The application of 3D-printing in batch and flow chemistry for the synthesis of heterocycles

The work described in this thesis focusses on 3D-printing as a novel technology and its use in both batch and flow chemistry. As such, fused deposition modelling and stereolithography printing were explored for their ability to affect organic synthesis. Initially, FDM printed column reactors for flow chemistry were developed and their scope in simple SNAr chemistry explored. This work was further expanded into the synthesis of quinoxalinones, wherein a two-step flow sequence using this SNAr step and an intramolecular acylal cyclisation step was able to generate the core structure in a single process from amino acids and environmentally benign solvents. The next phase of the project focussed on the development of devices for batch chemistry using SLA printing. A catalytic stirrer bead device that would improve the efficiency of batch reactions was developed. The initial formulation incorporated tosic acid and these stirrer bead devices were used in the synthesis of Hantzsch dihydropyridines. This formulation was then further improved so as to make it chemically inert and palladium(0) tetrakis(triphenylphosphine) containing devices were prepared. Their scope was explored through their use in Suzuki couplings under both thermal and microwave conditions. A third catalytic stirrer bead device containing yttrium triflate was also developed and its use in the protection of carbonyl groups in aldehydes with thiols was investigated using microwave conditions. In the last phase of the project, an SLA printed circular disc reactor was designed and fabricated using this new inert formulation. Its use in flow photochemistry has been explored shortly though C-H functionalisation chemistry and its limits have been explored. Last of all, the decarboxylation reaction in a synthetic sequence for Praziquantel was studied. It was found that a flow photo-decarboxylation using these newly developed reactors would be sufficient to carry out this key step in the synthetic sequence. The thesis closes with a description of the experimental conditions and full detail of the compounds produced in this thesis

Crafting mono- and novel bis-methylated pyrroloquinoxaline derivatives from a shared precursor and its application in the total synthesis of marinoquinoline A

The synthesis of mono- and novel bis-methylated pyrrolo[1,2-a]quinoxalines through the addition of unstable methyl radicals to aryl isocyanides is described contingent upon the reaction conditions employed. The strategy has been effectively employed in the total synthesis of the natural product marinoquinoline A

Three-Dimensional Printing of a Scalable Molecular Model and Orbital Kit for Organic Chemistry Teaching and Learning

Three-dimensional (3D) chemical models are a well-established learning tool used to enhance the understanding of chemical structures by converting two-dimensional paper or screen outputs into realistic three-dimensional objects. While commercial atom model kits are readily available, there is a surprising lack of large molecular and orbital models that could be used in large spaces. As part of a program investigating the utility of 3D printing in teaching, a modular size-adjustable molecular model and orbital kit was developed and produced using 3D printing and was used to enhance the teaching of stereochemistry, isomerism, hybridization, and orbitals

3D‐printed polypropylene continuous‐flow column reactors: exploration of reactor utility in SNAr reactions and the synthesis of bicyclic and tetracyclic heterocycles

3D printing has the potential to transform the way in which chemical reactions are carried out due to its low‐cost, ease‐of‐use as a technology and its capacity to expedite the development of iteratively enhanced prototypes. In this present study, we developed a novel, low‐cost polypropylene (PP) column reactor that was incorporated into an existing continuous‐flow reactor for the synthesis of heterocycles. The utility and solvent resistance of the printed devices were explored in SNAr reactions to produce substituted aniline derivatives and in the synthesis of bicyclic and tetracyclic heterocycles. Using this approach, a range of heterocyclic compounds was synthesised including the core structure of the natural product (±)‐γ‐lycorane and structurally complex compounds based on the tetracyclic core of the erythrina alkaloids