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

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.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.036
• wR factor = 0.099
• Data-to-parameter ratio = 7.4

checkCIF/PLATON results

No syntax errors found



Alert level A
DIFF019_ALERT_1_A  _diffrn_standards_number is missing
            Number of standards used in measurement.
DIFF020_ALERT_1_A  _diffrn_standards_interval_count and
            _diffrn_standards_interval_time are missing. Number of measurements
            between standards or time (min) between standards.
DIFF022_ALERT_1_A  _diffrn_standards_decay_% is missing
            Percentage decrease in standards intensity.
PLAT707_ALERT_1_A D...A   Calc   12.821(3), Rep    2.794(3), Dev..    3342.33 Sigma
              O1W  -O1W     1.555   3.665
PLAT726_ALERT_1_A H...A   Calc    12.70000, Rep     2.27000 Dev...      10.43 Ang.
              H1B  -O1W     1.555   3.665
PLAT728_ALERT_1_A D-H..A  Calc       96.00, Rep      120.00 Dev...      24.00 Deg.
              O1W  -H1B  -O1W     1.555   1.555   3.665

Alert level B
PLAT420_ALERT_2_B D-H Without Acceptor       O1W    -   H1B    ...          ?

Alert level C
ABSTY03_ALERT_1_C  The _exptl_absorpt_correction_type has been given as none.
            However values have been given for Tmin and Tmax. Remove
            these if an absorption correction has not been applied.
  From the CIF: _exptl_absorpt_correction_T_min   0.983
  From the CIF: _exptl_absorpt_correction_T_max   0.987
STRVA01_ALERT_4_C           Flack parameter is too small
           From the CIF: _refine_ls_abs_structure_Flack  -10.000
           From the CIF: _refine_ls_abs_structure_Flack_su   10.000
PLAT032_ALERT_4_C Std. Uncertainty in Flack Parameter too High ...      10.00
PLAT033_ALERT_2_C Flack Parameter Value Deviates from zero .......     -10.00
PLAT048_ALERT_1_C MoietyFormula Not Given ........................          ?
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) .....       7.45
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           25.02
           From the CIF: _reflns_number_total               1043
           Count of symmetry unique reflns         1044
           Completeness (_total/calc)             99.90%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          1

   6 ALERT level A = In general: serious problem
   1 ALERT level B = Potentially serious problem
   8 ALERT level C = Check and explain
   2 ALERT level G = General alerts; check

   9 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   2 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   4 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. 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).

Related literature

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

For related literature, see: Kim (1976).

S2. 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.

S3. 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.

Computing details

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

	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)

Crystal data

C11H14N2O·H2O	Melting point: 358 K
Mr = 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) Å^3	T = 296 K
Z = 4	Block, colourless
F(000) = 448	0.20 × 0.20 × 0.15 mm
Dx = 1.248 Mg m^−3

Data collection

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

Refinement

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

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)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

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)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1W^i	0.88 (5)	2.33 (4)	3.163 (3)	158 (4)

Symmetry code: (i) y, −x+1, z+1/4.