β-Polymorph of phenazepam: a powder study.

Area of Science:

• Crystallography
• Solid-state chemistry
• Pharmaceutical science

Background:

• Phenazepam is a known benzodiazepine with an established alpha-polymorph.
• Polymorphism in pharmaceuticals can significantly impact drug properties and efficacy.
• Understanding different crystal forms is crucial for drug development and manufacturing.

Purpose of the Study:

• To obtain and characterize a novel beta-polymorph of phenazepam.
• To investigate the structural differences between the alpha and beta polymorphs of phenazepam.
• To explore the effects of cryomodification on crystal structure.

Main Methods:

• Cryomodification of the known alpha-polymorph of phenazepam.
• Single-crystal X-ray diffraction analysis to determine molecular and crystal structures.
• Analysis of dihedral angles and intermolecular interactions (hydrogen bonding).

Main Results:

• The beta-polymorph of phenazepam (C15H10BrClN2O) was successfully synthesized via cryomodification.
• Molecules in both polymorphs form centrosymmetric dimers through N-H⋯O hydrogen bonds.
• The beta-polymorph exhibits a larger dihedral angle (86.2°) between aromatic rings compared to the alpha-polymorph (75.4°).
• Weak intermolecular C-H⋯O hydrogen bonds in the beta-polymorph create layered structures parallel to the bc plane.

Conclusions:

• Cryomodification is an effective method for obtaining new polymorphic forms of phenazepam.
• The beta-polymorph of phenazepam possesses distinct structural characteristics, particularly in its dihedral angles and intermolecular interactions.
• The identified structural differences may influence the physicochemical properties of phenazepam, warranting further investigation.