Carbamazepine trifluoro­acetic acid solvate

Carbamazepine forms a 1:1 solvate with trifluoro­acetic acid (systematic name: 5H-dibenzo[b,f]azepine-5-carboxamide trifluoro­acetic acid solvate), C₁₅H₁₂N₂O·C₂HF₃O₂. The compound crystallizes with one mol­ecule of carbamazepine and one of trifluoro­acetic acid in the asymmetric unit to form an R₂²(8) motif. The solvent mol­ecule is disordered over two sites, with site-occupancy factors 0.53 (1) and 0.47 (1).

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.003 Å
• Disorder in solvent or counterion
• R factor = 0.039
• wR factor = 0.102
• Data-to-parameter ratio = 12.1

checkCIF/PLATON results

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Alert level C
PLAT062_ALERT_4_C Rescale T(min) & T(max) by .....................       0.99
PLAT244_ALERT_4_C Low   'Solvent' Ueq as Compared to Neighbors for        C17
PLAT250_ALERT_2_C Large U3/U1 Ratio for Average U(i,j) Tensor ....       2.66
PLAT302_ALERT_4_C Anion/Solvent Disorder .........................      30.00 Perc.
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          2
              C2 H F3 O2

Alert level G
ABSTM02_ALERT_3_G  When printed, the submitted absorption T values will be
            replaced by the scaled T values. Since the ratio of scaled T's
            is identical to the ratio of reported T values, the scaling
            does not imply a change to the absorption corrections used in
            the study.
            Ratio of Tmax expected/reported      0.987
            Tmax scaled      0.987 Tmin scaled      0.902
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......         31

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   5 ALERT level C = Check and explain
   2 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
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Alert level A
PUBL024_ALERT_1_A The number of authors is greater than 5.
              Please specify the role of each of the co-authors
              for your paper.

Author Response: All authors have made a contribution to the structure report. Specifically, Fernandes, Johnston, Bardin and Florence were responsible for the crystallisation screening and powder diffraction fingerprinting that resulted in the title compound. Leech, David and Shankland were responsible for the structure solution and refinement.

   1 ALERT level A = Data missing that is essential or data in wrong format
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S1. Comment

The compound carbamazepine (CBZ) is known to crystallize in at least four anhydrous polymorphic forms (Grzesiak et al., 2003) and the crystal structures of several solvates and co-crystals have been reported (Fleischman et al., 2003, Florence, Johnston, Price et al., 2006 and Florence, Leech et al., 2006). This work forms part of a wider investigation that couples automated parallel crystallization (Florence, Johnston, Fernandes et al., 2006) with crystal structure prediction methodology to investigate the basic science underlying solid-state diversity of the antiepileptic drug CBZ. The sample was identified as a novel form using multi-sample foil transmission X-ray powder diffraction analysis (Florence et al., 2003). Subsequent manual recrystallization from a saturated trifluoroacetic acid solution (TFAA) by slow evaporation at 278 K yielded samples of the title compound suitable for single-crystal X-ray diffraction at 150 K (Fig. 1).

The compound crystallizes in space group P2₁/n with one molecule of CBZ and one molecule of TFAA in the asymmetric unit. The fluorine atoms in the solvent molecule are disordered over two sites, with site occupancy factors 0.53 (1) and 0.47 (1). In the crystal structure, each molecule is connected to a TFAA molecule by N–H···O and O–H···O hydrogen bonds (Table 1). Contacts 1 (syn-oriented) and 3 form the hydrogen-bonded R₂²(8) (Etter, 1990) hetero-dimer motif observed with other carboxylic acids (Fleischman et al., 2003) (Fig. 2). CBZ also forms a second N–H···O contact (anti-oriented, contact 2) with an adjacent solvent molecule to form a chain of dimers running along the b axis.

Related literature

For details on experimental methods used to obtain this form, see: Florence et al. (2003); Florence, Johnston, Fernandes et al. (2006). For related crystal structures of carbamazepine, see: Fleischman et al. (2003); Grzesiak et al. (2003); Florence, Johnston, Price et al. (2006); Florence, Leech et al. (2006). For other related literature, see: Etter (1990).

S2. Experimental

A single-crystal sample of the title compound was recrystallized from a saturated trifluoroacetic acid solution by isothermal solvent evaporation at room temperature.

S3. Refinement

All non-hydrogen atoms were identified by direct methods and the positions of all the hydrogen atoms were obtained from the use of difference Fourier maps. In the final refinement, all hydrogen atoms were constrained to geometrically sensible positions with a riding model (SHELX97), except for H13, which was allowed to refine subject to a distance restraint and H11/H12 which were allowed to refine freely. The CF3 group exhibits significant disorder which was modelled as two distinct CF3 grounds with refined occupancy factors of about 53% and 47% respectively.

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell refinement: CrysAlis RED (Oxford Diffraction, 2006); data reduction: CrysAlis RED (Oxford Diffraction, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003) and ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: enCIFer (Allen et al., 2004) and publCIF (Westrip, 2007).

Figures

	Fig. 1. The asymmetric unit of CBZ-TFAA solvate showing 50% probablility displacement ellipsoids. Minor occupancy disordered atomic sites (trifluoroacetic acid) have been omitted for clarity.
	Fig. 2. Hydrogen bonded contacts in CBZ-TFAA showing the ajacent R22^2(8) hydrogen-bonded dimers connected by N–H···O contact (2, Table 1). Minor disorder components have been omitted for clarity.

5H-dibenzo[b,f]azepine-5-carboxamide trifluoroacetic acid solvate

Crystal data

C15H12N2O·C2HF3O2	F(000) = 720
Mr = 350.29	Dx = 1.478 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 5963 reflections
a = 15.0142 (4) Å	θ = 2.8–28.6°
b = 5.2871 (1) Å	µ = 0.13 mm^−1
c = 20.2489 (6) Å	T = 150 K
β = 101.735 (3)°	Block, colourless
V = 1573.79 (7) Å^3	0.26 × 0.12 × 0.10 mm
Z = 4

Data collection

Oxford Diffraction Gemini diffractometer	3219 independent reflections
Radiation source: Enhance (Mo) X-ray Source	2345 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.036
Detector resolution: 15.9745 pixels mm^-1	θmax = 26.4°, θmin = 2.8°
φ and ω scans	h = −18→18
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006)	k = −6→6
Tmin = 0.914, Tmax = 1.000	l = −25→25
14283 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.039	Hydrogen site location: difference Fourier map
wR(F^2) = 0.102	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	w = 1/[σ^2(Fo^2) + (0.0497P)^2 + 0.1509P] where P = (Fo^2 + 2Fc^2)/3
3219 reflections	(Δ/σ)max < 0.001
266 parameters	Δρmax = 0.18 e Å^−3
31 restraints	Δρmin = −0.20 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.61349 (8)	0.1916 (2)	0.88720 (6)	0.0347 (3)
O2	0.73657 (9)	−0.1001 (3)	0.93120 (6)	0.0425 (4)
N1	0.50894 (9)	0.3825 (3)	0.80755 (7)	0.0278 (3)
C15	0.58756 (12)	0.2517 (3)	0.82554 (8)	0.0277 (4)
N2	0.63435 (12)	0.1896 (3)	0.77939 (9)	0.0370 (4)
C1	0.45500 (12)	0.4356 (3)	0.85706 (8)	0.0281 (4)
C13	0.49565 (13)	0.6039 (3)	0.69997 (9)	0.0343 (4)
H10	0.5419	0.7178	0.7206	0.041*
C8	0.35742 (12)	0.0624 (3)	0.74805 (9)	0.0336 (4)
H6	0.3343	−0.0869	0.7245	0.040*
C3	0.43009 (13)	0.6803 (4)	0.95088 (9)	0.0367 (5)
H2	0.4455	0.8194	0.9807	0.044*
C9	0.39615 (12)	0.2490 (3)	0.70935 (9)	0.0294 (4)
C7	0.35033 (12)	0.0752 (3)	0.81274 (9)	0.0330 (4)
H5	0.3216	−0.0643	0.8294	0.040*
O3	0.78814 (11)	−0.1266 (3)	0.83537 (7)	0.0581 (5)
C2	0.47840 (12)	0.6364 (3)	0.90077 (9)	0.0321 (4)
H1	0.5276	0.7439	0.8964	0.038*
C10	0.36087 (12)	0.2735 (4)	0.63999 (9)	0.0348 (4)
H7	0.3151	0.1593	0.6187	0.042*
C6	0.38155 (11)	0.2784 (3)	0.86079 (8)	0.0292 (4)
C5	0.33566 (12)	0.3238 (4)	0.91326 (9)	0.0353 (4)
H4	0.2870	0.2156	0.9184	0.042*
C16	0.78678 (13)	−0.1839 (4)	0.89305 (10)	0.0378 (5)
C4	0.35940 (13)	0.5216 (4)	0.95756 (9)	0.0380 (5)
H3	0.3271	0.5489	0.9927	0.046*
C14	0.46605 (11)	0.4149 (3)	0.73755 (8)	0.0280 (4)
C12	0.45728 (13)	0.6257 (4)	0.63196 (9)	0.0391 (5)
H9	0.4768	0.7558	0.6058	0.047*
C11	0.39068 (13)	0.4580 (4)	0.60228 (9)	0.0383 (5)
H8	0.3654	0.4706	0.5554	0.046*
C17	0.85526 (15)	−0.3839 (4)	0.92652 (11)	0.0485 (6)
F1	0.8383 (4)	−0.4625 (10)	0.9861 (2)	0.0683 (15)	0.531 (10)
F2	0.8464 (4)	−0.5985 (7)	0.8905 (2)	0.0780 (18)	0.531 (10)
F3	0.9375 (2)	−0.3149 (10)	0.9393 (4)	0.078 (2)	0.531 (10)
F2A	0.9013 (5)	−0.4712 (16)	0.88091 (17)	0.093 (3)	0.469 (10)
F1A	0.8259 (5)	−0.5511 (14)	0.9580 (6)	0.125 (4)	0.469 (10)
F3A	0.9226 (4)	−0.2545 (11)	0.9669 (3)	0.089 (2)	0.469 (10)
H11	0.6226 (15)	0.257 (4)	0.7391 (12)	0.052 (7)*
H12	0.6879 (16)	0.108 (4)	0.7928 (11)	0.055 (7)*
H13	0.6928 (16)	0.008 (4)	0.9118 (12)	0.084 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0331 (7)	0.0466 (8)	0.0232 (7)	0.0093 (6)	0.0028 (5)	0.0017 (6)
O2	0.0423 (8)	0.0537 (9)	0.0320 (7)	0.0178 (7)	0.0083 (6)	0.0050 (6)
N1	0.0255 (7)	0.0352 (8)	0.0212 (8)	0.0000 (6)	0.0015 (6)	0.0017 (6)
C15	0.0262 (9)	0.0312 (9)	0.0244 (9)	−0.0030 (7)	0.0022 (7)	−0.0009 (8)
N2	0.0327 (9)	0.0523 (10)	0.0259 (9)	0.0084 (8)	0.0056 (7)	0.0033 (8)
C1	0.0277 (9)	0.0325 (10)	0.0220 (9)	0.0067 (7)	0.0003 (7)	0.0047 (7)
C13	0.0376 (10)	0.0366 (10)	0.0278 (10)	−0.0031 (8)	0.0048 (8)	−0.0002 (8)
C8	0.0329 (10)	0.0301 (10)	0.0358 (11)	−0.0015 (8)	0.0021 (8)	−0.0022 (8)
C3	0.0438 (11)	0.0375 (11)	0.0254 (10)	0.0082 (9)	−0.0008 (8)	−0.0006 (8)
C9	0.0286 (9)	0.0305 (9)	0.0277 (10)	0.0023 (7)	0.0026 (7)	−0.0004 (7)
C7	0.0295 (9)	0.0322 (10)	0.0359 (11)	−0.0018 (8)	0.0031 (8)	0.0056 (8)
O3	0.0580 (10)	0.0832 (11)	0.0354 (9)	0.0306 (9)	0.0153 (7)	0.0042 (8)
C2	0.0353 (10)	0.0326 (10)	0.0257 (9)	0.0014 (8)	0.0002 (8)	0.0048 (8)
C10	0.0296 (9)	0.0432 (11)	0.0291 (10)	0.0000 (8)	−0.0002 (8)	−0.0039 (9)
C6	0.0265 (9)	0.0314 (10)	0.0277 (9)	0.0046 (7)	0.0010 (7)	0.0059 (8)
C5	0.0270 (9)	0.0470 (11)	0.0309 (10)	0.0034 (8)	0.0037 (8)	0.0080 (9)
C16	0.0353 (10)	0.0465 (12)	0.0309 (11)	0.0059 (9)	0.0050 (8)	−0.0051 (9)
C4	0.0353 (10)	0.0512 (12)	0.0263 (10)	0.0138 (9)	0.0033 (8)	0.0043 (9)
C14	0.0270 (9)	0.0331 (10)	0.0231 (9)	0.0031 (7)	0.0032 (7)	−0.0002 (7)
C12	0.0444 (11)	0.0426 (11)	0.0310 (10)	0.0024 (9)	0.0092 (9)	0.0084 (9)
C11	0.0387 (11)	0.0496 (12)	0.0245 (10)	0.0067 (9)	0.0013 (8)	0.0016 (9)
C17	0.0459 (13)	0.0552 (14)	0.0436 (13)	0.0144 (11)	0.0071 (11)	−0.0038 (12)
F1	0.078 (3)	0.068 (3)	0.062 (2)	0.043 (2)	0.0242 (17)	0.0320 (19)
F2	0.090 (3)	0.051 (2)	0.090 (3)	0.022 (2)	0.009 (2)	−0.0199 (18)
F3	0.0276 (16)	0.068 (3)	0.137 (6)	0.0041 (16)	0.015 (2)	0.043 (3)
F2A	0.104 (5)	0.119 (5)	0.057 (2)	0.082 (5)	0.016 (2)	−0.002 (3)
F1A	0.083 (4)	0.061 (4)	0.252 (11)	0.030 (3)	0.082 (6)	0.076 (6)
F3A	0.062 (3)	0.134 (4)	0.061 (3)	0.048 (3)	−0.015 (2)	−0.011 (2)

Geometric parameters (Å, º)

O1—C15	1.2704 (19)	C9—C10	1.403 (2)
O2—C16	1.264 (2)	C7—C6	1.461 (2)
O2—H13	0.900 (19)	C7—H5	0.9500
N1—C15	1.353 (2)	O3—C16	1.211 (2)
N1—C1	1.439 (2)	C2—H1	0.9500
N1—C14	1.443 (2)	C10—C11	1.369 (3)
C15—N2	1.320 (2)	C10—H7	0.9500
N2—H11	0.88 (2)	C6—C5	1.400 (3)
N2—H12	0.90 (2)	C5—C4	1.377 (3)
C1—C2	1.381 (2)	C5—H4	0.9500
C1—C6	1.395 (2)	C16—C17	1.533 (3)
C13—C14	1.383 (2)	C4—H3	0.9500
C13—C12	1.385 (3)	C12—C11	1.379 (3)
C13—H10	0.9500	C12—H9	0.9500
C8—C7	1.337 (2)	C11—H8	0.9500
C8—C9	1.453 (3)	C17—F1A	1.223 (5)
C8—H6	0.9500	C17—F3	1.263 (4)
C3—C4	1.381 (3)	C17—F2	1.340 (3)
C3—C2	1.382 (3)	C17—F2A	1.343 (4)
C3—H2	0.9500	C17—F1	1.348 (4)
C9—C14	1.398 (2)	C17—F3A	1.350 (5)
C16—O2—H13	115.4 (14)	C1—C6—C5	117.10 (16)
C15—N1—C1	119.75 (13)	C1—C6—C7	123.50 (16)
C15—N1—C14	121.05 (14)	C5—C6—C7	119.39 (17)
C1—N1—C14	117.35 (13)	C4—C5—C6	121.51 (18)
O1—C15—N2	122.21 (16)	C4—C5—H4	119.2
O1—C15—N1	117.95 (15)	C6—C5—H4	119.2
N2—C15—N1	119.84 (16)	O3—C16—O2	129.10 (18)
C15—N2—H11	121.6 (14)	O3—C16—C17	117.23 (18)
C15—N2—H12	118.4 (14)	O2—C16—C17	113.66 (17)
H11—N2—H12	118 (2)	C5—C4—C3	120.00 (18)
C2—C1—C6	121.60 (17)	C5—C4—H3	120.0
C2—C1—N1	119.38 (16)	C3—C4—H3	120.0
C6—C1—N1	118.99 (15)	C13—C14—C9	121.82 (16)
C14—C13—C12	119.48 (17)	C13—C14—N1	119.83 (15)
C14—C13—H10	120.3	C9—C14—N1	118.34 (15)
C12—C13—H10	120.3	C11—C12—C13	119.85 (18)
C7—C8—C9	127.90 (17)	C11—C12—H9	120.1
C7—C8—H6	116.0	C13—C12—H9	120.1
C9—C8—H6	116.0	C10—C11—C12	120.34 (17)
C4—C3—C2	119.91 (18)	C10—C11—H8	119.8
C4—C3—H2	120.0	C12—C11—H8	119.8
C2—C3—H2	120.0	F3—C17—F2	110.0 (3)
C14—C9—C10	116.76 (16)	F1A—C17—F2A	113.6 (4)
C14—C9—C8	123.75 (16)	F3—C17—F1	105.0 (4)
C10—C9—C8	119.46 (16)	F2—C17—F1	102.1 (3)
C8—C7—C6	127.64 (17)	F1A—C17—F3A	110.8 (5)
C8—C7—H5	116.2	F2A—C17—F3A	99.5 (3)
C6—C7—H5	116.2	F1A—C17—C16	116.6 (4)
C1—C2—C3	119.78 (18)	F3—C17—C16	115.6 (3)
C1—C2—H1	120.1	F2—C17—C16	111.1 (2)
C3—C2—H1	120.1	F2A—C17—C16	109.0 (2)
C11—C10—C9	121.66 (17)	F1—C17—C16	112.1 (3)
C11—C10—H7	119.2	F3A—C17—C16	105.7 (3)
C9—C10—H7	119.2

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H11···O3^i	0.88 (2)	2.30 (2)	2.966 (2)	134 (2)
N2—H12···O3	0.90 (2)	2.01 (2)	2.889 (2)	166 (2)
O2—H13···O1	0.90 (2)	1.54 (2)	2.4326 (18)	173 (2)

Symmetry code: (i) −x+3/2, y+1/2, −z+3/2.