Strain and Ring Size Effects on the 1,3-dipolar Cycloaddition reactions of the Medicine Efavirenz Derivatives; A Theoretical Studies

This study was focused on the theoretical and computational studies of the 1,3-dipolar cycloaddition (1,3-DC) reactions, which they have been applied in a numberof diverse fields [1]. An undeniable relation between the bond angle strain around of the triple bonds in simple cycloalkynes and the kinetic of 1,3-DC reactions with azidederivatives has been proven by theoretical analysis before [2], so herein the secondorder strain effect of a fused side ring on reactivity of alkyne in 1,3-DC reaction ofalkynes and azides was investigated. Efavirenz as an antiretroviral medication was applied to treat and prevent HIV/AIDS [3]. The molecule of this medicine was selected as a ring closed dipolarophile. In this study, the 1,3-dipole reaction of Efavirenz analogues (1-4) with azide derivatives (a-c) were applied to produce the 1,2,3-triazole derivatives. The energy levels of the reactants, transition states (TS), products (5-28), the free energies (in kcal mol-1) of reaction (ΔrG and ΔG#), rate constants by using Eyring s equation (k and k′), structural data were calculated by DFT-B3LYP/6-31G* method.