At the 2010 Fall American Chemical Society (ACS) meeting in Boston, Professor Steven V. Ley, BP (1702) Professor of Organic Chemistry at the University of Cambridge presented a novel approach to the use of flow chemistry as a synthetic technique. The rate of technology change continues to gather pace and recent economic events continue to dominate world headlines. Companies are continually asking their employees to do more with less and the time available to complete these tasks appears to be reducing. At the 2010 Fall ACS Meeting in Boston, Professor Steven V. Ley received the Tetrahedron Prize for Creativity in Organic Chemistry. As you would expect, his award address, “The Changing Face of Organic Synthesis”, contained the outline of some of Professor Ley’s brilliant work on the synthesis of natural products. There was also a related and very insightful detail. To paraphrase a comment made, “Synthetic chemists are very creative people, so why waste their time performing routine syntheses when you can get a machine to do it for them?” The machine, or technique, that Professor Ley was referring to was continuous flow chemistry, a method that takes advantage of the ability to choose reaction conditions that may not be possible to attain in a more traditional batch reactor, typically, leading to faster reactions with better yields.
One of the challenges with flow chemistry is that it has traditionally been difficult to optimize a chemical reaction using a flow reactor. It is essentially a process of trial and error as conditions and flow rates are altered until a steady state is found, producing the desired product at the desired yield. A change is made, a sample collected and an analysis performed. The time taken to perform these offline analyses leads to delays in optimizing the system, making it difficult to realize the full increase in productivity that this type of system can deliver.
Collaboration between Professor Ley and METTLER TOLEDO has resulted in the development of a reliable solution which accurately optimizes a flow reaction system quickly and easily. This method, consisting of a DS Micro Flow Cell coupled to a ReactIR™ instrument, makes the real time optimization of a flow reactor a reality. Typical control parameters, such as the flow rate of reactants or the temperature of the reaction cell can be changed and the impact of those adjustments immediately observed as the ReactIR™ system measures reactor output. The formation of products, by-products and reactive intermediates can all be followed and this information used to make immediate adjustments in order to optimize operating conditions for the entire system. As it is now possible to study dispersion effects and see when steady state has been achieved, the ReactIR™ system delivers additional benefits. It is easy to realize when a product can be collected from the reactor. In fact, the use of ReactIR™ technology means that final products can sometimes be collected before steady state is achieved saving time and reactants. Also, any issue such as a failed or blocked pump is immediately detected, giving the operator an early indication that the product being collected is not the desired one.