ABSTRACT This work presents an improved synthesis of endo‐isocamphanylamine and a comparative study of the reactivity of monoterpenoid‐based amines in alkylation reactions. An efficient route to endo ‐isocamphanylamine was developed by reducing the corresponding oxime with sodium borohydride in the presence of NiCl 2 . The kinetics of alkylation of endo ‐isocamphanylamine, endo ‐bornylamine, exo ‐fenchylamine, and endo ‐fenchylamine with methyl iodide, allyl bromide, benzyl bromide, and 2‐chloro‐1‐morpholinoethan‐1‐one were investigated. Where direct kinetic comparisons were possible, isocamphanylamine exhibited moderately higher reactivity than bornyl‐ and fenchylamines, particularly with sterically demanding electrophiles, consistent with its suggested greater steric accessibility. Distinct reactivity patterns were observed for the alkylation of isomeric amines with the selected halides: in the bornylamine series, the endo ‐isomer was more reactive, whereas for the fenchylamines, the exo ‐isomer demonstrated higher reactivity in all cases. Quantum‐chemical modeling, including activation energy calculations and analysis of transition state geometry and the reduced density gradient (RDG), provided evidence that the superior reactivity of exo ‐fenchylamine compared to endo ‐fenchylamine stems from a less sterically hindered environment.
Tishchenko et al. (Mon,) studied this question.