Quetiapine N-oxide–fumaric acid (2/1)

The title compound (systematic name: 2-{2-[4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl 1-oxide]ethoxy}ethanol–fumaric acid (2/1)), C21H25N3O3S·0.5C4H4O4, is one of the oxidation products of quetiapine hemifumaric acid. In the tricyclic fragment, the central thiazepine ring displays a boat conformation and the benzene rings are inclined to each other at a dihedral angle of 72.0 (2)°. The piperazine ring adopts a chair conformation with its ethoxyethanol side chain oriented equatorially. In addition to the main molecule, the asymmetric unit contains one-half molecule of fumaric acid, the complete molecule being generated by inversion symmetry. In the crystal, O—H⋯O hydrogen bonds link the components into corrugated layers parallel to bc plane.

The title compound (systematic name: 2-{2- [4-(dibenzo[b,f]-[1,4]thiazepin-11-yl)piperazin-1-yl 1-oxide]ethoxy}ethanolfumaric acid (2/1)), C 21 H 25 N 3 O 3 SÁ0.5C 4 H 4 O 4 , is one of the oxidation products of quetiapine hemifumaric acid. In the tricyclic fragment, the central thiazepine ring displays a boat conformation and the benzene rings are inclined to each other at a dihedral angle of 72.0 (2) . The piperazine ring adopts a chair conformation with its ethoxyethanol side chain oriented equatorially. In addition to the main molecule, the asymmetric unit contains one-half molecule of fumaric acid, the complete molecule being generated by inversion symmetry. In the crystal, O-HÁ Á ÁO hydrogen bonds link the components into corrugated layers parallel to bc plane.
Quetiapine N-oxide-fumaric acid (2/1) Jin Shen, Jing-Jing Qian, Su-Xiang Wu, Jian-Ming Gu and Xiu-Rong Hu Comment Quetiapine N-oxide hemifumarate is one of the oxidation or degradation products of quetiapine hemifumarate (Mittapelli et al., 2010;Trivedi et al., 2011& Belal et al., 2008. Quetiapine is one of the atypical antipsychotic licensed for the treatment of schizophrenia (Lieberman, 1996) or manic episodes associated with bipolar disorder. In the present study, we report the crystal structure of quetiapine N-oxide hemifumarate, (I), recrystallized from ethanol.
In the crystal structure of (I) (Fig.1), the asymmetric unit consists of one quetiapine N-oxide molecule and one-half of fumarate molecule; the latter one is situated on inversion center. The oxidized N atom is established as N3. The N-C bonds at N3 are lengthened [mean value 1.504 (5) Å compared to 1.427 (5) Å for N2], as would be expected for an oxidized system. The values of bond length for N3-O1 is 1.388 (4) Å. Consequently, N3 shows quaternary character in a tetrahedral configuration, with bond angles ranging from 108.5 (3)° to 110.3 (3)°.
The conformation of the title compound is similar to that of quetiapine hemifumarate (Ravikumar et al., 2005). The conformation of the central thiazepine ring in the (6,7,6)-tricyclic ring system can be described as a boat, with the atoms common to the benzene rings (C2, C7, C8 and C13) as the basal plane, the S atom as the bow and the N1=C1 bridge as the stern. The bow angle is 50.0 (2)° and the stern angle is 41.7 (2)°. This enables the dibenzothiazepine ring skeleton to form a flattened V-shaped conformation. The dihedral angle between the two benzene rings is 72.0 (2)°. The piperazine ring adopts a chair conformation. The thiazepine nucleus can be viewed as being in an equatorial orientation to the piperazine ring. The ethoxyethanol side chain at the oxidized N-atom site of the piperazine ring occupies an equatorial orientation and is in a folded conformation.
In the crystal structure, intermolecular hydrogen bonds O-H···O (Table 1) link all moieties into corrugated layers parallel to bc plane.

Experimental
The crude product synthesized by reacting quetiapine hemifumarate with hydrogen peroxideis was supplied by Zhejiang Supor Pharmaceuticals Co., Ltd. It was recrystallized from ethanol solution, giving colourless crystals of (I) suitable for X-ray diffraction.

Computing details
Data collection: PROCESS-AUTO (Rigaku, 2006); cell refinement: PROCESS-AUTO (Rigaku, 2006); data reduction: CrystalStructure (Rigaku, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software supplementary materials sup-2 Acta Cryst. (2012). E68, o1753-o1754 used to prepare material for publication: WinGX (Farrugia, 1999). Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. 119.2 (4) O2-C19-H19B 109.7 C6-C7-S1