β-Polymorph of phenazepam: a powder study

Abstract

The title compound [systematic name: 7-bromo-5-(2-chloro­phen­yl)-1H-1,4-benzodiazepin-2(3H)-one] (β-polymorph), C15H10BrClN2O, has been obtained via cryomodification of the known α-polymorph of phenazepam [Karapetyan et al. (1979 ▶). Bioorg. Khim. 5, 1684–1690]. In both polymorphs, the mol­ecules, which differ only in the dihedral angles between the aromatic rings [75.4 (2)° and 86.2 (3)° in the α- and β-polymorphs, respectively], are linked into centrosymmetric dimers via N—H⋯O hydrogen bonds. In the crystal structure of the β-polymorph, weak inter­molecular C—H⋯O hydrogen bonds further link these dimers into layers parallel to bc plane.

Validation of molecular crystal structures from powder diffraction data with dispersion-corrected density functional theory (DFT-D)

“…BCHBZP01 (0.26 Å ) (Sergeev et al, 2010). After energy minimization the structure, including the unit cell, is fairly different.…”

The Polymorphism of Drugs: New Approaches to the Synthesis of Nanostructured Polymorphs

“…Its analysis was performed by applying the powder X-ray diffraction technique. A comparison with the known literature data revealed that this is a new polymorphous form of phenazepam, while the lattice parameters were determined [41]. In this new polymorphous structure, two benzene rings form a dihedral angle of 86.2(3) • , whereas, in pharmaceutical phenazepam, this angle is 75.4(2) • .…”

“…In synthesizing and studying drug polymorphism, new possibilities have been opened up in light of an original strategy proposed in [41][42][43][44][45]. The developed technology is based on the conversion of the initial substance into a gaseous state in the course of its sublimation within the flow of an inert gas-carrier, followed by condensation on contact with a surface cooled by liquid nitrogen.…”

“…The cryochemical technology was used in the synthesis of nanoparticles of piroxicam [47], androstenediol [48], phenazepam [41], and DHEA [45]. Experiments with various molecules revealed the limitations for substances suitable for transformation.…”

Polymorphism and Solvatomorphism 2010

“…Such work included the monoclinic form-I of clopidogrel bisulfate, 62 the monoclinic form-II of racemic ibuprofen, 63 the triclinic form-A of mebendazole, 64 the monoclinic form-I and orthorhombic form-II of benfluorex hydrochloride, 65 and the monoclinic $-form of phenazepam. 66 Polymorphism has also been detected in saccharin salt of ciprofloxacin, where the single-crystal structure of monoclinic form-II has been reported and contrasted with the known form-I. 67 A rich solidstate system was found for the cocrystal formed by ethenzamide and 3,5-dinitrobenzoic acid, with the cocrystal being obtained as two nonsolvated polymorphs and several solvatomorphs (acetone, 1,4-dioxane, tetrahydrofuran, mesitylene, acetonitrile, ethyl acetate, toluene, and p-xylene).…”