Diazo compounds see wide use as metal-carbene precursors, due to the varied transformations they can achieve. Despite their popularity in academia, these energetic reagents are often avoided on process scale, owing to concerns over instability and explosivity. However, there was little reliable safety data on diazo compounds. This thesis reports a systematic study into the thermal hazards of diazo compounds, and development of a continuous flow process to generate and utilise diazo and azide compounds whilst avoiding isolation of these energetic compounds and bypassing many of the thermal hazards.
The first chapter introduces process safety and the chemistry of diazo and azide compounds, and describes the aims. In Chapter 2, a series of diazo compounds were analysed with differential scanning calorimetry to obtain thermal stability and energetic data, and predict impact sensitivity and explosivity. The structure-stability relationship was explored, highlighting the impact of substituent electronic effects, such that a predictive model was derived for the thermal stability of aryldiazoacetates. Whilst conducting this study, a reportedly “intrinsically safe” diazo transfer reagent was found to be in fact highly energetic. The misleading result was demonstrated to be caused by unsealed crucibles.
Continuous flow offers the potential to minimise inventory of hazardous reagents with telescoped reactions, which mitigates some of the hazards and could enable broader usage. Chapter 3 reports a continuous synthesis and purification of the diazo transfer reagent nonaflyl azide, with a unique hybrid gravity/membrane separation. Nonaflyl azide is then used for a continuous synthesis of acceptor/acceptor diazo compounds, and azides from primary amines. The azides were used directly to form triazoles in a one-pot batch procedure and semi-batch flow procedure. Optimisation of a fully telescoped procedure is ongoing.
A summary of specific conclusions and future work can be found in Chapter 4. Experimental details and methods are in Chapter 5.