A hydrogen sulfate salt of chlordiazepoxide

Crystals of the hydrogen sulfate salt of chlordiazepoxide (systematic name: 7-chloro-N-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-iminium 4-oxide hydrogen sulfate), C16H15ClN3O+·HSO4 −, were obtained from a solution of chlordiazepoxide and sulfuric acid in methanol. The structure features chlordiazepoxide molecules that are protonated at the imine N atom. The seven-membered ring adopts a boat conformation with the CH2 group as the prow and the two aryl C atoms as the stern. The dihedral angle between the benzene rings is 72.41 (6)°. In the crystal, the HSO4 − anion acts as a bridging group between two chlordiazepoxide cations. The H atom of the protonated imino N forms an N—H⋯O hydrogen bond with a hydrogen sulfate ion. The anion in turn forms two hydrogen bonds, O—H⋯O with the anion as donor and N—H⋯O with the anion as acceptor, to generate an R 2 2(10) loop. Each HSO4 − anion connects two chlordiazepoxide moieties of the same chirality.

Crystals of the hydrogen sulfate salt of chlordiazepoxide (systematic name: 7-chloro-N-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-iminium 4-oxide hydrogen sulfate), C 16 H 15 ClN 3 O + ÁHSO 4 À , were obtained from a solution of chlordiazepoxide and sulfuric acid in methanol. The structure features chlordiazepoxide molecules that are protonated at the imine N atom. The seven-membered ring adopts a boat conformation with the CH 2 group as the prow and the two aryl C atoms as the stern. The dihedral angle between the benzene rings is 72.41 (6) . In the crystal, the HSO 4 À anion acts as a bridging group between two chlordiazepoxide cations. The H atom of the protonated imino N forms an N-HÁ Á ÁO hydrogen bond with a hydrogen sulfate ion. The anion in turn forms two hydrogen bonds, O-HÁ Á ÁO with the anion as donor and N-HÁ Á ÁO with the anion as acceptor, to generate an R 2 2 (10) loop. Each HSO 4 À anion connects two chlordiazepoxide moieties of the same chirality.

Experimental
Chlordiazepoxide can be easily protonated and the protonation appears to occur on the imine nitrogen atom, which could be shown both by the structure determination of the hydrochloride (Herrnstadt et al. 1979) and by solution studies (Yang, 1995). In chlordiazepoxide, the dichloromethane solvate and the hydrochloride, dimers of chlordiazepoxide moieties are observed. In order to study the influence of the counterion on the hydrogen bonding pattern, we crystallized chlordiazepoxide hydrogen sulfate from a methanol solution.
The structure of the title compound features chlordiazepoxide molecules, that are protonated at N1 (Fig. 1). The sevenmembered ring adopts a boat conformation with the CH 2 group as the prow and the two aromatic C atoms as the stern.
The HSO 4acts as a bridging group between two chlordiazepoxide cations. The hydrogen atom of the protonated imino-N forms a N-H···O bond with a hydrogen sulfate ion. The anion forms in turn two hydrogen bonds, one O-H···O group where the anion acts as donor and one N-H···O group where it acts as acceptor. These three H bonds yield a R 2 2 (10) loop. Each HSO 4group connects two chlordiazepoxide moieties of the same chirality. Thus, each hydrogen sulfate group acts as a bridging group, linking two chlordiazepoxide moieties yielding infinite chains (Fig. 2). Each chain contains only one enantiomer of the molecule. The dihedral angle between the benzene rings is 72.41 (6)°.

Experimental
Chlordiazepoxide was synthesized according to the procedure described by Sternbach et al. (1961). Crystals of the title compound were obtained as hexagonal, yellow plates by slow evaporation of a solution of 25 mg chlordiazepoxide and 7.7 mg sulfuric acid (95%) in 5 ml of methanol at room temperature.

Refinement
C-H hydrogen atoms were placed at calculated positions and refined riding on the respective carrier atom with U iso =1.2U eq of the carrier atom (1.5 U eq for the methyl group) and with d(C-H)=0.95Å for aromatic H atoms, 0.99Å for methylene-H atoms and 0.98Å for methyl-H atoms. The torsion angle between the NH group the methyl group in the NHCH 3 side chain was refined as well. O-H and N-H hydrogen atoms were located from the difference-Fourier map and the respective bond lengths were refined. The interatomic distance N1-H1 was restrained to 0.88 (2) Å because free refinement did not yield a satisfactory result.

Figure 1
The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen bonds shown as dashed lines.  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.