An Efficient Synthesis of 1,4-Disubstituted Triazoles in Water via CuCl2/Zn-Catalyzed Huisgen Cycloaddition

Triazoles are an important class of heterocyclic compounds. In recent years 1,2,3-triazoles gained more and more interest due to their diverse biological activities and synthetic methodology [1 – 3]. An efficient approach for constructing the 1,2,3-triazole unit is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, which was discovered independently by the groups of Sharpless andMeldal [4, 5]. The sources of the copper(I) catalyst for a CuAAC reaction usually are Cu(I) salts, or Cu(II) salts together with a reducing agent (often sodium ascorbate or metallic copper). Furthermore, it was reported that metallic copper can be an alternative source for the CuAAC reaction. Using metallic copper as the catalyst was attractive because of a much easier work-up and purification. Unfortunately, the reaction times are usually long when using metallic copper as the catalyst [6, 7], except when physical techniques such as ultrasound irradiation are used [8]. In order to shorten the reaction time, nanosized copper was used as the catalyst. Orgueira successfully performed a CuAAC reaction utilizing an activated nanosized copper powder as the source of the catalytic species in the presence of amine hydrochloride salts [9]. A CuAAC reaction reported by Pachón was carried out in t-BuOH/H2O catalyzed by copper nanoclusters, and it took 18 h to complete the reaction [10]. In comparison with the nanosized copper mentioned above, copper nanoparticles prepared by mixing copper(II) chloride, lithium metal and a catalytic amount of 4,4′-di-tert-butyl-biphenyl (DTBB) in THF at r. t., showed a better catalytic effi-