Evaluation of substituent effects on the enthalpies of protonation of amines. An empirical formula of prediction

Abstract

An empirical formula is given which enables the enthalpy of protonation of amines to be calculated. The values of the heats of protonation of primary, secondary, and tertiary nitrogen having been fixed, it is necessary to add the positive effects of the carbon atoms or the negative ones of the nitrogen atoms, either charged or uncharged, present in the molecule, to get the enthalpy of protonation of amine. These effects decrease with increasing distance from the nitrogen being protonated. The calculated heats are compared with the experimental values for aliphatic mono- or poly-amines. Only the overall enthalpy of protonation has to be considered for amines containing different primary, secondary, or tertiary amino-groups in the one molecule. The formula can be used to evaluate the effect of other substituents on the heat of protonation of amino-groups. Two examples are given for the –CO₂^– and the –OH group in amino-acids or amino-alcohols.