Synthesis and crystal structure of 1-hydroxy-8-methyl-9H-carbazole-2-carbaldehyde

Two crystallographically independent molecules are present in the asymmetric unit. O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds form rings and chains and π–π stacks further connect molecules in the crystal.


Chemical context
Nitrogen-containing heterocyclic compounds are key building blocks used to develop chemicals of biological and medicinal interest. Among nitrogen heterocycles, carbazole alkaloids represent an important class of natural products. The Indian medicinal plant Murraya koenigii spreng (Rutaceae) is a rich source of carbazole alkaloids (Knö lker & Reddy, 2002), and a number of these natural products with novel structures and useful biological activities have been isolated from this plant over the past decades. The increase of isolable natural products as well as the pharmacological action of these carbazole derivatives has generated synthetic interest; consequently, the synthesis of carbazoles has been an active area of study.

Structural commentary
The title compound crystallizes in the monoclinic space group P2 1 /c with two independent molecules (A and B, Fig. 1) in the asymmetric unit. They are superimposable and both are essentially planar. Placing inverted molecule B on molecule A gives the best fit, with the overlay of the two independent molecules shown in Fig. 2. The weighted r.m.s. fit of the 17 non-H fitted atoms is 0.034 Å , the r.m.s. bond fit is 0.003 Å and the r.m.s. angle fit is 0.383 . Both independent molecules, including the hydroxy group at position 1, carbaldehyde group at position 2, and methyl group at position 8 (with the exception of two H atoms) are near planar. The dihedral angle between the two benzene rings of the carbazole is 2.20 (9) in molecule A and 2.01 (9) in molecule B. The pyrrole ring makes dihedral angles of 0.82 (10) and 1.40 (10) for molecule A and 0.84 (10) and 1.18 (10) for molecule B with the methylsubstituted and hydroxide/carbaldehyde-substituted benzene rings, respectively. The compound exhibits intramolecular O-HÁ Á ÁO hydrogen bonding between the hydroxide and aldehyde groups (Table 1). Hydrogen bonds similar to the O1-H1DÁ Á ÁO2 and O3-H3AÁ Á ÁO4 bonds observed in this structure, forming S(6) ring motifs, have previously been observed (Bernstein et al., 1995).

Supramolecular features
In the crystal, molecules are connected into chains parallel to the c axis by intermolecular N-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds (Table 1 The two crystallographically independent molecules with the atomnumbering scheme. Non-H atoms are shown at the 50% displacement ellipsoid probability level, H atoms are represented as small spheres.

Synthesis and crystallization
30% Sodium hydride in mineral oil (2.4 g) was washed with dry benzene and taken into a round-bottom flask containing dry benzene (100 ml). The flask was kept in an ice bath under stirring. Ethyl formate (8 ml) was added dropwise to the solution over a period of 10 minutes. Then 8-methyl-2,3,4,9tetrahydro-1H-carbazol-1-one (1.6 g, 0.008 mol) in dry benzene (25 ml) was added slowly and the reaction mixture was allowed to stir for another 36 h. The reaction was monitored by TLC. After completion of the reaction, benzene was removed in vacuo and the contents in the flask were transferred to a beaker containing water. It was neutralized with dilute HCl, filtered, washed with water and dried to get crude 1-hydroxy-8-methyl-9H-carbazole-2-carbaldehyde. It was purified by column chromatography over silica using petroleum ether:ethyl acetate (95:5) as eluant. The brown pure product obtained was recrystallized using glacial acetic acid (needle-shaped crystals, yield 0.965 g, 55%), m.p. 414 K (Fig. 5).

1-Hydroxy-8-methyl-9H-carbazole-2-carbaldehyde
Crystal data 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.