New ‘chemistry’ projects in the iPRD Purposes: Getting feedbacks on industrial relevance Discussing with potential interested partners Projects: Electrochemical flow-cells in chemical manufacturing ‘On water’ process development Fe NPs catalysis

Electrochemical flow-cells in manufacturing Faradaic efficiency as high as 100% Bao Nguyen, Charlotte Willans, Nikil Kapur Chem. Commun., 2015, 51, 1282 2

Electrochemical flow-cells in manufacturing Current electrochemical flow technologies: Org. Process Res. Dev., 2015, 19, 1424–1427 3

Electrochemical flow-cells in manufacturing Two new projects in the use of electrochemical flow-cells: Replacing oxidants/air with electrochemical flow-cells (John Blacker, Bao Nguyen) Versatile flow platform for high throughput catalyst screening and rapid optimisation (Charlotte Willans, Nik Kapur, Richard Bourne, Bao Nguyen). Bao Nguyen, Nikil Kapur, Charlotte Willans, Christopher Jones 4

High-throughput flow platform Problems: Tedious catalytic reactions (using base metals) screening for discovery and optimisation; many Cu/Fe complexes can be difficult to make/ isolate/use (quality control issues). Lack of reliable kinetic/ performance data for scaling up. Relevance: Faster discovery and optimisation of base metal catalysed reaction, leading to more successfully scaled up processes. Charlotte Willans, Nikil Kapur, Richard Bourne, Bao Nguyen 5

High-throughput flow platform Aims: Streamline discovery and optimisation with one platform which generate catalysts and evaluate/optimise reactions. Remove the need of specialists’ techniques. Collect large volumes of profiling data from a large volume of catalytic reactions to guide both scaling-up and subsequent mechanistic investigations. Charlotte Willans, Nikil Kapur, Richard Bourne, Bao Nguyen 6

High-throughput flow platform Methods: Design and optimise modular electrochemical flow-cells which allow easy swapping of metal electrodes and ligand precusors. Linking these with self-optimising reactors. HPLC, MS online analysis and data collection. Charlotte Willans, Nikil Kapur, Richard Bourne, Bao Nguyen 7

Replacing oxidants with electrochemical flow-cells Problems: Stoichiometric amount of oxidant will always lead to waste in synthesis. Air can be used in some cases, but poses fire hazard and normally the flow rate is very high (solvent and reagent evaporation!). The required intrinsic redox potential may often limit options. Relevance: Potentially applicable to a very wide range of synthetic reactions both catalytic and non-catalytic. Tunable applied potential means better functional group tolerance. J Blacker, Bao Nguyen 8

Replacing oxidants with electrochemical flow-cells 41-91% yield Aims: Using highly efficient electrochemical flow-cells designed in the iPRD to carry out the desired oxidation instead of oxidants. Demonstrating the use of these flow-cell in a ‘large scale’ reaction and evaluating its green metrics and power cost. J Blacker, Bao Nguyen 9

Replacing oxidants with electrochemical flow-cells Methods: Design: porous electrodes, split channels to separate the oxidation and reduction. Evaluate replacement of oxidants across a wide range of redox potential (e.g. PhI(OAc)2, H2O2, K2S2O8, NaIO4, etc.) A redox loop to enable sub-stoichiometric use of oxidant has also been demonstrated elsewhere. J Blacker, Bao Nguyen 10

‘On water’ process development “On water” and micellar acceleration effects 11

‘On water’ process development “On water” and micellar acceleration effects 12

‘On water’ process development Advantage: Simple work-up and little to no organic solvent required. Acceleration effect has been attributed to increased concentration and stabilisation of transition state at droplet surface. 13

‘On water’ process development Problems in process development: Lack of fundamental understanding of acceleration in micellar/droplet catalytic reactions. No recovery process for costly surfactants (currently removed by flash chromatography). Full understanding of kinetics and the dependence of reaction outcome on droplet size/shear rate/’concentration’ is still missing. Bao Nguyen, John Blacker, Nik Kapur, Guy Lloyd-Jones 14

‘On water’ process development Relevance: Significant reduction of organic solvent use (including workup), faster and more efficient continuous processes. The team: Bao Nguyen (synthetic and physical organic chemistry), Nik Kapur (fluid dynamics), John Blacker (process chemistry), Guy Lloyd-Jones (physical organic chemistry). Bao Nguyen, John Blacker, Nik Kapur, Guy Lloyd-Jones 15

‘On water’ process development Aims: Linking mixing efficiency, droplet size, input energy and thermal effect (by high energy mixing), concentration and functional groups of starting materials with ‘on water’/micellar reaction performance. Develop predictive capability for new ‘on water’/micellar reactions and chemical processes. Bao Nguyen, John Blacker, Nik Kapur, Guy Lloyd-Jones 16

‘On water’ process development Aims: Demonstrate proof-of-concept continuous processes to streamline workup and enable recycling of water and surfactants. Evaluate the green metrics of these new processes against industrial benchmarks for similar processes using organic solvents. Bao Nguyen, John Blacker, Nik Kapur, Guy Lloyd-Jones 17

‘On water’ process development Methods: Jet mixer and high shear mixer to control droplet size and mixing rate in batch and flow. ‘On water’ vs micellar reactions to differentiate between concentration effect and droplet surface catalysis. Bao Nguyen, John Blacker, Nik Kapur, Guy Lloyd-Jones 18

‘On water’ process development Methods: Colorimetry/fluorescence experiments with high speed camera to evaluate mixing, mass transfer between droplets. Population balance modelling of droplet and system energies and microscopic thermal imaging. Bao Nguyen, John Blacker, Nik Kapur, Guy Lloyd-Jones 19

Fe nanoparticles in catalysis Problems: Many reactions are catalysed by FexOy nanoparticles formed in situ, even asymmetric reactions. Characterisation of these are extremely difficult under catalytic conditions. There is no established relationship between particle size and ligand and catalytic activity/selectivity. Bao Nguyen, Patrick McGowan 20

Fe nanoparticles in catalysis Relevance: Expansion of substrate scope to C=C, O/NBn, O/NCbz will allow sector wide replacement of Pd/C with much cheaper and more sustainable alternatives. Aims: Establishing the relationship between ligand/stabiliser and particle size and catalytic activity/selectivity, including enantioselectivity; designing more reactive catalysts for other types of substrate. Bao Nguyen, Patrick McGowan 21

Fe nanoparticles in catalysis Methods: The team: Bao Nguyen (synthetic and physical organic chemistry), Patrick McGowan (inorganic chemistry). Bao Nguyen, Patrick McGowan 22

Please come and talk to us if the projects interest you.