Carbamazepine furfural hemisolvate

# 2005 International Union of Crystallography Printed in Great Britain – all rights reserved In the title compound, C15H12N2O 0.5C5H4O2, carbamazepine molecules retain the R2 (8) N—H O hydrogen-bonded dimer arrangement observed in the crystal structures of each of the four known anhydrous polymorphs. The furfural molecule is located between adjacent carbamazepine dimers and is hydrogen bonded to only one of the anti-oriented NH groups available on the dimer.


Comment
The antiepileptic compound carbamazepine (CBZ) is known to crystallize in at least four anhydrous polymorphic forms (Grzesiak et al., 2003) and the crystal structures of several solvates and co-crystals have also been reported (Fleischman et al., 2003). The title compound, (I), was produced during an automated parallel crystallization polymorph screen on CBZ. The sample was identified as a novel form using multisample X-ray powder diffraction analysis of all recrystallized samples (Florence et al., 2003). Subsequent manual recrystallization from a saturated furfural solution by slow evaporation at 278 K yielded samples of the carbamazepine furfural hemisolvate suitable for synchrotron-based single-crystal X-ray analysis (Cernik et al., 1997).
The asymmetric unit of (I) contains two molecules of CBZ and one of furfural (Fig. 1). Pairs of CBZ molecules are connected by two N-HÁ Á ÁO hydrogen bonds (contacts 1 and 2, Fig. 2) to form the R 2 2 (8) dimer motif. This motif is observed in all of the known polymorphs and the majority of CBZ solvate crystal structures (Fleischman et al., 2003). In all other CBZ solvate crystal structures, each of the NH donor groups is involved in hydrogen-bonding interactions; the syn-oriented NH group of CBZ forms the dimer motif and the anti-oriented NH donors connect to molecules of solvent. In (I), however, only one of the anti-oriented NH groups is utilized in a hydrogen bond between CBZ and solvent (contact 3, Fig. 2). The structure also contains four C-HÁ Á ÁO interactions: contacts 4, 6 and 7 connect CBZ and furfural molecules, and contact 5 connects molecules of CBZ. The molecules pack such that the polar groups (furfural and CBZ carboxamide moiety) and hydrophobic azepine rings are segregated into alternating polar and non-polar layers in the ac plane, which are stacked in the direction of the b axis.
The H atoms of the six-and five-membered rings of carbamazepine and furfural were positioned geometrically at distances of 0.95 Å (CH) from the parent C atoms; a riding model was used during the refinement process. The U iso (H) values were constrained to be 1.2 times U eq of the carrier atom. The remaining H atoms were located in a difference synthesis and were refined isotropically [C-H = 0.95 (2)-1.01 (2) Å and N-H = 0.85 (3)-0.93 (2) Å ].

Figure 1
View of the asymmetric unit of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

Figure 2
A packing diagram of (I Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.  (7) 0.0204 (7) 0.0018 (6) 0.0004 (6) 0.0001 (6)  C14A 0.0219 (7) 0.0220 (7) 0.0204 (7) 0.0031 (6) 0.0012 (5) 0.0000 (6)  C15 0.0203 (7) 0.0218 (7) (2)