5-Amino-1-methyl-1H-benzimidazole

The structure of the title compound, C8H9N3, a potential antitumour drug, was determined in order to give more insight into its structure–function relationships. The benzimidazole core of the molecule was found to be exactly planar, while the substituents are displaced slightly from the molecular plane [C—C—N—C and C—C—C—N torsion angles of 0.8 (3) and 179.0 (1)° for the methyl and amino groups, respectively]. The bond lengths are analysed in detail and compared with those of the parent unsubstituted analogues. The results show that the lone-pair electrons on the amino N atom are involved in conjugation with the adjacent π system and hence affect the charge distribution in the heterocycle. Two intermolecular N—H⋯N and C—H⋯N hydrogen bonds have been identified.

The structure of the title compound, C 8 H 9 N 3 , a potential antitumour drug, was determined in order to give more insight into its structure-function relationships. The benzimidazole core of the molecule was found to be exactly planar, while the substituents are displaced slightly from the molecular plane [C-C-N-C and C-C-C-N torsion angles of 0.8 (3) and 179.0 (1) for the methyl and amino groups, respectively]. The bond lengths are analysed in detail and compared with those of the parent unsubstituted analogues. The results show that the lone-pair electrons on the amino N atom are involved in conjugation with the adjacent system and hence affect the charge distribution in the heterocycle. Two intermolecular N-HÁ Á ÁN and C-HÁ Á ÁN hydrogen bonds have been identified.

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). Previously, it was shown that (a) introduction of a small substituent to the benzo-ring of 1H-benzimidazoles has a profound effect on the cytotoxic activity (Statkova-Abeghe et al., 2005) and (2) the activity is related to intercalative interaction of the drug molecule with the nuclear DNA or the DNA-topoisomerase binary complex (Kettmann et al., 2004). It is, however, unclear whether the influence of the substituents reflects their effect on the charge distribution of the heterocycle (and hence the intercalative energy) or results from interaction of the substituents with additional DNA or enzyme functionalities. Consequently, we prepared a series of 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 5-amino derivative, (I).
As expected, the ring system of the molecule is planar (Fig.1) to within experimental error and the substituents are slightly displaced to the same side of the plane, as indicated by torsion angles of 0.8 (3)° (C7-C8-N1-C10) and 179.0 (1)°( C9-C4-C5-N5) for the methyl and amino groups, respectively.
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  Burke-Laing & Laing, 1976) indicates that the amino group is conjugated with the benzimidazole ring. This further implies that for the present derivative the intercalative energy makes an important contribution to the overall drug-DNA binding energy and hence the enhanced cytotoxic activity of (I) relative to (II) (Kettmann et al., 2004).
These results will serve as a basis for subsequent molecular-modelling studies of the DNA-enzyme-ligand interactions.
The crystal packing is dominated by two intermolecular N-H···N and C-H···N hydrogen bonds (Table 1). It is notable that the amino N5 atom accepts a (weak) hydrogen bond but only one of the two N-H donors is involved in hydrogen bonding.

Experimental
As described in detail previously (Milata et al., 1989), the title compound, (I), was synthesized by starting from 2,4-dinitrochlorobenzene via nucleophilic substitution of the chlorine with methylamine, followed by partial Zinnin reduction of the supplementary materials sup-2 ortho-nitro group and subsequent cyclization to obtain 1-methyl-5-nitrobenzimidazole which after reduction gives the target compound (m.p. 430-432 K).