Organic Synthesis: March of the Machines

Abstract

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.

The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds

“…7,72,73 Several different analytical systems were used successfully, such as in-line FT-IR (predominantly with Attenuated Total Reflectance (ATR) cells), [74][75][76][77][78][79][80] NIR, 81,82 Raman 83 and NMR spectroscopy, 84,85 as well as on-line MS 86,87 and HPLC. 88,89 However, everyday application of these approaches is hindered by the fact that off-line solutions are usually more convenient, since a wider toolbox (consisting of existing equipment) is available for the analysis of less demanding analytes (i.e.…”

“…95 The existing methods 7,73 can be classified as in-line work-up or final product purification techniques, according to the position in a multistep sequence, where they are preferably used.…”

“…1a). On the other hand, flow chemical tools also provide many possibilities, 7,8 but their implementation into multistep processes requires the design of the system, reaction conditions, analytics, work-up and purification processes, while constantly keeping this goal in mind (Fig. 1b).…”

“…Our ongoing efforts in this field 9 inspired us to summarize the difficulties concerning the integration of individually optimized chemical reactions into multistep systems, as well as common problems and their innovative solutions described in the recent literature [6][7][8][10][11][12][13][14][15][16][17][18] of API continuous flow synthesis, including analytics and purification methods.…”

Beyond Organometallic Flow Chemistry: The Principles Behind the Use of Continuous-Flow Reactors for Synthesis

“…128,129 Obtaining reaction kinetics can be a time-consuming undertaking and, recently, a lot of effort has been devoted to develop completely automated systems. 130 This allows to reduce the manual labor, to increase the efficiency of results collection and to implement Design of Experiment methods (DOE). 131 This approach has been used to optimize the Mizoroki-Heck coupling between 4-chlorobenzotrifluoride with 2,3-dihydrofuran in a microreactor ( Figure 11).…”