Crystal structure of vardenafil hydrochloride trihydrate, C₂₃H₃₃N₆O₄ SCl (H₂O)₃

Journal Article · Thu Oct 04 00:00:00 EDT 2018 · Powder Diffraction

DOI:https://doi.org/10.1017/S0885715618000696· OSTI ID:1484780

Wheatley, Austin M.; Kaduk, James A. ; Gindhart, Amy M.; Blanton, Thomas N.

The crystal structure of vardenafil hydrochloride trihydrate has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Vardenafil hydrochloride trihydrate crystallizes in space group C2/c(#15) with a= 34.78347(16), b= 11.56752(4), c= 14.69308(5) Å,β= 93.3410(4), V= 5901.839(30) ų, and Z= 8. The fused ring system and the phenyl ring are nearly co-planar; the interplanar angle between them is 6.0°. Two intramolecular hydrogen bonds help determine this conformation. These planes stack along the c-axis. The side chains of these ring systems have a large U_iso and are neighbors in the stacks. Along the a-axis, these stacks are separated by hydrophilic layers of chloride, water molecules, and the positively charged nitrogen atoms of the vardenafil cation. Hydrogen bonds are prominent in the crystal structure. The protonated nitrogen atom forms a strong hydrogen bond to the chloride anion. The water molecules form a hexagon, making hydrogen bonds with themselves, as well as the C1 and a ring nitrogen atom. These discrete hydrogen bonds form a cluster, and there is no extended hydrogen bond network. There are many C–H⋯Cl, C–H⋯O, and C–H⋯N hydrogen bonds, which (although individually weak) contribute significantly to the crystal energy. The powder pattern is included in the Powder Diffraction File™ as entry 00-066-1620.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: INDUSTRY
• OSTI ID: 1484780
• Journal Information: Powder Diffraction, Vol. 33, Issue 4; ISSN 0885-7156
• Publisher: Cambridge University Press
• Country of Publication: United States
• Language: ENGLISH