As shown in Scheme 1A, the first benchmark is the optimisation of a nucleophilic aromatic substitution (S N Ar) reaction in a flow reactor. The benchmark is based on a kinetic model developed by Hone et al., for the reaction of difluoronitrobenzene 1 and pyrrolidine 2, which produces one desired product and two side products. The reaction is carried out in a virtual flow reactor, so the natural objective is to maximise space time yield (STY), the mass of product formed per unit residence time. Additionally, we minimise the E-factor, which is defined as the ratio of product formed to waste produced. The decision variables (i.e,. the reaction conditions) are the temperature (40-120 • C), residence time (0.5-2 minutes), equivalents of 2 (1.0-5.0) and concentration of difluoronitrobenzene (0.1-0.5M). Further details of the S N Ar benchmark can be found in the SI.