Nitroalkanes offer a strategic tool for cost reduction in pharmaceutical syntheses

The pharmaceutical industry is moving through a period of great change. Not only are the global players consolidating, but companies are fundamentally changing the way they approach the market. “Big Pharma” has learned to focus on what it does best that is, the discovery and marketing of new products. All other endeavours are increasingly being out-sourced to a growing number of support laboratories and pharmaceutical intermediate manufacturers. In fact, pharmaceutical companies that once took a vested interest in undertaking their own manufacturing are now taking the view that internal production is actually alien to their key business interests. As the pharmaceutical industry concentrates internally upon drug discovery, it is making much greater demands upon its suppliers for a broad range of complex intermediates and bulk actives. Successful intermediate suppliers have developed the ability rapidly to scale up a broad range of traditional processes, as well as innovative new chemistries and all of this while holding the line on manufacturing costs. Nitroalkane chemistry offers the pharmaceutical industry a strategic tool for success in this endeavour. Nitroalkanes specifically nitromethane, nitroethane, 1-nitropropane and 2-nitropropane are extremely versatile, inexpensive synthetic feedstocks (Figure 1). Although some highly successful pharmaceuticals such as ranitidine, methyldopa and ethambutol are based on nitroalkane chemistry, the full potential of this novel class of compounds has yet to be realised. The usefulness of nitroalkanes lies in their ability to provide new, cost-effective synthetic routes to existing compounds, as well as highly efficient routes to new compounds. While they are most recognised as a means of adding nitro or amino functionality to a molecule, their exceptional versatility offers synthetic chemists numerous other benefits. Nitroalkane chemistry can, for instance, provide a vehicle for connecting two halves of a complex molecule. It can also provide synthetic chemists with a set of unique tools to place a variety of functional groups at specific locations on a given compound. This nitroalkane chemistry is actually quite different from what many people are familiar with when they think of nitro compounds.