Untersuchungen an 1,3-Thiazinen, 25. Mitt. Transacylierende N-Acyl-tetrahydro- und N-Acyl-dihydro-1,3-thiazin-derivate

1,3-Thiazines, XXV: Transacylating Derivatives of N-Acyltetrahydro- and N-Acyldihydro-1,3-thiazine Novel N-acyl-2-thioxo-3,4-dihydro-1,3-thiazine-4-ones 4 and N-acyl-tetrahydro-1,3-thiazine-2,4-diones 7 were preparee by acylation of the N-unsubstituted 1,3-thiazine derivatives 3 and 6 with acid chlorides. Their characteristics are compared with those of known N-acylthiazine derivatives.     

Untersuchungen an 1,3-Thiazinen, 42. Mitt.: Carbazoylierungen und Thiocarbazoylierungen von 2-Thioxo-tetrahydro-1,3-thiazin-Derivaten

Investigations on 1,3-Thlazines, XLII¹⁾: Carbazoylations and Thiocarbazoylations of 2-Thioxo-tetrahydro-1,3-thiazine Derivatives⁺⁾ Carbazic acid chlorides react with 2-thioxo-tetrahydro-1,3-thiazines 6 and 7 yielding N-Carbazoyl-thiazine derivatives 9 and 11 . Thiocarbazic acid chlorides attack under kinetic control at the 2-thioxo sulfur yielding S-substitution products 10 and 12 , which can thermally be rearranged intramolecularly to the more stable N-substituted products 9 and 11 .     

Untersuchungen an 1,3-Thiazinen, 37. Mitt. Umsetzungen NH-acider Tetrahydro-1,3-thiazinderivate mit Sulfensäure- und Sulfonsäurechloriden

Investigations on 1.3-Thiazines, XXXVII; Reactions of NH-acidic Tetrahydro-1.3-thiazine Derivatives with Sulfenic and Sulfonic Acid Chlorides N-sulfenyl derivatives were obtained from 5,6-dihydro-2H-1,3-thiazine-2.4(3H)-diones 1 and sulfenic acid chlorides in the presence of triethylamine or from the sodium salts of 1, 3. 2-Thioxo-tetrahydro-4H-1,3-thiazine-4-ones 4 were on the other hand sulfenylated at sulfur to 5 which was easily cleaved hydrolytically to 1 . N-Sulfonylation was only achieved with methane sulfonyl chloride to yield 13.     

Untersuchungen an 1,3-Thiazinen, 36. Mitt. Aminierung von Salzen NH-acider Tetrahydro-1,3-thiazinderivate mit O-Diphenylphosphoryl-hydroxylamin

Investigations on 1.3-Thiazines, XXXVI; Amination of Salts from NH-acidic Tetrahydro- 1.3-thiazinederivatives with O-Diphenylphosphoryl-hydroxylamine NH-acidic 2-thioxo-4-oxo- or 2,4-dioxo-1,3-thiazine derivatives 3 or 5 were converted into their sodium-or thallium(I)-salts 4 and 6 , which were reacted with O-diphenylphosphoryl-hydroxylamine to yield the S-amination product 9 or the N-amination product 10. The N-amino-2-thioxo-thiazine 2, which could not be obtained in this way, resulted from cyclization of 1.     

Untersuchungen an 1,3-Thiazinen, 11. Mitt. 3-Acyl-4-oxo-2-thioxo-tetrahydro-1,3-thiazine,neuartige cyclische N,N-Bis-acyl-dithiourethane

1,3-Thiazines, XI: 3-Acyl-4-oxo-2-thioxotetrahydro-1,3-thiazines, a new Type of Cyclic N,N-Bisacyldithiourethanes The 4-oxo-2-thioxotetrahydro-1,3-thiazines 1 and 2 were reacted with acid chlorides in the presence of triethylamine yielding the 3-acyl derivatives 3 and 4 . These compounds were shown by hydrolysis, alcoholysis and aminolysis to be acylating agents.     

Untersuchungen an 1,3-Thiazinen, 38. Mitt.: Iminiumkohlensäurederivat-Salze, 2. Mitt.: Synthese N-substituierter 2-Chlor-5,6-dihydro-4H-1,3-thiazinium-salze und deren Reaktionen mit primären Aminoverbindungen

Synthesis of N-Substituted 2-Chloro-5,6-dihydro-4H-1,3-thiazinium Salts and Their Reactions with Primary Amino Compounds After a short review of synthesis and reactions of halogeno(organothio)methaniminiumsalts, the reactions of tetrahydro-1,3-thiazine-2-thiones 9 with thionyl chloride or phosgene to yield 2-chloro-5,6-dihydro-4H-1,3-thiazinium chlorides 10 are described. Compounds 10 can be converted to the more stable tetrafluoroborates 13 and hexafluorophosphates 12 , which can be conveniently characterized. Chloroiminium chlorides 10 generated in situ, react with primary amino compounds such as aliphatic or aromatic amines, carboxamides, sulfonamides, diphenylphosphinamide, cyanamide or N-substituted ureas to yield the N,N′-disubstituted 2-iminotetrahydro-1,3-thiazines 17 – 24 .     

Über 3H-1,4-Benzodiazepine mit semicyclischer Hydroxyamidin-Struktur und deren oxidoreduktive 1,3-Umlagerung zu 2-Alkylamino-3-acyloxy-3H-1,4-benzodiazepinen

The Oxidoreductive 1,3-Rearrangement of 3H-1,4-Benzodiazepines with Semicyclic Hydroxyamidine Structure to 2-Alkylamino-3-acyloxy-3H-1,4-benzodiazepines On treatment of N-alkyl-N-(3H-1,4-benzodiazepin-2-yl)-hydroxylamines with carboxylic anhydrides or chlorides an oxidoreductive rearrangement is observed in the presence of protons that leads to 1,4-benzodiazepines bearing the acylated hydroxylaminic oxygen at position 3. When the acylation is carried out with derivatives of carbonic acid decarboxylation takes place in the course of the rearrangement in some cases.     

Untersuchungen an 1,3-Thiazinen,VI. Ringschlußreaktionen N-monosubstituierter Thioharnstoffe mit 1,3-reaktiven Propionylderivaten

Cyclization Reactions of N-Monosubstituted Thioureas with 1,3-Reactive Derivatives of Propionic Acid N-Monosubstituted thioureas were reacted under various conditions with β-propiolacton or acrylic chloride. The cyclization products were identified as 1,3-thiazine- and 1,3-diazine derivatives by independent syntheses.     

Untersuchungen an 1,3-Thiazinen, 41. Mitt.: Iminiumkohlensäurederivat-Salze, 5. Mitt.1): Vilsmeier-artige Reaktionen mit N-substituierten 2-Chlor-5,6-dihydro-4H-1,3-thiaziniumsalzen

Investigations on 1,3-Thiazines, XLI¹); Iminium Carbonic Acid Derivative Salts, V¹): Vilsmeier-Type Reactions with N-Substituted 2-Chloro-5,6-dihydro-4H-1,3-thiazinium Salts The strongly electrophilic N-substituted 2-chloro-5,6-dihydro-4H-1,3-thiazinium salts 1 react in a Vilsmeier-type reaction with pyrrol derivatives and indol to yield the surprisingly stable salts 2–4 .     

Untersuchungen an 1,3-Thiazinen, 20. Mitt. Transacylierende N-Acyltetrahydro-1,3-thiazin-2-thione

On 1,3-Thiazines, XX: Transacylating N-Acyltetrahydro-1,3-thiazine-2-thiones The synthesis of novel N-acyltetrahydro-1,3-thiazine-2-thiones 3 with transacylating activity towards nucleophilic compounds is described.     

Synthesis of 1,3-thiazine derivatives and their evaluation as potential antimycobacterial agents.

A series of eight 5,6-dihydro-4H-1,3-thiazine derivatives was synthesized by the BF3 x Et2O-catalyzed reaction of selected alpha,beta-unsaturated ketones with thiobenzamide at room temperature. The antimycobacterial activities of these compounds were determined against Mycobacterium tuberculosis H37Rv (ATCC 27294) using the Alamar blue susceptibility assay. Three compounds, 5-hydroxy-3-phenyl-4-aza-2-thiabicyclo[3.3.1]none-3-ene 3a, 4-hydroxy-4-methyl-6-pentyl-2-phenyl-5,6-dihydro-4H-1,3-thiazine 3b, and 4-ethyl-4-hydroxy-2-phenyl-5,6-dihydro-4H-1,3-thiazine 3c exhibited inhibitory activities of 97, 77 and 76%, respectively, at a concentration of 6.25 microg/ml. The actual MIC99 for the most active of these compounds, 3a, was also determined to be >6.25 microg/ml. These results, and especially those for 3a, suggest that 1,3-thiazines are potential lead compounds in the search for new antitubercular agents.     

Über Derivate des 1,3-Oxazolidin-4,5-dions

Derivatives of 1,3-Oxazolidine-4,5-dione Condensation of oxalylchloride with N-hydroxymethylbenzamide ( 4 ) to N-benzoyl-1,3-oxazolidine-4,5-dione ( 8 ) is achieved if the hydrogen chloride formed is removed by means of potassium carbonate or a nitrogen stream. Otherwise formation of N-chloromethylbenzamide ( 6 ) takes place with elimination of hydrogen chloride, carbon monoxide and carbon dioxide. N-Acyl-2-trihalogenomethyl-1,3-oxazolidine-4,5-diones 11 were synthesized in good yields from chloral- or bromal-acylamides 10 with oxalyl chloride. No ring closure takes place during the reaction of malonyl chloride with chloral acylamides. Rather the bis-(1-acylamido-2-trichloroethyl)esters 12 of malonic acid are formed.     

Untersuchungen an 1,3-Thiazinen, 40. Mitt.1); Iminiumkohlensäurederivat-Salze, 4. Mitt.1): Cyclische Keten-S,N-acetale aus Iminiumthiokohlensäureesterchloridchloriden und doppelt aktivierten cyclischen Methylenkomponenten

Investigations on 1,3-Thiazines, XL¹); Iminium Carbonic Acid Derivative Salts, IV¹): Cyclic Ketene-S,N-acetales from Iminium Thiocarbonic: Acid Ester Chlorid-Chlorides and Doubly Activated Cyclic Methylene Compounds Cyclic iminium thiocarbonic acid ester chlorid-chlorides of the 1,3-thiazine type 1 react with twofold activated cyclic CH-acidic compounds yielding push-pull substituted ketene-S,N-acetales.     

Untersuchungen an 1,3-Thiazinen, 15. Mitt. Neue Synthese für N-substituierte Tetrahydro-1,3-thiazin-2-thione

1,3-Thiazines, XV: New Synthetic Route to N-Substituted Tetrahydro-1,3-thiazine-2-thiones. A new synthetic route to N-substituted tetrahydro-1,3-thiazine-2-thiones 5 giving good yields for N-aryl compounds is reported. It consists of carbon disulfide cleavage of N,N'-disubstituted 2-iminotetrahydro-1,3-thiazines 3 which leads to 5 and the isothiocyanates 6 .     

Diversity-oriented synthesis of spiro-substituted 1,3-thiazine library via a one-pot, two-step, three-component reaction

A sequential one-pot, two-step, three-component reaction for efficient synthesis of spiro-substituted 1,3-thiazine library has been developed. The syntheses were achieved by reacting cyanoacetamide with isothiocyanate derivatives to give rise to 2-cyano-3-mercaptoacrylamides, which are trapped in situ by various cycloketones through cyclization, providing multifunctionalized spiro-substituted 1,3-thiazine analogues. This procedure features short reaction time, generally good to excellent yields, easily available starting materials, and operational simplicity. This chemistry provides an efficient and promising synthetic strategy to diversity-oriented construction of the 1,3-thiazine skeleton.     

Untersuchungen an 1,3-Thiazinen, 21. Mitt. Neue Synthesemethoden für N-substituierte 3,6- und 3,4-Dihydro-1,3-thiazin-2-thione

1,3-Thiazines, XXI: New Synthetic Methods for N-substituted 3,6- and 3,4-Dihydro-1,3-thiazine-2-thiones Some N-substituted 3,6-dihydro-1,3-thiazine-2-thiones 4 and 3,4-dihydro-1,3-thiazine-2-thiones 9 have been prepared by new methods.     

Untersuchungen an 1,3-Dicarbonylverbindungen, 11. Mitt. Anellierte Chinolone II,N- und O-Alkylierungsprodukte

1,3-Dicarbonyl Compounds, XI: Fused Quinolones II, N- and O-Alkylated Products The 1,3-dicarbonyl compounds 2 and 6 cyclisize on heating with polyphosphoric acid (PPA) to form the quinolones 3 and 7 . The quinolones 3a, 7a and 10 react with ethyliodide/NaH/DMF to give exclusively O-alkylated quinolines 11 .     

Über Umsetzungsprodukte von N-(Diphenylmethylen)aminomethanol

Reaction Products of N-(Diphenylmethylene)aminomethanol The lithium compound 4 of N-(diphenylmethylene)aminomethanol (2) has been converted with aliphatic acid chlorides, α-haloethers and chloro(trimethyl)silane into the substitution products 5, 10 and 11 . With nucleophiles such as sodium methanolate, 2-methyl-1,3-indanedione-sodium or sodium cyanide the acetoxy derivative 5a reacts presumably via a 1,1-diphenyl-2-azaallenium cation to yield 7 , 8 or 9 with newly formed N-O, C-C and N-C bonds.     

Carbazoylierungen und Thiocarbazoylierungen von 2-Thioxo-thiazolidinen

Carbazoylations and Thiocarbazoylations of 2-Thioxo-thiazolidines¹⁾ Reactions of thiazolidine-2-thione (1) with carbazic and thiocarbazic acid chlorides 5 lead to S-substitution products 6 which only in case of the carb-azoic derivatives can be thermally rearranged to N-carbazoyl derivatives 7. Not rearrangeable heteroaromatic thiazoles 9 are obtained from 5 and 5-methylen-thiazolidine-2-thione (8). Thiazolidine-2,4-dione (10) only yields N-substitution products 11.     

Synthesen neuer überbrückter heterocyclen durch 1,3-dipolare cycloadditionen

Syntheses of New Bridged Heterocycles by 1,3-Dipolar Cycloaddition Cycloaddition of bridged Quinonehydrazones 1, 4, 5 with mesoionic reagents are studied; the p-nitrophenylhydrazone 1 reacts with 3-phenylsydnone (2) under elimination of CO₂ and dehydrogenation yielding the linearly annulated heterocyclic cycloadduct 3; as opposed to this reaction cycloaddition of phenylsydnone 2 with N-methyl-(4)- and N-benzyl-(5)-hydrazone derivatives produces the methanobridged heterocycles 6 and 7, respectively.