Lamellar Racemic Twinning as an Obstacle for the Resolution of Enantiomers by Crystallization:  The Case of Me(All)N+(CH2Ph)Ph X- (X = Br, I) Salts

Ammonium salts Me(All)N+(CH2Ph)Ph X- (X = Br, 1; X = I, 2) (Asymmetric nitrogen, communication 89, prev. see Kostyanovsky, R. G.; Kostyanovsky, V. R.; Kadorkina, G. K.; Lyssenko, K. A. Mendeleev Commun. 2003, 111) were historically the first compounds with a chiral nitrogen center obtained in optically pure forms via diastereoisomers. We were astonished by the fact that W. J. Pope, who first carried out the resolution (1899), mentioned in his articles that salts have features for conglomerate formation but nowhere did he note the registration of optical activity and manual sorting of left- and right-handed single crystals. We reinvestigated these salts with the help of X-ray diffraction and found that the space groups of both of them are P212121. However, despite the chiral space group, the enantiomeric composition of the majority of the crystals obtained by crystallization from solutions of racemates was found to be near racemic. Such crystal growth behavior, called lamellar twinning between enantiomers, represents a serious obstacle to the methods of enantiomeric resolution by straightforward crystallization that are used in the chiral industry. The phenomenon probably results from a high concentration in solution of heterochiral growth clusters, which promote the formation of the intergrowth region of twins. To glance experimentally at what might possibly be the first crystal growth units, electrospray ionization FT-ICR mass spectrometry was applied. We were able to register polyionic clusters containing up to five chiral cations. The relative stability of the simplest dimeric clusters (two cations linked by an anion) of 1 with homo- and heterochiral composition was estimated with a B3LYP/SDD calculation, and heterochiral one was found to be more stable by 0.883 kcal/mol.