Sulfate ionic liquids promoted FeCl3-catalyzed dehydration of propargyl alcohols

Abstract

Conjugated enynes are an important class of compounds that could be widely used in medicinal chemistry and organic synthesis. Herein, various sulfate ionic liquids with FeCl3 were used to catalyze the dehydration of propargyl alcohols to prepare conjugated enynes. Sulfate ionic liquids with different substituent chain lengths or cations exhibited high catalytic activity, affording the highest conjugated enyne yield of 96 % with selectivity of 97 %. At the same time, the by-product naphthofuran derivative was isolated and verified by the single crystal X-ray diffraction for the first time. Kinetic studies found that the addition of sulfate ionic liquids increased the rate of formation of desired product conjugated enyne and inhibited the production of by-product naphthofuran derivative. Deuterated kinetic isotope studies were carried out by using the deuterated substrate PhCC(CD3)2OH and PhCC(CH3)2OD. A large value of H/D kinetic isotope effects (KIE1 = 5.5) suggested that the βC—H bond cleavage was involved in the rate-determining step and the formation of desired conjugated enyne followed the E2 elimination mechanism. An inverse kinetic isotope effects (KIE3 = 0.66) suggested that the formation of by-product naphthofuran derivative followed the SN2 mechanism. Density functional theory (DFT) calculations were conducted to reveal the activation of sulfate anion on the methyl group of propargyl alcohol. Based on the crystal structure of by-product, kinetic studies, deuterated kinetic isotope studies and DFT calculations, a cooperative mechanism of dehydration of propargyl alcohol over sulfate ionic liquids and FeCl3 was proposed.