Next we study the acid catalyzed synthesis of a benzimidazole derivative starting from ortho-phenylenediamine and benzoic acid (Phillips method). The reaction is acid catalyzed so at each minimum along the path we try the different possible protonated structures and optimize with GFN2-xTB. Structures with energies < 30 kcal/mol relative to the lowest energy protonation structure are considered relevant for the analysis. The result of the search is summarized in Figure . For the reactant system, two protonation structures are possible: protonation at the nitrogen or at the carbonyl oxygen (which is Figure : Summary of the reaction path found using meta-MD to follow the acid-catalyzed synthesis from ortho-phenylenediamine and benzoic acid to 2-phenyl benzamidazole 17 kcal/mol higher than at nitrogen). We follow the path from the carbonyl protonated structure and find step 1 by meta-MD (Figure , step 1) where the lone pair of one of the nitrogen atoms is used to attack the carbonyl carbon. The next step is elimination of water which can be found in two ways: either by manually transferring the proton to one of the hydroxyl groups, resulting in water eliminated upon energy minimization, or by adding a water molecule that can aid in the proton-transfer during the meta-MD simulation (Figure , step 2). Step 3 is a ring closure initiated by attack of the other nitrogen atom. The second water elimination can again be found by manually moving the proton from the ammonium to the hydroxyl group (step 4) and subsequent geometry optimization which eliminates the water molecule (step 5) creating the product 2-phenyl benzamidazole. Contrary to the first water elimination, this second water elimination was only found by manually moving the proton and not by the meta-MD runs with an additional water molecule (the backward reaction is the preferred path). The manual proton transfers can easily be automated.