Efficient One-Pot Synthesis of Novel 1,4-Disubstituted Triazoles via Click Chemistry under Mild Conditions

The development of efficient and sustainable methodologies for the synthesis of 1,2,3-triazoles remains an important objective in modern organic chemistry due to the broad applicability of these heterocycles in medicinal chemistry, materials science, and chemical biology. In this work, we report an efficient one-pot synthetic approach to novel adamantane-based 1,4-disubstituted 1,2,3-triazoles via copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) under mild reaction conditions. The synthetic sequence involves the in situ generation of benzyl azides from the corresponding benzylic bromide intermediates, followed by direct cycloaddition with terminal alkynes in a single reaction vessel, avoiding the isolation and handling of potentially hazardous organic azides. The CuAAC reaction was performed in an ethanol/water (4:1) medium at room temperature using a catalytic system composed of Cu(OAc)₂, sodium ascorbate, and 1,10-phenanthroline, affording the desired 1,4-disubstituted triazoles in good yields with excellent regioselectivity. The methodology combines operational simplicity, mild reaction conditions, and reduced purification steps, providing an efficient and practical route to functionalized triazole derivatives. The structures of the synthesized compounds were unambiguously confirmed by ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry (HRMS). The developed one-pot protocol represents a versatile and reliable synthetic strategy for the preparation of adamantane-containing 1,2,3-triazoles and may facilitate the synthesis of structurally diverse triazole libraries for future applications in synthetic and medicinal chemistry.