rac-(3S,4S)-3-Hy­droxy-4-phenyl-1-[(S)-(3-phenyl-4,5-dihydro-1,2-oxazol-5-yl)meth­yl]-4,5-dihydro-1H-1,5-benzo­diazepin-2(3H)-one

Mohamed Rida; El Mokhtar Essassi; Stéphane Massip; Saïd Lazar; Hafid Zouihri

doi:10.1107/S1600536811010129

. 2011 Mar 23;67(Pt 4):o945–o946. doi: 10.1107/S1600536811010129

rac-(3S,4S)-3-Hydroxy-4-phenyl-1-[(S)-(3-phenyl-4,5-dihydro-1,2-oxazol-5-yl)methyl]-4,5-dihydro-1H-1,5-benzodiazepin-2(3H)-one

Mohamed Rida ^a,^*, El Mokhtar Essassi ^a,^b, Stéphane Massip ^c, Saïd Lazar ^d, Hafid Zouihri ^e

PMCID: PMC3100042 PMID: 21754212

Abstract

In the title compound, C₂₅H₂₃N₃O₃, the seven-membered diazepine ring adopts a boat conformation with the hydroxy-substituted C atom at the prow and fused-ring C atoms at the stern. The crystal packing features C—H⋯O, C—H⋯π and N—H ⋯π interactions

Related literature

For the preparation and biological activity of benzodiazepines, see: Ahabchane et al. (1999 ▶), Grunewald et al. (1996 ▶); Ding et al., (1999 ▶). For related structures, see: Saber et al. (2010a ▶,b ▶); Ballo et al. (2010 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₂₅H₂₃N₃O₃
M _r = 413.46
Triclinic,
a = 8.981 (2) Å
b = 9.044 (2) Å
c = 13.685 (1) Å
α = 95.373 (10)°
β = 102.433 (10)°
γ = 100.03 (2)°
V = 1058.9 (3) Å³
Z = 2
Cu Kα radiation
μ = 0.70 mm⁻¹
T = 293 K
0.15 × 0.10 × 0.08 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (North et al., 1968 ▶) T _min = 0.903, T _max = 0.946
3584 measured reflections
3584 independent reflections
3232 reflections with I > 2σ(I)
R _int = 0.000
2 standard reflections every 90 min intensity decay: none

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.157
S = 1.05
3584 reflections
286 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ▶); cell refinement: CAD-4 Software; data reduction: CAD-4 Software; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811010129/ld2003sup1.cif

e-67-0o945-sup1.cif^{(24.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811010129/ld2003Isup2.hkl

e-67-0o945-Isup2.hkl^{(175.7KB, hkl)}

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

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

Cg4 is the centroid of the C26–C31 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C16—H16⋯O22	0.93	2.44	3.206 (3)	140
C25—H25a⋯O14ⁱ	0.97	2.59	3.493 (3)	154
C27—H27⋯O15ⁱⁱ	0.93	2.40	3.302 (3)	162
C28—H28⋯O22ⁱ	0.93	2.52	3.152 (2)	125
C19—H19⋯Cg4ⁱⁱⁱ	0.93	2.78	3.534 (3)	139
N13—H13⋯Cg4ⁱⁱⁱ	0.93 (2)	2.77 (2)	3.671 (3)	164

Open in a new tab

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

supplementary crystallographic information

Comment

Benzodiazipines have found wide-spread clinical use as inhibitors of phenylethanolamine N-methyltransferase [Grunewald et al., 1996] and inhibitors of farnesyltransferase [Ding et al., 1999]. In view of their importance and to ascertain molecular conformation [Ahabchane et al., 1999. Saber et al. (2010a and 2010b) and Ballo et al. (2010)], a crystallographic study of the title compound has been carried out.

The molecular structure of the title compound is depicted in Fig.1. The seven-membred ring adopts a boat conformation with equatorial orientations of both phenyl and hydroxyl substituents. Its puckering parameters [Cremer & Pople, 1975] are q₂ = 0.997 (2) Å, q₃ = 0.1541 (19) Å, φ₂ = 317.05 (11)°, φ₃ = 185.2 (8)°.

Phenyl substituent at C24 atom is rotated out of the plane of the 4,5-dihydro-1,2-oxazole ring by 20.1 (1)°.

The crystal packing is controlled by C—H···O H-bonds and C—H ···π and N—H ···π interactions involving the C26-C31 (Cg4) benzene ring (Table 1).

Experimental

A solution of NaOCl (10 ml) was added to a mixture of 1-allylmethyl-3-hydroxy-4-phenyltetrahydro-1,5-benzodiazepin-2-one (2.58 g, 0.01 mmol) and benzaldoxime (1.21 g, 0.01 mmol) in chloroform (30 ml) under vigorous stirring. After 3 h, the organic layer was washed with water and dried by addition of anhydrous MgSO₄. After removal of the solvent by evaporation, the crude residual mixture obtained was purified by column chromatography on a silica gel column and eluted with an eluent composed of ether/petroleum ether (1/9). Crystals was obtained when solvent was allowed to evaporate.