Application of a Micromixer for the High Troughput Screening of Fluid-Liquid Molecular Catalysis

Abstract

High throughput synthesis methodologies, such as combinatorial techniques, are now applied to the discovery of molecular catalysts. I Libraries of ligands which can be turned into catalysts by complexation to transition metals, are accessible. The effectiveness of this approach has been demonstrated for restricted libraries of compounds and in the case of single liquid phase catalysisPl However, numerous reactions of interest such as olefm oligomerisation, hydrogenation, carbonylation, hydroformylation, etc. are operated in gas-liquid or liquid-liquid systems. Inadequate control of phase and catalyst presentation, resulting from non-optimised agitation, may effectively have dramatic consequences in the estimation of selectivity and reactivity. For example, enantio-and regioselective catalysed reactions susceptible to mass transport effects, are known. Thus, a major challenge is to develop special reactors for rapid catalyst screening that would ensure good mass and heat transport, in a small volume. Application of such apparatus for intrinsic kinetic determination would also be of high interest. In this paper, a new concept to achieve High Throughput Screening (HTS) of polyphasic fluid reactions is proposed. As test reactions, a gas-liquid asymmetric hydrogenation and a liquid-liquid isomerisation have been chosen to validate our approach of HTS experiments. A preliminary work with the liquid-liquid system has been published recently? ConceptTo our knowledge,3 commercial apparatus for High Throughput Screening of multiphase catalytic reactions are all based on the very simple concept (Figure 1): several batch type tank reactors are downscaled (step a) and placed in a rack (step b). Ideally, one reaction/catalyst or substrate can thus be screened in each of the millireactors (step c).That paralleVbatchwise approach is just derived from traditional glassware and pressure apparatus adding small scale parallelisation and ca. a tenfold downscaling of reaction volumes. Most of the commercial apparatus are equipped with agitation/heating devices and the consumption of gaseous reagents can also be monitored. Because of their batchwise concept, their familiar design and the M. Matlosz et al. (eds.), Microreaction Technology

Chemistry in Microstructured Reactors

“…[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.…”

Microchemical Engineering: Components, Plant Concepts, User Acceptance – Part II

“…Transient serial screening using pulse techniques, introduced by CNRS-LGPC, Lyon (France), is a truly pragmatic approach [199,200]. The multiphase reactions investigated rely on precious transition metal complexes that are often available only in very low amounts due to complex multistep synthesis.…”

Gas/Liquid Reactions: Sections 5.4–5.7

“…The hydrogenation of a methyl cinnamate was investigated as a model reaction for demonstrating the benefits of a new screening technique, based on transient serial screening of multi-phase reactions [63,64,66]. Besides ensuring proper pulse formation and reducing pulse broadening, one main issue concerns having large mass transfer by use of micro reactors to carry out reactions in a kinetically controlled manner [63,66].…”

“…By homogeneous reaction of the conjugated double bond system selectively the C=C double bond is hydrogenated [63][64][65][66]; the ester function is not affected. Moreover, by action of the chiral catalyst, a chiral hydrogenated product is created with good enantioselectivity.…”

“…[P 20] The reaction was carried out using ethylene glycol/water (60 : 40 wt.-%) and hydrogen [63,66]. To stabilize the gas/liquid interface, sodium dodecyl sulfate was added as surfactant.…”