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

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

doi:10.1107/S1600536808001773

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 64| Part 3| March 2008| Page o569

doi:10.1107/S1600536808001773

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

Fei Sha,^a Hao Xu,^a Shan Liu,^a Peng Wang ^b and Jin-tang Wang ^a ^*

^aDepartment of Applied Chemistry, College of Sciences, Nanjing University of Technology, Xinmofan Road No. 5 Nanjing, Nanjing 210009, People's Republic of China, and ^bCenter of Drug Discovery, China Pharmaceutical University, Nanjing 210009, People's Republic of China
^*Correspondence e-mail: shafei1983@163.com

(Received 7 December 2007; accepted 17 January 2008; online 8 February 2008)

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.

Related literature

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

Experimental

Crystal data

C₁₂H₁₆N₂O
M_r = 204.27
Monoclinic, P 2₁ /c
a = 12.602 (3) Å
b = 7.4920 (15) Å
c = 12.824 (3) Å
β = 111.00 (3)°
V = 1130.3 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 298 (2) K
0.20 × 0.10 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (North et al., 1968 ) T_min = 0.985, T_max = 0.992
2308 measured reflections
2205 independent reflections
1162 reflections with I > 2σ(I)
R_int = 0.053
3 standard reflections every 200 reflections intensity decay: none

Refinement

R[F² > 2σ(F²)] = 0.088
wR(F²) = 0.189
S = 0.99
2205 reflections
130 parameters
46 restraints
H-atom parameters constrained
Δρ_max = 0.52 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯Oⁱ	0.86	2.00	2.821 (5)	160
C4—H4B⋯Oⁱⁱ	0.97	2.51	3.377 (5)	149
Symmetry codes: (i) -x+1, -y-1, -z+1; (ii) -x+1, -y, -z+1.

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

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808001773/fl2179sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808001773/fl2179Isup2.hkl

checkCIF report

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.

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

	Fig. 1. The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
	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

C₁₂H₁₆N₂O	F(000) = 440
M_r = 204.27	D_x = 1.200 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 12.602 (3) Å	θ = 9–12°
b = 7.4920 (15) Å	µ = 0.08 mm⁻¹
c = 12.824 (3) Å	T = 298 K
β = 111.00 (3)°	BLOCK, colourless
V = 1130.3 (4) Å³	0.20 × 0.10 × 0.10 mm
Z = 4

Data collection top

Enraf–Nonius CAD-4 diffractometer	1162 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.053
Graphite monochromator	θ_max = 26.0°, θ_min = 1.7°
ω/2θ scans	h = −15→14
Absorption correction: ψ scan (North et al., 1968)	k = 0→9
T_min = 0.985, T_max = 0.992	l = 0→15
2308 measured reflections	3 standard reflections every 200 reflections
2205 independent reflections	intensity decay: none

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)] = 0.088	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.189	H-atom parameters constrained
S = 1.00	w = 1/[σ²(F_o²) + (0.04P)² + 1.65P] where P = (F_o² + 2F_c²)/3
2205 reflections	(Δ/σ)_max < 0.001
130 parameters	Δρ_max = 0.52 e Å⁻³
46 restraints	Δρ_min = −0.18 e Å⁻³

Crystal data top

C₁₂H₁₆N₂O	V = 1130.3 (4) Å³
M_r = 204.27	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 12.602 (3) Å	µ = 0.08 mm⁻¹
b = 7.4920 (15) Å	T = 298 K
c = 12.824 (3) Å	0.20 × 0.10 × 0.10 mm
β = 111.00 (3)°

Data collection top

Enraf–Nonius CAD-4 diffractometer	1162 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.053
T_min = 0.985, T_max = 0.992	3 standard reflections every 200 reflections
2308 measured reflections	intensity decay: none
2205 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.088	46 restraints
wR(F²) = 0.189	H-atom parameters constrained
S = 1.00	Δρ_max = 0.52 e Å⁻³
2205 reflections	Δρ_min = −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

	x	y	z	U_iso*/U_eq
N1	0.3935 (3)	−0.4319 (6)	0.5667 (3)	0.0870 (12)
H1A	0.4312	−0.5275	0.5667	0.104*
O	0.5027 (3)	−0.2681 (5)	0.4894 (3)	0.108
N2	0.2757 (3)	−0.1384 (4)	0.6724 (2)	0.0542 (8)
C1	0.2993 (4)	−0.4434 (5)	0.6094 (4)	0.0705 (12)
H1B	0.2940	−0.5657	0.6319	0.085*
H1C	0.2289	−0.4158	0.5487	0.085*
C2	0.3090 (4)	−0.3232 (5)	0.7059 (4)	0.0697 (11)
H2A	0.2613	−0.3696	0.7446	0.084*
H2B	0.3869	−0.3245	0.7579	0.084*
C3	0.3581 (3)	−0.0442 (5)	0.6349 (3)	0.0632 (10)
H3A	0.4334	−0.0571	0.6912	0.076*
H3B	0.3396	0.0820	0.6278	0.076*
C4	0.3596 (3)	−0.1132 (6)	0.5236 (3)	0.0683 (11)
H4A	0.2817	−0.1299	0.4735	0.082*
H4B	0.3932	−0.0222	0.4913	0.082*
C5	0.4230 (3)	−0.2848 (7)	0.5289 (4)	0.0765 (13)
C6	0.2595 (3)	−0.0404 (6)	0.7642 (3)	0.0685 (12)
H6A	0.3332	−0.0018	0.8157	0.082*
H6B	0.2272	−0.1204	0.8043	0.082*
C7	0.1827 (3)	0.1221 (5)	0.7265 (3)	0.0531 (9)
C8	0.1029 (3)	0.1333 (5)	0.6142 (4)	0.0643 (11)
H8A	0.1017	0.0489	0.5606	0.077*
C9	0.0285 (4)	0.2739 (6)	0.5892 (4)	0.0779 (13)
H9A	−0.0223	0.2845	0.5161	0.094*
C10	0.0241 (4)	0.3960 (7)	0.6626 (5)	0.0865 (15)
H10A	−0.0288	0.4879	0.6406	0.104*
C11	0.0969 (5)	0.3858 (6)	0.7691 (5)	0.0869 (15)
H11A	0.0954	0.4710	0.8213	0.104*
C12	0.1748 (4)	0.2447 (6)	0.7999 (4)	0.0713 (12)
H12A	0.2230	0.2354	0.8741	0.086*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.065 (2)	0.109 (3)	0.076 (3)	0.031 (2)	0.0121 (19)	−0.027 (2)
O	0.108	0.108	0.108	0.000	0.039	0.000
N2	0.0666 (19)	0.0520 (18)	0.0461 (17)	0.0091 (16)	0.0229 (15)	−0.0087 (15)
C1	0.084 (3)	0.048 (2)	0.083 (3)	0.011 (2)	0.034 (2)	−0.003 (2)
C2	0.085 (3)	0.050 (2)	0.073 (3)	−0.004 (2)	0.027 (2)	0.011 (2)
C3	0.072 (3)	0.055 (2)	0.070 (3)	−0.005 (2)	0.035 (2)	0.002 (2)
C4	0.054 (2)	0.089 (3)	0.065 (2)	0.012 (2)	0.0255 (19)	0.016 (2)
C5	0.051 (2)	0.100 (3)	0.084 (3)	0.017 (2)	0.030 (2)	−0.033 (3)
C6	0.069 (3)	0.079 (3)	0.055 (2)	0.025 (2)	0.020 (2)	0.003 (2)
C7	0.060 (2)	0.048 (2)	0.058 (2)	0.0113 (18)	0.0293 (19)	0.0002 (18)
C8	0.052 (2)	0.058 (2)	0.080 (3)	0.003 (2)	0.020 (2)	−0.009 (2)
C9	0.064 (3)	0.064 (3)	0.092 (3)	0.012 (2)	0.011 (2)	0.007 (3)
C10	0.066 (3)	0.074 (3)	0.131 (5)	0.018 (3)	0.050 (3)	−0.009 (3)
C11	0.098 (4)	0.061 (3)	0.119 (4)	0.001 (3)	0.061 (4)	−0.018 (3)
C12	0.078 (3)	0.064 (3)	0.084 (3)	−0.011 (2)	0.043 (3)	−0.003 (2)

Geometric parameters (Å, º) top

N1—C5	1.311 (6)	C4—H4A	0.9700
N1—C1	1.477 (5)	C4—H4B	0.9700
N1—H1A	0.8600	C6—C7	1.523 (5)
O—C5	1.284 (5)	C6—H6A	0.9700
N2—C6	1.462 (4)	C6—H6B	0.9700
N2—C2	1.465 (5)	C7—C12	1.345 (5)
N2—C3	1.471 (4)	C7—C8	1.433 (5)
C1—C2	1.500 (5)	C8—C9	1.370 (5)
C1—H1B	0.9700	C8—H8A	0.9300
C1—H1C	0.9700	C9—C10	1.328 (6)
C2—H2A	0.9700	C9—H9A	0.9300
C2—H2B	0.9700	C10—C11	1.347 (7)
C3—C4	1.525 (5)	C10—H10A	0.9300
C3—H3A	0.9700	C11—C12	1.400 (6)
C3—H3B	0.9700	C11—H11A	0.9300
C4—C5	1.502 (6)	C12—H12A	0.9300

C5—N1—C1	124.0 (4)	H4A—C4—H4B	107.4
C5—N1—H1A	118.0	O—C5—N1	126.5 (4)
C1—N1—H1A	118.0	O—C5—C4	112.2 (5)
C6—N2—C2	110.3 (3)	N1—C5—C4	121.3 (3)
C6—N2—C3	109.9 (3)	N2—C6—C7	113.7 (3)
C2—N2—C3	112.8 (3)	N2—C6—H6A	108.8
N1—C1—C2	115.6 (4)	C7—C6—H6A	108.8
N1—C1—H1B	108.4	N2—C6—H6B	108.8
C2—C1—H1B	108.4	C7—C6—H6B	108.8
N1—C1—H1C	108.4	H6A—C6—H6B	107.7
C2—C1—H1C	108.4	C12—C7—C8	117.6 (4)
H1B—C1—H1C	107.4	C12—C7—C6	121.5 (4)
N2—C2—C1	113.3 (3)	C8—C7—C6	120.2 (3)
N2—C2—H2A	108.9	C9—C8—C7	117.1 (4)
C1—C2—H2A	108.9	C9—C8—H8A	121.5
N2—C2—H2B	108.9	C7—C8—H8A	121.5
C1—C2—H2B	108.9	C10—C9—C8	124.2 (5)
H2A—C2—H2B	107.7	C10—C9—H9A	117.9
N2—C3—C4	113.0 (3)	C8—C9—H9A	117.9
N2—C3—H3A	109.0	C9—C10—C11	119.6 (5)
C4—C3—H3A	109.0	C9—C10—H10A	120.2
N2—C3—H3B	109.0	C11—C10—H10A	120.2
C4—C3—H3B	109.0	C10—C11—C12	118.9 (5)
H3A—C3—H3B	107.8	C10—C11—H11A	120.6
C5—C4—C3	115.7 (3)	C12—C11—H11A	120.6
C5—C4—H4A	108.4	C7—C12—C11	122.6 (4)
C3—C4—H4A	108.4	C7—C12—H12A	118.7
C5—C4—H4B	108.4	C11—C12—H12A	118.7
C3—C4—H4B	108.4

C5—N1—C1—C2	−58.5 (6)	C3—N2—C6—C7	77.8 (4)
C6—N2—C2—C1	165.8 (3)	N2—C6—C7—C12	−167.9 (4)
C3—N2—C2—C1	−70.9 (4)	N2—C6—C7—C8	22.3 (5)
N1—C1—C2—N2	79.5 (5)	C12—C7—C8—C9	3.2 (6)
C6—N2—C3—C4	−166.9 (3)	C6—C7—C8—C9	173.4 (4)
C2—N2—C3—C4	69.6 (4)	C7—C8—C9—C10	−1.8 (7)
N2—C3—C4—C5	−78.3 (4)	C8—C9—C10—C11	0.5 (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—N1	59.8 (6)	C10—C11—C12—C7	2.4 (7)
C2—N2—C6—C7	−157.2 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···Oⁱ	0.86	2.00	2.821 (5)	160
C4—H4B···Oⁱⁱ	0.97	2.51	3.377 (5)	149

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

Experimental details

Crystal data
Chemical formula	C₁₂H₁₆N₂O
M_r	204.27
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	298
a, b, c (Å)	12.602 (3), 7.4920 (15), 12.824 (3)
β (°)	111.00 (3)
V (Å³)	1130.3 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.08
Crystal size (mm)	0.20 × 0.10 × 0.10

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	ψ scan (North et al., 1968)
T_min, T_max	0.985, 0.992
No. of measured, independent and observed [I > 2σ(I)] reflections	2308, 2205, 1162
R_int	0.053
(sin θ/λ)_max (Å⁻¹)	0.616

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.088, 0.189, 1.00
No. of reflections	2205
No. of parameters	130
No. of restraints	46
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.52, −0.18

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), XCAD4 (Harms & Wocadlo, 1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···Oⁱ	0.86	2.00	2.821 (5)	160.3
C4—H4B···Oⁱⁱ	0.97	2.51	3.377 (5)	149.4

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

Acknowledgements

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

References

Enraf–Nonius (1989). CAD-4 Software. Version 5.0. Enraf–Nonius, Delft, The Netherlands. Google Scholar
Gopalakrishnan, M., Sureshkumar, P., Thanusu, J., Kanagarajan, V., Govindaraju, R. & Jayasri, G. (2007). J. Enzyme Inhib. Med. Chem. 22, 709–715. Web of Science CrossRef PubMed CAS Google Scholar
Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany. Google Scholar
North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359. CrossRef IUCr Journals Web of Science Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Wlodarczyk, N., Gilleron, P., Millet, R., Houssin, R., Goossens, J., Lemoine, A., Pommery, N., Wei, M. & Hénichart, J. (2006). Oncol. Res. 16, 107–118. CAS Google Scholar