Reactions of 1,3-thiazine-2,6-dithiones. Part 6 [1]. Synthesis of 2-alkylthio-2,3-dihydro-1,3-thiazine-6-thiones by reductive alkylation of 1,3-thiazine-2,6-dithiones

2-Alkylthio-2,3-dihydro-1,3-thiazine-6-thiones 4 are synthesized by the reductive alkylation of 1,3-thiazine-2,6-dithiones with thiolate anions.     

Synthesis of New Derivatives of 5-Acetyl-4-hydroxy-2H-1,3-thiazine-2,6(3H)-dione

Russian Journal of Organic Chemistry - 5-Acetyl-4-hydroxy-2H-1,3-thiazine-2,6(3H)-dione reacted with cyclohexyl and benzyl (4-aminophenyl)carbamates in boiling ethanol in the presence of a...     

Azines and azoles: CXXIII. Three-component condensation of 5-acetyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-dione with o-phenylenediamine and carbonyl compounds as a convenient synthesis of substituted 1,5-benzodiazepines

Readily accessible 5-acetyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-dione reacted with an equimolar amount of o-phenylenediamine under mild conditions (propan-2-ol, 5 min, reflux) to give the corresponding Schiff base. Reactions of the latter with aldehydes and ketones in propan-1-ol in the presence of a catalytic amount of trifluoroacetic acid or in acetic acid led to the formation of 4-hydroxy-5-(2-R-2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-2H-1,3-thiazine-2,6-diones.     

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.     

Multicomponent synthesis of 3,6-dihydro-2H-1,3-thiazine-2-thiones

Non-fused 3,6-dihydro-2H-1,3-thiazine-2-thiones constitute a so far rather unexplored class of compounds, with the latest report dating back more than two decades. Thiazine-2-thiones contain an endocyclic dithiocarbamate group, which is often found in pesticides, in substrates for radical chemistry and in synthetic intermediates towards thioureas and amidines. We now report the multicomponent reaction (MCR) of in situ-generated 1-azadienes with carbon disulfide. With this reaction, a one-step protocol towards the potentially interesting 3,6-dihydro-2H-1,3-thiazine-2-thiones was established and a small library was synthesized.     

Synthesis of substituted 2-amino-1,3-thiazine-6-thiones

The reaction of thiourea with l-acyl-2-bromoacetylenes in AcOH in the presence of BF₃·Et₂O affords 2-amino-4-phenyl(2-thienyl)-1,3-thiazine-6-thiones in high yields. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya. No. 11, pp. 1947–1949, November, 2000.     

Investigation of the ring-chain tautomerism of alkyl-substituted 6-hydroxytetrahydro-1,3-thiazine-2-thiones by IR spectroscopy and mass spectrometry

The ring-chain tautomerism of alkyl-substituted 6-hydroxytetrahydro-1,3-thiazine-2-thiones was studied by IR spectroscopy and mass spectrometry. The dependence of the tautomeric equilibrium on the number and location of the methyl groups in the molecule and the aggregate state of the substance was ascertained. Substituted 3,4-dihydro-2H-1,3-thiazine-2-thiones were obtained by the dehydration of the 6-hydroxytetrahydro-1,3-thiazine-2-thionesTranslated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 985–990, July, 1992.     

Facile and convenient synthesis of 2,6-disubstituted 4H-1,3-oxazin-4-one derivatives

Facile and convenient methods for the preparation of a variety of 2,6-disubstituted 4H-1,3-oxazin-4-ones 3 by three complementary methods are described. Treatment of the branched aliphatic imidate 2c,d with diketene 1 in the presence of a catalytic amount of acetic acid affords 2-substituted 6-methyl-1,3-oxazin-4-ones 3c,d , whereas the unbranched imidate 2b,e gave oxazines 3b,e and pyrimidines 4b,e (Method A). The reaction of acyl Meldrum's acid 5 with imidate 2 afford 2,6-disubstituted oxazine 3, though the alkylimidate with acetyl Meldrum's acid yielded 3 and 5-acetyl-1,3-oxazine-4,6-dione 8 (Method B). The cylodehydration of acylacetylcarboxamide 13 with acid, such as 70% perchloric acid or fluorosulfonic acid, afforded 1,3-oxazines 3 (Method C).     

A new synthesis of 1,3-thiazines and their transformation into 1-substituted-6-alkyluracils by extrusion of carbonyl sulfide

A simple synthesis of 5-acyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-diones from malonic acid, potassium thiocyanate and acid anhydrides is described. A new, general, regioselective method for the synthesis of 1-substituted-6-alkyluracils by the reaction of these thiazines with primary alkyl and arylamines is reported.     

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.     

Azines and azoles: CXXV. New regioselective synthesis of 1-amino-6-methyluracils

Readily accessible 5-acetyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-dione reacts with substituted hydrazines and carboxylic acid hydrazides under mild conditions to give the corresponding hydrazones. Under severe conditions (heating in boiling dimethylformamide) the reaction is accompanied by extrusion of COS with formation of substituted 1-amino-6-methyluracils. Reactions of 5-acetyl-4-hydroxy-3,6-dihydro-2H-1,3-thiazine-2,6-dione with monosubstituted alkyl-and arylhydrazines take different pathways, depending on the conditions. Heating of equimolar mixtures of the reactants in ethanol or propan-1-ol leads to the formation of 2-substituted 5-methyl-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxamides rather than 1-amino-6-methyluracil derivatives.     

Azines and azoles: CXXVI. First example of a novel heterocyclic system: Pyrimido[1,6-<Emphasis Type="Italic">a</Emphasis>][1,5]benzodiazepines

4-Hydroxy-5-(2-R-2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-2H-1,3-thiazine-2,6-diones readily undergo acylation at the N¹ atom of the benzodiazepine system by the action of acetic anhydride. Heating of the acetylated products in boiling dimethylformamide leads to the formation of 75–93% of the corresponding 7-acetyl-6-R-6,7-dihydropyrimido[1,6-a][1,5]benzodiazepine-1,3-diones that are derivatives of hitherto unknown fused heterocyclic system, pyrimido[1,6-a][1,5]benzodiazepine. 4-Hydroxy-5-(2-R-2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-2H-1,3-thiazine-2,6-diones are converted into 1-(2-aminophenyl)-6-(2-R-vinyl)uracils on heating in boiling DMF.     

Bildung von 5,6-Dihydro-1,3(4H)-thiazin-4-carbonsäure-estern aus 4-Allyl-1,3-thiazol-5(4H)-onen

Formation of Methyl 5,6-Dihydro-l, 3(4H)-thiazine-4-carboxyiates from 4-Allyl-l, 3-thiazol-5(4H)-ones . The reaction of N-[1-(N, N-dimethylthiocarbamoyl)-1-methyl-3-butenyl]benzamid ( 1 ) with HCl or TsOH in MeCN or toluene yields a mixture of 4-allyl-4-methyl-2-phenyl-1,3-thiazol-5(4H)-one ( 5a ) and allyl 4-methyl-2-phenyl-1,3-thiazol-2-yl sulfide ( 11 ; Scheme 3). Most probably, the corresponding 1,3-oxazol-5(4H)-thiones B are intermediates in this reaction. With HCl in MeOH, 1 is transformed into methyl 5,6-dihydro-4,6-dimethyl-2-phenyl-1,3(4H)-thiazine-4-carboxylate ( 12a ). The same product 12a is formed on treatment of the 1,3-thiazol-5(4H)-one 5a with HCl in MeOH (Scheme 4). It is shown that the latter reaction type is common for 4-allyl-substituted 1,3-thiazol-5(4H)-ones.     

Novel rearrangement of N-enoyl oxazolidinethiones to N-substituted 1,3-thiazine-2,4-diones promoted by NbCl5

NbCl₅ has been employed as promoter of a novel rearrangement to afford chiral N-substituted 1,3-thiazine-2,4-diones with one or two new stereogenic centers from di- and trisubstituted N-enoyl oxazolidinethiones. The trisubstituted E-isomers provide the anti-diastereomers mainly.     

Zur Umsetzung des 3,4,5,6-Tetrahydro-6-hydroxy-4,4,6-trimethyl-1,3-thiazin-2-thions mit sekundären Aminen

Tetrahydro-6-hydroxy-trimethyl-1,3-thiazine-2-thione (1) reacts with secondary amines via the dialkylammonium-3-oxoalkyldithiocarbamate3, either via isothiocyanates6 to 4-dialkylaminodihydro-2(1H)-pyridinethiones7 or to dialkylammonium dithiocarbamates (13), depending on the amine used and the reaction conditions. Subsequently, 6-dialkylaminotetrahydro-1,3-thiazine-2-thiones11 or tetrahydro-6-mercapto-1,3-thiazine-2-thione10 are formed. On being heated to reflux,11 reacts to pyridinethione7 and 4-dialkylaminodihydrothiopyranthione19. With secondary amines only13 is formed from tetrahydro-6-hydroxytetramethyl-1,3-thiazine-2-thione20. The reaction of dihydrotrimethyl-1,3-thiazine-2-thione21 with secondary amines leads to N,N-dialkylthioureas16 or dialkylammonium thiocyanates17 and with dialkylformamides 4-dialkylaminodihydropyridinethiones7 are formed. Dihydrotetramethyl-1,3-thiazine-2-thione24 reacts neither with secondary amines nor with dialkylformamides.     

Novel oxidations of 1,3-disubstituted indoles

A study of oxidation versus nitration of 1,3-disubstituted indole derivatives with nitric acid in acetic acid was carried out. Oxidation of methyl and ethyl 2-cyano-2-(1-alkoxycarbonyl-1H-indol-3-yl)acetates 1 and 2 under the above conditions gave rise to novel functionalized 2-hydroxyindolenines as single products possessing the Z-configuration, 8 and 10 , respectively. The structure of 10 was determined by an X-ray analysis. In contrast, 1-methoxycarbonyl-1H-indol-3-acetonitrile ( 3 ) was nitrated to the corresponding 6-nitroindole derivative 11 , whereas the reaction of ethyl 2-cyano-2-(1-methyl-1H-indol-3-yl)acetate ( 4 ) with nitric acid effected an oxidative nitration to provide the corresponding ethyl Z-5-nitroisatyliene cyanoacetate ( 12 ), which in solution isomerized to the E isomer.     

Synthesis of 1,3-dialkyl-5-(hetaryl-1-yl)-1,3-dihydrobenzimidazol-2-ones

Reactions of 5-amino-1,3-dialkyl-1,3-dihydrobenzimidazol-2-ones with 2,5-dimethoxytetrahydrofuran and 2,6-dimethyl-γ-pyranone led to the formation of 1,3-dialkyl-1,3-dihydro-5-(pyrrol-1-andл)benzimidazol-2-ones and 1-(1,3-dialkyl-2-oxo-1,3-dihydrobenzimidazol-5-yl)-2,6-dimethylpyridin-4-ones.     

Recyclization of 1-amino-3.5-diaryl-2.6,6-tricyanocyclohexa-1,3,-dienes to pyridine derivatives

The base-catalyzed recyclization of 1-amino-3,5-diaryl-2,6, 6-tricyanocyclohexa-1,3-dienes to 2,4-diaryl-5-cyano-6-dicyanomethylene-1,2,3,6-tetrahydropyridines, 4,6-diaryl-3-cyano-2-dicyanomethylene-1,2-dihydropyridines, and 4,6-diaryl-3-cyano-2-dicyanomethylpyridines has been investigated. The intermediate products of this reaction — cis, trans-2-amino,4,6-diaryl-1,1,3-tricyanohexa-1,3,5-trienes —have been isolated; on heating these are transformed reversibly into the initial cyclohexadienes or they isomerize irreversibly into trans, trans-hexatrienes, while in the presence of a base (piperidine, diethylamine, triethylamine, KOH), they cyclize to form the above-mentioned' pyridine derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, PP. 621–625, May, 1986.     

Synthesis of substituted 2-arylimino-2,3-dihydro-4H-1,3-thiazines

The synthesis of 3,4,4,6-tetramethyl-2-arylimino-2,3-dihydro-4H-1,3-thiazines, which have a fixed imino structure, was accomplished by two methods: by intramolecular rearrangement of 1,4,6,6-tetramethyl-3-aryl-1,2,3,6-tetrahydropyrimidine-2-thiones and by amination of 3,4,4,6-tetramethyl-2,3-dihydro-4H-1,3-thiazine-2-thione methiodide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 941–943, July, 1972.     

Azaindole derivatives. 66. 1,6-disubstituted 4-methyl-5-cyano-7-azaindolines

A general method was developed for the synthesis of 1,6-disubstituted 4-methyl-5-cyano-7-azalndolines from the readily available ammonium salt of 2,6-dihydroxy-3-(-hydroxyethyl)-4-methyl-5-cyanopyridine through the corresponding N-substituted ammonium salts and N-substituted 2-amino-3-(-hydroxyethyl)-4-methyl-5-cyano-6-hydroxypyridines with treatment of the latter by POCl₃. This method gives a 40% yield of 4-methyl-5-cyano-7-azaindoline compounds containing various aralkyl or alkyl substituents at N-1 and a hydroxy group or halogen atom at C-6 in three steps.For Communication 65, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 84–88, January, 1985.