Sulfonyl sulfur, nucleophilic substitution

Nucleophilic substitution at RSO2X is similar to attack at RCOX. Many of the reactions are essentially the same, though sulfonyl halides are less reactive than halides of carboxylic acids. The mechanisms are not identical, because a tetrahedral intermediate in this case (148) would have five groups on the central atom. Though this is possible (since sulfur can accommodate up to 12 electrons in its valence shell) it seems more likely that these mechanisms more closely resemble the Sn2 mechanism, with a trigonal bipyramidal transition state (148). There are two major experimental results leading to this conclusion. 

Reactivity toward nucleophiles and comparison with other electrophilic centers 152 Paths for nucleophilic substitution of sulfonyl derivatives 156 Direct substitution at sulfonyl sulfur stereochemistry 157 Direct substitution at sulfonyl sulfur stepwise or concerted 158 The elimination-addition path for substitution of alkanesulfonyl derivatives 166 Homolytic decomposition of a-disulfones 172 10 Concluding remarks 173 Acknowledgement 174 References 174... 

Earlier (Table 6, p. 119) we saw data on the reactivity of various nucleophiles toward an aryl sulfinyl sulfone in (139), a substitution that also involves an arenesulfinate as the leaving group, but one in which the substitution takes place at a sulfinyl ( S=0) rather than a sulfenyl ( S) sulfur. In Section 9 we present data on the rates of reaction of the same nucleophiles in an analogous substitution at a sulfonyl sulfur, Nu- + PhS02S02Ph - PhS02Nu + PhS02. At that point we will discuss how changing the oxidation state of the sulfur atom at which the substitution occurs... 

Rogne (1970) has measured the reactivity of some of the same nucleophiles toward benzenesulfonyl chloride in water at 25°. When log km for reaction of these nucleophiles with PhSOjCl is plotted vs. the log values for the same nucleophiles from Table 10, one obtains a good straight line relationship with a slope of about 0.8. This shows that the reactivity pattern observed with PhSOjSOjPh and shown in Table 10 is representative of what will be observed generally in nucleophilic substitution at the sulfonyl sulfur of reactive sulfonyl substrates. 

The reactions represented by (191) are all nucleophilic substitutions occurring at a sulfonyl sulfur. Besides cpdisulfones substitutions of this kind are also of frequent occurrence in the chemistry of many other types of sulfonyl derivatives such as sulfonyl halides, aryl esters of sulfonic acids, etc., and many of the general aspects of their behaviour and mechanism have been examined in considerable detail. Most of the remainder of this section will be devoted to consideration of the results of such studies. 

In contrast to the widely investigated stereochemistry of nucleophilic substitution at optically active tricoordinate sulfur, there have been few similar studies with optically active tetracoordinate sulfur systems. Sabol and Andersen (174) were the first to show that the reaction of p-tolylmagnesium bromide with (-)-menthyl phenyl-methane[ 0- 0]sulfonate 140 proceeds with inversion of configuration. Thus, the Grignard reaction at the sulfinyl and sulfonyl centers takes place with the same stereochemistry. 

The sulfonyl chloride is reactive towards nucleophilic substitution at sulfur. 

Sulfonic acids, like sulfuric acid, are much stronger acids than carboxylic acids. However, their chemical behavior resembles that of carboxylic acids in many other respects. Sulfonic acids form the same type of derivatives, sulfonyl chlorides, esters, amides, and so on, as do carboxylic acids. These derivatives are intercon-verted by nucleophilic substitution reactions that resemble those of carboxylic acid derivatives. 

Several thiols occur naturally for example, skunk secretion contains 3-methyll-butanethiol and cut onions evolve 1-propanethiol, and the thiol group of the natural amino acid cysteine plays a vital role in the biochemistry of proteins and enzymes (see Introduction, p. 2). Primary and secondary thiols may be prepared from alkyl halides (RX) by reaction with excess sodium thiolate (SN2 nucleophilic substitution by HST) or via the Grignard reagent and reaction with sulfur. Tertiary thiols can be obtained in good yields by addition of hydrogen sulfide to a suitable alkene. Thiols can also be prepared by reduction of sulfonyl chlorides (Scheme l).la,2a... 

Nucleophilic substitution reactions of anilines at a sulfonyl sulfur (tetra-coordinated sulfur) atom have been widely studied. Some of the works are presented in Table 9. 

In the nucleophilic substitution reactions of alkylsulfonyl chlorides and ring-substituted benzylsulfonyl chlorides, the operation of two competing reaction pathways has been established (a) E-A (sulfene) mechanism and (b) direct nucleophilic substitution at sulfur (general base catalysis). The relative significance of these competing mechanisms depends on the nature of the substrate and the precise reaction conditions. In the hydrolysis of cyclopropane-sulfonyl chloride 11 with tertiary amines in organic media, the sulfene 12 appears to be the crucial intermediate in the formation of cyclopropanesulfonic acid 13 (Equation 12). ... 

Organic sulfonate esters, like sulfonyl halides, also readily undergo nucleophilic substitution reactions as previously mentioned (p 23). For example, oxygen-labelled (-)menthyl phenylmethanesulfonate 18 reacted with / -tolylmagnesium bromide to give labelled benzyl p-tolyl sulfone 19 with inversion of stereochemical configuration at the chiral sulfur atom (Equation 16). 

On the other hand, reaction of the sulfonyl chloride 397 with excess morpholine, pyrrolidine and piperidine (three equivalents) afforded a mixture of the sulfonamides 400 and 401. The succinimidosulfonamide 401 was formed by simultaneous nucleophilic substitution at sulfur and Michael addition of the amine to the activated alkenic double bond. The pure maleimidosulfonamide 400 could be prepared by column chromatography of the mixture. The reaction of N- p-chlorosulfonylphenyl) maleimide 397 with excess dimethylamine or diethylamine in methanol as solvent resulted in the formation of ring-opened products. For instance, in the reaction with diethylamine, the methyl ester 402 was formed by base-catalysed nucleophilic ring-opening by the solvent (methanol) this ring... 

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