The synthesis and reduction of optically active 2-mercaptopropionic acid and some derivatives

Abstract

Nucleophilic displacement reactions, by thioacetate, thiobenzoate, methanethiolate, and toluene-α-thiolate, on methyl L-O-ptolysulphonyl-lactate, methyl L-2-chloropropionate, and sodium L-2-chloropropionate, have been used to prepare D-2-acylthio- and D-2-acylthio- and D-2-alkylthio-propionic acids and esters. Extensive racemisation occurs when an excess of thioacetate or thiobenzoate is used; this is attributed to further S_N2 displacement, with acetylthio or benzoylthio as a leaving group. Concomitant acyl exchange also occurs, with retention of configuration, by a different mechanism. Thus methyl D-2-acetylthiopropionate with potassium thiobenzoate gives methyl D-2-benzoylthiopropionate.

Reduction of L-(2-methylthio)propionic acid with diborane proceeds without racemisation, but the L-(2-methylthio)propanol obtained by reduction of the same acid with lithium aluminium hydride is of lower optical purity. Appreciable racemisation also occurs in the reduction, with lithium aluminium hydride, of methyl D-(2-methylthio)propionate and of methyl D-(2-benzoylthio)propionate.

The formation of D-2-mercaptopropanol, of known configuration, by reduction of (+)-2-mercaptopropionic acid, its acyl derivatives, and its esters, establishes the D-configuration of the latter compounds.