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Abstract
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Tetrazoles are an important class of heterocycles combining high nitrogen content with significant biological properties. Among these are activities as sedatives,1 antibacterials,2 anticancer drugs,3 antidiabetic medications,4 antifungals,5 anti-inflammatories,6 general antimicrobials,7 antitumor compounds,8 antivirals,9 carboxylic acid isosteres,10 diuretics11 and herbicides.12 In continuation of our previous work on the application of magnetic nanoparticle metal complexes as heterogeneous catalysts for the synthesis of heterocyclic compounds,13 we would now like to report the preparation of the novel title Cu nano-catalyst. Our motivation was to promote a new efficient nano-catalyst for greener methods and potentially lower costs for the synthesis of heterocycles. The catalyst preparation occurred via a multistep process including: the synthesis of the Fe3O4 magnetic nanoparticles, coating the latter with tetraethyl orthosilicate (TEOS) (Fe3O4/SiO2), functionalization of Fe3O4/SiO2 with 3-chloropropyltrimethoxysilane (CPTMS) and 3-mercapto- 1,2,4-triazole (MT) ligands (Fe3O4/SiO2/CPTMS/MT), and further complexation with CuCl2 (Fe3O4/SiO2/CPTMS/MT/Cu). In a demonstration of its utility for diversity in synthesis, the new Cu magnetic nano-catalyst was subsequently used for the synthesis of a variety of useful tetrazoles from the reaction of amino acids with sodium azide and triethyl orthoformate (TEOF) in H2O at 40 C (Scheme 1). To the best of our knowledge, this is the first such application. The catalyst activity was optimized in a model reaction. This was the synthesis of 3-(1H-indol-3-yl)-2-(1H-tetrazol-1-yl)propanoic acid (2c) from the reaction of tryptophan with sodium azide and TEOF. The model was run under different conditions of temperature, amount of the catalyst and solvents. The best result was obtained with 10 mmole of amino acid, 10 mmole of sodium azide, 30 mmole of TEOF and 20 mg of the Cu nano-particle catalyst in H2O at 407C (Tables 1-3). Applyin
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