17 th International Congress of Chemical & Process engineering, Prague, Czech Republic, 27-31 August 2006. Enhancing process development using high throughput technologies A case study using an L-proline catalysed aldol reaction K. Novakovic , C. Grosjean*, T. Schütz*, M. J. Willis, A. Wright and A.Whiting* School of Chemical Engineering and Advanced Materials, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK *Durham University, Department of Chemistry, Science Laboratories, Durham DH1 3LE, UK katarina.novakovic@ncl.ac.uk ; christophe.grosjean@durham.ac.uk ; thorben.schuetz@durham.ac.uk ; mark.willis@ncl.ac.uk ; a.r.wright@ncl.ac.uk ; andy.whiting@durham.ac.uk Abstract The objective of this work is to use a robotic workstation in conjunction with process systems analysis tools to enhance process development. A case study using an L-proline catalysed aldol reaction is used to demonstrate that, in conjunction with appropriate experimental designs, meaningful data streams for mechanistic / kinetic studies can be generated. It is shown that for this system small scale (13ml) reactors in a robotic high throughput platform may be used for (1) initial screening of potential solvents through assessment of the solubility and miscibility characteristics of the reactants and catalyst (2) determination of the concentrations of reactants and catalyst that maximise the production of aldol. To assess reaction thermo chemistry and at the same time generate data suitable for detailed mechanistic modelling a large scale (1 litre) calorimeter is used. The experimental data allowed a novel reaction network for the L-proline catalysed aldol reaction to be proposed and verified through a kinetic modelling exercise. Introduction Robotic workstations are used mainly to support combinatorial chemistry and screening for new compounds and catalysts. Their potential to provide useful information for use in commercial, chemical engineering, safety, and environmental aspects of process development is not yet fully explored. For instance it is known that downscaling can alter the relative significance of physical phenomena, in particular handling and dispensing, the accurate control of transport processes, mass transfer and mixing within the reaction mixture as well as solid and fluid dynamics, all of which may impact on the rate and reproducibility of reactions at larger scale. If HTT are to be successfully extended to process development, experimental results must be meaningful and reproducible throughout scale up. Using an advanced high throughput experimental platform (the Chemspeed SLT 106 synthesizer) and a reaction calorimeter the extent to which HTT experiments may be used to provide the necessary quantitative understanding of both physical and chemical phenomena are assessed through a three stage development program. The reaction system The chemical system used for this study was the L-proline catalysed aldol reaction between p- nitrobenzaledehyde and acetone 1 . This was chosen because it is a challenging system as it is potentially non homogenous, it suffers from undesired side reactions and the mechanistic understanding is not readily available 2 . The starting point for the development study was therefore knowledge of the reactants, desired products, the catalyst, typical solvents and possible reaction temperatures.