Intramolecular bifunctional catalysis of the racemization of phenyl benzenethiosulfinate

by Moguin, Alan Lathrop

Catalysis of the racemizationof optically active phenyl

benzenethiolsulfinate, (+)-I, by (a) methylthioacetic acid (II) and (b)

a -methylthio-m-toluic acid (III) has been investigated in aqueous

dioxane and anhydrous acetonitrile at 39.6°C. Added II did not cause

any increase in the rate of racemization of (+)-I in either solvent. In

aqueous dioxane containing added perchioric acid, III, acting solely

as a nucleophile, catalyzed the racemization of (+)-I via a process

that was first-order in (+)-I, first-order in perchloric acid and

first-order in III but no catalysis by III alone was observed in the

absence of perchloric acid in aqueous dioxane. Since the mechanism

of the acid and nucleophile catalyzed racemization has been previously

worked out, no attempt was made to study the third-order

process further. In acetonitrile, however, (+)-I was found to undergo

racemization due to catalysis by III alone. Under these conditions

the racemization followed clean second-order kinetics - -first-order

in (+)-1 and first-order in III, Since equimolar mixtures of benzoic

acid and benzyl methyl sulfide showed no catalysis of the racemization

under these conditions, catalysis of the racemization by III under

these conditions must involve intramolecular bifunctional catalysis.

The mechanism shown in Chart I is proposed for this process and

is in accord with the fact that such catalysis can be observed in

acetonitrile but not in aqueous dioxane where hydrogen-bonding with

the solvent greatly reduces the concentration of the key intermediate

complex (+)-A. The initial necessary formation of a complex between

(+)-I and III is followed by rate-determining attack by the sulfide

part of III on the sulfenyl sulfur of (+)-I accompanied by the

complete proton transfer from the carboxylic acid group of III to the

sulfinyl group of (+)-I.

Some further aspects of the racemization of (+)-I as catalyzed

by III in acetonitrile are discussed with the purpose of showing that

the process is formally analogous to simple enzyme-catalyzed

processes.