Microwave-assisted Fischer Indole Synthesis of 1,2,3,4-tetrahydrocarbazole using Pyridinium-based Ionic Liquids

Microwave-assisted organic synthesis using ionic liquids is believed to enhance efficiency of the reaction leading to a cleaner method, higher product yields and shorter reaction times. Six pyridinium-based ionic liquids were prepared from 2-methylpyridine and a series of alkyl bromides (R: n-C4, sec-C4, t-C4, C6, C8 and Bn) by oil bath heating at 80, 90, 100 and 110 °C. The ionic liquids product yield efficiency has direct relationship with heating temperatures affording highest yields at 110 °C of 71.15%, 8.20%, 45.96%, 57.75%, 48.02% and 80.45% for each respective alkyl bromides. The catalytic activities of the synthesized ionic liquids in the Fischer indole synthesis of THC were examined. The highest yield of 67.82% is found to be less satisfactory compared to the use of the Lewis acid standard, ZnCl2, which gave 79.89%. On the other hand, the use of the pyridinium-based ionic liquids in conjunction with ZnCl2 afforded better yields than individual test catalysts resulting to 89.66% of the THC. Structural effects such as branching and chain length of the alkyl bromides for the synthesis of ionic liquids and the THC have negative effects on the product yields.