Development of a continuous flow microreactor for chemical synthesis with in-line catalysis, heating and detection

Chaplain, Grant Thomas Robert

Abstract

The development of a micro fluidic flow organic synthetic system incorporating heterogeneous catalysis, novel heating regimes and in-line spectroscopic detection is described. The reactions used to model the flow synthesis include Suzuki and acetylation reactions using heterogeneous immobilised palladium and tungstosilicic acid catalyst respectively. Catalyst immobilisation was carried out on silica monoliths made using Tetraethyl orthasilicate (TEOS) as a precursor which produced surface areas of 240 ±9 m² g¯¹ and porosities between 0.65 and 0.70 with nano pore diameters of 1100 ±20 nm. Functionalisation of the TEOS monoliths with palladium was achieved through the formation of palladium nano clusters within the nano pores of the monolith. Once immobilised, the palladium bound monolith was placed into a flow stream as a capillary monolithic reactor (CMR). Microwave and conventional oven heating were applied to the catalyst as the reactants 4-bromobenzonitrile and phenyl boronic acid to produce 4-cyanobiphenyl flowed through with different residence times and temperatures. Under microwave heating, the monolithic structure and the tube connections present in the microwave were observed to break down, an effect thought to be associated with very high localised heating of the palladium. Heating however using convection from a column heater proved to be more successful and facilitated the continuous flow of reactants without flow disruption. In-line Raman spectroscopy was placed in to the flow system as a detection method replacing off-line gas chromatography-mass spectrometry (GC-MS). Calibration using Raman spectra was achieved using partial least square regression (PLSR) which gave results within ±10% to those obtained using the GC-MS method. Using the flow system with in-line Raman analysis, the reaction was optimised and kinetic studies were performed. For the reaction conditions used, the overall 2nd order rate constant k was 4.45 x 10¯³ M¯¹ s¯¹, and the optimal flow rate for 4-cyanobiphenyl production was 0.30 mL min¯¹ producing 53 g h¯¹ (with a 14% conversion). The optimal conversion under the flow parameters performed was at 0.02 mL min¯¹ showing 61% conversion (producing 17 g h¯¹).

The reaction was then altered to accommodate an acetylation reaction. Tungstosilicic acid was immobilised on the surface of TEOS monoliths and the CMRs were actively catalysing the reaction between 4-bromophenol and acetic anhydride to produce 4-bromophenyl acetate. Unfortunately, leaching of the tungstosilicic acid was observed from the monolith surface which interfered with Raman spectroscopic observations making detection of reactants and products difficult.

In conclusion the overall project was a successful venture. It allowed fast optimisation procedures for reaction scaling, and produced a significant amount of molecular data for each reaction ran. This model set-up was appropriate and versatile for the objectives of this project. Areas within the research to address were improving the catalyst immobilisation techniques, and different heating mechanisms. Despite this, the flow reaction system was an advance towards developing a fully automated flow synthetic optimisation system.

Citation

Chaplain, G. T. R. Development of a continuous flow microreactor for chemical synthesis with in-line catalysis, heating and detection. (Thesis). University of Hull. https://hull-repository.worktribe.com/output/4215638

• Thesis Type: Thesis
• Deposit Date: May 2, 2014
• Publicly Available Date: Feb 23, 2023
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4215638
• Additional Information: Department of Chemistry, The University of Hull
• Award Date: May 1, 2013