Products of Reaction of Tricyclo[4.1.0.02,7]heptane and 1-Bromotricyclo[4.1.0.02,7]heptane with Hydrogen Sulfide,and Syntheses Based Thereon

By reactions of 1-R-tricyclo[4.1.0.02,7]heptanes (R = H, Br) with hydrogen sulfide initiated by UV irradiation endo-6-bicyclo[3.1.1]heptanethiols and bis(endo-6-bicyclo[3.1.1]heptyl) sulfides were synthesized. The sulfides were oxidized to the corresponding sulfoxides and sulfones. The results of HBr elimination from the bromine-substituted sulfoxides and sulfones effected by potassium tert-butylate are discussed. The latter reaction results in the recovery of the system of 1-substituted tricyclo[4.1.0.02,7]heptane.     

Sodium Bicyclo[1.1.1]pentanesulfinate: A Bench-Stable Precursor for Bicyclo[1.1.1]pentylsulfones and Bicyclo- [1.1.1]pentanesulfonamides

Herein, we present the synthesis of the bench-stable sodium bicyclo[1.1.1]pentanesulfinate (BCP-SO₂Na) and its application in the synthesis of bicyclo[1.1.1]pentyl (BCP) sulfones and sulfonamides. The salt can be obtained in a four-step procedure from commercially available precursors in multigram scale without the need for column chromatography or crystallization. Sulfinates are known to be useful precursors in radical and nucleophilic reactions and are widely used in medicinal chemistry. This building block enables access to BCP sulfones and sulfonamides avoiding the volatile [1.1.1]propellane which is favorable for the extension of SAR studies. Further, BCP-SO₂Na enables the synthesis of products that were not available with previous methods. A chlorination of BCP-SO₂Na and subsequent reaction with a Grignard reagent provides a new route to BCP sulfoxides. Several products were analyzed by single-crystal X-ray diffraction.     

Heterotricyclodecane XI,Sulfoxide und Sulfone von 2-Oxa-7-thia-isotwistan und 2-Oxa-7-thia-twistan sowie Derivaten

The synthesis of sulfoxides and sulfones of 2-oxa-7-thia-isotwistane ( 24 ) and 2-oxa-7-thia-twistane ( 35 ) as well as of several of their derivatives is described. endo-2-Hydroxy-9-thiabicyclo[3.3.1]non-6-ene ( 5 ) was used as starting material. During the course of the reactions special attention was given to intramolecular hydroxy-mercuration and jododemercuration reactions, spectroscopic features, molecular rearrangements and stereospecificity of oxidations of sulfides to sulfoxides.     

Synthesis in the 2-mercaptobenzothiazole series V. Thiazolidino[2, 3-b]-benzothiazolines

Reaction of 2-mercaptobenzothiazoles substituted at position 6 by chlorine, dimethylsulfamido, benzamido, and nitro groups, with chlorobromoalkanes, is used to synthesize the corresponding 6-substituted 2-(-chloroalkylmercapto)benzothiazoles. Oxidation of these compounds with hydrogen peroxide in acetic acid converts them to sulfoxides and sulfones, while heating in nitrobenzene cyclizes them to 6 substituted 2,3-dihydrothiazolo[2,3-b]benzothiazolium chlorides. The latter and previously obtained quaternary salts are converted by sodium borohydride into derivatives of a new tricyclic system, thiazolidino[2,3-b]benzothiazoline.For Part IV see [1].     

Benzo[b] thiophene derivatives. XIV. Derivatives of naphtho[1,8-c] thiophene

In the course of our efforts to synthesize the sulfur isostere of lysergic acid, we have prepared a number of derivatives of the little known naphtho[1,8-bc]thiophene ring system. Two previously reported compounds, 2-bromo-3,4-dihydro-5-oxo-5H-naphtho[1,8-bc]thiophene and 2-bromo-5-hydroxy-3,4-dihydro-5H-naphtho[1,8-bc] thiophene have been obtained pure for the first time, and the syntheses and spectral data of eighteen new compounds are presented. The new compounds include alcohols, ketones, and halogen derivatives of partially reduced naphtho-[1,8-bc] thiophene, as well as the sulfones of several of these compounds.     

Preparation and Reactions of 2-Oxa-6-thiabicyclo[3.2.0]-heptanes and 2-Oxa-5-thiabicyclo[2.2.1]heptanes from Pentoses

Abstract:

The preparation of the two diastereoisomeric 3-methoxy-2-oxa-6-thiabicyclo-[3.2.0]heptan-4-ols 4 and 5 from D-xylose 1 via methyl 2,3-anhydro-α-D-ribofuranoside and the corresponding β-anomer is described. Oxidation of 4 and 5 yields the sulfoxides 6 and 7 and the sulfones 8. – On the other hand, the two diastereoisomeric 3-methoxybicyclo[2.2.1]heptan-7-ols 11 and 12 are obtained from methyl 5-acetylthio-5-deoxy-2-O-mesyl-D-xylofuranosides 9 and 10 via Mitsunobu reaction and intramolecular cyclization. – The stereoisomeric counterparts of 4 and 5, 13 and 14, are obtained in only four steps from L-arabinose.     

Use of sulfur derivatives as an ortho directing group for the metalation of diazines. Metalation of diazines. XVIII

The metalation of thioethers, methyl and phenyl sulfoxides and sulfones of pyrazine and pyridazine has been performed. Methyl sulfoxides and sulfones were first metalated on the methyl group. The ortho directing effect of thioethers, sulfoxides and sulfones have been compared with the methoxy group. The sulfoxides were shown to be very good ortho directing groups.     

Synthesis and carbon-13 nuclear magnetic resonance spectroscopy of 5,6-dihydro-2-methyl-1,4-oxathiin,trans-tetrahydro-1,4-benzoxathiin, 1,4-tetrahydro-[9,10]benzoxathiin,the 4-oxides, 4,4-dioxides and related acyclic compounds

The results of a ¹³C NMR spectral investigation involving 5,6-dihydro-1,4-oxathiins, 1,4-tetrahydro[9,10]benzoxathiin, trans-tetrahydro-1,4-benzoxathiin, and the corresponding sulfoxides and sulfones are reported. An interpretation involving a dipolar structure with (2p→2p)π conjugation as opposed to (2p→3d)π interactions with the vinyloxy sulfides seems consistent with trends in the ¹³C NMR shifts. For the sulfoxides and sulfones, the substitutent-induced chemical shift (SCS) effects at the β vinylic carbons (βSO and βSO₂ effects) are considerably less than those at sp³ carbons. The γSO and γSO₂ values at the sp²γ carbons indicate deshielding, in contrast to the shielding at the sp³ carbons.     

A simple synthesis of azabicyclo[1.1.0]butane sulfones and sulfoxides

Azirines react with carbanions derived from α-chloro sulfones and sulfoxides, under mild conditions, to form functionalized azabicyclo[1.1.0]butanes.     

Oxidative addition of Pd0 to Ar-SO2R bonds: heck-type reactions of sulfones

[reaction: see text] Phenyl vinyl sulfones and sulfoxides react with Pd(OAc)(2) to form styryl sulfoxides and sulfones according to the first Mizoroki-Heck reaction reported for these thio derivatives. Only sulfones are able to react by using catalytic amounts of Pd (up to 1 mol %) in the presence of Ag(2)CO(3). 1,2-Diphenylsulfonyl ethenes, alkynylphenyl sulfones, and other sulfones, less prone to act as acceptors in the Heck-type reactions, can transfer the aryl group to alkyl acrylates forming cinnamic esters.     

Sulfides,sulfones, and sulfoxides of the furan-2(5H)-one series. synthesis and structure

A number of 4- and 5-R-sulfanylfuran-2(5H)-one derivatives were synthesized, and their oxidation with various reagents was studied. The corresponding sulfones were obtained using hydrogen peroxide in acetic acid. 4-R-sulfanyl derivatives were selectively oxidized to sulfoxides with m-chloroperoxybenzoic acid. The molecular and crystal structures of some new sulfones and sulfoxides were determined by X-ray analysis.     

Conformational analysis of the stereoisomers of 3-methyl-2-oxo-2-thiabicyclo[4.4.0]decane

The conditions for the separation of the stereoisomeric sulfones and sulfoxides of 3-methyl-2-thiabicyclo[4.4.0]decane were found by means of capillary gas-liquid chromatography, and the relative thermodynamic stabilities of the latter were determined. The configuration of the stereoisomeric sulfoxides was established on the basis of oxidation data, the characteristics of the physicochemical properties, and the Kerr effect.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 621–624, May, 1976.     

Reaction of 6-arylidenehydrazino-1,3-dimethyluracils with thionyl chloride leading to purine,thiazolo[4,5-d]pyrimidine,pyrimido[4,5-e][1,3,4]thiadiazine,pyrazolo[3,4-d]pyrimidine,and [1,2,3]thiadiazolo[4,5-d]pyrimidine derivativese

The reaction of 6-arylidenehydrazino-1,3-dimethyluracils with thionyl chloride in benzene afforded purine, thiazolo[4,5-d]pyrimidine, pyrimido[4,5-e][1,3,4]thiadiazine, pyrazolo[3,4-d]pyrimidine, and [1,2,3]thiadiazolo[4,5-d]pyrimidine derivatives, while the treatment of 6-(benzylidene-1′-methylhydrazino)-1,3-dimethyluracil with thionyl chloride in benzene gave 4-methylpyrimido[4,5-e][1,3,4]thiadiazine and 1-methylpyrazolo-[3,4-d]pyrimidine derivatives. Plausible mechanisms for the formation of these fused pyrimidines are also described.     

Ring opening reactions of 6H-anthra[1,9-cd]isoxazol-6-ones and related compounds

Nucleophilic attack of anthra[1,9-cd]isoxazol-6-ones, and of anthra[1,9-cd:5,10-c'd']isoxazole by various sulfoxides, triphenyl phosphine, and aliphatic or aromatic phosphites proceeded with cleavage of the nitrogen? oxygen bond of the isoxazole ring. This method provided ready access to substituted anthraquinones bearing sulfoximido-, triphenylphosphazo-, and dialkyl(aryl)phosphoramidic groups attached to the 1- and the 1,5-positions of the anthraquinone system. The structures of the newly synthesized anthraquinone derivatives were supported by analytical and spectral data. l-S,S-dimethyl-N-(5-benzamidoanthraquinon-1-yl)-sulfoximide yielded in 90% sulfuric acid the l-amino-5-sulfoximido anthraquinone without hydrolyzing the sulfoximido group.     

The synthesis of [1]benzothieno[2,3-c]quinolines, [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline,and [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamide 10 afforded [1]benzothieno[2,3-c]-quinolin-6(5H)-one 11 which was chlorinated to 6-chloro[1]benzothieno[2,3-c]quinoline 12 followed by dechlorination to give [1]benzothieno[2,3-c]quinoline 5 . A series of 6-substituted alkoxy and thioalkoxy[1]benzothieno[2,3-c]quinoline derivatives were prepared along with the N-methyl quaternary salt 13 of 5 . 6-Chloro[1]-benzothieno[2,3-c]quinoline 12 was converted into 6-hydrazino[1]benzothieno[2,3-c]quinoline 23 which upon treatment with formic acid yielded [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline 6 . Treatment of 23 with nitrous acid resulted in [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline 7 . Compounds 6 and 7 are novel heterocyclic ring systems.     

Synthesis,reactions, and antimicrobial activity of some novel pyrazolo[3,4-d]pyrimidine,pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine,and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c]pyrimidine derivatives

Treatment of N-phenyl-substituted benzenecarbo-hydrazonoyl chlorides 1a - d with malononitrile in sodium ethoxide solution gave 5-amino-4-cyanopyrazole derivatives 2 - 5 . Compounds 2 - 5 were converted to formidate derivatives 6 - 9 upon treatment with TEOF in acetic anhydride. The reaction of the latter products 6 - 9 with hydrazine hydrate gave imino-amino derivatives 10 - 13 , which was converted to hydrazino derivatives 14 - 17 by refluxing with hydrazine hydrate. Hydrazino as well as imino-amino derivatives undergo condensation, cyclization, and cycloaddition reactions to give pyrazolo[3,4-d]pyrimidine 18 - 21 , pyrazolo[4,3-e][1,2,4]triazolo-[3,4-c]pyrimidine 22 - 27 , and pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazine 42 - 44 derivatives. Antimicrobial studies are performed using two Gram-positive bacteria and two Gram-negative bacteria. Data indicated that compounds 5 , 28D , 29B , and 31D are exploring elevated antibacterial effects against all strains tested. Compound 28D is the most promising antibacterial agent against the delicate bacterial strain Bacillus subtilis and Pseudomonas aeruginosa with high effectiveness (low minimum inhibitory concentration [MIC] value) 40 and 60 μg/mL, respectively.     

Synthesis of 1H-pyrazolo[3,4-e]-s-triazolo[3,4-c]-as-triazines, 8H-pyrazolo[3,4-e]tetrazolo[5,1-c]-as-triazine and 1,7-dihydro-8H-pyrazolo[3,4-e]-as-triazine derivatives

3-Hydrazino-7-methyl-5-phenyl-5H-pyrazolo[3,4-c]-as-triazine 1 underwent ring closure and/or condensation reaction with formic acid, acetic acid, acetic anhydride and benzoyl chloride to afford 1H-pyrazolo-[3,4-d]-s-triazolo[3,4-c]-as-triazines 2, 5 and 7a and/or N-acyl derivatives 3, 4 and 6 . N-Acyl derivatives 3 and 6 underwent cyclisation reaction on treatment with phosphoryl chloride to give 5 and 7a . 3-Methyl-1-phenyl-8-aryl-1H-pyrazolo[3,4-e]-s-triazolo[34,-c]-as-triazines 7 were also prepared by the reaction of the hydrazono derivatives 8 wit thionyl chloride. On treatment of 1 with nitrous acid gave the 8H-pyrazolo[3,4-e]tetrazolo-[5,1-c]-as-triazine 9 . Compound 1 underwent ring closure with carbon disulphide or ethyl chloroformate to 1,7-dihydro-8H-pyrazolo[3,4-e]-s-triazolo[3,4-c]-as-triazine derivatives 10 and 12 . Reaction of 1 with ethyl acetoacetate or acetylacetone gave 3-pyrazolo derivatives 13 and 14 .     

Syntheses and reactions of [1,3,4]thiadiazolo[3,2-a]pyrimidinone derivatives

5-Imino-6H-7-one, 7-amino-5-one and 5-isocyano-7-one derivatives of [1,3,4]thiadiazolo- and -[1,3]thiazolo-[3,2-a]pyrimidines were synthesized. 5-Isocyano-7-one derivatives were obtained by the reaction of the corresponding 5-imino-6H-7-ones with the Vilsmeier reagent in one step.     

Synthesis of new fluorine-containing pyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridinones as promising drug precursors

Methods for the synthesis of 4-R-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones (R = CF₂SAr and 4-CFHSAr) were developed. The derivatives with R = CF₂SAr were obtained by both heterocyclization of 1-substituted 5-aminopyrazoles with ethyl 4,4-difluoro-3-oxo-4-phenylsulfanylbutanoate and replacement of the Br atom in 4-bromodifluoromethyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones by sodium arenethiolates. The fragment 4-CF-HSAr was introduced by replacement of the Cl atom in 4-chlorofluoromethyl-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones by sodium arenethiolates. Oxidation of 4-CF₂SPh-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-ones gave the corresponding sulfoxides; their structures were confirmed by X-ray diffraction data.     

The mass spectra of thiochromanone and related compounds

The mass spectra of thiochromanone (I), isothiochromanone (II)-2-, 3- and 8-methylthiochromanone and the sulfoxides and sulfones derived from these cyclic sulfides have been determined and the major fragmentation routes established. For the iso series loss of SO or SO₂ competes effectively with the retro-Diels-Alder reaction; however, for the thiochromanone derivatives the retro-Diels-Alder reaction is the major fragmentation route. There is no evidence for rearrangement of the sulfoxides or sulfones to sulfenates or sulfinates, respectively, prior to fragmentation.