Sulphones nucleophilic substitution reactions

As an alternative to the oxidation of sulphides and sulphoxides (see Chapter 10), sulphones can be prepared by the nucleophilic substitution reaction of the sulphinite anion on haloalkanes. In the absence of a phase-transfer catalyst, the reaction times are generally long and the yields are low, and undesirable O-alkylation of the sulphinite anion competes with S-alkylation. The stoichiometric reaction of the preformed tetra-n-butylammonium salt of 4-toluenesulphinic acid with haloalkanes produces 4-tolyl sulphones in high yield [1], but it has been demonstrated that equally good... 

Polymeric phosphonium salt-bound carboxylate, benzenesulphinate and phenoxide anions have been used in nucleophilic substitution reactions for the synthesis of carboxylic acid esters, sulphones and C/O alkylation of phenols from alkyl halides. The polymeric reagent seems to increase the nucleophilicity of the anions376 and the yields are higher than those for corresponding polymer phase-transfer catalysis (reaction 273). 

Nucleophilic substitution reactions of the secondary sulphonyloxy groups of sulphonate derivatives of cellulose have been investigated in hexamethyl phosphorus triamide using acetoxy-ions as the nucleophile. ... 

In Volume 13 reactions of aromatic compounds, excluding homolytic processes due to attack of atoms and radicals (treated in a later volume), are covered. The first chapter on electrophilic substitution (nitration, sulphonation, halogenation, hydrogen exchange, etc.) constitutes the bulk of the text, and in the other two chapters nucleophilic substitution and rearrangement reactions are considered. 

Nucleophilic substitution of toluene- -sulphonates (tosy-lates) and other sulphonic esters of secondary steroidal alcohols has received much attention, both in studies of reaction mechanisms, and also as a route for the conversion of alcohols into their epimers. One of the most important practical objectives has been the synthesis of 3a-hydroxy-5a-steroids, which include androsterone and a wide variety of metabolites of the steroid hormones, Tosylates of equatorial 3jS-alcohols (15) give 3a-alcohols or their derivatives (16) in acceptable... 

Many steroid secondary alcohols are resistant to acid-catalysed dehydration, but can be converted into olefins by elimination reactions of their sulphonate esters, usually the toluene 3 -sulphonate ( tosylate ) or methanesulphonate ( mesylate ). These elimination reactions always accompany attempted nucleophilic substitution of the sulphonate (p. 41), and can be made to predominate by appropriate choice of reaction conditions. Activated alkaline alumina has been used to prepare A - and AH-olehns from the sulphonates of 3 - [131] and i2a-alcohols [132]. In the latter case the naphthalene-i-sulphonate was most effective, and the methanesulphonate distinctly less so, suggesting that steric acceleration occurs with the more bulky naphthalenesulphonate [ 132c]. This view is strengthened by the enhanced efficiency of elimination of a i2a-sulphonate in the presence of a 17a-methyl group, which increases the compression at C(i2) [132b]. The mechanism and stereochemical features of these heterogeneous reactions have not been described in detail. 

Reaction of nitrosyl disulphonate, 0N(S03), with hydroxylamine-N-sulphonate is reported to be subject to catalysis by ferric salts at low concentrations, and to depend on the alkalinity through the hydrolysis of the catalyst . In mildly alkaline solution (pH 6-11), the rates of decomposition of this sul-phonate have been shown to be consistent with the existence of two reaction paths, one forming NO and the other sulphite radicals . The processes are assumed to represent bimolecular nucleophilic substitution by water. 

The above brief outline indicates that secondary deuterium isotope effect studies provide a powerful supplementary isotopic technique, shedding new light on obscure kinetic problems encountered in nucleophilic solvolytic substitution reactions with sulphonate esters215-217. 

Reactivities of brosylates, mesylates and tosylates are similar (Table 3), and show relatively small variations with solvent and alkyl group (R). Tosylate/mesylate rate ratios vary from 0.5 to 2.0 in S l solvolytic reactions of adamantyl sulphonates48. Slightly higher ratios may be observed for SN2 reactions in dipolar aprotic solvents, e.g. second-order rate constants for nucleophilic substitution in n-octyl sulphonates by thiocyanate anion show tosylate/mesylate rate ratios increasing from 0.7 in methanol to 1.5 in chlorobenzene and in cyclohexane, and to 4.4 in DMSO12. 

Hammett treatment showed that substitution in the phenyl ring of the sulphone influenced the reaction more than substitution in the thiol, indicating that the transition state resembles a carbanion intermediate. The second-order rate constant for the nucleophilic addition of p-MeCgH4S-to phenyl vinyl sulphone has been detected at 0-45°C, the energy, free... 

The t-butylsulphonyl group readily undergoes nucleophilic displacement by RS and RO groups, making this a preparatively useful route. t-Butyl 3-thienyl sulphone is also easily dimetalated in the 2- and 5-positions. The dialdehyde formed upon reaction with DMF does not, however, undergo nucleophilic substitution. 

Miscellaneous reactions of cr-sulphonyl carbanions with electrophiles include processes involving arylsulphonylmethyl methyl ether anions, cr-sulphinyl sulphone anions, perfluorobutylsulphonylmethylmagnesium halides, nucleophilic substitution in aromatic nitro-compounds by cr-halogenosulphonyl... 

Ring Substitution of Aryl Sulphones.—The influence of the sulphonyl group on reactions of substituted phenyl sulphones has been studied in relation to nucleophilic substitution of p-h dogenophenyl aryr or trifluoromethyl aryl sulphones/ by phenoxide anions and other species. 

The reaction mechanism(Following fig.) involves the alcohol oxygen acting as a nucleophilic centre and substituting the chloride ion from the sulphonate. The base then removes a proton from the intermediate to give the sulphonate product. Neither of these steps affects the... 

Pyrrole anion is unreactive in liquid ammonia under irradiation with PhBr or 1-chloro-naphthalene. However, the reactions of aryl chlorides (p-chlorobenzonitrile, 3- and 4-chloropyridines and 4-chlorodiphenyl sulphone) with 2,5-dimethylpyrrole anion under electrochemical inducement in the presence of a redox mediator gave the C3-substituted product in moderate yields (35-40%) (equation 120)225. The rate constant of the coupling reaction between this nucleophile and aryl radicals is about 5-8 x 109 M"1 s 1 determined by electrochemical methods225. 

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