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Acta Cryst. (2008). E64, o1935    [ doi:10.1107/S160053680802895X ]

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

W. Liu, H.-J. Yuan, L. Chen, L. Hai and Y. Wu

Abstract top

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.

Comment top

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).

Related literature top

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

Experimental top

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 top

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).

Computing details top

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

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), with displacement ellipsoids for the non-hydrogen atoms drawn at the 50% probability level.
1-Methyl-3-(3-oxocyclohex-1-enyl)azepan-2-one top
Crystal data top
C13H19NO2F(000) = 480
Mr = 221.29Dx = 1.224 Mg m−3
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 mm−1
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 top
Enraf–Nonius CAD-4
diffractometer		Rint = 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 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)] = 0.055Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.163H-atom parameters constrained
S = 1.06 w = 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 Å−3
0 restraintsΔρmin = −0.25 e Å−3
Crystal data top
C13H19NO2V = 1200.5 (7) Å3
Mr = 221.29Z = 4
Monoclinic, P21/cMo Kα radiation
a = 9.450 (4) ŵ = 0.08 mm−1
b = 10.665 (3) ÅT = 294 K
c = 11.963 (4) Å0.46 × 0.44 × 0.40 mm
β = 95.33 (3)°
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.005
2361 measured reflectionsθmax = 25.5°
2198 independent reflections3 standard reflections every 150 reflections
1235 reflections with I > 2σ(I) intensity decay: 0.7%
Refinement top
R[F2 > 2σ(F2)] = 0.055H-atom parameters constrained
wR(F2) = 0.163Δρmax = 0.34 e Å−3
S = 1.06Δρmin = −0.25 e Å−3
2198 reflectionsAbsolute structure: ?
146 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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
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) top
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, °) top
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, °) top
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.
Table 1
Hydrogen-bond geometry (Å, °) top
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.
references
References top

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. Am. Crystallogr. Assoc. Pittsburgh Meet., Abstract PA 104.

Hoskin, P. J. & Hanks, G. W. (1991). Drugs, 41, 326–344.

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