The Development of Continuous Process for Alkene Ozonolysis Based on Combined in Situ FTIR, Calorimetry, and Computational Chemistry

Two continuous apparatuses were designed that are capable of safely scaling the highly energetic ozonolysis reaction to multikilogram scale where flow chemistry allowed excellent temperature control and minimized the inventory of the highly unstable ozonide intermediate. First, a continuous stirred tank reactor was developed and proven capable of generating product at a rate of 77 mmol of product per hour while maintaing <46 mmol of ozonide. Then, a larger-scale continuous bubble reactor was designed to deliver 770 mmol of product per hour while maintaing 950 mmol of ozonide present at any given time, and the latter was utilized to deliver 2.5 kg of product. The development of these reactors relied on careful evaluation of the thermal stability and heat of reaction of ozonolysis using computational chemistry and calorimetric measurement. In addition, the reactor design benefited from in situ ATR/FTIR monitoring of the rate of ozonolysis under nonflow conditions which allowed for the flow of substrate to be matched with ozone generation, enabling complete reaction of the alkene with minimal excess of ozone.