Cytenamide–formic acid (1/1)

Johnston, A.; Florence, A.J.; Miller, G.J.; Kennedy, A.R.; Bedford, C.T.

doi:10.1107/S1600536808019181

organic compounds

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ISSN: 2056-9890

Volume 64| Part 8| August 2008| Pages o1379-o1380

doi:10.1107/S1600536808019181

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Cytenamide–formic acid (1/1)

Andrea Johnston,^a Alastair J. Florence,^a ^* Gary J. Miller,^a Alan R. Kennedy ^b and Colin T. Bedford ^c

^aSolid-State Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, The John Arbuthnott Building, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland, ^bWestCHEM, Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland, and ^cUniversity College London, Department of Chemistry, 20 Gordon Street, London WC1H 0AJ, England
^*Correspondence e-mail: alastair.florence@strath.ac.uk'

(Received 16 May 2008; accepted 24 June 2008; online 5 July 2008)

In the crystal structure of the title compound [systematic name: 5H-dibenzo[a,d]cycloheptatriene-5-carboxamide–methanoic acid (1/1)], C₁₆H₁₃NO·CH₂O₂, the cytenamide and solvent molecules form a hydrogen-bonded R₂²(8) dimer motif, which is further connected to form a centrosymmetric double-motif arrangement. The asymmetric unit contains two formula units.

Related literature

For details on experimental methods used to obtain this form, see: Davis et al. (1964 ); Florence et al. (2003 ); Florence, Johnston, Fernandes et al. (2006 ). For related literature on cytenamide, see: Florence, Bedford et al. (2008 ). For cytenamide analogues, see: Cyr et al. (1987 ); Fleischman et al. (2003 ); Florence, Johnston, Price et al. (2006 ); Florence, Leech et al. (2007 ); Bandoli et al. (1992 ); Harrison et al. (2006 ); Leech et al. (2006 ); Florence, Shankland et al. (2008 ). For graph-set motifs, see: Etter (1990 ).

Experimental

Crystal data

C₁₆H₁₃NO·CH₂O₂
M_r = 281.3
Monoclinic, P 2₁ /c
a = 11.5351 (13) Å
b = 13.9095 (15) Å
c = 17.6904 (19) Å
β = 95.846 (5)°
V = 2823.6 (5) Å³
Z = 8
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 123 (2) K
0.25 × 0.15 × 0.05 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2002 ) T_min = 0.978, T_max = 0.996
55762 measured reflections
12996 independent reflections
9356 reflections with I > 2/s(I)
R_int = 0.025

Refinement

R[F² > 2σ(F²)] = 0.047
wR(F²) = 0.142
S = 1.02
12996 reflections
411 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.58 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯O4	0.884 (15)	2.035 (15)	2.9096 (12)	170.2 (13)
O3—H1O⋯O1	0.927 (18)	1.679 (19)	2.5971 (12)	169.9 (18)
O6—H2O⋯O2	0.91 (2)	1.66 (2)	2.5517 (12)	168.3 (19)
N2—H3N⋯O5	0.895 (15)	2.103 (15)	2.9645 (12)	161.2 (14)
N2—H4N⋯O4	0.843 (16)	2.237 (15)	2.9129 (12)	137.3 (13)
N1—H2N⋯O5	0.866 (16)	2.151 (16)	2.9088 (12)	145.9 (13)

Data collection: APEX2 (Bruker, 2007 ); cell refinement: APEX2; data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997 ) and Mercury (Macrae et al., 2006 ); software used to prepare material for publication: PLATON (Spek, 2003 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808019181/rn2044sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808019181/rn2044Isup2.hkl

checkCIF report

Comment top

Cytenamide (CYT) is an analogue of carbamazepine (CBZ), a dibenzazepine drug used to control seizures (Cyr et al., 1987). CYT-formic acid solvate was produced during an automated parallel crystallization study (Florence 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., 2007) and its closely related analogues: CYT (Florence, Bedford et al., 2008), 10,11-dihydrocarbamazepine (DHC) (Bandoli et al., 1992; Harrison et al., 2006; Leech et al., 2006) 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 formic acid solution by slow evaporation at 278 K yielded a sample suitable for single-crystal X-ray diffraction (Fig. 1).

The molecules crystallize in the space group P2₁/c with two CYT and two solvent molecules in the asymmetric unit. Both CYT molecules form an R₂²(8) (Etter, 1990) dimer motif with adjacent solvent molecules via contacts 1 - 4 (Table 1). In addition, two N—H···O contacts (5 and 6) join adjacent dimers to form a R₄²(8) centrosymmetric double motif (Fig. 2).

This packing arrangement is similar to that in CBZ-formic acid solvate which, in contrast, crystallizes with Z' = 1 in the monoclinic space group P2₁/c (Fig. 2). The main difference being a doubling of the a axis in CYT-formic acid solvate (Z' = 2) (Fleischman et al., 2003)

Related literature top

For details on experimental methods used to obtain this form, see: Davis et al. (1964); Florence et al. (2003); Florence, Johnston, Fernandes et al. (2006). For related literature on cytenamide, see: Florence, Bedford et al. (2008). For associated dibenzazepine molecules, see: Cyr et al. (1987); Fleischman et al. (2003); Florence, Johnston, Price et al. (2006); Florence, Leech et al. (2007); Bandoli et al. (1992); Harrison et al. (2006); Leech et al. (2006); Florence, Shankland et al. (2008). For graph-set motifs, see: Etter (1990).

Experimental top

A sample of cytenamide was synthesized according to a modification of the published method (Davis et al., 1964). A single-crystal sample of the title compound was recrystallized from a saturated formic acid solution by isothermal solvent evaporation at 278 ^oK.

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: APEX2 (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2006); software used to prepare material for publication: PLATON (Spek, 2003).

Figures top

	Fig. 1. The molecular structure and atomic labelling of CYT formic acid, showing 50% probability displacement ellipsoids.
	Fig. 2. The crystal packing in CYT-formic acid (top) and CBZ-formic acid (bottom), viewed down the a-axis. Molecules are coloured according to symmetry equivalence.

5H-dibenzo[a,d]cycloheptatriene-5-carboxamide–methanoic acid (1/1) top

Crystal data top

C₁₆H₁₃NO·CH₂O₂	F(000) = 1184
M_r = 281.3	D_x = 1.323 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 9893 reflections
a = 11.5351 (13) Å	θ = 2.5–35.6°
b = 13.9095 (15) Å	µ = 0.09 mm⁻¹
c = 17.6904 (19) Å	T = 123 K
β = 95.846 (5)°	Block, colourless
V = 2823.6 (5) Å³	0.25 × 0.15 × 0.05 mm
Z = 8

Data collection top

Bruker APEXII CCD diffractometer	12996 independent reflections
Radiation source: fine-focus sealed tube	9356 reflections with I > 2/s(I)
Graphite monochromator	R_int = 0.025
ϕ and ω scans	θ_max = 35.7°, θ_min = 2.3°
Absorption correction: multi-scan (SADABS; Sheldrick, 2002)	h = −18→18
T_min = 0.978, T_max = 0.996	k = −18→22
55762 measured reflections	l = −28→28

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)] = 0.047	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.142	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ²(F_o²) + (0.0728P)² + 0.6562P] where P = (F_o² + 2F_c²)/3
12996 reflections	(Δ/σ)_max = 0.002
411 parameters	Δρ_max = 0.58 e Å⁻³
0 restraints	Δρ_min = −0.23 e Å⁻³

Crystal data top

C₁₆H₁₃NO·CH₂O₂	V = 2823.6 (5) Å³
M_r = 281.3	Z = 8
Monoclinic, P2₁/c	Mo Kα radiation
a = 11.5351 (13) Å	µ = 0.09 mm⁻¹
b = 13.9095 (15) Å	T = 123 K
c = 17.6904 (19) Å	0.25 × 0.15 × 0.05 mm
β = 95.846 (5)°

Data collection top

Bruker APEXII CCD diffractometer	12996 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 2002)	9356 reflections with I > 2/s(I)
T_min = 0.978, T_max = 0.996	R_int = 0.025
55762 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.047	0 restraints
wR(F²) = 0.142	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	Δρ_max = 0.58 e Å⁻³
12996 reflections	Δρ_min = −0.23 e Å⁻³
411 parameters

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	0.36614 (7)	0.30926 (5)	0.65575 (4)	0.02658 (15)
O2	0.10330 (7)	0.67015 (5)	0.37463 (4)	0.02342 (14)
O3	0.19631 (8)	0.37994 (6)	0.72402 (4)	0.02951 (16)
O4	0.14455 (7)	0.47636 (6)	0.62510 (4)	0.02896 (16)
O5	0.30232 (7)	0.49021 (6)	0.40062 (4)	0.03007 (17)
O6	0.23678 (8)	0.57335 (6)	0.29680 (4)	0.03242 (18)
N1	0.33490 (8)	0.39736 (6)	0.54859 (5)	0.02341 (16)
N2	0.11769 (8)	0.58059 (5)	0.48157 (5)	0.02066 (15)
C1	0.50028 (8)	0.29386 (6)	0.47664 (5)	0.01748 (14)
C2	0.57461 (8)	0.35519 (7)	0.44219 (5)	0.02202 (17)
H2	0.6303	0.3921	0.4731	0.026*
C3	0.56919 (9)	0.36362 (8)	0.36373 (6)	0.02555 (19)
H3	0.6216	0.4050	0.3413	0.031*
C4	0.48681 (10)	0.31127 (7)	0.31820 (6)	0.02523 (19)
H4	0.4826	0.3166	0.2645	0.030*
C5	0.41066 (9)	0.25107 (7)	0.35153 (5)	0.02272 (17)
H5	0.3528	0.2170	0.3201	0.027*
C6	0.41737 (8)	0.23938 (6)	0.43097 (5)	0.01853 (15)
C7	0.33783 (8)	0.17138 (6)	0.46164 (6)	0.02090 (16)
H7	0.2639	0.1641	0.4332	0.025*
C8	0.35587 (9)	0.11767 (6)	0.52507 (6)	0.02140 (16)
H8	0.2934	0.0769	0.5355	0.026*
C9	0.45948 (8)	0.11419 (6)	0.57986 (5)	0.02008 (16)
C10	0.48622 (11)	0.02677 (7)	0.61783 (6)	0.0281 (2)
H10	0.4344	−0.0261	0.6094	0.034*
C11	0.58653 (11)	0.01640 (7)	0.66714 (6)	0.0307 (2)
H11	0.6032	−0.0431	0.6923	0.037*
C12	0.66267 (10)	0.09340 (8)	0.67957 (6)	0.0282 (2)
H12	0.7329	0.0861	0.7120	0.034*
C13	0.63592 (9)	0.18121 (7)	0.64440 (5)	0.02332 (17)
H13	0.6877	0.2340	0.6537	0.028*
C14	0.53432 (8)	0.19277 (6)	0.59577 (5)	0.01848 (15)
C15	0.50395 (8)	0.29080 (6)	0.56232 (5)	0.01808 (15)
H15	0.5692	0.3343	0.5819	0.022*
C16	0.39403 (8)	0.33227 (6)	0.59203 (5)	0.01896 (15)
C17	−0.00637 (8)	0.82307 (6)	0.44107 (5)	0.01786 (15)
C18	−0.10409 (9)	0.85561 (7)	0.39547 (5)	0.02321 (17)
H18	−0.1708	0.8155	0.3872	0.028*
C19	−0.10533 (10)	0.94622 (8)	0.36176 (6)	0.0293 (2)
H19	−0.1734	0.9683	0.3321	0.035*
C20	−0.00710 (11)	1.00399 (7)	0.37167 (6)	0.0306 (2)
H20	−0.0070	1.0654	0.3481	0.037*
C21	0.09067 (10)	0.97183 (7)	0.41602 (6)	0.0263 (2)
H21	0.1585	1.0110	0.4216	0.032*
C22	0.09204 (8)	0.88216 (6)	0.45311 (5)	0.01954 (16)
C23	0.19633 (9)	0.85676 (7)	0.50299 (6)	0.02165 (16)
H23	0.2679	0.8812	0.4887	0.026*
C24	0.20378 (8)	0.80303 (6)	0.56672 (5)	0.02076 (16)
H24	0.2799	0.7946	0.5918	0.025*
C25	0.10967 (8)	0.75612 (6)	0.60205 (5)	0.01819 (15)
C26	0.12267 (9)	0.74452 (7)	0.68148 (5)	0.02342 (18)
H26	0.1936	0.7635	0.7095	0.028*
C27	0.03445 (11)	0.70599 (7)	0.71980 (5)	0.0276 (2)
H27	0.0446	0.6996	0.7735	0.033*
C28	−0.06874 (10)	0.67688 (8)	0.67918 (6)	0.02705 (19)
H28	−0.1303	0.6518	0.7051	0.032*
C29	−0.08193 (9)	0.68443 (7)	0.60040 (5)	0.02195 (17)
H29	−0.1521	0.6629	0.5729	0.026*
C30	0.00612 (8)	0.72303 (6)	0.56107 (5)	0.01725 (14)
C31	−0.00718 (8)	0.72319 (6)	0.47516 (5)	0.01655 (14)
H31	−0.0865	0.6964	0.4595	0.020*
C32	0.07859 (8)	0.65615 (6)	0.44077 (5)	0.01707 (14)
C33	0.13195 (9)	0.44576 (7)	0.68783 (6)	0.02455 (18)
C34	0.30291 (11)	0.50955 (7)	0.33411 (6)	0.0285 (2)
H1N	0.2766 (13)	0.4268 (10)	0.5677 (8)	0.029 (3)*
H2N	0.3531 (13)	0.4124 (11)	0.5038 (9)	0.034 (4)*
H3N	0.1661 (13)	0.5407 (11)	0.4605 (8)	0.029 (3)*
H4N	0.1007 (13)	0.5752 (10)	0.5266 (9)	0.029 (4)*
H34	0.3583 (14)	0.4788 (12)	0.3007 (10)	0.043 (4)*
H33	0.0717 (13)	0.4695 (10)	0.7176 (8)	0.029 (3)*
H1O	0.2537 (16)	0.3588 (14)	0.6949 (10)	0.053 (5)*
H2O	0.1899 (17)	0.6011 (14)	0.3288 (11)	0.057 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0355 (4)	0.0284 (3)	0.0168 (3)	0.0098 (3)	0.0073 (3)	0.0041 (2)
O2	0.0336 (4)	0.0227 (3)	0.0146 (3)	0.0073 (3)	0.0055 (3)	0.0018 (2)
O3	0.0336 (4)	0.0363 (4)	0.0190 (3)	0.0070 (3)	0.0042 (3)	0.0048 (3)
O4	0.0346 (4)	0.0314 (3)	0.0216 (3)	0.0098 (3)	0.0064 (3)	0.0046 (3)
O5	0.0367 (4)	0.0318 (4)	0.0218 (3)	0.0112 (3)	0.0033 (3)	0.0044 (3)
O6	0.0484 (5)	0.0313 (4)	0.0181 (3)	0.0163 (3)	0.0061 (3)	0.0017 (3)
N1	0.0319 (4)	0.0219 (3)	0.0171 (3)	0.0081 (3)	0.0055 (3)	0.0027 (3)
N2	0.0279 (4)	0.0188 (3)	0.0154 (3)	0.0048 (3)	0.0030 (3)	0.0018 (2)
C1	0.0186 (4)	0.0186 (3)	0.0152 (3)	0.0005 (3)	0.0015 (3)	0.0000 (3)
C2	0.0198 (4)	0.0244 (4)	0.0219 (4)	−0.0018 (3)	0.0023 (3)	0.0028 (3)
C3	0.0260 (5)	0.0298 (4)	0.0220 (4)	0.0015 (4)	0.0080 (4)	0.0050 (3)
C4	0.0325 (5)	0.0270 (4)	0.0169 (4)	0.0063 (4)	0.0064 (3)	0.0006 (3)
C5	0.0285 (5)	0.0217 (4)	0.0176 (4)	0.0025 (3)	0.0005 (3)	−0.0035 (3)
C6	0.0198 (4)	0.0181 (3)	0.0177 (4)	0.0011 (3)	0.0022 (3)	−0.0019 (3)
C7	0.0201 (4)	0.0200 (3)	0.0222 (4)	−0.0022 (3)	0.0005 (3)	−0.0029 (3)
C8	0.0218 (4)	0.0189 (3)	0.0239 (4)	−0.0020 (3)	0.0042 (3)	−0.0019 (3)
C9	0.0233 (4)	0.0186 (3)	0.0188 (4)	0.0018 (3)	0.0045 (3)	−0.0006 (3)
C10	0.0395 (6)	0.0184 (4)	0.0266 (5)	0.0036 (4)	0.0037 (4)	0.0008 (3)
C11	0.0432 (6)	0.0241 (4)	0.0245 (5)	0.0135 (4)	0.0020 (4)	0.0023 (3)
C12	0.0300 (5)	0.0342 (5)	0.0204 (4)	0.0128 (4)	0.0019 (4)	0.0017 (4)
C13	0.0219 (4)	0.0305 (4)	0.0175 (4)	0.0035 (3)	0.0016 (3)	0.0014 (3)
C14	0.0195 (4)	0.0208 (3)	0.0155 (3)	0.0020 (3)	0.0038 (3)	0.0000 (3)
C15	0.0198 (4)	0.0187 (3)	0.0156 (3)	−0.0019 (3)	0.0007 (3)	−0.0004 (3)
C16	0.0250 (4)	0.0168 (3)	0.0149 (3)	0.0008 (3)	0.0012 (3)	−0.0018 (3)
C17	0.0212 (4)	0.0191 (3)	0.0137 (3)	0.0049 (3)	0.0042 (3)	0.0008 (3)
C18	0.0239 (4)	0.0300 (4)	0.0160 (4)	0.0089 (3)	0.0034 (3)	0.0027 (3)
C19	0.0377 (6)	0.0325 (5)	0.0186 (4)	0.0182 (4)	0.0071 (4)	0.0063 (3)
C20	0.0505 (7)	0.0216 (4)	0.0219 (4)	0.0135 (4)	0.0140 (4)	0.0056 (3)
C21	0.0401 (6)	0.0175 (3)	0.0232 (4)	0.0015 (3)	0.0123 (4)	0.0011 (3)
C22	0.0254 (4)	0.0172 (3)	0.0170 (4)	0.0030 (3)	0.0069 (3)	0.0000 (3)
C23	0.0218 (4)	0.0209 (3)	0.0228 (4)	−0.0014 (3)	0.0053 (3)	−0.0028 (3)
C24	0.0191 (4)	0.0214 (3)	0.0214 (4)	0.0011 (3)	0.0004 (3)	−0.0034 (3)
C25	0.0224 (4)	0.0174 (3)	0.0144 (3)	0.0031 (3)	0.0004 (3)	−0.0015 (3)
C26	0.0310 (5)	0.0224 (4)	0.0160 (4)	0.0028 (3)	−0.0021 (3)	−0.0026 (3)
C27	0.0418 (6)	0.0274 (4)	0.0138 (4)	0.0026 (4)	0.0045 (4)	−0.0012 (3)
C28	0.0345 (5)	0.0297 (4)	0.0182 (4)	−0.0001 (4)	0.0091 (4)	0.0016 (3)
C29	0.0244 (4)	0.0245 (4)	0.0175 (4)	−0.0001 (3)	0.0046 (3)	0.0013 (3)
C30	0.0208 (4)	0.0172 (3)	0.0139 (3)	0.0020 (3)	0.0022 (3)	0.0001 (3)
C31	0.0180 (4)	0.0187 (3)	0.0129 (3)	0.0008 (3)	0.0013 (3)	0.0005 (3)
C32	0.0200 (4)	0.0168 (3)	0.0141 (3)	0.0006 (3)	0.0002 (3)	−0.0005 (3)
C33	0.0256 (5)	0.0288 (4)	0.0190 (4)	0.0013 (3)	0.0014 (3)	−0.0025 (3)
C34	0.0377 (6)	0.0260 (4)	0.0221 (4)	0.0095 (4)	0.0044 (4)	−0.0006 (3)

Geometric parameters (Å, º) top

O1—C16	1.2451 (11)	C12—H12	0.9500
O2—C32	1.2473 (11)	C13—C14	1.3907 (13)
O3—C33	1.3047 (13)	C13—H13	0.9500
O3—H1O	0.926 (19)	C14—C15	1.5132 (12)
O4—C33	1.2111 (13)	C15—C16	1.5338 (13)
O5—C34	1.2076 (13)	C15—H15	1.0000
O6—C34	1.3048 (13)	C17—C18	1.3932 (13)
O6—H2O	0.91 (2)	C17—C22	1.4000 (13)
N1—C16	1.3300 (12)	C17—C31	1.5149 (12)
N1—H1N	0.884 (15)	C18—C19	1.3937 (14)
N1—H2N	0.866 (16)	C18—H18	0.9500
N2—C32	1.3277 (11)	C19—C20	1.3855 (19)
N2—H3N	0.895 (15)	C19—H19	0.9500
N2—H4N	0.843 (15)	C20—C21	1.3811 (16)
C1—C2	1.3931 (13)	C20—H20	0.9500
C1—C6	1.4086 (12)	C21—C22	1.4087 (13)
C1—C15	1.5126 (12)	C21—H21	0.9500
C2—C3	1.3879 (14)	C22—C23	1.4611 (14)
C2—H2	0.9500	C23—C24	1.3480 (14)
C3—C4	1.3878 (15)	C23—H23	0.9500
C3—H3	0.9500	C24—C25	1.4604 (13)
C4—C5	1.3877 (15)	C24—H24	0.9500
C4—H4	0.9500	C25—C26	1.4072 (13)
C5—C6	1.4091 (13)	C25—C30	1.4099 (13)
C5—H5	0.9500	C26—C27	1.3867 (16)
C6—C7	1.4601 (13)	C26—H26	0.9500
C7—C8	1.3465 (14)	C27—C28	1.3867 (16)
C7—H7	0.9500	C27—H27	0.9500
C8—C9	1.4608 (14)	C28—C29	1.3904 (14)
C8—H8	0.9500	C28—H28	0.9500
C9—C14	1.4034 (13)	C29—C30	1.3956 (13)
C9—C10	1.4082 (13)	C29—H29	0.9500
C10—C11	1.3838 (16)	C30—C31	1.5119 (12)
C10—H10	0.9500	C31—C32	1.5300 (12)
C11—C12	1.3883 (17)	C31—H31	1.0000
C11—H11	0.9500	C33—H33	0.972 (15)
C12—C13	1.3911 (14)	C34—H34	1.008 (17)

C33—O3—H1O	110.6 (11)	N1—C16—C15	116.82 (8)
C34—O6—H2O	109.2 (12)	C18—C17—C22	119.54 (8)
C16—N1—H1N	117.3 (9)	C18—C17—C31	119.41 (8)
C16—N1—H2N	122.4 (10)	C22—C17—C31	121.04 (8)
H1N—N1—H2N	120.3 (14)	C17—C18—C19	120.93 (10)
C32—N2—H3N	117.1 (9)	C17—C18—H18	119.5
C32—N2—H4N	119.1 (10)	C19—C18—H18	119.5
H3N—N2—H4N	123.6 (13)	C20—C19—C18	119.85 (10)
C2—C1—C6	119.38 (8)	C20—C19—H19	120.1
C2—C1—C15	120.00 (8)	C18—C19—H19	120.1
C6—C1—C15	120.50 (8)	C21—C20—C19	119.61 (9)
C3—C2—C1	121.48 (9)	C21—C20—H20	120.2
C3—C2—H2	119.3	C19—C20—H20	120.2
C1—C2—H2	119.3	C20—C21—C22	121.40 (10)
C4—C3—C2	119.63 (9)	C20—C21—H21	119.3
C4—C3—H3	120.2	C22—C21—H21	119.3
C2—C3—H3	120.2	C17—C22—C21	118.59 (9)
C5—C4—C3	119.71 (9)	C17—C22—C23	123.70 (8)
C5—C4—H4	120.1	C21—C22—C23	117.70 (9)
C3—C4—H4	120.1	C24—C23—C22	128.14 (9)
C4—C5—C6	121.37 (9)	C24—C23—H23	115.9
C4—C5—H5	119.3	C22—C23—H23	115.9
C6—C5—H5	119.3	C23—C24—C25	128.22 (9)
C1—C6—C5	118.36 (8)	C23—C24—H24	115.9
C1—C6—C7	123.44 (8)	C25—C24—H24	115.9
C5—C6—C7	118.20 (8)	C26—C25—C30	118.33 (9)
C8—C7—C6	128.27 (9)	C26—C25—C24	118.05 (8)
C8—C7—H7	115.9	C30—C25—C24	123.61 (8)
C6—C7—H7	115.9	C27—C26—C25	121.58 (9)
C7—C8—C9	128.16 (9)	C27—C26—H26	119.2
C7—C8—H8	115.9	C25—C26—H26	119.2
C9—C8—H8	115.9	C28—C27—C26	119.57 (9)
C14—C9—C10	118.46 (9)	C28—C27—H27	120.2
C14—C9—C8	123.52 (8)	C26—C27—H27	120.2
C10—C9—C8	118.02 (9)	C27—C28—C29	119.86 (10)
C11—C10—C9	121.28 (10)	C27—C28—H28	120.1
C11—C10—H10	119.4	C29—C28—H28	120.1
C9—C10—H10	119.4	C28—C29—C30	121.19 (9)
C10—C11—C12	119.63 (9)	C28—C29—H29	119.4
C10—C11—H11	120.2	C30—C29—H29	119.4
C12—C11—H11	120.2	C29—C30—C25	119.38 (8)
C11—C12—C13	119.91 (10)	C29—C30—C31	119.82 (8)
C11—C12—H12	120.0	C25—C30—C31	120.68 (8)
C13—C12—H12	120.0	C30—C31—C17	113.42 (7)
C14—C13—C12	120.85 (10)	C30—C31—C32	113.29 (7)
C14—C13—H13	119.6	C17—C31—C32	111.73 (7)
C12—C13—H13	119.6	C30—C31—H31	105.9
C13—C14—C9	119.76 (8)	C17—C31—H31	105.9
C13—C14—C15	119.54 (8)	C32—C31—H31	105.9
C9—C14—C15	120.68 (8)	O2—C32—N2	122.41 (8)
C1—C15—C14	113.51 (7)	O2—C32—C31	119.78 (7)
C1—C15—C16	113.15 (7)	N2—C32—C31	117.64 (8)
C14—C15—C16	111.80 (7)	O4—C33—O3	125.51 (10)
C1—C15—H15	105.9	O4—C33—H33	122.5 (9)
C14—C15—H15	105.9	O3—C33—H33	112.0 (9)
C16—C15—H15	105.9	O5—C34—O6	125.69 (10)
O1—C16—N1	122.24 (9)	O5—C34—H34	122.9 (10)
O1—C16—C15	120.82 (8)	O6—C34—H34	111.4 (9)

C6—C1—C2—C3	−0.25 (14)	C22—C17—C18—C19	−0.09 (13)
C15—C1—C2—C3	−176.46 (9)	C31—C17—C18—C19	−178.49 (8)
C1—C2—C3—C4	1.11 (15)	C17—C18—C19—C20	1.91 (15)
C2—C3—C4—C5	0.03 (15)	C18—C19—C20—C21	−1.09 (15)
C3—C4—C5—C6	−2.05 (15)	C19—C20—C21—C22	−1.53 (15)
C2—C1—C6—C5	−1.70 (13)	C18—C17—C22—C21	−2.46 (13)
C15—C1—C6—C5	174.50 (8)	C31—C17—C22—C21	175.92 (8)
C2—C1—C6—C7	178.35 (9)	C18—C17—C22—C23	176.71 (8)
C15—C1—C6—C7	−5.46 (13)	C31—C17—C22—C23	−4.92 (13)
C4—C5—C6—C1	2.87 (14)	C20—C21—C22—C17	3.31 (14)
C4—C5—C6—C7	−177.17 (9)	C20—C21—C22—C23	−175.91 (9)
C1—C6—C7—C8	−31.43 (15)	C17—C22—C23—C24	−31.25 (15)
C5—C6—C7—C8	148.62 (10)	C21—C22—C23—C24	147.93 (10)
C6—C7—C8—C9	0.51 (16)	C22—C23—C24—C25	0.29 (16)
C7—C8—C9—C14	30.22 (15)	C23—C24—C25—C26	−149.76 (10)
C7—C8—C9—C10	−148.87 (10)	C23—C24—C25—C30	29.39 (14)
C14—C9—C10—C11	−2.97 (15)	C30—C25—C26—C27	−3.13 (13)
C8—C9—C10—C11	176.17 (10)	C24—C25—C26—C27	176.06 (9)
C9—C10—C11—C12	−0.07 (16)	C25—C26—C27—C28	0.85 (15)
C10—C11—C12—C13	2.07 (16)	C26—C27—C28—C29	1.48 (15)
C11—C12—C13—C14	−0.98 (15)	C27—C28—C29—C30	−1.49 (15)
C12—C13—C14—C9	−2.12 (14)	C28—C29—C30—C25	−0.84 (13)
C12—C13—C14—C15	176.15 (9)	C28—C29—C30—C31	175.30 (9)
C10—C9—C14—C13	4.02 (14)	C26—C25—C30—C29	3.08 (12)
C8—C9—C14—C13	−175.07 (9)	C24—C25—C30—C29	−176.06 (8)
C10—C9—C14—C15	−174.22 (9)	C26—C25—C30—C31	−173.03 (8)
C8—C9—C14—C15	6.69 (14)	C24—C25—C30—C31	7.83 (12)
C2—C1—C15—C14	−119.84 (9)	C29—C30—C31—C17	119.16 (9)
C6—C1—C15—C14	63.99 (11)	C25—C30—C31—C17	−64.75 (10)
C2—C1—C15—C16	111.37 (9)	C29—C30—C31—C32	−112.12 (9)
C6—C1—C15—C16	−64.80 (10)	C25—C30—C31—C32	63.98 (10)
C13—C14—C15—C1	117.00 (9)	C18—C17—C31—C30	−118.43 (9)
C9—C14—C15—C1	−64.75 (11)	C22—C17—C31—C30	63.20 (11)
C13—C14—C15—C16	−113.52 (9)	C18—C17—C31—C32	112.05 (9)
C9—C14—C15—C16	64.73 (11)	C22—C17—C31—C32	−66.32 (10)
C1—C15—C16—O1	157.50 (8)	C30—C31—C32—O2	−157.63 (8)
C14—C15—C16—O1	27.83 (12)	C17—C31—C32—O2	−28.05 (11)
C1—C15—C16—N1	−26.25 (11)	C30—C31—C32—N2	26.99 (11)
C14—C15—C16—N1	−155.92 (8)	C17—C31—C32—N2	156.57 (8)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O4	0.884 (15)	2.035 (15)	2.9096 (12)	170.2 (13)
O3—H1O···O1	0.927 (18)	1.679 (19)	2.5971 (12)	169.9 (18)
O6—H2O···O2	0.91 (2)	1.66 (2)	2.5517 (12)	168.3 (19)
N2—H3N···O5	0.895 (15)	2.103 (15)	2.9645 (12)	161.2 (14)
N2—H4N···O4	0.843 (16)	2.237 (15)	2.9129 (12)	137.3 (13)
N1—H2N···O5	0.866 (16)	2.151 (16)	2.9088 (12)	145.9 (13)

Experimental details

Crystal data
Chemical formula	C₁₆H₁₃NO·CH₂O₂
M_r	281.3
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	123
a, b, c (Å)	11.5351 (13), 13.9095 (15), 17.6904 (19)
β (°)	95.846 (5)
V (Å³)	2823.6 (5)
Z	8
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.25 × 0.15 × 0.05

Data collection
Diffractometer	Bruker APEXII CCD diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 2002)
T_min, T_max	0.978, 0.996
No. of measured, independent and observed [I > 2/s(I)] reflections	55762, 12996, 9356
R_int	0.025
(sin θ/λ)_max (Å⁻¹)	0.821

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.047, 0.142, 1.02
No. of reflections	12996
No. of parameters	411
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.58, −0.23

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2006), PLATON (Spek, 2003).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O4	0.884 (15)	2.035 (15)	2.9096 (12)	170.2 (13)
O3—H1O···O1	0.927 (18)	1.679 (19)	2.5971 (12)	169.9 (18)
O6—H2O···O2	0.91 (2)	1.66 (2)	2.5517 (12)	168.3 (19)
N2—H3N···O5	0.895 (15)	2.103 (15)	2.9645 (12)	161.2 (14)
N2—H4N···O4	0.843 (16)	2.237 (15)	2.9129 (12)	137.3 (13)
N1—H2N···O5	0.866 (16)	2.151 (16)	2.9088 (12)	145.9 (13)

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 (www.cposs.org.uk) and AstraZeneca for funding GJM.

References

Bandoli, G., Nicolini, M., Ongaro, A., Volpe, G. & Rubello, A. (1992). J. Chem. Crystallogr. 22, 177–183. CAS Google Scholar
Bruker (2007). APEX2 andSAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cyr, T. D., Matsui, F., Sears, R. W., Curran, N. M. & Lovering, E. G. (1987). J. Assoc. Off. Anal. Chem. 70, 836–840. CAS PubMed Web of Science Google Scholar
Davis, M. A., Winthrop, S. O., Thomas, R. A., Herr, F., Charest, M.-P. & Gaudry, R. (1964). J. Med. Chem. 7, 88–94. CrossRef PubMed CAS Web of Science Google Scholar
Etter, M. C. (1990). Acc. Chem. Res. 23, 120–126. CrossRef CAS Web of Science Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Fleischman, S. G., Kuduva, S. S., McMahon, J. A., Moulton, B., Walsh, R. D. B., Rodriguez-Hornedo, N. & Zaworotko, M. J. (2003). Cryst. Growth Des. 3, 909–919. Web of Science CSD CrossRef CAS Google Scholar
Florence, A. J., Baumgartner, B., Weston, C., Shankland, N., Kennedy, A. R., Shankland, K. & David, W. I. F. (2003). J. Pharm. Sci. 92, 1930–1938. Web of Science CSD CrossRef PubMed CAS Google Scholar
Florence, A. J., Bedford, C. T., Fabbiani, F. P. A., Shankland, K., Gelbrich, T., Hursthouse, M. B., Shankland, N., Johnston, A. & Fernandes, P. (2008). CrystEngComm. DOI: 10.1039/b719717a. Google Scholar
Florence, A. J., Johnston, A., Fernandes, P., Shankland, N. & Shankland, K. (2006). J. Appl. Cryst. 39, 922–924. Web of Science CrossRef CAS IUCr Journals Google Scholar
Florence, A. J., Johnston, A., Price, S. L., Nowell, H., Kennedy, A. R. & Shankland, N. (2006). J. Pharm. Sci. 95, 1918–1930. Web of Science CrossRef PubMed CAS Google Scholar
Florence, A. J., Leech, C. K., Shankland, N., Shankland, K. & Johnston, A. (2006). CrystEngComm, 8, 746–747. Web of Science CSD CrossRef CAS Google Scholar
Florence, A. J., Shankland, K., Gelbrich, T., Hursthouse, M. B., Shankland, N., Johnston, A., Fernandes, P. & Leech, C. K. (2008). CrystEngComm, 10, 26–28. Web of Science CSD CrossRef CAS Google Scholar
Harrison, W. T. A., Yathirajan, H. S. & Anilkumar, H. G. (2006). Acta Cryst. C62, o240–o242. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Leech, C. K., Florence, A. J., Shankland, K., Shankland, N. & Johnston, A. (2007). Acta Cryst. E63, o675–o677. CSD CrossRef IUCr Journals Google Scholar
Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2002). SADABS. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13. Web of Science CrossRef CAS IUCr Journals Google Scholar