Carbon monoxide moves from villain to hero
A problematic waste product may soon be the key to new pharmaceuticals. Joel F. Hooper reports.
Scientists from RUDN University in Russia have developed a new method to create important nitrogen-containing molecules using carbon-monoxide as the key chemical agent, turning this waste product into valuable drug-like molecules.
A survey of the top 30 pharmaceuticals on the markets reveals some striking similarities among the chemical structures found. Drug molecules, except for protein-based drugs, tend to be smallish and have lots of cyclic structures. But the common feature among all these drugs is that they contain nitrogen atoms bound to carbon. It’s little wonder, then, that chemists who are looking to make new drugs, or more efficient ways to make old drugs, are always searching for better ways to make these key C–N bonds.
Perhaps the most useful tool that chemists have at their disposal for creating carbon-nitrogen bonds is a reaction called reductive amination. This reaction brings together a nitrogen-containing molecule (an amine) with a molecule containing a carbon-oxygen double bond. In the presence of a reducing agent (reduction being the opposite of oxidation) the oxygen atom is removed and a new bond is formed with the amine.
The efficiency and environmental impact of a reductive amination reaction is largely determined by which chemical is used as the reducing agent. Traditional reducing reagents, such as metal hydrides, produce waste by-products which must be separated from the reaction products and disposed of. Hydrogen gas can also be used as the reducing agent, producing little waste, but the “green” credentials of hydrogen are dependent on how the gas is produced. Most of the world’s commercial hydrogen is still produced from fossil fuels.
The team at RUDN University, led by Denis Chusov, looked at using carbon monoxide gas – produced as a by-product from the steel industry in huge volumes – as the reducing agent in reductive amination reactions.
“At the moment, carbon monoxide is simply burned to carbon dioxide,” says Chusov. “We suggest using carbon monoxide not only to heat the atmosphere, but to carry out important organic synthesis reactions.”
Chusov's team found that the key to using CO as the reducing agent in their reactions was to find the right catalyst.
They looked at catalysts based on the metal iridium, finding that one that promoted the reductive amination with high efficiency. The team still has some work to do, because the reaction requires high temperatures and high pressures to work well.
But if these obstacles can be overcome, carbon monoxide might drive many of the drugs that extend and improve our lives.