Sulfonation and Chlorosulfonation of Organic Compounds

Sulfonation is a bimolecular electrophilic substitution reaction (Se2) which may be depicted in general terms as shown (Equation 1)  

Sulfonation, unlike nitration, is a reversible process which enables the sulfonic acid group (SO3H) to be employed in organic synthesis as a blocking and orientation-directing group. An example is provided by the synthesis of o-nitroaniline 3 from acetanilide 4 (Equation 2). 

sulfonation of naphthalene with concentrated sulfuric acid at 80 C afforded 96% of the 1-sulfonic acid 5, whereas at 165 °C 85% of the 2-sulfonic acid 6 was obtained. 

In the sulfonation of monosubstituted benzenes by concentrated sulfuric acid, electron-donating substituents (X) such as acetamido, alkoxy, hydroxy or alkyl groups facilitate the reaction and, in such cases, sulfonation occurs under relatively mild conditions (0-35 C) to give a mixture of the o- and p-sulfonic acids (Equation 4). 

In sulfonation, disulfonation may occur and also formation of byproducts when free sulfur trioxide is present, e.g. sulfonic anhydrides (from intermolecular dehydration of monosulfonic acids or from intramolecular dehydration of ortho-disulfonic acids). Sulfones may also be produced by electrophilic substitution by the sulfonic acid or by the sulfonyl chloride when chlorosulfonic acid is the sulfonating reagent the latter reagent also tends to form sulfonyl chlorides as byproducts. 

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Sulfonyl chlorides (51) may also be obtained by heating the sulfonic acid or its sodium salt with thionyl chloride or phosphorus pentachloride (Scheme 31). The reaction with thionyl chloride is catalysed by the addition of a few drops of DMF. The chlorosulfonation of organic compounds may also be achieved by reaction with sulfur dioxide and chlorine this is an important industrial process (the Reed reaction) (Scheme 32). 

Trimethylsilyl chlorosulfonate 459 is useful as a mild sulfonating agent and it reacts with a range of organic compounds containing the trimethylsilyl group as illustrated by Equations 144-146. " It was by this synthetic route that cyclopropanesulfonic acid 460 was first prepared (Equation 145). The general mechanism of these reactions is depicted in Scheme 14. 

The presence of iodine is known to catalyse the chlorination of organic compounds by chlorosulfonic acid, enabling the reaction to proceed under comparatively mild conditions. So chlorination is a feature of the attempted sulfonation of aromatic iodo compounds with chlorosulfonic acid (see Chapter 2, p 19) for instance, reaction of />-diiodobenzene with excess reagent (five equivalents) at 50 C yields tetrachlorodiiodobenzene (82%), (Chapter 6, ref. 13). The chlorination is catalysed by traces of iodine and the reaction under these conditions probably involves both homolytic and heterolytic steps (see Chapter 4, p 49). Hexachloro-/7-xylene, by treatment with a mixture of chlorosulfonic acid, iodine and chlorine afforded either the 2,5-dichloro derivative or tetrachloro-terephthaloyl chloride depending on the experimental conditions (see Chapter 4, p 51). 

Continuous operations are feasible and practical (1) where the organic compound (benzene or naphthalene) can be volatilized, (2) when reaction rates are high (as in the chlorosulfonation of paraffins and the sulfonation of alcohols), and (3) where production is large (as in the manufacture of detergents, such as alkylaryl sulfonates). 

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