Nifedipine–pyrazine (2/1)

In the title compound, 2C17H18N2O6·C4H4N2 [systematic name: 3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate–pyrazine (2/1)], the complete pyrazine molecule is generated by crystallographic inversion symmetry. The center of the pyrazine ring lies on an inversion center. The nifedipine molecules are linked into chains along the c axis through N—H⋯O hydrogen bonds, while the pyrazine molecules are organized in the structure through van der Waals interactions.


Related literature
Co-crystalline materials are of pharmaceutical interest due to their ability to alter the physicochemical properties of active pharmaceutical ingredients (APIs) (Schultheiss et al., 2009) and provide drug repositioning or life-cycle management (Trask, 2007). The corresponding crystal structure of nifedipine has been reported (Triggle et al., 2003) and it also forms chains through N-HÁ Á ÁO hydrogen bonds. Other crystalline forms also exist: polymorphs (Burger et al., 1996) solvates/ hydrates (Caira et al., 2003) and a metal complex (Bontchev et al., 2003), as well as a non-crystalline, amorphous phase (Miyazaki et al., 2007).
Suprisingly, examples of nifedipine cocrystals have yet to be published in the open literature, and thus we report here the 2:1 cocrystal of nifedipine and pyrazine.
A view of the asymmetric unit of the title compound and its numbering scheme are displayed in Fig. 1. The material crystallizes in a 2:1 (nifedipine:pyrazine) stoichiometric ratio, although the asymmetric unit contains the components in a 1:0.5 ratio, because the center of the pyrazine ring resides on an inversion center. It should also be noted that the nitro-substituted phenyl ring is relatively orthogonal ("axial") to the dihydropyridine ring (Table 1) which is displayed in Fig. 1. Nonetheless, the nifedipine molecules are linked into linear, one-dimensional chains with a graph set notation of C(6) through N-H···O hydrogen bonds from the N-H moiety to a carbonyl moiety, Table 2. The hydrogen bonds are running along the crystallographic c axis. Interestingly, the pyrazine molecules are not participating in hydrogen bonding with nifedipine, but are organized in between nifedipine rows through multiple van der Waals interactions (Fig. 2). Upon extending the structure into three-dimensions, the organization of the pyrazine molecules within the crystal structure are clearly shown. The pyrazine molecules are not only between one-dimensional rows of nifedipine, but also 'sandwiched' between methyl-ester groups from neighboring nifedipine molecules.

Experimental
The title compound was prepared by adding solid nifedipine to a nearly saturated solution of pyrazine in methanol and allowed to stir for ~24 h at ambient temperature before filtering. Crystals of suitable size for single-crystal analysis were obtained directly from the experiment.

Refinement
The amino H-atom was located in a difference Fourier map. All other H-atoms were positioned geometrically and allowed to ride on their parent atoms with U(H) set to 1.5U eq (C) for methyl and 1.2U eq (C) for all other carbon atoms.
supplementary materials sup-2 Figures Fig. 1. The asymmetric unit of the title compound, with the atom labeling scheme and 50% probability displacement ellipsoids. Fig. 2. View down the b axis displaying the hydrogen bonding (black-dashed lines) between nifedipine molecules. The pyrazine molecules (ball-and-stick mode) are positioned between the one-dimensional nifedipine rows (right). The direction of the a axis is the red line, the b axis is green, and the c axis is blue.