The same and not the same. Similarities and differences in the resolution of trans-chrysanthemic acid of industrial origin by the enantiomers of some threo-1-aryl-2-dimethylamino-1,3-propanediols

Abstract

The enantiomers of threo-dimethylamino-1-[4-(methylthio)phenyl]propane-1,3-diol (MTDP) were found to be effective resolving agents for trans-chrysanthemic acid (trans-ChA) on an industrial scale. (1S,2S)-(+)-MTDP and (1R,2R)-(−)-MTDP were revealed to be “blind” towards the enantiomers of cis-ChA. They work well on racemic and/or scalemic trans/cis mixtures of industrial production and are used in a stoichiometric amount with respect to the enantiomer of trans-ChA to be collected. Isopropyl ether is the solvent of choice, and it does not need the presence of co-solvents such as methanol to promote nucleation and crystal growth of the n salts as previously reported for threo-dimethylamino-1-[4-(nitro)phenyl]propane-1,3-diol (DMAD) enantiomers. X-ray crystal structures of the n salts of trans-ChA and MTDP revealed the peculiar features of two pseudopolymorphs. MTDP enantiomers are low cost, non-toxic, safe, and easily available from important precursors of thiamphenicol through a single straightforward reaction. After the resolution, they can be recovered almost quantitatively and reused without any loss of their chiral integrity. Similarities and differences of these resolving agents for trans-ChA with respect the behaviour of the enantiomers of DMAD and of the enantiomers of the parent compound, 1-phenyl-2-dimethylamino-1,3-propane-diol (DMPP), are shown in a comparative analysis of their performances.