Reactions of protonated 12-crown-4 ether (Cr4 . H+) and its ammonium (Cr4 . AH(+)) and methoxonium (Cr4 . MH(+)) ion complexes with a series of base molecules were studied using a selected ion flow tube. Reaction efficiencies are enhanced for base molecules capable of forming multiple hydrogen bonded structures. The association kinetics of Cr4 . H+ were compared with those of the protonated dimer of 1,2-dimethoxyethane ((G1H+). insertion of ammonia into Cr4 . H+ is 8.8 times more efficient than its insertion into (G1H+. The preferred reaction channel of Cr4 . MH(+) reactions is switching, while Cr4 . AH(+) undergoes association as well as switching reactions. The reactivity and reaction patterns of Cr4 . H+ and Cr4 . MH(+) are comparable to those of alkyl-blocked protonated dimers and trimers studied previously, while Cr4 . AH(+) has a different reactivity due to its hydrogen-bonding capabilities.