Green Fischer Indole Synthesis Using a Steroidal Ketone in a Conductively Heated Sealed-Vessel Reactor for the Advanced Undergraduate Laboratory
Chemistry, Organic, Heterocyclic Compounds, Steroids, Chemistry, Pharmaceutical
Green chemistry, Chemistry, Organic, Heterocyclic compounds, Steroids, Pharmaceutical chemistry
Chemical Engineering | Chemistry
Highly efficient microwave-assisted organic synthesis is now commonplace in both industry and academia. Recently, a conductively heated sealed-vessel reactor was introduced that acts very similarly to a microwave reactor and is more affordable. Application of such reactors in teaching laboratories is advantageous because of the restricted window of time available to perform experiments and because it avoids long reaction times that are unpopular with students. These reactors thus allow reactions that were previously considered impractical for the teaching laboratory, such as the Fischer indole synthesis, to now be very feasible. We designed a clean and efficient Fischer indole synthesis to introduce advanced undergraduate students to this important method in heterocycle synthesis, which has been highly under-represented in the curriculum. It also introduces it in the context of a more complex ketone of biological relevance (a steroid). This laboratory exercise can be used to teach about Green Chemistry Principles, product analysis (TLC, NMR, MS, UV–vis), and a complex multistep mechanism. It can also act as a starting point to teach terpenoid biosynthesis, some key concepts in medicinal chemistry such as pharmacophores and pro-drugs, and even to open discussions on the societal impacts of steroids.
Cirillo, Pier F.; Caccavale, Alexis; and DeLuna, Alicia, "Green Fischer Indole Synthesis Using a Steroidal Ketone in a Conductively Heated Sealed-Vessel Reactor for the Advanced Undergraduate Laboratory" (2020). Chemistry and Chemical Engineering Faculty Publications. 38.