Study On One-Pot Synthesis Of The Thiazolo[1,2,4]Triazoles Using Low-Load Copper(Ⅱ)as Catalyst In Water

The thiazolo-triazoles are those compounds which contain two fused rings of thiazole and triazole in their structure. Benzothiazole and triazole compounds are widely used in medicine, pesticide and other fields, which are two kinds of very important molecules. So the thiazolo-triazoles fused the thiazole ring and triazole ring are bound to have potential biological activities, which is worthy of people’s in-depth research.Isothiocyanate and its derivatives are important organic synthetic intermediates. They are widely used in medicine and pesticide synthesis, particularly used in the synthesis of some heterocyclic compounds with biological activities. In addition, they can be used as fluorescent markers, and also used for the determination of amino acids order. In recent years, metal organic catalysis has been the research hotspot and important means in modern organic synthesis. Through the catalyst of cheap metal copper, it can make the nucleophilicity of carbon, nitrogen, oxygen, sulfur, etc and electrical unsaturated carbon atoms (sp or sp2) directly form bonds. This copper catalyzed cross-coupling reaction is one of the hotspots in modern organic synthesis.In recent years, with the development of green chemistry, how to make reactions in green solvent is the focus of the study of people, for example, recently it is often reported that using water, ionic liquid, supercritical carbon dioxide and other more mild and relatively clean green solvents to participate in the reaction. Water as the most cheap, abundant natural resources on earth, has less impact on the environment, therefore, using water as reaction medium to develop green chemistry technology is particularly important.This article first briefly introduces the important application of isothiocyanates in the field of organic synthesis, copper catalyzed cross-coupling reaction progress and water as solvent in reactions. In addition, it also introduces the medical background and the synthesis of the thiazolo-triazoles.In the second chapter, a new method for synthesis of substituted o-bromo phenyl isothiocyanates has been established. In this method, we use NaH as the base,1,4-dioxane as the solvent, under refluxing conditions to synthesize the products. This method is particularly suitable for the isothiocyanates containing the electron withdrawing group, while whose synthesizes were not available using the conventional method. The present method shows fascinating properties such as simple method, avoids the use of transition metals and high yields.Then, the synthesis of thiazolo[1,2,4]triazoles has been developed via one-pot, three-step reaction by using hydrazides and substituted o-bromo phenylisothiocyanates as substrates, copper as catalyst. Taking into account all the experimental results, the optimal condition for the reaction is:CuCl2·2H2O (1%mmol),1,10-phen (1%mmol) and Na2CO3(2equiv) as base at90℃. With water as the solvent, low load of copper alt as catalyst, and phenanthroline as ligand, the reaction process is economic, environmental and the yields were up to97%. It is worth noting that the reaction does not require separation of the intermediate and the target product directly separate out in the system without further purification such as column chromatography and recrystallization.The structures of all the target compounds were confirmed by IR,H NMR,13C NMR, and HRMS, and the plausible mechanism was also presented. The unambiguous molecular structure of3h was determined by X-ray diffraction analysis.