Organic disulfides and related substances. XXXI. Possible anchimeric involvement of an ortho carboxylate moiety in disproportionation of unsymmetrical o-carboxyphenyl disulfides

Abstract

Disproportionation of 2-(phenyldithio)benzoic acid (2) to phenyl disulfide and 2,2'-dithiodibenzoic acid is much faster for the salt than for the acid. Among the facts which suggest that the o-carboxylate moiety of the salt anchimerically facilitates disproportionation are the following: an increase in rapidity with increasing pH near pH 7; decreased rapidity for the meta isomer; lack of a marked effect of dilution; inhibition of disproportionation by A-ethylmaleimide (through trapping of benzenethiolate ion) but acceleration by addition of thiolate ion; accordance with expectation as to the relative rapidity of disproportionation of other dithiobenzoic acids; and, evidence for existence and consistent reactions of o-sulfenobenzoic acid anhydride (5a) as an unstable intermediate generated by anchimeric displacement of benzenethiolate ion by the o-carboxylate moiety.o-(2-Protoaminoethyldithio)benzoate ( 1) is active as an antiradiation drug.2 That the methyl ester, the meta isomer, and the para isomer of 1 showed no significant antiradiation activity2a led us to suspect anchimeric involvement of the carboxylate moiety of 1 with the disulfide linkage. In a similar vein, inactivity of the cyclohexyl analog of l2b is understandable, since this analog is believed to have trans substituents, which should resist anchimeric involvement. This suspicion of anchimeric involvement was strengthened during work with a phenyl counterpart (2) of 1, since the sodium salt of 2 (3) disproportionated far more readily to the two symmetrical disulfides than did 2 itself (eq l).This paper further supports the probability of such an anchimeric involvement in the reaction of eq 1.The extent of disproportionation of 2 proved to be highly dependent on the pH of the solution (Table I).At pH 14 disproportionation is 95% complete in 0.6 hr (calculated as usual).4 *Attack of the hydroxyl ion on(1) (a) Paper XXX:

An Adenosine Triphosphate-Phosphate Exchange Catalyzed by a Soluble Enzyme Couple Inhibited by Uncouplers of Oxidative Phosphorylation

“…The disproportionation of 2-(phenyldithio)benzoic acid to phenyldisulfide and 2,2'-dithiobenzoic acid depends on pH in a manner that suggests that the o-carboxyl group participates in the reaction (14). It was postulated (14) [12] H 0°OS-S C HO0 0 0~-0 isomer undergoes a much slower disproportionation and that the disproportionation is concentration independent is part of the evidence that supports this reaction scheme.…”

“…Sulfenyl carboxylates have been implicated recently as intermediates in the disproportionation of unsymmetrical o-carboxyphenyl disulfides (14) and in the overoxidation of 3-carboxymercaptans by iodine (15)(16)(17). The disproportionation of 2-(phenyldithio)benzoic acid to phenyldisulfide and 2,2'-dithiobenzoic acid depends on pH in a manner that suggests that the o-carboxyl group participates in the reaction (14).…”

“…It was postulated (14) [12] H 0°OS-S C HO0 0 0~-0 isomer undergoes a much slower disproportionation and that the disproportionation is concentration independent is part of the evidence that supports this reaction scheme. Evidence for the synthesis of the cyclic sulfenyl carboxylate has been presented (14).…”

“…Atldw boncentrations, the uncouplers would compete with Pi for the sulfenyl carboxylate in Eq. 14 (26).…”

Forty-Five Years With a Hydra, Organosulfur Chemistry

“…46);30. "8 reaction RS02 I + RSAg L RSO 2SR + Agi (46) RS%-i LBuSCJ L R S O~S -@ I (48) of thiosulfonate salts with alkylene dihalides (eq. 47);% and the reaction of a thionitrite with a sulfinic acid (Scheme 11, 67+72).…”