1-Methyl-6-nitro-1H-benzimidazole

The title compound, C8H7N3O2, a potential antitumour drug and an antioxidant agent, was studied in order to give more insight into structure–function relationships. The 1-methylbenzimidazole unit of the molecule was found to be exactly planar and the nitro group is inclined at an angle of 10.4 (2)° to the plane of the heterocycle. The bond lengths in the present derivative were analyzed in details and compared with those of the parent unsubstituted analogues in the Cambridge Structural Database. The results have shown that the additional nitro group is not involved in conjugation with the adjacent π-system and hence has no effect on the charge distribution of the heterocyclic ring.

The title compound, C 8 H 7 N 3 O 2 , a potential antitumour drug and an antioxidant agent, was studied in order to give more insight into structure-function relationships. The 1-methylbenzimidazole unit of the molecule was found to be exactly planar and the nitro group is inclined at an angle of 10.4 (2) to the plane of the heterocycle. The bond lengths in the present derivative were analyzed in details and compared with those of the parent unsubstituted analogues in the Cambridge Structural Database. The results have shown that the additional nitro group is not involved in conjugation with the adjacent -system and hence has no effect on the charge distribution of the heterocyclic ring.

Comment
Benzimidazole derivatives are known to possess a variety of biological properties (Le et al., 2004), the anti-cancer activity being one of the most important (Nguyen et al., 2004). Recently, it has been reported that the cytotoxic activity of 1H-benzimidazoles is related to inhibition of the DNA-topoisomerase binary complex and is potentiated by introduction to the 6-position of a small substituent containing an oxygen atom able to accept a hydrogen bond (e.g. nitro, acetyl, amide) (Alpan et al., 2007;Statkova-Abeghe et al., 2005). It was, however, unclear whether the influence of the substituents reflects their effect on the charge distribution of the heterocycle or results from interaction of the substituents with additional DNA or enzyme functionalities. Consequently, we prepared a series of 6-substituted 1-methylbenzimidazoles and determined and compared their molecular and electronic structures by using theoretical and experimental techniques. In this communication we report the crystal structure of the 6-nitro derivative, (I). Another point of interest in (I) stems from its use in paper processing as an antioxidant agent (Katuščák, 2003;Hanus et al., 2004), a property which is also dependent on the molecular and electronic structures of the compound.
As expected, the 1-methylbenzimidazole substructure is planar to within experimental error and the nitro group is rotated by 10.4 (2)° from the plane of the heterocycle (Fig.1).
As mentioned above, the main purpose of this work was to compare precise molecular dimensions in the present derivative, (I), with those of the unsubstituted 1-methylbenzimidazole. As the latter compound has no entry in the Cambridge Structural Database (CSD, Version of 2007; Allen & Kennard, 1983), the CSD was searched for compounds possessing the benzimidazole nucleus and just 1-substituent with methylene group in the α-position; 42 such compounds [hereafter (II)] were found. The comparison have shown that the corresponding bond lengths in the benzimidazole heterocycle in (I) and in the molecules of (II) are equal within the limits of experimental error. This, along with the single-bond character of C6-N4 (Adler et al., 1976) indicates that the nitro group is deconjugated with the benzimidazole ring. This implies that the large difference in cytotoxic activities between (I) and (II) lies in the interaction of the 6-substituent with additional DNA intercalation component or enzyme amino acid residues which surrounds the intercalation site (Kettmann et al., 2004).
These results will serve as a basis for subsequent molecular-modelling studies of the DNA-enzyme-ligand interactions.