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The title compound, C17H16N2O3, is an antagonist for AMPA/kainate receptors. The mol­ecule has its seven-membered oxa­diazo­le ring in a boat conformation. Asymmetry of the two methoxy bond angles is evident, with (Me)O—C—C angles of 115.45 (12) and 124.78 (13)°, and 114.67 (12) and 125.31 (12)°. A centrosymmetric dimer involving the HN—CO moieties, with an N...O distance of 2.876 (2) Å, graph set R{_2^2}(8), is further linked into chains through methoxy Csp3—H...N hydrogen bonds, with a C...N distance of 3.418 (2) Å.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270101011805/gg1067sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270101011805/gg1067Isup2.hkl
Contains datablock I

CCDC reference: 174849

Comment top

In previous publications (De Sarro et al., 1995; Chimirri et al., 1997, 1998), we reported on chemical and biological studies of some 2,3-benzodiazepine derivatives which have been shown to behave as anticonvulsants, acting as non-competitive antagonists against AMPA/kainate receptors. This paper describes the crystal structure analysis of 4,5-dihydro-7,8-dimethoxy-1-phenyl-3H-2,3-benzodiazepin-4-one, (I), one of the most active compounds of the series, with the aim of comparing the molecular geometry with the analogous 2,3-benzodiazepines reported in the literature (Anderson et al., 1996). The results of this study will be used for the study of structure-activity relationships, in order to understand better the structural characteristics necessary for AMPA/kainate receptor antagonists. \sch

Although there are several crystal structure reports on benzodiazepines, the 1,2- or 2,3-derivatives are relatively rare. In (I) (Fig. 1), the bond lengths and angles of the seven-membered ring are in good agreement with the corresponding values reported for the parent compound 7,11-dihydro-9,10-dimethoxy-3,11b-diphenyl[1,2,4]oxadiazolo[5,4-a][2,3]benzodiazepin-6(5H)-one, (II) (Bruno et al., 1999), and for the rare analogous 2,3-benzodiazepine reported in the Cambridge Structural Database (CSD; April 2001 release, version 5.21; Allen & Kennard, 1993).

In the diazepinone fragment, the bond lengths agree reasonably well with the system of localized single and double bonds (Table 1). Slight deviations from the expected values may be explained by the intra- and intermolecular hydrogen bonds involving this fragment. Atom N3 is involved in an intramolecular contact with the H atom on C13, and this contact is critical for the orientation of the phenyl ring bonded to C4. A strong intermolecular hydrogen bond involves a pair of molecules related by the inversion centre through the HN—CO groups, with graph set R22(8) (Bernstein et al., 1995). This centrosymmetric dimer is connected to adjacent units by intermolecular methoxy C18—H18A···N3 hydrogen bonds, graph set R44(24), along the b axis. Both intra- and intermolecular contacts and interactions are responsible for the molecular packing observed in the solid state.

The seven-membered ring has a boat conformation [ϕ2 = 53.9 (1), ϕ3 = -102.7 (4) and θ = 76.6 (1)°, and Q = 0.892 (2) Å; Cremer & Pople, 1975). As in compound (II) (Bruno et al., 1999), and in the organic structures in the CSD containing the fragment depicted in Fig. 2, in (I) a large asymmetry in the dimethoxy ring angles is noticeable: O2—C9—C10 = 115.5 (1), O2—C9—C8 = 124.8 (1), O3—C10—C9 = 114.7 (1) and O3—C10—C11 = 125.3 (1)°. Although the planarity of the methoxy groups with the phenyl ring was noted in previous work, these authors attributed such an orientation either to the `presumable' steric interaction between the methyl and phenyl H atoms (Salem et al., 1988; Sharma et al., 1997; Dijksma et al., 1998; Kumar et al., 1998) or to the correct balance between no (non-bonding orbital) and the π delocalization of the oxygen lone pairs and the cited H···H interaction (Bock et al., 1995). The latter explanation was also proposed in a statistical analysis of crystal structure data for mono-substituted methoxyphenyl compounds (Hummel et al., 1988). The significant asymmetry in the above methoxyphenyl angles [mean 10.0 (2)°] also causes a close contact of 2.557 (2) Å between the two methoxy O atoms, which is smaller than their van der Waals radii sum (2.80 Å; ref?).

A search was undertaken of the CSD database and 478 organic compounds (with R < 0.081) were located containing the fragment shown in Fig. 2, which gives the mean values for the significant structural parameters. We deduce that the planarity of the methoxy group with respect to the phenyl ring is determined by conjugation effects. In order to rationalize this problem still further, we have in progress research into statistical analysis on methoxy-phenyl substituted compounds, and are carrying out semi-empirical and ab initio calculations on this fragment model. This research will be the subject of a forthcoming publication (Bruno & Nicoló, 2001).

Experimental top

The title compound was obtained as described previously by De Sarro et al. (1995). Suitable single crystals of (I) were obtained by recrystallization from an ethanol solution.

Refinement top

The amine hydrogen H2 was located from a difference map and refined freely. The remaining H atoms were located in idealized positions and allowed to ride on their parent C atoms, with Uiso(H) = 1.2Ueq(C) and C—H = 0.93–0.97 Å.

Computing details top

Data collection: P3/V (Siemens, 1989); cell refinement: P3/V; data reduction: SHELXTL-Plus (Sheldrick, 1990); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XPW (Siemens, 1996); software used to prepare material for publication: PARST97 (Nardelli, 1995) and SHELXL97.

Figures top
[Figure 1] Fig. 1. A molecular view of (I) with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii. Dotted lines represent hydrogen bonds with symmetry-related molecules [symmetry codes: (i) 1 - x, 1 - y, 1 - z; (ii) x, 1 + y, z; (iii) x, y - 1, z].
[Figure 2] Fig. 2. Diagram showing the mean geometric values (Å, °) for the dimethoxyphenyl fragments reported in the CSD.
4,5-Dihydro-7,8-dimethoxy-1-phenyl-3H-2,3-benzodiazepin-4-one top
Crystal data top
C17H16N2O3F(000) = 624
Mr = 296.32Dx = 1.356 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 8.207 (2) ÅCell parameters from 30 reflections
b = 10.312 (2) Åθ = 6.4–13.8°
c = 17.236 (2) ŵ = 0.09 mm1
β = 95.60 (1)°T = 298 K
V = 1451.7 (5) Å3Irregular, colourless
Z = 40.26 × 0.24 × 0.12 mm
Data collection top
Siemens P4
diffractometer
Rint = 0.008
Radiation source: fine-focus sealed tubeθmax = 25.1°, θmin = 2.3°
Graphite monochromatorh = 19
ω/2θ scansk = 312
2903 measured reflectionsl = 2020
2567 independent reflections3 standard reflections every 197 reflections
1734 reflections with I > 2σ(I) intensity decay: none
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.032H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.080 w = 1/[σ2(Fo2) + (0.0519P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.84(Δ/σ)max = 0.001
2567 reflectionsΔρmax = 0.16 e Å3
204 parametersΔρmin = 0.15 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0045 (9)
Crystal data top
C17H16N2O3V = 1451.7 (5) Å3
Mr = 296.32Z = 4
Monoclinic, P21/nMo Kα radiation
a = 8.207 (2) ŵ = 0.09 mm1
b = 10.312 (2) ÅT = 298 K
c = 17.236 (2) Å0.26 × 0.24 × 0.12 mm
β = 95.60 (1)°
Data collection top
Siemens P4
diffractometer
Rint = 0.008
2903 measured reflections3 standard reflections every 197 reflections
2567 independent reflections intensity decay: none
1734 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0320 restraints
wR(F2) = 0.080H atoms treated by a mixture of independent and constrained refinement
S = 0.84Δρmax = 0.16 e Å3
2567 reflectionsΔρmin = 0.15 e Å3
204 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
xyzUiso*/Ueq
C10.44184 (17)0.62315 (14)0.58707 (9)0.0392 (4)
O10.56570 (12)0.64626 (10)0.55456 (7)0.0502 (3)
N20.33046 (15)0.53575 (13)0.55707 (9)0.0431 (4)
H20.360 (2)0.4848 (18)0.5208 (11)0.066 (6)*
N30.19281 (14)0.48951 (12)0.58928 (8)0.0418 (3)
C40.09083 (17)0.56974 (14)0.61556 (9)0.0349 (4)
C50.10517 (16)0.71263 (13)0.61856 (8)0.0324 (3)
C60.25402 (16)0.77126 (14)0.64210 (8)0.0329 (3)
C70.40348 (16)0.68860 (15)0.66093 (9)0.0398 (4)
H7A0.49510.74190.68140.048*
H7B0.3830.62430.69990.048*
C80.26573 (16)0.90642 (14)0.64534 (8)0.0360 (4)
H80.36530.94530.6620.043*
C90.13049 (17)0.98247 (13)0.62402 (8)0.0344 (4)
C100.01944 (15)0.92377 (14)0.59857 (8)0.0318 (3)
C110.03263 (16)0.79086 (14)0.59738 (8)0.0332 (3)
H110.13330.75230.58250.04*
C120.05541 (16)0.50662 (13)0.64471 (9)0.0361 (4)
C130.11398 (19)0.38906 (15)0.61385 (10)0.0489 (4)
H130.06170.34880.57480.059*
C140.2495 (2)0.33216 (17)0.64108 (12)0.0632 (5)
H140.28810.25370.620.076*
C150.3284 (2)0.38962 (17)0.69880 (11)0.0574 (5)
H150.42080.35110.71610.069*
C160.26981 (19)0.50438 (16)0.73070 (10)0.0478 (4)
H160.32090.5430.77070.057*
C170.13526 (17)0.56232 (15)0.70350 (9)0.0401 (4)
H170.09720.64060.72510.048*
O20.12966 (12)1.11411 (10)0.62487 (7)0.0481 (3)
C180.27701 (19)1.17974 (16)0.65132 (10)0.0524 (4)
H18A0.2591.27170.64880.079*
H18B0.36111.15690.61880.079*
H18C0.31051.1550.70420.079*
O30.14385 (11)1.00856 (9)0.57731 (6)0.0418 (3)
C190.30176 (18)0.95579 (17)0.55732 (11)0.0521 (5)
H19A0.37791.02470.54360.078*
H19B0.3360.90880.6010.078*
H19C0.29850.89810.51380.078*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0325 (8)0.0317 (9)0.0543 (10)0.0061 (7)0.0089 (7)0.0012 (7)
O10.0402 (6)0.0439 (7)0.0694 (8)0.0028 (5)0.0198 (5)0.0096 (6)
N20.0391 (7)0.0366 (8)0.0565 (9)0.0011 (6)0.0189 (6)0.0107 (7)
N30.0386 (7)0.0325 (7)0.0563 (9)0.0015 (6)0.0153 (6)0.0026 (6)
C40.0346 (8)0.0303 (8)0.0400 (9)0.0016 (7)0.0048 (6)0.0014 (7)
C50.0327 (7)0.0285 (8)0.0371 (8)0.0009 (6)0.0089 (6)0.0010 (7)
C60.0325 (8)0.0320 (8)0.0350 (8)0.0035 (6)0.0071 (6)0.0019 (7)
C70.0339 (8)0.0373 (9)0.0484 (10)0.0050 (7)0.0044 (7)0.0028 (7)
C80.0303 (8)0.0355 (9)0.0423 (9)0.0029 (6)0.0045 (6)0.0052 (7)
C90.0374 (8)0.0266 (8)0.0399 (9)0.0002 (6)0.0076 (7)0.0006 (7)
C100.0296 (7)0.0318 (8)0.0346 (8)0.0035 (6)0.0061 (6)0.0016 (6)
C110.0278 (7)0.0331 (8)0.0391 (8)0.0023 (6)0.0055 (6)0.0014 (7)
C120.0346 (8)0.0285 (8)0.0451 (9)0.0018 (6)0.0039 (7)0.0052 (7)
C130.0502 (9)0.0319 (9)0.0657 (11)0.0016 (8)0.0117 (8)0.0032 (8)
C140.0595 (11)0.0369 (10)0.0941 (15)0.0148 (9)0.0118 (10)0.0001 (10)
C150.0476 (10)0.0467 (11)0.0797 (14)0.0067 (9)0.0158 (9)0.0193 (10)
C160.0443 (9)0.0513 (11)0.0494 (11)0.0034 (8)0.0126 (8)0.0121 (8)
C170.0385 (8)0.0376 (9)0.0444 (9)0.0007 (7)0.0049 (7)0.0007 (7)
O20.0446 (6)0.0258 (6)0.0725 (8)0.0016 (5)0.0011 (5)0.0018 (5)
C180.0522 (10)0.0334 (9)0.0703 (12)0.0088 (8)0.0006 (8)0.0044 (9)
O30.0332 (5)0.0333 (6)0.0583 (7)0.0049 (5)0.0008 (5)0.0039 (5)
C190.0348 (8)0.0514 (11)0.0678 (12)0.0046 (8)0.0058 (8)0.0032 (9)
Geometric parameters (Å, º) top
C1—O11.231 (2)C13—C141.380 (2)
C1—N21.350 (2)C14—C151.373 (2)
C1—C71.501 (2)C15—C161.372 (2)
N2—N31.391 (2)C16—C171.377 (2)
N3—C41.290 (2)N2—H20.87 (2)
C4—C51.479 (2)C7—H7A0.97
C4—C121.495 (2)C7—H7B0.97
C5—C61.388 (2)C8—H80.93
C5—C111.4080 (19)C11—H110.93
C6—C81.398 (2)C13—H130.93
C6—C71.503 (2)C14—H140.93
C8—C91.3793 (19)C15—H150.93
O2—C91.358 (2)C16—H160.93
O3—C101.367 (2)C17—H170.93
O2—C181.421 (2)C18—H18A0.96
O3—C191.417 (2)C18—H18B0.96
C9—C101.4027 (19)C18—H18C0.96
C10—C111.375 (2)C19—H19A0.96
C12—C171.384 (2)C19—H19B0.96
C12—C131.391 (2)C19—H19C0.96
O1—C1—N2120.9 (1)C5—C11—H11119.8
O1—C1—C7123.4 (1)C17—C12—C13118.11 (14)
N2—C1—C7115.8 (1)C17—C12—C4121.23 (13)
C1—N2—N3128.5 (1)C13—C12—C4120.66 (14)
C1—N2—H2117 (1)C14—C13—C12120.04 (16)
N3—N2—H2112 (1)C14—C13—H13120
N2—N3—C4120.0 (1)C12—C13—H13120
N3—C4—C5126.8 (1)C15—C14—C13121.04 (17)
N3—C4—C12114.1 (1)C15—C14—H14119.5
C5—C4—C12119.1 (1)C13—C14—H14119.5
C6—C5—C11119.22 (13)C16—C15—C14119.39 (16)
C4—C5—C6120.6 (1)C16—C15—H15120.3
C11—C5—C4120.18 (13)C14—C15—H15120.3
C5—C6—C8120.08 (13)C15—C16—C17119.95 (16)
C5—C6—C7119.5 (1)C15—C16—H16120
C8—C6—C7120.36 (13)C17—C16—H16120
C1—C7—C6107.8 (1)C16—C17—C12121.45 (15)
C1—C7—H7A110.1C16—C17—H17119.3
C6—C7—H7A110.1C12—C17—H17119.3
C1—C7—H7B110.1C9—O2—C18118.3 (1)
C6—C7—H7B110.1O2—C18—H18A109.5
H7A—C7—H7B108.5O2—C18—H18B109.5
C9—C8—C6120.39 (13)H18A—C18—H18B109.5
C9—C8—H8119.8O2—C18—H18C109.5
C6—C8—H8119.8H18A—C18—H18C109.5
O2—C9—C8124.78 (13)H18B—C18—H18C109.5
O2—C9—C10115.45 (12)C10—O3—C19117.5 (1)
C8—C9—C10119.77 (13)O3—C19—H19A109.5
O3—C10—C11125.31 (12)O3—C19—H19B109.5
O3—C10—C9114.67 (12)H19A—C19—H19B109.5
C11—C10—C9120.01 (13)O3—C19—H19C109.5
C10—C11—C5120.48 (13)H19A—C19—H19C109.5
C10—C11—H11119.8H19B—C19—H19C109.5
O1—C1—N2—N3173.64 (14)O2—C9—C10—C11178.38 (13)
C7—C1—N2—N36.6 (2)C8—C9—C10—C112.2 (2)
C1—N2—N3—C450.0 (2)O3—C10—C11—C5178.23 (13)
N2—N3—C4—C52.5 (2)C9—C10—C11—C52.6 (2)
N2—N3—C4—C12177.05 (13)C6—C5—C11—C101.2 (2)
N3—C4—C5—C642.8 (2)C4—C5—C11—C10178.71 (13)
C12—C4—C5—C6137.75 (14)N3—C4—C12—C17150.78 (14)
N3—C4—C5—C11137.15 (16)C5—C4—C12—C1729.7 (2)
C12—C4—C5—C1142.3 (2)N3—C4—C12—C1328.5 (2)
C11—C5—C6—C80.6 (2)C5—C4—C12—C13151.02 (15)
C4—C5—C6—C8179.45 (14)C17—C12—C13—C141.0 (2)
C11—C5—C6—C7176.94 (12)C4—C12—C13—C14179.72 (15)
C4—C5—C6—C73.0 (2)C12—C13—C14—C150.2 (3)
O1—C1—C7—C6113.45 (16)C13—C14—C15—C161.1 (3)
N2—C1—C7—C666.28 (17)C14—C15—C16—C171.5 (3)
C5—C6—C7—C165.53 (17)C15—C16—C17—C120.7 (2)
C8—C6—C7—C1112.03 (15)C13—C12—C17—C160.5 (2)
C5—C6—C8—C91.1 (2)C4—C12—C17—C16179.83 (13)
C7—C6—C8—C9176.48 (13)C8—C9—O2—C181.6 (2)
C6—C8—C9—O2179.73 (14)C10—C9—O2—C18178.95 (13)
C6—C8—C9—C100.3 (2)C11—C10—O3—C194.4 (2)
O2—C9—C10—O30.88 (19)C9—C10—O3—C19174.81 (13)
C8—C9—C10—O3178.59 (12)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2···O1i0.87 (2)2.01 (2)2.876 (2)174 (2)
C18—H18A···N3ii0.962.513.418 (2)158
C13—H13···N30.932.542.793 (2)96
Symmetry codes: (i) x+1, y+1, z+1; (ii) x, y+1, z.

Experimental details

Crystal data
Chemical formulaC17H16N2O3
Mr296.32
Crystal system, space groupMonoclinic, P21/n
Temperature (K)298
a, b, c (Å)8.207 (2), 10.312 (2), 17.236 (2)
β (°) 95.60 (1)
V3)1451.7 (5)
Z4
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.26 × 0.24 × 0.12
Data collection
DiffractometerSiemens P4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
2903, 2567, 1734
Rint0.008
(sin θ/λ)max1)0.597
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.032, 0.080, 0.84
No. of reflections2567
No. of parameters204
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.16, 0.15

Computer programs: P3/V (Siemens, 1989), P3/V, SHELXTL-Plus (Sheldrick, 1990), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), XPW (Siemens, 1996), PARST97 (Nardelli, 1995) and SHELXL97.

Selected geometric parameters (Å, º) top
C1—O11.231 (2)C5—C61.388 (2)
C1—N21.350 (2)C6—C71.503 (2)
C1—C71.501 (2)O2—C91.358 (2)
N2—N31.391 (2)O3—C101.367 (2)
N3—C41.290 (2)O2—C181.421 (2)
C4—C51.479 (2)O3—C191.417 (2)
O1—C1—N2120.9 (1)C4—C5—C6120.6 (1)
O1—C1—C7123.4 (1)C5—C6—C7119.5 (1)
C1—N2—N3128.5 (1)C9—O2—C18118.3 (1)
N2—N3—C4120.0 (1)C10—O3—C19117.5 (1)
N3—C4—C5126.8 (1)
N2—C1—C7—C666.28 (17)C8—C9—O2—C181.6 (2)
C5—C4—C12—C1729.7 (2)C11—C10—O3—C194.4 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2···O1i0.87 (2)2.01 (2)2.876 (2)174 (2)
C18—H18A···N3ii0.962.513.418 (2)158
C13—H13···N30.932.542.793 (2)96
Symmetry codes: (i) x+1, y+1, z+1; (ii) x, y+1, z.
 

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