Sulfur trioxide adduct, pyridine

The pyridine-sulfur trioxide adduct is a valuable reagent for the sulfonation of acid sensitive substrates like the heterocycles furan and pyrrole, which are polymerised by strong acids like sulfuric acid. Pyridine-sulfur trioxide thus converts furan (40) and pyrrole (41) into the corresponding 2-sulfonic acids (Scheme 21). 

Nitration of l-phenylpyrazolo[3,4-i>]quinoxalines occurs in the para-position of the pendent phenyl ring. Reduction of the nitro group followed by diazotization and coupling with, for example, 8-naphthol has given several azo dyes. Sulfonation of the parent heterocycle with the pyridine-sulfur trioxide adduct again provides 3-substituted products. 

The powerful oxidizing action of sulfur trioxide can be overcome by using the sulfur trioxide addition compounds mentioned above (page 612) their activity in sulfonation depends on their stability.167 Disulfur hexaoxide or its adducts to mineral acids (e.g., H2S207) are more powerful sulfonating agents than the stable adducts to dioxan55,101 or tertiary amines very mild conditions can be used with the latter 172 compounds that are especially sensitive to acids can be sulfonated by the pyridine-sulfur trioxide adduct without decomposition. 

Pyridine-sulfur trioxide adduct 173 Pyridine (1 mole) is added, with stirring and good cooling, to sulfur trioxide (1 mole) in three parts of carbon tetrachloride. The adduct produced is filtered off, washed with a little ice-water (to remove small amounts of pyridinium sulfate), and dried. The yield is about 90%. 

Heterocyclic compounds, in particular, are readily sulfonated by the pyridine-sulfur trioxide adduct 2-pyrrolesulfonic acid is formed from pyrrole,174 and 5-acetyl-3-pyrrolesulfonic acid from 2-acetylpyrrole.175... 

Furansulfonic acid176 provides an example Pure furan, b.p. 31.2-31.5°, is prepared from technical furan by way of the maleic anhydride adduct, which is then decomposed at 140 to 150°. This furan is treated with the pyridine-sulfur trioxide adduct in a bomb-tube for 8-10 h at 100°. This product is treated with a paste of barium carbonate in water for 30-40 min, then filtered hot, and concentrated, and the barium sulfonate is precipitated by ethanol. The following yields are obtained from 1.9 g of furan with 4.4 g of pyridine-sulfur trioxide 30%, with 8.8 g 56%, and with 13.4 g 90%, S-Benzylthiouronium 2-furansulfonate melts at 205°. 

Indole (benzopyrrole) 9 is sulfonated by treatment widi the pyridine-sulfur trioxide adduct to avoid acid-catalysed polymerization. If the reaction is conducted at low temperature, iV-sulfonation occurs to give the 1-sulfonic acid 10, whereas at 120 C, the reaction gave indole-3-sulfonic acid 11 (Scheme 1). ... 

Pyridine 23 (two equivalents) reacts with chlorosulfonic acid in an inert organic solvent, e.g. carbon tetrachloride, to yield equimolar quantities of the pyridine-sulfur trioxide complex and pyridinium chloride this behaviour is typical of the reaction of a tertiary amine with the reagent (see Chapter 4, p 101). The potentiometric curve for the neutralization of chlorosulfonic acid by pyridine in nitromethane has been determined and showed two steps. Pyridine 1-oxonium chloride similarly yields the pyridine-sulfur trioxide adduct on treatment with chlorosulfonic acid. ... 

Sulfur trioxide reactivity can also be moderated through the use of SO adducts. The reactivity of such complexes is inversely proportional to their stabihty, and consequentiy they can be selected for a wide variety of conditions. Whereas moderating SO reactivity by adducting agents is generally beneficial, the agents add cost and may contribute to odor and possible toxicity problems in derived products. CeUulosic material has been sulfated with SO.—trimethyl amine adduct in aqueous media at 0 to 5°C (16). Sulfur trioxide—triethyl phosphate has been used to sulfonate alkenes to the corresponding alkene sulfonate (17). Sulfur trioxide—pyridine adduct sulfates oleyl alcohol with no attack of the double bond (18). 

A second synthetic technique has employed either pyridine or dioxane adducts of sulfur trioxide as sulfonating agents. Both ferrocene and ferrocenecarboxylic acid have been sulfonated in this manner (61, 72). Cyclopentadienylmanganese tricarbonyl is also readily sulfonated (10). 

Related to, but quite distinct in purpose from, the usual notions of masking is the use of coordination to moderate the action of a very vigorous Lewis acid. An example of this may be seen in the use of the pyridine and dioxane complexes of sulfur trioxide in place of the parent compound 19), Because the complexes used here must release sulfur trioxide to other reactants, it is imperative that no reaction beyond coordination occurs. Thus, pyridine reacts only to give the adduct below. 

The sulfur trioxide is not used in the free state but in the form of an adduct with, e.g., pyridine, dimethylformamide, or dioxane the yields of sodium alkyl sulfonates obtained after alkaline hydrolysis are up to about 70%. 

Chlorosulfonic acid, and in particular adducts of sulfur trioxide with dioxan or pyridine have been used for aliphatic sulfonation. These adducts, which are to be considered as betaine-like internal oxonium salts, very easily transfer... 

Sulfur trioxide is a strong Lewis acid and reacts with Lewis bases (indicated below as L) such as pyridine and triphenylphosphine to give stable adducts ... 

E.E. Gilbert, Chem. Rev., 1962, 62, 549 (reviews the sulfonation of organic compounds by sulfur trioxide and its adducts with, for example, dioxan, pyridine, triethylamine). 

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