In recent years, chemistry in flowing systems has become more prominent as a method of carrying out chemical transformations, ranging in scale from analytical-scale (microchemistry) through to kilogram-scale synthesis (macrochemistry). The advantages are readily apparentincreased control of conditions leading to greater reproducibility, scaleability, and increased safety/reduced lossalthough its acceptance as a viable synthesis technique has been limited due to its drawbacks, primarily precipitation, liquid handling, and diffusion of the reaction within the reactor. Here, we present details of a system which bridges the gap between micro- and macroreactors and has enabled fast reaction optimisation (using small amounts of reagents) and subsequent multigram scale-up using a commercial reactor.

Microwave-assisted organic synthesis in a laboratory-scale monomodal microwave reactor is investigated for continuous flow applications using fluorous spacer technology. The benchtop continuous flow microwave described allows sequential processing of multiple plugs using small amounts of reagents for reaction optimization, scale-up and array synthesis. The system features online monitoring of temperature, pressure and microwave power. Several different reactions have been scaled up, including a Suzuki-Miyaura cross-coupling reaction and nucleophilic substitutions. In all cases it was possible to optimize the reaction conditions on a small scale (∼300 µL processing volume), and achieve similar conversions on an intermediate scale (∼30 mL), offering the potential for further scale-up without modifying the optimized conditions (direct scalability) producing similar isolated yields in the C-C bond formation reaction.

This paper reports a novel evaporator and its integration with an automated sample handling system to create a high throughput evaporation platform. The Vaportec V-10 evaporator uses a high speed rotation motor ( approximately 6000 rpm) to spin the vial containing a sample, creating a thin film of solvent which can be readily evaporated by the application of heat to the vial, while the consequent centrifugal force prevents "bumping". An intelligent algorithm controls pressure and temperature for optimum solvent removal conditions and end of run detection, critical for automation. The system allows the option of evaporation directly from a sample source vial, or alternatively, integrated liquid handling facilities provide the capability of transferring samples portionwise from a (large) source vial or bottle to a (small) daughter container, enabling efficient sample reformatting, with minimum user intervention. The open access system makes significant advances over current vacuum centrifugal evaporators in terms of evaporation rate and ease of automation. The evaporator's main features, the integration of robotics to provide automation, and examples of evaporation rates of a wide range of solvents from a variety of containers are described.