Ethyl 5,5-dichloro-3-(4-chloro­phen­yl)-3a-methyl-4a-phenyl-3a,4,4a,5-tetra­hydro-3H-aziridino[2,1-d][1,2,4]triazolo[4,3-a][1,5]benzodiazepine-1-carboxyl­ate

Aicha Boudina; Abdesselam Baouid; Mohamed Driss; El Hassane Soumhi

doi:10.1107/S1600536811014115

. 2011 Apr 29;67(Pt 5):o1211. doi: 10.1107/S1600536811014115

Ethyl 5,5-dichloro-3-(4-chlorophenyl)-3a-methyl-4a-phenyl-3a,4,4a,5-tetrahydro-3H-aziridino[2,1-d][1,2,4]triazolo[4,3-a][1,5]benzodiazepine-1-carboxylate

Aicha Boudina ^a, Abdesselam Baouid ^a, Mohamed Driss ^b, El Hassane Soumhi ^c,^*

PMCID: PMC3089256 PMID: 21754510

Abstract

In the title compound, C₂₇H₂₃Cl₃N₄O₂, the seven-membered diazepine ring adopts a boat conformation. The triazole ring makes dihedral angles of 17.24 (8) and 82.86 (8)°, respectively, with the chlorobenzene ring and the benzene ring of the benzodiazepine unit.

Related literature

For background to benzodiazepine derivatives, see: Barltrop et al. (1959 ▶); El Hazazi et al. (2003 ▶); Sharp & Hamilton (1946 ▶). For related structures, see: Chiaroni et al. (1995 ▶); El Hazazi et al. (2000 ▶).

Experimental

Crystal data

C₂₇H₂₃Cl₃N₄O₂
M _r = 541.84
Triclinic,
a = 9.679 (3) Å
b = 11.256 (3) Å
c = 12.661 (2) Å
α = 79.09 (2)°
β = 76.46 (2)°
γ = 73.04 (2)°
V = 1271.8 (6) Å³
Z = 2
Mo Kα radiation
μ = 0.39 mm⁻¹
T = 300 K
0.3 × 0.15 × 0.1 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
6860 measured reflections
5536 independent reflections
4616 reflections with I > 2σ(I)
R _int = 0.010
2 standard reflections every 60 min intensity decay: 1.0%

Refinement

R[F ² > 2σ(F ²)] = 0.036
wR(F ²) = 0.101
S = 1.05
5536 reflections
327 parameters
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1989 ▶); cell refinement: CAD-4 EXPRESS; data reduction: MolEN (Fair, 1990 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811014115/is2697sup1.cif

e-67-o1211-sup1.cif^{(25.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811014115/is2697Isup2.hkl

e-67-o1211-Isup2.hkl^{(265.5KB, hkl)}

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

supplementary crystallographic information

Comment

In order to develop work carried out before in our laboratory we were interested in the synthesis of new derivatives benzodiazepinic (El Hazazi et al., 2003). These reactions are either of the reactions of cycloadditions [2 + 1] realising generated carbenes in situ or reactions of transfer of methelyne.

In the present work, we report the synthesis of new benzodiazepine derivatives via addition of dichlorocarbene to [1,2,4]triazolo[4,3-a][1,5]benzodiazepine obtained stereospecifically by the addition of nitrilimines (Sharp et al., 1946) on 1,5-benzodiazepine (Barltrop et al., 1959).

Dichloroazacyclopropanation of [1,2,4]triazolo[4,3-a][1,5]benzodiazepine occurs readily under phase transfer catalysis conditions (liquid-liquid) with chloroform, aqueous sodium hydroxide and benzyltriethylammonium chloride (TBA-Cl) to give the corresponding bichloroadduct 2 (Fig. 1). Thus, the reaction of [1,2,4]triazolo[4,3-a][1,5]benzodiazepine 1 with dichlorocarbene in these conditions produce gem-dichloroaziridino[2,1-d][1,2,4] triazolo[4,3-a][1,5]benzodiazepine 2 in good yield.

The crystallographic study made it possible to determine the stereochemistry of the product 2. The crystalline structure confirms that the condensation of dichlorocarbene is carried out on double bond C=N substituted by the phenyl and shows that the product 2α obtained is of trans relative stereochemistry (Fig. 2). The main geometric features of this group are in good agreement it those observed in similar compound (Chiaroni et al., 1995; El Hazazi et al., 2000).

Experimental

[1,2,4]Triazolo[4,3-a][1,5]benzodiazepine 1 (0.65 mm l) in 2 ml of chloroform were stirred with 2 ml of aqueous 50% NaOH solution and a catalytic amount of triethylbenzylammonium chloride (TBA-Cl). After 4 h the mixture was poured into 5 ml of water and extracted with ether. The organic phase was then dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The crude product was chromatographied on a silica gel column (eluent: hexane/ethyl acetate 95/5) and recrystallized from ethanol/chloroform to give a compound 2α

The observation to be noted is that the condensation of dichlorocarbene to [1,2,4]triazolo[4,3-a][1,5]benzodiazepine is streospecific. The structure elucidation of the compound 2 was determinate on spectral data (¹H NMR, ¹³C NMR and mass spectroscopy). The compound revealed in their spectra of mass the molecular peak located at m/z = 541 compatible with their empirical formula. The NMR spectrum of this product shows that the decalage of the chemical shifts of different grouping from monoadduct. In the ¹³C NMR spectrum of compound, we remarked the absence of the signals attributed to the double bond C5=N6 of cycle diazepinic. The ¹³C NMR spectrum of product was consistent with the presence of only one diasterioisomer. These spectral analyses do not enable us to determine relative stereochemistry of the aziridino[2,1-d][1,2,4]]triazolo[4,3-a][1,5]benzodiazepine (trans 2α or cis 2β).