2670 Chem. Commun., 2011, 47, 2670–2672 This journal is c The Royal Society of Chemistry 2011 Cite this: Chem. Commun., 2011, 47, 2670–2672 Quininium mandelates—a systematic study of chiral discrimination in crystals of diastereomeric saltsw Nikoletta B. Ba´thori,* a Luigi R. Nassimbeni a and Clive L. Oliver b Received 7th October 2010, Accepted 10th December 2010 DOI: 10.1039/c0cc04279j The selectivity profile for the resolution of mandelic acid by quinine is dominated by structures comprising (QUIN + )- (MAND À ) salts with Z 0 = 3 which contain (R)-, (R)- and (S)-mandelate anions. The resolution of racemic modifications by a chiral resolving agent is generally achieved either by diastereomer salt formation or by inclusion with a chiral host compound. The former method is the most common, and has been reviewed. 1 The cinchona alkaloids, of which quinine is the most abundant, have been used extensively as resolving agents for acids 1,2 and the pairs quinine/quinidine and cinchonidine/ cinchonine have been described as ‘‘quasi-enantiomeric’’. 3 Larsen 4,5 has described the structures of the salts formed by cinchonine and cinchonidine with both (R)- and (S)-mandelic acids. She concluded that cinchoninium (R)-mandelate is the less soluble salt and its structure displays disorder in the –CH=CH 2 moiety. In contrast, cinchonidinium-(S)-mandelate is the less soluble salt. The thermal and solubility parameters of the four salts were reconciled with their crystal structures and it was noted that the packing of the cinchonidinium salts was significantly different from their corresponding cinchoninium salts. We have taken a somewhat different approach to the question of enantiomeric resolution in order to understand the mechanism of the molecular recognition that drives the differentiation of the resolving agent for one particular enantiomer. We have thus set up a series of competition experiments where the resolving agent, quinine (QUIN) was exposed to mixtures of mandelic acid, where the mole fraction of the starting mixture was varied systematically. The ensuing solutions were allowed to crystallise and the mole fraction of the entrapped enantiomer was measured by analysing the crystal structure. This is an extension of the technique employed to measure the selectivity profile of a given host compound (H) towards a pair of guests A and B, whereby H is dissolved in a series of solutions where the mole fraction X A varies in steps from 0 to 1. The resulting crystals are analysed, yielding mole fractions of A as Z A . The selectivity coefficient at each point is then defined as K A:B =(K B:A ) À1 = Z A /Z B Â X B /X A ;(X A + X B = 1) and is a measure of the discrimination of the host for a given guest. In our case the two guests are replaced by (R)- and (S)-mandelic acids. The crystals were grown by slow evaporation from solution containing 1 mmol of quinine (QUIN) and 1 mmol of mandelic acid (MAND) in 20 mL of ethanol. The mole fraction of the (R)-mandelic acid in the starting solution was varied systematically as X R (%) = 15, 30, 70 and 100. The crystals were analysed by X-ray diffraction and the crystallo- graphic data are summarised in the ESIw in Table 1S.z Refinement revealed that all structures are salts of quininium cations and mandelate anions (Scheme 1). In all cases we checked that the structure of the single crystals was representative of the bulk by measuring the X-ray powder patterns. The (QUIN + )(15R-MAND À ) structure (1) crystallises in P2 1 2 1 2 1 with Z 0 = 1 and only the (S)-mandelate ion was captured, and is essentially the same as that published by Gjerlov and Larsen 6 (data at 122 K). However, our data were collected at 173 K because prior data collections for the other structures in this study were performed at this temperature. The metrics of the hydrogen bonds for this and the subsequent structures are reported in Table 2S.w The (QUIN + )(30R-MAND À ) structure (2) crystallises in the space group P2 1 with Z 0 = 3. There are thus three pairs of ions in the asymmetric unit. The (QUIN + )(MAND À ) ion pairs are labelled A, B and C, and the configurations of the Scheme 1 a Centre for Crystal Engineering, Department of Chemistry, Cape Peninsula University of Technology, P.O. Box 652, Cape Town, 8000, South Africa. E-mail: bathorin@cput.ac.za; Fax: +27 21 460 3854; Tel: +27 21 460 8354 b Centre for Supramolecular Chemistry Research, Department of Chemistry, University of Cape Town, South Africa w Electronic supplementary information (ESI) available: X-Ray data collection and structure refinement details, 9 crystallographic information of structures 1–5, hydrogen bond parameters, torsion angles. CCDC 795245–795249. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c0cc04279j ChemComm Dynamic Article Links www.rsc.org/chemcomm COMMUNICATION Downloaded by University of Bristol on 01 March 2012 Published on 12 January 2011 on http://pubs.rsc.org | doi:10.1039/C0CC04279J View Online / Journal Homepage / Table of Contents for this issue