Studies On The Huisgen-click Reaction And Its Application Of Maleimide’s Modification

Copper catalyzed azide-alkyne cycloaddition reaction (Huisgen-click reaction) is one of the mostimportant reactions in organic chemistry. Since Sharpless and Meldal independently discovered thatcopper(I) catalysts could facilitate the Huisgen s azide-alkyne cycloaddition in a regiospecific manner togive only1,4-disubstituted triazoles, the copper(I)-catalyzed azide-alkyne cycloaddition reaction(Huisgen-click reaction) have attracted much attention due to their applications in the synthesis ofpharmaceuticals, agrochemicals, dyes, corrosion inhibitors, biochemicals, polymers and functionalmaterials. It was of great significance to study catalyst systems and their applications. The following threeaspects were studied in this paper.We have presented a novel and high yielding Cu(OAc)2·H2O/NH2NH2·H2O catalyst system, whichcould in situ generate Cu2O-NPs and HOAc to catalyze Huisgen-click reactions in water at roomtemperature with relatively short reaction times. Such a method is interesting as it avoids not only the useof stabilizers, additional ligands and supports, but also the production of harmful substances. The reducedproduct is proved to be hollow spherical Cu2O-NPs with sizes of400-500nm. The in situ generated HOAcplays three important roles in the reaction:(a) HOAc breaks the crystal structure of Cu2O to allow theformation of copper(I) carboxylates, which are highly efficient catalysts for the Huisgen-click reaction;(b)AcO-acts as a bidentate ligand coordinated to the Cu(I) species of the monomer to promote the formationof dinuclear alkynyl-copper(I) intermediate;(c) the acidity of HOAc is also necessary for the success ofthis conversion, which it has an active effect on the cycloaddition and protonation of the C-Cu bond.A thermal-promoted, simple and efficient protocol for the Huisgen-click reaction by usingCuSO4·5H2O as the catalyst in water at100oC was developed. This catalyst system was highly efficient inlow loading without any additives or ligands. Two model reactions were selected for investigating the effectof CuSO4·5H2O on the acceleration and regioselectivity of the Huisgen-click reaction. The protocol wasproved to be not only suitable for the reactions between organic azides and alkynes, but also suitable forone-pot three-component reactions among alkyl halides, NaN3and alkynes. It is worth mentioning that thereaction could proceed smoothly even both the alkynes and the azides are in solid states. A series of maleimide derivatives bearing the1,2,3-triazole moiety were designed, and synthesizedvia the Huisgen-click reaction catalyzed by CuSO4·5H2O. The characterizations of this new class ofcompounds were performed using IR, NMR, MS and HRMS. The maleimide derivatives were evaluatedfor their in vitro cytotoxicity against the Hela cell line, antibacterial and antifungal activity. The resultshave established principal foundation for further studies.