Isolation and identification of the metolachlor stereoisomers using high-performance liquid chromatography, polarimetric measurements, and enantioselective gas chromatography

Because of the presence of two chiral elements (an asymmetrically substitut ed carbon and a chiral axis), the herbicide metolachlor consists of four st ereoisomers stable at ambient temperature with aSS-, aRS-, aSR-, and aRR-co nfigurations (aSS, the isomer with aS,1'S-configuration, etc.). Metolachlor , initially introduced into the market as the racemic product containing al l four stereoisomers, is currently being replaced worldwide by S-metolachlo r, the product enantiomerically enriched with the herbicidally active 1'S-i somers (aSS, aRS). The isomer-specific analysis of metolachlor requires not only enantioselective ("chiral") analytical techniques but also suitable r eference compounds. In this study, two of the four metolachlor isomers were isolated from rac-metolachlor in enantio- (ee > 98%) and diastereomericall y pure forms by a combination of achiral and chiral high-performance liquid chromatography (HPLC). The two isomers were identified as the aSS- and the aRR-isomers by polarimetric measurements, in reference to previous data. T he two isomers were then thermally equilibrated to 1:1 mixtures of the aSS/ aRS and aRR/aSR diastereomers, respectively, so that analytical data of all four metolachlor isomers became available; they were then used to identify these isomers in technical products by chiral high-resolution gas chromato graphy (HRGC). The kinetics of the thermally induced interconversion of the atropisomers was studied and the consequences, such as for CTC analysis, a re discussed. A comparison of on-column and split/splitless injection indic ated that the latter technique results in significant isomerization prior t o separation and, therefore, cannot be used for accurate isomer analysis.