The　N-acylation　of　2-aminobenzimidazole　is　widely　used　in　the　synthesis　of　its　derivatives,　the　products　exhibit　different　regioselectivity　when　reacting　with　acylation　reagents.　5-Bromo-2-aminobenzimidazole　was　acylated　in　our　laboratory　and　found　the　more　complex　regioselectivity　than　2-aminobenzimidazole.　When　the　reaction　temperature　was　at　room　temperature　and　using　triethylamine　as　acid　acceptor,　5-bromo-2-aminobenzimidazole　afford　the　N-acylation　product　at　primary　amine　by　acyl　chloride,　while　the　products　at　tertiary　amines　were　obtained　by　di-tert-butyl　dicarbonate.　To　explain　this　regioselective　N-acylation,　the　double　descriptor　(DD),　condensed　dual　descriptor　(CDD)　of　5-bromo-2-aminobenzimidazole　and　molecular　electrostatic　potential　(MEP)　of　reactants　were　calculated.　The　possible　N-acylation　paths　of　the　5-bromo-2-aminobenzimidazole　with　different　acylation　agents　was　studied　by　density　functional　theory　(DFT)　at　M062X/def2TZVP//B3LYP-D3/def-SVP　level.　©　2022　Elsevier　Ltd