Enabling Tools Reviews

Organic Synthesis: March of the Machines  Organic synthesis is changing; in a world where budgets are constrained and the environmental impacts of practice are scrutinized, it is increasingly recognized that the efficient use of human resource is just as important as material use. New technologies and machines have found use as methods for transforming the way we work, addressing these issues encountered in research laboratories by enabling chemists to adopt a more holistic systems approach in their work. Modern developments in this area promote a multi-disciplinary approach and work is more efficient as a result. This Review focuses on the concepts, procedures and methods that have far-reaching implications in the chemistry world. Technologies have been grouped as topics of opportunity and their recent applications in innovative research laboratories are described.

Angew. Chem. Int. Ed.
 2015, 54, 3449-3464, S.V. Ley, D.E. Fitzpatrick, R.J. Ingham, R.M. Myers

Flow Chemistry: Intelligent Processing of Gas-Liquid Transformations using a Tube-in-Tube Reactor  This Account examines our efforts toward the development of a simple, unified methodology for the processing of gaseous reagents in flow by way of development of a tube-in-tube reactor device and applications to key C–C, C–N, and C–O bond forming and hydrogenation reactions. We further describe the application to multistep reactions using solid-supported reagents and extend the technology to processes utilizing multiple gas reagents. A key feature of our work is the development of computer-aided imaging techniques to allow automated in-line monitoring of gas concentration and stoichiometry in real time. We anticipate that this Account will illustrate the convenience and benefits of membrane tube-in-tube reactor technology to improve and concomitantly broaden the scope of gas/liquid/solid reactions in organic synthesis.

Acc. Chem. Res. 2015, 48, 349-362, M. Brzozowski, M. O’Brien, S.V. Ley, A. Polyzos

Flow Chemistry Meets Advanced Functional Materials  Flow chemistry and continuous processing techniques are beginning to have a profound impact on the production of functional materials ranging from quantum dots, nanoparticles and metal organic frameworks to polymers and dyes. These techniques provide robust procedures which not only enable accurate control of the product material’s properties but they are also ideally suited to conducting experiments on scale. The modular nature of flow and continuous processing equipment rapidly facilitates reaction optimisation and variation in function of the products.

Chem. Eur. J. 2014, 20, 12348-12366, R.M. Myers, D.E. Fitzpatrick, R.M. Turner, S.V. Ley

Camera Enabled Techniques for Organic Synthesis  A great deal of time is spent within synthetic chemistry laboratories on non-value-adding activities such as sample preparation and work-up operations, and labour intensive activities such as extended periods of continued data collection. Using digital cameras connected to computer vision algorithms, camera-enabled apparatus can perform some of these processes in an automated fashion, allowing skilled chemists to spend their time more productively. In this review we describe recent advances in this field of chemical synthesis and discuss how they will lead to advanced synthesis laboratories of the future.

Beilstein J. Org. Chem. 2013, 9, 1051-1072, S.V. Ley, R.J. Ingham, M. O’Brien, D.L. Browne

Flow Microwave Technology and Microreactors in Synthesis  A bespoke microwave reactor with a glass containment cell has been developed for performing continuous flow reactions under microwave heating. The prototype unit has been evaluated using a series of standard organic chemical transformations enabling scale-up of these chemical processes. As part of the development, a carbon-doped PTFE reactor insert was utilized to allow the heating of poorly absorbing reaction media, increasing the range of solvents and scope of reactions that can be performed in the device.

Aust. J. Chem., 2013, 66, 131-144, I.R. Baxendale, C. Hornung, S.V. Ley, J. de M. Muñoz Molina, A. Wikström

Lesser-known Enabling Technologies for Organic Synthesis  In this review we summarise both new emerging technologies as well as some overlooked methods which are beneficial to a variety of synthesis applications. Separation Methods: Low-Temperature Chromatography; Reflux Chromatography; Phase-Switching Methods e.g. Affinity-Based Phase-Switching, Fluorous Tags, Acid-Base and Polarity Tags, Transition-Metal and Ligand Affinity Tags; Hydrogen-Bonding Interactions, Polyaromatic Affinity Tags, Crown Ether Tags; Redox-Switchable Tags; Reactive and Irreversible Tags e.g. Click Tags, Diels-Alder Tags; Phase-Switching Involving Precipitation e.g. Precipitation by Polymerisation, Solubility-Switching, Temperature-Dependent Solubility; Size-Exclusion Tags. Synthesis Methods: Cooled Microwave Heating; Ball-Milling; Design of Experiments and Related Techniques.

Synthesis 2011, 1157-1192, M. O’Brien, R. Denton and S.V. Ley

Lab of the Future: the Importance of Remote Monitoring and Control  Chemical laboratories and the equipment within them have changed very little over the last two centuries. However, the introduction of enabling technologies and their impact on current working practices is starting to redefine the laboratory environment. In this article the application of remote control software applied to real applications of flow-based synthesis are demonstrated and the related improvements in efficiency and safety discussed. The use of webcams to remotely monitor synthetic procedures is described along with the associated enhancements that can be achieved.

Chim. Oggi./Chemistry Today 2011, 29, 28-32, M.D. Hopkin, I.R. Baxendale and S.V. Ley