High-Throughput Screening of Molecular Catalysts Using Automated Liquid Handling, Injection, and Microdevices

Abstract

A new concept for the high-throughput screening of multiphase reactions involving molecular catalysts is described. It combines pulse injections of catalysts and substrate and mixing in a microdevice. The novelty of the concept resides in dynamic sequential vs. batchwise operations. Some advantages over traditional batch parallel operations are lower inventory of sample (down to~g) coupled with accurate control of reaction time, larger range of operating conditions (pressure, temperature), simpler and fewer electromechanical moving parts and easy automation. Results on liquid-liquid (biphasic allylic alcohol isomerization), and gas-liquid (asymmetric hydrogenation) reactions indicates that the number of tests per day can easily reach 50 d-1 with inventory of sample (Rh) per test as low as 5~g.

Chemistry in Microstructured Reactors

“…Organometallic reactions can also be carried out in microstructured reactors with higher efficiency than in batch reactors, as exemplified by the studies of Haswell, Fletcher, and co-workers, [80,176] who investigated the Kumada-Corriu reaction by reacting 4-bromoanisol with phenylmagnesium bromide in the presence of the Merrifield-resinimmobilized salen-type nickel complex A (Scheme 15), which in the form of small pellets were packed into capillaries of 1-2 mm diameter; the reagents were then pumped through these microstructures. The reaction rate constant was determined through kinetic measurements, which determined that continuous flow in microchannels led to an increase in the rate by a remarkably large factor of 3.…”

“…[175][176][177][178][179] The organic phase, substrate, and water were continuously pumped into an interdigital mixer (IMM) and analyzed after flowing through a residence-time module.…”

Organic Synthesis with Microstructured Reactors

“…Vice versa, it can be deduced that future research studies need the gathering and comparison of kinetic data for batch and continuous microreactor processing in much more detail. One study did anticipate this trend and describes the influence of mixing performance and of experimental protocols on the conversion for a homogeneously catalyzed isomerization of homologous allyl alcohols using four different types of equipment commonly used in the field of reaction screening, including a micro-mixer-tube-reactor set-up [19]. The corresponding conversions vary depending on the choice of equipment from 20 % to nearly 100 % for the same reaction.…”

“…A particularly well documented benchmarking of the interplay between interface, respective mixing efficiency, and gross reaction results such as conversion is given for the transition-metal catalyzed isomerization of allyl alcohols in a two-phase system [19,31] (see Scheme 12).…”

“…Isomerization of allyl alcohols in a liquid/liquid two-phase system, performed by diverse reactors. From left to right: Conversion in a stirred test tube with pre-mixing by a micro mixer (medium grey); conversion in a stirred test tube without pre-mixing (black); conversion in a special mini batch apparatus used for kinetic investigations (light grey); conversion in a continuously operating micromixer/tube reactor (white) [19] (by courtesy of Swiss Chemical Society).…”