A Facile Synthesis of Quino[2,3-fl]carbazoles

In general pyrano, pyrazino and simple benzocarbazole derivatives were reported to have phar­ macological properties like antihistaminic, antiin­ flammatory, antibiotic and antimicrobial activity [1-11]. Pyridocarbazoles are well known antican­ cer agents [12-15]. To our knowledge there is no report on the synthesis of quinocarbazoles, which can be considered as substituted pyridocarbazoles, probably due to the nonavailability of viable gene­ ral methods for the construction of this system. The present investigation was aimed to device a new synthetic route for the hitherto unknown title compounds which can be expected to exhibit anti­ cancer properties. In this connection 1-oxo-l,2,3,4tetrahydrocarbazole which has a -CH2COgroup is condensed with the amino group of o-aminoa­ cetophenone under acidic conditions as in the Friedländer synthesis of simple quinolines [1617], 8 -Methyl l-oxo-l,2,3,4-tetrahydrocarbazole (la) prepared according to our reported procedure [6 ,1 1 ] on condensation with o-aminoacetophenone 2 in glacial acetic acid in the presence of a drop of concentrated sulphuric acid gave, after work-up, a single product. It showed IR absorptions at 3284 cm 1 and 1685 cm 1 corresponding to -NH stretching and -C=N vibrations. The ’H NMR spectrum showed two three proton singlets at d 2.25 and 2.79 ppm and nine aromatic protons and a NH proton appeared as a multiplet in the 7.228 .6 6 region. Elemental analysis and the molecular ion peak at m/e 296 agreed well with the molecular formula C2]H16N2. The peaks at m/e 130 and 142 are characteristic of substituted quinoline nucleus and peaks at m/e 115, 130 and 157 confirm the presence of carbazole nucleus. Based on the above mentioned spectral data the product was attested to be 6,12-dimethylquino[2,3-a]carbazole (3a). A similar series of compounds 3b, 3c, 3d and 3e were obtained from lb, lc, Id and le respectively (Scheme 1). A plausible mechanism for the forma­ tion of the product 3 comprises a two fold conden­ sation reaction between 1 and 2 followed by an aerial oxidation of the pentacyclic intermediate 4 (Scheme 2).