Making new chemical compounds, like new drugs, isn’t as easy as putting together one of those colored balls and sticks you may have seen in a beginner chemistry class. No, it is often a complex process with many steps and many chemical participants, some of which are toxic and hazardous to the environment.
A technique used in chemical synthesis is called hydrogen atom transfer or HAT. It is a potentially powerful and versatile chemical aid, but technical limitations have limited its use. Now, chemists at the University of Utah, Scripps Research, and their colleagues have borrowed a technique from energy storage chemistry to achieve HAT with fewer chemicals and less cost.
“HAT holds the potential for incredibly beneficial transformations,” said Samer Gnaim of Scripps Research, lead author of a study reporting the researchers’ findings. “By introducing a fundamentally new concept, these chemical challenges can be solved, making HAT an accessible tool for the vast majority of organic chemicals in both industrial and academic settings.”
The study, with U co-authors Shelley Minteer, Matthew Sigman, David Vogt, Tianhua Tang and Christian Malapit, is published in Nature and supported by the National Science Foundation Center for Synthetic Organic Electrochemistry.
“This is a classic example of the need for multidisciplinary centers that bring together organic chemists, electrochemistry and computer scientists to tackle major problems in organic synthesis,” said Minteer, distinguished professor of chemistry.
HAT .’s Promises and Challenges
HAT is a process where a hydrogen atom is simply moved from one molecule to another. It is useful to take advantage of unsaturated carbon-carbon bonds – the most common useful chemical bond in organic chemistry – to create a wide variety of new bonds, such as carbon-carbon, carbon-oxygen and carbon-nitrogen bonds . These are all important steps in building complex molecules. Making new bonds from a carbon-carbon double bond is called ‘functionalization’.
“Functionalizing such bonds is an attractive strategy to construct molecules and achieve molecular complexity in an efficient way,” says Gnaim.
But as useful as it is, HAT has its drawbacks. The simple process of moving a hydrogen atom requires additional chemicals such as oxidizing agents and reducing agents to create an active catalyst, a compound that helps the reaction proceed. The oxidants and reducing agents are required in large quantities, making it impractical to apply HAT on a large scale, and almost impossible to apply for industrial chemical processes.
Insight from energy storage
At the same time, as chemists struggle to improve HAT, energy storage researchers have developed a process that can help. When storing energy in the form of hydrogen, positively charged protons are converted into hydrogen molecules using a cobalt hydride catalyst. It is the same kind of catalyst that is needed for the HAT process.
But the energy storage field has managed to build cobalt hydride catalysts using protons and electrons as replacements for oxidants and reductants — a very different chemical process to achieve the same end product.
So Gnaim and his colleagues compared how the electrochemical process compares to conventional HAT chemistry by evaluating its performance in a wide range of organic chemical reactions. The results were very encouraging. Using electrochemistry to make cobalt hydride catalysts was more durable and efficient, they found, and made the process even more accurate and tunable.
What can we do now?
The electrochemical process offered other advantages. It can be run in small or large batches, without the complicated steps of removing all air or water from the process and without the need for expensive oxidizing agents and reducing agents.
“Chemists are constantly trying to expand chemical reactivity into new spaces, discovering new transformations that can enhance the discovery processes of new drugs,” Gnaim says. “In our case, we can access novel molecular motifs by using environmentally friendly and inexpensive substances that rely on the use of classical HAT reactions and novel transformations.”
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