Pyridine 1-oxide sulfonation

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... 

Keywords Alkyl hydroperoxides Amination Ammonia Benzimidazole Benzisoxazole Carbanions Heterocycles Hydroxylation Indole Nitro compounds Nucleophiles Nucleophilic substitution Oxidation Phenazine Potassium permanganate Pyridine Quinoline Sulfones Vicarious... 

Sulfation by sulfamic acid has been used ia the preparation of detergents from dodecyl, oleyl, and other higher alcohols. It is also used ia sulfating phenols and phenol—ethylene oxide condensation products. Secondary alcohols react ia the presence of an amide catalyst, eg, acetamide or urea (24). Pyridine has also been used. Tertiary alcohols do not react. Reactions with phenols yield phenyl ammonium sulfates. These reactions iaclude those of naphthols, cresol, anisole, anethole, pyrocatechol, and hydroquinone. Ammonium aryl sulfates are formed as iatermediates and sulfonates are formed by subsequent rearrangement (25,26). 

Hydroxylamine-O-sulfonic acid for N-amination of pyridine, 43, 1 Hydroxylation of indene, 41, 53 2-Hydroxy-3-methylbenzoic add, oxidation to 2-hydroxyisophthalic acid by lead dioxide, 40, 48 Rydroxymethyleerrocene. 40, 52... 

All of the sulfone diols were able to form oligomers in the second step of the reaction sequence, the Ullmann ether synthesis. As with the synthesis of the mono(bromophenoxy)phenol products, two methods were used to form the dibromo materials. Method A used pyridine, potassium carbonate and cuprous iodide, while Method B employed collidine and cuprous oxide with the dibromobenzene and higher molecular weight diol (IV). The major difference between the syntheses of the mono(bromophenoxy)phenols described earlier and these lies in the stoichiometry of the reactions. In order to... 

Bromination of (-)-(5 )-benzyl methyl sulfoxide 34 with bromine in pyridine affords a mixture of two regioisomers a-bromomethyl benzyl sulfoxide 328 and a-bromobenzyl methyl sulfoxide 329, in a molar ratio of 3 2 (325). Oxidation of thp latter gives the corresponding sulfone (-)-(S)-330, the absolute configuration of which was determined by X-ray analysis. In this context, it is interesting to point out that the formation of the sulfoxide 328 is accompanied by retention at sulfur, whereas 329 is formed with inversion at sulfur. 

A rare case of asymmetric induction caused by isotopic substitution was observed (326) when optically active (+)-() )-a,a-dideuteriodi-benzyl sulfoxide 331 was chlorinated with dichloroiodobenzene in pyridine, a,a-Dideuteriobenzyl a -chlorobenzyl sulfoxide 332 was obtained as a major regioisomer with at least 78% isotopic purity. The high stereospecificity of the reaction is indicated by formation of essentially only one of the possible diastereomers. Oxidation of sulfoxide 332 affords the sulfone 334, which has high optical rotation. 

Shono et al. (1979) recommend the use of thioanisole as a catalyst that allows lowering the electrode potential in the oxidation of the secondary alcohols into ketones. The cation-radical of thioanisole is generated at a potential of up to +1.5 V in acetonitrile containing pyridine (Py) and a secondary alcohol. (The background electrolyte was tetraethylammonium p-toluene sulfonate.) Thioanisole is recovered and, therefore, a ratio of RXR )CHOH PhSMe = 1 0.2 is sufficient. The yield of ketones depends on the nature of the alcohol and varies from 70 to 100%. 

Methacycline Methacycline, 4-dimethylamino-l,4,4a,5,5a,6,ll,12a-octahydro-3,6,10, 12,12a-pentahydroxy-6-methylen-l,ll-dioxo-2-naphthacencarboxamide (32.3.6), is synthesized from oxytetracycline (32.3.2), which is reacted with a sulfur trioxide— pyridine complex, resulting in an oxidation reaction. Simultaneous sulfonation gives a naphthacen-snlfotetrahydrofuran derivative intermediate (32.3.5), which when reacted with hydrofluoric acid forms methacycline (32.3.6) [222-225]. 

Japanese workers have also displaced a methyl sulfone group with a variety of nucleophiles. Thus they were able to introduce, ethoxy, thiophenyl, aniline, and malonic acid groups in to the pyridine A -oxide derivative (105). Acid hydrolysis produced the 2-one compound, while reduction with sodium borohydride cleaved off the methylsulfone group <87CPB1030>. 

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