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

Abstract

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.

Related literature

For related literature, see: Allen et al. (1987 ▶); Ding et al. (1999 ▶); Grunewald et al. (1996 ▶); Kim (1976 ▶).

Experimental

Crystal data

• C₁₁H₁₄N₂O·H₂O

• M _r = 208.26

• Tetragonal,

• a = 10.8251 (8) Å

• c = 9.4569 (14) Å

• V = 1108.2 (2) ų

• Z = 4

• Mo Kα radiation

• μ = 0.09 mm⁻¹

• T = 296 (2) K

• 0.20 × 0.20 × 0.15 mm

Data collection

• Bruker APEXII CCD diffractometer

• Absorption correction: none

• 5758 measured reflections

• 1043 independent reflections

• 972 reflections with I > 2σ(I)

• R _int = 0.016

Refinement

• R[F ² > 2σ(F ²)] = 0.035

• wR(F ²) = 0.098

• S = 1.07

• 1043 reflections

• 140 parameters

• 1 restraint

• H atoms treated by a mixture of independent and constrained refinement

• Δρ_max = 0.21 e Å⁻³

• Δρ_min = −0.20 e Å⁻³

Data collection: APEX2 (Bruker, 2000 ▶); cell refinement: SAINT (Bruker, 2000 ▶); data reduction: SAINT; 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.

Supplementary Material

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1Wi	0.88 (5)	2.33 (4)	3.163 (3)	158 (4)

Symmetry codes: (i) ; (ii) .

supplementary crystallographic information

Comment

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).

Experimental

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

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 U_eq of the parent atoms.

Figures

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.

Fig. 2.

The crystal packing of (I), viewed along the c-axis. Hydrogen bonds are shown as dashed lines.

Crystal data

C11H14N2O·H2O	F000 = 448
Mr = 208.26	Dx = 1.248 Mg m−3
Tetragonal, P4(3)	Melting point: 358 K
a = 10.8251 (8) Å	Mo Kα radiation λ = 0.71073 Å
b = 10.8251 (8) Å	Cell parameters from 3047 reflections
c = 9.4569 (14) Å	θ = 2.7–26.0º
α = 90º	µ = 0.09 mm−1
β = 90º	T = 296 (2) K
γ = 90º	Block, colourless
V = 1108.2 (2) Å3	0.20 × 0.20 × 0.15 mm
Z = 4

Data collection

Bruker SMART CCD diffractometer	972 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.016
Monochromator: graphite	θmax = 25.0º
T = 296(2) K	θmin = 2.7º
phi and ω scans	h = −12→8
Absorption correction: none	k = −12→12
5758 measured reflections	l = −9→11
1043 independent reflections

Refinement

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H 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 = 1.07	Δρmax = 0.21 e Å−3
1043 reflections	Δρmin = −0.19 e Å−3
140 parameters	Extinction correction: none
1 restraint	Absolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methods	Flack parameter: −10 (10)
Secondary atom site location: difference Fourier map

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
O1W	0.40813 (19)	0.43417 (18)	0.4076 (2)	0.0676 (6)
H1A	0.4427	0.3641	0.3986	0.081*
H1B	0.3401	0.4358	0.4525	0.081*
C1	0.6424 (2)	0.9826 (2)	0.3856 (3)	0.0460 (5)
C2	0.7330 (3)	1.0679 (2)	0.4220 (3)	0.0580 (7)
H2	0.7462	1.1362	0.3642	0.070*
C3	0.8037 (3)	1.0533 (3)	0.5422 (3)	0.0701 (8)
H3	0.8639	1.1112	0.5653	0.084*
C4	0.7843 (3)	0.9525 (3)	0.6272 (3)	0.0735 (9)
H4	0.8310	0.9425	0.7090	0.088*
C5	0.6966 (3)	0.8663 (3)	0.5923 (3)	0.0638 (8)
H5	0.6853	0.7980	0.6505	0.077*
C6	0.6240 (2)	0.8789 (2)	0.4716 (3)	0.0490 (6)
C7	0.5295 (3)	0.7284 (2)	0.3073 (4)	0.0613 (7)
H7A	0.4792	0.6547	0.3164	0.074*
H7B	0.6133	0.7023	0.2867	0.074*
C8	0.4817 (2)	0.8038 (3)	0.1833 (3)	0.0604 (7)
H8A	0.4760	0.7516	0.1002	0.072*
H8B	0.3996	0.8343	0.2047	0.072*
C9	0.5604 (2)	1.0065 (2)	0.2601 (3)	0.0514 (6)
H9A	0.4761	1.0164	0.2928	0.062*
H9B	0.5853	1.0835	0.2160	0.062*
C10	0.6485 (2)	0.8995 (2)	0.0517 (3)	0.0513 (6)
C11	0.7359 (3)	1.0053 (3)	0.0322 (3)	0.0689 (8)
H11A	0.7950	0.9850	−0.0398	0.103*
H11B	0.7783	1.0213	0.1195	0.103*
H11C	0.6906	1.0776	0.0044	0.103*
N1	0.5291 (2)	0.7936 (2)	0.4415 (3)	0.0596 (6)
N2	0.56359 (19)	0.90814 (18)	0.1536 (2)	0.0500 (5)
O1	0.6565 (2)	0.80907 (18)	−0.0269 (2)	0.0685 (6)
H1	0.519 (3)	0.747 (4)	0.517 (5)	0.082*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1W	0.0770 (13)	0.0662 (11)	0.0596 (12)	0.0001 (9)	−0.0051 (10)	0.0138 (10)
C1	0.0511 (12)	0.0457 (12)	0.0412 (12)	0.0081 (10)	0.0042 (10)	−0.0016 (10)
C2	0.0669 (16)	0.0523 (13)	0.0547 (16)	0.0004 (12)	0.0037 (13)	−0.0129 (12)
C3	0.0711 (18)	0.0773 (19)	0.0620 (19)	0.0076 (15)	−0.0121 (15)	−0.0284 (16)
C4	0.0722 (19)	0.101 (2)	0.0476 (16)	0.0341 (18)	−0.0147 (14)	−0.0216 (17)
C5	0.0764 (18)	0.0692 (17)	0.0457 (15)	0.0306 (15)	0.0060 (14)	0.0082 (13)
C6	0.0502 (13)	0.0513 (13)	0.0455 (13)	0.0126 (10)	0.0072 (11)	0.0053 (11)
C7	0.0599 (15)	0.0437 (13)	0.080 (2)	−0.0070 (11)	0.0064 (14)	0.0074 (14)
C8	0.0514 (13)	0.0617 (15)	0.0682 (19)	−0.0105 (11)	−0.0053 (13)	−0.0020 (14)
C9	0.0596 (14)	0.0441 (12)	0.0507 (15)	0.0070 (11)	−0.0044 (12)	0.0048 (11)
C10	0.0640 (15)	0.0508 (13)	0.0392 (12)	−0.0015 (11)	−0.0085 (12)	0.0050 (11)
C11	0.087 (2)	0.0663 (17)	0.0529 (17)	−0.0163 (15)	0.0089 (15)	0.0064 (14)
N1	0.0602 (13)	0.0577 (13)	0.0610 (15)	0.0020 (10)	0.0131 (12)	0.0183 (12)
N2	0.0582 (12)	0.0469 (11)	0.0449 (11)	−0.0001 (9)	−0.0078 (10)	0.0040 (9)
O1	0.0907 (14)	0.0624 (11)	0.0525 (11)	−0.0061 (10)	0.0010 (11)	−0.0097 (10)

Geometric parameters (Å, °)

O1W—H1A	0.8500	C7—H7A	0.9700
O1W—H1B	0.8499	C7—H7B	0.9700
C1—C2	1.390 (4)	C8—N2	1.463 (3)
C1—C6	1.401 (4)	C8—H8A	0.9700
C1—C9	1.505 (3)	C8—H8B	0.9700
C2—C3	1.379 (4)	C9—N2	1.466 (3)
C2—H2	0.9300	C9—H9A	0.9700
C3—C4	1.372 (5)	C9—H9B	0.9700
C3—H3	0.9300	C10—O1	1.233 (3)
C4—C5	1.372 (5)	C10—N2	1.334 (3)
C4—H4	0.9300	C10—C11	1.497 (4)
C5—C6	1.392 (4)	C11—H11A	0.9600
C5—H5	0.9300	C11—H11B	0.9600
C6—N1	1.411 (4)	C11—H11C	0.9600
C7—N1	1.452 (4)	N1—H1	0.88 (4)
C7—C8	1.519 (4)
H1A—O1W—H1B	116.8	N2—C8—H8A	109.5
C2—C1—C6	119.3 (3)	C7—C8—H8A	109.5
C2—C1—C9	119.9 (2)	N2—C8—H8B	109.5
C6—C1—C9	120.8 (2)	C7—C8—H8B	109.5
C3—C2—C1	121.3 (3)	H8A—C8—H8B	108.0
C3—C2—H2	119.4	N2—C9—C1	113.81 (19)
C1—C2—H2	119.4	N2—C9—H9A	108.8
C4—C3—C2	119.3 (3)	C1—C9—H9A	108.8
C4—C3—H3	120.3	N2—C9—H9B	108.8
C2—C3—H3	120.3	C1—C9—H9B	108.8
C5—C4—C3	120.4 (3)	H9A—C9—H9B	107.7
C5—C4—H4	119.8	O1—C10—N2	122.7 (2)
C3—C4—H4	119.8	O1—C10—C11	119.2 (3)
C4—C5—C6	121.4 (3)	N2—C10—C11	118.1 (2)
C4—C5—H5	119.3	C10—C11—H11A	109.5
C6—C5—H5	119.3	C10—C11—H11B	109.5
C5—C6—C1	118.3 (3)	H11A—C11—H11B	109.5
C5—C6—N1	120.8 (2)	C10—C11—H11C	109.5
C1—C6—N1	120.7 (2)	H11A—C11—H11C	109.5
N1—C7—C8	114.4 (2)	H11B—C11—H11C	109.5
N1—C7—H7A	108.7	C6—N1—C7	119.5 (2)
C8—C7—H7A	108.7	C6—N1—H1	107 (3)
N1—C7—H7B	108.7	C7—N1—H1	116 (3)
C8—C7—H7B	108.7	C10—N2—C8	120.1 (2)
H7A—C7—H7B	107.6	C10—N2—C9	124.3 (2)
N2—C8—C7	110.9 (2)	C8—N2—C9	114.5 (2)
C6—C1—C2—C3	−1.0 (4)	C6—C1—C9—N2	−60.6 (3)
C9—C1—C2—C3	175.2 (2)	C5—C6—N1—C7	−123.7 (3)
C1—C2—C3—C4	0.1 (4)	C1—C6—N1—C7	60.3 (3)
C2—C3—C4—C5	0.7 (4)	C8—C7—N1—C6	−79.0 (3)
C3—C4—C5—C6	−0.8 (4)	O1—C10—N2—C8	5.0 (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—C9	172.1 (2)
C2—C1—C6—C5	0.9 (3)	C11—C10—N2—C9	−8.6 (4)
C9—C1—C6—C5	−175.3 (2)	C7—C8—N2—C10	97.6 (3)
C2—C1—C6—N1	177.0 (2)	C7—C8—N2—C9	−70.8 (3)
C9—C1—C6—N1	0.8 (3)	C1—C9—N2—C10	−84.2 (3)
N1—C7—C8—N2	65.5 (3)	C1—C9—N2—C8	83.6 (3)
C2—C1—C9—N2	123.2 (3)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1Wi	0.88 (5)	2.33 (4)	3.163 (3)	158 (4)

Symmetry codes: (i) y, −x+1, z+1/4.