Study On The CuAAC Reaction In ScCO₂ And Its Application In The Modification Of 4,6-Dimethyl-2-Sulfydryl Pyrimidine

Copper catalyzed azide-alkyne cycloaddition reaction,also known as CuAAC reaction,has gradually become the most striking reaction within the "click chemistry" concept since Sharpless and Meldal independently found that cuprous salt could efficiently catalyze Huisgen cycloaddition to produce 1,4-disubstituted 1,2,3-triazoles in high selectivity.Because not only the 100% atom economy of the CuAAC reaction,but also the wide application of the obtained 1,2,3-triazoles in fields including medicine,pesticide and functional materials and so on.The development of the catalytic system of CuAAC reaction was reviewed in this paper.Regarded as a kind of green reaction medium,supercritical carbon dioxide?scCO₂?fluid has been increasingly drawn widespread attention.However,there were only two reports about the CuAAC reaction catalyzed by Cu???salts in the scCO₂,which were applied to the synthesis of polymer in the presence of ligand.Therefore,the CuAAC reaction catalyzed by the common copper source in the absence of ligand or base in the scCO₂ was systematically studied in this paper.Firstly,the CuAAC reaction catalyzed by Cu?0?in the scCO₂ was studied.Although the CuAAC reaction catalyzed by metal copper,copper nanopartilcles or supported copper nanoparticles had been reported,the mentioned catalytic systems usually had a series of drawbacks such as organic solvent consumption,long reaction time,complex preparation of catalyst and so on.Combined with scCO₂,copper wire separated from electric wire was selected as the source of copper for CuAAC reaction to obtain the 1,2,3-triazoles.Subsequently,reaction conditions such as reaction temperature and catalyst loading of the copper wire were studied,and the catalyst recycle and leaching were also studied.In comparison,the CuAAC reactioncatalyzed by the copper wire in scCO₂ has advantages in solvent-free reaction,mild reaction conditions,easy work-up procedure,etc.Secondly,CuAAC reaction catalyzed by CuBr?CuI?Cu2O and other Cu???salts in the scCO₂ was discussed.Under the same conditions,the scCO₂/H2 O two-phase system as reaction solvent performed better than scCO₂ when catalyzed by Cu2 O.Subsequently,the optimization conditions and mechanism about this reaction system was studied.Thirdly,CuAAC reaction catalyzed by CuCl2?CuBr2?CuSO4·5H2O?Cu?OAc?2·H2O and other Cu???salts in the scCO₂ was implemented.Phenylacetylene and phenyl azide were selected as model reaction substrates for the CuAAC reaction catalyzed by Cu???salts.Among the tested Cu???salts,Cu?OAc?2·H2O performed best,and the catalyst loading could be decreased to 1/10000.Subsequently,the applicable scope of the catalytic system was studied,and the catalytic system was effective for the CuAAC reaction of small molecules and polymers.Finally,4,6-dimethyl-2-sulfydryl pyrimidine,which had antifungal,antitumor and other biological activity,was modified through the CuAAC reaction catalyzed by copper wire in scCO₂,and obtained a series of 4,6-dimethyl-2-sulfydryl pyrimidine derivatives bearing 1,2,3-triazoles ring.This new class of derivatives were characterized by IR,NMR,MS and melting point determination apparatus.And then,the obtained 1,2,3-triazoles were tested with IDO protein by computer virtual screening.