Fluoride has come to play an important role within human health, primarily within our dental health where it prevents the growth of caries-causing bacteria and strengthens our tooth enamel when consumed at low concentrations (3 – 4 mg/day). However, an intake of fluoride exceeding 14 mg/day has been observed to cause adverse health effects such as fluorosis of the teeth and demineralisation of bones. An elevated intake of fluoride is commonly caused by contamination of soil used for agricultural purposes and drinking water sources resulting from the use of fluoride-containing fertilisers, pesticides, and minerals within agriculture and industrial production.

2,1,3-benzothiadiazole (BTD) is a privileged electron acceptor which provides easy access to visible-light absorption, fluorescence, and phosphorescence upon extension of its pi-system. Though BTD-based derivatives have gained a vide application range from organic light-emitting diodes to near-infrared bioimaging, functionalisation of its benzenoid ring has proved difficult with limited methods being available. Direct functionalisation is almost fully restricted to its C4/C7 positions with functionalisation of the C5/C6 positions often requiring a bottom-up approach. 

The aim of this thesis project was to develop and optimise a synthetic pathway for formation of fluorescent BTD-based derivatives aimed for detection of fluoride. Installation of aryl groups carrying electron-withdrawing and electron-donating functional groups initially struggled with regioselectivity, resulting in the starting material becoming overfunctionalised and the product unable to be used for further synthesis. Attempts at introducing chemo- and regioselectivity via the use of boronic esters failed to give the desired results. Chemoselectivity could be achieved via the use of an asymmetric halogenated BTD-derivative which allowed for a sensor to be synthesised, though difficulties remain regarding purification.