Studies Of Copper And Iodine Mediated Synthesis Of 1,2,3-Triazoles

Nitrogen-containing heterocycles widely exist in the nature and synthetic compounds, which have a high proportion of heterocyles. They serve as the core framework of many bioactive natural products and organic funcitional molecules and have found wide application in medicine, funcitional materials, dye and pesticide. In recent years, much attention has been paid towards transition metal catalyzed or mediated nitrogen-containing heterocycles. In particular, tremendous progess have been made about the research of copper mediated synthesis of nitrogen-containing heterocycles. In addition, iodine, which acts as an inexpensive, low-toxic and efficient metal-free catalyst and oxidant, has been applied as an alternative catalyst for transition metal to paticipate in the synthesis of heterocycles.1,2,3-Triazoles are identified as a kind of extremely important heterocycle compound and have found extensive application of numerous fields.This dissertation mainly focused on the studies of copper and iodine mediated azide-free synthesis of 1,2,3-triazoles, and falled into three parts as follows.1. Copper-mediated synthesis of 1,2,3-triazoles from N-tosylhydrazones and anilinesWe have developed a new general method for the synthesis of 1,4-disubstituted and 1,4,5-trisubstituted triazoles from N-tosylhydrazones and anilines through a copper-mediated reaction. Notable features of this transformation include the exclusive formation of 1,4- or 1,4,5-substituted regioisomers, its broad scope with respect to both the N-tosylhydrazone and the aniline substrate, the low cost of reagents, and the convenient operating conditions. More importantly, this reaction avoids the utilization of expensive alkynes and potentially shock-sensitive (explosive) organic azides. This discovery could have important consequences for the synthesis of triazole structures.2. Efficient synthesis of 1,2,3-triazoles by copper-mediated C-N and N-N bond formation starting from N-tosylhydrazones and aminesAn effective copper-mediated regioselective synthesis of 1,5-dialkyl-4-aryl-1,2,3-triazoles and 1,4-dialkyl-5-aryl-1,2,3-triazoles has been achieved by the use of different N-tosylhydrazones and alkyl amines. The scope of the substrates could be extended from anilines to aliphatic amines when 30 mol% amino acid is added into the reaction mixture. This methodology exhibits many features, such as broad substrates scope, high efficiency, and good regioselectivity. Preliminary mechanistic studies indicated that the reaction probably proceeded through a 1-tosyl-2-vinyldiazene intermediate and subsequent aza-Michael addition and N-N bond formation process.3. Metal-free C-N and N-N bond formation:synthesis of 1,2,3-triazoles from ketones, N-tosylhydrazines, and amines in one potBased on our previous research of the synthesis of 1,2,3-triazoles, a novel synthetic approach toward 1,4-disubstitued 1,2,3-triazoles via C-N and N-N bond formation has been firstly established under transition-metal-free conditions. Complete control of regioselectivity was successfully achieved and commercially available reactants of amines, ketones and N-tosylhydrazines were treated with molecular iodine in one pot to allow for the regioselective generation of 1,4-disubstitued 1,2,3-triazoles in high yields without the use of azides. We performed the reaction on the gram scale and were pleased to find that the triazole product was obtained in excellent yield. This satisfactory result provides a possibility for the large-scale applications of this methodology.