<p>The present paper describes a comparative study of nitration of 2-arylimidazo[1,2-<i>a</i>]pyridines using synergistic approach of iodobenzene diacetate and copper nitrate trihydrate as a nitrating medium and a conventional mixed acid system (concentrated nitric acid/sulphuric acid). The devised methodologies afforded <i>ortho</i>-nitro products and C-3 nitrated products respectively. While a single example related to latter protocol has been previously reported, the present study expands it to a series of 3-nitro-2-arylimidazo[1,2-<i>a</i>]pyridines. A plausible mechanism involving electrophilic substitution <i>via in situ</i> generated nitronium ion is proposed for C-3 nitration and clear comparison with the synthesis of <i>ortho</i>-nitro products in synergetic approach is presented. The structures and regioselectivity of the products were confirmed by spectroscopic techniques, including ¹H-NMR, ¹³C-NMR, mass spectrometry and FT-IR analysis. The protocol offers several advantages, such as moderate to higher yields (68–96% in case of classical nitration media and 46–96% under the synergetic approach), shorter reaction times (0.5&#xa0;h in case of conc. HNO₃/H₂SO₄ and 24&#xa0;h in case of IBD/CuNO₃.3H₂O), and the elimination of chromatographic purification. This study provides an efficient and site-selective approach for the synthesis of C-3 nitrated 2-arylimidazo[1,2-<i>a</i>]pyridines.</p> Graphical abstract <p></p>