The structure of a psychoactive agent: 7-chloro-3-hydroxy-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (temazepam)

Abstract

The structure of temazepam was solved by direct methods and then refined to R = 0.057 (R w = 0.040) for 5108 intensities collected on a diffractometer. conformation with AC] = 3.5, 3.1 and 3.3 o for the three independent molecules. The 3-hydroxy group is in an equatorial position and the angles between the planes of both the phenyl rings are 66.0, 66.8 and 58.7 ° for the three molecules. The conformations and the bond lengths and angles in all three molecules are similar to each other and to those found in other 1,3-dihydro-2H-1,4-benzodiazepin-2-ones.

Experimental and Solid-State Computational Study of Structural and Dynamic Properties in the Equilibrium Form of Temazepam

“…Temazepam was purchased in a hermetically sealed container from Polfa Tarchomin S.A., Poznań. Its structure was controlled by PXRD, confirming the crystallographic structure reported in ref (Form 0). The differential scanning calorimetry measurements, made in the range from 100 K to the melting point (431–433 K), have shown no phase transition in this temperature range.…”

“…The seven-membered diazepinone ring assumes a boat conformation with the hydroxyl group at the equatorial position. The possibility of hydrogen bond formation is a probable reason for different packing of molecules in the crystal …”

“…Solid-state density functional theory (DFT) , computations were applied in order to understand the structural properties and magnetic response of the title system. The structure reported by Gałdecki was used as the starting point in further geometry optimization. Periodic boundary conditions (PBC) calculations were carried out using a plane-wave pseudopotential method as implemented in CASTEP version 6.1. , …”

“…The fixed-cell optimization was performed relaxing the fractional coordinates as well as optimizing only the hydrogen positions in the frame of the Gałdecki structure . The optimization was performed with the convergence criteria for the total energy, maximum force, maximum atomic displacement, and SCF iterations smaller than 5 × 10 –7 eV/atom, 0.0025 eV/Å, 5 × 10 –5 Å, and 1 × 10 –9 eV/atom, respectively.…”

“…The patent literature − gives information concerning the melting point of different polymorphs of temazepam as well as infrared (IR) absorption and powder X-ray diffraction (PXRD) data, which are used to identify the polymorph. For the first time the structure of temazepam (form 0, anhydrous) was determined in ref , and very recently the authors solved the crystallographic structure of the two anhydrous forms of temazepam (named forms X and forms VI).…”