Cycloaddition and Homocoupling Reactions Catalyzed by Cu(II)Fe(III)-Layered Double Hydroxide in a Flow System

Cu(II)Fe(III)-layered double hydroxide (CuFe-LDH) is shown to efficiently catalyze 1,3-dipolar cycloadditions of organic azides to alkynes leading to valuable 1,2,3-triazoles as well as oxidative dimerizations of aromatic amines and acetylenes without the need for any auxiliary substances. Mostly, the dimerization reactions need the use of extraneous bases and ligands bearing significant disadvantages as far as environmental impacts and process costs are concerned. In this work, the inherent basic character of a copper-containing layered double hydroxide to facilitate the catalytic reaction was exploited. The reactions were studied in a continuous-flow system to achieve extended parameter spaces for chemical intensification, and to avoid undesired reaction pathways by means of strategic control over the residence time. Other benefits are the safe production as well as scalability. Valuable 1,2,3-triazoles, 1,4-disubstituted 1,3-diynes and diversely substituted aromatic azo compounds were achieved with high chemoselectivity in excellent yields and in short process times even on preparative scales.

The freshly prepared as well as the used CuFe-LDH samples were characterized by a range of state-of-the art instrumental methods (X-ray powder diffractometry, infrared, inductively coupled plasma atomic emission, energy dispersive X-ray and X-ray photoelectron spectroscopies, scanning and transmission electron microscopies and thermal methods). It was established that the catalytic activity of the as-prepared material could be derived from in situ reduction of Cu(II), generating lattice defects containing the catalytically active Cu(I) species. It was verified that oxidative homocoupling of the alkyne component was responsible for the conversion of Cu(II) to Cu(I), but a cooperation of certain structural items of the hydrotalcite-like material could also contribute to the outstanding catalytic efficiency. After successful gram-scale syntheses under high-pressure/high-temperature conditions, no destruction of the catalyst structure was found suggesting that the layered double hydroxide acted as a highly robust catalytic system.