Synthesis, Structure Analysis, Theoretical Calculations and Relative Protonation Constants by NMR of Secondary Amino...

Ten secondary amino alcohols were synthesized through condensation reactions using 3-aminopropanol or 2-aminoethanol with cyclohexanone, adamantanone, norcamphor, benzaldehyde, salicylaldehyde, p-hydroxy-benzaldehyde and m-hydroxy-benzaldehyde under pressure with a monowave reactor. Secondary amino alcohols were characterized by ¹H, ¹³C and ¹⁵N. NMR and two-dimensional experiments were used to determine the correct structures and the relative positions of amino alcohols on cyclohexyl and norbornyl groups. To compare their reactivity, the relative protonation constants were determined for 10 mixtures of two compounds by ¹H NMR in an acidic medium using DCl/CD₃OD solution. The steric effects of cyclic groups such as adamantyl and norbornyl, along with para- and ortho-OH effects in benzyl compounds, were analysed to assess their influence on reactivity. In all cases, compound 1 was the most susceptible to protonation, while compound 4 was the least susceptible. A linear relationship exists between the ¹⁵N NMR chemical shifts of cyclic compounds (1, 2, 8, 9 and 10) and their protonation energies. Theoretical calculations, such as molecular electrostatic potential, natural bond orbital, Fukui function and protonation energy, helped us to support the experimental results.