Mandelic Acid: An Efficient Organo-catalyst for the Synthesis of 3-substituted-3- Hydroxy-indolin-2-ones and Related Derivatives in Aqueous Ethanol at Room Temperature

Abstract

Indoles and various indolyl derivatives are very common in naturally occurring biologically active compounds. Many methods are being developed for the synthesis of various bioactive indole derivatives. Synthesis of biologically promising structurally diverse indole derivatives under mild and environmentally benign conditions. Synthesis of 3-hydroxy-3-(5-(trifluoromethoxy)-1H-indol-3-yl)indolin-2-one was achieved by the reaction of an equimolar mixture of isatin and 3-(trifluoromethoxy)-1H-indol using 20 mol% of mandelic acid as catalyst in aqueous ethanol at room temperature. Under the same optimized reaction conditions, synthesis of 3-(3-hydroxy-2-oxoindolin-3-yl)chroman-2,4-diones was accomplished via the reactions of substituted isatins and 4-hydroxycoumarin. On the other hand, 2-hydroxy-2-(indol-3-yl)- indene-1,3-diones and 10-hydroxy-10-(5-methoxy-1H-indol-3- yl)phenanthren-9(10H)-one were synthesized from the reactions of indoles and ninhydrin or 9,10-phenanthrenequinone respectively using the same 20 mol% of mandelic acid as an efficient organo-catalyst in aqueous ethanol at room temperature. Mild, safe and clean reaction profiles, energy efficiency, high atom-economy, use of naturally occurring non-toxic organo-catalyst, easy isolation procedure by avoiding column chromatographic purification and gram scale production are some the major advantages of this developed protocol. A simple, straightforward and eco-friendly protocol has been developed for the efficient synthesis of biologically promising novel 3-hydroxy-3-(5-(trifluoromethoxy)-1H-indol- 3-yl)indolin-2- one, 3-(3-hydroxy-2-oxoindolin-3-yl)chroman-2,4-diones, 2-hydroxy-2-(indol-3- yl)-indene-1,3-diones and 10-hydroxy-10-(5-methoxy-1H-indol-3-yl)phenanthren-9(10H)-one using a catalytic amount of mandelic acid in aqueous ethanol at room temperature.