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Acta Crystallogr Sect E Struct Rep Online. 2008 October 1; 64(Pt 10): o1935.
Published online 2008 September 13. doi:  10.1107/S160053680802895X
PMCID: PMC2959380

1-Methyl-3-(3-oxocyclo­hex-1-en­yl)azepan-2-one

Abstract

The title compound, C13H19NO2, is a inter­mediate in the synthesis of the opioid analgesic meptazinol. In the crystal structure, a weak inter­molecular C—H(...)O inter­action occurs.

Related literature

For related literature, see: Bradley et al. (1980 [triangle]); Hoskin & Hanks (1991 [triangle]).

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Object name is e-64-o1935-scheme1.jpg

Experimental

Crystal data

  • C13H19NO2
  • M r = 221.29
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1935-efi1.jpg
  • a = 9.450 (4) Å
  • b = 10.665 (3) Å
  • c = 11.963 (4) Å
  • β = 95.33 (3)°
  • V = 1200.5 (7) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.08 mm−1
  • T = 294 (2) K
  • 0.46 × 0.44 × 0.40 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: none
  • 2361 measured reflections
  • 2198 independent reflections
  • 1235 reflections with I > 2σ(I)
  • R int = 0.005
  • 3 standard reflections every 150 reflections intensity decay: 0.7%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.055
  • wR(F 2) = 0.163
  • S = 1.06
  • 2198 reflections
  • 146 parameters
  • H-atom parameters constrained
  • Δρmax = 0.34 e Å−3
  • Δρmin = −0.25 e Å−3

Data collection: DIFRAC (Gabe & White, 1993 [triangle]); cell refinement: DIFRAC; data reduction: NRCVAX (Gabe et al., 1989 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 (Farrugia, 1997 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680802895X/hb2790sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053680802895X/hb2790Isup2.hkl

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

supplementary crystallographic information

Comment

Meptazinol, 1-methyl-3-ethyl-3-(3-hydroxyphenyl)hexahydro-1H-azepin hydrochloride, is a synthetic hexahydroazepine derivative with opioid agonist and antagonist properties (Hoskin & Hanks, 1991). The title compound, (I) is a key intermediate for the synthesis of Meptazinol (Bradley et al., 1980) and we report its structure here (Fig. 1).

The molecule of (I) is chiral. In the arbitrarily chosen asymmetric molecule, C2 has S configuration, but crystal symmetry generates a racemic mixture. In the crystal, a weak C—H···O interaction may help to consolidate the packing (Table 1).

Experimental

A solution of butyl lithium (164 mmol) in hexane, maintained at 248 K was treated with diisopropylamine (13.5 ml, 164 mol) in THF (15 ml), followed by 1-methylazepan-2-one (8.1 g, 64 mmol) in THF (15 ml). After 10 min, a solution of 3-isopropoxy-2-cyclohexxenone (7.0 g, 45 mmol) in THF (10 ml) was added, the mixture allowed to warm to room temperature and after a further 2 h was acidified with 2 M hydrochloric acid. After 30 min, the aqueous layer was extracted with dichloromethane, the combined organic layer washed with brine and evaporated. Recrystallization of the residue was from an ethyl acetate and hexane mixture. Colourless blocks of (I) were obtained by spontaneous evaporation in ethyl acetate and hexane (20:1 v/v).

Refinement

The H atoms were positioned geometrically (C—H = 0.93–0.98 Å) and refined as riding with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C).

Figures

Fig. 1.
The molecular structure of (I), with displacement ellipsoids for the non-hydrogen atoms drawn at the 50% probability level.

Crystal data

C13H19NO2F(000) = 480
Mr = 221.29Dx = 1.224 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 20 reflections
a = 9.450 (4) Åθ = 4.2–7.3°
b = 10.665 (3) ŵ = 0.08 mm1
c = 11.963 (4) ÅT = 294 K
β = 95.33 (3)°Block, colourless
V = 1200.5 (7) Å30.46 × 0.44 × 0.40 mm
Z = 4

Data collection

Enraf–Nonius CAD-4 diffractometerRint = 0.005
Radiation source: fine-focus sealed tubeθmax = 25.5°, θmin = 2.2°
graphiteh = −11→11
ω/2θ scansk = 0→12
2361 measured reflectionsl = −4→14
2198 independent reflections3 standard reflections every 150 reflections
1235 reflections with I > 2σ(I) intensity decay: 0.7%

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.055Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.163H-atom parameters constrained
S = 1.06w = 1/[σ2(Fo2) + (0.0788P)2 + 0.1025P] where P = (Fo2 + 2Fc2)/3
2198 reflections(Δ/σ)max < 0.001
146 parametersΔρmax = 0.34 e Å3
0 restraintsΔρmin = −0.25 e Å3

Special details

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)

xyzUiso*/Ueq
O10.95711 (19)0.09365 (17)0.84861 (15)0.0577 (5)
O20.5608 (2)0.4437 (2)0.8362 (2)0.0810 (7)
N10.8874 (2)−0.0883 (2)0.76476 (17)0.0513 (6)
C10.8668 (3)0.0106 (2)0.83106 (19)0.0419 (6)
C20.7256 (2)0.0187 (2)0.88309 (18)0.0426 (6)
H20.64950.00470.82300.051*
C30.7118 (3)−0.0828 (2)0.9732 (2)0.0539 (7)
H3A0.8030−0.09301.01650.065*
H3B0.6442−0.05461.02400.065*
C40.6637 (3)−0.2092 (3)0.9246 (2)0.0638 (8)
H4A0.6529−0.26640.98620.077*
H4B0.5709−0.19890.88370.077*
C50.7628 (3)−0.2687 (3)0.8468 (2)0.0659 (8)
H5A0.8541−0.28340.88870.079*
H5B0.7243−0.34950.82240.079*
C60.7860 (3)−0.1915 (3)0.7444 (2)0.0608 (8)
H6A0.8194−0.24630.68770.073*
H6B0.6954−0.15710.71420.073*
C71.0154 (3)−0.0913 (3)0.7053 (2)0.0669 (9)
H7A0.9931−0.06260.62970.100*
H7B1.0509−0.17560.70430.100*
H7C1.0863−0.03770.74280.100*
C80.7091 (2)0.1503 (2)0.9263 (2)0.0435 (6)
C90.6343 (3)0.2358 (2)0.8651 (2)0.0477 (7)
H90.58710.21070.79710.057*
C100.6223 (3)0.3659 (3)0.8985 (2)0.0553 (7)
C110.6880 (3)0.4006 (3)1.0140 (3)0.0702 (9)
H11A0.72470.48541.01150.084*
H11B0.61420.40041.06520.084*
C120.8034 (4)0.3173 (3)1.0592 (3)0.0766 (10)
H12A0.81930.33161.13950.092*
H12B0.88950.34181.02660.092*
C130.7821 (3)0.1819 (3)1.0404 (2)0.0631 (8)
H13A0.72580.14901.09750.076*
H13B0.87380.14041.04900.076*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0533 (11)0.0494 (12)0.0708 (12)−0.0065 (9)0.0074 (9)−0.0010 (9)
O20.0766 (15)0.0520 (14)0.1098 (18)0.0121 (11)−0.0160 (13)0.0039 (12)
N10.0595 (14)0.0449 (14)0.0509 (12)0.0038 (11)0.0122 (10)−0.0052 (11)
C10.0468 (14)0.0371 (14)0.0404 (13)0.0028 (12)−0.0037 (11)0.0059 (12)
C20.0436 (14)0.0423 (16)0.0398 (12)0.0036 (11)−0.0066 (10)−0.0034 (12)
C30.0548 (16)0.0517 (18)0.0549 (16)−0.0035 (13)0.0043 (13)0.0060 (13)
C40.0605 (17)0.0525 (18)0.0776 (19)−0.0097 (15)0.0017 (15)0.0109 (16)
C50.0652 (18)0.0398 (16)0.091 (2)−0.0055 (14)−0.0008 (17)−0.0046 (16)
C60.0668 (18)0.0487 (17)0.0656 (17)0.0024 (14)−0.0002 (14)−0.0200 (15)
C70.080 (2)0.061 (2)0.0636 (17)0.0157 (16)0.0262 (16)0.0046 (15)
C80.0421 (13)0.0441 (16)0.0440 (13)0.0013 (12)0.0018 (11)−0.0048 (12)
C90.0455 (14)0.0474 (16)0.0487 (14)0.0036 (13)−0.0042 (11)−0.0061 (13)
C100.0407 (14)0.0518 (18)0.0734 (19)0.0042 (14)0.0057 (13)−0.0026 (16)
C110.075 (2)0.0511 (19)0.084 (2)0.0028 (16)0.0042 (17)−0.0231 (17)
C120.097 (3)0.067 (2)0.0618 (19)−0.0014 (19)−0.0136 (17)−0.0134 (17)
C130.0736 (19)0.062 (2)0.0505 (16)0.0072 (16)−0.0119 (14)−0.0152 (14)

Geometric parameters (Å, °)

O1—C11.234 (3)C6—H6A0.9700
O2—C101.225 (3)C6—H6B0.9700
N1—C11.344 (3)C7—H7A0.9600
N1—C71.459 (3)C7—H7B0.9600
N1—C61.465 (3)C7—H7C0.9600
C1—C21.527 (3)C8—C91.330 (3)
C2—C81.509 (3)C8—C131.509 (3)
C2—C31.542 (3)C9—C101.452 (4)
C2—H20.9800C9—H90.9300
C3—C41.520 (4)C10—C111.507 (4)
C3—H3A0.9700C11—C121.470 (4)
C3—H3B0.9700C11—H11A0.9700
C4—C51.520 (4)C11—H11B0.9700
C4—H4A0.9700C12—C131.473 (4)
C4—H4B0.9700C12—H12A0.9700
C5—C61.509 (4)C12—H12B0.9700
C5—H5A0.9700C13—H13A0.9700
C5—H5B0.9700C13—H13B0.9700
C1—N1—C7118.5 (2)H6A—C6—H6B107.6
C1—N1—C6124.0 (2)N1—C7—H7A109.5
C7—N1—C6117.5 (2)N1—C7—H7B109.5
O1—C1—N1121.8 (2)H7A—C7—H7B109.5
O1—C1—C2120.4 (2)N1—C7—H7C109.5
N1—C1—C2117.7 (2)H7A—C7—H7C109.5
C8—C2—C1108.3 (2)H7B—C7—H7C109.5
C8—C2—C3113.3 (2)C9—C8—C2121.0 (2)
C1—C2—C3112.3 (2)C9—C8—C13121.3 (2)
C8—C2—H2107.6C2—C8—C13117.6 (2)
C1—C2—H2107.6C8—C9—C10123.7 (2)
C3—C2—H2107.6C8—C9—H9118.1
C4—C3—C2113.4 (2)C10—C9—H9118.1
C4—C3—H3A108.9O2—C10—C9121.7 (3)
C2—C3—H3A108.9O2—C10—C11121.5 (3)
C4—C3—H3B108.9C9—C10—C11116.8 (2)
C2—C3—H3B108.9C12—C11—C10114.6 (2)
H3A—C3—H3B107.7C12—C11—H11A108.6
C5—C4—C3115.1 (2)C10—C11—H11A108.6
C5—C4—H4A108.5C12—C11—H11B108.6
C3—C4—H4A108.5C10—C11—H11B108.6
C5—C4—H4B108.5H11A—C11—H11B107.6
C3—C4—H4B108.5C11—C12—C13116.7 (3)
H4A—C4—H4B107.5C11—C12—H12A108.1
C6—C5—C4114.4 (2)C13—C12—H12A108.1
C6—C5—H5A108.7C11—C12—H12B108.1
C4—C5—H5A108.7C13—C12—H12B108.1
C6—C5—H5B108.7H12A—C12—H12B107.3
C4—C5—H5B108.7C12—C13—C8113.6 (2)
H5A—C5—H5B107.6C12—C13—H13A108.8
N1—C6—C5114.6 (2)C8—C13—H13A108.8
N1—C6—H6A108.6C12—C13—H13B108.8
C5—C6—H6A108.6C8—C13—H13B108.8
N1—C6—H6B108.6H13A—C13—H13B107.7
C5—C6—H6B108.6
C7—N1—C1—O1−5.0 (3)C1—C2—C8—C996.5 (3)
C6—N1—C1—O1177.8 (2)C3—C2—C8—C9−138.2 (2)
C7—N1—C1—C2173.9 (2)C1—C2—C8—C13−82.6 (3)
C6—N1—C1—C2−3.4 (3)C3—C2—C8—C1342.6 (3)
O1—C1—C2—C814.2 (3)C2—C8—C9—C10−175.7 (2)
N1—C1—C2—C8−164.7 (2)C13—C8—C9—C103.4 (4)
O1—C1—C2—C3−111.7 (3)C8—C9—C10—O2174.7 (3)
N1—C1—C2—C369.4 (3)C8—C9—C10—C11−5.8 (4)
C8—C2—C3—C4154.6 (2)O2—C10—C11—C12−156.1 (3)
C1—C2—C3—C4−82.2 (3)C9—C10—C11—C1224.4 (4)
C2—C3—C4—C561.1 (3)C10—C11—C12—C13−41.6 (4)
C3—C4—C5—C6−60.1 (3)C11—C12—C13—C838.6 (4)
C1—N1—C6—C5−64.5 (3)C9—C8—C13—C12−19.4 (4)
C7—N1—C6—C5118.2 (3)C2—C8—C13—C12159.8 (3)
C4—C5—C6—N179.0 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C7—H7B···O1i0.962.543.436 (4)155

Symmetry codes: (i) −x+2, y−1/2, −z+3/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HB2790).

References

  • Bradley, G., Cavalla, J. F., Edington, T., Shepherd, R. G., White, A. C., Bushell, B. J., Johnson, J. R. & Weston, G. O. (1980). Chim. Ther 15, 374–385.
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Gabe, E. J., Le Page, Y., Charland, J.-P., Lee, F. L. & White, P. S. (1989). J. Appl. Cryst.22, 384–387.
  • Gabe, E. J. & White, P. S. (1993). DIFRAC American Crystallographic Association Pittsburgh Meeting, Abstract PA 104.
  • Hoskin, P. J. & Hanks, G. W. (1991). Drugs, 41, 326–344. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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