College
College of Arts & Sciences
Mentor Information
Minsoo Ju
Description
Nitroalkanes are valuable drug precursors due to their versatile and chemoselective reactivity. Particularly, reducing the nitro group can directly form the amine species, a prevalent functional group in modern day pharmaceuticals. However, α-tertiary amines are conventionally much harder to synthesize than the primary or secondary species. Our method of producing the nitro group via α-nitroalkyl radicals would make green synthesis possible and address selectivity and scalability issues. We begin with constructing the α-iodonitroalkane from a secondary or primary nitroalkane which underwent electrochemical iodination. From here, homolysis of the weak carbon-iodine bond is conducted under visible light sources, resulting in the α-nitroalkyl radical. We investigated the radical’s coupling potential with alkenes and its ability to react intramolecularly with an arene, producing a nitro-containing benzocyclobutene. Optimal conditions for the intramolecular reactivity were tested through the presence of pyridine and adjusting temperature and solvent conditions. Nuclear magnetic resonance spectroscopy was used to determine the purity and structure of synthesized products. Both reactivities prove viable options for forming α-tertiary amines, a class of molecules that can provide superior water solubility, binding, and pharmacokinetic properties when incorporated into medically relevant targets. Our results paint a hopeful, catalyst-free future for the green synthesis of α-tertiary-nitroalkanes.
Valuable Transformations of α-nitroalkyl Radicals Following Iodination and Photolysis
Nitroalkanes are valuable drug precursors due to their versatile and chemoselective reactivity. Particularly, reducing the nitro group can directly form the amine species, a prevalent functional group in modern day pharmaceuticals. However, α-tertiary amines are conventionally much harder to synthesize than the primary or secondary species. Our method of producing the nitro group via α-nitroalkyl radicals would make green synthesis possible and address selectivity and scalability issues. We begin with constructing the α-iodonitroalkane from a secondary or primary nitroalkane which underwent electrochemical iodination. From here, homolysis of the weak carbon-iodine bond is conducted under visible light sources, resulting in the α-nitroalkyl radical. We investigated the radical’s coupling potential with alkenes and its ability to react intramolecularly with an arene, producing a nitro-containing benzocyclobutene. Optimal conditions for the intramolecular reactivity were tested through the presence of pyridine and adjusting temperature and solvent conditions. Nuclear magnetic resonance spectroscopy was used to determine the purity and structure of synthesized products. Both reactivities prove viable options for forming α-tertiary amines, a class of molecules that can provide superior water solubility, binding, and pharmacokinetic properties when incorporated into medically relevant targets. Our results paint a hopeful, catalyst-free future for the green synthesis of α-tertiary-nitroalkanes.
