Steric Hindrance and the Kinetic Nature of the Protonation Process in 4-Amino-1-Methoxycyclohexanes upon Chemical Ionization

The abundant [MH – MeOH]⁺ ions in the isobutane-chemical ionization (CI) mass spectra of trans-4-amino-1-methoxycyclohexanes (where proton transfer between the two sites does not take place, in contrast to the cis-isomers) indicate protonation at the two basic sites, affording two isomeric MH⁺ ions in each case, one protonated at the dimethylamino group, MH⁺(N), and the other at the less basic oxygen function, MH⁺(O). This result shows that the isobutane-CI protonation of the aminoethers is a kinetically controlled process, occurring competitively at both basic sites (despite the large difference between their proton affinities, ∼105–145 kJ mol⁻¹), and the ion abundance ratio [MH⁺] / [MH – MeOH]⁺ reflects the ratio of abundances of the isomeric MH⁺ ions, MH⁺(N) and MH⁺(O), initially protonated at one of the two sites. The latter ion abundance ratio decreases with the bulkiness of the N-substituents (by a factor of more than 10 between N,N-dimethyl- and N,N-diisopropyl-derivatives), indicating lower rates of protonation at the amino group when the approach of the protonating reagent (C₄H₉⁺ ion in our measurements) to the nitrogen atom is increasingly hindered by the N-substituents. Another effect of steric hindrance in the CI process involves enhanced formation of the molecular radical cations M^+• (presumably by a charge exchange mechanism), in competition with the usual protonation, in aminoethers with bulky N-substituents.