Benzo thiophene 2,2-dioxides

H. Benzo[ >]thiophene- 1,1-dioxides 1. From Thiophene-1,l-dioxides... 

The cycloaddition of a variety of sulfur heterocycles to alkenes has also been reported. Dibromomaleic anhydride undergoes [ 2 + 2] cycloaddition to thiophen295 and to benzo[b]thiophen.296 The photoaddition of benzo-[(>]thiophen 1,1-dioxides to alkenes also affords cyclobutane derivatives.297 Of particular interest is the addition of 3-acetoxybenzo[6]thiophen (350) to cyclohexene to give the adduct (351), which on treatment with base, undergoes a retro-aldol ring opening to benzo[6]thiepinone (352).298 A mixture of stereoisomeric cyclobutane derivatives were obtained on irradiation of 2,6-diphenyl-4//-thiopyran-4-one 1,1-dioxide in cyclohexene.299 The [ 2 + 2] cycloaddition of sulfolen to maleic anhydride and to maleimide has been reported.300... 

Diels-Alder cycloadditions of thiophene-1,1-dioxides with cyclopentadiene can take place either in the (2-1-4) or (4-1-2) mode depending on whether the thiophene dioxide has two or one electron-withdrawing substituents <2006T4139>. 1,3-Dipolar cycloaddition of benzo[/)]thiophene 1,1-dioxide with azomethine ylides has been reported <2006TL5139>. 

Benzo[ ]thiophene 1,1-dioxides could be also prepared by the following reductive methods (Scheme 4) [65-67]. 

A report in 1974 claimed that benzo[ ]thiophene 1,1-dioxide 38 reacted with diazomethane at room temperature to give the adduct 48 in a good yield, which isomerized to 49 on heating [124]. However, a more recent report proposed the isomeric structure 50 to this adduct based on H NMR analyses (Scheme 25) [125]. The adduct 50 was converted into compound 51 on photolysis [126]. Also reported was the reaction of the dioxide 52 with methyldiazomethane (Scheme 26) [125]. 

As a typical cyclic a,/ -unsaturated sulfone, benzo[ ]thiophene 1,1-dioxide 38 participates in [2+4] cycloadditions (Scheme 31) [135]. 

Benzo[ ]thiophene 1,1-dioxide 38 and its derivatives act as typical a, ft-unsaturated sulfones, and a variety of nucleophiles add to the carbon atom at the 3-position. Thus, amines and the conjugated bases of water, alcohols, thiophenol, and diethyl malonate all add to 38 to give the corresponding adducts 110 in excellent yields (Scheme 65) [189]. Even hydrogen bromide can add to 38. When 2-bromobenzo[b]thiophene 1,1-dioxide 111 was treated with piperidine and morpholine under appropriate conditions, excellent yields of adducts 112 were isolated without being accompanied by dehydrobromination (Scheme 66) [190]. 

Bromobenzo [ ] thiophene 1,1-dioxide 117 and 3-bromo-2-phenylbenzo-[b]thiophene 1,1-dioxide 119 reacted with ammonia and primary and secondary amines to give the corresponding 3-aminobenzothiophene dioxides, 118 and 120, in good yields (Scheme 68) [17, 192-194]. 2-Benzoyl-3-chloro-benzo[ ]thiophene 1,1-dioxide 121 also reacted with a series of nitrogen nucleophiles to give substitution products 122 in good yields (Scheme 69) [195]. 

Michael addition of appropriate nucleophiles to benzo [ ] thiophene 1,1-dioxides followed by intramolecular condensation leads to the formation of heterocycle-annelated benzothiophene 1,1-dioxides. Thus, a wide variety of heterocycle-annelated compounds such as 138-142 were synthesized by addition of nucleophiles to 2-benzoyl-3-chlorobenzo[b] thiophene 1,1-dioxide 121 (Scheme 75) [195,203,204]. 

Monocyclic thiophene 1,1-dioxides [186, 232] and benzo [ ] thiophene 1,1-dioxide [233] are reduced to the corresponding thiophenes by zinc in a mixture of acetic acid and hydrochloric acid (Scheme 92). Dibenzothiophene 5,5-dioxide is reduced to dibenzothiophene in many ways (Scheme 93) BuLi/NaH in ether/THF [234], NaH/ferf-AmONa/Ni(OAc)2/2,2 -bipyridyl in DME [235], LiAlH4/nickelocene in THF [236], and S8 (320°C) [237] are the reagents used for this conversion. 

Benzo[fr]thiophene 1,1-dioxide and its derivatives are reduced to the corresponding 2,3-dihydro derivatives by catalytic hydrogenation in good yields (Scheme 94). In this reduction, the sulfonyl moiety remains unchanged [13,189, 238, 239]. However, reduction of benzo[ ]thiophene 1,1-dioxide with LiAlH4 affords deoxygenated 2,3-dihydrobenzo[ ]thiophene in 79% yield [233]. Benzo[fr]thiophene 1,1-dioxide was also reduced to the 2,3-dihydro derivative by an electrochemical method (Scheme 95) [240]. 

Oxidation of benzo[b] thiophene 1,1-dioxide with KMn04 affords the sulfonic acid 172 [189], while oxidation with alkaline H202 yields the ketone 173 (Scheme 97) [244]. Oxidation of 3-substituted benzo[ ]thiophene 1,1-dioxides 174 with alkaline H202 affords the alcohols 175 as the principal product (Scheme 98) [244]. Compounds 173 and 175 are presumably formed through Michael addition of HOO to the 3-position of the substrates. Indeed, the reaction of 3,4-di-ferf-butylthiophene 1,1-dioxide 83 with H202 under alkaline conditions at room temperature afforded the Michael adduct 177 in 91 % yield, while the reaction carried out at 50-60 °C gave the ring-opened product 178 in 15% yield in addi-... 

Reaction at Sulphur.—The oxidation of benzo[6]thiophens to sulphoxides by t-butyl hypochlorite has been studied. In the presence of a ruthenium catalyst, dibenzothiophen was oxidized by oxygen to the sulphone. The reactions of benzo[ >]thiophen 1,1-dioxides with various reagents such as amines, amino-alcohols,3-aminopropylsilanes, and aromatic sulphonyl chlorides have been studied. Four detailed papers on the reaction of dibenzophenonium salts with aryl-lithiums have appeared in which the mechanism of ligand exchange was elucidated. " ... 

The two principal categories of compounds studied have been diaryl or aryl alkyl sulphones (not dialkyl sulphones, which are polarographically not reducible) and S-dioxides of certain heterocyclic compounds, such as thiophene (also benzo- and dibenzothiophenes) and phenothiazines. The first named have half-wave potentials in the region of — 2.0 V, the thiophene dioxides near — 1.0 V. Some examples of each category may be given. 

Q Why should thiophene 1.1-dioxide behaves as a diene in cycload-dition reactions, whereas benzo[/))thiophene . I-dioxide acts as a dienophilc ... 

During thermal dimerization of thiophene dioxides, one molecule functions as the 2ir-component and the other as the 477-component (B-67MI31401, 70AHC(11)177>. The initially formed dimer (513) eliminates a molecule of S02 to form the dihydrobenzo[6]thiophene (514) when R is chlorine, aromatization occurs by loss of HC1. Pyrolysis of benzo[6]thio-phene 1,1-dioxide at 185-200 °C similarly leads to (515). 

Benzo[Z> jthiophene 1,1-dioxide cycloadds to acetylenedicarboxylic ester to yield naphthalene-1,2-dicarboxylic ester after extrusion of S02. However, maleic anhydride and benzoquinone are reported not to react with benzo[Z>]thiophene dioxide (70AHC(ll)l77). 

The normal reactions of benzo[6]thiophene 1,1-dioxides have been reviewed (70AHC(11)177). Electrophilic substitution (nitration, bromination) takes place at position 6. 3-Halo derivatives undergo normal nucleophilic displacement reactions, but 2-bromobenzo[6]thiophene dioxide gives the 3-ethoxy derivative in ethanolic NaOH. The reaction of 3-methoxy derivatives with secondary amines can give rise either to enamines... 

Similarly, 3-oxospiro[benzo[ ]thiophene-2(3//)-T-cyclopropane] 5 ,5-dioxides 3 and 4 were synthesized starting from phenyliodonium ylide 2 and alkenes with catalysis by bis(acetyl-acetonato)copper(II).49 The ylide is easily obtained in 95% yield from 3-oxo-2,3-dihydro-benzo[6]thiophene 1,1-dioxide and bis(trifluoroacetoxy)iodobenzene. 

Other examples of heterocycle-annelation using a carboxylic acid or an acid chloride derivative of benzo[b] thiophene dioxides are given below (Scheme 76) [205-207]. ... 

Benzo[Z>]thiophen 5-Oxides. - Mild methods for the oxidation of 2,3-dihydrobenzo[Z>] thiophens to the sulphoxide have been developed. The photochemical reactions of various 2- and 3-substituted benzo[ ]-thiophen 1-oxides led to different photodimers. From 3-chlorobenzo[b]-thiophen-2-carboxylic acid 1,1-dioxide, 1,3-oxazinones of biological interest were obtained through cyclization reactions with cyanamides and carbodi-imides. Secondary amines add to 2-phenylbenzo [b] thiophen 1,1-dioxide to give 3-amino-substituted 2,3-dihydro-2-phenylbenzo[b]thiophen 1,1-dioxides. " ... 

Bordwell et a/.354 358 have made an extensive study of the rearrangement reactions brought about by nucleophilic attack on a range of substituted halogenobenzo[b]thiophene-1,1-dioxides. 3-Chloromethyl- and 2-bromo-3-methylbenzo[b]thiophene-l,1-dioxide each give the same product with piperidine, the structure of which (Ref. 2, p. 358) has now been amended to 84 (R1 = R2 = H). With piperidine, 2-bromo-3-ethyl- and 2-ethyl-3-bromo-benzo[/>]thiophene-l,1-dioxides give amines 82a and 82b, respectively.354... 

Taking together the biological activity, the physicochemical and toxicological data, N-Cyclohexyl-benzo-thiophen-2-carboxamid-S,S-dioxid was the best candidate for the use in waterbased emulsion paints and was developed as Preventol TP OC 3082 and TP OC 3061 by Bayer. As can be seen from Table 2, it has a broad fungicidal and a slight algicidal activity. 

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