The para-like substituent effect on the thermolysis of a number of 5-substituted (-Me, -SiMe₃, -COMe, COCF₃) 2-azidothiophenes 1a–4a is investigated experimentally and at the AM1 and RHF/6-31G* + ZPE levels of theory. Calculated structures located along the reaction coordinate from the reactant azides 1a–4a show that the extrusion of the N₂ molecule is the rate determining step of the process and leads to neutral ring-opened 4-cyano-1-heterodiene products 1c–4c in a concerted manner. The activating 5-methyl substituent of 1a causes rate enhancement with respect to the 2-azidothiophene (2ATh), whereas decreasing rates are observed in the cases of the deactivating 5-COMe and 5-COCF₃ groups, 3a and 4a. Theoretical results provide a reasonable description of the para-like substituent effects on the dissociation, giving electronic structural changes and the corresponding energies involved, as practical support to the experimental data.