Fluphenazine dihydro­chloride dimethanol solvate

Joanna Petrus; Rafał Petrus; Bogusława Czarnik-Matusewicz

doi:10.1107/S1600536812008707

. 2012 Mar 10;68(Pt 4):o1004–o1005. doi: 10.1107/S1600536812008707

Fluphenazine dihydrochloride dimethanol solvate

Joanna Petrus ^a,^*, Rafał Petrus ^a, Bogusława Czarnik-Matusewicz ^a

PMCID: PMC3343971 PMID: 22589880

Abstract

In the title compound {systematic name: 1-(2-hydroxyethyl)-4-[3-(2-trifluoromethyl-10H-phenothiazin-10-yl)propyl]piperazine-1,4-diium dichloride dimethanol disolvate}, C₂₂H₂₈F₃N₃OS²⁺·2Cl⁻·2CH₃OH, the dihedral angle between the planes of the two outer benzene rings of the tricyclic phenothiazine system is 46.91 (13)°. The piperazine ring adopts a chair conformation. The crystal structure is stabilized by O—H⋯Cl, N—H⋯Cl, C—H⋯O, C—H⋯Cl and C—H⋯F hydrogen bonds and contacts.

Related literature

For the properties of phenothiazines, see: Ford et al. (1988 ▶); Ohlow & Moosmann (2011 ▶); Tsakovska & Pajeva (2006 ▶) and for the biological properties of fluphenazine, see: Gasiorowski et al. (2001 ▶); Szabó et al. (1999 ▶). For related structures, see: Dahl et al. (1986 ▶); Dutkiewicz et al. (2010 ▶); McDowell (1978 ▶, 1980 ▶); Yathirajan et al. (2007 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶);.

Experimental

Crystal data

C₂₂H₂₈F₃N₃OS²⁺·2Cl⁻·2(CH₄O)
M _r = 574.53
Orthorhombic,
a = 39.76 (2) Å
b = 9.952 (8) Å
c = 7.127 (5) Å
V = 2820 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.35 mm⁻¹
T = 85 K
0.24 × 0.02 × 0.01 mm

Data collection

Oxford Diffraction Xcalibur PX κ-geometry diffractometer with Onyx CCD camera
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2007 ▶) T _min = 0.850, T _max = 1.000
43952 measured reflections
13922 independent reflections
10615 reflections with I > 2σ(I)
R _int = 0.052

Refinement

R[F ² > 2σ(F ²)] = 0.084
wR(F ²) = 0.197
S = 1.19
13922 reflections
330 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 1.25 e Å⁻³
Δρ_min = −0.85 e Å⁻³
Absolute structure: Flack (1983 ▶), 5579 Friedel pairs
Flack parameter: 0.09 (7)

Data collection: CrysAlis CCD (Oxford Diffraction, 2007 ▶); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2007 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP in SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812008707/bt5828sup1.cif

e-68-o1004-sup1.cif^{(35.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812008707/bt5828Isup2.hkl

e-68-o1004-Isup2.hkl^{(680.5KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812008707/bt5828Isup3.cdx

Supplementary material file. DOI: 10.1107/S1600536812008707/bt5828Isup4.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N16—H16⋯Cl2	0.93	2.12	3.017 (3)	161
N18—H18⋯Cl1	0.93	2.16	3.078 (3)	171
O24—H24⋯Cl1	0.84	2.31	3.147 (3)	172
O22—H22⋯Cl2ⁱ	0.84	2.27	3.065 (3)	157
O23—H23⋯Cl2ⁱⁱ	0.84	2.36	3.169 (3)	163
C18—H18A⋯O22	0.99	2.23	2.924 (4)	126
C21—H21A⋯O23	0.99	2.39	3.266 (5)	147
C2—H2⋯F13Aⁱⁱⁱ	0.95	2.45	3.381 (4)	165
C14—H14A⋯O23ⁱⁱ	0.99	2.51	3.482 (5)	169
C17—H17A⋯O24^iv	0.99	2.24	3.215 (4)	166
C17—H17B⋯O22ⁱ	0.99	2.55	3.379 (5)	141
C16—H16B⋯Cl2^v	0.99	2.67	3.619 (4)	161
C19—H19B⋯Cl2ⁱⁱ	0.99	2.75	3.529 (3)	136

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

This work was supported by the Polish Ministry of Sciences and Higher Education (grant Nos. N N204 150440 and N N204 150338) and the European Social Funds (ESF) in the areas of Human Capital Strategy Program and the Marshal’s Office of Lower Silesia.

supplementary crystallographic information

Comment

Fluphenazine (2-(4-(3-(2-(trifluoromethyl)-10H-phenothiazin-10-yl)propyl) piperazin-1-yl)ethanol)) (FPh) belongs to one of the oldest and the biggest family of antipsychotic drugs known as phenothiazines (Ohlow & Moosmann, 2011). Apart from its application in the treatment of many psychoses (mainly schizophrenia, mania and paranoid syndromes), it exhibits also a broad spectrum of biological effects, among them the anti-MDR (multidrug resistance) potency. (Gasiorowski et al., 2001; Szabó et al., 1999). Due to the anti-MDR activity of phenothiazines is strictly correlated with their structure (Tsakovska & Pajeva, 2006; Ford et al., 1988), the aim of our work is to characterize the solid state structure of fluphenazine. In the crystal structure of I (Fig. 1), the dihedral angle between the planes of the two outer benzene rings of the phenothiazine system known as 'butterfly angle', correlates with values find for phenothiazines with high biological activity (Dahl et al., 1986; McDowell, 1978; Yathirajan et al., 2007). The piperazine ring adopts a chair conformation, as in the case before reported fluphenazine dipicrate (Dutkiewicz et al., 2010), described by the Cremer & Pople (1975) puckering parameters q₂ = 0.019 Å, φ₂ = 13.9°, q₃ = -0.593 Å, Q = 0.593 Å, θ = 178.2°. The crystal structure is stabilized by O—H···Cl, N—H···Cl, C—H···O, C—H···Cl and C—H···F hydrogen bonds and contacts (Table 1 and Fig. 2), that are very similar to those in trifluperazine dihydrochloride (McDowell, 1980).

Experimental

The FPh^2+.2Cl^-.2CH₃OH crystals were obtained by slow evaporation of methanol solution of dihydrochloride fluphenazine (Jelfa) at -15°C.