Fixed Bed Continuous Hydrogenations in Trickle Flow Mode: A Pharmaceutical Industry Perspective

Since the 1930s, fixed bed reactors (FBR) have been operated for continuous hydrogenation reactions in the petrochemical/fine chemical industries, with publications each year detailing engineering principles, scientific breakthroughs, equipment design and setup, from these industries. Only in the last two decades, FBR have started to be utilized in the pharmaceutical industry as a result of sustainability commitment and growing demand of complex and specialized drugs. Most of the engineering knowledge is transferable across industries; however, there are differentiators inherent to each industry, with the pharmaceutical industry having its own unique challenges. One of the main differentiators between industries is the reactor scale and, consequently, reactor catalyst requirements. Petrochemicals or fine chemicals operate on a large industrial scale, with up to 72 m high reactors, with an internal diameter on the order of 5 m (China Petroleum & Chemical Corporation), and require large volumes of catalysts because of the high product demand for thousands of tonnes per year, while for the pharmaceutical industry, a smaller scale reactor is required for product demand in the thousands of kilograms per year range. It is the reactor size that defines catalyst specifications, such as particle size and geometry. Many transformations have emerged from academic and medicinal chemistry groups utilizing the ThalesNano H-Cube; however, there are relatively few reported processes that have been scaled within the pharmaceutical industry. This Perspective outlines a review of continuous flow hydrogenation technologies; focusing on the trickle bed reactor (TBR) and the respective process operation and effect of process variables on reaction rate requirements for the pharmaceutical industry; it also reflects on transformation examples using TBR across the pharmaceutical industry.