A low-temperature redetermination of cyhepta­mide

Leech, C.K.; Florence, A.J.; Shankland, K.; Shankland, N.; Johnston, A.

doi:10.1107/S160053680604983X

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 63| Part 1| January 2007| Pages o205-o206

https://doi.org/10.1107/S160053680604983X

A low-temperature redetermination of cyheptamide

Charlotte K. Leech,^a Alastair J. Florence,^b ^* Kenneth Shankland,^a Norman Shankland ^b and Andrea Johnston ^b

^aISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot, Oxon OX11 0QX, England, and ^bSolid-State Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland
^*Correspondence e-mail: alastair.florence@strath.ac.uk

(Received 1 November 2006; accepted 20 November 2006; online 8 December 2006)

In the title compound [systematic name: 10,11-dihydro-5H-dibenz[a,d]cycloheptene-5-carboxamide], C₁₆H₁₅NO, N—H⋯O and N—H⋯π interactions combine to create a catemeric motif that is also observed in crystal structures of the closely related compound dihydrocarbamazepine.

Comment

Cyheptamide, (I), is an analogue of dihydrocarbamazepine, (II), the latter being a recognized impurity (Cyr et al., 1987 ) in the widely used antiepileptic drug carbamazepine, (III). The crystal structure of (I) was first reported by Codding et al. (1984 ) and the structure reported here (Fig. 1) is a low-temperature redetemination. 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 the solid-state diversity of (III) and its analogues (Florence, Johnston, Price et al., 2006 ).

The intermolecular interactions in (I) combine to create the catemeric motif shown in Fig. 2, with the geometric parameters listed in Table 1. Infinite [010] chains of molecules are linked by an N1⋯O1ⁱ [symmetry code: (i) −x + 1, y + $[{1\over 2}]$ , −z + $[{1\over 2}]$ ] hydrogen bond, supplemented by an N—H⋯π interaction, N1⋯Cg2ⁱⁱ [symmetry code: (ii) −x + 1, y − $[{1\over 2}]$ , −z + $[{1\over 2}]$ ], where Cg2 is the centroid of ring R2 (atoms C10–C15). The robustness of this motif is reflected in the fact that it is observed in all three polymorphic forms of (II) (monoclinic: Bandoli et al., 1992 ; orthorhombic: Harrison et al., 2006 ; triclinic: Leech et al., 2006 ) and in a predicted crystal structure of (III) that is isostructural with the orthorhombic form of (II) (Florence, Leech et al., 2006 ). It is notable also that the crystal structure of (I) is essentially isostructural with the monoclinic form of (II) [P2₁/c; a = 5.433 (3) Å, b = 9.129 (2) Å, c = 24.196 (5) Å, β = 96.47 (3)°, V = 1192.4 (8) Å³ at T = 150 K; Leech, 2006 ].

Figure 1
The molecular structure of (I)

, showing the atom-numbering scheme and 50% probability displacement ellipsoids.

Figure 2
The catemeric motif of (I)

. Hydrogen bonds are indicated by dashed lines.

Experimental

A single-crystal of the title compound was selected from the sample as supplied (Sigma–Aldrich Co.) without recrystallization.

Crystal data

C₁₆H₁₅NO
M_r = 237.29
Monoclinic, P 2₁ /c
a = 5.6035 (7) Å
b = 9.1716 (11) Å
c = 23.579 (3) Å
β = 96.752 (12)°
V = 1203.4 (3) Å³
Z = 4
D_x = 1.310 Mg m⁻³
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 150 (2) K
Block, colourless
0.26 × 0.17 × 0.16 mm

Data collection

Oxford Diffraction Gemini diffractometer
ω and φ scans
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006 $[Oxford Diffraction (2006). CrysAlis CCD and CrysAlis RED. Versions 1.171.29.2 (release 20-01-2006 CrysAlis171 . NET). Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]$ ) T_min = 0.956, T_max = 0.983
11433 measured reflections
2407 independent reflections
1928 reflections with I > 2σ(I)
R_int = 0.029
θ_max = 26.4°

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.035
wR(F²) = 0.086
S = 1.04
2407 reflections
223 parameters
All H-atom parameters refined
w = 1/[σ²(F_o²) + (0.0353P)² + 0.4305P] where P = (F_o² + 2F_c²)/3
(Δ/σ)_max < 0.001
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O1ⁱ	0.91 (2)	2.13 (2)	2.842 (2)	135 (1)
N1—H1B⋯Cg2ⁱⁱ	0.93 (2)	2.78 (2)	3.676 (1)	162 (1)
Symmetry codes: (i) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) $[-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

All H atoms were located in a Fourier difference map and the atomic coordinates and U_iso parameters were refined freely. X—H distances refined to N1—H1A = 0.90 (2) Å, N1—H1B = 0.93 (2) Å, C1—H1 = 1.03 (2) and 0.96 (2)–1.01 (2) Å for aromatic H atoms and 0.98 (2)–1.00 (2) Å for the CH₂ H atoms.

Data collection: CrysAlis CCD (Oxford Diffraction, 2006 $[Oxford Diffraction (2006). CrysAlis CCD and CrysAlis RED. Versions 1.171.29.2 (release 20-01-2006 CrysAlis171 . NET). Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]$ ); cell refinement: CrysAlis RED (Oxford Diffraction, 2006 $[Oxford Diffraction (2006). CrysAlis CCD and CrysAlis RED. Versions 1.171.29.2 (release 20-01-2006 CrysAlis171 . NET). Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]$ ); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Version 011105; Spek, 2003 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S160053680604983X/ez2051sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S160053680604983X/ez2051Isup2.hkl

Computing details top

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, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Version 011105; Spek, 2003); software used to prepare material for publication: SHELXL97.

10,11-dihydro-5H-dibenz[a,d]cycloheptene-5-carboxamide top

Crystal data top

C₁₆H₁₅NO	F(000) = 504
M_r = 237.29	D_x = 1.310 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 5695 reflections
a = 5.6035 (7) Å	θ = 2.4–28.0°
b = 9.1716 (11) Å	µ = 0.08 mm⁻¹
c = 23.579 (3) Å	T = 150 K
β = 96.752 (12)°	Block, colourless
V = 1203.4 (3) Å³	0.26 × 0.17 × 0.16 mm
Z = 4

Data collection top

Oxford Diffraction Gemini diffractometer	2407 independent reflections
Radiation source: Enhance (Mo) X-ray Source	1928 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.029
Detector resolution: 15.9745 pixels mm^-1	θ_max = 26.4°, θ_min = 2.8°
ω and φ scans	h = −6→6
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006)	k = −11→11
T_min = 0.956, T_max = 0.983	l = −29→28
11433 measured reflections

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)] = 0.035	Hydrogen site location: difference Fourier map
wR(F²) = 0.086	All H-atom parameters refined
S = 1.04	w = 1/[σ²(F_o²) + (0.0353P)² + 0.4305P] where P = (F_o² + 2F_c²)/3
2407 reflections	(Δ/σ)_max < 0.001
223 parameters	Δρ_max = 0.18 e Å⁻³
0 restraints	Δρ_min = −0.16 e Å⁻³

Special details top

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	0.37581 (17)	0.71849 (10)	0.21007 (4)	0.0258 (2)
C1	0.1185 (2)	0.91677 (14)	0.17364 (6)	0.0188 (3)
N1	0.4738 (2)	0.94199 (15)	0.24450 (5)	0.0266 (3)
C2	0.0314 (2)	0.81878 (14)	0.12290 (6)	0.0198 (3)
C7	0.1170 (2)	0.82304 (14)	0.06934 (6)	0.0217 (3)
C11	0.3338 (2)	1.27115 (15)	0.11228 (6)	0.0221 (3)
C16	0.3378 (2)	0.85046 (14)	0.21032 (6)	0.0201 (3)
C15	0.1420 (2)	1.07749 (14)	0.15933 (6)	0.0181 (3)
C9	0.4629 (2)	1.01088 (15)	0.09812 (6)	0.0219 (3)
C3	−0.1529 (2)	0.72033 (15)	0.13157 (7)	0.0239 (3)
C14	−0.0075 (2)	1.18044 (15)	0.18046 (6)	0.0216 (3)
C8	0.3149 (3)	0.92184 (16)	0.05173 (6)	0.0242 (3)
C6	0.0123 (3)	0.72846 (16)	0.02645 (7)	0.0292 (3)
C4	−0.2550 (3)	0.62948 (16)	0.08836 (7)	0.0296 (4)
C10	0.3137 (2)	1.12316 (15)	0.12427 (6)	0.0194 (3)
C12	0.1827 (3)	1.37355 (16)	0.13308 (6)	0.0245 (3)
C13	0.0110 (3)	1.32744 (16)	0.16701 (6)	0.0246 (3)
C5	−0.1717 (3)	0.63338 (16)	0.03540 (7)	0.0319 (4)
H3	−0.207 (3)	0.7207 (17)	0.1690 (8)	0.031 (4)*
H9B	0.594 (3)	1.0627 (16)	0.0810 (6)	0.022 (4)*
H9A	0.537 (2)	0.9436 (16)	0.1282 (7)	0.018 (4)*
H11	0.455 (3)	1.3047 (17)	0.0885 (7)	0.028 (4)*
H8B	0.239 (3)	0.9875 (17)	0.0219 (7)	0.024 (4)*
H6	0.076 (3)	0.7306 (18)	−0.0120 (8)	0.036 (5)*
H4	−0.388 (3)	0.5642 (18)	0.0965 (7)	0.032 (4)*
H14	−0.129 (3)	1.1473 (17)	0.2044 (7)	0.027 (4)*
H8A	0.422 (3)	0.8596 (18)	0.0326 (7)	0.031 (4)*
H1	−0.013 (3)	0.9104 (15)	0.2006 (7)	0.022 (4)*
H12	0.204 (3)	1.4789 (18)	0.1245 (7)	0.030 (4)*
H13	−0.097 (3)	1.3978 (18)	0.1810 (7)	0.032 (4)*
H5	−0.237 (3)	0.5704 (18)	0.0052 (8)	0.032 (4)*
H1B	0.596 (3)	0.900 (2)	0.2693 (8)	0.042 (5)*
H1A	0.452 (3)	1.040 (2)	0.2440 (8)	0.040 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0307 (5)	0.0183 (5)	0.0277 (6)	0.0030 (4)	−0.0002 (4)	0.0034 (4)
C1	0.0190 (6)	0.0194 (7)	0.0186 (7)	0.0007 (5)	0.0051 (5)	0.0008 (5)
N1	0.0313 (7)	0.0229 (7)	0.0237 (7)	−0.0003 (5)	−0.0049 (5)	0.0015 (5)
C2	0.0188 (6)	0.0168 (7)	0.0232 (7)	0.0047 (5)	0.0001 (5)	0.0006 (5)
C7	0.0235 (7)	0.0184 (7)	0.0224 (8)	0.0055 (5)	0.0000 (5)	0.0002 (5)
C11	0.0224 (7)	0.0228 (7)	0.0204 (8)	−0.0014 (6)	−0.0005 (6)	0.0029 (5)
C16	0.0230 (7)	0.0219 (8)	0.0162 (7)	−0.0004 (5)	0.0055 (5)	0.0027 (5)
C15	0.0187 (6)	0.0184 (7)	0.0166 (7)	0.0008 (5)	−0.0006 (5)	0.0002 (5)
C9	0.0210 (7)	0.0228 (7)	0.0231 (8)	0.0023 (6)	0.0066 (6)	0.0033 (6)
C3	0.0212 (7)	0.0194 (7)	0.0310 (9)	0.0032 (5)	0.0023 (6)	0.0033 (6)
C14	0.0213 (7)	0.0234 (7)	0.0202 (7)	0.0020 (6)	0.0023 (6)	−0.0020 (5)
C8	0.0292 (8)	0.0244 (8)	0.0202 (8)	0.0044 (6)	0.0080 (6)	0.0001 (6)
C6	0.0374 (8)	0.0254 (8)	0.0235 (8)	0.0059 (6)	−0.0022 (7)	−0.0020 (6)
C4	0.0247 (7)	0.0190 (7)	0.0428 (10)	0.0005 (6)	−0.0053 (7)	0.0012 (6)
C10	0.0181 (6)	0.0219 (7)	0.0176 (7)	0.0014 (5)	−0.0009 (5)	0.0002 (5)
C12	0.0291 (7)	0.0190 (7)	0.0236 (8)	0.0013 (6)	−0.0044 (6)	0.0020 (6)
C13	0.0254 (7)	0.0228 (7)	0.0245 (8)	0.0068 (6)	−0.0012 (6)	−0.0033 (6)
C5	0.0360 (8)	0.0220 (8)	0.0341 (9)	0.0022 (6)	−0.0116 (7)	−0.0057 (6)

Geometric parameters (Å, º) top

O1—C16	1.2291 (16)	C9—C8	1.529 (2)
C1—C15	1.5214 (18)	C9—H9B	1.000 (15)
C1—C2	1.5296 (19)	C9—H9A	0.994 (15)
C1—C16	1.5423 (18)	C3—C4	1.386 (2)
C1—H1	1.028 (15)	C3—H3	0.966 (18)
N1—C16	1.3381 (18)	C14—C13	1.392 (2)
N1—H1B	0.93 (2)	C14—H14	0.983 (16)
N1—H1A	0.904 (19)	C8—H8B	0.985 (16)
C2—C7	1.403 (2)	C8—H8A	0.978 (17)
C2—C3	1.405 (2)	C6—C5	1.385 (2)
C7—C6	1.407 (2)	C6—H6	1.013 (19)
C7—C8	1.527 (2)	C4—C5	1.384 (2)
C11—C12	1.392 (2)	C4—H4	0.993 (17)
C11—C10	1.3937 (19)	C12—C13	1.388 (2)
C11—H11	0.982 (16)	C12—H12	0.996 (16)
C15—C14	1.3927 (19)	C13—H13	0.967 (17)
C15—C10	1.4044 (19)	C5—H5	0.956 (17)
C9—C10	1.5034 (19)

C15—C1—C2	115.08 (11)	C4—C3—C2	121.75 (15)
C15—C1—C16	114.98 (11)	C4—C3—H3	121.7 (10)
C2—C1—C16	111.51 (11)	C2—C3—H3	116.5 (10)
C15—C1—H1	106.2 (8)	C13—C14—C15	120.75 (13)
C2—C1—H1	105.3 (8)	C13—C14—H14	120.3 (9)
C16—C1—H1	102.2 (8)	C15—C14—H14	118.9 (9)
C16—N1—H1B	116.4 (11)	C7—C8—C9	118.20 (12)
C16—N1—H1A	123.0 (12)	C7—C8—H8B	106.8 (9)
H1B—N1—H1A	120.5 (16)	C9—C8—H8B	109.8 (9)
C7—C2—C3	118.94 (13)	C7—C8—H8A	106.6 (9)
C7—C2—C1	125.19 (12)	C9—C8—H8A	109.3 (10)
C3—C2—C1	115.86 (13)	H8B—C8—H8A	105.4 (13)
C2—C7—C6	118.15 (13)	C5—C6—C7	122.24 (15)
C2—C7—C8	126.67 (12)	C5—C6—H6	119.7 (10)
C6—C7—C8	115.17 (13)	C7—C6—H6	118.1 (10)
C12—C11—C10	121.24 (14)	C5—C4—C3	119.58 (14)
C12—C11—H11	118.8 (9)	C5—C4—H4	122.1 (10)
C10—C11—H11	119.9 (9)	C3—C4—H4	118.3 (10)
O1—C16—N1	122.28 (13)	C11—C10—C15	119.15 (12)
O1—C16—C1	120.84 (12)	C11—C10—C9	121.46 (13)
N1—C16—C1	116.76 (12)	C15—C10—C9	119.31 (12)
C14—C15—C10	119.41 (12)	C13—C12—C11	119.30 (13)
C14—C15—C1	120.41 (12)	C13—C12—H12	121.2 (9)
C10—C15—C1	120.18 (11)	C11—C12—H12	119.5 (9)
C10—C9—C8	112.23 (11)	C12—C13—C14	120.12 (13)
C10—C9—H9B	108.1 (8)	C12—C13—H13	119.7 (10)
C8—C9—H9B	109.1 (9)	C14—C13—H13	120.2 (10)
C10—C9—H9A	109.9 (8)	C4—C5—C6	119.32 (14)
C8—C9—H9A	109.0 (8)	C4—C5—H5	121.0 (10)
H9B—C9—H9A	108.4 (11)	C6—C5—H5	119.7 (10)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1ⁱ	0.91 (2)	2.13 (2)	2.842 (2)	135 (1)
N1—H1B···Cg2ⁱⁱ	0.93 (2)	2.78 (2)	3.676 (1)	162 (1)

Symmetry codes: (i) −x+1, y+1/2, −z+1/2; (ii) −x+1, y−1/2, −z+1/2.

Acknowledgements

We thank the Basic Technology programme of the UK Research Councils for funding under the project Control and Prediction of the Organic Solid State (URL: https://www.cposs.org.uk).

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