Structural Assessment of Hydrogen Bonds on Methylpentynol–Azide Clusters To Achieve Regiochemical Outcome of 1,3-Dipolar Cycloaddition Reactions Using Density Functional Theory

[Image: see text] This study was focused on the geometries and properties of the structural isomers obtained from a random walk of methylpentynol–HN(3) clusters. The theoretical aspects of hydrogen bonding effects on the discussed 1,3-dipolar cycloaddition (1,3-DC) reactions [between methylpentynol (a) as a dipolarophile and azide (b) as a 1,3-dipole] have shown regioselective output concepts. The dipolarophile methylpentynol (a) was applied for the treatment of insomnia. Both methylpentynol (a) and azide (b) can be H-bond acceptor and H-bond donor agents. Because of this trait of them, structures of H-bonding arrays (c–f) and methylpentynol–azide clusters (g–m) can be probable. In this work, regioselectivity of the 1,3-DC reaction [between methylpentynol (a) as a dipolarophile and azide (b) as a 1,3-dipole] was determined based on these structures (c–m) using density functional theory (DFT). The energy levels of the reactants (a and b) and the structures of H-bonding arrays (c–f), methylpentynol–azide clusters (g–m), transition states, and products (1 and 2) were studied, and also, the free energies of the reaction (Δ(r)G and ΔG(#), in kcal mol(–1)) and rate constants were determined using Eyring’s equation (k). Structural data were calculated and obtained by the DFT/B3LYP method. Seven different basis sets have been used to obtain the most appropriate results from comparison of data.