Synthesis of cis- and trans-perhydrothieno[3,4-d]imidazole-2-thione 5,5-dioxides

It is shown that the cis and trans isomers of perhydrothieno[3,4-d]imidazole-2-thione 5,5-dioxides can be obtained in good yields from the accessible derivatives of thiolane and 2-thiolene 1,1-dioxides.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 328–330, March, 1982.     

Condensed thiolane 1,1-dioxide systems. 2. Brominated cis-perhydrothieno[3,4-d]oxazoles and imidazoles

Bromocyclization of 2-bromo-4-ureido-2-thiolene 1,1-dioxide has given perhydrothieno[3,4-d]oxazol-2-imino 5,5-dioxide, in which hydrogen atoms are absent from one of the -methylene groups. In weakly basic media, this undergoes conversion into the corresponding aminooxazoline. Treatment of an aqueous solution of 2-bromo-4-ureido-2-thiolene 1,1-dioxide with bases gives a mixture of perhydrothieno[3,4-d]imidazol-2-one 5,5-dioxides in which the bromine atoms have the exo- and endo-orientations. In all the bicyclic compounds, the two rings are cis-fused.For Communication 1, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1264–1268, September, 1988.     

Rearrangement of 2-iminoperhydrothieno-[3,4-d]-thiazole-5,5-dioxides

The reaction of 4-bromo-2-thiolene 1,1-dioxide with thiosemicarbazide and thiosemicarbazones gave 2-iminoperhydrothieno[3,4]-d]thiazole 5,5-dioxides, which contain a nitrogen function at the imino group. The recyclization of these compounds was studied.Institute of Bioorganic Chemistry and Petyrochemistry, 252160 Kiev. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1274–1277, September, 1994. Original article submitted July 25, 1994.     

Condensed systems from thilane 1,1-dioxide. 4. PMR spectra of cis- and trans-perhydrothieno[3,4-d]-oxa(thia)zole 5,5-dioxides

Examination of the PMR spectra of eleven bicyclic thiolane 1,1-dioxide derivatives has enabled those features of the spectral parameters characteristic of the cis- and trans-orientation of the two condensed five-membered heterocycles to be established. The proton coupling constants show that the conformation of the 1,1-dioxothiolane ring in both types of compound in solution differs from that in the crystalline state, as determined by x-ray analysis.For Communication 3, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1685–1689, December, 1989.     

Condensed thiolane 1,1-dioxide systems. 3. Two modes of cyclization of N-substituted trans-3-chloro-4-thioureidothiolane 1,1-dioxides

Reaction of trans-3-chloro-A-aminothiolane 1,1-dioxide hydrochloride with aryl isothiocyanates gives, according to the base involved, cis-perhydrothieno[3,4-d]imidazole-2-thione 5,5-dioxides or the hitherto undescribed cis-2-aryliminoperhydrothieno 3,4-d] thiazole 5,5-dioxides.For Part 2, see [1].Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1420–1423, October, 1988.     

Sulfur-containing derivatives of thiolan-1,1-dioxide 3. Reactions of salts of 2-(n,n-dialkyl)iminio-5,5-dioxoperhydrothieno[3,4-d]-1,3-dithiolans with bases

Salts of condensed 2-(N,N-dialkyl)iminio-1,3-dithiolan and 1,1-dioxothiolan rings are converted in alkaline media to 1,1-dioxothiolen esters of N,N-dialkyldithiocarbamic acids and into unsaturated bicyclic compounds. The latter are formed when the initial salts contain a bromine atom to the sulfonyl group.For Communication 2, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 40–47, January, 1993.     

Aminoethyl derivatives of 4-substituted pyrazolo[3,4-d]pyrimidines

New 3-aminoethyl derivatives of pyrazolo[3,4-d]pyrimidine were synthesized by reduction of 3-cyanomethylpyrazolo[3,4-d]pyrimidines with hydrazine hydrate in the presence of Raney nickel in alcohol.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 846–847, June, 1972.     

The preparation of 2H-1,2,3-benzothiadiazine-1,1-dioxides, 11H-11a-dihydrobenzimidazo[1,2-b] [1,2] benzisothiazole-5,5-dioxides, 6H-dibenzo[c,g] [1,2,5] thiadiazocine-5,5-dioxides and 5H-Dibenzo[c,g] [1,2,6] thiadiazocine-6,6-dioxides

o-Benzoylbenzenesulfonyl chlorides (I) were prepared conveniently from aminobenzophenones by diazotization followed by reaction with sulphur dioxide in the presence of Cu⁺, according to the general method of Meerwein. Reaction of the sulfonyl chlorides with hydrazine led to 4-phenyl-2H-1,2,3-benzothiadiazine-1,1-dioxides (II). The latter compounds could be methylated and acetylated readily in the 2-position. The 2-methyl derivative (III) could be prepared also by reaction of the sulfonyl chloride (Ia) with methylhydrazine. Catalytic hydrogenation of 6-chloro-4-phenyl-2H-1,2,3-benzothiadiazine-1,1-dioxide (IIa) gave the 3,4-dihydro derivative (V). Reaction of the sulfonyl chlorides (I) with o-phenylenediamine followed by cyclodehydration led to 11H-11,11a-dihydrobenzimidazo[1,2-b] [1,2]benzisothiazole-5,5-dioxides (VII). One of the latter compounds (VIIa) in sodium hydroxide solution in the presence of methyl iodide or benzyl chloride was transformed into 6-methyl- and 6-benzyl-5H-dibenzo[c,g] [1,2,6]thiadiazocine-5,5-dioxides (VIII), respectively. 5H-Dibenzo[c,g] [1,2,6] thiadiazocine-6,6-dioxides (XIV) were prepared also by cyclodehydration of 2-amino-2′-benzoylbenzenesulfonanilides (XIII).     

Reactions of aroylhydrazines with nitrosulfodienes of the 2-benzylidene-3-methyl-4-nitro-3-thiolene-1,1-dioxide series

Reactions of s-trans-nitrosulfodienes of the 2-benzylidene-3-methyl-4-nitro-3-thiolene-1,1-dioxide series with aroylhydrazines occur as nucleophilic 1,4-addition to give the aza-Michael adducts. Activity of the studied substrates depends on the nature of the substituents in the benzene ring of benzylidene fragment. Previously unexplored representatives of the 2-benzylidene-3-methyl-4-nitro-3-thiolene-1,1-dioxides have been synthesized.     

Synthesis of 3-substituted 4-methylmercapto- and 4-aminopyrazolo-[3,4-d]pyrimidines and their ribosides

3-Cyano-4-methylmercaptopyrazolo[3,4-d]pyrimidine, fusion of which with 1,2,3,5-tetra-0-acetyl--D-ribofuranose gave its per-0-acetylated 1--D-ribofuranoside in 61% yield, was synthesized from 3,4-dicyano-5-aminopyrazole. 0-Deacetylation of the per-0-acetylated 1--D-ribofuranoside was carried out by the action of 1% HCl in methanol. New pyrazolo[3,4-d]pyrimidines were obtained by the reaction of 3-cyano-4-methylmercaptopyrazolo[3,4-d]pyrimidine and its 1-riboside, as well as 3-cyano-4-aminopyrazolo[3,4-d]pyrimidine, with a number of nucleophilic reagents. The cytotoxic activities of the compounds obtained were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 253–258, February, 1984.     

Pyrazolopyrimidine nucleosides. Part VIII The synthesis of certain 4-substituted pyrazolo[3,4-d]pyrimidine nucleosides

1-(β-D-Ribofuranosyl)pyrazolo[3,4-b]pyrimidine-4-thione ( 6 ), obtained by a three-step synthesis from allopurinol riboside (3), was treated with certain alkyl and aryl halides to provide the corresponding 4-alkylthio derivatives. The nucleoside 4-methylthio-1-(β-D-ribofuranosyl)pyra-zolo[3,4-d]pyritnidine ( 7 ) has served as the precursor for the preparation of the 4-methylamino ( 11 ), 4-dimethylamino ( 12 ), 4-hydrazino ( 13 ), and the 4-hydroxylamino ( 14 ) analogs.     

Alkoxide-induced reactions of N-substituted saccharins. Synthesis of 1,2-benzothiazocine 1,1-dioxide and 2,3-dihydropyrrolo[1,2-b]-[1,2]benzisothiazole 5,5-dioxide derivatives

The reactions of saccharin derivatives 1 with sodium alkoxides were studied. Under mild conditions, compounds 1a-f gave the corresponding open sulfonamides 5a-f . Under drastic conditions, β-(saccharin-2)propionic acid derivatives 1a,b reacted with sodium ethoxide affording saccharin and β-ethoxypropionic acid derivatives 4a,b . γ-(Saccharin-2)butyric acid derivatives 1c,d and γ-(saccharin-2)-butyrophenone 1f reacted with sodium t-butoxide in dimethyl sulfoxide affording 5-substituted 6-hydroxy-3,4-dihydro-2H-1,2-benzothiazocine 1,1-dioxides 9 . From mother liquors, 1-substituted 2,3-dihydro-pyrrolo[1,2-b][1,2]benzisothiazole 5,5-dioxides 10 were isolated several hours later, though not detected immediately after completing the reaction. When the reactions were carried out in t-butyl alcohol, the yields of 9 diminished and those of 10 increased with product ratio inversion. Different experimental observations on the possible pathway generating 9 and 10 are discussed.     

Heterocycles with a Benzothiadiazeypine Moiety. I. Synthesis of Pyrrolo[1,2-b]-s-triazolo[3,4-d] [1,2,5]benzothiadiazepine 5,5-Dioxide

Condensation of 2-nitrobenzenesulfonyl chloride with 2-ethoxycarbonyl-1H-pyrrole in the presence of potassium tert-butoxide and 18-crown-6 furnished 2-ethoxycarbonyl-1-(2-nitrobenzenesulfonyl)-1H-pyrrole. Reduction of nitro group to amino and subsequent cyclization by heating the aminoester in the presence of 2-hydroxypyridine as a bifuctional catalyst led to 11-oxo(10H)-pyrrolo[1,2-b] [1,2,5]benzothiadiazepine 5,5-dioxide. Treatment of the latter compound with di-4-morpholinylphosphinic chloride gave the corresponding phosphinyloxyimine, which on reacting with formylhydrazine underwent intramolecular cyclization to afford the title tetracyclic ring.     

Reaction of 6-hydrazino-3,4-dimethyl-1H-pyrazolo[3,4-d]pyrimidine with pregnenolone derivatives

New androsteno[17,16-d]pyrazoles and -pyrazolines with pyrazolo[3,4-d]pyrimidine fragments were synthesized. A reaction of 3β-hydroxypregna-5,16-dien-20-one and its 3-O-acetyl derivative with 6-hydrazino-3,4-dimethyl-1H-pyrazolo[3,4-d]pyrimidine led to hydrazones at position 20 of the pregnenolone molecule, a possibility of their cyclization was studied. Upon melting, the hydrazones cyclize with the formation of pyrazoline ring annulated with ring D of the steroid at positions 16 and 17. Reflux of the hydrazones in mesitylene with AcOH leads to a mixture of two reaction products: androsteno[17,16-d]pyrazole and a dodecahydro-13H-phenanthro[1′,2′:5,6]pyrano[2,3-d]pyrazole derivative. Apparently, this transformation proceeds through the corresponding epoxide with subsequent rearrangement, which leads to the ring D expansion.