4-Benzoyl-3,4-dihydro-2H-1,4-benzoxazine-2-carbonitrile: refinement using a multipolar atom model

The structural model for the title compound, C₁₆H₁₂N₂O₂, was refined using a multipolar atom model transferred from an experimental electron-density database. The refinement showed some improvements of crystallographic statistical indices when compared with a conventional spherical neutral-atom refinement. The title compound adopts a half-chair conformation. The amide N atom lies almost in the plane defined by the three neighbouring C atoms. In the crystal structure, mol­ecules are linked by weak inter­molecular C—H...O and C—H...π hydrogen bonds.

S1. Comment

1,4-Benzoxazines and their derivatives have attracted much attention over the past few decades (Bartsch & Schwarz, 1982). Amongst these systems cyano-substituted oxazines have been extensively studied (Bartsch & Schwarz, 1983) and cycloaddition reactions with the cyano group reviewed (Myers & Sircar, 1970). More recently, [3 + 2] cycloadditions of donor–acceptor cyclopropanes and nitriles have found interesting applications in the field of glycal chemistry (Yu & Pagenkopf, 2003). Recently, as part of a more complex 3,4-dihydropyrrole sugar-fused synthesis, we isolated the title N-acylated oxine, (II), from the known racemic oxine, (I) (Bartsch & Schwarz, 1983).

The molecular structure of (II) exists in a half-chair conformation, as depicted with the atomic numbering scheme in Fig. 1. The amide atom N2 is almost exactly in the plane defined by three neighbouring C atoms (C7, C14 and C15), with all four atoms within 0.05 Å of the plane. The sum of the valence angles around the N atom of 359.7° demonstrates clear sp² hybridization (328° for sp³ and 360° for sp²). The other geometric parameters of (II) (Table 1) are normal and compare well with those found in other crystal structures (Bartsch & Schwarz, 1983; Black et al., 1987; Garbauskas et al., 1985; Heine et al., 1988; Feng et al., 2007). Compound (II) also exhibits a slight shortening of the carbonyl-N bond (1.369 Å), indicative of partial double-bond character; this is typical behaviour for amides.

The crystal structure of (II) is presented in Fig. 2. Molecules of (II) are linked into a three-dimensional framework by three weak C–H···O hydrogen bonds (Table 2). [A C—H···π interaction is shown in Fig. 2 - please give brief details here.]

Initially, in the independent atom model (IAM) refinement, a conventional spherical neutral atom model was applied. Scale factors, atomic positions and displacement parameters for all atoms were refined using the MOPRO program (Guillot et al., 2001; Jelsch et al., 2005) until convergence. In the experimental library multipolar atom model (ELMAM) refinement, the same parameters were varied but a multipolar charged atom model was applied. The electron-density parameters were transferred from the ELMAM library (Pichon-Pesme et al., 2004; Zarychta et al., 2007) and subsequently kept fixed. Riding constraints on H-atom isotropic displacement parameters were applied similarly in both refinements, which were carried out with the same diffraction data and using all reflections. The H–X distances were constrained to standard values in neutron diffraction studies (Allen, 1986) in the IAM and ELMAM refinements. The ELMAM refinement shows a slight improvement in statistical indexes when compared with the IAM refinement. The I>2σ(I) crystallographic factors are reduced from 7.32 to 6.09% for R(F) and from 2.22 to 2.19% for wR2(F). The minimum and maximum peaks in the residual electron density are -0.095 and +0.148 e Å^-3 after the IAM refinement, and -0.103 and +0.139 e Å^-3 after the ELMAN refinement. The improvement is not significant and indicates that the random noise in the residual Fourier map is here larger than the effect of not modelling the bonding electron density.

The largest effect of the multipole transfer on the crystallographic structure is observed on the atomic thermal motion (Jelsch et al., 1998). The average value of U_eq (geometric mean of eigenvalues U_i) derived from the IAM refinement is 0.0247 Ų, which is slightly higher than the value of 0.0218 Ų from the ELMAM refinement. The correlation coefficient between both U_eq sets is only 95%. With the IAM spherical atom model, the displacement parameters are incorrect as they incorporate some significant deformation electron density, due to improper deconvolution between these two features (Jelsch et al., 1998). The transfered multipolar refinement changes the values of the U^ij thermal parameters and improves their accuracy.

When no rigid bond restrains are applied, the r.m.s. of the Hirshfeld (1976) test is 0.0042Ų for spherical atom and 0.0040Ų for multipolar atom models. As the Hirshfeld test was not satisfied, rigid bond restraints were applied in the refinement. The Hishfeld test may not systematically improve a lot in a multipolar atom refinement compared to a spherical atom model. This is partly because the bonding electron density shared between two atoms is generally located in the middle of the bond and the two U^ij values are similarly perturbed along the bond direction when a spherical atom model is used. Also, the U^ij values may be mainly affected by the errors in the diffraction data which explains the necessity here to use rigid bond restrains even in the multipolar refinement. The improvement of residual electron-density maps, of R factors and of thermal U^ij parameters is limited in the case of this structure due to the predominance of errors in the diffraction data versus errors in electron-density modelling.

S2. Experimental

To a solution of the racemic secondary amine, (I) (Bartsch & Schwarz, 1983) (0.32 g, 2 mmol), in absolute pyridine (25 ml) at 277 K under an argon atmosphere were added benzoyl chloride dropwise (75 µl, 2 equivalents) and a crystal (Size? Mass?) of DMAP [Please define]. The mixture was stirred for 14 h at room temperature and the solvent and reagent excess evaporated under reduced pressure. The residue was dissolved in CH₂Cl₂ (50 ml), washed with water (3 × 10 ml), isolated, dried over MgSO₄, and finally concentrated under reduced pressure. The resulting gum solidified on standing in the dark and was crystallized from hot 96% EtOH to give white monocrystals [yield 78%, 0.412 g; m.p. 434–435 K (Tottoli [An instrument?])]. Spectroscopic analysis: IR (NaCl neat, ν, cm^-1): 3056, 2948, 2361, 2350, 2240, 1657, 1495, 1370, 1266; ¹H NMR (250 MHz, CDCl₃, δ, p.p.m.): 3.81 (dd, 1H, J = 2.9 and 13.9 Hz, H13), 4.74 [dd, 1H, J = 3.6 and 13.9 Hz, H15A(B)], 5.3 [t, 1H, J = 3.3 and 13.9 Hz, H15B(A)], 6.7–6.8 (m, 2H, Ar), 6.95–7.1 (m, 2H, Ar), 7.35–7.65 (m, 5H, Bz); ES—MS⁺: 265.2 (100) [M + H]⁺, 238.2 (17) [M - CN]⁺. Elemental analysis, calculated for C₁₆H₁₂N₂O₂: C 72.72, H 4.58, N 10.60%; found: C 73.02, H 4.48, N 10.66%.

S3. Refinement

Least-squares refinement, based on |F|, were carried out using the program MoPro (Guillot et al., 2001; Jelsch et al., 2005) using the ELMAM electron-density database (Zarychta et al., 2007). Refinement of F against all reflections. No reflection had a negative intensity. The weighted R-factor wR and goodness of fit S are based on F, and conventional R-factors R are based on F. The threshold expression of F² > 2σ(F²) is used only for calculating R-factors(gt) and is not relevant to the choice of reflections for refinement. The reflection weights were set equal to 7.29/σ²(F_o). The U_iso(H) values were constrained to be 1.2U_eq of the parent atom.

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED (Oxford Diffraction, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: MoPro (Guillot et al., 2001; Jelsch et al., 2005); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: MoPro (Guillot et al., 2001; Jelsch et al., 2005).

Figures

	Fig. 1. The molecular structure of (II), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. A packing diagram for (II). Dashed lines indicate hydrogen bonds. [Cg is the centroid of which ring?] [Symmetry codes: (i) x, -y + 1/2, z + 1/2; (ii) -x + 1, y + 1/2, -z + 1/2; (iii) -x + 1, -y + 1, -z + 1; (iv) -x + 1, y - 1/2, -z - 1/2.]

4-Benzoyl-3,4-dihydro-2H-1,4-benzoxazine-2-carbonitrile

Crystal data

C16H12N2O2	F(000) = 552
Mr = 264.28	Dx = 1.322 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 21257 reflections
a = 11.8920 (4) Å	θ = 3.1–34.9°
b = 7.3590 (2) Å	µ = 0.09 mm^−1
c = 15.886 (1) Å	T = 100 K
β = 107.200 (4)°	Prismatic, colourless
V = 1328.06 (11) Å^3	0.35 × 0.22 × 0.17 mm
Z = 4

Data collection

Oxford Diffraction Xcalibur2 diffractometer	4047 independent reflections
Radiation source: Enhance (Mo) X-ray Source	2724 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.032
Detector resolution: 10.4508 pixels mm^-1	θmax = 30.6°, θmin = 2.7°
ω scans	h = 0→17
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008)	k = 0→10
Tmin = 0.950, Tmax = 1.000	l = −22→21
53523 measured reflections

Refinement

Refinement on F	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)] = 0.061	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.023	H-atom parameters constrained
S = 1.01	w = 1/[7.29σ^2(Fo^2)]
4047 reflections	(Δ/σ)max = 0.029
181 parameters	Δρmax = 0.14 e Å^−3
13 restraints	Δρmin = −0.10 e Å^−3

Special details

Experimental. Absorption correction: CrysAlis RED, Oxford Diffraction Ltd., Version 1.171.32.29 (release 10-06-2008 CrysAlis171.NET) (compiled Jun 10 2008,16:49:55) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

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

	x	y	z	Uiso*/Ueq
C1	0.1941 (1)	0.0050 (2)	0.21563 (9)	0.0190 (2)
C2	0.1190 (1)	0.1310 (2)	0.23588 (9)	0.0254 (2)
C3	−0.0009 (1)	0.1235 (2)	0.1938 (1)	0.0309 (2)
C4	−0.0470 (1)	−0.0096 (2)	0.13133 (10)	0.0284 (3)
C5	0.0273 (1)	−0.1360 (2)	0.11021 (10)	0.0281 (3)
C6	0.1477 (1)	−0.1284 (2)	0.15188 (10)	0.0241 (2)
C7	0.3192 (1)	0.0642 (2)	0.40680 (9)	0.0167 (2)
C8	0.2445 (1)	−0.0775 (2)	0.41318 (9)	0.0213 (2)
C9	0.1901 (1)	−0.0780 (2)	0.48008 (10)	0.0243 (3)
C10	0.2145 (1)	0.0605 (2)	0.54282 (10)	0.0245 (2)
C11	0.2941 (1)	0.1969 (2)	0.53963 (9)	0.0236 (2)
C12	0.3470 (1)	0.1978 (2)	0.47180 (10)	0.0184 (2)
C13	0.4725 (1)	0.3478 (2)	0.40127 (9)	0.0210 (2)
C14	0.3251 (1)	0.0183 (2)	0.25258 (9)	0.0167 (2)
C15	0.4888 (1)	0.1629 (2)	0.36372 (9)	0.0198 (2)
C16	0.3878 (1)	0.4611 (2)	0.3346 (1)	0.0269 (3)
N1	0.3182 (1)	0.5489 (2)	0.28530 (9)	0.0387 (2)
N2	0.37379 (10)	0.0715 (2)	0.33823 (7)	0.0199 (2)
O1	0.38754 (8)	−0.0041 (1)	0.20429 (6)	0.0243 (2)
O2	0.42847 (8)	0.3315 (1)	0.47577 (6)	0.0260 (2)
H2	0.15592	0.23887	0.28220	0.03045*
H3	−0.05868	0.21761	0.21320	0.03710*
H4	−0.14091	−0.01898	0.09955	0.03406*
H5	−0.01020	−0.24125	0.06250	0.03372*
H6	0.20901	−0.22495	0.13855	0.02887*
H8	0.22739	−0.18725	0.36566	0.02554*
H9	0.13282	−0.19104	0.48257	0.02921*
H10	0.17729	0.06457	0.59732	0.02943*
H11	0.31722	0.30276	0.58915	0.02835*
H13	0.55840	0.41625	0.42296	0.02514*
H15A	0.51960	0.17382	0.30562	0.02378*
H15B	0.54957	0.08009	0.41410	0.02378*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0192 (9)	0.0200 (10)	0.0156 (9)	0.0037 (8)	0.0033 (7)	−0.0030 (6)
C2	0.0217 (6)	0.029 (1)	0.0222 (10)	0.0066 (9)	0.0026 (7)	−0.0052 (8)
C3	0.0225 (6)	0.040 (1)	0.0262 (10)	0.0088 (9)	0.0010 (7)	−0.0064 (7)
C4	0.0203 (10)	0.037 (1)	0.0239 (10)	−0.0026 (9)	0.0022 (7)	−0.0010 (7)
C5	0.0224 (6)	0.031 (1)	0.027 (1)	−0.0031 (9)	0.0031 (7)	−0.0057 (8)
C6	0.0227 (6)	0.0254 (10)	0.0210 (9)	−0.0017 (8)	0.0032 (6)	−0.0066 (6)
C7	0.0179 (7)	0.0146 (9)	0.0161 (5)	−0.0044 (8)	0.0051 (3)	−0.0001 (7)
C8	0.0238 (9)	0.020 (1)	0.0185 (9)	−0.0052 (8)	0.0087 (7)	−0.0023 (7)
C9	0.0258 (10)	0.026 (1)	0.0200 (9)	−0.0056 (9)	0.0088 (7)	−0.0004 (8)
C10	0.0282 (9)	0.025 (1)	0.0183 (9)	−0.0068 (7)	0.0090 (7)	−0.0021 (8)
C11	0.0286 (9)	0.025 (1)	0.0167 (9)	−0.0061 (7)	0.0104 (8)	−0.0019 (7)
C12	0.0223 (9)	0.0160 (9)	0.0154 (9)	−0.0023 (6)	0.0066 (7)	−0.0025 (7)
C13	0.0233 (9)	0.023 (1)	0.0158 (8)	0.0005 (9)	0.0090 (6)	0.0026 (8)
C14	0.0179 (9)	0.0174 (9)	0.0135 (6)	0.0005 (8)	0.0057 (5)	−0.0022 (6)
C15	0.0169 (7)	0.020 (1)	0.0205 (9)	−0.0015 (6)	0.0047 (7)	−0.0004 (7)
C16	0.030 (1)	0.023 (1)	0.027 (1)	0.0037 (7)	0.0154 (7)	0.0016 (7)
N1	0.0388 (9)	0.032 (1)	0.043 (1)	0.0111 (7)	0.0173 (7)	0.0116 (7)
N2	0.0179 (5)	0.0248 (8)	0.0152 (4)	−0.0030 (5)	0.0047 (3)	−0.0037 (5)
O1	0.0238 (6)	0.0296 (7)	0.0188 (6)	0.0007 (6)	0.0107 (4)	−0.0036 (5)
O2	0.0366 (7)	0.0220 (7)	0.0191 (6)	−0.0111 (5)	0.0156 (5)	−0.0064 (5)

Geometric parameters (Å, º)

O1—C14	1.227 (1)	C5—C6	1.390 (2)
O2—C12	1.370 (2)	C5—H5	1.083
O2—C13	1.434 (2)	C6—H6	1.083
N2—C7	1.424 (2)	C7—C8	1.393 (2)
N2—C14	1.369 (2)	C7—C12	1.393 (2)
N2—C15	1.470 (2)	C8—C9	1.398 (2)
C13—C16	1.483 (2)	C8—H8	1.083
N1—C16	1.155 (2)	C9—C10	1.395 (2)
C1—C2	1.389 (2)	C9—H9	1.083
C1—C6	1.401 (2)	C10—C11	1.391 (2)
C1—C14	1.497 (2)	C10—H10	1.083
C2—C3	1.385 (2)	C11—C12	1.399 (2)
C2—H2	1.083	C11—H11	1.083
C3—C4	1.387 (2)	C13—C15	1.521 (2)
C3—H3	1.083	C13—H13	1.099
C4—C5	1.391 (2)	C15—H15A	1.092
C4—H4	1.083	C15—H15B	1.092
C7—N2—C14	126.5 (2)	C4—C5—C6	119.8 (1)
C7—N2—C15	113.8 (1)	C4—C5—H5	119.2
C14—N2—C15	119.4 (1)	C5—C6—H6	122.6
O1—C14—N2	120.2 (2)	C5—C4—H4	119.1
O1—C14—C1	119.9 (1)	C6—C5—H5	121.0
N2—C14—C1	119.6 (1)	C6—C1—C14	118.1 (1)
C13—C16—N1	176.6 (2)	C7—C8—C9	120.4 (2)
C13—C15—N2	107.5 (1)	C7—C8—H8	120.0
C15—C13—O2	111.7 (1)	C7—C12—C11	120.4 (2)
C16—C13—O2	107.4 (1)	C12—C11—H11	118.7
C15—C13—C16	111.2 (1)	C8—C9—C10	119.7 (2)
C7—C12—O2	123.4 (1)	C8—C9—H9	117.9
C8—C7—N2	121.9 (1)	C8—C7—C12	119.4 (1)
C11—C12—O2	116.2 (1)	C9—C10—C11	120.1 (1)
C12—O2—C13	116.6 (1)	C9—C10—H10	122.9
C12—C7—N2	118.6 (2)	C9—C8—H8	119.6
C1—C2—C3	120.1 (2)	C10—C11—C12	119.8 (2)
C1—C2—H2	119.2	C10—C11—H11	121.5
C1—C6—C5	120.2 (2)	C10—C9—H9	122.4
C1—C6—H6	117.2	C11—C10—H10	116.9
C2—C3—C4	120.4 (2)	C13—C15—H15A	112.3
C2—C3—H3	119.1	C13—C15—H15B	110.2
C2—C1—C6	119.5 (2)	C15—C13—H13	108.6
C2—C1—C14	122.1 (1)	C16—C13—H13	109.8
C3—C2—H2	120.6	N2—C15—H15A	108.6
C3—C4—C5	120.0 (2)	N2—C15—H15B	107.9
C3—C4—H4	120.9	O2—C13—H13	108.2
C4—C3—H3	120.3	H15A—C15—H15B	110.2
C1—C14—N2—C7	20.9 (1)	C8—C7—N2—C15	−149.8 (1)
C1—C14—N2—C15	−152.4 (1)	C8—C7—C12—O2	173.3 (1)
C2—C1—C14—N2	39.2 (1)	C8—C7—C12—C11	−4.4 (1)
C7—N2—C14—O1	−165.0 (1)	C9—C10—C11—C12	1.9 (1)
C7—N2—C15—C13	−52.8 (1)	C9—C10—C11—H11	−177.4
C8—C7—N2—C14	36.6 (1)	C9—C8—C7—N2	−178.4 (1)
C7—C12—O2—C13	9.7 (1)	C9—C8—C7—C12	5.2 (1)
C12—O2—C13—C16	84.3 (1)	C10—C11—C12—O2	−177.0 (1)
C12—O2—C13—C15	−37.9 (1)	C10—C9—C8—H8	178.2
C12—C7—N2—C15	26.6 (1)	C11—C10—C9—H9	176.2
C13—C15—N2—C14	121.4 (1)	C11—C12—O2—C13	−172.5 (1)
C1—C2—C3—C4	0.09 (13)	C11—C12—C7—N2	179.1 (1)
C1—C2—C3—H3	176.3	C12—O2—C13—H13	−157.3
C1—C6—C5—C4	0.7 (1)	C12—C11—C10—H10	178.9
C1—C6—C5—H5	−177.8	C12—C7—N2—C14	−147.0 (1)
C2—C3—C4—C5	−0.4 (1)	C12—C7—C8—H8	−175.5
C2—C3—C4—H4	178.1	C14—N2—C15—H15A	−0.4
C2—C1—C6—C5	−1.0 (1)	C14—N2—C15—H15B	−119.8
C2—C1—C6—H6	−179.3	C14—C1—C2—H2	−2.9
C2—C1—C14—O1	−135.0 (2)	C14—C1—C6—H6	7.1
C3—C2—C1—C6	0.6 (1)	C15—N2—C14—O1	21.7 (1)
C3—C2—C1—C14	173.9 (1)	C16—C13—C15—N2	−61.2 (1)
C3—C4—C5—C6	0.00 (15)	C16—C13—C15—H15A	58.2
C3—C4—C5—H5	178.5	C16—C13—C15—H15B	−178.5
C4—C3—C2—H2	176.8	N2—C7—C8—H8	0.9
C4—C5—C6—H6	179.0	N2—C7—C12—O2	−3.2 (1)
C5—C6—C1—C14	−174.5 (1)	N2—C15—C13—O2	58.8 (1)
C5—C4—C3—H3	−176.5	N2—C15—C13—H13	178.0
C6—C5—C4—H4	−178.5	O2—C12—C11—H11	2.3
C6—C1—C2—H2	−176.2	O2—C13—C15—H15A	178.1
C6—C1—C14—O1	38.4 (1)	O2—C13—C15—H15B	−58.6
C6—C1—C14—N2	−147.5 (1)	H2—C2—C3—H3	−7.0
C7—N2—C15—H15A	−174.5	H3—C3—C4—H4	2.0
C7—N2—C15—H15B	66.1	H4—C4—C5—H5	0.0
C7—C8—C9—C10	−2.5 (1)	H5—C5—C6—H6	0.5
C7—C8—C9—H9	−179.9	H8—C8—C9—H9	0.8
C7—C12—C11—C10	0.9 (1)	H9—C9—C10—H10	−0.6
C7—C12—C11—H11	−179.8	H10—C10—C11—H11	−0.4
C8—C9—C10—C11	−1.0 (1)	H13—C13—C15—H15A	−62.7
C8—C9—C10—H10	−177.9	H13—C13—C15—H15B	60.6

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C11—H11···O1^i	1.08	2.31	3.387 (2)	172
C13—H13···O1^ii	1.10	2.37	2.902 (2)	108
C13—H13···O2^iii	1.10	2.43	3.068 (2)	115
C15—H15B···Cg^iv	1.09	2.57	3.633 (2)	165

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