Conformations of some semi-rigid neuroleptic drugs. Part 1. Crystal structures of loxapine, clozapine, and HUF-2046 monohydrate {2-chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine, 8-chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,e][1,4]diazepine, and 2-chloro-11(4-methylpiperazin-1-yl)dibenzo[b,e][1,4]diazepine monohydrate}

Abstract

The crystal structures of three closely related rigid neuroleptic drugs have been determined from diffractometer data. Crystals of Loxapine (II) are orthorhombic, space group Pbca, with a= 1 796(5), b= 1 413(4), c= 1 301 (3) pm, Z= 8. Crystals of Clozapine (III) are also orthorhombic, space group P2₁2₁2₁, with a= 1 804(3), b= 957(1), c= 950(1) pm, Z= 4. Crystals of HUF-2046 (IV) are monoclinic, space group P2₁/n, with a= 936(2), b= 1 717(4), c= 1 102(3) pm, β= 102.61(1)°, Z= 4. All three structures were solved by direct methods and refined by block-diagonal least squares to the following R and R′(no. of significant reflections and total no. of observations respectively in parentheses) : (II) 0.064 (1 657), 0.081 (2 410) : (III) 0.036 (1 295), 0.043 (1 468); (IV) 0.068 (2 469), 0.073 (2 843). Hydrogen atoms were located and their positions were refined in all structures.

The molecular conformations of all three molecules are practically identical, despite the differing substitutions. The dihedral angle between the planes of the two benzene rings is (II) 114, (III) 115, and (IV) 117.5° and a partial double bond between the piperazine ring and the bicyclic system effectively prevents rotation of this former moiety.