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

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

doi:10.1107/S160053680802895X

organic compounds

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Volume 64| Part 10| October 2008| Page o1935

doi:10.1107/S160053680802895X

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

Wei-jia Liu,^a Hua-Jie Yuan,^a Lei Chen,^a Li Hai ^a and Yong Wu ^a ^*

^aKey Laboratory of Drug Targeting of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China
^*Correspondence e-mail: smile.hl@hotmail.com

(Received 4 September 2008; accepted 10 September 2008; online 13 September 2008)

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 ); Hoskin & Hanks (1991 ).

Experimental

Crystal data

C₁₃H₁₉NO₂
M_r = 221.29
Monoclinic, P 2₁ /c
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[F² > 2σ(F²)] = 0.055
wR(F²) = 0.163
S = 1.06
2198 reflections
146 parameters
H-atom parameters constrained
Δρ_max = 0.34 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H7B⋯O1ⁱ	0.96	2.54	3.436 (4)	155
Symmetry code: (i) $[-x+2, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Data collection: DIFRAC (Gabe & White, 1993 ); cell refinement: DIFRAC; 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.

Supporting information

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

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

checkCIF report

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).

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

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

C₁₃H₁₉NO₂	F(000) = 480
M_r = 221.29	D_x = 1.224 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 20 reflections
a = 9.450 (4) Å	θ = 4.2–7.3°
b = 10.665 (3) Å	µ = 0.08 mm⁻¹
c = 11.963 (4) Å	T = 294 K
β = 95.33 (3)°	Block, colourless
V = 1200.5 (7) Å³	0.46 × 0.44 × 0.40 mm
Z = 4

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.005
Radiation source: fine-focus sealed tube	θ_max = 25.5°, θ_min = 2.2°
Graphite monochromator	h = −11→11
ω/2θ scans	k = 0→12
2361 measured reflections	l = −4→14
2198 independent reflections	3 standard reflections every 150 reflections
1235 reflections with I > 2σ(I)	intensity decay: 0.7%

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.055	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.163	H-atom parameters constrained
S = 1.06	w = 1/[σ²(F_o²) + (0.0788P)² + 0.1025P] where P = (F_o² + 2F_c²)/3
2198 reflections	(Δ/σ)_max < 0.001
146 parameters	Δρ_max = 0.34 e Å⁻³
0 restraints	Δρ_min = −0.25 e Å⁻³

Crystal data top

C₁₃H₁₉NO₂	V = 1200.5 (7) Å³
M_r = 221.29	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 9.450 (4) Å	µ = 0.08 mm⁻¹
b = 10.665 (3) Å	T = 294 K
c = 11.963 (4) Å	0.46 × 0.44 × 0.40 mm
β = 95.33 (3)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.005
2361 measured reflections	3 standard reflections every 150 reflections
2198 independent reflections	intensity decay: 0.7%
1235 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.055	0 restraints
wR(F²) = 0.163	H-atom parameters constrained
S = 1.06	Δρ_max = 0.34 e Å⁻³
2198 reflections	Δρ_min = −0.25 e Å⁻³
146 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

	x	y	z	U_iso*/U_eq
O1	0.95711 (19)	0.09365 (17)	0.84861 (15)	0.0577 (5)
O2	0.5608 (2)	0.4437 (2)	0.8362 (2)	0.0810 (7)
N1	0.8874 (2)	−0.0883 (2)	0.76476 (17)	0.0513 (6)
C1	0.8668 (3)	0.0106 (2)	0.83106 (19)	0.0419 (6)
C2	0.7256 (2)	0.0187 (2)	0.88309 (18)	0.0426 (6)
H2	0.6495	0.0047	0.8230	0.051*
C3	0.7118 (3)	−0.0828 (2)	0.9732 (2)	0.0539 (7)
H3A	0.8030	−0.0930	1.0165	0.065*
H3B	0.6442	−0.0546	1.0240	0.065*
C4	0.6637 (3)	−0.2092 (3)	0.9246 (2)	0.0638 (8)
H4A	0.6529	−0.2664	0.9862	0.077*
H4B	0.5709	−0.1989	0.8837	0.077*
C5	0.7628 (3)	−0.2687 (3)	0.8468 (2)	0.0659 (8)
H5A	0.8541	−0.2834	0.8887	0.079*
H5B	0.7243	−0.3495	0.8224	0.079*
C6	0.7860 (3)	−0.1915 (3)	0.7444 (2)	0.0608 (8)
H6A	0.8194	−0.2463	0.6877	0.073*
H6B	0.6954	−0.1571	0.7142	0.073*
C7	1.0154 (3)	−0.0913 (3)	0.7053 (2)	0.0669 (9)
H7A	0.9931	−0.0626	0.6297	0.100*
H7B	1.0509	−0.1756	0.7043	0.100*
H7C	1.0863	−0.0377	0.7428	0.100*
C8	0.7091 (2)	0.1503 (2)	0.9263 (2)	0.0435 (6)
C9	0.6343 (3)	0.2358 (2)	0.8651 (2)	0.0477 (7)
H9	0.5871	0.2107	0.7971	0.057*
C10	0.6223 (3)	0.3659 (3)	0.8985 (2)	0.0553 (7)
C11	0.6880 (3)	0.4006 (3)	1.0140 (3)	0.0702 (9)
H11A	0.7247	0.4854	1.0115	0.084*
H11B	0.6142	0.4004	1.0652	0.084*
C12	0.8034 (4)	0.3173 (3)	1.0592 (3)	0.0766 (10)
H12A	0.8193	0.3316	1.1395	0.092*
H12B	0.8895	0.3418	1.0266	0.092*
C13	0.7821 (3)	0.1819 (3)	1.0404 (2)	0.0631 (8)
H13A	0.7258	0.1490	1.0975	0.076*
H13B	0.8738	0.1404	1.0490	0.076*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0533 (11)	0.0494 (12)	0.0708 (12)	−0.0065 (9)	0.0074 (9)	−0.0010 (9)
O2	0.0766 (15)	0.0520 (14)	0.1098 (18)	0.0121 (11)	−0.0160 (13)	0.0039 (12)
N1	0.0595 (14)	0.0449 (14)	0.0509 (12)	0.0038 (11)	0.0122 (10)	−0.0052 (11)
C1	0.0468 (14)	0.0371 (14)	0.0404 (13)	0.0028 (12)	−0.0037 (11)	0.0059 (12)
C2	0.0436 (14)	0.0423 (16)	0.0398 (12)	0.0036 (11)	−0.0066 (10)	−0.0034 (12)
C3	0.0548 (16)	0.0517 (18)	0.0549 (16)	−0.0035 (13)	0.0043 (13)	0.0060 (13)
C4	0.0605 (17)	0.0525 (18)	0.0776 (19)	−0.0097 (15)	0.0017 (15)	0.0109 (16)
C5	0.0652 (18)	0.0398 (16)	0.091 (2)	−0.0055 (14)	−0.0008 (17)	−0.0046 (16)
C6	0.0668 (18)	0.0487 (17)	0.0656 (17)	0.0024 (14)	−0.0002 (14)	−0.0200 (15)
C7	0.080 (2)	0.061 (2)	0.0636 (17)	0.0157 (16)	0.0262 (16)	0.0046 (15)
C8	0.0421 (13)	0.0441 (16)	0.0440 (13)	0.0013 (12)	0.0018 (11)	−0.0048 (12)
C9	0.0455 (14)	0.0474 (16)	0.0487 (14)	0.0036 (13)	−0.0042 (11)	−0.0061 (13)
C10	0.0407 (14)	0.0518 (18)	0.0734 (19)	0.0042 (14)	0.0057 (13)	−0.0026 (16)
C11	0.075 (2)	0.0511 (19)	0.084 (2)	0.0028 (16)	0.0042 (17)	−0.0231 (17)
C12	0.097 (3)	0.067 (2)	0.0618 (19)	−0.0014 (19)	−0.0136 (17)	−0.0134 (17)
C13	0.0736 (19)	0.062 (2)	0.0505 (16)	0.0072 (16)	−0.0119 (14)	−0.0152 (14)

Geometric parameters (Å, º) top

O1—C1	1.234 (3)	C6—H6A	0.9700
O2—C10	1.225 (3)	C6—H6B	0.9700
N1—C1	1.344 (3)	C7—H7A	0.9600
N1—C7	1.459 (3)	C7—H7B	0.9600
N1—C6	1.465 (3)	C7—H7C	0.9600
C1—C2	1.527 (3)	C8—C9	1.330 (3)
C2—C8	1.509 (3)	C8—C13	1.509 (3)
C2—C3	1.542 (3)	C9—C10	1.452 (4)
C2—H2	0.9800	C9—H9	0.9300
C3—C4	1.520 (4)	C10—C11	1.507 (4)
C3—H3A	0.9700	C11—C12	1.470 (4)
C3—H3B	0.9700	C11—H11A	0.9700
C4—C5	1.520 (4)	C11—H11B	0.9700
C4—H4A	0.9700	C12—C13	1.473 (4)
C4—H4B	0.9700	C12—H12A	0.9700
C5—C6	1.509 (4)	C12—H12B	0.9700
C5—H5A	0.9700	C13—H13A	0.9700
C5—H5B	0.9700	C13—H13B	0.9700

C1—N1—C7	118.5 (2)	H6A—C6—H6B	107.6
C1—N1—C6	124.0 (2)	N1—C7—H7A	109.5
C7—N1—C6	117.5 (2)	N1—C7—H7B	109.5
O1—C1—N1	121.8 (2)	H7A—C7—H7B	109.5
O1—C1—C2	120.4 (2)	N1—C7—H7C	109.5
N1—C1—C2	117.7 (2)	H7A—C7—H7C	109.5
C8—C2—C1	108.3 (2)	H7B—C7—H7C	109.5
C8—C2—C3	113.3 (2)	C9—C8—C2	121.0 (2)
C1—C2—C3	112.3 (2)	C9—C8—C13	121.3 (2)
C8—C2—H2	107.6	C2—C8—C13	117.6 (2)
C1—C2—H2	107.6	C8—C9—C10	123.7 (2)
C3—C2—H2	107.6	C8—C9—H9	118.1
C4—C3—C2	113.4 (2)	C10—C9—H9	118.1
C4—C3—H3A	108.9	O2—C10—C9	121.7 (3)
C2—C3—H3A	108.9	O2—C10—C11	121.5 (3)
C4—C3—H3B	108.9	C9—C10—C11	116.8 (2)
C2—C3—H3B	108.9	C12—C11—C10	114.6 (2)
H3A—C3—H3B	107.7	C12—C11—H11A	108.6
C5—C4—C3	115.1 (2)	C10—C11—H11A	108.6
C5—C4—H4A	108.5	C12—C11—H11B	108.6
C3—C4—H4A	108.5	C10—C11—H11B	108.6
C5—C4—H4B	108.5	H11A—C11—H11B	107.6
C3—C4—H4B	108.5	C11—C12—C13	116.7 (3)
H4A—C4—H4B	107.5	C11—C12—H12A	108.1
C6—C5—C4	114.4 (2)	C13—C12—H12A	108.1
C6—C5—H5A	108.7	C11—C12—H12B	108.1
C4—C5—H5A	108.7	C13—C12—H12B	108.1
C6—C5—H5B	108.7	H12A—C12—H12B	107.3
C4—C5—H5B	108.7	C12—C13—C8	113.6 (2)
H5A—C5—H5B	107.6	C12—C13—H13A	108.8
N1—C6—C5	114.6 (2)	C8—C13—H13A	108.8
N1—C6—H6A	108.6	C12—C13—H13B	108.8
C5—C6—H6A	108.6	C8—C13—H13B	108.8
N1—C6—H6B	108.6	H13A—C13—H13B	107.7
C5—C6—H6B	108.6

C7—N1—C1—O1	−5.0 (3)	C1—C2—C8—C9	96.5 (3)
C6—N1—C1—O1	177.8 (2)	C3—C2—C8—C9	−138.2 (2)
C7—N1—C1—C2	173.9 (2)	C1—C2—C8—C13	−82.6 (3)
C6—N1—C1—C2	−3.4 (3)	C3—C2—C8—C13	42.6 (3)
O1—C1—C2—C8	14.2 (3)	C2—C8—C9—C10	−175.7 (2)
N1—C1—C2—C8	−164.7 (2)	C13—C8—C9—C10	3.4 (4)
O1—C1—C2—C3	−111.7 (3)	C8—C9—C10—O2	174.7 (3)
N1—C1—C2—C3	69.4 (3)	C8—C9—C10—C11	−5.8 (4)
C8—C2—C3—C4	154.6 (2)	O2—C10—C11—C12	−156.1 (3)
C1—C2—C3—C4	−82.2 (3)	C9—C10—C11—C12	24.4 (4)
C2—C3—C4—C5	61.1 (3)	C10—C11—C12—C13	−41.6 (4)
C3—C4—C5—C6	−60.1 (3)	C11—C12—C13—C8	38.6 (4)
C1—N1—C6—C5	−64.5 (3)	C9—C8—C13—C12	−19.4 (4)
C7—N1—C6—C5	118.2 (3)	C2—C8—C13—C12	159.8 (3)
C4—C5—C6—N1	79.0 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C7—H7B···O1ⁱ	0.96	2.54	3.436 (4)	155

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

Experimental details

Crystal data
Chemical formula	C₁₃H₁₉NO₂
M_r	221.29
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	294
a, b, c (Å)	9.450 (4), 10.665 (3), 11.963 (4)
β (°)	95.33 (3)
V (Å³)	1200.5 (7)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.08
Crystal size (mm)	0.46 × 0.44 × 0.40

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	2361, 2198, 1235
R_int	0.005
(sin θ/λ)_max (Å⁻¹)	0.606

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.055, 0.163, 1.06
No. of reflections	2198
No. of parameters	146
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.34, −0.25

Computer programs: DIFRAC (Gabe & White, 1993), NRCVAX (Gabe et al., 1989), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C7—H7B···O1ⁱ	0.96	2.54	3.436 (4)	155

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

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. Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Gabe, E. J., Le Page, Y., Charland, J.-P., Lee, F. L. & White, P. S. (1989). J. Appl. Cryst. 22, 384–387. CrossRef CAS Web of Science IUCr Journals Google Scholar
Gabe, E. J. & White, P. S. (1993). DIFRAC. American Crystallographic Association Pittsburgh Meeting, Abstract PA 104. Google Scholar
Hoskin, P. J. & Hanks, G. W. (1991). Drugs, 41, 326–344. CrossRef PubMed CAS Web of Science Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

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doi:10.1107/S160053680802895X

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