Sulfonation of pyridine

Succinic acid, 2,2-difluoeo-, 42, 44 SuCCINIMIDE, N-IODO-, 42, 73 Sulfonation of pyridine, 43, 97 Sulfur tetrafluoride, in conversion of carboxylic acids to 1,1,1-trifluoro compounds, 41, 104/ toxicity of, 41,105 / ... 

The sulfonate salts of the --deficient heterocycles will undergo many reactions typical of arenesulfonates, such as displacement by hydroxide, on fusion with alkali (e.g. Scheme 129), or by cyanide on fusion with potassium or sodium cyanide. Also, the sulfonation of pyridine is reversible when pyridine-3-sulfonic acid is heated with 100% sulfuric acid and mercury(II) sulfate at approximately 330 °C a mixture is obtained containing mainly pyridine (58RTC963). 

Sulfonation of pyridine affords the 3-sulfonic acid in 70% yield, but vigorous conditions (H2S04-S03, 230°C) and HgS04 catalyst are required (90AHC(47)310). The picolines form -sulfonic acids similarly. Sulfonation of pyridine at 360°C gives a considerable amount of the 4-sulfonic acid. Heating the 3-sulfonic acid at this temperature produces a similar result presumably, thermodynamic control takes over. 

Sulfonation of pyridine 1-oxide requires vigorous conditions (H2S04-S03-Hg2+, 230°C) and gives the 3-sulfonic acid (cf Section 3.2.1.4.1). 

Since sulfonation of pyridine iV-oxide is about as difficult as is that of pyridine itself and takes place at the 3-position,17 it has been assumed18 that, in fuming sulfuric acid, pyridine iV-oxide reacts only in the salt form (3), when the prediction is that substitution at C-3 would take place. It is, however, difficult to account for the fact that bromination, even at 110° in the presence of iron powder, does not occur.17 Bromination in chloroform solution in the presence of acetic anhydride and sodium acetate (when the O-acetate is the the probable substrate) take place readily, however, to give 3,5-dibromopyridine JV-oxide.19 The predicted order of nucleophilic reactivity, on the basis of both atom localization energies and ground-state v-electron density calculations, is 4 > 2 > 3. The same order is predicted for the nucleophilic substitution reactions of the salts of pyridine JV-oxide. In actual practice, iV-alkoxypyridinium derivatives undergo nucleophilic attack preferentially at C-2.20-23 The reaction of some pyridine iV-oxides with phosphorus pentachloride may involve the formation... 

Sulfonation of pyridine A-oxide requires the use of 20% fuming sulfuric acid and a mercuric sulfate catalyst with prolonged heating at 230°. Under these conditions, the main product is the 3-sulfonic acid (40-45%) together with small amounts of the 2- (0.5-1%) and 4-sulfonic acids (2-2.5%).214 2,6-Lutidine V-oxide reacts under similar conditions, substitution taking place at C-3.215... 

Propose a mechanism for the sulfonation of pyridine, pointing out why sulfonation occurs at the 3-position. 

Most heterocyclic nuclei undergo the sulfonation reaction. Sulfonation of pyridine is difficult. The yield of 3"pyridinesulfonic acid by sulfonation at 390° with oleum is only 13%. The yield is greatly improved by the use of vanadium or mercury salts as catalysts. A critical study of the factors influencing the yield has been made, and a maximum yield of 71% is reported. Fuming sulfuric acid converts quinoline to practically pure 8-quinolinesulfonic acid (54%). The action of concentrated sulfuric acid on dibenzofuran gives 2-dibenzofuransulfonic acid (75%). ... 

The method can also be applied to the conversion of 4-chloropyridine (49) to pyridine-4-sulfonic acid (50) (Scheme 28). In compound (49), the chlorine atom is activated to nucleophilic attack by the electron-withdrawing nitrogen atom. Scheme 28 is a useful synthetic sequence since direct sulfonation of pyridine only yields the 3-sulfonic acid as a consequence of the electrophilic nature of the nitrogen atom. Sulfonic acids can also be obtained by oxidation of sulfides, disulfides and sulfinic acids. The introduction of a sulfonic acid group into an organic molecule provides a useful method of increasing the aqueous solubility of the compound. Many sulfonic acids as their sodium salts are... 

Nitration in the 3-position with N205 and a sulfur nucleophile Scope, limitations and mechanism Sulfonation of Pyridines... 

In the sulfonation of pyridine with SO3 or oleum, the addition of a small percentage of mercury raises the yield from 50 to 71 per cent.i Mercury is also added in converting benzenedisulfonic to the trisulfonic acid. Both of these sulfonations are run under drastic conditions. 

Sulfonation of pyridine with oleum at 250°C with Hg(II) catalysis yields the pyridine-3-sulfonic acid 18 in 70% yield ... 

The effect of the Hg(II) in this reaction is attributed to A-coordination and suppression of the strongly deactivated A-protonation. Sulfonation of pyridine at 360°C or heating of 18 at this temperature yields the pyridine-4-sulfonic acid 19, which is indicative of a thermodynamic control of the 4-substitution. 

Pyridine-3-stdfonic acid is a crystalline compound with a molecular weight of 159.11 m.p. 357° its ammonium salt melts at 243°. It is prepared by sulfonation of pyridine with fuming sulfuric acid at temjieratures above 200°. The reaction at 225° with mercuric sulfate as catalyst delds only pyridine-3-sulfonic acid. 

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