10,11-Dihydro­carbamazepine formic acid solvate

Johnston, A.; Florence, A.J.; Fernandes, P.; Shankland, N.; Kennedy, A.R.

doi:10.1107/S1600536807008124

organic compounds

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ISSN: 2056-9890

Volume 63| Part 3| March 2007| Pages o1469-o1470

https://doi.org/10.1107/S1600536807008124

10,11-Dihydrocarbamazepine formic acid solvate

Andrea Johnston,^a Alastair J. Florence,^a ^* Philippe Fernandes,^a Norman Shankland ^a and Alan R. Kennedy ^b

^aSolid-State Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland, and ^bWestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland
^*Correspondence e-mail: alastair.florence@strath.ac.uk

(Received 5 January 2007; accepted 18 February 2007; online 28 February 2007)

In the title compound [systematic name: 10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide methanoic acid solvate], C₁₅H₁₄N₂O·CH₂O₂, the dihydrocarbamazepine and formic acid molecules are hydrogen bonded to form an R²₂(8) motif, which is further connected into a centrosymmetric double motif arrangement.

Comment

10,11-Dihydrocarbamazepine (DHC) is a recognized impurity in carbamazepine (CBZ), a dibenzazepine drug used to control seizures (Cyr et al., 1987 ). DHC is known to crystallize in three polymorphic forms: monoclinic form I (Bandoli et al., 1992 ), orthorhombic form II (Harrison et al., 2006 ) and triclinic form III (Leech et al., 2007a ). The title compound, (I), was produced during an automated parallel crystallization search (Florence, Johnston, Fernandes et al., 2006 ) on DHC as part of a wider study into the predicted and experimental structures of CBZ (Florence, Johnston, Price et al., 2006 ; Florence, Leech et al., 2006 ) and related molecules (Leech et al., 2007b ). 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 formic acid solution by slow evaporation at 298 K yielded samples of (I) suitable for single-crystal diffraction (Fig. 1).

The molecules in (I) adopt a hydrogen-bonded arrangement similar to that observed in the CBZ formic acid (1/1) solvate (Fleischman et al., 2003 ). Specifically, the DHC and formic acid molecules are connected via O2—H2⋯O1 and N2—H2A⋯O3 hydrogen bonds to form an R₂²(8) (Etter, 1990 ) dimer motif (Table 1). A third hydrogen bond, N2—H2B⋯O3ⁱ [symmetry code: (i) −x + 1, −y + 1, −z] joins adjacent dimers to form a centrosymmetric double motif arrangement (Fig. 2).

Figure 1
The asymmetric unit of (I)

, showing the atomic numbering used. Displacement ellipsoids are drawn at the 50% probability level; H atoms are shown as circles of arbitrary radius and hydrogen bonds as dashed lines.

Figure 2
Plot showing the hydrogen-bonded dimer arrangement in (I)

with two R₂²(8) dimers joined in a centrosymmetric arrangement via an R₄²(8) motif.

Experimental

DHC was used as received from Sigma–Aldrich and a single-crystal sample of the title compound was obtained by slow evaporation of a saturated formic acid solution at 298 K.

Crystal data

C₁₅H₁₄N₂O·CH₂O₂
M_r = 284.31
Triclinic, $[P \overline 1]$
a = 5.2298 (4) Å
b = 9.3849 (12) Å
c = 14.4858 (18) Å
α = 83.853 (5)°
β = 88.230 (7)°
γ = 88.221 (7)°
V = 706.28 (14) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 123 (2) K
0.40 × 0.10 × 0.04 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: none
9817 measured reflections
1956 independent reflections
1260 reflections with I > 2σ(I)
R_int = 0.075
θ_max = 23.0°

Refinement

R[F² > 2σ(F²)] = 0.049
wR(F²) = 0.105
S = 1.10
1956 reflections
202 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O1	1.04 (4)	1.52 (4)	2.552 (3)	170 (4)
N2—H2A⋯O3	0.88 (3)	2.08 (3)	2.933 (4)	163 (3)
N2—H2B⋯O3ⁱ	0.89 (3)	2.13 (3)	2.873 (4)	141 (2)
Symmetry code: (i) -x+1, -y+1, -z.

The three H-atoms attached to N2 and O2 were located in a difference map and refined isotropically [N—H = 0.88 (3) and 0.89 (3) Å; O—H = 1.04 (4) Å]. All other H atoms were constrained to idealized geometries and included in the refinement using the riding-model approximation: U_iso(H) = 1.2U_eq(C) and C—H = 0.95 or 0.99 Å.

Data collection: COLLECT (Hooft, 1988 ) and DENZO (Otwinowski & Minor, 1997 ); cell refinement: DENZO and COLLECT; data reduction: DENZO; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536807008124/ya2039sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536807008124/ya2039Isup2.hkl

Computing details top

Data collection: COLLECT (Hooft, 1988) and DENZO (Otwinowski & Minor, 1997); cell refinement: DENZO and COLLECT; data reduction: DENZO; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97.

10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide–methanoic acid (1/1) top

Crystal data top

C₁₅H₁₄N₂O·CH₂O₂	Z = 2
M_r = 284.31	F(000) = 300
Triclinic, P1	D_x = 1.337 Mg m⁻³
a = 5.2298 (4) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.3849 (12) Å	Cell parameters from 1893 reflections
c = 14.4858 (18) Å	θ = 2.9–23.0°
α = 83.853 (5)°	µ = 0.09 mm⁻¹
β = 88.230 (7)°	T = 123 K
γ = 88.221 (7)°	Cut needle, colourless
V = 706.28 (14) Å³	0.40 × 0.10 × 0.04 mm

Data collection top

Nonius KappaCCD diffractometer	1260 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.075
Graphite monochromator	θ_max = 23.0°, θ_min = 3.4°
φ and ω scans	h = −5→5
9817 measured reflections	k = −10→10
1956 independent reflections	l = −15→15

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.105	H atoms treated by a mixture of independent and constrained refinement
S = 1.10	w = 1/[σ²(F_o²) + (0.0384P)² + 0.1228P] where P = (F_o² + 2F_c²)/3
1956 reflections	(Δ/σ)_max < 0.001
202 parameters	Δρ_max = 0.21 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

Special details top

Experimental. Sample crystals twinned. "Single" small piece cut out from a larger, twinned sample.

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 (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.8138 (3)	0.2089 (2)	0.16182 (13)	0.0296 (5)
O2	0.4587 (4)	0.0846 (2)	0.08699 (14)	0.0334 (6)
O3	0.3740 (4)	0.2814 (2)	−0.01018 (15)	0.0396 (6)
N1	0.9571 (4)	0.4012 (2)	0.22662 (16)	0.0210 (6)
N2	0.7533 (5)	0.4307 (3)	0.08607 (19)	0.0303 (7)
C1	0.8391 (5)	0.3413 (3)	0.1576 (2)	0.0240 (7)
C2	1.0350 (5)	0.3108 (3)	0.3085 (2)	0.0228 (7)
C3	1.2318 (5)	0.2098 (3)	0.2976 (2)	0.0287 (8)
H3	1.3057	0.2014	0.2376	0.034*
C4	1.3197 (5)	0.1222 (3)	0.3728 (2)	0.0346 (8)
H4	1.4536	0.0535	0.3649	0.042*
C5	1.2126 (6)	0.1347 (3)	0.4601 (2)	0.0375 (8)
H5	1.2707	0.0737	0.5123	0.045*
C6	1.0202 (5)	0.2364 (3)	0.4710 (2)	0.0316 (8)
H6	0.9502	0.2454	0.5314	0.038*
C7	0.9255 (5)	0.3262 (3)	0.3960 (2)	0.0251 (7)
C8	0.7116 (5)	0.4311 (3)	0.4178 (2)	0.0316 (8)
H8A	0.7784	0.4946	0.4612	0.038*
H8B	0.5737	0.3753	0.4516	0.038*
C9	0.5902 (5)	0.5259 (3)	0.3387 (2)	0.0302 (8)
H9A	0.5071	0.4645	0.2976	0.036*
H9B	0.4552	0.5877	0.3646	0.036*
C10	0.7779 (5)	0.6198 (3)	0.2814 (2)	0.0260 (7)
C11	0.9627 (5)	0.5542 (3)	0.22754 (19)	0.0222 (7)
C12	1.1457 (5)	0.6342 (3)	0.1759 (2)	0.0292 (8)
H12	1.2713	0.5880	0.1398	0.035*
C13	1.1451 (5)	0.7815 (3)	0.1770 (2)	0.0351 (8)
H13	1.2703	0.8366	0.1416	0.042*
C14	0.9616 (6)	0.8484 (3)	0.2297 (2)	0.0379 (9)
H14	0.9604	0.9495	0.2305	0.046*
C15	0.7796 (6)	0.7672 (3)	0.2813 (2)	0.0330 (8)
H15	0.6540	0.8136	0.3173	0.040*
C16	0.3294 (5)	0.1610 (4)	0.0221 (2)	0.0313 (8)
H16	0.1873	0.1172	−0.0015	0.038*
H2	0.603 (7)	0.143 (4)	0.112 (3)	0.095 (13)*
H2A	0.661 (6)	0.390 (3)	0.047 (2)	0.051 (11)*
H2B	0.772 (5)	0.525 (3)	0.0820 (19)	0.030 (9)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0344 (11)	0.0196 (13)	0.0353 (14)	0.0023 (9)	−0.0079 (9)	−0.0045 (10)
O2	0.0402 (13)	0.0269 (13)	0.0332 (14)	−0.0025 (10)	−0.0093 (10)	−0.0005 (11)
O3	0.0433 (13)	0.0257 (14)	0.0488 (15)	−0.0036 (10)	−0.0159 (11)	0.0054 (12)
N1	0.0267 (12)	0.0143 (14)	0.0217 (15)	0.0005 (10)	−0.0032 (11)	0.0006 (12)
N2	0.0413 (17)	0.0199 (18)	0.0294 (18)	−0.0020 (13)	−0.0108 (13)	0.0013 (15)
C1	0.0231 (16)	0.024 (2)	0.025 (2)	0.0050 (13)	0.0009 (14)	−0.0047 (17)
C2	0.0234 (15)	0.0192 (17)	0.026 (2)	−0.0019 (13)	−0.0043 (13)	−0.0014 (15)
C3	0.0330 (17)	0.0253 (18)	0.028 (2)	0.0018 (14)	−0.0029 (14)	−0.0052 (16)
C4	0.0389 (18)	0.0260 (19)	0.038 (2)	0.0112 (15)	−0.0112 (17)	−0.0015 (17)
C5	0.0461 (19)	0.031 (2)	0.034 (2)	0.0018 (16)	−0.0160 (16)	0.0034 (17)
C6	0.0371 (18)	0.0312 (19)	0.026 (2)	−0.0037 (15)	−0.0027 (14)	0.0011 (16)
C7	0.0271 (16)	0.0203 (17)	0.028 (2)	−0.0037 (13)	−0.0025 (14)	−0.0009 (15)
C8	0.0298 (17)	0.0327 (19)	0.031 (2)	−0.0003 (14)	0.0045 (14)	−0.0014 (16)
C9	0.0268 (16)	0.0319 (19)	0.032 (2)	0.0054 (14)	−0.0015 (14)	−0.0052 (16)
C10	0.0243 (16)	0.0237 (19)	0.030 (2)	0.0013 (14)	−0.0091 (14)	−0.0003 (16)
C11	0.0244 (16)	0.0190 (18)	0.0226 (18)	0.0025 (13)	−0.0055 (13)	0.0009 (14)
C12	0.0249 (17)	0.031 (2)	0.031 (2)	−0.0007 (14)	−0.0043 (14)	0.0036 (16)
C13	0.0354 (19)	0.028 (2)	0.039 (2)	−0.0085 (15)	−0.0083 (15)	0.0097 (17)
C14	0.050 (2)	0.0170 (18)	0.047 (2)	−0.0040 (17)	−0.0233 (18)	0.0026 (18)
C15	0.0417 (19)	0.021 (2)	0.037 (2)	0.0062 (15)	−0.0113 (16)	−0.0072 (16)
C16	0.0299 (17)	0.034 (2)	0.031 (2)	0.0000 (16)	−0.0053 (15)	−0.0073 (18)

Geometric parameters (Å, º) top

O1—C1	1.249 (3)	C6—H6	0.9500
O2—C16	1.311 (3)	C7—C8	1.515 (4)
O2—H2	1.04 (4)	C8—C9	1.517 (4)
O3—C16	1.203 (3)	C8—H8A	0.9900
N1—C1	1.370 (3)	C8—H8B	0.9900
N1—C11	1.439 (3)	C9—C10	1.509 (4)
N1—C2	1.444 (3)	C9—H9A	0.9900
N2—C1	1.341 (4)	C9—H9B	0.9900
N2—H2A	0.88 (3)	C10—C15	1.384 (4)
N2—H2B	0.89 (3)	C10—C11	1.393 (4)
C2—C7	1.393 (4)	C11—C12	1.385 (4)
C2—C3	1.394 (4)	C12—C13	1.384 (4)
C3—C4	1.375 (4)	C12—H12	0.9500
C3—H3	0.9500	C13—C14	1.385 (4)
C4—C5	1.382 (4)	C13—H13	0.9500
C4—H4	0.9500	C14—C15	1.387 (4)
C5—C6	1.383 (4)	C14—H14	0.9500
C5—H5	0.9500	C15—H15	0.9500
C6—C7	1.396 (4)	C16—H16	0.9500

C16—O2—H2	112 (2)	C7—C8—H8B	107.6
C1—N1—C11	121.2 (2)	C9—C8—H8B	107.6
C1—N1—C2	119.3 (2)	H8A—C8—H8B	107.0
C11—N1—C2	118.4 (2)	C10—C9—C8	113.6 (2)
C1—N2—H2A	114 (2)	C10—C9—H9A	108.8
C1—N2—H2B	122.6 (18)	C8—C9—H9A	108.8
H2A—N2—H2B	123 (3)	C10—C9—H9B	108.8
O1—C1—N2	121.9 (3)	C8—C9—H9B	108.8
O1—C1—N1	120.8 (3)	H9A—C9—H9B	107.7
N2—C1—N1	117.2 (3)	C15—C10—C11	118.4 (3)
C7—C2—C3	120.7 (3)	C15—C10—C9	123.3 (3)
C7—C2—N1	121.9 (2)	C11—C10—C9	118.2 (2)
C3—C2—N1	117.4 (3)	C12—C11—C10	120.9 (3)
C4—C3—C2	120.6 (3)	C12—C11—N1	121.0 (2)
C4—C3—H3	119.7	C10—C11—N1	118.1 (2)
C2—C3—H3	119.7	C13—C12—C11	119.9 (3)
C3—C4—C5	119.7 (3)	C13—C12—H12	120.1
C3—C4—H4	120.1	C11—C12—H12	120.1
C5—C4—H4	120.1	C12—C13—C14	119.9 (3)
C4—C5—C6	119.6 (3)	C12—C13—H13	120.1
C4—C5—H5	120.2	C14—C13—H13	120.1
C6—C5—H5	120.2	C13—C14—C15	119.8 (3)
C5—C6—C7	122.1 (3)	C13—C14—H14	120.1
C5—C6—H6	118.9	C15—C14—H14	120.1
C7—C6—H6	118.9	C10—C15—C14	121.1 (3)
C2—C7—C6	117.2 (3)	C10—C15—H15	119.4
C2—C7—C8	126.3 (3)	C14—C15—H15	119.4
C6—C7—C8	116.5 (3)	O3—C16—O2	126.0 (3)
C7—C8—C9	119.1 (3)	O3—C16—H16	117.0
C7—C8—H8A	107.6	O2—C16—H16	117.0
C9—C8—H8A	107.6

C11—N1—C1—O1	−173.2 (2)	C6—C7—C8—C9	−176.6 (2)
C2—N1—C1—O1	−4.9 (4)	C7—C8—C9—C10	−58.4 (3)
C11—N1—C1—N2	6.9 (4)	C8—C9—C10—C15	−110.7 (3)
C2—N1—C1—N2	175.2 (2)	C8—C9—C10—C11	67.7 (3)
C1—N1—C2—C7	−114.7 (3)	C15—C10—C11—C12	0.6 (4)
C11—N1—C2—C7	53.9 (3)	C9—C10—C11—C12	−177.8 (2)
C1—N1—C2—C3	67.4 (3)	C15—C10—C11—N1	−178.9 (2)
C11—N1—C2—C3	−124.0 (3)	C9—C10—C11—N1	2.6 (4)
C7—C2—C3—C4	0.7 (4)	C1—N1—C11—C12	−83.4 (3)
N1—C2—C3—C4	178.6 (2)	C2—N1—C11—C12	108.2 (3)
C2—C3—C4—C5	−0.1 (4)	C1—N1—C11—C10	96.2 (3)
C3—C4—C5—C6	−0.8 (4)	C2—N1—C11—C10	−72.2 (3)
C4—C5—C6—C7	1.3 (4)	C10—C11—C12—C13	−0.4 (4)
C3—C2—C7—C6	−0.3 (4)	N1—C11—C12—C13	179.2 (2)
N1—C2—C7—C6	−178.1 (2)	C11—C12—C13—C14	0.0 (4)
C3—C2—C7—C8	180.0 (2)	C12—C13—C14—C15	0.1 (4)
N1—C2—C7—C8	2.2 (4)	C11—C10—C15—C14	−0.5 (4)
C5—C6—C7—C2	−0.7 (4)	C9—C10—C15—C14	177.9 (3)
C5—C6—C7—C8	179.0 (3)	C13—C14—C15—C10	0.1 (4)
C2—C7—C8—C9	3.1 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O1	1.04 (4)	1.52 (4)	2.552 (3)	170 (4)
N2—H2A···O3	0.88 (3)	2.08 (3)	2.933 (4)	163 (3)
N2—H2B···O3ⁱ	0.89 (3)	2.13 (3)	2.873 (4)	141 (2)

Symmetry code: (i) −x+1, −y+1, −z.

Acknowledgements

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 (https://www.cposs.org.uk).

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