supplementary materials


pk2501 scheme

Acta Cryst. (2013). E69, o1837    [ doi:10.1107/S1600536813031863 ]

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

S. Chunjuan and Y. Zhao

Abstract top

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.

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.

Refinement top

All H atoms were positioned geometrically and refined using a riding model, with C—H = 0.98 and 0.97 Å, for methine and methylene H-atoms, and N—H = 0.86 Å, for amido H-atoms, respectively. The Uiso(H) were allowed at 1.2Ueq(C).

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
[Figure 1] 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.
[Figure 2] 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
C13H22N2O2Z = 2
Mr = 238.33F(000) = 260
Triclinic, P1Dx = 1.203 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 5.007 (1) ÅCell parameters from 25 reflections
b = 11.642 (2) Åθ = 9–13°
c = 12.739 (3) ŵ = 0.08 mm1
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 tubeRint = 0.073
Graphite monochromatorθmax = 25.4°, θmin = 1.8°
ω/2θ scansh = 06
Absorption correction: ψ scan
(North et al., 1968)
k = 1314
Tmin = 0.976, Tmax = 0.992l = 1515
2700 measured reflections3 standard reflections every 200 reflections
2400 independent reflections intensity decay: 1%
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)] = 0.062Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.177H-atom parameters constrained
S = 1.01 w = 1/[σ2(Fo2) + (0.095P)2]
where P = (Fo2 + 2Fc2)/3
2400 reflections(Δ/σ)max < 0.001
154 parametersΔρmax = 0.16 e Å3
0 restraintsΔρmin = 0.21 e Å3
Crystal data top
C13H22N2O2γ = 82.75 (3)°
Mr = 238.33V = 658.0 (2) Å3
Triclinic, P1Z = 2
a = 5.007 (1) ÅMo Kα radiation
b = 11.642 (2) ŵ = 0.08 mm1
c = 12.739 (3) ÅT = 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)
Rint = 0.073
Tmin = 0.976, Tmax = 0.992θmax = 25.4°
2700 measured reflections3 standard reflections every 200 reflections
2400 independent reflections intensity decay: 1%
Refinement top
R[F2 > 2σ(F2)] = 0.062H-atom parameters constrained
wR(F2) = 0.177Δρmax = 0.16 e Å3
S = 1.01Δρmin = 0.21 e Å3
2400 reflectionsAbsolute structure: ?
154 parametersAbsolute structure 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
N10.3592 (4)0.2916 (2)0.81058 (18)0.0438 (6)
H1A0.52520.30960.79360.053*
O10.0132 (4)0.2579 (2)0.74942 (18)0.0665 (7)
C10.4450 (6)0.1452 (3)0.6317 (3)0.0548 (8)
H1B0.54150.08990.70030.066*
H1C0.27220.11100.64070.066*
O20.5524 (4)0.42401 (18)0.90229 (15)0.0477 (5)
N20.2504 (4)0.3723 (2)1.05959 (17)0.0430 (6)
H2A0.32720.42101.07940.052*
C20.6071 (7)0.1457 (3)0.5219 (3)0.0714 (10)
H2B0.78500.17380.51610.086*
H2C0.62950.05920.52760.086*
C30.4643 (7)0.2349 (4)0.4128 (3)0.0727 (11)
H3A0.57180.23570.34360.087*
H3B0.29120.20370.41630.087*
C40.4213 (8)0.3700 (3)0.4037 (3)0.0719 (10)
H4A0.59510.40400.39300.086*
H4B0.32280.42490.33570.086*
C50.2662 (6)0.3715 (3)0.5124 (2)0.0508 (7)
H5A0.08500.34710.51760.061*
H5B0.25120.45820.50600.061*
C60.3986 (5)0.2813 (2)0.6235 (2)0.0376 (6)
H6A0.57420.31170.62100.045*
C70.2294 (5)0.2772 (2)0.7325 (2)0.0408 (6)
C80.2270 (5)0.2776 (2)0.9237 (2)0.0382 (6)
H8A0.03590.30770.91360.046*
C90.3562 (5)0.3637 (2)0.9613 (2)0.0353 (6)
C100.0196 (5)0.3088 (3)1.1375 (2)0.0468 (7)
H10A0.13600.33131.09190.056*
H10B0.02250.34111.19640.056*
C110.0673 (7)0.1631 (3)1.1989 (2)0.0549 (8)
H11A0.24690.14051.22670.066*
H11B0.06170.13011.26700.066*
C120.0410 (6)0.0989 (3)1.1204 (2)0.0534 (8)
H12A0.13960.12091.09370.064*
H12B0.06110.00641.16670.064*
C130.2449 (6)0.1356 (3)1.0132 (2)0.0479 (7)
H13A0.22240.08390.97310.057*
H13B0.42500.11301.04040.057*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0397 (12)0.0635 (15)0.0449 (12)0.0215 (10)0.0136 (10)0.0387 (11)
O10.0423 (12)0.1187 (19)0.0656 (14)0.0274 (11)0.0159 (10)0.0641 (14)
C10.0622 (18)0.0482 (17)0.0599 (18)0.0033 (14)0.0042 (15)0.0314 (15)
O20.0554 (11)0.0538 (11)0.0469 (10)0.0262 (9)0.0179 (9)0.0336 (9)
N20.0517 (13)0.0472 (13)0.0420 (12)0.0192 (10)0.0138 (10)0.0306 (10)
C20.068 (2)0.079 (2)0.099 (3)0.0141 (18)0.022 (2)0.071 (2)
C30.073 (2)0.111 (3)0.062 (2)0.033 (2)0.0272 (18)0.065 (2)
C40.094 (3)0.077 (2)0.0431 (17)0.029 (2)0.0159 (17)0.0247 (16)
C50.0596 (18)0.0468 (16)0.0490 (16)0.0079 (13)0.0016 (14)0.0242 (13)
C60.0378 (13)0.0428 (14)0.0415 (14)0.0134 (11)0.0080 (11)0.0270 (12)
C70.0373 (14)0.0506 (16)0.0474 (15)0.0141 (11)0.0088 (12)0.0332 (13)
C80.0371 (13)0.0455 (15)0.0413 (14)0.0134 (11)0.0101 (11)0.0281 (12)
C90.0370 (13)0.0357 (13)0.0369 (13)0.0098 (11)0.0065 (11)0.0199 (11)
C100.0506 (16)0.0488 (16)0.0448 (15)0.0134 (12)0.0154 (13)0.0263 (13)
C110.0694 (19)0.0503 (17)0.0468 (16)0.0218 (14)0.0153 (15)0.0236 (14)
C120.0667 (18)0.0439 (16)0.0517 (17)0.0234 (14)0.0096 (15)0.0215 (13)
C130.0565 (16)0.0448 (16)0.0565 (17)0.0137 (13)0.0070 (14)0.0351 (14)
Geometric parameters (Å, º) top
N1—C71.334 (3)C4—H4B0.9700
N1—C81.455 (3)C5—C61.513 (4)
N1—H1A0.8600C5—H5A0.9700
O1—C71.238 (3)C5—H5B0.9700
C1—C21.523 (4)C6—C71.516 (3)
C1—C61.530 (3)C6—H6A0.9800
C1—H1B0.9700C8—C91.524 (3)
C1—H1C0.9700C8—C131.536 (4)
O2—C91.241 (3)C8—H8A0.9800
N2—C91.337 (3)C10—C111.522 (4)
N2—C101.462 (3)C10—H10A0.9700
N2—H2A0.8600C10—H10B0.9700
C2—C31.519 (5)C11—C121.516 (4)
C2—H2B0.9700C11—H11A0.9700
C2—H2C0.9700C11—H11B0.9700
C3—C41.515 (5)C12—C131.526 (4)
C3—H3A0.9700C12—H12A0.9700
C3—H3B0.9700C12—H12B0.9700
C4—C51.505 (4)C13—H13A0.9700
C4—H4A0.9700C13—H13B0.9700
C7—N1—C8121.7 (2)C5—C6—H6A108.5
C7—N1—H1A119.2C7—C6—H6A108.5
C8—N1—H1A119.2C1—C6—H6A108.5
C2—C1—C6110.7 (2)O1—C7—N1122.0 (2)
C2—C1—H1B109.5O1—C7—C6121.9 (2)
C6—C1—H1B109.5N1—C7—C6116.1 (2)
C2—C1—H1C109.5N1—C8—C9108.04 (19)
C6—C1—H1C109.5N1—C8—C13110.16 (19)
H1B—C1—H1C108.1C9—C8—C13113.2 (2)
C9—N2—C10127.8 (2)N1—C8—H8A108.5
C9—N2—H2A116.1C9—C8—H8A108.5
C10—N2—H2A116.1C13—C8—H8A108.5
C3—C2—C1110.5 (3)O2—C9—N2121.3 (2)
C3—C2—H2B109.5O2—C9—C8121.0 (2)
C1—C2—H2B109.5N2—C9—C8117.7 (2)
C3—C2—H2C109.5N2—C10—C11113.6 (2)
C1—C2—H2C109.5N2—C10—H10A108.8
H2B—C2—H2C108.1C11—C10—H10A108.8
C4—C3—C2110.5 (3)N2—C10—H10B108.8
C4—C3—H3A109.6C11—C10—H10B108.8
C2—C3—H3A109.6H10A—C10—H10B107.7
C4—C3—H3B109.6C12—C11—C10113.2 (2)
C2—C3—H3B109.6C12—C11—H11A108.9
H3A—C3—H3B108.1C10—C11—H11A108.9
C5—C4—C3111.0 (2)C12—C11—H11B108.9
C5—C4—H4A109.4C10—C11—H11B108.9
C3—C4—H4A109.4H11A—C11—H11B107.8
C5—C4—H4B109.4C11—C12—C13114.7 (2)
C3—C4—H4B109.4C11—C12—H12A108.6
H4A—C4—H4B108.0C13—C12—H12A108.6
C4—C5—C6112.5 (2)C11—C12—H12B108.6
C4—C5—H5A109.1C13—C12—H12B108.6
C6—C5—H5A109.1H12A—C12—H12B107.6
C4—C5—H5B109.1C12—C13—C8116.1 (2)
C6—C5—H5B109.1C12—C13—H13A108.3
H5A—C5—H5B107.8C8—C13—H13A108.3
C5—C6—C7111.7 (2)C12—C13—H13B108.3
C5—C6—C1110.5 (2)C8—C13—H13B108.3
C7—C6—C1109.0 (2)H13A—C13—H13B107.4
C6—C1—C2—C357.4 (3)C7—N1—C8—C9150.4 (2)
C1—C2—C3—C457.9 (3)C7—N1—C8—C1385.5 (3)
C2—C3—C4—C556.5 (4)C10—N2—C9—O2179.3 (2)
C3—C4—C5—C655.4 (4)C10—N2—C9—C80.4 (4)
C4—C5—C6—C7176.0 (2)N1—C8—C9—O24.5 (3)
C4—C5—C6—C154.5 (3)C13—C8—C9—O2117.8 (3)
C2—C1—C6—C555.1 (3)N1—C8—C9—N2175.3 (2)
C2—C1—C6—C7178.2 (2)C13—C8—C9—N262.5 (3)
C8—N1—C7—O13.9 (4)C9—N2—C10—C1165.1 (3)
C8—N1—C7—C6174.2 (2)N2—C10—C11—C1278.0 (3)
C5—C6—C7—O151.0 (3)C10—C11—C12—C1362.3 (3)
C1—C6—C7—O171.4 (3)C11—C12—C13—C863.3 (3)
C5—C6—C7—N1131.0 (3)N1—C8—C13—C12160.1 (2)
C1—C6—C7—N1106.7 (3)C9—C8—C13—C1278.9 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O1i0.862.373.158 (3)152
N2—H2A···O2ii0.862.092.927 (3)165
Symmetry codes: (i) x+1, y, z; (ii) x+1, y+1, z+2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···O1i0.862.373.158 (3)152
N2—H2A···O2ii0.862.092.927 (3)165
Symmetry codes: (i) x+1, y, z; (ii) x+1, y+1, z+2.
references
References top

Enraf–Nonius (1989). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands.

Fox, D. J., Reckless, J., Lingard, H., Warren, S. & Grainger, D. J. (2009). J. Med. Chem. 52, 3591–3595.

Grainger, D. J. & Fox, D. J. (2006). Patent WO 2006016152A1.

Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.

North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.

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

Spek, A. L. (2009). Acta Cryst. D65, 148–155.

Zhu, N., Tran, P., Bell, N. & Stevens, C. L. K. (2007). J. Chem. Crystallogr. 37, 670–683.