A New Paradigm in Oxidative Cleavage Reaction: The Use of Continuous Reactors To Enable Safe Scale Up of Ozonolysis

Scale-Up of Ozonolysis using Inherently Safer Technology in Continuous Flow under Pressure: Case Study on β-Pinene

“…As implementation of ozonolysis in flow could be an asset in the pharmaceutical industry, a relevant substrate was selected: β-pinene. It is a byproduct from the pulp and paper industry . Upon ozonolysis, β-pinene turns into nopinone, an important building block used in the synthesis of pharmaceutical products (Scheme ).…”

“…Upon ozonolysis, β-pinene turns into nopinone, an important building block used in the synthesis of pharmaceutical products (Scheme ). ,− This model reaction was identified to assess the scalability of the system.…”

“…Even though the carbon−carbon double-bond oxidative cleavage of β-pinene has been reported, 27 the industrial scale application of the process relies on the reactivity of metal to push forward the transformation. More specifically, it involves precious metals or dangerous chemicals (NaIO 4 with KMnO 4 , NaIO 4 with OsO 4 , or NaIO 4 with RuCl 3 ).…”

“…Flow chemistry appears as a viable alternative approach, both in terms of risk management ,− and environment control as it involves a low reactive inventory. There has been significant interest in developing ozonolysis reactions in flow − including scale-up aspects, as well as pharmaceutically relevant targets. − …”

“…17 Flow chemistry appears as a viable alternative approach, both in terms of risk management 9,18−22 and environment control 23 as it involves a low reactive inventory. There has been significant interest in developing ozonolysis reactions in flow 24−26 including scale-up aspects, 27 as well as pharmaceutically relevant targets. 28−30 In the academic field, flow ozonolysis research has been carried out in tubular systems, 31−38 microreactors, 39−45 sometimes with a film, 46 or film-shear reactors, 47 usually at a small scale (mmol).…”