Selective ortho-methylthiomethylation of phenols with dimethyl sulphoxide and thionyl chloride

Abstract

Thionyl chloride and phenyl chlorosulphinate have been shown to be useful activators for dimethyl sulphoxide in the selective preparation of ortho-methylthiomethylphenol via a [2,3]sigmatropic rearrangement. By this process, ortho-methylthiomethylated phenols having a variety of 2or 4substituents (Me, CI, OMe, NOz, and C0,Me) have been prepared in good yields. In contrast, similar reactions of 3-substituted phenols were affected by the electronic characters of the substituents. With more electron-donating groups such as OH and OMe in the 3-position, none of the expected products were obtained, but in the case of other 3-substituted phenols, two possible rearrangement products were obtained in moderate yields. o-Alkylphenols are useful intermediates in organic synthesesand there are many methods ' for the alkylation of phenol nuclei.In most cases, however, the products are mixtures of o-and psubstituted and polysubstituted phenols. The most effective procedure for selective ortho-alkylation of phenols seems to be that which involves a [2,3]sigmatropic rearrangement of a sulphonium ylide (4), the latter being generated oia abstraction of a proton from a sulphonium salt (3).

A Synthesis‐Driven Structure Revision of Berkelic Acid Methyl Ester

“…[18] Oxidation of the resulting diastereomeric alcohols 29 furnished (22S)-23 b. Even though this final oxidation turned out to be difficult and was plagued by formation of the corresponding methylthiomethyl adduct 30 (Scheme 7), [19] the final product could be obtained in sufficient quantity to allow for an unambiguous analysis. The match between the recorded data and the reported spectrum of berkelic acid methyl ester in CDCl 3 is excellent, and leaves no room for interpretation (see the Supporting Information).…”

A C‐Linked Disaccharide Analogue of Thomsen–Friedenreich Epitope Induces a Strong Immune Response in Mice

“…Oxidation of the resulting diastereomeric alcohols 29 furnished (22 S )‐ 23 b . Even though this final oxidation turned out to be difficult and was plagued by formation of the corresponding methylthiomethyl adduct 30 (Scheme ),19 the final product could be obtained in sufficient quantity to allow for an unambiguous analysis. The match between the recorded data and the reported spectrum of berkelic acid methyl ester in CDCl 3 is excellent, and leaves no room for interpretation (see the Supporting Information).…”

Synthetic Uses of Phenols

“…Reaction of a sulfoxide and phenol in the presence of dehydrating reagents such as thionyl chloride or benzenesulfonyl chloride provides phenoxysulfonium salts, which on treatment with triethylamine are converted to o-(α-alkylthioalkyl)phenols 134,135 . Since the benzylic thio group can be readily removed, the overall transformation provides the o-alkylated phenols.…”