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Acta Cryst. (2008). E64, o802    [ doi:10.1107/S1600536808008787 ]

3-(3-Chloropropyl)-7,8-dimethoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-2-one at 125 K

X.-W. Cheng

Abstract top

In the title compound, C15H20ClNO3, the seven-membered ring adopts a distorted boat-sofa conformation; the methylene C atoms of this ring are coplanar with the benzene ring. Both methoxy groups are almost coplanar with the attached benzene ring [C-C-O-C = 6.5 (2) and -13.5 (3)°]. An intramolecular C-H...O hydrogen bond is observed in the molecular structure. In the crystal structure, a C-H...[pi] interaction involving the benzene ring is observed.

Comment top

Benzazepine derivatives have been of considerable medicinal interest, partly because the skeleton is a component of amaryllydaceae alkaloids such as galanthamine as well as of ribasine alkaloids represented by ribasine (Ishihara et al., 1994). Many benzazepine derivatives have been reported to possess interesting biological activities. The title compound is an important intermediate of ivabradine, which was listed in market in 2006 as the representative of a novel pharmacological class termed specific bradycardic agents. Here the crystal structure of the title compound is reported.

In the title molecule (Fig.1), the seven-membered ring adopts a distorted boat-sofa conformation with a pseudo mirror plane through C7 and the centre of the N1—C10 bond. Atoms C9, C12 and C13 of the seven-membered ring are coplanar with the benzene ring. The dihedral angle between the C3-C9/C12/C13 and C9/C10/N1/C12 planes is 60.61 (8)°. The chloropropyl substituent group is in a (-)-synclinal conformation, as evidenced by the torsion angle N1—C14—C15—C16 of -68.9 (2)°, similar to that in a related structure (-62.63 (2)°, Reiffen et al., 1990). The methoxy groups are almost coplanar with the benzene ring [C8—C3—O1—C1 = 6.5 (2)° and C5—C4—O2—C2 = -13.5 (3)°].

An intramolecular C—H···O hydrogen bond is observed in the molecular structure (Fig.1). In the crystal structure, a C—H···π interaction involving the benzene ring is observed (Table 1).

Related literature top

For details of the synthesis, see: Reiffen et al. (1981). For general background, see: Ishihara et al. (1994). For a related structure, see: Reiffen et al. (1990).

Experimental top

The title compound was prepared according to the literature method (Reiffen et al., 1981). Crystals suitable for X-ray analysis were obtained by slow evaporation of an isopropanol solution at 295 K.

Refinement top

H atoms were positioned geometrically (C-H = 0.93-0.97 Å) and refined using a riding model, with Uiso(H) = 1.2–1.5Ueq(C).

Computing details top

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Molecular structure of the title compound, showing 30% probability displacement ellipsoids and the atomic numbering.
[Figure 2] Fig. 2. Crystal packing of the title compound, viewed approximately down the b axis. Dashed lines indicate intramolecular hydrogen bonds.
3-(3-Chloropropyl)-7,8-dimethoxy-2,3,4,5-tetrahydro-1H- 3-benzazepin-2-one top
Crystal data top
C15H20ClNO3Z = 2
Mr = 297.77F000 = 316
Triclinic, P1Dx = 1.339 Mg m−3
Hall symbol: -P 1Mo Kα radiation
λ = 0.71073 Å
a = 8.134 (3) ÅCell parameters from 2542 reflections
b = 8.498 (3) Åθ = 1.8–25.0º
c = 11.701 (4) ŵ = 0.27 mm−1
α = 92.880 (12)ºT = 125 K
β = 105.981 (12)ºBlock, colourless
γ = 106.440 (12)º0.29 × 0.28 × 0.22 mm
V = 738.5 (5) Å3
Data collection top
Bruker SMART CCD area-detector
diffractometer		2542 independent reflections
Radiation source: fine-focus sealed tube2137 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.020
T = 123(2) Kθmax = 25.0º
φ and ω scansθmin = 1.8º
Absorption correction: multi-scan
(SADABS; Bruker, 2002)		h = −9→9
Tmin = 0.927, Tmax = 0.944k = −9→9
6809 measured reflectionsl = −13→11
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)] = 0.039H-atom parameters constrained
wR(F2) = 0.112  w = 1/[σ2(Fo2) + (0.0588P)2 + 0.1232P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max = 0.001
2542 reflectionsΔρmax = 0.19 e Å−3
183 parametersΔρmin = −0.23 e Å−3
Primary atom site location: structure-invariant direct methodsExtinction correction: none
Crystal data top
C15H20ClNO3γ = 106.440 (12)º
Mr = 297.77V = 738.5 (5) Å3
Triclinic, P1Z = 2
a = 8.134 (3) ÅMo Kα
b = 8.498 (3) ŵ = 0.27 mm−1
c = 11.701 (4) ÅT = 125 K
α = 92.880 (12)º0.29 × 0.28 × 0.22 mm
β = 105.981 (12)º
Data collection top
Bruker SMART CCD area-detector
diffractometer		2542 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2002)		2137 reflections with I > 2σ(I)
Tmin = 0.927, Tmax = 0.944Rint = 0.020
6809 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.039183 parameters
wR(F2) = 0.112H-atom parameters constrained
S = 1.06Δρmax = 0.19 e Å−3
2542 reflectionsΔρmin = −0.23 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
xyzUiso*/Ueq
C10.2530 (3)0.0704 (3)1.09762 (17)0.0633 (5)
H1A0.37220.06741.13710.095*
H1B0.17320.01821.14130.095*
H1C0.25440.18341.09450.095*
C2−0.0455 (3)−0.2072 (3)0.63151 (18)0.0689 (6)
H2A−0.0677−0.11410.59420.103*
H2B−0.1580−0.28940.62430.103*
H2C0.0232−0.25390.59270.103*
C30.2849 (2)0.0480 (2)0.90096 (14)0.0445 (4)
C40.2103 (2)−0.02661 (19)0.78048 (15)0.0445 (4)
C50.2973 (2)0.0306 (2)0.69805 (14)0.0450 (4)
H50.2487−0.02100.61890.054*
C60.4565 (2)0.1640 (2)0.72932 (14)0.0430 (4)
C70.5290 (2)0.2400 (2)0.84825 (14)0.0439 (4)
C80.4413 (2)0.1789 (2)0.93214 (14)0.0451 (4)
H80.49070.22871.01170.054*
C90.5404 (2)0.2131 (2)0.62888 (15)0.0501 (4)
H9A0.47210.13450.55680.060*
H9B0.53210.32140.61140.060*
C100.7353 (2)0.2180 (2)0.66095 (15)0.0493 (4)
N10.85388 (18)0.33947 (17)0.74910 (12)0.0489 (4)
C120.7942 (2)0.4582 (2)0.80910 (17)0.0539 (5)
H12A0.71250.49770.74910.065*
H12B0.89750.55260.85060.065*
C130.7006 (2)0.3845 (2)0.89834 (16)0.0556 (5)
H13A0.67250.47180.93830.067*
H13B0.78480.34820.95890.067*
C141.0354 (2)0.3319 (2)0.80602 (16)0.0544 (4)
H14A1.04200.22470.77890.065*
H14B1.05680.34030.89220.065*
C151.1839 (2)0.4668 (2)0.77991 (16)0.0556 (5)
H15A1.17040.57430.79800.067*
H15B1.30010.46610.83070.067*
C161.1757 (3)0.4392 (3)0.65120 (18)0.0636 (5)
H16A1.05950.44030.60050.076*
H16B1.18840.33140.63320.076*
O10.19242 (16)−0.01575 (16)0.97846 (11)0.0577 (3)
O20.05252 (16)−0.15427 (16)0.75527 (11)0.0600 (4)
O30.78269 (18)0.11586 (17)0.61105 (12)0.0660 (4)
Cl11.35151 (9)0.59760 (9)0.61897 (6)0.0942 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0704 (12)0.0768 (13)0.0502 (11)0.0225 (10)0.0293 (9)0.0132 (9)
C20.0645 (12)0.0601 (11)0.0607 (12)0.0006 (9)0.0060 (9)−0.0011 (9)
C30.0455 (9)0.0489 (9)0.0460 (9)0.0206 (7)0.0177 (7)0.0124 (7)
C40.0421 (8)0.0410 (8)0.0499 (9)0.0140 (7)0.0120 (7)0.0066 (7)
C50.0470 (9)0.0471 (9)0.0397 (9)0.0171 (7)0.0095 (7)0.0026 (7)
C60.0453 (9)0.0453 (9)0.0416 (9)0.0180 (7)0.0137 (7)0.0076 (7)
C70.0451 (9)0.0439 (8)0.0442 (9)0.0160 (7)0.0141 (7)0.0041 (7)
C80.0472 (9)0.0512 (9)0.0378 (8)0.0180 (7)0.0121 (7)0.0028 (7)
C90.0516 (10)0.0584 (10)0.0392 (9)0.0150 (8)0.0142 (7)0.0059 (7)
C100.0556 (10)0.0540 (10)0.0420 (9)0.0171 (8)0.0199 (8)0.0094 (8)
N10.0456 (8)0.0517 (8)0.0505 (8)0.0153 (6)0.0166 (6)0.0040 (6)
C120.0520 (10)0.0473 (9)0.0595 (11)0.0093 (8)0.0198 (8)0.0011 (8)
C130.0565 (10)0.0529 (10)0.0523 (10)0.0074 (8)0.0200 (8)−0.0039 (8)
C140.0516 (10)0.0603 (11)0.0518 (10)0.0201 (8)0.0133 (8)0.0098 (8)
C150.0487 (9)0.0630 (11)0.0538 (11)0.0186 (8)0.0126 (8)0.0048 (8)
C160.0696 (12)0.0699 (12)0.0594 (12)0.0288 (10)0.0245 (10)0.0111 (9)
O10.0544 (7)0.0688 (8)0.0494 (7)0.0114 (6)0.0225 (6)0.0116 (6)
O20.0532 (7)0.0581 (7)0.0558 (7)0.0010 (6)0.0136 (6)0.0044 (6)
O30.0664 (8)0.0721 (9)0.0619 (8)0.0255 (7)0.0217 (7)−0.0058 (7)
Cl10.1040 (5)0.0999 (5)0.1101 (5)0.0398 (4)0.0683 (4)0.0438 (4)
Geometric parameters (Å, °) top
C1—O11.428 (2)C9—H9A0.97
C1—H1A0.96C9—H9B0.97
C1—H1B0.96C10—O31.227 (2)
C1—H1C0.96C10—N11.357 (2)
C2—O21.425 (2)N1—C121.463 (2)
C2—H2A0.96N1—C141.465 (2)
C2—H2B0.96C12—C131.515 (2)
C2—H2C0.96C12—H12A0.97
C3—O11.3697 (19)C12—H12B0.97
C3—C81.375 (2)C13—H13A0.97
C3—C41.407 (2)C13—H13B0.97
C4—O21.372 (2)C14—C151.524 (3)
C4—C51.377 (2)C14—H14A0.97
C5—C61.401 (2)C14—H14B0.97
C5—H50.93C15—C161.492 (3)
C6—C71.394 (2)C15—H15A0.97
C6—C91.533 (2)C15—H15B0.97
C7—C81.403 (2)C16—Cl11.805 (2)
C7—C131.519 (2)C16—H16A0.97
C8—H80.93C16—H16B0.97
C9—C101.513 (2)
O1—C1—H1A109.5O3—C10—C9121.63 (16)
O1—C1—H1B109.5N1—C10—C9116.40 (15)
H1A—C1—H1B109.5C10—N1—C12121.13 (14)
O1—C1—H1C109.5C10—N1—C14120.32 (15)
H1A—C1—H1C109.5C12—N1—C14117.01 (14)
H1B—C1—H1C109.5N1—C12—C13112.78 (15)
O2—C2—H2A109.5N1—C12—H12A109.0
O2—C2—H2B109.5C13—C12—H12A109.0
H2A—C2—H2B109.5N1—C12—H12B109.0
O2—C2—H2C109.5C13—C12—H12B109.0
H2A—C2—H2C109.5H12A—C12—H12B107.8
H2B—C2—H2C109.5C12—C13—C7116.64 (15)
O1—C3—C8124.96 (15)C12—C13—H13A108.1
O1—C3—C4116.39 (14)C7—C13—H13A108.1
C8—C3—C4118.64 (15)C12—C13—H13B108.1
O2—C4—C5125.10 (15)C7—C13—H13B108.1
O2—C4—C3115.54 (15)H13A—C13—H13B107.3
C5—C4—C3119.36 (14)N1—C14—C15114.14 (15)
C4—C5—C6122.21 (15)N1—C14—H14A108.7
C4—C5—H5118.9C15—C14—H14A108.7
C6—C5—H5118.9N1—C14—H14B108.7
C7—C6—C5118.52 (15)C15—C14—H14B108.7
C7—C6—C9124.80 (14)H14A—C14—H14B107.6
C5—C6—C9116.68 (14)C16—C15—C14110.34 (15)
C6—C7—C8118.89 (15)C16—C15—H15A109.6
C6—C7—C13125.75 (15)C14—C15—H15A109.6
C8—C7—C13115.34 (14)C16—C15—H15B109.6
C3—C8—C7122.35 (15)C14—C15—H15B109.6
C3—C8—H8118.8H15A—C15—H15B108.1
C7—C8—H8118.8C15—C16—Cl1110.88 (14)
C10—C9—C6112.81 (14)C15—C16—H16A109.5
C10—C9—H9A109.0Cl1—C16—H16A109.5
C6—C9—H9A109.0C15—C16—H16B109.5
C10—C9—H9B109.0Cl1—C16—H16B109.5
C6—C9—H9B109.0H16A—C16—H16B108.1
H9A—C9—H9B107.8C3—O1—C1117.37 (14)
O3—C10—N1121.96 (16)C4—O2—C2116.36 (14)
O1—C3—C4—O20.3 (2)C6—C9—C10—N1−68.2 (2)
C8—C3—C4—O2−178.75 (15)O3—C10—N1—C12−178.83 (16)
O1—C3—C4—C5−179.49 (14)C9—C10—N1—C120.1 (2)
C8—C3—C4—C51.4 (2)O3—C10—N1—C14−13.4 (3)
O2—C4—C5—C6178.70 (15)C9—C10—N1—C14165.52 (15)
C3—C4—C5—C6−1.5 (3)C10—N1—C12—C1375.6 (2)
C4—C5—C6—C70.3 (3)C14—N1—C12—C13−90.34 (18)
C4—C5—C6—C9179.18 (15)N1—C12—C13—C7−61.8 (2)
C5—C6—C7—C80.9 (2)C6—C7—C13—C123.9 (3)
C9—C6—C7—C8−177.88 (15)C8—C7—C13—C12−177.43 (15)
C5—C6—C7—C13179.47 (16)C10—N1—C14—C15112.96 (18)
C9—C6—C7—C130.7 (3)C12—N1—C14—C15−81.02 (19)
O1—C3—C8—C7−179.23 (15)N1—C14—C15—C16−68.9 (2)
C4—C3—C8—C7−0.3 (2)C14—C15—C16—Cl1−179.73 (13)
C6—C7—C8—C3−0.9 (3)C8—C3—O1—C16.5 (2)
C13—C7—C8—C3−179.66 (16)C4—C3—O1—C1−172.49 (15)
C7—C6—C9—C1052.6 (2)C5—C4—O2—C2−13.5 (3)
C5—C6—C9—C10−126.15 (16)C3—C4—O2—C2166.68 (16)
C6—C9—C10—O3110.71 (19)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C14—H14A···O30.972.362.768 (2)104
C1—H1A···Cg10.962.843.705 (3)150
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C14—H14A···O30.972.362.768 (2)104
C1—H1A···Cg10.962.843.705 (3)150
Acknowledgements top

The author acknowledges financial support from Zhejiang Police College, China.

references
References top

Bruker (2002). SADABS, SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.

Ishihara, Y., Tanaka, S. T., Miwatashi, B. S., Fujishimab, A. A. & Gotoa, G. (1994). J. Chem. Soc. Perkin Trans. 1, pp. 2293–2298.

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Reiffen, M., Eider, J., Hauel, N., Austel, V., Eberlein, W., Kobinger, W., Lillie, C., Noll, K., Pieper, H., Kruger, G. & Keck, J. (1981). Eur. Pat. Appl. EP 65 229.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.