In the past few decades, 1,2,3-benzotriazole derivatives have been commonly used for anti-fungal, anti-cancer, and even anti-parasitic medications. Triazoles are the second major chemical class of antifungal derivatives due to their wider range of activity and lower toxicity levels when compared to other antifungal drugs. 1,2,3-Triazole antifungals act by inhibiting the conversion of lanosterol 14-α-demethylase (CYP51) into ergosterol, the primary sterol in fungal cell membranes. During our previous study using gold(I) salts to catalyze etherification reactions, we discovered that 1,2,3-benzotriazoles have nucleophilic reactivity in preference to the etherification pathway. We were able to successfully achieve N-alkylated products using microwave conditions. From this, our lab has developed the first microwave-assisted, gold(I)-catalyzed substitution reaction of 1,2,3-benzotriazole with benzylic alcohols to afford N-substituted 1,2,3-benzotriazole derivatives. To our knowledge, while examples of base-catalyzed and phase transfer catalysis displacement reactions are well-known, a microwave assisted, gold(I)-catalyzed substitution reaction is currently unprecedented in the literature. Microwave irradiation allows this one-step reaction to be completed in only six hours. Our reaction protocol results in higher yield and regioselectivity than comparable conventional heating techniques. All products are isolated by column chromatography and analyzed using 1H-NMR. Reaction optimization and substrate scope investigation will be presented. Furthermore, we present the synthesis of 1-[(4-chlorophenyl) phenylmethyl]-1H-benzotriazole, an antifungal medication to treat candida, with our gold(I) reaction methodology. Candida is a fungus with over 20 species and cause infections. Using our gold(I) protocol, this compound was prepared in 92% yield in only 6 hours.

Gold-catalyzed arylation of benzylic alcohols to afford bioactive 1,2,3-benzotriazole derivatives

2019 Spring National Meeting

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