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Acta Crystallogr Sect E Struct Rep Online. 2008 May 1; 64(Pt 5): o906.
Published online 2008 April 26. doi:  10.1107/S1600536808011264
PMCID: PMC2961294

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

Abstract

In the title compound, C15H18ClNO3, the seven-membered ring has a mirror plane passing through the methyl­ene C atom and bis­ecting the C=C bond. It adopts a bent conformation, inter­mediate between the boat and chair forms. Both meth­oxy groups are coplanar with the attached benzene ring [C—C—O—C = −0.5 (3) and 2.2 (3)°]. In the crystal structure, inversion-related mol­ecules are linked via C—H(...)O hydrogen bonds and π–π inter­actions involving the benzene ring [centroid–centroid distance = 3.6393 (12)Å].

Related literature

For the synthesis, see: Reiffen et al. (1990 [triangle]). For general background, see: Franke et al. (1987 [triangle]); Ishihara et al. (1994 [triangle]). For a related structure, see: Cheng (2008 [triangle]). For asymmetry parameters, see: Duax et al. (1976 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-0o906-scheme1.jpg

Experimental

Crystal data

  • C15H18ClNO3
  • M r = 295.75
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-0o906-efi1.jpg
  • a = 9.3141 (17) Å
  • b = 9.5924 (17) Å
  • c = 9.6359 (17) Å
  • α = 103.667 (6)°
  • β = 114.701 (6)°
  • γ = 94.460 (6)°
  • V = 744.7 (2) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.26 mm−1
  • T = 123 (2) K
  • 0.29 × 0.26 × 0.21 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2002 [triangle]) T min = 0.928, T max = 0.947
  • 7023 measured reflections
  • 2574 independent reflections
  • 2092 reflections with I > 2σ(I)
  • R int = 0.019

Refinement

  • R[F 2 > 2σ(F 2)] = 0.043
  • wR(F 2) = 0.115
  • S = 1.01
  • 2574 reflections
  • 181 parameters
  • H-atom parameters constrained
  • Δρmax = 0.21 e Å−3
  • Δρmin = −0.34 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808011264/ci2582sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808011264/ci2582Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

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

supplementary crystallographic information

Comment

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 reducing heart rate without concomitant negative inotropic or hypotensive effects (Franke et al., 1987). Rencently, in our previous research, a crystal structure of another important intermediate of ivabradine, 7,8-Dimethoxy-3-(3-chloropropyl)- 2,3,4,5-tetrahydro-1H-3-benzazepin-2-one was reported (Cheng, 2008). Here the crystal structure of the title compound is reported.

In the title molecule (Fig.1), the seven-membered ring adopts a bent conformation, intermediate between the boat and chair forms. The seven-membered ring possesses a mirror symmetry about the plane passing through atom C10 and bisecting the C7—C8 bond. The asymmetry parameter (Duax et al., 1976), ΔCs(C10), is 2.9 (2)°. The dihedral angle between the C1-C7/C10/C14/C15/O1/O2 and C8-C11/N1/O3 planes is 59.17 (6)°. The chloropropyl substituent group is in a (-)-synclinal conformation, as evidenced by the torsion angle N1—C11—C12—C13 of -63.4 (3)°, similar to that in a related structure (-68.9 (2)°, Cheng, 2008). The methoxy groups are coplanar with the benzene ring [C14—C1—O1—C6 = -0.5 (3)° and C15—C2—O2—C3 = 2.2 (3)°].

An intermolecular C—H···O hydrogen bond is observed in the crystal structure. Also, a π-π interaction involving the benzene ring is observed [centroid to centroid distance = 3.6393 (12) Å].

Experimental

The title compound was prepared according to the literature method (Reiffen et al., 1990). Crystals suitable for X-ray analysis were obtained by slow evaporation of an ethanol solution at 295 K.

Refinement

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).

Figures

Fig. 1.
Molecular structure of the title compound, showing 30% probability displacement ellipsoids and the atomic numbering.
Fig. 2.
Crystal packing of the title compound, viewed approximately down the b axis. Dashed lines indicate intermolecular hydrogen bonds.

Crystal data

C15H18ClNO3Z = 2
Mr = 295.75F000 = 312
Triclinic, P1Dx = 1.319 Mg m3
Hall symbol: -P 1Mo Kα radiation λ = 0.71073 Å
a = 9.3141 (17) ÅCell parameters from 2574 reflections
b = 9.5924 (17) Åθ = 2.2–25.0º
c = 9.6359 (17) ŵ = 0.26 mm1
α = 103.667 (6)ºT = 123 (2) K
β = 114.701 (6)ºBlock, yellow
γ = 94.460 (6)º0.29 × 0.26 × 0.21 mm
V = 744.7 (2) Å3

Data collection

Bruker SMART CCD area-detector diffractometer2574 independent reflections
Radiation source: fine-focus sealed tube2092 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.019
T = 123(2) Kθmax = 25.0º
[var phi] and ω scansθmin = 2.2º
Absorption correction: multi-scan(SADABS; Bruker, 2002)h = −11→11
Tmin = 0.928, Tmax = 0.947k = −11→10
7023 measured reflectionsl = −11→11

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.043H-atom parameters constrained
wR(F2) = 0.115  w = 1/[σ2(Fo2) + (0.0542P)2 + 0.2173P] where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max = 0.001
2574 reflectionsΔρmax = 0.21 e Å3
181 parametersΔρmin = −0.34 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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)

xyzUiso*/Ueq
Cl10.40282 (11)−0.14655 (9)0.18804 (11)0.1048 (3)
O1−0.20936 (16)0.23306 (15)0.46481 (17)0.0598 (4)
O2−0.31187 (14)0.39739 (15)0.28346 (16)0.0535 (3)
O30.15852 (19)0.32805 (18)−0.03080 (19)0.0722 (4)
N10.31547 (18)0.24927 (17)0.17583 (19)0.0513 (4)
C2−0.16173 (19)0.37032 (18)0.3119 (2)0.0422 (4)
C40.0877 (2)0.39343 (19)0.2909 (2)0.0445 (4)
C60.0472 (2)0.2518 (2)0.4511 (2)0.0476 (4)
H60.08580.19490.51960.057*
C1−0.1044 (2)0.28198 (19)0.4125 (2)0.0447 (4)
C100.1945 (2)0.4592 (2)0.2308 (3)0.0557 (5)
H10A0.29800.50930.32030.067*
H10B0.14520.53060.17970.067*
C3−0.0662 (2)0.42458 (19)0.2514 (2)0.0450 (4)
H3−0.10460.48230.18390.054*
C50.1450 (2)0.30533 (19)0.3888 (2)0.0455 (4)
C70.3048 (2)0.2705 (2)0.4297 (2)0.0536 (5)
H70.36130.26250.53210.064*
C90.2193 (2)0.3412 (2)0.1127 (3)0.0540 (5)
C80.3789 (2)0.2489 (2)0.3359 (2)0.0556 (5)
H80.48310.23180.38150.067*
C110.3610 (2)0.1450 (2)0.0693 (3)0.0623 (6)
H11A0.46570.12570.13240.075*
H11B0.37070.1894−0.00780.075*
C15−0.3741 (2)0.4838 (2)0.1797 (3)0.0607 (5)
H15A−0.47940.49580.16840.091*
H15B−0.38140.43610.07680.091*
H15C−0.30370.57800.22340.091*
C14−0.1591 (3)0.1435 (3)0.5654 (4)0.0892 (8)
H14A−0.24260.11690.59340.134*
H14B−0.06300.19570.66070.134*
H14C−0.13730.05660.51070.134*
C120.2402 (3)0.0012 (3)−0.0196 (3)0.0729 (7)
H12A0.13580.0215−0.08190.088*
H12B0.2723−0.0581−0.09400.088*
C130.2220 (3)−0.0865 (3)0.0846 (3)0.0822 (7)
H13A0.1351−0.17100.01880.099*
H13B0.1932−0.02700.16180.099*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.1226 (6)0.1022 (6)0.1229 (7)0.0475 (5)0.0735 (5)0.0491 (5)
O10.0562 (8)0.0706 (9)0.0752 (10)0.0200 (7)0.0406 (7)0.0384 (8)
O20.0394 (7)0.0670 (8)0.0629 (8)0.0175 (6)0.0249 (6)0.0286 (7)
O30.0810 (10)0.0901 (11)0.0677 (10)0.0291 (9)0.0454 (9)0.0361 (9)
N10.0452 (8)0.0567 (9)0.0566 (10)0.0119 (7)0.0297 (8)0.0114 (7)
C20.0367 (9)0.0438 (9)0.0426 (10)0.0078 (7)0.0173 (8)0.0078 (8)
C40.0442 (9)0.0422 (9)0.0490 (10)0.0096 (7)0.0248 (8)0.0092 (8)
C60.0506 (10)0.0504 (10)0.0446 (10)0.0176 (8)0.0214 (8)0.0164 (8)
C10.0455 (9)0.0452 (10)0.0460 (10)0.0091 (8)0.0240 (8)0.0112 (8)
C100.0543 (11)0.0504 (11)0.0753 (14)0.0134 (9)0.0394 (10)0.0208 (10)
C30.0485 (10)0.0426 (9)0.0468 (10)0.0129 (8)0.0232 (8)0.0141 (8)
C50.0428 (9)0.0477 (10)0.0449 (10)0.0115 (8)0.0221 (8)0.0067 (8)
C70.0459 (10)0.0654 (12)0.0476 (11)0.0191 (9)0.0196 (9)0.0135 (9)
C90.0480 (10)0.0581 (12)0.0679 (14)0.0088 (9)0.0358 (10)0.0216 (10)
C80.0384 (9)0.0649 (12)0.0582 (12)0.0154 (9)0.0199 (9)0.0111 (9)
C110.0614 (12)0.0692 (13)0.0696 (14)0.0187 (10)0.0442 (11)0.0145 (11)
C150.0469 (11)0.0752 (14)0.0683 (13)0.0253 (10)0.0250 (10)0.0335 (11)
C140.0905 (18)0.111 (2)0.121 (2)0.0422 (15)0.0707 (17)0.0788 (19)
C120.0688 (14)0.0743 (15)0.0642 (14)0.0169 (11)0.0305 (12)−0.0015 (12)
C130.0774 (16)0.0664 (14)0.0969 (19)−0.0032 (12)0.0500 (15)−0.0006 (13)

Geometric parameters (Å, °)

Cl1—C131.783 (3)C3—H30.93
O1—C11.372 (2)C5—C71.460 (2)
O1—C141.405 (3)C7—C81.338 (3)
O2—C21.367 (2)C7—H70.93
O2—C151.416 (2)C8—H80.93
O3—C91.225 (2)C11—C121.515 (3)
N1—C91.368 (3)C11—H11A0.97
N1—C81.404 (3)C11—H11B0.97
N1—C111.476 (2)C15—H15A0.96
C2—C31.381 (2)C15—H15B0.96
C2—C11.403 (2)C15—H15C0.96
C4—C51.384 (3)C14—H14A0.96
C4—C31.398 (2)C14—H14B0.96
C4—C101.510 (3)C14—H14C0.96
C6—C11.375 (2)C12—C131.504 (4)
C6—C51.409 (3)C12—H12A0.97
C6—H60.93C12—H12B0.97
C10—C91.510 (3)C13—H13A0.97
C10—H10A0.97C13—H13B0.97
C10—H10B0.97
C1—O1—C14117.58 (15)N1—C9—C10115.85 (18)
C2—O2—C15116.59 (14)C7—C8—N1126.72 (17)
C9—N1—C8125.16 (16)C7—C8—H8116.6
C9—N1—C11117.85 (17)N1—C8—H8116.6
C8—N1—C11116.96 (16)N1—C11—C12112.93 (16)
O2—C2—C3124.88 (16)N1—C11—H11A109.0
O2—C2—C1115.42 (15)C12—C11—H11A109.0
C3—C2—C1119.69 (15)N1—C11—H11B109.0
C5—C4—C3120.30 (16)C12—C11—H11B109.0
C5—C4—C10119.48 (15)H11A—C11—H11B107.8
C3—C4—C10120.20 (16)O2—C15—H15A109.5
C1—C6—C5121.25 (17)O2—C15—H15B109.5
C1—C6—H6119.4H15A—C15—H15B109.5
C5—C6—H6119.4O2—C15—H15C109.5
O1—C1—C6125.56 (16)H15A—C15—H15C109.5
O1—C1—C2114.89 (15)H15B—C15—H15C109.5
C6—C1—C2119.54 (16)O1—C14—H14A109.5
C4—C10—C9110.38 (15)O1—C14—H14B109.5
C4—C10—H10A109.6H14A—C14—H14B109.5
C9—C10—H10A109.6O1—C14—H14C109.5
C4—C10—H10B109.6H14A—C14—H14C109.5
C9—C10—H10B109.6H14B—C14—H14C109.5
H10A—C10—H10B108.1C13—C12—C11115.1 (2)
C2—C3—C4120.54 (16)C13—C12—H12A108.5
C2—C3—H3119.7C11—C12—H12A108.5
C4—C3—H3119.7C13—C12—H12B108.5
C4—C5—C6118.65 (15)C11—C12—H12B108.5
C4—C5—C7120.94 (17)H12A—C12—H12B107.5
C6—C5—C7120.40 (17)C12—C13—Cl1111.93 (17)
C8—C7—C5127.12 (18)C12—C13—H13A109.2
C8—C7—H7116.4Cl1—C13—H13A109.2
C5—C7—H7116.4C12—C13—H13B109.2
O3—C9—N1121.47 (18)Cl1—C13—H13B109.2
O3—C9—C10122.68 (19)H13A—C13—H13B107.9
C15—O2—C2—C32.2 (3)C10—C4—C5—C7−2.4 (3)
C15—O2—C2—C1−178.74 (16)C1—C6—C5—C41.9 (3)
C14—O1—C1—C6−0.5 (3)C1—C6—C5—C7−179.24 (17)
C14—O1—C1—C2179.7 (2)C4—C5—C7—C8−35.3 (3)
C5—C6—C1—O1178.90 (16)C6—C5—C7—C8145.9 (2)
C5—C6—C1—C2−1.3 (3)C8—N1—C9—O3−174.47 (18)
O2—C2—C1—O11.4 (2)C11—N1—C9—O37.6 (3)
C3—C2—C1—O1−179.52 (15)C8—N1—C9—C105.9 (3)
O2—C2—C1—C6−178.43 (15)C11—N1—C9—C10−172.03 (16)
C3—C2—C1—C60.7 (3)C4—C10—C9—O3109.0 (2)
C5—C4—C10—C968.9 (2)C4—C10—C9—N1−71.4 (2)
C3—C4—C10—C9−112.88 (19)C5—C7—C8—N1−2.8 (4)
O2—C2—C3—C4178.40 (16)C9—N1—C8—C737.8 (3)
C1—C2—C3—C4−0.6 (3)C11—N1—C8—C7−144.2 (2)
C5—C4—C3—C21.2 (3)C9—N1—C11—C12−88.5 (2)
C10—C4—C3—C2−176.99 (16)C8—N1—C11—C1293.4 (2)
C3—C4—C5—C6−1.8 (3)N1—C11—C12—C13−63.4 (3)
C10—C4—C5—C6176.41 (16)C11—C12—C13—Cl1−64.6 (2)
C3—C4—C5—C7179.33 (16)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C3—H3···O3i0.932.563.473 (2)169

Symmetry codes: (i) −x, −y+1, −z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: CI2582).

References

  • Bruker (2002). SADABS, SMART and SAINT Bruker AXS Inc., Madison, Wisconsin, USA.
  • Cheng, X.-W. (2008). Acta Cryst. E64, o802. [PMC free article] [PubMed]
  • Duax, W. L., Weeks, C. M. & Rohrer, D. C. (1976). Topics in Stereochemistry, Vol. 9, edited by E. L. Eliel & N. Allinger, pp. 271–383. New York: John Wiley.
  • Franke, H., Su, C. A., Schumacher, K. & Seiberling, M. (1987). Eur. Heart J.8, 91–98. [PubMed]
  • Ishihara, Y., Tanaka, S. T., Miwatashi, B. S., Fujishimab, A. A. & Gotoa, G. (1994). J. Chem. Soc. Perkin Trans. 1, pp. 2293–2298.
  • 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. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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