6-Nitro-2,3-dihydro-1H-pyrrolo­[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione

Abdessamad Jebani; Hafid Zouihri; Ahmed El Hakmaoui; Saïd Lazar; Mohamed Akssira

doi:10.1107/S1600536811024500

. 2011 Jul 9;67(Pt 8):o2003. doi: 10.1107/S1600536811024500

6-Nitro-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione

Abdessamad Jebani ^a, Hafid Zouihri ^b, Ahmed El Hakmaoui ^a,^*, Saïd Lazar ^c, Mohamed Akssira ^a

PMCID: PMC3213458 PMID: 22091037

Abstract

In the two molecules of the asymmetric unit of the title compound, C₁₂H₁₁N₃O₄, the seven-membered diazepine ring adopts a boat conformation (with the two phenylene C atoms representing the stern and the methine C atom the prow). The five-membered pyrrole ring, which has an envelope conformation, makes dihedral angles of 60.47 (10) and 54.69 (9)° with the benzene ring of the benzodiazepine unit in the two molecules. In the crystal, intermolecular N—H⋯O hydrogen bonds and π–π stacking interactions [centroid–centroid distance = 3.8023 (7)–3.8946 (7) Å] lead to the formation of a three-dimensional framework.

Related literature

For the biological activity of pyrrolo[2,1-c][1,4]benzodiazepine derivatives, see: Dervan (1986 ▶); Leimgruber et al. (1975 ▶); Da Settimo et al. (2007 ▶); Herpin et al. (2000 ▶); Arima et al. (1983 ▶).

Experimental

Crystal data

C₁₂H₁₁N₃O₄
M _r = 261.24
Monoclinic,
a = 10.7364 (2) Å
b = 6.8925 (1) Å
c = 16.3901 (3) Å
β = 101.870 (1)°
V = 1186.94 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 296 K
0.23 × 0.20 × 0.15 mm

Data collection

Bruker APEXII CCD detector diffractometer
14768 measured reflections
2543 independent reflections
2452 reflections with I > 2σ(I)
R _int = 0.021

Refinement

R[F ² > 2σ(F ²)] = 0.030
wR(F ²) = 0.080
S = 1.04
2543 reflections
351 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); data reduction: SAINT; 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 datablock(s) I, global. DOI: 10.1107/S1600536811024500/vm2102sup1.cif

e-67-o2003-sup1.cif^{(30.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811024500/vm2102Isup2.hkl

e-67-o2003-Isup2.hkl^{(124.9KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811024500/vm2102Isup3.cml

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
N10—H10N⋯O11ⁱ	0.85 (3)	1.98 (3)	2.821 (2)	169 (3)
N20—H20N⋯O22ⁱⁱ	0.84 (3)	2.15 (3)	2.980 (2)	169 (2)

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

Acknowledgments

The authors thank the Unit of Support for Technical and Scienti&filig;c Research (UATRS, CNRST) for the X-ray measurements.

supplementary crystallographic information

Comment

Benzodiazepines form a well known and widely applied class of biologically active compounds (Da Settimo et al., 2007) and are representatives of the family of privileged structures (Herpin et al., 2000). In the area of molecular recognition considerable efforts have been devoted to the synthesis of pyrrolo[2,1 c][1,4]benzodiazepines (PBDs) that can recognize and bind to specific sequences of DNA. They are potential regulators of gene expression with possible application as therapeutic agents in the treatment of genetic disorders including cancer. Furthermore, they can be used as affinity-cleavage reagents in molecular biology (Dervan, 1986). The PBD ring system is also found in natural antitumor antibiotics from Streptomyces species such as Anthramycin (Leimgruber et al., 1975), Tomaymycine (Arima et al., 1983).

The compound, C₂₄H₂₂N₆O₈, crystallizes with two reasonably similar molecules in the asymmetric unit (Fig. 1, r.m.s. deviation of 0.1051 Å for 19 non-H atoms fitted). The nitro and benzene systems are inclined at dihedral angles of 30.0 (3) and 41.0 (3)° in the first and second molecule of the asymetric unit, respectively. The seven-membered diazepine ring adopts a boat conformation (with the two phenylene C atoms representing the stern and the methine C atom the prow). The five-membered pyrrolo ring, which has an envelope conformation, makes dihedral angles of 60.47 (10)° and 54.69 (9)° with the benzene ring of the benzodiazepine in the two independent molecules of the unit.

In the crystal structure, intermolecular N—H···O hydrogen bonds (Fig. 2, Table 1) and π–π stacking interactions (centroid-centroid distance = 3.8023 (7) Å to 3.8946 (7) Å) lead to the formation of a three-dimensional framework.

Experimental

5-Nitro-1H-benzo[d][1,3]oxazine-2,4-dione (0.5 g, 2.5 mmol) and L-proline (0.29 g, 2.5 mmol) were dissolved in DMF (10 ml) and were then heated under reflux for 3 h. After cooling, the solvent was removed under reduced pressure to yield an oily residue; the residue was then purified over silica gel column chromatography using a mixture of hexane and ethyl acetate (3:1) as eluent. Under these conditions the compound was obtained as colourless crystals.