Altering the mobile phase composition to enhance self-disproportionation of enantiomers in achiral chromatography

The influence of mobile phase composition on the efficiency of enantiomer separation by achiral chromatography (ACh) was investigated. The separation was induced by the phenomenon of self-disproportionation of 
enantiomers (SDE) triggered by their homo and hetero-chiral interactions in an achiral environment. Typically, 
SDE occurs in apolar mobile phases of weak elution strength, which causes the separation time to extend and the 
process productivity to deteriorate. To mitigate that effect, we altered the content of a strong solvent (modifier) 
in the mobile phase by use of a solvent gradient in which the target enantiomer was separated in the presence of 
the weak solvent, whereas the unresolved mixture of enantiomers was eluted by increasing the modifier content 
in the mobile phase. This enabled accelerating the solute elution while preserving the separation selectivity. The 
approach was examined for the separation of nonracemic mixtures of two structurally different compounds that 
exhibited the SDE effect in ACh, i.e., metalaxyl (MX) and methyl p-tolyl sulfoxide (MTSO). The target compound 
of the separation was the more abundant enantiomer in the enantiomeric mixture. The process realization was 
preceded by the determination of the effect of the modifier content on the separation yield for enantiomeric 
mixtures of MX and MTSO of different enantiomeric excess (ee). In the case of MX, yield of the pure target 
enantiomer varied from 2 %, for the maximum concentration of the modifier, to 45 % for the minimum modifier 
concentration and the largest ee used in the experiments. In the case of MTSO, the yield varied from minimum 40 
% to maximum 66 %. To predict the process, we employed a dynamic model, in which underlying thermodynamic dependencies were implemented.