DMF mediated Henry reaction of isatins: an efficient synthesis of 3-hydroxy-2-oxindole

Abstract

An efficient Henry reaction has been described for the synthesis of 3-hydroxy-3-(nitroalkyl)-2-oxindole by the reaction of isatins with nitroalkanes in N,N-dimethylformamide (DMF) under anhydrous condition. This method provides high yield of 3-hydroxy-2-oxindoles under mild reaction condition. Moreover, the procedure is environmentally benign in nature, efficient, and applicable to variety of isatins as well as nitroalkanes.

Hit optimization studies of 3-hydroxy-indolin-2-one analogs as potential anti-HIV-1 agents

“…Next, to enhance the yield, solvent and base was replaced with ethanol and diethyl amine, respectively and reaction mixture was stirred at room temperature. After six hours, reaction ended-up as single spot and desired compound 3a was obtained in 88% yield [31][32][33][34][35]. Rest of the compounds 3b-5j were synthesized in good to excellent yield (78-96%) using the optimized reaction conditions of compound a3.…”

“…After completion of reaction, ethanol was evaporated on rotary evaporator to half of its original volume and 15 ml of ice cold water was added to the reaction mixture. Resulting precipitates were filtered using vacuum filtration and twice washed with cold ethanol (2 × 10 ml), followed by diethyl ether (10 ml) and finally dried in oven at 45°C to get desired compounds 3a-5j [31][32][33][34][35]. Synthesized compounds were first characterized using non-spectral techniques like TLC and melting point and then by different spectral techniques like IR, 1 H NMR, 13 C NMR, ESI-MS and elemental analysis.…”

Unprecedented, catalyst‐free, and rapid one‐pot, three‐component green synthesis of substituted 3‐hydroxy‐2‐oxindoles in water

“…In continuation of our interest in the development of novel and eco-friendly protocols [25][26][27][28][29][30][31][32], we developed an unprecedented, catalyst-free method for the synthesis of substituted 3-hydroxy-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)indolin-2-one. Among many approaches that have been published to synthesize a variety of 3-hydroxy-2-oxindoles, our method holds a special tag of a new route.…”

BMIm[OH] Catalyzed Rapid, Mild and Improved Protocol for the Synthesis of 3‐Hydroxy‐3‐(nitroalkyl)indolin‐2‐one Derivatives in Water

“…The nucleophilic addition to isatin is a direct route for the generation of quarternary centre at C‐3 position of 3‐hydroxy‐3‐(nitroalkyl)‐oxindole that includes the condensation of nitromethane with isatin using diethylamine in ethanolic medium, DBU (1,8‐diazabicyclo[ 5.4.0]undec‐7‐ene) and DABCO (1,4‐diaza‐bicyclo [2.2.2]‐octane) as bases for the formation of adduct or alkali metal halides with electrochemical setup . DMF mediated Henry reaction of istatins with nitroalkanes under catalyst free anhydrous condition is also reported . These methods suffer from some serious limitations such as tedious work‐up, long reaction time, unsatisfactory yields and narrow scope of substrates.…”