Substitution, electrophilic sulfonation, mechanism

Unlike most other electrophilic substitution reactions, sulfonation shows a moderate isotope effect ordinary hydrogen (protium) is displaced from an aromatic ring about twice as fast as deuterium. Docs this mean that sulfonation takes place by a different mechanism than nitration, one involving a single step Almost certainly not. 

Aromatic sulfonation, like nitration, balogenation, alkylation, and acylation, is a typical electrophilic substitution reaction. Sulfonation, however, differs from these other reactions in two marked respects it is reversible, and reaction temperature can, in certain cases, have an important influence on the position of the entering group, as shown on p. 344. These characteristics have tended to complicate studies of the reaction mechanism and rate of sulfonation and to render difficult the drawing of general conclusions. Other factors having the same effect are the tendency of sulfur trioxide to form a complex with the sulfonic acids and the pronounced tendency of all Lubs, pp. 534ff. 

Complexation of bromine with iron(III) bromide makes bromine more elec trophilic and it attacks benzene to give a cyclohexadienyl intermediate as shown m step 1 of the mechanism (Figure 12 6) In step 2 as m nitration and sulfonation loss of a proton from the cyclohexadienyl cation is rapid and gives the product of electrophilic aromatic substitution... 

The azo coupling reaction proceeds by the electrophilic aromatic substitution mechanism. In the case of 4-chlorobenzenediazonium compound with l-naphthol-4-sulfonic acid [84-87-7] the reaction is not base-catalyzed, but that with l-naphthol-3-sulfonic acid and 2-naphthol-8-sulfonic acid [92-40-0] is moderately and strongly base-catalyzed, respectively. The different rates of reaction agree with kinetic studies of hydrogen isotope effects in coupling components. The magnitude of the isotope effect increases with increased steric hindrance at the coupler reaction site. The addition of bases, even if pH is not changed, can affect the reaction rate. In polar aprotic media, reaction rate is different with alkyl-ammonium ions. Cationic, anionic, and nonionic surfactants can also influence the reaction rate (27). 

Except for these studies of their protonation behavior, almost the only other aspect of the chemistry of sulfonic acids that has been investigated to any extent from a mechanistic point of view is the desulfonation of aromatic sulfonic acids or sulfonates. Since this subject has been well reviewed by Cerfontain (1968), and since the reaction is really more of interest as a type of electrophilic aromatic substitution than as sulfur chemistry, we shall not deal with it here. One should note that the mechanism of formation of aromatic sulfonic acids by sulfonation of aromatic hydrocarbons has also been intensively investigated, particularly by Cerfontain and his associates, and several... 

A historically important method, first used about 1900, is sulfonation of benzene followed by desulfonation with caustic. This is classic aromatic chemistry. In 1924 a chlorination route was discovered. Both the sulfonation and chlorination reactions are good examples of electrophilic aromatic substitution on an aromatic ring. Know the mechanism of these reactions. These routes are no longer used commercially. 

The addition reactions which were discussed in Sections 4.1 and 4.2 are initiated by interaction of a proton with the alkene, which causes nucleophilic attack on the double bond. The role of the initial electrophile can be played by metal cations as well. Mercuric ion is the reactive electrophile in several synthetically valuable procedures.12 13 The most commonly used reagent is mercuric acetate, but the trifluoroacetate, trifluoromethane-sulfonate, or nitrate salts are preferable in some applications. A general mechanism depicts a mercurinium ion as an intermediate.14 Such species can be detected by physical measurements when alkenes react with mercuric ions in nonnucleophilic solvents.15 Depending on the structure of the particular alkene, the mercurinium ion may be predominantly bridged or open. The addition is completed by attack of a nucleophile at the more substituted carbon ... 

Aromatic compounds react mainly by electrophilic aromatic substitution, in which one or more ring hydrogens are replaced by various electrophiles. Typical reactions are chlorination, bromination, nitration, sulfonation, alkylation, and acylation (the last two are Friedel-Crafts reactions). The mechanism involves two steps addition of the electrophile to a ring carbon, to produce an intermediate benzenonium ion, followed by proton loss to again achieve the (now substituted) aromatic system. 

Predict products and propose mechanisms for the common electrophilic aromatic substitutions halogenation, nitration, sulfonation, and Friedel-Crafts alkylation and acylation. Problems 17-44, 47, 48, 51, 59, G4, and 70... 

These steps illustrate how to generate the electrophile E for nitration and sulfonation, the process that begins any mechanism for electrophilic aromatic substitution. To complete either of these mechanisms, you must replace the electrophile by either or S03H in the general mechanism (Mechanism 18.1). Thus, the two-step sequence that replaces H by E is the same r ardless of E. This is shown in Sample Problem 18.1 u.sing the reaction of benzene with the nitronium ion. 

In al this we have estimated the stability of a carbonium ion on the same basis the dispersal or concentration of the charge due to electron release or electron withdrawal by the substituent groups. As wc shall see, the approach that has worked so well for elimination, for addition, and for electrophilic aromatic substitution works for still another important class of organic reactions in which a positive charge develops nucleophilic aliphatic substitution by the S l mechanism (Sec. 14.14). It works equally well for nucleophilic aromatic substitution (Sec. 25.9), in which a negative charge develops. Finally, we shall find that this approach will help us to understand acidity or basicity of such compounds as carboxylic acids, sulfonic acids, amines, and phenols. 

Aromatic rings can be sulfonated by reaction with fuming sulfuric acid, a mixture ofH2S04 and SO. The reactive electrophile is either HSO / or neu-i tral SO3, depending on reaction conditions. Substitution occurs by the sar two-step mechanism seen previously for bromination and nitration (Fig 16.7). Note, however, that the sulfonation reaction is readily reversible i can occur either forward or backward, depending on the reaction condition... 

Sulfonation is a bimolecular electrophilic substitution reaction (SE2) and the electrophile is sulfur trioxide.3a Sulfur trioxide is a powerful electrophile because of the electron-withdrawing effect of the three double-bonded oxygen atoms. Consequently, oleum (fuming sulfuric acid), which contains approximately 10% of excess sulfur trioxide, is a much more powerful sulfonating agent than concentrated sulfuric acid. Sulfur trioxide is a sufficiently powerful electrophile to attack benzene (23) directly. The mechanism of the sulfonation of benzene by hot concentrated sulfuric acid to give benzenesulfonic acid (24) is shown in Scheme 15.4a... 

Some reactions thought of as normal electrophilic substitution may in fact proceed by this mechanism. One example might be the sulfonation of 2-hydroxy-nicotinic acid used in the synthesis of a component27 190 of Pfizer s successor to Viagra 188. 

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