Cytenamide trifluoro­acetic acid solvate

Andrea Johnston; Alastair J Florence; Francesca J A Fabbiani; Kenneth Shankland; Colin T Bedford; Julie Bardin

doi:10.1107/S1600536808016577

. 2008 Jun 7;64(Pt 7):o1215–o1216. doi: 10.1107/S1600536808016577

Cytenamide trifluoroacetic acid solvate

Andrea Johnston ^a, Alastair J Florence ^a,^*, Francesca J A Fabbiani ^b, Kenneth Shankland ^c, Colin T Bedford ^d, Julie Bardin ^a

PMCID: PMC2961719 PMID: 21202853

Abstract

Cytenamide forms a 1:1 solvate with trifluoroacetic acid (systematic name: 5H-dibenzo[a,d]cycloheptatriene-5-carboxamide trifluoroacetic acid solvate), C₁₆H₁₃NO·C₂HF₃O₂. The compound crystallizes with one molecule of cytenamide and one of trifluoroacetic acid in the asymmetric unit; these are linked by O—H⋯O and N—H⋯O hydrogen bonds to form an R ₂ ²(8) motif. The trifluoromethyl group of the solvent molecule displays rotational disorder over two sites, with site-occupancy factors of 0.964 (4) and 0.036 (4).

Related literature

For details on the experimental methods used to obtain this form, see: Davis et al. (1964 ▶); Florence et al. (2003 ▶); Florence, Johnston, Fernandes et al. (2006 ▶). For literature on carbamazepine and other related structures, see: Cyr et al. (1987 ▶); Fleischman et al. (2003 ▶); Florence, Johnston, Price et al. (2006 ▶); Florence, Leech et al. (2006 ▶); Bandoli et al. (1992 ▶); Harrison et al. (2006 ▶); Leech et al. (2007 ▶); Florence, Bedford et al. (2008 ▶); Florence, Shankland et al. (2008 ▶); Fernandes et al. (2007 ▶). For hydrogen-bond motifs, see: Etter (1990 ▶); Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₁₆H₁₃NO·C₂HF₃O₂
M _r = 349.31
Monoclinic,
a = 12.1673 (11) Å
b = 6.3235 (6) Å
c = 21.4525 (15) Å
β = 101.932 (8)°
V = 1614.9 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 160 K
0.16 × 0.13 × 0.08 mm

Data collection

Oxford Diffraction Gemini S diffractometer
Absorption correction: multi-scan (ABSPACK/CrysAlis RED; Oxford Diffraction, 2006 ▶) T _min = 0.83, T _max = 0.99
10796 measured reflections
2995 independent reflections
1423 reflections with I > 2σ(I)
R _int = 0.094

Refinement

R[F ² > 2σ(F ²)] = 0.080
wR(F ²) = 0.178
S = 1.04
2984 reflections
236 parameters
24 restraints
H-atom parameters not refined
Δρ_max = 0.73 e Å⁻³
Δρ_min = −0.60 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2006 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2006 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2008 ▶) and PLATON (Spek, 2003 ▶).

Supplementary Material

Crystal structure: contains datablocks I. DOI: 10.1107/S1600536808016577/cf2202sup1.cif

e-64-o1215-sup1.cif^{(17.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808016577/cf2202Isup2.hkl

e-64-o1215-Isup2.hkl^{(149.8KB, hkl)}

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
O3—H5⋯O2ⁱ	0.89	1.58	2.462 (4)	173
N1—H11⋯O1ⁱⁱ	0.86	2.23	2.976 (4)	144
N1—H12⋯O1ⁱⁱⁱ	0.87	2.16	2.982 (5)	159

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

Acknowledgments

The authors thank the Basic Technology Programme of the UK Research Councils for funding this work under the project Control and Prediction of the Organic Solid State (www.cposs.org.uk).

supplementary crystallographic information

Comment

Cytenamide (CYT) is an analogue of carbamazepine (CBZ), a dibenzazepine drug used to control seizures (Cyr et al., 1987). Cytenamide-trifluoroacetic acid solvate (CYT-TFAA) was produced during an automated parallel crystallization study (Florence, Johnston, Fernandes et al., 2006) of CYT as part of a wider investigation that couples automated parallel crystallization with crystal structure prediction methodology to investigate the basic science underlying the solid-state diversity of CBZ (Florence, Johnston, Price et al., 2006; Florence, Leech et al., 2006) and its closely related analogues: CYT (Florence, Bedford et al., 2008), 10,11-dihydrocarbamazepine (Bandoli et al., 1992; Harrison et al., 2006; Leech et al., 2007) and cyheptamide (Florence, Shankland et al., 2008). The sample was identified as a new form using multi-sample foil transmission X-ray powder diffraction analysis (Florence et al., 2003). Subsequent manual recrystallization from a saturated TFAA solution by slow evaporation at 278 K yielded a sample suitable for single-crystal X-ray diffraction (Fig. 1).

The compound crystallizes in space group P2₁/n with one molecule of CBZ and one molecule of TFAA in the asymmetric unit. As in the structure of CBZ-TFAA solvate (Fernandes et al., 2007) the solvent molecule displays rotational disorder and the fluorine atoms were refined over two sites yielding site occupancy factors 0.964 (4), 0.036 (4) and 0.53 (1), 0.47 (1) for CYT-TFAA and CBZ-TFAA respectively. The molecules also adopt a hydrogen-bonded arrangement similar to that observed in CBZ-TFAA solvate whereby the amide group of each CYT molecule is connected to the carboxylic acid group of a TFAA molecule by N–H···O and O–H···O contacts (Table 1) to form an R₂²(8) hydrogen-bonded motif (Etter, 1990; Bernstein et al., 1995). CYT also forms a second N—H···O contact with an adjacent solvent molecule to form a chain extending along the [010] direction.

Experimental

A sample of cytenamide was synthesized according to a modification of the published method (Davis et al., 1964). A single-crystal sample of cytenamide-TFAA was grown from a saturated TFAA solution by isothermal solvent evaporation at 278 K.