Development of novel continuous flow reaction methodology for fine chemical production

Alotaibi, Mohammed

Abstract

At present, synthesising complex chemical compounds is a process that is facilitated by employing conventional batch based laboratory approaches. This path, which can to some extent be automated, frequently suffers from inefficient and uncontrollable chemical conversions cannot be controlled over the course of the numerous possible steps of the synthesis process and, which in turn leads to generally lacks in terms of product yields and a poor of product selectivity.
In this research chemical synthesis was conducted in combination with small meso (μm) and micron-scale flow reactors, to offer more effective control over chemical reactions compared to conventional batch chemistry. The work capitalised the unique high surface area and excellent thermal transfer characteristics available in meso/micro flow systems, facilitating the creation of controllable, non-uniform, and time-dependent localised reactant, intermediates, and product concentrations, which generate a novel dimension in reaction control that is similar to the chemical control engaged in with biological systems. One factor investigated in the current research was the production of a stable monolithic structure via a sol-gel approach. The macroporous silica-monoliths were fabricated through controlled processes from two precursors tetramethoxysilane (TMOS) and tetraethyl orthosilicate (TEOS) with different polymer templates. Commercial available Candida antarctica lipase (CAL) was employed, to produce an active and stable microreactor for biocatalysis reactions. Its activity was investigated through the hydrolysis of 4-nitrophenyl butyrate by using a water-decane biphasic system.
The kinetic studies were performed using Candida antarctica lipase (CAL) immobilized on macroporous silica monolith. Interestingly, the kinetic studies had identified that a similar value for kcat is obtained for the immobilized Candida antarctica lipase was (in the range 0.13 to 0.61 min-1) and the free lipase in solution (0.12 min-1) whilst the immobilized apparent Michaelis constant Km was 12 times lower than the free lipase in solution. The considerable higher rates gained with the immobilised lipases, due to the establishment of a favourable biphasic system in the continuous flowing microreactor setup. In addition to this, it was found that the optimisation of the outward features of the monolith eliminate lipase aggregation and pore obstruction, thereby increasing lipase specific activity and the accessibility of the substrate to the biphasic system. A range of studies in the literature also, attest to this finding. It should be noted that these optimised monoliths were revealed as highly efficient with regard to various reactions including transesterification reactions. This is important as, owing to this, beneficial aspects could be generated in biodiesel production.
The quest for alternative sources of energy has received extensive coverage owing to the increasing pace with which the current fossil fuel stores are being consumed. An additional factor is that there are a range of concerns relating to growing prices and, critically, climate change brought about by the use of carbon-based fuels. In light of these considerations, biodiesel, also known as fatty acid methyl ester, is notable as it is obtained from the transesterification of triglycerides and, hence, is a possible replacement for petroleum-based diesel. Biodiesel exhibits several advantages over diesel fuel such as low toxicity, high biodegradation, lower emission of particulate matter and its derivation from renewable energy sources. In this work, the use of lipase immobilised on a silica monolith as a microreactor for performing transestrification reactions is reported. Silica monolithic microreactor channels provide a large surface area for enzyme immobilisation. Candida antarctica lipase was trapped onto the silica monolith and was tested for the transestrification of tributyrin (TB). TB was quantitatively transformed into methyl butyrate when using flow rates of 0.8 μL min-1. The immobilised lipase microreactor was also shown to be reusable without loss of activity for 105 hours when operated at 30o C and flow rates of 0.8 μL min-1.
Two simple, reproducible methods of preparing evenly distributed gold (Au) nanoparticle-containing mesoporous silica monoliths were also, investigated. These Au nanoparticle containing monoliths were applied as flow reactors for the selective oxidation of cyclohexene. In the first strategy, the silica monolith was directly impregnated with preformed Au nanoparticles during the formation of the monolith. The second approach was to pre-functionalise the monolith with thiol groups tethered within the silica mesostructure. These can act as evenly distributed anchors for the Au nanoparticles to be incorporated by flowing an Au nanoparticle solution through the thiol functionalised monolith. Both methods led to an even distribution of Au nanoparticles along the length of the monolith as demonstrated by ICP-OES. However, the impregnation method led to a strong agglomeration of the Au nanoparticles during subsequent heating steps while the thiol-anchoring procedure maintained the nanoparticles in the range of 6.8 ± 1.4 nm. Both Au nanoparticle containing monoliths as well as samples with no Au incorporated were tested for the selective oxidation of cyclohexene under constant flow at 30 °C. The Au-free materials were found to be catalytically inactive with Au being the minimum necessary requirement for the reaction to proceed. The impregnated Au-containing monolith was found to be less active than the thiol-functionalised Au-containing material, attributable to the low metal surface area of the Au nanoparticles. The reaction on the thiol-functionalised Au-containing monolith was found to depend strongly on the type of oxidant used: tert-butyl hydroperoxide (TBHP) was more active than H2O2, likely due to the thiol-induced hydrophobicity of the monolith.
In conclusions, this project was successfully completed, and a stable monolithic structure through a sol-gel method was successfully produced. One implication of this was the production of a considerable quantity of molecular information for all of the reactions that were operated. The project’s goals were achievable with the model set-up due to the fact that it fulfilled a degree of appropriateness and versatility. The main topics addressed by the project were the improvement of catalyst immobilisation methods, and the flow reaction system represented a movement in the direction of the development of an entirely automated flow synthetic optimisation system.

Citation

Alotaibi, M. Development of novel continuous flow reaction methodology for fine chemical production. (Thesis). University of Hull. https://hull-repository.worktribe.com/output/4223586

• Thesis Type: Thesis
• Deposit Date: Nov 8, 2021
• Publicly Available Date: Feb 24, 2023
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4223586
• Additional Information: Department of Chemistry, The University of Hull
• Award Date: Jun 1, 2016