Cocrystal of cis- and trans-N-phenyl­formamide

N-Phenyl­formamide, C₇H₇NO, crystallizes with two mol­ecules in the asymmetric unit which have different conformations of the formyl­amino group, one being cis and the other trans. This is the first example of an aryl­formamide crystal containing both conformational isomers and it may thus be considered a cocrystal of the two conformers. The two mol­ecules in the unit cell are linked through N—H...O hydrogen bonding to two other mol­ecules, thereby forming hydrogen-bonded tetra­mers within the crystal structure.

S1. Comment

The study of the title compound, (I), has attracted considerable interest in recent years. However, no crystallographic studies on N-phenylformamide have been reported previously. Previous studies of the compound have been largely theoretical (Moreno et al., 2006; Moisan & Danneberg, 2003; Kobko & Danneberg, 2003; Vargas et al., 2001; Bock et al., 1996; Manea et al., 1997), including density functional theory (DFT) studies (Doerksen et al., 2004), and experimental investigations on resonant two-photon ionization spectroscopy (Federov & Cable, 2000) and laser-induced fluorescence excitation (Dickinson et al., 1999). The study of (I) has also been improtant as a model for the understanding of the structure, folding and stability of proteins. This understanding has typically been gained from an interpretation of IR, Raman or NMR spectra of model systems such as formamide (the most simple representative of this class of compounds), N-alkyl- or N-phenylamide–water clusters, either isolated in a matrix or dispersed in an aqueous solution (Dickinson et al., 1999). The solution NMR spectrum of a powdered sample of (I) in CDCl₃ showed equal concentrations of both cis and trans isomers which is in agreement with the dynamic solution behaviour of amide systems reported previously (Siddall et al., 1968, and references therein; Omondi et al., 2005).

N-Phenylformamide crystallizes with two molecules in the asymmetric unit (Fig. 1). One of the molecules adopts a cis conformation, while the other shows a trans conformation. The formation of a cocrystal of the two conformations is unusual as N-phenylformamides and N-phenylthioamides usually crystallize as only one of these isomers (Omondi, 2007; Omondi et al., 2005), even though both conformers exist in solution. The two conformers show similar bond lengths and angles that compare well to those of related compounds in the literature. The N11—C17 and O11—C17 bond lengths are, as expected for conjugated π-systems, in the regions of 1.33 and 1.22 Å respectively. Both molecules adopt the almost planar geometry that would be preferred in order to extend π-conjugation from the ring system to the formamide group. This, in turn, shortens the N11—C11 single-bond length. The shortening of this bond is, however, not very significant. A notable difference between the two conformers is in the angle between the plane defined by the phenyl ring (C11–C16 or C21—C26) and the plane defined by the formamide group (C11—N11—C17—O11 or C21—N21—C27—O21). In the cis isomer, the angle between the two mean planes is approximately equal to zero, whereas in the trans isomer the formamide group is slightly out of the plane of the phenyl ring by about 9.1 (1)°. This angle varies in related compounds, such as acetanilide, and also in the calculated structures of the cis and trans isomers of N-phenylformamide. The gas-phase conformation of the trans isomer is reported to be nonplanar (Manea et al., 1997), in contrast to what is observed here in the crystalline phase.

The two molecules in the unit cell have a dihedral angle of 19.07 (6)° between their mean planes. Each molecule of a particular conformation (cis or trans) is related to its nearest neighbor of the same conformation through a glide plane.

Each molecule is connected to another molecule of a different conformation through N—H···O hydrogen bonding, resulting in a tetrameric arrangement, with graph-set R₄⁴(16), such that each tetramer contains two molecules of each conformation. Due to the nearly planar backbone of the molecule, the hydrogen bonds are almost linear, with N—H···O angles of 178 and 176° for the cis and trans conformers, respectively. The intramolecular N···O distances are slightly shorter than those in acetanilide and other related acetamides, such as paracetamol (2.894–2.967 Å; Wasserman et al., 1985; Johnson et al., 1995), all of which adopt only the trans conformation in the solid state.

Related literature

For related literature, see: Bock et al. (1996); Dickinson et al. (1999); Doerksen et al. (2004); Federov & Cable (2000); Johnson et al. (1995); Kobko & Danneberg (2003); Manea et al. (1997); Moreno et al. (2006); Omondi (2007); Omondi et al. (2005); Siddall, Stewart & Marston (1968); Ugi et al. (1965); Vargas et al. (2001); Wasserman et al. (1985).

S2. Experimental

N-Phenylformamide was synthesized according to the procedure of Ugi et al. (1965). Commercially available aniline (Aldrich, purity > 95%) was heated in a tenfold excess of formic acid for a period of 15 h at 363 K. The excess formic acid was removed under vacuum to give a brown liquid which was treated with dilute hydrochloric acid (0.1 M HCl) and ethyl acetate. The organic layer was separated from the aqueous layer, dried over magnesium sulfate and distilled under vacuum. An off-white solid was obtained in good yield. The first suitable single crystals of N-phenylformamide were obtained by crystallization from ethyl acetate on work-up of the reaction mixture. Only subsequent to their growth, which took almost one year, was it possible to grow the same crystals (as established by X-ray powder diffraction) from various solvents by slow evaporation (chloroform, ethanol, dichloromethane, ethyl acetate, dimethyl sulfoxide and tetrahydrofuran). The powder was recrystallized from a variety of solvents giving crystals suitable for single-crystal X-ray diffraction studies. ¹H NMR (DMSO): δ 7.02, 7.22, 7.47 (m; cis and trans, para, meta and ortho Ar—H; trans, NH), 8.37 (d, trans, CHO, J_H—H = 1.13 Hz), 8.70 (d, cis, CHO, J_H—H = 11.38), 8.46 (s, broad, cis, NH).

S3. Refinement

H atoms were positioned geometrically and allowed to ride on their respective parent atoms, with bond lengths of 0.95 (CH) and 0.88 Å (NH), and isotropic displacement parameters 1.2 times U_eq of the parent atom.

Computing details

Data collection: SMART-NT (Bruker, 1998); cell refinement: SAINT-Plus (Bruker, 1999); data reduction: SAINT-Plus (Bruker, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2003) and ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures

Fig. 1. View of (I) down the a axis, showing N—H···O hydrogen-bonded tetramers (50% probability displacement ellipsoids).

N-Phenylformamide

Crystal data

C7H7NO	F(000) = 1024
Mr = 121.14	Dx = 1.285 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 2001 reflections
a = 31.177 (3) Å	θ = 2.9–27.1°
b = 6.1229 (5) Å	µ = 0.09 mm^−1
c = 14.3335 (12) Å	T = 173 K
β = 113.771 (2)°	Block, pale green
V = 2504.1 (4) Å^3	0.53 × 0.20 × 0.14 mm
Z = 16

Data collection

Bruker SMART CCD area-detector diffractometer	1953 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.026
Graphite monochromator	θmax = 27.0°, θmin = 1.4°
ϕ and ω scans	h = −39→39
7327 measured reflections	k = −6→7
2732 independent reflections	l = −18→9

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)] = 0.040	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.110	H-atom parameters constrained
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0522P)^2 + 0.7143P] where P = (Fo^2 + 2Fc^2)/3
2732 reflections	(Δ/σ)max < 0.001
163 parameters	Δρmax = 0.19 e Å^−3
0 restraints	Δρmin = −0.18 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
C11	0.66832 (5)	0.7492 (2)	0.78636 (10)	0.0299 (3)
C12	0.70000 (5)	0.9093 (2)	0.78800 (11)	0.0377 (4)
H12	0.6890	1.0435	0.7534	0.045*
C13	0.74744 (5)	0.8749 (3)	0.83952 (12)	0.0454 (4)
H13	0.7689	0.9853	0.8398	0.054*
C14	0.76399 (5)	0.6826 (3)	0.89039 (12)	0.0470 (4)
H14	0.7967	0.6602	0.9268	0.056*
C15	0.73264 (6)	0.5229 (3)	0.88795 (13)	0.0513 (4)
H15	0.7440	0.3892	0.9228	0.062*
C16	0.68483 (5)	0.5527 (3)	0.83581 (12)	0.0438 (4)
H16	0.6636	0.4399	0.8340	0.053*
C17	0.58388 (5)	0.6706 (3)	0.72146 (12)	0.0404 (4)
H17	0.5896	0.5306	0.7527	0.048*
N11	0.62025 (4)	0.7959 (2)	0.73282 (8)	0.0331 (3)
H11	0.6136	0.9247	0.7032	0.040*
O11	0.54320 (4)	0.7262 (2)	0.67274 (9)	0.0529 (3)
C21	0.57124 (5)	1.5283 (2)	0.46422 (10)	0.0300 (3)
C22	0.54546 (5)	1.6725 (3)	0.38727 (11)	0.0368 (3)
H22	0.5131	1.6466	0.3482	0.044*
C23	0.56680 (6)	1.8534 (3)	0.36752 (11)	0.0451 (4)
H23	0.5491	1.9513	0.3145	0.054*
C24	0.61379 (6)	1.8928 (3)	0.42463 (11)	0.0452 (4)
H24	0.6285	2.0182	0.4116	0.054*
C25	0.63909 (5)	1.7487 (3)	0.50050 (12)	0.0425 (4)
H25	0.6714	1.7757	0.5397	0.051*
C26	0.61848 (5)	1.5657 (2)	0.52082 (11)	0.0357 (3)
H26	0.6365	1.4667	0.5730	0.043*
C27	0.56217 (5)	1.2025 (2)	0.55652 (12)	0.0405 (4)
H27	0.5413	1.0870	0.5538	0.049*
N21	0.54716 (4)	1.34647 (19)	0.48004 (9)	0.0362 (3)
H21	0.5186	1.3252	0.4336	0.043*
O21	0.60001 (4)	1.20441 (18)	0.62962 (8)	0.0472 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C11	0.0314 (7)	0.0311 (7)	0.0275 (6)	−0.0010 (6)	0.0123 (5)	−0.0024 (6)
C12	0.0356 (7)	0.0301 (8)	0.0446 (8)	−0.0001 (6)	0.0132 (6)	0.0023 (6)
C13	0.0335 (8)	0.0425 (9)	0.0559 (9)	−0.0047 (7)	0.0138 (7)	−0.0059 (8)
C14	0.0342 (8)	0.0512 (10)	0.0493 (9)	0.0097 (7)	0.0101 (7)	−0.0023 (8)
C15	0.0504 (9)	0.0457 (10)	0.0538 (10)	0.0154 (8)	0.0171 (8)	0.0143 (8)
C16	0.0448 (9)	0.0351 (9)	0.0523 (9)	0.0015 (7)	0.0204 (7)	0.0105 (7)
C17	0.0380 (8)	0.0368 (8)	0.0455 (8)	−0.0071 (7)	0.0160 (7)	−0.0078 (7)
N11	0.0309 (6)	0.0310 (6)	0.0352 (6)	−0.0015 (5)	0.0110 (5)	0.0034 (5)
O11	0.0314 (5)	0.0608 (8)	0.0588 (7)	−0.0083 (5)	0.0102 (5)	−0.0108 (6)
C21	0.0319 (7)	0.0278 (7)	0.0312 (7)	−0.0006 (6)	0.0137 (6)	−0.0031 (5)
C22	0.0346 (7)	0.0380 (8)	0.0340 (7)	−0.0005 (6)	0.0098 (6)	0.0003 (6)
C23	0.0528 (9)	0.0395 (9)	0.0379 (8)	0.0014 (7)	0.0129 (7)	0.0084 (7)
C24	0.0531 (9)	0.0406 (9)	0.0435 (8)	−0.0122 (8)	0.0210 (7)	0.0037 (7)
C25	0.0347 (7)	0.0473 (10)	0.0435 (8)	−0.0091 (7)	0.0137 (6)	0.0018 (7)
C26	0.0311 (7)	0.0358 (8)	0.0382 (7)	0.0005 (6)	0.0119 (6)	0.0031 (6)
C27	0.0382 (8)	0.0310 (8)	0.0484 (9)	−0.0049 (6)	0.0133 (7)	0.0039 (7)
N21	0.0281 (6)	0.0331 (7)	0.0406 (7)	−0.0050 (5)	0.0066 (5)	0.0022 (5)
O21	0.0424 (6)	0.0397 (6)	0.0478 (6)	−0.0048 (5)	0.0060 (5)	0.0114 (5)

Geometric parameters (Å, º)

C11—C12	1.385 (2)	C21—C26	1.3846 (18)
C11—C16	1.386 (2)	C21—C22	1.3884 (19)
C11—N11	1.4103 (17)	C21—N21	1.4114 (18)
C12—C13	1.377 (2)	C22—C23	1.379 (2)
C12—H12	0.9500	C22—H22	0.9500
C13—C14	1.371 (2)	C23—C24	1.381 (2)
C13—H13	0.9500	C23—H23	0.9500
C14—C15	1.373 (2)	C24—C25	1.375 (2)
C14—H14	0.9500	C24—H24	0.9500
C15—C16	1.384 (2)	C25—C26	1.380 (2)
C15—H15	0.9500	C25—H25	0.9500
C16—H16	0.9500	C26—H26	0.9500
C17—O11	1.2239 (17)	C27—O21	1.2219 (17)
C17—N11	1.3238 (18)	C27—N21	1.3359 (19)
C17—H17	0.9500	C27—H27	0.9500
N11—H11	0.8800	N21—H21	0.8800
C12—C11—C16	119.35 (13)	C26—C21—C22	119.90 (13)
C12—C11—N11	117.40 (12)	C26—C21—N21	123.06 (12)
C16—C11—N11	123.24 (13)	C22—C21—N21	117.03 (12)
C13—C12—C11	120.35 (14)	C23—C22—C21	120.10 (13)
C13—C12—H12	119.8	C23—C22—H22	120.0
C11—C12—H12	119.8	C21—C22—H22	120.0
C14—C13—C12	120.60 (15)	C22—C23—C24	120.18 (14)
C14—C13—H13	119.7	C22—C23—H23	119.9
C12—C13—H13	119.7	C24—C23—H23	119.9
C13—C14—C15	119.10 (15)	C25—C24—C23	119.33 (15)
C13—C14—H14	120.4	C25—C24—H24	120.3
C15—C14—H14	120.4	C23—C24—H24	120.3
C14—C15—C16	121.37 (15)	C24—C25—C26	121.35 (14)
C14—C15—H15	119.3	C24—C25—H25	119.3
C16—C15—H15	119.3	C26—C25—H25	119.3
C15—C16—C11	119.20 (15)	C25—C26—C21	119.12 (13)
C15—C16—H16	120.4	C25—C26—H26	120.4
C11—C16—H16	120.4	C21—C26—H26	120.4
O11—C17—N11	123.25 (15)	O21—C27—N21	126.51 (14)
O11—C17—H17	118.4	O21—C27—H27	116.7
N11—C17—H17	118.4	N21—C27—H27	116.7
C17—N11—C11	128.26 (13)	C27—N21—C21	128.27 (12)
C17—N11—H11	115.9	C27—N21—H21	115.9
C11—N11—H11	115.9	C21—N21—H21	115.9
C16—C11—C12—C13	−0.9 (2)	C26—C21—C22—C23	−0.3 (2)
N11—C11—C12—C13	179.53 (13)	N21—C21—C22—C23	−179.86 (14)
C11—C12—C13—C14	−0.4 (2)	C21—C22—C23—C24	−0.5 (2)
C12—C13—C14—C15	1.0 (3)	C22—C23—C24—C25	0.7 (3)
C13—C14—C15—C16	−0.4 (3)	C23—C24—C25—C26	−0.1 (3)
C14—C15—C16—C11	−1.0 (3)	C24—C25—C26—C21	−0.7 (2)
C12—C11—C16—C15	1.6 (2)	C22—C21—C26—C25	0.9 (2)
N11—C11—C16—C15	−178.91 (14)	N21—C21—C26—C25	−179.59 (14)
O11—C17—N11—C11	−179.64 (14)	O21—C27—N21—C21	1.7 (3)
C12—C11—N11—C17	−179.39 (14)	C26—C21—N21—C27	10.2 (2)
C16—C11—N11—C17	1.1 (2)	C22—C21—N21—C27	−170.34 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N11—H11···O21	0.88	1.97	2.8444 (16)	176
N21—H21···O11^i	0.88	1.94	2.8206 (15)	178

Symmetry code: (i) −x+1, −y+2, −z+1.