Investigations in rearrangements of sulfonamides to diaryl sulfones

Sulfonanilides and Sulfones have long been of great biological interest and importance. Diaryl sulfones, in particular, have shown activity as non-nucleoside reverse transcriptase inhibitors of HIV-1, thus preventing replication of the Human Immunodeficiency Virus.;A convenient route to these valuable diaryl sulfones is through the acid catalyzed rearrangement of their precursor sulfonanilides. These rearrangements, their mechanisms and scope remain a focus of this laboratory. In an effort to improve our understanding of the acid-catalyzed rearrangements of aryl sulfonanilides to diaryl sulfones, various heterocyclic and acyclic sulfonanilides were synthesized and rearranged with under a variety of conditions.;In the past, concentrated sulfuric acid was used as the catalyst for rearrangements. Recently, polyphosphoric acid (PPA) demonstrated its utility in the rearrangement of dihydroindole sulfonanilides (DHI) to diaryl sulfones, a rearrangement which proved unsuccessful using sulfuric acid. The results of the DHI studies indicate that the rearrangement mechanism is clearly affected by different acid catalysts. Potential new acid catalysts were investigated in phase one of this study. After testing a panel of potential acid catalysts, trifluoromethane sulfonic acid (triflic acid; TfOH) was identified as an effective new catalyst for further studies.;In phase two, traditional heating methods were compared to microwave for various heterocyclic sulfonanilides using known rearrangement catalysts. Results of microwave studies of the rearrangement of phenothiazine sulfonanilides to diaryl sulfones showed how microwave energy can improve efficiency of rearrangement in some heterocyclic systems.;In the final phase of this project, the new techniques and information gained from the results of phase one and two were applied to the rearrangement of a series of new 5,6-dihydrophenanthridine sulfonanilides to diaryl sulfones. All 5,6-dihydrophenanthridine sulfonanilides and sulfones are previously uncharacterized and have valuable structural moieties for biological potential.