Efforts to develop renewable energy and material sources are extending into pharmaceuticals such as paracetamol, more commonly known as acetaminophen. Since its introduction in the early 1900s, this analgesic drug—one of the most widely used pharmaceuticals globally—has typically been derived from petroleum, coal tar, or crude oil. A group of scientists at the University of Wisconsin-Madison has now demonstrated a way to economically produce paracetamol from plant biomass as part of a broader framework for synthesizing common useful chemicals in a more environmentally sustainable manner. See also: Acetaminophen; Analgesic; Biomass; Renewable resource

Researchers have developed an efficient way to convert pHB, a compound found in plants including poplar trees (pictured), into the common pain reliever paracetamol. (Credit: Roadrunner1866/Shutterstock)

Open in new tab

To share with users who are connected to your same network, click <Link> below to copy the page URL.

To share in a Learning Management System (LMS).

1. Contact [email protected] to confirm that your LMS has been correctly set up in our Subscription Management System (be sure to provide the name of your institution and the link for your LMS course)

2. Click <Link> button below to copy the page URL and paste it into your LMS.

Link

Share

The paracetamol molecule consists of a benzene ring—a hexagonal configuration of six carbon atoms bonded by alternating single and double bonds—with two chemical groups attached. Some plants’ cell walls contain a similar compound called p-hydroxybenzoate (pHB) as part of a polymer called lignin. Lignin is one of the two main components of wood (the other being cellulose), and provides structure by binding plant sugars together. Lignin contains plenty of valuable compounds that could help replace petrochemicals in a variety of applications, but the main barrier to its usefulness lies in breaking individual pieces from their complex and irregular polymer chain. Past research has shown that pHB is relatively easy to break off of lignin using chemical treatment, although the yield of paracetamol from the pHB was too low to be considered commercially viable. See also: Cellulose; Lignin; Plant cell wall; Polymer; Wood chemical

The University of Wisconsin-Madison group has debuted a novel and generally less expensive method to convert nearly all of the pHB into another chemical that can then be converted into paracetamol much more efficiently. The team focused on building a scalable and environmentally friendly framework using water as the primary solvent, utilizing green organic solvents where otherwise required, and using low-cost and scalable purification steps such as counter-current extraction, crystallization, and distillation for low-boiling-point products. One compatible precursor chemical matching these criteria is p-hydroxybenzoic acid, or pHBA, which can be converted into paracetamol via four steps: esterification, conversion into p-hydroxybenzamide (pHBAm), transformation into p-aminophenol (pAmP) via the Hofmann rearrangement, and finally acetylation into paracetamol. In addition to synthesizing paracetamol, pHBA as an intermediary chemical can be utilized for other applications including black dyes or inks and polymers for textile or material production. Conveniently, pHBA can be extracted from many common plants—willow, poplar, aspen, cottonwood, coconut, date, and oil palms, to name a few. The researchers used poplar and palm wood to test their process. See also: Green chemistry; Solvent; Solvent extraction; Poplar; Tree

Despite the promise of this new process, the researchers face a few potential barriers to successfully pivoting away from petroleum and related chemicals as primary paracetamol sources. The research team outlined some of these issues and several approaches to solving them, taking advantage of the ways in which chemical reactions' yields can be shifted towards one product or another based on varied input to the production system. For example, when converting pHBAm into pAmP, the yield is initially 57% with a recovery of 30% of the pHBAm. However, through a stepwise purification setup, the recovered pHBAm can be recycled through the process repeatedly until the paracetamol yield reaches 90%. The team outlined a framework in which many smaller facilities could extract the earlier precursor chemicals, eventually shipping their products to fewer, larger labs for the final steps of refinement. Through this approach, the researchers hope to ease some of the disparate volumes of raw material required for each step of synthesis. If popularized, the team anticipates that their process will help to further reduce reliance on petrochemicals. See also: Petrochemical