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Updated: Jun 4, 2025

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach
Published on: June 10, 2021
Cu(II)-mediated tautomerization for the pyrazole-nitrile coupling reaction
Chang-Chih Hsieh1, Chia-Wei Chen2, Ming-Hsi Chiang1,3
1Institute of Chemistry, Academia Sinica, Taipei 11528, Taiwan.
Abstract:
This study investigates the mechanism of prototropic tautomerization in metal-bound asymmetric pyrazole (R-PzH) ligands during Cu(II)-mediated PzH-MeCN coupling reactions. Intrinsic prototropic tautomerization of metal-bound ligands has not been previously documented. Various new bis-pyrazolylamidino Cu(II) complexes, [Cu(R-Pz(HNC(Me)))2(ClO4)2], from the coupling reaction, and tetrakis pyrazole Cu(II) complexes, [Cu(R-PzH)4(ClO4)2], with symmetric and asymmetric C-monosubstituted R-PzH ligands were synthesized and characterized. Kinetic UV-vis studies revealed slower coupling rates with asymmetric R-PzH ligands, further reduced with increasing substituent size due to steric hindrance impeding tautomerization. Structural analysis showed preferential binding of asymmetric 3(5)-R-PzH to Cu(II) ions at the C5 position of PzH, requiring a tautomeric shift to the C3 position for the subsequent coupling reaction. DFT calculations confirmed the greater stability of the C5-tautomeric [Cu(R-PzH)4(ClO4)2] complexes over their C3 counterparts, explaining the rate discrepancies. A mechanism involving counteranion-mediated proton transfer during tautomerization is proposed to account for coupling product formation.
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