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Acta Cryst. (2008). E64, o969    [ doi:10.1107/S1600536808007927 ]

4-Acetyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

Q.-J. Zhao, Z. Liu, J. Zheng and J.-S. Shen

Abstract top

The title compound, C11H14N2O·H2O, crystallizes with one formula unit in the asymmetric unit. The seven-membered ring has a chair conformation with the C=O group turned away from the benzene ring. N-H...O and O-H...O hydrogen bonds are present in the crystal structure.

Comment top

The title molecule (Fig. 1) is an important imtermediate used to synthesize a variety of pharmaceuticals, such as inhibitors of phenylethanolamine N-methyltransferase (Grunewald et al., 1996) and inhibitors of Farnesyltransferase (Ding et al., 1999). In our recent research for exploring new methods for synthesis of benzodiazepine derivatives, 4-acetyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine is synthesized in 96% yield from 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine (Ding et al., 1999). We report here the crystal structure of the title compound, which crystallizes in the tetragonal space group P4(3) with one H2O molecule in the asymmetric unit.

A view of the molecular structure of title compound is depicted in Fig.1. The central seven-membered ring has an chair conformation, which is consistent with reported exo conformational form with the C=O group turns away from benzene ring (Kim et al., 1976). All bond lengths and angles are normal (Allen et al., 1987). Molecules related by an c-axis translation are stacked over each other and stabilized by van de waals (Fig. 2). The stacked columns are linked together via an intermolecular hydrogen bond, in which the amine H1 act as a donor to H2O O1w atom and H2O H1A as a donor to H2O O1w atom (Fig. 2 and Table 1).

Related literature top

For related literature, see: Allen et al. (1987); Ding et al. (1999); Grunewald et al. (1996).

For related literature, see: Kim (1976).

Experimental top

Acetyl chloride (6 ml) was added dropwise to CH2Cl2 solution (80 ml) containing 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine (14.8 g, 0.1 mol) at ice-water bath. After addition, the reaction temperature was raised to room temperature. The resulting mixture was crashed to ice-water bath after stirring for 5 hrs. The organic layer was separated and dried over MgSO4. After filtration, the filtrate was evaporated to give an oil which can be crystallized from acetone to give title compound in 96% yield. Single crystals suitable for X-ray analysis (m.p. 358 K) were obtained by slow evaporation of a ethyl acetate/n-hexane/H2O solution at 298 K.

Refinement top

The water H atoms and imine H atom were located from Fourier difference maps and refined subject to an O—H restraint of 0.85Å and N—H 0.88 Å. Other H atoms were introduced at calculated positions (C—H = 0.93–0.97 Å) and refined using a riding model. The isotropic displacement parameters of all H atoms were set to 1.2 times Ueq of the parent atoms.

Computing details top

Data collection: SMART (Bruker, 2000); cell refinement: SMART (Bruker, 2000); data reduction: SAINT (Bruker, 2000); 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. View of the molecule of (I) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 2] Fig. 2. The crystal packing of (I), viewed along the c-axis. Hydrogen bonds are shown as dashed lines.
(I) top
Crystal data top
C11H14N2O·H2OF000 = 448
Mr = 208.26Dx = 1.248 Mg m−3
Tetragonal, P4(3)Melting point: 358 K
a = 10.8251 (8) ÅMo Kα radiation
λ = 0.71073 Å
b = 10.8251 (8) ÅCell parameters from 3047 reflections
c = 9.4569 (14) Åθ = 2.7–26.0º
α = 90ºµ = 0.09 mm−1
β = 90ºT = 296 (2) K
γ = 90ºBlock, colourless
V = 1108.2 (2) Å30.20 × 0.20 × 0.15 mm
Z = 4
Data collection top
Bruker SMART CCD
diffractometer		972 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.016
Monochromator: graphiteθmax = 25.0º
T = 296(2) Kθmin = 2.7º
phi and ω scansh = −12→8
Absorption correction: nonek = −12→12
5758 measured reflectionsl = −9→11
1043 independent reflections
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH atoms treated by a mixture of
independent and constrained refinement
R[F2 > 2σ(F2)] = 0.035  w = 1/[σ2(Fo2) + (0.0638P)2 + 0.1073P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.098(Δ/σ)max < 0.001
S = 1.07Δρmax = 0.21 e Å−3
1043 reflectionsΔρmin = −0.19 e Å−3
140 parametersExtinction correction: none
1 restraintAbsolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methodsFlack parameter: −10 (10)
Secondary atom site location: difference Fourier map
Crystal data top
C11H14N2O·H2Oγ = 90º
Mr = 208.26V = 1108.2 (2) Å3
Tetragonal, P4(3)Z = 4
a = 10.8251 (8) ÅMo Kα
b = 10.8251 (8) ŵ = 0.09 mm−1
c = 9.4569 (14) ÅT = 296 (2) K
α = 90º0.20 × 0.20 × 0.15 mm
β = 90º
Data collection top
Bruker SMART CCD
diffractometer		1043 independent reflections
Absorption correction: none972 reflections with I > 2σ(I)
5758 measured reflectionsRint = 0.016
Refinement top
R[F2 > 2σ(F2)] = 0.035H atoms treated by a mixture of
independent and constrained refinement
wR(F2) = 0.098Δρmax = 0.21 e Å−3
S = 1.07Δρmin = −0.19 e Å−3
1043 reflectionsAbsolute structure: Flack (1983)
140 parametersFlack parameter: −10 (10)
1 restraint
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
O1W0.40813 (19)0.43417 (18)0.4076 (2)0.0676 (6)
H1A0.44270.36410.39860.081*
H1B0.34010.43580.45250.081*
C10.6424 (2)0.9826 (2)0.3856 (3)0.0460 (5)
C20.7330 (3)1.0679 (2)0.4220 (3)0.0580 (7)
H20.74621.13620.36420.070*
C30.8037 (3)1.0533 (3)0.5422 (3)0.0701 (8)
H30.86391.11120.56530.084*
C40.7843 (3)0.9525 (3)0.6272 (3)0.0735 (9)
H40.83100.94250.70900.088*
C50.6966 (3)0.8663 (3)0.5923 (3)0.0638 (8)
H50.68530.79800.65050.077*
C60.6240 (2)0.8789 (2)0.4716 (3)0.0490 (6)
C70.5295 (3)0.7284 (2)0.3073 (4)0.0613 (7)
H7A0.47920.65470.31640.074*
H7B0.61330.70230.28670.074*
C80.4817 (2)0.8038 (3)0.1833 (3)0.0604 (7)
H8A0.47600.75160.10020.072*
H8B0.39960.83430.20470.072*
C90.5604 (2)1.0065 (2)0.2601 (3)0.0514 (6)
H9A0.47611.01640.29280.062*
H9B0.58531.08350.21600.062*
C100.6485 (2)0.8995 (2)0.0517 (3)0.0513 (6)
C110.7359 (3)1.0053 (3)0.0322 (3)0.0689 (8)
H11A0.79500.9850−0.03980.103*
H11B0.77831.02130.11950.103*
H11C0.69061.07760.00440.103*
N10.5291 (2)0.7936 (2)0.4415 (3)0.0596 (6)
N20.56359 (19)0.90814 (18)0.1536 (2)0.0500 (5)
O10.6565 (2)0.80907 (18)−0.0269 (2)0.0685 (6)
H10.519 (3)0.747 (4)0.517 (5)0.082*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O1W0.0770 (13)0.0662 (11)0.0596 (12)0.0001 (9)−0.0051 (10)0.0138 (10)
C10.0511 (12)0.0457 (12)0.0412 (12)0.0081 (10)0.0042 (10)−0.0016 (10)
C20.0669 (16)0.0523 (13)0.0547 (16)0.0004 (12)0.0037 (13)−0.0129 (12)
C30.0711 (18)0.0773 (19)0.0620 (19)0.0076 (15)−0.0121 (15)−0.0284 (16)
C40.0722 (19)0.101 (2)0.0476 (16)0.0341 (18)−0.0147 (14)−0.0216 (17)
C50.0764 (18)0.0692 (17)0.0457 (15)0.0306 (15)0.0060 (14)0.0082 (13)
C60.0502 (13)0.0513 (13)0.0455 (13)0.0126 (10)0.0072 (11)0.0053 (11)
C70.0599 (15)0.0437 (13)0.080 (2)−0.0070 (11)0.0064 (14)0.0074 (14)
C80.0514 (13)0.0617 (15)0.0682 (19)−0.0105 (11)−0.0053 (13)−0.0020 (14)
C90.0596 (14)0.0441 (12)0.0507 (15)0.0070 (11)−0.0044 (12)0.0048 (11)
C100.0640 (15)0.0508 (13)0.0392 (12)−0.0015 (11)−0.0085 (12)0.0050 (11)
C110.087 (2)0.0663 (17)0.0529 (17)−0.0163 (15)0.0089 (15)0.0064 (14)
N10.0602 (13)0.0577 (13)0.0610 (15)0.0020 (10)0.0131 (12)0.0183 (12)
N20.0582 (12)0.0469 (11)0.0449 (11)−0.0001 (9)−0.0078 (10)0.0040 (9)
O10.0907 (14)0.0624 (11)0.0525 (11)−0.0061 (10)0.0010 (11)−0.0097 (10)
Geometric parameters (Å, °) top
O1W—H1A0.8500C7—H7A0.9700
O1W—H1B0.8499C7—H7B0.9700
C1—C21.390 (4)C8—N21.463 (3)
C1—C61.401 (4)C8—H8A0.9700
C1—C91.505 (3)C8—H8B0.9700
C2—C31.379 (4)C9—N21.466 (3)
C2—H20.9300C9—H9A0.9700
C3—C41.372 (5)C9—H9B0.9700
C3—H30.9300C10—O11.233 (3)
C4—C51.372 (5)C10—N21.334 (3)
C4—H40.9300C10—C111.497 (4)
C5—C61.392 (4)C11—H11A0.9600
C5—H50.9300C11—H11B0.9600
C6—N11.411 (4)C11—H11C0.9600
C7—N11.452 (4)N1—H10.88 (4)
C7—C81.519 (4)
H1A—O1W—H1B116.8N2—C8—H8A109.5
C2—C1—C6119.3 (3)C7—C8—H8A109.5
C2—C1—C9119.9 (2)N2—C8—H8B109.5
C6—C1—C9120.8 (2)C7—C8—H8B109.5
C3—C2—C1121.3 (3)H8A—C8—H8B108.0
C3—C2—H2119.4N2—C9—C1113.81 (19)
C1—C2—H2119.4N2—C9—H9A108.8
C4—C3—C2119.3 (3)C1—C9—H9A108.8
C4—C3—H3120.3N2—C9—H9B108.8
C2—C3—H3120.3C1—C9—H9B108.8
C5—C4—C3120.4 (3)H9A—C9—H9B107.7
C5—C4—H4119.8O1—C10—N2122.7 (2)
C3—C4—H4119.8O1—C10—C11119.2 (3)
C4—C5—C6121.4 (3)N2—C10—C11118.1 (2)
C4—C5—H5119.3C10—C11—H11A109.5
C6—C5—H5119.3C10—C11—H11B109.5
C5—C6—C1118.3 (3)H11A—C11—H11B109.5
C5—C6—N1120.8 (2)C10—C11—H11C109.5
C1—C6—N1120.7 (2)H11A—C11—H11C109.5
N1—C7—C8114.4 (2)H11B—C11—H11C109.5
N1—C7—H7A108.7C6—N1—C7119.5 (2)
C8—C7—H7A108.7C6—N1—H1107 (3)
N1—C7—H7B108.7C7—N1—H1116 (3)
C8—C7—H7B108.7C10—N2—C8120.1 (2)
H7A—C7—H7B107.6C10—N2—C9124.3 (2)
N2—C8—C7110.9 (2)C8—N2—C9114.5 (2)
C6—C1—C2—C3−1.0 (4)C6—C1—C9—N2−60.6 (3)
C9—C1—C2—C3175.2 (2)C5—C6—N1—C7−123.7 (3)
C1—C2—C3—C40.1 (4)C1—C6—N1—C760.3 (3)
C2—C3—C4—C50.7 (4)C8—C7—N1—C6−79.0 (3)
C3—C4—C5—C6−0.8 (4)O1—C10—N2—C85.0 (4)
C4—C5—C6—C1−0.1 (4)C11—C10—N2—C8−175.7 (3)
C4—C5—C6—N1−176.2 (3)O1—C10—N2—C9172.1 (2)
C2—C1—C6—C50.9 (3)C11—C10—N2—C9−8.6 (4)
C9—C1—C6—C5−175.3 (2)C7—C8—N2—C1097.6 (3)
C2—C1—C6—N1177.0 (2)C7—C8—N2—C9−70.8 (3)
C9—C1—C6—N10.8 (3)C1—C9—N2—C10−84.2 (3)
N1—C7—C8—N265.5 (3)C1—C9—N2—C883.6 (3)
C2—C1—C9—N2123.2 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1Wi0.88 (5)2.33 (4)3.163 (3)158 (4)
Symmetry codes: (i) y, −x+1, z+1/4.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1Wi0.88 (5)2.33 (4)3.163 (3)158 (4)
Symmetry codes: (i) y, −x+1, z+1/4.
Acknowledgements top

Acknowledgement is made to the crew of Topharman Shanghai Co. Ltd for their active cooperation in this work. We also thank the Instrument Analysis and Research Center of Shanghai University for structural confirmation.

references
References top

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