The Engineering of Chemical Synthesis: Humans and Machines Working in Harmony

摘要

“Chemical synthesis has previously tended to rely heavily on robust labour-intensive processes. We have been advocating a machine-assisted approach to synthesis for many years. To replace a bench chemist with a machine is not only unrealistic but impossible. What is realistic is to use this rapidly developing array of equipment and novel concepts to take us way beyond where we are today …”. Read more in the Guest Editorial by Steven V. Ley. Indeed, for a number of years we have been advocating a machine-assisted approach to synthesis. This makes sense for so many reasons, not least of which is how to best maximize the human resource by increasing efficiency and giving people more time to think, plan, and make discoveries. As in all the sciences, collaboration between the different disciplines leads to synergistic benefits. Nowadays engineering of multistep chemical synthesis adopts a holistic systems approach to the subject that requires full integration of all the chemical steps together with the device engineering and the necessary underpinning informatics. Continuous-flow-chemistry methodology has added yet another component to our armoury. When linked to current batch methods, this generates new capabilities and process windows to provide enhanced robustness through better control and data feedback. The coordination of multiple pieces of equipment through cheap microprocessors such as the Arduino and Raspberry Pi allows a new level of laboratory management, making way for machine-to-machine learning algorithms and the upcoming artificial-intelligence revolution. The beginnings of augmented and virtual reality techniques are already impacting on how we present our science today. Video capture of information with digital cameras for monitoring or for thermal and high-speed imagery, provide a rapid return of kinetic data and adds a further safety element to our experimental audit trails. This leads naturally to the future use of head-up displays and other wearable or handheld devices. Even mundane facilities such as fume hoods are evolving to be more responsive to energy-saving techniques or the use of face-recognition software to map equipment configurations and their dynamics during usage. Mobility and flexibility are also features of any new laboratory design. Repetitive tasks for scaleup, reaction optimization, and during original reaction discovery programs can all be relegated to machinery and advanced robotics. With this said, it is also imperative however, to understand that synthesis is a highly complex task that requires the marshalling of a huge range of experience and skills, both intellectual and practical, acquired over a significant period of time. Serendipity also has a role to play; it is not easy to automate synthesis. As a serious synthetic chemist with many years experience, I recognize that to replace a bench chemist with a machine is not only unrealistic but impossible. What is realistic is to use this rapidly developing array of equipment and novel concepts to supplement and enable new events to take us way beyond where we are today. To use the word automation is to do a disservice to what will be possible in the future. Our machines will aid us in the decision-making process and reinforce learning and understanding. Computational algorithms and predictive methods should be an integral part of any modern synthesis program. Interestingly, how we deliver electrons to a chemical process, whether through the increasingly popular methods of electro- or photochemical means, is reliant to some extent on the innovative design of the equipment used. Harnessing enzymes in synthesis also goes beyond the basic biotransformation to exploit directed evolution methods, immobilization, and recyclability of the systems for multistep applications. Compartmentalisation techniques, plug flow reactors, and sequential processing are all ideas more akin with how a cell assembles complex functional materials. Clearly there are