Ringerweiterung von sechs- zu neungliedrigen Heterocyclen: Umsetzung von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin mit 3,4-Dihydro-2H-1,2,4-benzothiadiazin-3-on-1,1-dioxiden

Ring Enlargement of Six- to Nine-Membered Heterocycles: Reaction of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine with 3,4-Dihydro-2H-1,2,4-benzothiadiazin-3-one 1,1-Dioxides Reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) and N-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazin-3-one 1,1-dioxides ( 4 ) in CHCl₃ yields 3-(dimethylamino)-4,5,6,7-tetrahydro-1,2,5,7-benzothiatriazonin-6-one 1,1-dioxides 5 , a novel nine-membered heterocyclic system, by ring enlargement (Schemes 2 and 4). In refluxing MeOH, the heterocycle 5a rearranges to give the N-[1-methyl-1-(1,1-dioxo-4H-1,2,4-benzothiadiazin-3-yl)ethyl]-N′, N′-dimethylurea 10 . The three isomeric 2-(methylamino)benzenesufonamides 8,9 , and 11 (Scheme 3) are obtained by naBH₄ reduction of 5a and 10 , respectively. Mechanisms for the thermal isomerization 5a → 10 and the NaBH₄ reduction of 5a are proposed in Schemes 5 and 6.     

Synthesis of 3-carboethoxy-4,11-dihydro-11-alkyl/phenyl-4-oxopyrimido[1,2-b][1,2,4]benzothiadiazine 6,6-dioxides. A novel heterocyclic ring system

The synthesis of some novel 3-carboethoxy-4,11-dihydro-11-alkyl/phenyl-4-oxopyrimido[1,2-b][1,2,4]benzo-thiadiazine 6,6-dioxides ( IVa-c ) from 3-amino-4-alkyl/phenyl-4H-1,2,4-benzothiadiazine 1,1-dioxides ( 1a-c ) and diethyl ethoxymethylenemalonate ( II ) is described. The compounds have been screened for their antibacterial activity.     

1,2,4-benzothiadiazine 1,1-dioxides 3. Reactions of 2-aminobenzenesulfonamide with chloroalkyl isocyanates

Reactions of 2-aminobenzenesulfonamide ( 1 ) with allyl, methyl, 2-chloroethyl aor 3-chloropropyl isocyanates gave 2-(methylureido)-, 2-(allylureido)-, 2-(2′-chloroethylureido)- and 2-(3′-chloropropylureido)-benzene sulfonamides 3a,b and 7a,b in excellent yields. Treatment of 3a,b at refluxing temperature of DMF afforded 2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide ( 4 ) in good yield. However, when compounds 7a,b were refluxed in 2-propanol, 3-(2′-aminoethoxy)-2H-1,2,4-benzothiadiazine 1,1-dioxide ( 11a ) and 3-(3′-aminopropoxy)-2H-1,2,4-benzothiadiazine 1,1-dioxide ( 11b ) were obtained in a form of the hydrochloride salts 10a,b in 87% and 78% yields respectively. Heating 11b in ethanol gave a dimeric form of 2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide and 3-(3′-aminopropoxy)-2H-1,2,4-benzothiadiazine 1,1-dioxide ( 12 ) in 55% yield. Treating of 7a,b or 11a,b with triethylamine at the refluxing temperature of 2-propanol afforded 3-(2′-hydroxyethylamino)-2H-1,2,4-benzothiadiazine 1,1-dioxide ( 2a ) and 3-(3′-hydroxypropylamine)-2H-1,2,4-benzothiadiazine 1,1-dioxide ( 2b ) via a Smiles rearrangement.     

Multigram scale synthesis of 3,4- and 3,6-dihydro-2H-thiopyran 1,1-dioxides and features of their NMR spectral behavior

A new four-step synthesis of 3,4- and 3,6-dihydro-2H-thiopran-1,1-dioxides from dihydro-2H-thiopyran-3(4H)-one is reported. The title compounds are synthesized starting with oxidation of the ketone with a 30% aqueous solution of hydrogen peroxide in a mixture of AcOH-Ac₂O. The keto group is then reduced by sodium borohydride followed by mesylation and elimination of methanesulfonic acid under basic conditions (pyridine for 3,4-isomer and aqueous NaOH for 3,6-isomer). This sequence is simpler, than previously known methods, uses cheaper and more readily available reagents, and leads to 2H-thiopran-1,1-dioxides on multigram scale with 64% and 74% total yields, respectively. The structure and purity of the compounds were confirmed by 2D NMR and GCMS methods. The proposed method expands the means to access functionalized cyclic sulfones as building blocks in the synthesis of combinatorial libraries of new biologically active compounds.     

3,5-dibromo-1-(1,1-dioxothietanyl-3)-1,2,4-triazole, new reagent for preparation of substituted thietane 1,1-dioxides

A new reagent, 3,5-dibromo-1-(1,1-dioxothietanyl-3)-1,2,4-triazole, was introduced for the synthesis of 3-substituted thietane 1,1-dioxides that were treated with sodium alcoholates and phenolates to prepare 3-alkoxyand 3-aryloxythietane 1,1-dioxides.     

Synthesis of 3-substituted 4,1,2-benzothiadiazine 4,4-dioxides and 2 or 3-substituted 1,4-benzothiazine 1,1-dioxides

The title compounds were prepared starting from the synthones 6 using two different synthetic approaches: 3-substituted 1,4-benzothiazine 1,1-dioxides were synthesised by cyclisation with phosphorus oxychloride as the Vilsmeier reagent, while 4,1,2-benzothiadiazine 4,4-dioxides and 3-substituted 1,4-benzothiazine 1,1-dioxides were obtained by direct diazotisation or by cyclisation with triethyl orthoformate.     

Synthesis of 3-amino-1,2,4-benzothiadi- azine 1,1-dioxides via a tandem aza-Wittig/heterocumulene annulation

[reaction: see text] Reaction of o-azidobenzenesulfonamides with polymer-supported triphenylphosphine affords the corresponding iminophosphoranes. Subsequent reaction with isocyanates gives 3-amino-1,2,4-benzothiadiazine 1,1-dioxides in high yields and purities. The reaction has been successfully applied to the synthesis of derivatives with various substituents at the 2- and 3-positions and in the benzenoid ring.     

A one-pot, non-catalytic approach to 1,2,4-benzothiadiazine-1,1-dioxides

Condensations of o-halo-substituted benzenesulfonyl chlorides with 2-aminopyridines and amidines may give the corresponding 1,2,4-benzothiadiazine-1,1-dioxides under mild, non-catalytic conditions in nearly quantitative yields. The successful one-pot cyclization depends on three factors: (i) the nature of the o-halogen, (ii) the electronic character of the benzene ring substituent, and (iii) the steric load around the amidine unit. O-Fluorobenzenesulfonyl chlorides bearing methylcarboxyl- or nitro-group and o-chloro- and o-bromobenzenesulfonyl chlorides bearing nitro-group are reactive enough to give the desired 1,2,4-benzothiadiazine-1,1-dioxides in a one-pot base-promoted reaction. In all other cases, open-chain sulfonylated amidine intermediates are isolated. The latter are converted to the title compounds either in the presence of potassium carbonate or upon the addition of a copper(I) catalyst.     

A Ring-Enlargement Reaction Yielding 1,2,5-Benzothiadiazonin-6-one 1,1-Dioxides

At room temperature or under reflux in MeCN, 3-amino-2H-azirines 2 and 3,4-dihydro-2H-1,2-benzothiazin-3-one 1,1-dioxide ( 4 ) give 1,2,5-benzothiadiazonin-6-one 1,1-dioxides 5 in fair-to-good yield (Scheme 2). The structure of this novel type of heterocyclic compounds has been established by X-ray crystallography of 5a (Fig.). A ring expansion via a zwitterionic intermediate of type A ' is proposed as the reaction mechanism of the formation of 5 .     

Catalytic Synthesis of Some Sulfur-containing Heterocyclic Compounds. (Review)

Researches on the synthesis of sulfur-containing heterocyclic compounds at the G. K. Boreskov Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, are reviewed. They include the synthesis of thiolane by the recyclization of THF in hydrogen sulfide; the synthesis thiacycloalkanes by the hydrogenation of thiophenes; the synthesis of 4-methylthiazole by the reaction of SO₂ with methylisopropylideneamine; the synthesis of thiophenes by the heterocyclization of aliphatic compounds of sulfur and dehydrogenation of thiacycloalkanes; the synthesis of thiolane 1,1-dioxide by the hydrogenation of 2- and 3-thiolene 1,1-dioxides and 3-alkoxythiolane 1,1-dioxides; the synthesis of sulfoxides by the oxidation of thiacycloalkanes with atmospheric oxygen.     

Fused-ring systems containing 1,2,4-benzo thiadiazines. II. Reactions of o-amino-n-hydroxybenzenesulfonamides

o-Amino-N-hydroxybenzenesulfonamides have been treated with aldehydes to prepare 2-hydroxy-1,2,4-benzothiadiazine 1,1-dioxides. These products have permitted the fusion of an additional ring to the “b” face of the benzothiadiazine. Analogs of the tricyclic compounds have been made in other ways.     

Alkylation of 5-nitro-l,2,4-triazol-3-one

The alkylation of 5-nitro-1,2,4-triazol-3-one with dialkyl sulfates and alkyl iodides has given N-alkyl-5-nitro-1,2,4-triazolones. The structure of the compounds obtained has been shown by independent synthesis via the corresponding N-alkyl derivatives of 1,2,4-triazol-3-one.     

Synthesis of 1,2,5-Thiadiazepine Derivatives by Ring Enlargement of 1,2-Thiazetidin-3-one 1,1-Dioxides with 3-Amino-2H-azirines

At 0° in MeCN, 2,2-disubstituted 3-amino-2H-azirines 1 and 4,4-disubstituted 1,2-thiazetidin-3-one 1,1-dioxides 7 react smoothly to give 1,2,5-thiadiazepin-6-one 1,1-dioxides of type 8 (Scheme 2). The reaction mechanism of this regiospecific ring enlargement to seven-membered heterocycles follows previously described pathways. The structures of 7a and 8b were established by X-ray crystallography (see Figs. 1 and 2).     

A convenient synthesis of nitro-substituted 1,2-benzisothiazol-3(2H)-one 1,1-dioxides (nitrosaccharins)

Nitro-substituted 1,2-benzisothiazol-3(2H)-one 1,1-dioxides (nitrosaccharins) have been synthesized by amminolysis of nitro 2-chlorosulfonylbenzoate esters. This method appears to have advantages over the original procedure of oxidation of an ortho-toluenesulfonamide.     

2H-1,2,4-benzothiadiazine 1,1-dioxides 2. A condensation of 2-aminobenzenesulfonamide with chloroalkyl isothiocyanates

A reaction of 2-aminobenzenesulfonamide ( 1 ) with 2-chloroethyl or 3-chloropropyl isothiocyanate in isopropanol afforded 2-(2′-chloroethylthioureido)- and 2-(3′-chloropropylthioureido)benzenesulfonamides ( 2a,b ) in 67% and 55% yield respectively. Treatment of 2a,b with triethylamine in methanol at room temperature furnished 3-(2′-aminoethylthio)- and 3-(3′-aminopropylthio)-2H-1,2,4-benzothiadiazine 1,1-dioxides ( 9a,b ) in quantitative yield. Heating 2b to reflux in methanol under neutral conditions gave 9b but in the form of the hydrochloride 8b which could be converted into the free base 9b by treating with ammonia water. When compounds 2a,b were treated with triethylamine in methanol at elevated temperature, 3-(2′-mercaptoethylamino)- and 3-(3′-mercaptopropylamino)-2H-1,2,4-benzothiadiazine 1,1-dioxides ( 10a,b ) were obtained in good yield. Alternatively, 10a,b could also be prepared from 9a,b in 95% and 77% yield respectively.     

Isothiazoles XI. Diels-alder adducts of 4-isothiazolin-3-one 1-oxides and 1,1-dioxides

4-Isothiazolin-3-one 1-oxides and 1,1-dioxides react with a variety of cyclic and acyclic dienes to afford cycloaddition products.     

Regioselective synthesis of novel N2- and N4-substituted 7-methylpyrazolo[4,5-e][1,2,4]thiadiazines

The new compound 7-methylpyrazolo[4,5-e][1,2,4]thiadiazin-3(2H,4H)-one1,1-dioxide (5) was synthesized and its novel mono N2- or N4-substituted derivatives 6 and 7 were prepared by regioselective N-alkylation of 5 with different molar ratios of NaH and alkyl halides. Based on the regioselective alkylation conditions found a facile one-pot synthesis of N2,N4-disubstituted pyrazolo[4,5-e][1,2,4] thiadiazines 8 was developed. The structures of the newly synthesized compounds were confirmed by IR,(1)H-NMR, (13)C-NMR and MS spectral analysis.     

Condensed thiolane 1,1-dioxide system

Alkylation of trans-N-alkyl(or aryl)-N'-(3-hydroxy-1,1-dioxothiolan-4-yl) thioureas with ethyl p-toluenesulfonate, and the reaction of cyanogen bromide wiht an ethyl p-toluenesulfonate, and the reaction of cyanogen bromide with trans-3-hydroxy-4-aminothiolan-1,1-dioxides have given salts of trans-2-iminoperhydrothieno[3,4-d]-oxazole 5,5-dioxides. Rearrangement of these oxazolidines in the presence of bases afford perhydrothieno[3,4-d]imidazole-2-one 5,5-dioxides.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 268–271, February, 1988.     

Metal free oxidative CC bond cleavage: Facile and one-pot tandem synthesis of benzothiadiazine-1,1-dioxides

An interesting protocol for the synthesis of benzothiadiazine-1,1-dioxides through iodine-catalyzed one-pot dehomologative oxidation of styrenes and readily available 2-aminobenzenesulfonamide has been developed. Diverse benzothiadiazine-1,1-dioxides were prepared using I₂ as a catalyst, TBHP as an oxidant and Na₂CO₃ as a base. This reliable, metal and ligand free conversion involves dehomologation of styrene to aromatic aldehyde which on subsequent cyclisation affords benzothiadiazine-1,1-dioxides in good yield.     

Synthesis of oxidized 1,2,3-thiadiazines by hydroperoxy-induced ring enlargement of 2-benzenesulfonylaminoisothiazolium salts

Oxidation of 2-benzenesulfonylaminoisothiazolium salts 1, 2 and their imines 3, 4 with hydrogen peroxide gave 1,2,3-thiadiazine 1-oxides 5, 6, which were converted into the corresponding 1,2,3-thiadiazine 1,1-dioxides 7, 8 using m-chloroperoxybenzoic acid. Oxidation of 5, 6 with hydrogen peroxide furnished isothiazol-3(2H)-one 1,1-dioxides 9, 10 as ring contraction products.