Protonated sulfur trioxide

Sulfur trioxide (rather than protonated sulfur trioxide) could also act as the electrophile in these reactions. 

In aromatic sulfonation reactions (eq. 4.19), we use either concentrated or fuming sulfuric acid, and the electrophile may be sulfur trioxide, SO3, or protonated sulfur trioxide, SOjIT. The following resonance structures demonstrate that SO3 is a strong electrophile at sulfur. 

According to Figure 3, hydroperoxides are reduced to alcohols, and the sulfide group is oxidized to protonic and Lewis acids by a series of stoichiometric reactions. The sulfinic acid (21), sulfonic acid (23), sulfur trioxide, and sulfuric acid are capable of catalyzing the decomposition of hydroperoxides to nonradical species. 

Koeberg-Telder and Cerfontain (1975) also examined the nmr behavior of both CH3S03H and p-BrC6H4S03H in fuming sulfuric acid. They felt that the changes observed in the nmr spectra were best accounted for by a combination of protonation of the sulfonic acid to RS03HJ (161) and reaction of the sulfonic acid with sulfur trioxide to form the pyrosulfonic acid RS03S03H (162). 

One of the first compounds to be introduced to the clinic, aztreonam (40-9), has been produced by total synthesis. Constmction of the chiral azetidone starts with amide formation of L-threonine (40-1) via its acid chloride treatment with ammonia leads to the corresponding amide (40-2). The primary amino group in that product is then protected as its carbobenzyloxy derivative (40-3). Reaction of that product with methanesulfonyl chloride affords the mesylate (40-4). Treatment of that intermediate with the pyridine sulfur trioxide complex leads to the formation of the A -sulfonated amide (40-5). Potassium bicarbonate is sufficiently basic to ionize the very acidic proton on the amide the resulting anion then displaces the adjacent mesylate to form the desired azetidone the product is isolated as its tetrabutyl ammonium salt (40-6). Catalytic hydrogenation over palladium removes the carbobenzyloxy protecting group to afford the free primary amine (40-7). The... 

In contrast, the acid-catalyzed hydrolysis of alkyl selenates is A-2158. The actual species which undergoes decomposition to alcohol and sulfur trioxide is probably the zwitterion as in the case of phosphate monoester monoanions. Evidence for sulfur trioxide as the reactive initial product of the A-1 solvolysis is obtained from the product compositions arising with mixed alcohol-water solvents. The product distribution is identical to that found for sulfur trioxide solvolysis, with the latter exhibiting a three-fold selectivity for methanol. Although the above entropies of activation and solvent deuterium isotope effects do not distinguish between the conventional A-l mechanism and one involving rate-limiting proton transfer, a simple calculation, based on the pKa of the sulfate moiety and the fact that its deprotonation is diffusion controlled. 

The available studies imply that general catalysis will be operative in systems involving sulfate monoesters and potential six-membered ring transition states. Salicyl sulfate hydrolyzes at pH 4 via intramolecular carboxyl group participation involving pre-equilibrium proton transfer leading to sulfur trioxide expulsion (Fig. 9)2HH, viz. 

The details of protonation of several alkyl-substituted phenanthrenes by superacids have been reported.73 The observed mono- and di-cations are usually in agreement with those predicted by AMI MO calculations. Molecular modelling studies have suggested a multi-step pathway for the sulfonation of toluene widi sulfur trioxide.74 Intermediate 71-complcx. Wheland intermediate and pyrosulfonate species (34) are suggested, the product (p-toluenesulfonic acid) arising from an exothermic reaction between toluene and the acid (35) fonned by a facile prototropic rearrangement of (34). The sulfur trioxide monosulfonation of isopyrene and some derivatives leads usually to sulfonated... 

Desulfonation follows the same mechanistic path as sulfonation, except in the opposite order. A proton adds to a ring carbon to form a sigma complex, then loss of sulfur trioxide gives the unsubstituted aromatic ring. Excess water removes SO3 from the equilibrium by hydrating it to sulfuric acid. 

The strongly electrophilic sulfur trioxide is then added to the hydroxyl group and the intermediate oxonium ion is decomposed to sulfate ester and proton ... 

The cationic intermediate can also be formed by the protonation of sulfur trioxide, SO3, and another way to do sulfonations is to use concentrated sulfuric acid with S03 added. These solutions have the industrial name oleum. It is possible that the sulfonating agent in all these reactions is not protonated SO3 but SO3 itself. 

A study of the reaction of sulfur trioxide with water clusters has also been made (4). The ion clusters observed in these experiments were a series of protonated water clusters H+(H20)n with n up to 14 and another less abundant series of the form S03(H20)nH+ with n up to 9. The H+(H20)n series could result from the ionization of unreacted water clusters and also from the ionization of S03(H20)m clusters. The relative distribution of the H+(H20)n series, however, was not appreciably affected by the introduction of SO3. The distribution was very similar... 

In sulfonation, protonation of sulfur trioxide, SO3, forms a positively charged sulfur species ( S03H) that acts as an electrophile (Mechanism 18.4). 

The methyne proton of tris(pyrazolyl)methane is sufficiently acidic to be removed by raBuLi, and the resulting reactive intermediate readily reacts with electrophiles. Klaui prepared two new anionic tripodal nitrogen water-soluble ligands (the lithium salts of tris(pyrazolyl)- and tris(3-tert-butylpyrazol)-methanesulfonic, Tpms and Tmps B" respectively) by addition of lithiated tris(pyr-azolyl)methane to a sulfur trioxide-trimethylamine complex (Scheme 25).146... 

As the following mechanism shows, a substantial amount of electrophilic sulfur trioxide (SO3) is generated when concentrated sulfuric acid is heated, as a result of the SO3H electrophile losing a proton. Take a minute to note the similarities in the mechanisms for forming the SOsH electrophile for sulfonation and the T J02 electrophile for nitration. 

Note that as the water molecule attaches to sulfur trioxide, a proton shift occurs to form suifuric acid. 

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