tert-Butyl 6-bromo-1,4-dimethyl-9H-carbazole-9-carboxylate

The title compound, C19H20BrNO2, consists of a carbazole skeleton with methyl groups at positions 1 and 4, a protecting group located at the N atom and a Br atom at position 6. The pyrrole ring is oriented at dihedral angles of 1.27 (7) and 4.86 (7)° with respect to the adjacent benzene rings. The dihedral angle between the benzene rings is 5.11 (7). The crystal structure is determined mainly by intramolecular C—H⋯O and intermolecular π–π interactions. π-stacking between adjacent molecules forms columns with a parallel arrangement of the carbazole ring systems. The presence of the tert-butoxycarbonyl group on the carbazole N atom and the intramolecular hydrogen bond induce a particular conformation of the exocyclic N—C bond within the molecule.

The title compound, C 19 H 20 BrNO 2 , consists of a carbazole skeleton with methyl groups at positions 1 and 4, a protecting group located at the N atom and a Br atom at position 6. The pyrrole ring is oriented at dihedral angles of 1.27 (7) and 4.86 (7) with respect to the adjacent benzene rings. The dihedral angle between the benzene rings is 5.11 (7). The crystal structure is determined mainly by intramolecular C-HÁ Á ÁO and intermolecularinteractions. -stacking between adjacent molecules forms columns with a parallel arrangement of the carbazole ring systems. The presence of the tertbutoxycarbonyl group on the carbazole N atom and the intramolecular hydrogen bond induce a particular conformation of the exocyclic N-C bond within the molecule.

Comment
Over the past few years, large interest has been observed in chemistry of carbazole derivatives since they can be widely used as organic materials due to their electroactivity and luminescent properties (Grazulevicius et al., 2003) or their applications in the light-emitting field (Zhang et al., 2006). This class of compounds also displays various pharmacological activities such as, among others, anticancer (Itoigawa et al., 2000;Laronze et al., 2005), antibacterial and antifungal activities (Thevissen et al., 2009).
Many elegant methods for the synthesis of ellipticine and related carbazole alkaloids have been reported (Ergün et al., 1998;Knölker et al., 2002;Liu et al., 2007). In our laboratory, the quest to discover new potential bioactive compounds possessing a carbazole core has attracted all our attention and recently, we have synthesized and characterized a series of carbazole derivatives (Caruso et al., 2007;Sopková-de Oliveira Santos et al., 2008). In this paper, we present the results of structural investigation of a new intermediate (Scheme 1): 6-bromo-9-tert-butoxycarbonyl-1,4-dimethyl-9H-carbazole ( Fig. 1) which constitutes a very interesting, cheap and reactive intermediate for the preparation of new analogs of the anticancer agent 9-methoxyellipticine (Le Pecq et al., 1974). The carbazole ring system (C1-C9A/N9) is nearly planar and the maximum deviation from the least-squares planes does not exceed 0.0662 (14) Å. The pyrrole ring is oriented with respect to the adjacent benzene rings at dihedral angles of 1.27 (7) and 4.86 (7)°.
The N-C bond lengths, namely N9-C8A and N9-C9A [1.408 (2)Å and 1.417 (2) Å] deviate slightly from the normal mean value reported in the literature (Allen et al., 1987). This indicates that the presence of protecting group at atom N9, probably through its electron-withdrawing character, causes the lengthening of N-C bond lengths which has been already observed with similar compounds (Back et al., 2001;Terpin et al., 1998;Chakkaravarthi et al., 2009). Methyl substituent C9 is coplanar with the aromatic rings, methyl substituent C10 closed to N-protecting group displays slight deviation from the carbazole plane with torsion angle values C4A-C9A-C1-C10 of -172.72 (15). This is probably due to minimize the steric hinderance induced by the carbamate group. No particular increase in the widening angle, namely C9A-C1-C10, has been observed compared to non substituted nitrogen atom analogs (Viossat et al., 1988). Weak intramolecular C-H···O interaction is present in the molecule. In fact, atom C8 acts, throught H8, as hydrogen-bond donor to O2, distance between H8 and O2 being 2.33 Å (Table 1). Thus, in order to optimize previous H-bond and minimize steric hinderance of N-protecting group, carbamate is forced to adopt a particular conformation, specially a very twisted torsion angle which have been also seen with N-sulfonyl carbazole derivatives displaying intramolecular H-bonds (Chakkaravarthi et al., 2008). Thus, the torsion angle C1-C9A-N9-C11 is as high as 30.8 (2)°.
In conclusion, the crystal structure of an interesting carbazole intermediate has been elucidated. A strong displacement of the N-protecting group out of the plane has been observed. Nevertheless, presence of the tert-Butyloxycarbonyl group does not prevent parallel arrangement of carbazole systems by π stacking. Thus, flat similar compounds could be used as anticancer agents through their intercalation effect like ellipticine.

Refinement
All non-hydrogen atoms were refined anisotropically. The H atoms were refined with fixed geometry, riding on their carrier atoms with U iso (H) values set at 1.2 (1.5 for methyl H atoms) times U eq of the parent atom (C-H = 0.93-0.96 Å) for (I). Fig. 1. the title compound showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability levels; For the sake of clarity H atoms have been omitted. 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 > σ(F 2 ) is used only for calculating Rfactors(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.