Microwave-assisted Aqueous Multicomponent Reaction: Facile Synthesis of Polyfunctionalized Indoline-spiro Fused Pyran Derivatives

Abstract

A green and highly efficient method for the synthesis of polyfunctionalized indoline-spiro fused pyran derivatives has been established. This reaction was conducted by reacting readily available and inexpensive starting materials, such as isatins, cyclic-1,3-dicarbonyl compounds, and malononitrile in aqueous media without any catalysts under microwave irradiation. The present green synthesis shows fascinating properties such as the use of water as the reaction solution, concise one-pot conditions, short reaction periods (8-14 min), and easy purifications. The synthesis could also set a good example to GAP (Group-Assistant-Purification) chemistry in which purification via chromatography can be avoided and the pure products can be easily acquired only by washing the crude products with 95% EtOH.

Advances in the Synthesis of Benzo‐Fused Spiro Nitrogen Heterocycles: New Approaches and Modification of Old Strategies

“…Similar synthesis of compound 34 (R 1 =R 3 =Me, R 2 =H, R 4 =CO 2 Me) was also described [123] . There are publications of the results of non‐catalytic synthesis analogs of heterocycle 34 from isatins, cyclic α‐methylenedicarbonyl compounds and malononitrile in an aqueous medium under microwave irradiation [124] …”

“…[123] There are publications of the results of non-catalytic synthesis analogs of heterocycle 34 from isatins, cyclic α-methylenedicarbonyl compounds and malononitrile in an aqueous medium under microwave irradiation. [124] The approaches through the use of multicomponent condensation reactions of isatins, pyrazoles and CH activated molecules with different acidity of the medium are effective in obtaining spirocycles to which pyrazole fragments are annulated. [127 -131]…”

“…Multicomponent reactions of isatins with malononitrile or ethyl ester of cyanoacetic acid are quite often also used in the preparation of indolone‐pyran spiro‐fused heterocycles [116–126] . The electrocatalytic multicomponent synthesis of nanoparticles of spirooxindole 31 was carried out using an electrogenerated base of the propanol anion in a one‐pot, three component condensations of isatins 22 , dimedone 32a , and malononitrile in an undivided cell in the presence of sodium bromide as an electrolyte at 50 °C.…”

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

“…A detailed mechanism was proposed, with the initial formation of benzo[a]phenazin-5-ol A through condensation of diamine 23 and 2-hydroxynaphthalene-1,4-dione (11). A simultaneous The synthesis of indoline-spiro fused pyran derivatives 53 was reported by Jiang and co-workers [57] employing a multicomponent reaction between substituted isatins 35, cyclic 1,3-diketones 6 and malononitrile (51) in an aqueous medium without any catalyst. Reaction diversity was examined by using different 1,3-diketones and isatins (Scheme 19).…”

Synthesis of spiro-fused heterocyclic scaffolds through multicomponent reactions involving isatin

“…161 Wu et al used an aqueous media without any catalysts under microwave irradiation. 162 In another study, glycerol as a biodegradable and reusable promoting medium was applied under catalyst-free conditions. 163 This reaction was also conducted under catalyst-free condition in deep eutectic solvent (DES based choline chloride) 164 or under catalyst-free conditions in DMSO at 70 °C.…”