Synthesis Of Indole Derivatives With Mesoporous MCM-41Silica Catalyst Functionalized With Sulfonic Acid Groups

Indole derivatives are widespread in nature and of important biological activities. Generally, strong mineral acids, such as H2SO4, HC1or lewis acids like ZnCl2and FeCl3are used for synthesis of indole derivatives. However, this typical homogeneous catalysis system suffers from reactor corrosion, waster neutralization, difficult separations and inability to reuse catalyst, which is associated with a number of environmental problems. In recent years’research, solid acid is a new type of environmentally friendly acid catalyst with a wide range of industrial application. Solid acid catalyzed reaction is characterized by increased yield, decreased by-product, easy purification of the product and catalyst recoverability. Therefore, the investigation of indole derivatives synthesis with solid acid is of considerable current interests.A series of MCM-41silica functionalized with sulfonic acid groups (SO3H-MCM-41) with different acid amount were prepared through the condensation of MCM-41with benzyl alcohol followed with sulfonation. The acid amount was measured by NaOH titration and the amount of sulfur loading was determined by elemental analysis. SO3H-MCM-41was characterized by XRD, FT-IR, and nitrogen adsorption.. Synthesis of7-ethyltryptophol under solid acid was studyed with phenylhydrazine hydrochlorides and2,3-dihydrofuran, which was selected as a model experiment to survey the catalyst acidity, reaction temperature, the amount of catalyst and reactant molar ratios. Optimized conditions involved reaction of2-ethylphenyl hydrazine hydrochloride with2,3-dihydrofuran (1equiv) under the catalysis of SO3H-MCM-41-0.6(0.05g/g2-ethylphenyl hydrazine hydrochloride) at90℃, which gave7-ethyltryptophol in50%yield higher than that of H2SO4catalyzed method. A series of tryptophols were synthesized successfully under the optimized conditions in better yields than those of conventional methods reported. All the products were characterized by1H-NMR and MS.Synthesis of etodolac methyl ester with SO3H-MCM-41-0.6catalyst was investigated with7-ethyltryptophol and methyl3-oxopentanoate. The reaction temperature, catalyst amount, reaction solvent and reactant molar ratios were examined to improve the yield of products. Optimized conditions involved reaction of7-ethyltryptophol with methyl3-oxopentanoate (1.2equiv) under the catalysis of SO3H-MCM-41-0.6(0.1g/g2-ethylphenyl hydrazine hydrochloride) in1,4-dioxane at reflux temperature, which gave etodolac methyl ester in50%yield.