalkanes with sodium hydrosulfide or amines gives substituted tetrahydro-1,3-thiazine-2-thiones or 2-amino-5,6-dihydro-1,3-thiazines.     

Chemistry of oxalyl derivatives of methyl ketones

It was established by IR, UV, and PMR spectroscopy that 2-phenacylidenebenzo-1,4-thiazin-3-ones are formed in the reaction of o-aminothiophenol with aroylpyruvic acids or 5-arylfuran-2,3-diones. 2-Carbomethoxy-2-phenacyl-1,3-benzothiazolines were isolated in the reaction of o-aminothiophenol with aroylpyruvic acid esters.See [1] for communication IV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 755–757, June, 1977.     

Mass-spectrometric study of the cyclization of diazo ketones. 4. Cyclization of N'-phenyl-3-ureido- and N'-phenyl-3-thioureido-1-diazoalkan-2-ones. 2-Anilino-5,6-dihydro-4H-1,3-thiazin-5-ones

A comparison of the mass spectra of N'-phenyl-3-thioureido-1-diazo-alkan-2-ones (I) with the mass spectra of 2-anilino-5,6-dihydro-4H-1,3-thiazin-5-ones (II) and N'-phenyl-3-ureido-1-diazoalkan-2-ones (III) makes it possible to conclude that under the influence of electron impact the molecular ions of the diazo ketones, through the loss of a molecule of nitrogen, undergo only partial cyclization to the corresponding thiazinones (oxazinones in the case of III). In the case of diazo ketones III virtually all of the [M-N₂]⁺ ions undergo fragmentation without cyclization. Under chemical-ionization conditions (with isobutane as the gas-reactant) the principal fragmentation of the protonated ions of I and III entails cleavage of the C-N bonds. Only a small part of these ions lose a molecule of nitrogen, but it is impossible to establish the structures of the resulting [MH-N₂]⁺ ions from the mass-spectrometric data.See [1], for communication 3.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 473–480, April, 1983.     

Mercaptoacetic acid based expeditious synthesis of polyfunctionalised 1,3-thiazines

A novel three-component expeditious synthesis of 3,6-diaryl-5-mercaptoperhydro-2-thioxo-1,3-thiazin-5-ones from 2-methyl-2-phenyl-1,3-oxathiolan-5-one, an aromatic aldehyde and an N-aryldithiocarbamic acid is reported. The synthesis is diastereoselective and involves tandem Knoevenagel, Michael and ring transformation reactions under solvent-free microwave irradiation in a one-pot procedure.     

Highly regioselective synthesis of tetrahydro-2H-1,3-thiazin-2-ones via rhodium-catalyzed carbonylation of N-alkylisothiazolidines

[reaction: see text] The [Rh(COD)Cl]2- and KI-catalyzed carbonylation of functionalized N-alkylisothiazolidines in toluene gives the corresponding tetrahydro-2H-1,3-thiazin-2-ones in good yield. The carbonylation reaction occurred site-selectively at the S-N bond of the isothiazolidine ring. The reaction is believed to proceed via oxidative addition, followed by CO insertion and reductive elimination to form the tetrahydro-2H-1,3-thiazin-2-one derivatives.     

Cycloacylation of 3-oxo-3-R1-N-R2-propanethioamides by 3-aryl-2-propenoyl chlorides

The products of cyclocondensation of 3-oxo-3-R¹-N-R²-propanethioamides with 3-aryl-2-propenoyl chlorides in acetone in the presence of potassium carbonate are 5-acyl-1-aryl(alkyl)-4-aryl-6-thioxopiperidin-2-ones, 5-acyl-2-aryl-6-aryl(alkyl)amino-2,3-dihydro-4H-thiopyran-4-ones, and 2-acetonylidene-3,6-diaryl-5,6-dihydro-4H-1,3-thiazin-4-ones, the structure of which is proven by both spectral methods and chemical conversions. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 623–628, April, 2006     

Synthesis and properties of z-1,3-bis-(aryl)-4-bromo-2-buten-1-ones

Bromination of 1,3-bis(aryl)-2-buten-1-ones by N-bromosuccinimide in anhydrous carbon tetrachloride gives Z-1,3-bis(aryl)-4-bromo-2-buten-1-ones. The effect of the nature of substituent in the benzene ring on the course of a reaction with nucleophiles has been studied. Heating an alcohol solution of these ketones (Ar = 4-MeOC₆H₄, 4-ClC₆H₄) in the presence of acid or in the presence of base (Ar = Ph) gave 2,4-bis(aryl)furans. Treatment of 1,3-bis(aryl)-4-bromo-2-buten-1-ones with thioacetamide gave 2,4-bis(aryl)thiophenes. The oxidation of the halo-substituted dypnones with H₂O₂/NaOH gave (3-bromomethyl-3-aryl-2-oxiranyl)(aryl)methanones. The reaction of halo-substituted dypnones with aryl hydrazines gave 1,3,5-triaryl-1,6-dihydropyridazines or 1,3,5-triarylpyridazinium bromides depending on the structure of the reagents.     

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.     

Azines and azoles: CXXIV. New synthesis of 2-oxochromene-3-carboxamides

2-Aryl-4-hydroxy-6H-1,3-thiazin-6-ones react with substituted 2-hydroxybenzaldehydes in polar solvents to give N-arylcarbothioyl-2-oxochromene-3-carboxamides in 60–70% yield.     

Cycloacylation of N-phenyl-N′-R-thioureas with 3-aryl-2-propenoyl chlorides

Cycloalkylation of N-phenyl-N′-R-thiourea with 3-aryl-2-propenoyl chlorides in acetone gives as products 6-aryl-3-phenyl-2-(R-imino)-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one and their hydrochlorides. The same reaction carried out in acetone in the presence of K₂CO₃ leads to the formation of 6-aryl-3-phenyl-2-(R-imino)-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-ones, N-(3-aryl-2-propenoyl)-N-phenylthioureas, 3-aryl-2-propenoylanilides, and phenyl isothiocyanate.     

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.     

A study of the reactions of 2-aryl-4-hydroxy-6H-1,3-thiazin-6-ones with chromone-3-carboxaldehydes

Reaction of 3-formylchromones with 2-aryl-4-hydroxy-6H-1,3-thiazin-6-ones in the presence of pyridine leads to formation of a mixture of novel N-thioaroyl-5-hydroxy-2H,5H-pyrano[3,2-с]chromen-2-one-3-carboxamides and 2-aryl-5-(4′-oxochromen-3′-yl)-6,7-dihydro-4H,5H-pyrano[2,3-d][1,3]thiazine-4,7-diones. The yields of these compounds clearly depend on the nature of the substituent on the 3-formylchromone and on the reaction conditions.     

Synthesis of allylic thiocyanates and novel 1,3-thiazin-4-ones from 2-(bromomethyl)alkenoates and S-nucleophiles in aqueous medium

Allylic thiocyanates and novel heterocycles containing the 1,3-thiazin-4-one core are easily obtained in high yields and mild conditions by nucleophilic displacement of 2-(bromomethyl)alkenoates (derived from Morita-Baylis-Hillman adducts) with sulphur-centred nucleophiles in aqueous acetone at 25 °C. Treatment of allylic bromides with NaSCN gave the corresponding (Z)-2-(thiocyanomethyl)alkenoates, while the reaction with thiourea followed by a basic work-up selectively produced (5Z)-2-amino-5-arylidene-1,3-thiazin-4-ones. The structural assignments were confirmed by X-ray diffraction analysis.     

Cycloacylation of <Emphasis Type="Italic">N</Emphasis>-Phenyl-3-oxobutanethioamide with 3-Aryl-2-propenoyl Chlorides

Reactions of N-phenyl-3-oxobutanethioamide with 3-aryl-2-propenoyl chlorides in acetone in the presence of potassium carbonate give rise to 4-aryl-5-acetyl-1-phenyl-6-thioxopiperidin-2-ones, 2-aryl-5-acetyl-6-phenylamino-2,3-dihydro-4H-thiopyran-4-ones, and 6-aryl-2-acetonylidene-3-phenyl-5,6-dihydro-4H-1,3-thiazin-4-ones whose structure was proved both by spectral methods and chemical transformations.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 2, 2005, pp. 292–296.Original Russian Text Copyright © 2005 by Britsun, Borisevich, Samoilenko, Lozinskii.     

Reaction of polychloroacetaldehyde arylsulfonylimines with 2-amino-6<Emphasis Type="Italic">H</Emphasis>-1,3-thiazine-6-thiones and 2-amino-4-phenyl-6<Emphasis Type="Italic">H</Emphasis>-1,3-thiazin-6-one

2-Amino-4-R-6H-1,3-thiazine-6-thiones and 2-amino-4-phenyl-6H-1,3-thiazin-6-one react with highly electrophilic N-arylsulfonylimines of chloral and phenyldichloroacetic aldehyde at the exocyclic amino group affording in good yields products of nucleophilic addition to the azomethine group of imines: N-[2-polychloro-1-(6-thioxo-4-R-6H-1,3-thiazin-2-ylamino)ethyl]- or -[2-polychloro-1-(6-oxo-4-phenyl-6H-1,3-thiazin-2-ylamino)ethyl]arenesulfonamides.