New Continuous Flow Oxidation Methodology

Abstract

The HOF.MeCN complex, formed from the reaction of elementary fluorine with aqueous acetonitrile, was discovered by Shlomo Rozen in 1987 and, in a series of publications, he demonstrated that the complex is a uniquely effective electrophilic oxygen transfer agent. However, it is estimated that the HOF.MeCN complex has a half life of a few hours at 0ºC and thus, must be produced and used immediately when required. In addition to this, highly exothermic, rapid oxidation processes can be problematic with reaction control and safety when reagents are added into an excess of a highly oxidizing medium. Consequently, scale-up of oxidations to a larger industrial level using the HOF.MeCN complex in batch processes would not be possible.

In recent years, continuous flow reactors using microchannels have been viewed as a viable method for avoiding many of the problems encountered when a laboratory process is scaled-up. The low chemical inventory of such reactors means that even highly reactive reactions can be performed safely and, with the application of multiple reaction channels in parallel, large quantities of product can be easily obtained.

In this thesis we present new continuous flow methodology for the in situ generation of HOF.MeCN and, without isolation, immediate substrate oxidation in a two-step process. The continuous process, therefore, provides a genuine method for oxidizing large quantities of material, without the problems associated with batch oxidations. Scale-up oxidations of various amines, alkenes, and anilines are also presented along with a safe and accurate method for calibrating HOF.MeCN amounts.