RegioSQM18 was developed and tested using 535 EAS reactions collected from the literature and we use the same data set to guide the development of RegioSQM20. RegioSQM18 predicts the correct regioselectivity for 488 of the 535 reactions, while 30 and 17 are predicted semi-correctly and incorrectly, respectively (Table ). A correct prediction is one where all experimentally observed sites have predicted proton affinities within 1 kcal/mol of the highest proton affinity (marked as green in Fig. ). The definition of a semi-correct prediction is the same as a correct prediction except that the 1 kcal/mol cutoff is changed to 3 kcal/mol (marked as red in Fig. ). Finally, an incorrect (or failed) prediction is one where at least one experimentally observed site is not predicted correctly. We repeated the calculations with GFN1-xTB and GFN2-xTB in combinations with a variety of solvents and found that GFN1-xTB and methanol gave the most accurate results with 486, 27, and 22 correct, semi-correct, and failed predictions (Table and Fig. ). This result is very similar to those obtained with PM3 and shows that an open source method can be used instead of PM3.