Chlordiazepoxide dichloromethane monosolvate

In the title compound (systematic name: 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide dichloromethane monosolvate), C16H14ClN3O·CH2Cl2, the seven-membered ring adopts a boat conformation with the CH2 group as the prow and the two aromatic C atoms as the stern. The dihedral angle between the benzene rings is 75.25 (6)°. The crystal structure features centrosymmetric pairs of chlordiazepoxide molecules linked by pairs of N—H⋯O hydrogen bonds, which generate R 2 2(12) loops.

The Swedish Research Council is acknowledged for providing funding for the single-crystal diffractometer. determined in 1979determined in (Herrnstadt et al., 1979, the structure of the pure compound in 1982 (Bertolasi et al., 1982). The reason for the study of chlordiazepoxide salts was the presence of three potential protonation sites (Herrnstadt et al. 1979). In order to study a number of different chlordiazepoxide salts, we synthesized the compound according to the description by Sternbach et al. (1961). The final step in this synthesis is the crystallization from dichloromethane. It turned out that the crystallization product that forms initially is a chlordiazepoxide dichloromethane solvate, whose structure is described here. The title compound ( Fig. 1) features pairs of chlordiazepoxide molecules, which are hydrogen-bonded via two symmetry-equivalent N-H···O bonds across an inversion centre (Fig. 2). The same pattern could be found in the hydrochloride (Herrnstadt et al., 1979). In the structure of pure chlordiazepoxide, pairs of molecules of the same chirality (due to the high energy barrier of ring inversion, benzodiazepines are chiral) were observed and it was argued that this arrangement might be more stable than dimers of two different enantiomers.
However, this effect must be quite subtle since the only interactions between the chlordiazepoxide and dichloromethane molecules are due to van der Waals forces. The dihedral angle between the two phenyl groups is 75.25 (6)°.

Experimental
Chlordiazepoxide was synthesized according to the procedure described by Sternbach et al.(1961), starting from commercial 2-amino-5-chlorobenzophenone. Slow evaporation of the solution of the final product in dichloromethane yielded colourless, block-shaped crystals of the title compound. Once removed from the mother liquor, the crystals decomposed slowly (within days), yielding solvent-free chlordiazepoxide.

Refinement
All H atoms except that attached to N were placed at calculated positions and refined riding. The N-H atom was located from the Fourier map and refined with the N-H distance restrained to 0.88 (2) Å.  The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level.  The centrosymmetric chlordiazepoxide dimers in the title compound. The half-transparent moiety is generated by (i)-x+1, -y+1, -z+2.

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. 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) 0.0051 (7)  C2 0.0296 (10) 0.0209 (9) 0.0205 (9) 0.0104 (8) 0.0026 (7) 0.0002 (7)  C3 0.0275 (10) 0.0175 (9) 0.0247 (9) 0.0094 (8) −0.0012 (8) 0.0030 (7)  C4 0.0233 (9) 0.0206 (9) 0.0214 (9) 0.0059 (7) 0.0006 (7) 0.0067 (7) (2)