Getting Ring‐Closing Metathesis off the Bench: Reaction‐Reactor Matching Transforms Metathesis Efficiency in the Assembly of Large Rings

Abstract

Reported is the first study of the influence of reactor configuration on the efficiency of a challenging ring-closing metathesis (RCM) reaction. With the intention of increasing the generality of RCM scaleup and reducing its dependence on substrate modification, macrocyclization of an unmodified, low effective-molarity diene was explored using different reactor types, in conjunction with a commercial, homogeneous Grubbs catalyst. Optimized performance is compared for a conventional batch reactor (BR), a continuous plug-flow reactor (PFR), and a continuous stirred-tank reactor (CSTR). In the PFR, maximum conversion is achieved most rapidly, but product yields and selectivity are adversely affected by co-entrapment of ethylene with the catalyst, substrate, and product in the traveling "plug". Use of the CSTR, in which ethylene is efficiently swept out, affords an order-of-magnitude increase in total turnover numbers, and reduces the required catalyst loadings by 25× relative to the BR (to 0.2 mol %), while improving RCM yields and selectivity to quantitative levels. Continuous-flow methodologies that support liberation of the ethylene co-product thus show great promise for industrial uptake of RCM.

Continuous Platform To Generate Nitroalkanes On-Demand (in Situ) Using Peracetic Acid-Mediated Oxidation in a PFA Pipes-in-Series Reactor

“…Alternative solutions to entrapment of the gases in reaction by switching to continuous stirred tank reactor or using unique annular flow regime in PFR have been successfully utilized. 27…”

Continuous Flow Metathesis for Direct Valorization of Food Waste: An Example of Cocoa Butter Triglyceride

“… 26 − 30 A comparison of batch, continuous stirred tank reactors and tubular continuous flow reactors for ring-closing metathesis has recently been presented. 31 This work clearly shows the impact of different types of residence time distributions characterizing batch, continuous stirred tank and plug-flow reactors on transformations with reaction orders over unity, and the possibility to attain high space-time yields in continuous reactors. Plug-flow reactors with heterogeneous catalysts offer the simplicity of catalyst separation, as well as the frequently desired plug-flow regime.…”

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

“…In 2009, McQuade and co-workers achieved the FC reaction of isobutylbenzene (620) and propionic acid (621) in flow for the synthesis of ibuprofen (625, Scheme 140) [534].…”