The association reactions undergone by 12-crown-4-ether, 12c4H(+), with NH3, CH3OH, CH3NH2, (CH3)(2)NH, and (CH3)(3)N have been studied using the B3LYP density functional method and a variety of basis sets. For comparison purposes the insertion reactions for the same bases into protonated dimethoxyethane ("glyme"), Gl.H+, and protonated glyme dimer, (Gl)(2)H+, have also been modeled. The B3LYP/aug-cc-pVDZ//B3LYP/4-21G(*) level of theory was found to be a particularly favorable compromise between accuracy and computational expense for the calculation of proton affinities of medium-sized species. The protonated glyme, Gl.H+ the protonated glyme dimer, (Gl)(2)H+, and the protonated crown ether, 12c4H(+), form two internal hydrogen bonds with NH3, CH3OH, CH3NH2, and (CH3)(2)NH, except for (Gl)(2)H+. NH3 which has four O ... H bonds. In Gl.NH(CH3)(3)(+), there is a single O ... H bond and the protons of the methyl groups assist weakly in O ... HC bonding. The insertion energy of methanol, ammonia, and the series of amines into 12c4H(+) increases with increasing proton affinity of the inserting base. A similar trend is observed for insertion into (Gl)(2)H+. Trimethylamine does not follow the expected trend because it forms proton-bound complexes that have a single O ... HN bond instead of two. The association energy of CH3OH2+, NH4+, etc., with 12c4 or Gl(2) decreases with increasing proton affinity (of methanol, ammonia, etc.).