W Tungsten

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.Go with the flow: Remarkably efficient ring-closing metathesis (RCM) macrocyclization is achieved by judicious matching of reaction and reactor. In a comparative study of batch, plug-flow, and continuous stirred-tank reactors, the last example enabled significantly higher yields and selectivity, in shorter reaction times, by using 25× less catalyst (0.2 mol %) than the conventional batch reaction.