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

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

doi:10.1107/S1600536808007927

organic compounds

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ISSN: 2056-9890

Volume 64| Part 6| June 2008| Page o969

doi:10.1107/S1600536808007927

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

Qing-Jie Zhao,^a Zheng Liu,^a Jin Zheng ^a and Jing-Shan Shen ^a ^*

^aShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People's Republic of China
^*Correspondence e-mail: jsshen@mail.shcnc.ac.cn

(Received 3 March 2008; accepted 24 March 2008; online 3 May 2008)

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, P 4₃
a = 10.8251 (8) Å
c = 9.4569 (14) Å
V = 1108.2 (2) Å³
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[F² > 2σ(F²)] = 0.035
wR(F²) = 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

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) $[y, -x+1, z+{\script{1\over 4}}]$ ; (ii) $[-y+1, x+1, z+{\script{3\over 4}}]$ .

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.

Supporting information

Crystal structure: contains datablocks I, New_Global_Publ_Block. DOI: 10.1107/S1600536808007927/om2218sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808007927/om2218Isup2.hkl

checkCIF report

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.

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

	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.

(I) top

Crystal data top

C₁₁H₁₄N₂O·H₂O	Melting point: 358 K
M_r = 208.26	Mo Kα radiation, λ = 0.71073 Å
Tetragonal, P4₃	Cell parameters from 3047 reflections
a = 10.8251 (8) Å	θ = 2.7–26.0°
c = 9.4569 (14) Å	µ = 0.09 mm⁻¹
V = 1108.2 (2) Å³	T = 296 K
Z = 4	Block, colourless
F(000) = 448	0.20 × 0.20 × 0.15 mm
D_x = 1.248 Mg m⁻³

Data collection top

Bruker SMART CCD diffractometer	972 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.016
Graphite monochromator	θ_max = 25.0°, θ_min = 2.7°
phi and ω scans	h = −12→8
5758 measured reflections	k = −12→12
1043 independent reflections	l = −9→11

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.035	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.098	w = 1/[σ²(F_o²) + (0.0638P)² + 0.1073P] where P = (F_o² + 2F_c²)/3
S = 1.07	(Δ/σ)_max < 0.001
1043 reflections	Δρ_max = 0.21 e Å⁻³
140 parameters	Δρ_min = −0.20 e Å⁻³
1 restraint	Absolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −10 (10)

Crystal data top

C₁₁H₁₄N₂O·H₂O	Z = 4
M_r = 208.26	Mo Kα radiation
Tetragonal, P4₃	µ = 0.09 mm⁻¹
a = 10.8251 (8) Å	T = 296 K
c = 9.4569 (14) Å	0.20 × 0.20 × 0.15 mm
V = 1108.2 (2) Å³

Data collection top

Bruker SMART CCD diffractometer	972 reflections with I > 2σ(I)
5758 measured reflections	R_int = 0.016
1043 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.035	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.098	Δρ_max = 0.21 e Å⁻³
S = 1.07	Δρ_min = −0.20 e Å⁻³
1043 reflections	Absolute structure: Flack (1983)
140 parameters	Absolute structure 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

	x	y	z	U_iso*/U_eq
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 (Å²) top

	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, º) top

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, º) top

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 code: (i) y, −x+1, z+1/4.

Experimental details

Crystal data
Chemical formula	C₁₁H₁₄N₂O·H₂O
M_r	208.26
Crystal system, space group	Tetragonal, P4₃
Temperature (K)	296
a, c (Å)	10.8251 (8), 9.4569 (14)
V (Å³)	1108.2 (2)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.20 × 0.20 × 0.15

Data collection
Diffractometer	Bruker SMART CCD diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	5758, 1043, 972
R_int	0.016
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.035, 0.098, 1.07
No. of reflections	1043
No. of parameters	140
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.21, −0.20
Absolute structure	Flack (1983)
Absolute structure parameter	−10 (10)

Computer programs: SMART (Bruker, 2000), SAINT (Bruker, 2000), 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—H1···O1Wⁱ	0.88 (5)	2.33 (4)	3.163 (3)	158 (4)

Symmetry code: (i) y, −x+1, z+1/4.

Acknowledgements

Acknowledgement is made to the staff 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

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