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

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.

In the two molecules of the asymmetric unit of the title compound, C 12 H 11 N 3 O 4 , 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-HÁ Á ÁO hydrogen bonds andstacking interactions [centroid-centroid distance = 3.8023 (7)-3.8946 (7) Å ] lead to the formation of a three-dimensional framework.   Table 1 Hydrogen-bond geometry (Å , ).

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, C 24 H 22 N 6 O 8 , 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.
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.

Refinement
The H atoms bound to C were treated as riding with their parent atoms [C-H distances are 0.93Å for CH groups with U iso (H) = 1.2 U eq (C), and 0.97 Å for CH3 groups with U iso (H) = 1.5 U eq (C)]. The nitrogen-bound H atoms were located in a difference Fourier map, and were refined with distance restraints of N-H 0.88±0.01. 2133 Friedel pairs were merged.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.