A bug in enantiomer separation: double salt formation – diastereomeric and double salt structures of 1-cyclohexylethylammonium 2- and 4-chloromandelate

Abstract

The number of crystal structures of diastereomeric salt pairs and especially of double salts is limited in the literature. This work exceptionally presents the structures of two constitutional isomer double...

Strategies for chiral separation: from racemate to enantiomer

“…[51][52][53] Currently, a broad variety of substrates can be successfully resolved via classical chemical resolution (CCR, Section 4.4.2) with high yield, high enantiomeric excess (ee), and acceptable cost. Nevertheless, CCR cannot be regarded as an eco-friendly process and fails to exhibit enantiospecic recognition toward enantiomers, 54 reducing its popularity in recent publications. Fortuitously, in the past decade, cocrystal-based resolution (CBR, Section 4.4.3) and Dutch resolution (DR, Section 4.4.4) have shown great potential to address the aforementioned issues in CCR by replacing strong acid-base interactions with non-covalent interactions (hydrogen bonding, halogen bonding, p-p interactions, van der Waals interaction, etc.…”

Enantiomer separation of 2‐halomandelic acids via diastereomeric salt formation with chiral N‐substituted 2‐amino‐2‐phenylethanols

“…10 The enantioseparation of racemic o-Cl-MA via diastereomeric salt formation using chiral amines has been reported. [11][12][13][14][15][16] However, the enantioseparation of o-halomandelic acids (o-X-MA) with larger halogen groups has been less explored. These halogen-substituted MAs enable the synthesis of pharmaceuticals and natural products via further derivatization, such as ortho-arylation.…”

“…The ( R )‐enantiomer of o ‐Cl‐MA is an important synthetic intermediate of chiral drugs, such as clopidogrel, an antiplatelet agent that prevents heart disease 10 . The enantioseparation of racemic o ‐Cl‐MA via diastereomeric salt formation using chiral amines has been reported 11–16 . However, the enantioseparation of o ‐halomandelic acids ( o ‐X‐MA) with larger halogen groups has been less explored.…”