Spectral investigation of intramolecular interaction in sulfur-organic compounds

Earlier¹ it was reported that 4-aryl-4,5-dihydrothiophene-1,1-dioxides (I) are converted in aqueous and alcohol solution of bases to isomeric 3-aryl-2,5-dihydrothiophene dioxides (II) and 3-aryl-4,5-dihydrothiophene-1,1-dioxides (III) (Fig. 1).In the presence of electron-donor substituents in the p-position of the phenyl ring, IIb, c compounds are practically irreversibly isomerised to III b, c. For unsubstituted phenyldihydrothiophene-1,1-dioxides IIa and IIIa the reaction proceeds riversibly but equilibrium is shifted towards isomer IIIa indicating its high thermodynamic stability. It is known² that 2,5-dihydrothiophene-1,1 -dioxide is more stable than 4,5-dihydrothiophene-1,1-dioxide. Consequently, the observed stability increase of 3-aryl-4,5-dihydrothiophene-1,1-dioxides (IIIa–c) is due to interaction of the substituent C₆H₄X with the sulfonyl group. This paper investigates the nature of this interaction.     

A general synthesis of quinolinones and benzothiazine 1,1-dioxides via ring closing metathesis

A general synthesis of quinolinones and benzothiazine 1,1-dioxides is presented. A series of N-phenylacrylamides and N-phenylethylenesulfonamides were studied for their ability to undergo ring closing methathesis to yield the corresponding quinolinones and benzothiazine 1,1-dioxides, respectively. The reactions are general in scope and represents a mild method for the preparation of these heterocycles.     

Staudinger and retro-Staudinger reactions. The dichloro-β-lactam moiety as a useful handle for the synthesis of 4-aryl-2H-1,3-benzothiazine 1,1-dioxides

The dichloro-β-lactam ring, obtained via Staudinger reaction of 4-aryl-2H-1,3-benzothiazines, proved to be a useful protecting strategy for the synthesis of 4-aryl-2H-1,3-benzothiazine 1,1-dioxides. After oxidation of the 1,1-dichloroazeto[2,1-c][1,3]-benzothiazin-2-ones, the thiazine ring could be recovered selectively and in good yield by treatment with base. Thus, novel 4-aryl-2H-1,3-benzothiazine 1,1-dioxides were obtained efficiently.     

Reactions of acceptor substituted thiophene-1,1-dioxides with cyclopentadiene: control of selectivity by substitution

Diels-Alder reactions of thiophene-1,1-dioxides with strong electron withdrawing groups (EWG) were studied experimentally and theoretically. Thiophene-1,1-dioxides with two strong EWG behave as dienophiles and regio- and stereoselectively react with cyclopentadiene to give [2+4] cycloadducts 2a-c, which are derivatives of benzothiophene. In contrast, thiophene-1,1-dioxides with one EWG behave as dienes in the inverse electron demand Diels-Alder reaction yielding dihydro-1H-indenes derivatives. Cope [3,3]-sigmatropic rearrangement of adducts 2a-c was also demonstrated. MP2 calculations successfully rationalize the contrasting regioselectivities of these cycloaddition reactions.     

Synthesis and thermal behaviour of new benzo-1,2-thiazine long-chain aryl-piperazine derivatives

A series of potential biologically active 2-[3-(4-phenyl-1-piperazinyl)propyl]-3-(4-substituted-benzoyl)-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides was synthesized in a straightforward manner by condensation of respective 3-substituted-4-hydroxy-1,2-benzothiazine 1,1-dioxides with 1-(1-chloropropyl)-4-phenylpiperazine. The structures of all of the newly formed compounds were identified by elemental analysis, FTIR and ¹H NMR. The synthesized compounds were subjected to preliminary evaluation using differential scanning calorimetry (DSC) to determine the existence of multiple crystal forms. The DSC scans for all compounds show more than one endothermic effect, which might suggest dynamic proton transfer between two or three possible tautomeric forms: O-keto/O-enol, O-enol/O-keto and O-keto/O-keto/CH₂ in crystals 2-[3-(4-phenyl-1-piperazinyl)propyl]-3-(4-substituted-benzoyl)-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides.     

Efficient access to chiral N-substituted saccharin analogues via the directed ortho-lithiation of 3-N-arylsulfonyloxazolidin-2-ones

Chiral 3-N-arylsulfonyloxazolidin-2-ones 1a-f, prepared from (l)-amino acids, were reacted with lithium diisopropylamide in anhydrous THF and HMPA. The resulting new, optically active benzisothiazolinone 1,1-dioxides 2a-c and naphthisothiazolinone 1,1-dioxides 2d-f were obtained in good yields.     

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.     

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, structure, and electrochemical properties of biferrocenes annulated with 1,2-dithiin and 1,2-dithiin 1,1-dioxides

2,2″-Bis(N,N-dimethylaminosulfonyl)-1,1″-biferrocene (6), a precursor of biferrocenes annulated with 1,2-dithiin and 1,2-dithiin 1,1-dioxides, was prepared by a sequence of selective ortho-lithiation and dimerization reaction from N,N-dimethylaminosulfonylferrocene. New biferrocenes annulated with 1,2-dithiin (1) and 1,2-dithiin 1,1-dioxides (2) and (3) were successfully synthesized in satisfactory yields by the reaction of compound 6 with lithium aluminum hydride followed by treatment with chlorotrimethylsilane. The electrochemical properties of the biferrocenes (1)-(3) were furnished by voltammetric studies.     

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 2,5-dihydroimidazo[4,5-<Emphasis Type="Italic">e</Emphasis>][1,2,3]thiadiazine 1,1-dioxides—Derivatives of a novel heterocyclic system

5-Formyl-1H-imidazole-4-sulfonyl chlorides reacted with hydrazine hydrate or alkylhydrazines to give 2,5-dihydroimidazo[4,5-e][1,2,3]thiadiazine 1,1-dioxides.     

Synthetic Modification of 1,3-Thiazolidin-4-One 1,1-Dioxides

Abstract

The reactivity of EWG (electron withdrawing group)-activated methylene group in 1,3-thiazolidin-4-one 1,1-dioxides were investigated. Novel derivatives of 1,3-thiazolidin-4-one 1,1-dioxides were prepared (the heterocyclic core was modified with carboxamide and carboxthioamide moieties as carbonyl group analogues). The products, which have functional groups for possible future modifications, are described and characterized.     

N,N′-Linked 1,2-benzisothiazol-3(2H)-one 1,1-dioxides: synthesis, biological activity, and derived radicals

A number of N,N′-linked benzoannelated isothiazol-3(2H)-one 1,1-dioxides, not available via oxidation of isothiazolium salts, were obtained with good yields by reaction of N-amino heterocycles with 2-chlorosulfonylbenzoyl chloride and evaluated for their inhibitory activity toward human leukocyte elastase (HLE) and acetylcholinesterase (AChE). 2-(Phthalimid-1-yl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxide and 2-(2-methyl-4-oxo-3(4H)-quinazolinyl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxide were found to be inhibitors of HLE and tested as potential precursors of nitrogen-centered radicals using 266 nm laser flash photolysis.     

Regioselective construction of six-membered fused heterocyclic rings via Pd/C-mediated C-C coupling followed by iodocyclization strategy: a new entry to 2H-1,2-benzothiazine-1,1-dioxides

We describe a practical and elegant method of constructing a thiazine ring fused with benzene under mild reaction conditions. A variety of 4-iodo-2H-benzo[e][1,2]thiazine-1,1-dioxides were prepared with high regioselectivity via a two-step process involving Pd/C-mediated C-C coupling of o-halobenzenesulfonamides with terminal alkynes, followed by iodocyclization of the resulting o-(1-alkynyl)arenesulfonamide using elemental iodine in acetonitrile. The coupling reaction was carried out using 10% Pd/C-PPh₃-CuI as a catalyst system in the presence of Et₃N. The process worked well for bromides and iodides, and a wide array of terminal alkynes containing alkyl and aryl substituents were employed. The iodocyclization step tolerated a variety of functional groups such as hydroxy, chloro, cyano, and methoxy, producing the six-membered heterocyclic ring selectively. The resulting 4-iodo-2H-benzo[e][1,2]thiazine-1,1-dioxides participated in Sonogashira, Heck, and Suzuki reactions producing a wide range of functionally substituted benzothiazines in good yields.     

Synthese von basisch substituierten 2-Methyl-2,3-dihydro-benzo[b]thiophenen

N-substituted {2-methyl-benzo[b]thienyl-(3)}-acetamides were oxidized to the corresponding 1,1-dioxides, catalytic hydrogenation of which gave N-substituted {2-methyl-2,3-dihydro-benzo[b]thienyl-(3)}-acetamide-S,S-dioxides. The latter were reduced by LiAlH₄ to give N-substituted 2-methyl-3-(β-amino-ethyl)-2,3-dihydro-benzo[b]thiophenes.     

Synthesis of isomeric N-substituted 5-methyl-2H-1,2,6-thiadiazin-3(6H)one 1,1-dioxides from sulfamides and diketene

The reaction of N-n-butyl and N-benzylsulfamides with diketene in acetic acid solution in the presence of mercuric cyanide as a catalyst, afforded the corresponding 5-methyl-2-substituted-2H-1,2,6-thiadiazin-3(6H)one 1,1-dioxides. The reaction of the above mentioned sulfamides with diketene in an aqueous alkaline medium resulted in the isolation of the corresponding N-aceto-acetyl-N' -substituted-sulfamides, which were then converted into 5-methyl-6-substituted-2H-1,2,6-thiadiazin-3(6H)one 1,1-dioxides. Catalytic hydrogenation of the 5-methyl-2- and 6-n-butyl-2H-1,2,6-thiadiazin-3(6H)one 1,1-dioxides furnished the corresponding dihydro-derivatives. The structures of the isomeric 1,2,6-thiadiazine 1,1-dioxide derivatives obtained were assigned on the basis of nmr spectroscopic studies.     

Reaction of chlorosulfonylthiolene- and -thiolane-1,1-dioxides with amines and hydroxycompounds

Sulfonylamides and sulfonylesters of thiolene- and thiolane-1,1-dioxides are prepared by reaction of chlorosulfonylthiolene- and -thiolane-1,1-dioxides with amines and hydroxycompounds. The structure of the compounds is proved based on IR spectra and ¹³C NMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 475–478, April, 1989.     

Ringerweiterung von 1,2-Thiazol-3(2H)-on-1,1-dioxiden und 3-Amino-2H-azirinen zu 4H-1,2,5-Thiadiazocin-6-on-1,1-dioxiden

Ring Enlargement of 1,2-Thiazol-3(2H)-one-1,1-dioxides and 3-Amino-2H-azirines to 4H-1,2,5-Thiadiazocin-6-one-1,1-dioxides Reaction of 3-amino-2H-azirines 2 with the 1,1-dioxides 4 and 7 of 1,2-thiazol-3(2H)-ones and 1,2-thiazoli-din-3-ones, respectively, in i-PrOH at room temperature leads to 4H-1,2,5-thiadiazocin-6(5H)-one-1,1-dioxides 5 (Scheme 2, Table) and the corresponding 7,8-dihydro derivatives 8 (Scheme 4), respectively. The structure of some of the new 8-membered heterocycles as well as the structure of the minor by-product 6 (Scheme 3) have been established by X-ray crystallography (Chapt. 4). The proposed reaction mechanism for the ring expansion to 5 and 8 (Scheme 2) is in accordance with previously published results of reactions of 2 and NH-acidic heterocycles and is further supported by the results of the reaction of 4a and the (1-¹⁵N)-labelled aminoazirine 2a *.     

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).     

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.