UNC Scientists Transform Chemicals from Oil Refinery Waste into Compounds for Anesthetics, Antidepressants
Chemists at UNC-Chapel Hill develop a more eco-friendly method to convert chemicals from petroleum waste into compounds for study as anesthetics and antidepressants.
April 23, 2025 | By Emily Sherman
More eco-friendly chemical tools are needed to access novel compounds for drug discovery and mitigate the tons of chemical waste produced every year. Chemists in the Johnson Lab at UNC-Chapel Hill tackled this problem in their Journal of Organic Chemistry study, “Formal Dearomative Hydroamination of 2‑Arylphenols,” by converting chemicals from petroleum waste into compounds for study as anesthetics and antidepressants.
When lead author Dr. Bob Wiley began investigating a path to these compounds, he discovered two key roadblocks. First, many approaches used toxic, lead-containing chemicals. When disposed of, these can contaminate the soil, water and air, decreasing plant growth while potentially harming neurological development in children and decreasing memory and concentration in adults.
Second, these methods only produce a few iterations of the core molecular structure — preventing scientists from easily testing drug candidates. Like trying on multiple pairs of jeans to find the right fit, quickly producing many variants is key to finding the best-performing molecule.
“This investigation would allow us to put our own spin on a classic problem in chemistry,” said Wiley. “Other methods produced a select few variants of these biologically relevant structures and used harsh chemicals, so we hoped to synthesize a broader scope of these molecules with more benign conditions.”
Wiley and co-authors tackled these two issues with a chemical method called dearomatization which transformed phenols — a type of molecule found in plant or petroleum waste — into the target molecules. To understand how dearomatization works, think of a group of children playing “Ring Around the Rosie.” While they sing, they tightly hold each other’s hands until a stimulus is introduced — like a tray of cupcakes. Naturally, at least one child will take a treat, disrupting their grip on their friend’s hand.
Much like the children’s ring, the bonds in phenols are strong and unlikely to break unless a stimulus is introduced. When the chemists added a stimulus — a weak nitrogen-oxygen bond — a variety of inexpensive phenols reacted and rapidly transformed into new molecules. By using dearomatization, the chemists avoided hazardous lead-containing chemicals and developed a method with less toxic waste to quickly access molecules for drug discovery.
“Without dearomatization, producing these molecules would require multiple chemical reactions,” said Michael Eng, the paper’s second author. “These additional synthetic steps would generate more waste and potentially higher production costs.”
“Synthetic methods like this dearomatization are challenging because of the stability of the phenols,” said Dr. Jeffrey Johnson, senior author and A. Ronald Gallant Distinguished Professor. “By disrupting this stability without lead-based chemicals, a diverse array of inexpensive molecules can be transformed to advance available drug technologies.”