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Acta Cryst. (2008). E64, o569    [ doi:10.1107/S1600536808001773 ]

1-Benzyl-1,4-diazepan-5-one

F. Sha, H. Xu, S. Liu, P. Wang and J. Wang

Abstract top

The title compound, C12H16N2O, is a diazepane intermediate that can be used as an inhibitor of human nitric oxide synthesis. In the molecule, the seven-membered ring has a chair-like conformation and the two rings are approximately perpendicular to one another, with a C-N-C-C torsion angle of 77.8 (4)°. Intermolecular N-H...O hydrogen bonds link the molecules into dimers around a centre of symmetry, with C-H...O interactions linking the dimers into infinite sheets.

Comment top

The title compound is a 1-substituted 1,4-diazepan-5-one; an important class of heterocyclic compounds that have widespread applications from pharmaceuticals (Wlodarczyk et al., 2006) to biology (Gopalakrishnan et al., 2007). As part of our studies in this area, we report herein the synthesis and crystal structure of the title compound, (I).

In the molecule (Fig. 1) the 7-membered ring has a chair-like conformation with C1,C2,C3 and C4 forming the planar seat of the chair and N2 out of the plane on one side and N1—C5 out of the plane on the other side. The two rings are approximately perpendicular to one another with a C3—N2—C6—C7 torsion angle of 77.8 (4)°. Intermolecular N—H···O hydrogen bonds link the molecules into dimers around a center of symmetry with C—H···O interactions linking the dimers into infinite sheets (Fig. 2).

Related literature top

For related literature, see: Gopalakrishnan et al. (2007); Wlodarczyk et al. (2006).

Experimental top

1-Benzyl-piperidin-4-one (18.9 g,0.1 mol) was added into a stirred mixture of sulfuric acid (40 ml) and dichloromethane (80 ml) at 273 K. Then, at 273 K, sodium azide (32.5 g,0.5 mol) was cautiously added over a period of 3 h and the resulting mixture was stirred for 1 h with the temperature kept at approximately 278 K. Then ice (1 kg) was quickly added and the solution was alkalized with ammonium hydroxide (15%,200 mL) to pH=11. The organic layer was separated with the water fraction extracted with dichloromethane (3x100mL). The organic extracts were combined,dried over NaSO4, and concentrated in vacuo. The residue was recrystallized from EtOAc to give the title compound, (I) (yield: 13.0 g, 65%). Crystals of (I) suitable for X-ray analysis were obtained by slow evaporation of an ethanol solution.

Refinement top

H atoms were positioned geometrically, with N—H = 0.86 Å (for NH) and 0.93 Å fro aromatic carbons and 0.97 Å for all others, and constrained to ride on their parent atoms, with Uiso(H) = xUeq(C,N), where x = 1.5 for methyl H, and x = 1.2 for all other H atoms.

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (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: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
[Figure 2] Fig. 2. A packing diagram for (I). Hydrogen bonds are shown as dashed lines.
1-Benzyl-1,4-diazepan-5-one top
Crystal data top
C12H16N2OF000 = 440
Mr = 204.27Dx = 1.200 Mg m−3
Monoclinic, P21/cMo Kα radiation
λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 25 reflections
a = 12.602 (3) Åθ = 9–12º
b = 7.4920 (15) ŵ = 0.08 mm−1
c = 12.824 (3) ÅT = 298 (2) K
β = 111.00 (3)ºBLOCK, colourless
V = 1130.3 (4) Å30.20 × 0.10 × 0.10 mm
Z = 4
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.053
Radiation source: fine-focus sealed tubeθmax = 26.0º
Monochromator: graphiteθmin = 1.7º
T = 298(2) Kh = −15→14
ω/2θ scansk = 0→9
Absorption correction: ψ scan
(North et al., 1968)		l = 0→15
Tmin = 0.985, Tmax = 0.9923 standard reflections
2308 measured reflections every 200 reflections
2205 independent reflections intensity decay: none
1162 reflections with I > 2σ(I)
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.088H-atom parameters constrained
wR(F2) = 0.189  w = 1/[σ2(Fo2) + (0.04P)2 + 1.65P]
where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
2205 reflectionsΔρmax = 0.52 e Å−3
130 parametersΔρmin = −0.18 e Å−3
46 restraintsExtinction correction: none
Primary atom site location: structure-invariant direct methods
Crystal data top
C12H16N2OV = 1130.3 (4) Å3
Mr = 204.27Z = 4
Monoclinic, P21/cMo Kα
a = 12.602 (3) ŵ = 0.08 mm−1
b = 7.4920 (15) ÅT = 298 (2) K
c = 12.824 (3) Å0.20 × 0.10 × 0.10 mm
β = 111.00 (3)º
Data collection top
Enraf–Nonius CAD-4
diffractometer		1162 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al., 1968)		Rint = 0.053
Tmin = 0.985, Tmax = 0.9923 standard reflections
2308 measured reflections every 200 reflections
2205 independent reflections intensity decay: none
Refinement top
R[F2 > 2σ(F2)] = 0.08846 restraints
wR(F2) = 0.189H-atom parameters constrained
S = 1.00Δρmax = 0.52 e Å−3
2205 reflectionsΔρmin = −0.18 e Å−3
130 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
xyzUiso*/Ueq
N10.3935 (3)−0.4319 (6)0.5667 (3)0.0870 (12)
H1A0.4312−0.52750.56670.104*
O0.5027 (3)−0.2681 (5)0.4894 (3)0.108
N20.2757 (3)−0.1384 (4)0.6724 (2)0.0542 (8)
C10.2993 (4)−0.4434 (5)0.6094 (4)0.0705 (12)
H1B0.2940−0.56570.63190.085*
H1C0.2289−0.41580.54870.085*
C20.3090 (4)−0.3232 (5)0.7059 (4)0.0697 (11)
H2A0.2613−0.36960.74460.084*
H2B0.3869−0.32450.75790.084*
C30.3581 (3)−0.0442 (5)0.6349 (3)0.0632 (10)
H3A0.4334−0.05710.69120.076*
H3B0.33960.08200.62780.076*
C40.3596 (3)−0.1132 (6)0.5236 (3)0.0683 (11)
H4A0.2817−0.12990.47350.082*
H4B0.3932−0.02220.49130.082*
C50.4230 (3)−0.2848 (7)0.5289 (4)0.0765 (13)
C60.2595 (3)−0.0404 (6)0.7642 (3)0.0685 (12)
H6A0.3332−0.00180.81570.082*
H6B0.2272−0.12040.80430.082*
C70.1827 (3)0.1221 (5)0.7265 (3)0.0531 (9)
C80.1029 (3)0.1333 (5)0.6142 (4)0.0643 (11)
H8A0.10170.04890.56060.077*
C90.0285 (4)0.2739 (6)0.5892 (4)0.0779 (13)
H9A−0.02230.28450.51610.094*
C100.0241 (4)0.3960 (7)0.6626 (5)0.0865 (15)
H10A−0.02880.48790.64060.104*
C110.0969 (5)0.3858 (6)0.7691 (5)0.0869 (15)
H11A0.09540.47100.82130.104*
C120.1748 (4)0.2447 (6)0.7999 (4)0.0713 (12)
H12A0.22300.23540.87410.086*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.065 (2)0.109 (3)0.076 (3)0.031 (2)0.0121 (19)−0.027 (2)
O0.1080.1080.1080.0000.0390.000
N20.0666 (19)0.0520 (18)0.0461 (17)0.0091 (16)0.0229 (15)−0.0087 (15)
C10.084 (3)0.048 (2)0.083 (3)0.011 (2)0.034 (2)−0.003 (2)
C20.085 (3)0.050 (2)0.073 (3)−0.004 (2)0.027 (2)0.011 (2)
C30.072 (3)0.055 (2)0.070 (3)−0.005 (2)0.035 (2)0.002 (2)
C40.054 (2)0.089 (3)0.065 (2)0.012 (2)0.0255 (19)0.016 (2)
C50.051 (2)0.100 (3)0.084 (3)0.017 (2)0.030 (2)−0.033 (3)
C60.069 (3)0.079 (3)0.055 (2)0.025 (2)0.020 (2)0.003 (2)
C70.060 (2)0.048 (2)0.058 (2)0.0113 (18)0.0293 (19)0.0002 (18)
C80.052 (2)0.058 (2)0.080 (3)0.003 (2)0.020 (2)−0.009 (2)
C90.064 (3)0.064 (3)0.092 (3)0.012 (2)0.011 (2)0.007 (3)
C100.066 (3)0.074 (3)0.131 (5)0.018 (3)0.050 (3)−0.009 (3)
C110.098 (4)0.061 (3)0.119 (4)0.001 (3)0.061 (4)−0.018 (3)
C120.078 (3)0.064 (3)0.084 (3)−0.011 (2)0.043 (3)−0.003 (2)
Geometric parameters (Å, °) top
N1—C51.311 (6)C4—H4A0.9700
N1—C11.477 (5)C4—H4B0.9700
N1—H1A0.8600C6—C71.523 (5)
O—C51.284 (5)C6—H6A0.9700
N2—C61.462 (4)C6—H6B0.9700
N2—C21.465 (5)C7—C121.345 (5)
N2—C31.471 (4)C7—C81.433 (5)
C1—C21.500 (5)C8—C91.370 (5)
C1—H1B0.9700C8—H8A0.9300
C1—H1C0.9700C9—C101.328 (6)
C2—H2A0.9700C9—H9A0.9300
C2—H2B0.9700C10—C111.347 (7)
C3—C41.525 (5)C10—H10A0.9300
C3—H3A0.9700C11—C121.400 (6)
C3—H3B0.9700C11—H11A0.9300
C4—C51.502 (6)C12—H12A0.9300
C5—N1—C1124.0 (4)H4A—C4—H4B107.4
C5—N1—H1A118.0O—C5—N1126.5 (4)
C1—N1—H1A118.0O—C5—C4112.2 (5)
C6—N2—C2110.3 (3)N1—C5—C4121.3 (3)
C6—N2—C3109.9 (3)N2—C6—C7113.7 (3)
C2—N2—C3112.8 (3)N2—C6—H6A108.8
N1—C1—C2115.6 (4)C7—C6—H6A108.8
N1—C1—H1B108.4N2—C6—H6B108.8
C2—C1—H1B108.4C7—C6—H6B108.8
N1—C1—H1C108.4H6A—C6—H6B107.7
C2—C1—H1C108.4C12—C7—C8117.6 (4)
H1B—C1—H1C107.4C12—C7—C6121.5 (4)
N2—C2—C1113.3 (3)C8—C7—C6120.2 (3)
N2—C2—H2A108.9C9—C8—C7117.1 (4)
C1—C2—H2A108.9C9—C8—H8A121.5
N2—C2—H2B108.9C7—C8—H8A121.5
C1—C2—H2B108.9C10—C9—C8124.2 (5)
H2A—C2—H2B107.7C10—C9—H9A117.9
N2—C3—C4113.0 (3)C8—C9—H9A117.9
N2—C3—H3A109.0C9—C10—C11119.6 (5)
C4—C3—H3A109.0C9—C10—H10A120.2
N2—C3—H3B109.0C11—C10—H10A120.2
C4—C3—H3B109.0C10—C11—C12118.9 (5)
H3A—C3—H3B107.8C10—C11—H11A120.6
C5—C4—C3115.7 (3)C12—C11—H11A120.6
C5—C4—H4A108.4C7—C12—C11122.6 (4)
C3—C4—H4A108.4C7—C12—H12A118.7
C5—C4—H4B108.4C11—C12—H12A118.7
C3—C4—H4B108.4
C5—N1—C1—C2−58.5 (6)C3—N2—C6—C777.8 (4)
C6—N2—C2—C1165.8 (3)N2—C6—C7—C12−167.9 (4)
C3—N2—C2—C1−70.9 (4)N2—C6—C7—C822.3 (5)
N1—C1—C2—N279.5 (5)C12—C7—C8—C93.2 (6)
C6—N2—C3—C4−166.9 (3)C6—C7—C8—C9173.4 (4)
C2—N2—C3—C469.6 (4)C7—C8—C9—C10−1.8 (7)
N2—C3—C4—C5−78.3 (4)C8—C9—C10—C110.5 (8)
C1—N1—C5—O−178.8 (4)C9—C10—C11—C12−0.7 (7)
C1—N1—C5—C4−1.4 (7)C8—C7—C12—C11−3.6 (6)
C3—C4—C5—O−122.4 (4)C6—C7—C12—C11−173.7 (4)
C3—C4—C5—N159.8 (6)C10—C11—C12—C72.4 (7)
C2—N2—C6—C7−157.2 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···Oi0.862.002.821 (5)160
C4—H4B···Oii0.972.513.377 (5)149
Symmetry codes: (i) −x+1, −y−1, −z+1; (ii) −x+1, −y, −z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···Oi0.862.002.821 (5)160
C4—H4B···Oii0.972.513.377 (5)149
Symmetry codes: (i) −x+1, −y−1, −z+1; (ii) −x+1, −y, −z+1.
Acknowledgements top

The authors thank the Center of Testing and Analysis, Nanjing University, for the support.

references
References top

Enraf–Nonius (1989). CAD-4 Software. Version 5.0. Enraf–Nonius, Delft, The Netherlands.

Gopalakrishnan, M., Sureshkumar, P., Thanusu, J., Kanagarajan, V., Govindaraju, R. & Jayasri, G. (2007). J. Enzyme Inhib. Med. Chem. 22, 709–715.

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.

Wlodarczyk, N., Gilleron, P., Millet, R., Houssin, R., Goossens, J., Lemoine, A., Pommery, N., Wei, M. & Hénichart, J. (2006). Oncol. Res. 16, 107–118.