Continuous-flow synthesis and application of polymer-supported BODIPY Photosensitisers for the generation of singlet oxygen; process optimised by in-line NMR spectroscopy

Abstract

Commercial polystyrene Merrifield-type resins have been post-synthetically functionalised with BODIPY photosensitisers via a novel aryl ester linking strategy in continuous-flow. A unique synthetic advantage of post-synthetically modifying heterogeneous materials in flow was identified. The homogeneous analogues of the polymer-supported BODIPYs were synthesised and used as reference to assess photophysical properties altered by the polymer-support and linker. The homogeneous and polymer-supported BODIPYs were applied in visible-light photosensitisation of singlet oxygen for the conversion of α-terpinene to ascaridole. Materials produced in flow were superior to batch in terms of functional loading and photosensitisation efficiency. Flow photochemical reactions generally outperformed batch by a factor of 4 with respect to rate of reaction. The polymer-supported BODIPY resins could be irradiated for 96 h without loss of photosensitising ability. Additional material synthetic modification and conditions optimisation using an in-line NMR spectrometer resulted in a 24-fold rate enhancement from the initial material and conditions.

Heterogeneous photocatalysis in flow chemical reactors

“…The system achieved full conversion for a variety of aromatic heterocycle substrates within 8-20 min, transformations that would require days in batch protocols (Scheme 1) [62]. Flow systems can be pressurised easily with back pressure regulators, enhancing the solubility of gaseous reagents in the reaction solvents [36,63]. Flow processes are also commonly monitored with in-line and on-line spectroscopies, such as UV-vis, FTIR, mass spectrometry, and NMR [63][64][65][66][67][68].…”

“…Both of these were applied as HPCats in a commercial flow reactor for photocatalysis. Whilst flow chemistry is generally used to enhance the efficiency of HPC processes, we recently demonstrated that it can also enhance the efficiency of synthesising and purifying immobilised photosensitisers [63]. A BODIPY photosensitiser was immobilised to an aldehyde-functionalised Merrifield resin (poly(styrene-co-divinylbenzene-co-4-formylstyrene)) in continuous flow and concurrently in an analogous batch procedure.…”

“…A BODIPY photosensitiser was immobilised to an aldehyde-functionalised Merrifield resin (poly(styrene-co-divinylbenzene-co-4-formylstyrene)) in continuous flow and concurrently in an analogous batch procedure. The coupling efficiency was initially found to be almost double in flow versus batch [63]. The materials were also purified in flow and Soxhlet extractions, respectively, with the same solvent mixtures and time periods.…”

“…The flow-purified resins displayed no loss of efficiency over the recycles, indicating the flow purification had effectively removed the homogeneous photocatalyst. The flow synthesis also prevented the formation of a chlorinated byproduct identified on the batch resins as an intermediate, and purification could be applied to wash out reactants from the first step of the one-pot synthesis, a potentially useful synthetic advantage of postsynthetic modifications in flow [63].…”

Continuous Flow Organophosphorus Chemistry

“…Photochemistry and electrochemistry have recently attracted a renewed and increasing interest from the organic chemistry community. [29,[81][82][83][84][85] Photochemistry and electrochemistry are efficiently combined with continuous flow processes, hence leading to much more robust, reproducible and scalable processes. Recent reports also feature these techniques for innovative P-H insertion reactions.…”