Graebe-Ullman carbazole synthesis

The Graebe-Ullman carbazole synthesis is normally carried out in sealed tubes and at high temperature. The carbazoles/substituted carbazoles are obtained in general in poor to moderate yields.  

The Graebe-Ullman carbazole synthesis has been enmloyed in the preparation of substituted carbolines, as well as indolo[2,3-i] quinolines, which are often difficult to synthesize via other approaches, for example, the Fischer indole process. 

Hagan et al. utilized the Graebe-Ullmann process to synthesize polycyclic acridines 14 which exhibit anti-tumor activity.  

Triazole 15 was mixed with polyphosphorie aeid (150 mL) and the mixture was heated until gas evolution eeased (130-180 C) (Caution It is important to note that one mole of is evolved). After eooling, the syrup was poured into iee water (2 L), and the precipitate was eolleeted, washed with H2O, heated on a steam bath with 25% ammonia (100 mL), and filtered. The produet was then washed with H2O and erystallized from pyridine to furnish 16 in 30% yield. 

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