Unexpected Differences in the α-Halogenation and Related Reactivity of Sulfones with Perhaloalkanes in KOH−t-BuOH

Abstract

Most alkyl phenyl sulfones are readily alpha-chlorinated with CCl(4) and alpha-brominated with CBrCl3 in KOH-t-BuOH via radical-anion radical pair (RARP) reactions. While isopropyl mesityl sulfone (4) is easily alpha-chlorinated with CCl(4), it was completely recovered when treated with the more reactive CBrCl3. Subsequent investigations showed the latter result to be due to the poor acidity of 4 together with the rapid depletion of CBrCl3 and KOH by their reaction with each other, and led to a variety of other important results. 4-Hydroxyphenyl isopropyl sulfone (6) is unreactive with either CCl4 or CBrCl3 in KOH-t-BuOH, its phenoxide anion strongly reducing the electronegativity of the sulfonyl group, thereby inhibiting alpha-anion formation. This effect is reversed by the electron-withdrawing influence of two alpha-phenyls, so that benzhydryl 4-hydroxyphenyl sulfone (8) is readily alpha-halogenated in KOH-t-BuOH with CCl4 or CBrCl3. On further contact with KOH-t-BuOH the alpha-halogenated sulfones from 8 are decomposed into benzophenone and phenol. While the alpha-halogenated derivatives of 4-methoxyphenyl benzhydryl sulfone (9) are stable to base, they are decomposed even under mildly acidic conditions into 4-methoxyphenyl 4-methoxybenzenethiolsulfonate (9c), phenol, and benzophenone. Mono-alpha-halogenation of benzyl phenyl sulfone (10) enhances the rate of the subsequent halogenation, so that alpha,alpha-dihalogenation is attained while much substrate is still present and the mono-alpha-halogenated product is not detected. The ease of reductive debromination of alpha-bromo sulfones with Cl3C- was correlated with the stability of the formed alpha-anions, explaining the success with alpha-bromobenzylic sulfones but failure with alpha-bromoalkyl sulfones. In the presence of air and the absence of competing halogenation, formation of the alpha-anions of alkyl aryl sulfones is quickly accompanied by oxidative cleavage by atmospheric O2, leading to the formation of arenesulfonyl alcohols, arenesulfonyl halides, and haloarenes.

Zinc Dichromate Trihydrate (ZnCr2O7×3H2O) as an Efficient Reagent for the One-Pot Synthesis of Thiosulfonates from Thiols

“…d = 128.9, 129.2, 129.9, 130.3, 137.7, 138.6, 140.5, 141.3 a Yields refer to isolated pure products characterized by spectroscopic methods and compared with authentic spectra. 8,9,[14][15][16] …”

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

“…We propose that KO t -Bu assists in α-bromination of 2a to form the intermediate 6 via single electron transfer (SET). Recent mechanistic work by Murphy and co-workers showed that in the presence of polyhalomethane CBr 4 , KO t -Bu undergoes a SET reaction, forming •CBr 3 and t -BuO• radicals [ 95 ]. Furthermore, with other strong bases of similar strength including NaH and KOEt the reaction proceeded with significantly lower yields.…”

“…This radical attacks the α-hydrogen of 2a via hydrogen atom transfer (HAT), to form intermediate A with a radical at the α-carbon. A then undergoes α-bromination to form the intermediate 6 [ 95 ]. Attack at the α-carbon of 6 by 2-aminobenzothiazole ( 1a ) via an Ortoleva–King type of reaction forms B [ 96 – 97 ].…”

Bromotrichloromethane

“…8a,b (D) Radical-anion radical pair reactions (RARP) allowed a-bromination of alkylphenyl sulfones in the presence of a KOH/t-BuOH mixture. 9 The products are formed in high yields and are stable under these reaction conditions. …”