N-(2-Oxo-2,3,4,5,6,7-hexa­hydro-1H-azepin-3-yl)cyclo­hexa­necarboxamide

Chunjuan, S.; Zhao, Y.

doi:10.1107/S1600536813031863

organic compounds

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ISSN: 2056-9890

Volume 69| Part 12| December 2013| Page o1837

doi:10.1107/S1600536813031863

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N-(2-Oxo-2,3,4,5,6,7-hexahydro-1H-azepin-3-yl)cyclohexanecarboxamide

Shi Chunjuan ^a and Yang Zhao ^b ^*

^aSuzhou University Experimental Material Supply Center, Suzhou 215123, People's Republic of China, and ^bCollege of Pharmacy, China Pharmaceutical University, Tongjiaxiang No. 24 Nanjing, Nanjing 210009, People's Republic of China
^*Correspondence e-mail: yzcpu@163.com

(Received 25 October 2013; accepted 22 November 2013; online 30 November 2013)

In the title compound, C₁₃H₂₂N₂O₂, both the six-membered ring and the seven-membered lactam ring adopt chair conformations. In the crystal, molecules are linked by pairs of N—H⋯O hydrogen bonds between inversion-related lactam rings into centrosymmetric dimers with an R₂²(8) graph-set motif. Further N—H⋯O hydrogen bonds link the molecules into [100] chains.

CCDC reference: 973240

Related literature

For background information on 3-(acylamino)azepan-2-ones, see: Fox et al. (2009 ); Grainger & Fox (2006 ). For a related crystal structure, see: Zhu et al. (2007 ).

Experimental

Crystal data

C₁₃H₂₂N₂O₂
M_r = 238.33
Triclinic, $[P \overline 1]$
a = 5.007 (1) Å
b = 11.642 (2) Å
c = 12.739 (3) Å
α = 63.66 (3)°
β = 82.69 (3)°
γ = 82.75 (3)°
V = 658.0 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (North et al., 1968 ) T_min = 0.976, T_max = 0.992
2700 measured reflections
2400 independent reflections
1581 reflections with I > 2σ(I)
R_int = 0.073
3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F² > 2σ(F²)] = 0.062
wR(F²) = 0.177
S = 1.01
2400 reflections
154 parameters
H-atom parameters constrained
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O1ⁱ	0.86	2.37	3.158 (3)	152
N2—H2A⋯O2ⁱⁱ	0.86	2.09	2.927 (3)	165
Symmetry codes: (i) x+1, y, z; (ii) -x+1, -y+1, -z+2.

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1989 ); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 ); 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: PLATON (Spek, 2009 ).

Supporting information

CCDC reference: 973240

Crystal structure: contains datablocks Y, I. DOI: 10.1107/S1600536813031863/pk2501sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536813031863/pk2501Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536813031863/pk2501Isup3.cml

checkCIF report

Comment top

N-(hexahydro-2-oxo-1H-azepin-3-yl)-cyclohexanecarboxamide (I), Fig. 1, is a 3-(acylamino)azepan-2-one, a series of compounds that are broad spectrum chemokine inhibitors and act as stable, orally available powerful anti-inflammatory agents (Fox et al., 2009; Grainger et al., 2006). We report herein the synthesis and crystal structure of the title compound (I).

In the crystal structure, molecules are linked by pairs of N—H···O hydrogen bonds between inversion-related lactam rings into centrosymmetric dimers with an R₂²(8) graph-set motif (see Fig. 2).

Related literature top

For background information on 3-(acylamino)azepan-2-ones, see: Fox et al. (2009); Grainger & Fox (2006). For a related crystal structure, see: Zhu et al. (2007).

Experimental top

3-amino-caprolactam hydro-pyrrolidine-5-carboxylate (5 mmol) and Na₂CO₃ (15 mmol) in water (25 ml) were added to a solution of cyclohexanecarbonyl chloride (5 mmol) in CH₂Cl₂ (25 ml) at room temperature and the reaction was stirred for 12 h. The organic layer was then separated and the aqueous phase was extracted with additional CH₂Cl₂ (2 × 25 ml). The combined organic layers were dried over Na₂CO₃ and reduced in vacuo. The residue was purified by recrystallization from EtOAc / hexane to give the title compound (540 mg, 45% yield). (Grainger et al., 2006).

Crystals of (I) suitable for X-ray diffraction were obtained by slow evaporation of an ethanol solution.

Computing details top

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1989); cell refinement: CAD-4 EXPRESS (Enraf–Nonius, 1989); data reduction: XCAD4 (Harms & Wocadlo, 1995); 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: PLATON (Spek, 2009).

Figures top

	Fig. 1. The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level. H atoms are presented as small spheres of arbitrary radius.
	Fig. 2. A view of the unit cell packing of the title compound, projected down the a axis. Hydrogen bonds are drawn as dashed lines.

N-(2-Oxoazepan-3-yl)cyclohexanecarboxamide top

Crystal data top

C₁₃H₂₂N₂O₂	Z = 2
M_r = 238.33	F(000) = 260
Triclinic, P1	D_x = 1.203 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 5.007 (1) Å	Cell parameters from 25 reflections
b = 11.642 (2) Å	θ = 9–13°
c = 12.739 (3) Å	µ = 0.08 mm⁻¹
α = 63.66 (3)°	T = 293 K
β = 82.69 (3)°	Block, colorless
γ = 82.75 (3)°	0.30 × 0.20 × 0.10 mm
V = 658.0 (2) Å³

Data collection top

Enraf–Nonius CAD-4 diffractometer	1581 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.073
Graphite monochromator	θ_max = 25.4°, θ_min = 1.8°
ω/2θ scans	h = 0→6
Absorption correction: ψ scan (North et al., 1968)	k = −13→14
T_min = 0.976, T_max = 0.992	l = −15→15
2700 measured reflections	3 standard reflections every 200 reflections
2400 independent reflections	intensity decay: 1%

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)] = 0.062	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.177	H-atom parameters constrained
S = 1.01	w = 1/[σ²(F_o²) + (0.095P)²] where P = (F_o² + 2F_c²)/3
2400 reflections	(Δ/σ)_max < 0.001
154 parameters	Δρ_max = 0.16 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Crystal data top

C₁₃H₂₂N₂O₂	γ = 82.75 (3)°
M_r = 238.33	V = 658.0 (2) Å³
Triclinic, P1	Z = 2
a = 5.007 (1) Å	Mo Kα radiation
b = 11.642 (2) Å	µ = 0.08 mm⁻¹
c = 12.739 (3) Å	T = 293 K
α = 63.66 (3)°	0.30 × 0.20 × 0.10 mm
β = 82.69 (3)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	1581 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.073
T_min = 0.976, T_max = 0.992	3 standard reflections every 200 reflections
2700 measured reflections	intensity decay: 1%
2400 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.062	0 restraints
wR(F²) = 0.177	H-atom parameters constrained
S = 1.01	Δρ_max = 0.16 e Å⁻³
2400 reflections	Δρ_min = −0.21 e Å⁻³
154 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
N1	0.3592 (4)	0.2916 (2)	0.81058 (18)	0.0438 (6)
H1A	0.5252	0.3096	0.7936	0.053*
O1	−0.0132 (4)	0.2579 (2)	0.74942 (18)	0.0665 (7)
C1	0.4450 (6)	0.1452 (3)	0.6317 (3)	0.0548 (8)
H1B	0.5415	0.0899	0.7003	0.066*
H1C	0.2722	0.1110	0.6407	0.066*
O2	0.5524 (4)	0.42401 (18)	0.90229 (15)	0.0477 (5)
N2	0.2504 (4)	0.3723 (2)	1.05959 (17)	0.0430 (6)
H2A	0.3272	0.4210	1.0794	0.052*
C2	0.6071 (7)	0.1457 (3)	0.5219 (3)	0.0714 (10)
H2B	0.7850	0.1738	0.5161	0.086*
H2C	0.6295	0.0592	0.5276	0.086*
C3	0.4643 (7)	0.2349 (4)	0.4128 (3)	0.0727 (11)
H3A	0.5718	0.2357	0.3436	0.087*
H3B	0.2912	0.2037	0.4163	0.087*
C4	0.4213 (8)	0.3700 (3)	0.4037 (3)	0.0719 (10)
H4A	0.5951	0.4040	0.3930	0.086*
H4B	0.3228	0.4249	0.3357	0.086*
C5	0.2662 (6)	0.3715 (3)	0.5124 (2)	0.0508 (7)
H5A	0.0850	0.3471	0.5176	0.061*
H5B	0.2512	0.4582	0.5060	0.061*
C6	0.3986 (5)	0.2813 (2)	0.6235 (2)	0.0376 (6)
H6A	0.5742	0.3117	0.6210	0.045*
C7	0.2294 (5)	0.2772 (2)	0.7325 (2)	0.0408 (6)
C8	0.2270 (5)	0.2776 (2)	0.9237 (2)	0.0382 (6)
H8A	0.0359	0.3077	0.9136	0.046*
C9	0.3562 (5)	0.3637 (2)	0.9613 (2)	0.0353 (6)
C10	0.0196 (5)	0.3088 (3)	1.1375 (2)	0.0468 (7)
H10A	−0.1360	0.3313	1.0919	0.056*
H10B	−0.0225	0.3411	1.1964	0.056*
C11	0.0673 (7)	0.1631 (3)	1.1989 (2)	0.0549 (8)
H11A	0.2469	0.1405	1.2267	0.066*
H11B	−0.0617	0.1301	1.2670	0.066*
C12	0.0410 (6)	0.0989 (3)	1.1204 (2)	0.0534 (8)
H12A	−0.1396	0.1209	1.0937	0.064*
H12B	0.0611	0.0064	1.1667	0.064*
C13	0.2449 (6)	0.1356 (3)	1.0132 (2)	0.0479 (7)
H13A	0.2224	0.0839	0.9731	0.057*
H13B	0.4250	0.1130	1.0404	0.057*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0397 (12)	0.0635 (15)	0.0449 (12)	−0.0215 (10)	0.0136 (10)	−0.0387 (11)
O1	0.0423 (12)	0.1187 (19)	0.0656 (14)	−0.0274 (11)	0.0159 (10)	−0.0641 (14)
C1	0.0622 (18)	0.0482 (17)	0.0599 (18)	−0.0033 (14)	0.0042 (15)	−0.0314 (15)
O2	0.0554 (11)	0.0538 (11)	0.0469 (10)	−0.0262 (9)	0.0179 (9)	−0.0336 (9)
N2	0.0517 (13)	0.0472 (13)	0.0420 (12)	−0.0192 (10)	0.0138 (10)	−0.0306 (10)
C2	0.068 (2)	0.079 (2)	0.099 (3)	−0.0141 (18)	0.022 (2)	−0.071 (2)
C3	0.073 (2)	0.111 (3)	0.062 (2)	−0.033 (2)	0.0272 (18)	−0.065 (2)
C4	0.094 (3)	0.077 (2)	0.0431 (17)	−0.029 (2)	0.0159 (17)	−0.0247 (16)
C5	0.0596 (18)	0.0468 (16)	0.0490 (16)	−0.0079 (13)	0.0016 (14)	−0.0242 (13)
C6	0.0378 (13)	0.0428 (14)	0.0415 (14)	−0.0134 (11)	0.0080 (11)	−0.0270 (12)
C7	0.0373 (14)	0.0506 (16)	0.0474 (15)	−0.0141 (11)	0.0088 (12)	−0.0332 (13)
C8	0.0371 (13)	0.0455 (15)	0.0413 (14)	−0.0134 (11)	0.0101 (11)	−0.0281 (12)
C9	0.0370 (13)	0.0357 (13)	0.0369 (13)	−0.0098 (11)	0.0065 (11)	−0.0199 (11)
C10	0.0506 (16)	0.0488 (16)	0.0448 (15)	−0.0134 (12)	0.0154 (13)	−0.0263 (13)
C11	0.0694 (19)	0.0503 (17)	0.0468 (16)	−0.0218 (14)	0.0153 (15)	−0.0236 (14)
C12	0.0667 (18)	0.0439 (16)	0.0517 (17)	−0.0234 (14)	0.0096 (15)	−0.0215 (13)
C13	0.0565 (16)	0.0448 (16)	0.0565 (17)	−0.0137 (13)	0.0070 (14)	−0.0351 (14)

Geometric parameters (Å, º) top

N1—C7	1.334 (3)	C4—H4B	0.9700
N1—C8	1.455 (3)	C5—C6	1.513 (4)
N1—H1A	0.8600	C5—H5A	0.9700
O1—C7	1.238 (3)	C5—H5B	0.9700
C1—C2	1.523 (4)	C6—C7	1.516 (3)
C1—C6	1.530 (3)	C6—H6A	0.9800
C1—H1B	0.9700	C8—C9	1.524 (3)
C1—H1C	0.9700	C8—C13	1.536 (4)
O2—C9	1.241 (3)	C8—H8A	0.9800
N2—C9	1.337 (3)	C10—C11	1.522 (4)
N2—C10	1.462 (3)	C10—H10A	0.9700
N2—H2A	0.8600	C10—H10B	0.9700
C2—C3	1.519 (5)	C11—C12	1.516 (4)
C2—H2B	0.9700	C11—H11A	0.9700
C2—H2C	0.9700	C11—H11B	0.9700
C3—C4	1.515 (5)	C12—C13	1.526 (4)
C3—H3A	0.9700	C12—H12A	0.9700
C3—H3B	0.9700	C12—H12B	0.9700
C4—C5	1.505 (4)	C13—H13A	0.9700
C4—H4A	0.9700	C13—H13B	0.9700

C7—N1—C8	121.7 (2)	C5—C6—H6A	108.5
C7—N1—H1A	119.2	C7—C6—H6A	108.5
C8—N1—H1A	119.2	C1—C6—H6A	108.5
C2—C1—C6	110.7 (2)	O1—C7—N1	122.0 (2)
C2—C1—H1B	109.5	O1—C7—C6	121.9 (2)
C6—C1—H1B	109.5	N1—C7—C6	116.1 (2)
C2—C1—H1C	109.5	N1—C8—C9	108.04 (19)
C6—C1—H1C	109.5	N1—C8—C13	110.16 (19)
H1B—C1—H1C	108.1	C9—C8—C13	113.2 (2)
C9—N2—C10	127.8 (2)	N1—C8—H8A	108.5
C9—N2—H2A	116.1	C9—C8—H8A	108.5
C10—N2—H2A	116.1	C13—C8—H8A	108.5
C3—C2—C1	110.5 (3)	O2—C9—N2	121.3 (2)
C3—C2—H2B	109.5	O2—C9—C8	121.0 (2)
C1—C2—H2B	109.5	N2—C9—C8	117.7 (2)
C3—C2—H2C	109.5	N2—C10—C11	113.6 (2)
C1—C2—H2C	109.5	N2—C10—H10A	108.8
H2B—C2—H2C	108.1	C11—C10—H10A	108.8
C4—C3—C2	110.5 (3)	N2—C10—H10B	108.8
C4—C3—H3A	109.6	C11—C10—H10B	108.8
C2—C3—H3A	109.6	H10A—C10—H10B	107.7
C4—C3—H3B	109.6	C12—C11—C10	113.2 (2)
C2—C3—H3B	109.6	C12—C11—H11A	108.9
H3A—C3—H3B	108.1	C10—C11—H11A	108.9
C5—C4—C3	111.0 (2)	C12—C11—H11B	108.9
C5—C4—H4A	109.4	C10—C11—H11B	108.9
C3—C4—H4A	109.4	H11A—C11—H11B	107.8
C5—C4—H4B	109.4	C11—C12—C13	114.7 (2)
C3—C4—H4B	109.4	C11—C12—H12A	108.6
H4A—C4—H4B	108.0	C13—C12—H12A	108.6
C4—C5—C6	112.5 (2)	C11—C12—H12B	108.6
C4—C5—H5A	109.1	C13—C12—H12B	108.6
C6—C5—H5A	109.1	H12A—C12—H12B	107.6
C4—C5—H5B	109.1	C12—C13—C8	116.1 (2)
C6—C5—H5B	109.1	C12—C13—H13A	108.3
H5A—C5—H5B	107.8	C8—C13—H13A	108.3
C5—C6—C7	111.7 (2)	C12—C13—H13B	108.3
C5—C6—C1	110.5 (2)	C8—C13—H13B	108.3
C7—C6—C1	109.0 (2)	H13A—C13—H13B	107.4

C6—C1—C2—C3	−57.4 (3)	C7—N1—C8—C9	−150.4 (2)
C1—C2—C3—C4	57.9 (3)	C7—N1—C8—C13	85.5 (3)
C2—C3—C4—C5	−56.5 (4)	C10—N2—C9—O2	179.3 (2)
C3—C4—C5—C6	55.4 (4)	C10—N2—C9—C8	−0.4 (4)
C4—C5—C6—C7	−176.0 (2)	N1—C8—C9—O2	−4.5 (3)
C4—C5—C6—C1	−54.5 (3)	C13—C8—C9—O2	117.8 (3)
C2—C1—C6—C5	55.1 (3)	N1—C8—C9—N2	175.3 (2)
C2—C1—C6—C7	178.2 (2)	C13—C8—C9—N2	−62.5 (3)
C8—N1—C7—O1	3.9 (4)	C9—N2—C10—C11	65.1 (3)
C8—N1—C7—C6	−174.2 (2)	N2—C10—C11—C12	−78.0 (3)
C5—C6—C7—O1	51.0 (3)	C10—C11—C12—C13	62.3 (3)
C1—C6—C7—O1	−71.4 (3)	C11—C12—C13—C8	−63.3 (3)
C5—C6—C7—N1	−131.0 (3)	N1—C8—C13—C12	−160.1 (2)
C1—C6—C7—N1	106.7 (3)	C9—C8—C13—C12	78.9 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1ⁱ	0.86	2.37	3.158 (3)	152
N2—H2A···O2ⁱⁱ	0.86	2.09	2.927 (3)	165

Symmetry codes: (i) x+1, y, z; (ii) −x+1, −y+1, −z+2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1ⁱ	0.86	2.37	3.158 (3)	152
N2—H2A···O2ⁱⁱ	0.86	2.09	2.927 (3)	165

Symmetry codes: (i) x+1, y, z; (ii) −x+1, −y+1, −z+2.

References

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North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359. CrossRef IUCr Journals Web of Science Google Scholar
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doi:10.1107/S1600536813031863

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