Sulfur trioxide electrophilic substitution

For example, 3-bromopyridine is formed when pyridine is reacted with bromine in the presence of oleum (sulfur trioxide in cone, sulfuric acid) at 130 °C (Scheme 2.4). Direct electrophilic substitution is not involved, however, aszwitterionic (dipolar) pyridinium-A-sulfonate is the substrate for an addition of bromide ion. Subsequently, the dihydropyridine that is formed reacts, possibly as a dienamine, with bromine to generate a dibromide, which then eliminates bromide ion from C-2. It is notable that no bromination occurs under similar conditions when oleum is replaced by cone, sulfuric acid alone instead, pyridinium hydrogensul-fate is produced. 

The preferred position for electrophilic substitution in the pyridine ring is the 3 position. Because of the sluggishness of the reactions of pyridine, these are often carried out at elevated temperatures, where a free radical mechanism may be operative. If these reactions are eliminated from consideration, substitution at the 3 position is found to be general for electrophilic reactions of coordinated pyridine, except for the nitration of pyridine-N-oxide (30, 51). The mercuration of pyridine with mercuric acetate proceeds via the coordination complex and gives the anticipated product with substitution in the 3 position (72). The bromina-tion of pyridine-N-oxide in fuming sulfuric acid goes via a complex with sulfur trioxide and gives 3-bromopyridine-N-oxide as the chief product (80). In this case the coordination presumably deactivates the pyridine nucleus in the 2 and... 

The range of preparatively useful electrophilic substitution reactions is often limited by the acid sensitivity of the substrates. Whereas thiophene can be successfully sulfonated in 95% sulfuric acid at room temperature, such strongly acidic conditions cannot be used for the sulfonation of furan or pyrrole. Attempts to nitrate thiophene, furan or pyrrole under conditions used to nitrate benzene and its derivatives invariably result in failure. In the case of sulfonation and nitration milder reagents can be employed, i.e. the pyridine-sulfur trioxide complex and acetyl nitrate, respectively. Attempts to carry out the Friedel-Crafts alkylation of furan are often unsuccessful because the catalysts required cause polymerization. 

Example 4.20. Electrophilic substitution of toluene by sulfur trioxide. 

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... 

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. 

In the preceding section, benzene reacted with cations to form substituted benzene derivatives. The cations of interest include Br+, C1+, the nitronium ion, and sulfur trioxide or sulfuric acid, which react as electrophiles. In principle, benzene may react with any cation, including carbocations, once that cation is formed. Carbocations are generated by several different methods they react with nucleophiles, as described for reactions of alkenes with acids such as HX (Chapter 10, Section 10.2) and for S l reactions (Chapter 11, Section 11.4). If benzene reacts with a carbocation, a new carbon-carbon bond is formed, and electrophilic aromatic substitution will give an arene. The reaction of benzene and its derivatives with carbocations is generically called the Friedel-Crafts reaction, after the work of French chemist Charles Friedel (France 1832-1899) and his American protege, James M. Crafts (1839-1917). The reaction takes two fundamental forms Friedel-Crafts alkylation and Friedel-Crafts acylation. Both variations will be discussed, beginning with the alkylation reaction. 

Propargylic Anion Equivalent. (TMS)allene reacts with electrophiles at the C-3 position in an Se2 process analogous to electrophilic substitution reactions of allyl- andpropargylsilanes. For example, upon treatment with trimethylsilyl chlorosulfonate or sulfur trioxide-1,4-dioxane, (TMS)allene yields silyl esters of sulfonic acids (eq 3). (TMS)allene undergoes conjugate addition with a, 8-unsaturated acyl cyanides to yield 5,e-acetylenic acyl cyanides. ... 

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. 

In two other typical electrophilic substitutions of benzene, the electrophiles are the nitronium ion (N02 ), leading to nitrobenzene, and sulfur trioxide (SO3), giving ben-zenesulfonic acid. 

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