Thematic Section: Preparative Research. _____________________________________________________ Full Paper Subsection: Organic Chemistry and Catalysis. The Reference Object Identifier – ROI: jbc-01/19-57-2-1 Kazan. The Republic of Tatarstan. Russia. __________ © Butlerov Communications. 2019. Vol.57. No.2. _________ 1 The Digital Object Identifier – DOI: 10.37952/ROI-jbc-01/19-57-2-1 Submitted on February 10, 2019. The catalytic activity of copper nanoparticles on aminomodified silica support in the flow azide-alkyne cycloaddition reaction using macrocyclic substrates © Albina T. Nurmukhametova, Roman N. Belov, Vladimir A. Burilov,* + and Igor S. Antipin Department of Organic Chemistry. A.M. Butlerov Chemical Institute. Kazan Federal University. Kremlyovskaya St., 18. Kazan, 420008. Russia. Phone: +7 (843) 233-73-44. E-mail: ultrav@bk.ru ___________________________________ *Supervising author; + Corresponding author Keywords: Modified silica, azide-alkyne cycloaddition reaction, heterogeneous catalysis, copper nanoparticles, flow chemistry. Abstract Using the chemical reduction method, a copper-containing catalyst on an amino-modified silica was obtained. The structure and composition of the catalyst were characterized by low-temperature nitrogen adsorption and inductively coupled plasma mass spectrometry. It was found that the modification of silica with amino groups and copper nanoparticles leads to a significant change in textural characteristics: nanoparticles and the modifier fill the pores in the size range of 5-10 nm. Obtained catalyst showed good activity in the flow cycloaddition of azides and alkynes of various nature. The comparative activity of azides and alkynes was analyzed. It has been established that among the azides studied (benzyl azide, p-nitrobenzylazide, p-methoxybenzylazide, 2-azidoethylacetate and 1-azidodecane), alkyl and aryl azides with electron-withdrawing groups were most active due to an increase in the electrophilicity of the terminal nitrogen atom of the azide group. Among the studied acetylenes (phenylacetylene, hexin-1, trimethylsilylacetylene and propargyl alcohol), propargyl alcohol was the most and trimethylsilylacetylene was the less active. Increased activity of propargyl alcohol may be due to a donor hydroxyl group capable of coordinating with copper; reduced activity of trimethylsilylacetylene can be resulted from steric hindrances. p-tert-Butyl and p-H-calix[4]arens were also used in the reaction. Full conversion of macrocycles was achieved after 3 consecutive reaction cycles. The resulting triazoles were isolated and characterized by a complex of physical methods. Thus, It has been demonstrated that carrying out the reaction in a flow by maintaining stable and fully reproducible reaction parameters makes it possible to quickly evaluate the relative reactivity of molecules. References [1] R. Huisgen. 1,3-Dipolar Cycloadditions. Past and Future. Angew. Chem. Int. Ed. Engl. 2. 1963. Vol.2. Iss.10. P.565-598. DOI: 10.1002/anie.196305651 [2] C.W. Tornøe, C. Christensen, M. Meldal. Peptidotriazoles on Solid Phase:  [1,2,3]-Triazoles by Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides. J. Org. Chem. 2002. Vol.67. Iss.9. P.3057-3062. DOI: 10.1021/jo011148j [3] V.V. Rostovtsev, L.G. Green, V.V. Fokin, K.B. Sharpless. A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal Alkynes. Angew. Chem. Int. Ed. 2002. Vol.41. P.2596-2599. DOI: 10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4 [4] C. Wang, D. Ikhlef, S. Kahlal, J.-Y. Saillard, D. Astruc. Metal-catalyzed azide-alkyne “click” reactions: Mechanistic overview and recent trends. Coord. Chem. Rev. 2016. Vol.316. P.1-20. DOI: 10.1016/j.ccr.2016.02.010 [5] J.E. Hein, V.V. Fokin. Copper-catalyzed azide–alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(I) acetylides. Chem. Soc. Rev. 2010. Vol.39. Iss.4. P.1302-1315. DOI: 10.1039/B904091A [6] X.-P. He, Y.-L. Zeng, Y. Zang, J. Li, R.A. Field, G.-R. Chen. Carbohydrate CuAAC click chemistry for therapy and diagnosis. Carbohydr. Res. 2016. Vol.429. P.1-22. DOI: 10.1016/j.carres.2016.03.022. [7] A.Y. Mitrofanov, A.V. Murashkina, I. Martín-García, F. Alonso, I.P. Beletskaya. Formation of C–C, C–S and C–N bonds catalysed by supported copper nanoparticles. Catal. Sci. Technol. 2017. Vol.7. Iss.19. P.4401-4412. DOI: 10.1039/C7CY01343D [8] M.B. Gawande, A. Goswami, F.-X. Felpin, T. Asefa, X. Huang, R. Silva, X. Zou, R. Zboril, R.S. Varma. Cu and Cu-Based Nanoparticles: Synthesis and Applications in Catalysis. Chem. Rev. 2016. Vol.116. P.3722-3811. DOI: 10.1021/acs.chemrev.5b00482