Crystal structures of anhydrous and hydrated N-benzylcinchonidinium bromide

The crystal structures of anhydrous N-benzylcinchonidinium bromide and the sesquihydrate are reported. O—H hydrogen-bond donor interactions and numerous C—H⋯Br contacts dominate the intermolecular features.


Chemical context
Cinchona-derived enantioselective phase-transfer catalysts have been used in a variety of applications including [2,3]-Wittig rearrangements (Denmark & Cullen, 2015), synthesis of unnatural -amino acids (O'Donnell et al., 1989), and even industrial-scale synthesis of pharmaceuticals (Moccia et al., 2015). As this class of phase-transfer catalysts are easy to prepare from the parent natural product alkaloids, and demonstrate aspects of green and sustainable chemistry, they are attractive organocatalysts for further development. Mechanistic studies of N-benzylcinchonidinium bromide and substrates in solution provide evidence for the importance of quaternary ammonium benzylic C-H hydrogen-bond donor interactions as well as the classical OH donor (Bencivenni et al., 2021). Anion effects also demonstrate differences in the binding mode of substrates with mechanistic implications and potential enantioselectivity.
While structures are reported for analogs of this cation, that of the commercially available bromide salt is unpublished. We report here the structures of N-benzylcinchonidinium bromide (I) and the sesquihydrate (II).

Structural commentary
The anhydrous compound (I) (Fig. 1) crystallizes in the monoclinic space group P2 1 . The asymmetric unit of (I) consists of one molecular cation and one bromide anion. The sesquihydrate (II) (Fig. 2) crystallizes in the tetragonal space group P4 1 2 1 2. The asymmetric unit of (II) consists of one molecular cation, one bromide anion, and one water on a general position and one half water, as O3 lies on a twofold axis at z = 0.5. For (I) and (II), the absolute configuration of chiral atoms N1, C2, C3, C7, and C8 are determined as S, R, S, S, and R, respectively, by anomalous dispersion and are consistent with previous structures of cinchonidine.

Figure 1
Molecular structure of (I) with displacement ellipsoids drawn at the 50% probability level.

Supramolecular features
The extended structure of (I) displays a simple isolated charge-assisted hydrogen bond with the alcohol donor O1 and Br1 anion acceptor (Table 3, Fig. 4). The quinoline N2 acceptor does not participate in any hydrogen-bonding interactions. Each bromide also has four short C-HÁ Á ÁBr contacts with the same cation (phenyl, benzyl, quinoline, and vinyl) as well as an additional quinuclidine methine C-H.
The sesquihydrate (II) shows very different hydrogenbonding interactions (Table 4, Fig. 5). The alcohol group O1 acts as a donor with a water acceptor, O2. Water O2 hydrogen bonds as donor with Br1 and quinoline N2, while water O3 acts a donor to two bromide acceptors. This pattern of hydrogen bonds forms a chain with terminal O1 donors and water and bromide links, with the water O2 relating the two halves of the chain. Quinoline N2 acceptors of O2 hydrogenbond donors link the chains forming an extended network. Each bromide also has four short C-HÁ Á ÁBr contacts with the same cation (benzyl, vinyl, and two quinuclidine) as well as two additional quinuclidine contacts with a neighboring molecular cation (Figs. 5 and 6).

Figure 6
Intermolecular hydrogen-bonding pattern of (II). Symmetry codes: Crystals of the sesquihydrate (II) were obtained by slow evaporation of an ethanol solution of N-benzylcinchonidinium bromide.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 5. The O-H hydrogen positions were assigned from residual electron-density peaks and positions were refined. All remaining hydrogen atoms were placed in calculated positions and refined in the riding-model approximation with distances of C-H = 0.93, 0.93, 0.93, 0.97, and 0.98 Å for the aromatic C-H, terminal vinyl CH 2 , vinyl C9-H9, methylene C-H, and methine C-H, respectively, and with U iso (H) = kÁU eq (C), k = 1.2 for all C-H and 1.5 for the hydroxyl H1. SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).   (5) Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.