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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

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

aZhejiang Police College Experience Center, Zhejiang Police College, Hangzhou 310053, People's Republic of China
*Correspondence e-mail: zpccxw@126.com

(Received 29 March 2008; accepted 1 April 2008; online 4 April 2008)

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⋯π inter­action involving the benzene ring is observed.

Related literature

For details of the synthesis, see: Reiffen et al. (1981[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.]). For general background, see: Ishihara et al. (1994[Ishihara, Y., Tanaka, S. T., Miwatashi, B. S., Fujishimab, A. A. & Gotoa, G. (1994). J. Chem. Soc. Perkin Trans. 1, pp. 2293-2298.]). For a related structure, see: Reiffen et al. (1990[Reiffen, M., Eberlein, W., Muller, P., Psiorz, M., Noll, K., Heider, J., Lillie, C., Kobinger, W. & Lugerl, P. (1990). J. Med. Chem. 33, 1496-1504.]).

[Scheme 1]

Experimental

Crystal data
  • C15H20ClNO3

  • Mr = 297.77

  • Triclinic, [P \overline 1]

  • a = 8.134 (3) Å

  • b = 8.498 (3) Å

  • c = 11.701 (4) Å

  • α = 92.880 (12)°

  • β = 105.981 (12)°

  • γ = 106.440 (12)°

  • V = 738.5 (5) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.27 mm−1

  • T = 125 K

  • 0.29 × 0.28 × 0.22 mm

Data collection
  • Bruker SMART CCD area-detector diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2002[Bruker (2002). SADABS, SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.927, Tmax = 0.944

  • 6809 measured reflections

  • 2542 independent reflections

  • 2137 reflections with I > 2σ(I)

  • Rint = 0.020

Refinement
  • R[F2 > 2σ(F2)] = 0.039

  • wR(F2) = 0.112

  • S = 1.06

  • 2542 reflections

  • 183 parameters

  • H-atom parameters constrained

  • Δρmax = 0.19 e Å−3

  • Δρmin = −0.23 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
C14—H14A⋯O3 0.97 2.36 2.768 (2) 104
C1—H1ACg1 0.96 2.84 3.705 (3) 150
Cg1 is the centroid of the benzene ring.

Data collection: SMART (Bruker, 2002[Bruker (2002). SADABS, SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2002[Bruker (2002). SADABS, SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


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 = 297.77F(000) = 316
Triclinic, P1Dx = 1.339 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 8.134 (3) ÅCell parameters from 2542 reflections
b = 8.498 (3) Åθ = 1.8–25.0°
c = 11.701 (4) ŵ = 0.27 mm1
α = 92.880 (12)°T = 125 K
β = 105.981 (12)°Block, colourless
γ = 106.440 (12)°0.29 × 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)
Graphite monochromatorRint = 0.020
ϕ and ω scansθmax = 25.0°, θmin = 1.8°
Absorption correction: multi-scan
(SADABS; Bruker, 2002)
h = 99
Tmin = 0.927, Tmax = 0.944k = 99
6809 measured reflectionsl = 1311
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.039Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.112H-atom parameters constrained
S = 1.06 w = 1/[σ2(Fo2) + (0.0588P)2 + 0.1232P]
where P = (Fo2 + 2Fc2)/3
2542 reflections(Δ/σ)max = 0.001
183 parametersΔρmax = 0.19 e Å3
0 restraintsΔρmin = 0.23 e Å3
Crystal data top
C15H20ClNO3γ = 106.440 (12)°
Mr = 297.77V = 738.5 (5) Å3
Triclinic, P1Z = 2
a = 8.134 (3) ÅMo Kα radiation
b = 8.498 (3) ŵ = 0.27 mm1
c = 11.701 (4) ÅT = 125 K
α = 92.880 (12)°0.29 × 0.28 × 0.22 mm
β = 105.981 (12)°
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)] = 0.0390 restraints
wR(F2) = 0.112H-atom parameters constrained
S = 1.06Δρmax = 0.19 e Å3
2542 reflectionsΔρmin = 0.23 e Å3
183 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
C10.2530 (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*
C20.0455 (3)0.2072 (3)0.63151 (18)0.0689 (6)
H2A0.06770.11410.59420.103*
H2B0.15800.28940.62430.103*
H2C0.02320.25390.59270.103*
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)
H50.24870.02100.61890.054*
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, º) 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—N168.2 (2)
C8—C3—C4—O2178.75 (15)O3—C10—N1—C12178.83 (16)
O1—C3—C4—C5179.49 (14)C9—C10—N1—C120.1 (2)
C8—C3—C4—C51.4 (2)O3—C10—N1—C1413.4 (3)
O2—C4—C5—C6178.70 (15)C9—C10—N1—C14165.52 (15)
C3—C4—C5—C61.5 (3)C10—N1—C12—C1375.6 (2)
C4—C5—C6—C70.3 (3)C14—N1—C12—C1390.34 (18)
C4—C5—C6—C9179.18 (15)N1—C12—C13—C761.8 (2)
C5—C6—C7—C80.9 (2)C6—C7—C13—C123.9 (3)
C9—C6—C7—C8177.88 (15)C8—C7—C13—C12177.43 (15)
C5—C6—C7—C13179.47 (16)C10—N1—C14—C15112.96 (18)
C9—C6—C7—C130.7 (3)C12—N1—C14—C1581.02 (19)
O1—C3—C8—C7179.23 (15)N1—C14—C15—C1668.9 (2)
C4—C3—C8—C70.3 (2)C14—C15—C16—Cl1179.73 (13)
C6—C7—C8—C30.9 (3)C8—C3—O1—C16.5 (2)
C13—C7—C8—C3179.66 (16)C4—C3—O1—C1172.49 (15)
C7—C6—C9—C1052.6 (2)C5—C4—O2—C213.5 (3)
C5—C6—C9—C10126.15 (16)C3—C4—O2—C2166.68 (16)
C6—C9—C10—O3110.71 (19)
Hydrogen-bond geometry (Å, º) 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

Experimental details

Crystal data
Chemical formulaC15H20ClNO3
Mr297.77
Crystal system, space groupTriclinic, P1
Temperature (K)125
a, b, c (Å)8.134 (3), 8.498 (3), 11.701 (4)
α, β, γ (°)92.880 (12), 105.981 (12), 106.440 (12)
V3)738.5 (5)
Z2
Radiation typeMo Kα
µ (mm1)0.27
Crystal size (mm)0.29 × 0.28 × 0.22
Data collection
DiffractometerBruker SMART CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2002)
Tmin, Tmax0.927, 0.944
No. of measured, independent and
observed [I > 2σ(I)] reflections
6809, 2542, 2137
Rint0.020
(sin θ/λ)max1)0.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.039, 0.112, 1.06
No. of reflections2542
No. of parameters183
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.19, 0.23

Computer programs: SMART (Bruker, 2002), SAINT (Bruker, 2002), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) 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

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

References

First citationBruker (2002). SADABS, SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationIshihara, Y., Tanaka, S. T., Miwatashi, B. S., Fujishimab, A. A. & Gotoa, G. (1994). J. Chem. Soc. Perkin Trans. 1, pp. 2293–2298.  Google Scholar
First citationReiffen, M., Eberlein, W., Muller, P., Psiorz, M., Noll, K., Heider, J., Lillie, C., Kobinger, W. & Lugerl, P. (1990). J. Med. Chem. 33, 1496–1504.  CSD CrossRef CAS PubMed Web of Science Google Scholar
First citationReiffen, 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.  Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
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