5-Dichloro­acetyl-4-methyl-2,3,4,5-tetra­hydro-1H-1,5-benzodiazepin-2-one hemihydrate

K Ravichandran; P Sakthivel; S Ponnuswamy; M Shalini; M N Ponnuswamy

doi:10.1107/S1600536809036940

. 2009 Sep 26;65(Pt 10):o2551–o2552. doi: 10.1107/S1600536809036940

5-Dichloroacetyl-4-methyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-one hemihydrate

K Ravichandran ^a, P Sakthivel ^b, S Ponnuswamy ^b, M Shalini ^b, M N Ponnuswamy ^a,^*

PMCID: PMC2970202 PMID: 21577993

Abstract

There are two crystallographically independent organic molecules in the asymmetric unit of the title compound, C₁₂H₁₂Cl₂N₂O₂·0.5H₂O. The benzodiazepine ring adopts a distorted boat conformation in both molecules. The crystal packing is controlled by N—H⋯O, C—H⋯O and O—H⋯O intra- and intermolecular hydrogen bonds. A graph-set motif of R ³ ₃(14) dimer formation by a combination of N—H⋯O, O—H⋯O and C—H⋯O hydrogen bonds stabilizes the molecules and extends along a axis.

Related literature

For the anticonvulsant activity of benzodiazepine, see: MacDonald (2002 ▶). For their hypnotic effect, see: Gringauz (1999 ▶). For their use in the treatment of gastrointestinal and central nervous system disorders, see: Rahbaek et al. (1999 ▶). For other therapeutic applications, see: Albright et al. (1998 ▶); Lee et al. (1999 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For puckering and asymmetry parameters, see: Cremer & Pople (1975 ▶); Nardelli (1983 ▶). For details of the preparation of the title compound, see: Venkatraj et al. (2008 ▶).

Experimental

Crystal data

C₁₂H₁₂Cl₂N₂O₂·0.5H₂O
M _r = 592.29
Monoclinic,
a = 8.5470 (3) Å
b = 18.0837 (6) Å
c = 8.8697 (3) Å
β = 95.405 (2)°
V = 1364.82 (8) Å³
Z = 2
Mo Kα radiation
μ = 0.48 mm⁻¹
T = 293 K
0.26 × 0.24 × 0.22 mm

Data collection

Bruker Kappa APEXII area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2001 ▶) T _min = 0.884, T _max = 0.901
14191 measured reflections
5599 independent reflections
4873 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.110
S = 1.04
5599 reflections
352 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.46 e Å⁻³
Δρ_min = −0.62 e Å⁻³
Absolute structure: Flack (1983 ▶), 2698 Friedel pairs
Flack parameter: 0.06 (6)

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809036940/bt5048sup1.cif

e-65-o2551-sup1.cif^{(25.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809036940/bt5048Isup2.hkl

e-65-o2551-Isup2.hkl^{(268.6KB, hkl)}

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
N1A—H1A⋯O3	0.87 (4)	2.08 (4)	2.927 (4)	164 (3)
O3—H2W⋯O1Bⁱ	0.80 (4)	2.02 (4)	2.815 (4)	173 (4)
C8A—H8A⋯O2Aⁱⁱ	0.93	2.51	3.268 (4)	139
C10B—H10B⋯O2Bⁱⁱⁱ	0.93	2.39	3.179 (4)	143

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

KR thanks Dr Babu Varghese, SAIF, IIT-Madras, India, for his help with the data collection and the management of Kandaswami Kandar’s College, Velur, Namakkal, India, for their encouragement to pursue the programme.

supplementary crystallographic information

Comment

The anticonvulsant activity of benzodiazepines has been utilized clinically in patients to treat specific seizure types or conditions, i.e., akinetic, myoclonic, absence variant seizures as well as to help terminate status epilepticusor serial seizures (MacDonald, 2002). Benzodiazepines are used for the purpose of hypnotic effects, owing to their less toxic and less severe withdrawal effects when compared with barbiturates (Gringauz, 1999). Benzodiazepines from aspergillus include asperlicin, which is used for treatment of gastrointestinal and central nervous system (CNS) disorders (Rahbaek et al.,1999). The other therapeutic applications (Lee et al., 1999) of benzodiazepines include vasopressin antagonists (Albright et al., 1998). In view of these importance and to ascertain the molecular conformation, crystallographic study of the title compound has been carried out.

The ORTEP diagram of the title compound is shown in Fig.1. There are two crystallographically independent molecules in the asymmetric unit. The benzodiazepine rings in the two molecules adopt a distorted boat conformation. The puckering parameters (Cremer & Pople, 1975) and the asymmetry parameters (Nardelli, 1983) for the ring in molecule A are: q₂ = 0.959 (3) Å, q₃ = 0.150 (3) Å, φ₂ = 136.1 (2)°, φ₃ = 359.8 (1)° and Δ2(C4A)= 8.1 (3)°; for the ring in molecule B are: q₂ = 0.962 (3) Å, q₃ = 0.168 (3) Å, φ₂ = 141.4 (2)°, φ₃ = 5.3 (1)° and Δ2(C4B)= 3.4 (3)°. The sum of the bond angles at N1A(359.0°), N1B(359.2), N5A(358.8) and N5B(359.9°) of the benzodiazepine rings in both the molecules are in accordance with sp² hybridization.

The crystal packing is controlled by N—H···O, C—H···O and O—H···O types of intermolecular interactions in addition to van der Waals forces. The water molecule connects the molecules A and B through N1A—H1A···O3 and O3—H2W···O1B hydrogen bonds. Thus the combination of N1A—H1A···O3, O3—H2W···O1B and C3A—H3A···O2B hydrogen bonds form a graph set motif of R³₃(14) dimer (Bernstein et al., 1995) which stabilize the molecules. Atom C8A at (x, y, z) donates a proton to O2A (x - 1, y, z), which forms a C7 one dimensional chain running along a–axis. The intermolecular hydrogen bond C10B—H10B···O2B also connects the molecule into an another C7 chain running along b–axis (Fig. 2).

Experimental

To a solution of tetrahydro-4-methyl-1,5-benzodiazepin-2-one (0.88 g) in anhydrous benzene (50 ml) was added triethylamine (2.8 ml) and dichloroacetyl chloride (1.90 ml). The contents were allowed to reflux on a water bath for 6hrs. The reaction mixture was washed with sodium bicarbonate solution (10%), water and dried. Evaporation of the solvent results a crude mass and further crystallization from ethanol gives colorless crystals (Venkatraj et al., 2008).