Scientists have developed a simple, low-cost method to drive key chemical reactions, which they say could make large-scale drug manufacturing faster and more affordable.
By heating two common, inexpensive chemicals together, the researchers were able to trigger the electron transfer reactions regularly used in industry.
Lead researcher, Dr Michael James, a lecturer in synthetic organic chemistry at The University of Manchester, UK, said the goal was to develop a broadly accessible and low-cost way to promote electron transfer reactions for industrial applications.
"By using something as simple as heat - something every chemistry lab already has - we’ve created a process that can be scaled more easily and used by companies without the need for expensive, specialised equipment, opening up new possibilities for chemists all over the world," he said.
Radical chain initiation strategies are fundamental to the synthesis of small molecule drugs and macromolecular materials. Many of these chemical reactions rely on photochemical and electrochemical technologies to kick start electron transfer reactions. But these can be difficult to scale up for industrial use as they require specialist reactors and costly infrastructure.
The Manchester team’s approach uses two widely available chemicals - a type of azo compound and a formate salt. When heated together in a standard industrial reactor, these reagents form a highly reactive carbon dioxide radical anion - a simple yet powerful species capable of driving a wide range of chemical transformations.
The study was published in the journal Nature Synthesis. The controlled initiation of radical chains is a subject of fundamental importance to polymer science, organic synthesis, atmospheric chemistry and biochemistry, the paper notes. "Considering the multidisciplinary importance of radical chain chemistry, we anticipate that this inexpensive initiation strategy will find widespread application in both industry and academia," the paper notes.
Dr Cristina Trujillo, a lecturer in computational and theoretical chemistry at The University of Manchester, added: "Radical chain chemistry underpins so many areas of science and manufacturing, so we hope this simple initiation method will be of wide use across both industry and academia. Beyond large-scale applications, it could also become a valuable tool for researchers studying new chemical reactions."
James told C&I the team successfully demonstrated the application of this method of initiation to six different reaction types, and hopes this method could be broadly applied wherever a strong one-electron reductant is required for initiation. 'Aside from the development of new synthetic method, we're also excited about the potential of our approach to be used as a tool to probe the mechanisms of other reactions,' he said.
He said that one of the greatest strengths of this approach is its accessibility because the key reagents used – [4-cyanopentanoic acid] ACVA and potassium formate - are widely available and inexpensive. “It is effectively already commercialised. There are no barriers to scientists around the world using this method,” he said.
So why has this approach not been considered before? James says this is difficult to answer. Milder - lower temperature - more technologically advanced methods are often prioritised in academic research in order to develop reactions which tolerate more sensitive molecular structures. “However, this can come at the cost of scalability. The developed method perhaps finds an effective middle ground,” he says.
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