We have then revealed the reaction pathways leading to the BLG functionalization in methanol using metadynamics. The presence of a single vacancy on the BLG surface is found to reduce by more than 20 times the free energy barrier for -OCH3 functionalization, making the process feasible at 6.8 GPa and ambient temperature conditions. We attribute the microscopic origin of such effect to the presence of an undercoordinated carbon atom at the vacancy, that facilitates the nucleophilic attack of the metoxy group (CH 3 O -).