The Pros and Cons of Cheap Metals
In addition to the large price advantage that comes with substituting a prevalent, cheap metal for a rare, expensive metal, cheap metals are often environmentally more benign. Losses of metal are more easily tolerated in an industrial process, which can reduce or eliminate the recycling steps that are almost mandatory with expensive metal catalysts. In the pharmaceutical industry, the Food and Drug Administration may or may not allow trace levels of residual catalyst in a final drug product. As Bullock stated, “How much palladium can you have in a pharmaceutical body compared to how much iron?”
The reasons that more cheap metal catalysts are not widely used today are many, and Bullock listed several of them. One reason is that reactions catalyzed by cheap metals have not been widely studied to date, though they are receiving more attention now. Another reason is that the selectivity of cheap metal catalysts is not as good as is obtained with palladium catalysts, and the scope of the reactions is not as broad. Boosting the activity of cheap metal catalysts can mean using more expensive ligands; for example, catalysts based on aryl iodides are more reactive, but more expensive, than aryl chlorides.
Cheap metal catalysts are often less tolerant of functional groups on the reactants. A reaction that works with an ester moiety present may not work when an alcohol or carboxylic acid functional group is present. In contrast, palladium-based catalysts often work with a wide range of modified starting materials. In addition, cheap metals may require a higher catalyst loading than when palladium is used, negating some of the cost advantage. Bullock added, though, that this may be a result of the fact that cheap metal catalysis has not been studied as exhaustively as has palladium-based catalysis, and that additional research is likely to make headway on this problem.
The final problem facing cheap metal catalysts is one of motivation. For a pharmaceutical company making a high-value-added drug at small scale, and for which catalyst cost is not a major factor in the final price of the drug, there is often little motivation to expend research dollars solving a relatively small problem.
To illustrate some of the challenges in developing cheap metal catalysts, Bullock discussed the fact that reaction mechanisms may not be universal, making the search for new catalysts difficult. For example, an important class of chemical reactions hydrogenate carbon-oxygen double bonds. These carbonyl hydrogenation reactions use ruthenium- and rhodium-based catalysts to convert ketones and aldehydes into alcohols. One such ruthenium catalyst, for which the Nobel Prize was awarded, does not operate via the traditional mechanism for ketone hydrogenation. Normally, the reacting ketone would first coordinate with the metal, after which oxygen inserts itself into a metal-hydrogen bond. With this particular ruthenium catalyst, no coordination or insertion is required. Instead, the reaction occurs through a hydride ion on the ruthenium and a proton from the ligand-attached nitrogen coordinated to the ruthenium. The end result is the same, but the mechanism is completely different than expected (Noyori et al., 2001).
“The overall point I want to make is that if you’re trying to develop a new type of catalyst with a different metal, it is going to look a lot different,” said Bullock. “You don’t want to replace platinum or palladium with iron or copper and try to use the same ligand set. The ligands will almost certainly change.” The idea, he explained, is to not try to emulate what precious metals are doing as catalysts. Instead, the intention is to look at the reactivity characteristics of the cheap metals, understand the electronics of the reactions and the energy states, and then build a catalyst around those metals from the ground up using fundamental principles.
As an example, Bullock discussed work done in his laboratory developing a molybdenum-based catalyst for hydrogenating ketones to make alcohols at low temperature and hydrogen pressure and under mild conditions (Bullock and Voges, 2000). This reaction occurs by a different mechanism, one that capitalizes on the reactivity patterns of molybdenum hydrides and involves delivering a proton to the oxygen atom in the ketone first, leaving a metal hydride that then delivers hydride to the carbon atom, creating the saturated alcohol. Fundamental research on the acidity of metal hydrides and both the kinetics and thermodynamics of metal hydride behavior made the development of this catalyst possible.
The same types of basic research studies were done by other researchers to develop an iron-based catalyst that also performs a heterolytic cleavage of hydrogen as the key step in the hydrogenation of carbon-oxygen double bonds (Casey and Guan, 2009). But equally important is the fact that the catalyst is regenerated under low-pressure hydrogen conditions. More recently, another group created an iron-based catalyst that under similarly mild conditions works at very low catalyst loadings of 0.05 mole percent (Langer et al., 2011).
Iron-based catalysts also can be used to hydrogenate carbon-carbon double bonds. Again, this work was based on solid fundamental chemistry research to create redox-active ligands that help drive the reaction. One of these catalysts achieves turnover frequencies of up to 1,800 per hour in the conversion of 1-hexene to hexane (Bart et al., 2004).
High-Volume Applications of Cheap Metal Catalysts
Although the examples cited above show that it is possible to create potent catalysts for the production of the type of low-volume specialty chemicals used in the pharmaceutical and agricultural industries, the impact on the overall demand for expensive and rare metals is not likely to be substantial. An area where a real impact could be had is in the area of