Abstract
The exploration of the synthesis of three tricyclic nitrogen-containing fused ring systems was achieved through the employment of a microwave assisted organic synthesis (MAOS) approach via a one-pot methodology. The ring systems (which included quinoxalines, benzodiazepines, and diazocines) were synthesized through novel procedures which considered and utilized environmentally friendly approaches such as the complete removal of heavy metal catalysts, multistep syntheses, and extraneous purification methods. Tricyclic pyrrolo-fused quinoxalines were made via the reaction of 1-(2-aminophenyl)pyrrole and a variety of aromatic aldehydes in the presence of catalytic acidic acid with isolated yields ranging from 63-88% without the need of purification beyond simple filtrations from the crude reaction mixture. The versatility of the reaction was further subjected to optimization via a set of catalyst loading, solvent, and temperature studies which provided excellent results both in yield and environmental consideration. For instance, the desired fused ring was successfully made in 30 minutes, with 1% catalyst, using ethanol as solvent and without the need for purification while maintaining a 63% isolated yield.
The synthesis of tricyclic benzodiazepines was achieved through a newly designed reaction of o-phenylenediamines and 2-fluoro-5-nitrobenzoic acid. This novel reaction was designed to perform a nucleophilic aromatic substitution in tandem with an amide condensation to form a fused ring system. This approach was optimized through a variety of studies which included solvent and base studies. Furthermore, the reaction was performed without the need for any heavy metal catalysts and only employed safe solvents (relative to other more hazardous options). The results of this synthesis provided a variety of benzodiazepines with calculated yields ranging from 62-88%.
Lastly, the formation of tricyclic diazocines was accomplished by allowing a variety o-phenylenediamines to react with phthalic acid in the presence of triethylamine with ethanol as solvent. Large ring structures such as diazocines are notoriously problematic and traditionally require multistep syntheses. This approach managed its formation in as little as three hours without the need for catalysts or coupling reagents. Given the problematic nature of larger ring systems, it is not surprising that these tricyclic diazocines were not isolated in a completely pure form, and therefore their synthesis is presented as an initial exploration of the MAOS approach.