Considering the very important medicinal and biological properties of heterocycles including isatin skeleton, synthesis of isatin-containing compounds has attracted the attention of medicinal and organic chemists, especially researchers involved in the synthesis of heterocycles. The present review focuses on the recent investigation in the synthesis of heterocycles with isatin moiety using isatin derivatives as reaction reactants via multi-component for the period of 2014–2024. The reports were classified according to the conditions of the reactions, which distinguishes this review from similar studies. In some reports, green chemistry has been used, such as the use of green solvent, green and reusable catalyst, solvent-free conditions, microwave irradiations and ultrasonic irradiations. Most reviews of isatin published so far have focused only on spirooxindoles, but this review not only addresses the condition for the synthesis of spirooxindoles, but also the synthesis of other isatin-contaning heterocycles such as pyrroloquinolines, imidazole-indoles and pyrazoloquinoline. The main objective of this review is to present an overview of the latest methodologies involving isatin in the multicomponent synthesis of heterocyclic compounds, specifically for organic and medicinal chemists.

An efficient, three-component, catalyst free synthesis of dipyrazolo[1,5-a:3',4'-d]pyramid scaffolds has been carried out using 3-methyl-1H-pyrazol-5(4H)-one (1), 5-amino pyarazole (2a-b) and substituted aromatic aldehydes. The reaction underwent cyclocondensation reaction in reflux condition with moderate to good (62%–90 %) yields. The twenty newly prepared molecules were analyzed by means of 1H & 13C NMR, Mass, and IR spectroscopies and their activities against the bacterial and fungal strains were screened. Some of tested compounds have shown excellent antibacterial activities while another four were found to have good antifungal activity.

We report ammonium metavanadate catalyzed one-pot synthesis of 3,4-dihydropyrano[3,2-c]chromenes, from aldehydes, active methylene compounds malononitrile and 4-hydroxycoumarin in water:ethanol(1:1) under reflux. The attractive features of this process are mild reaction conditions, short reaction times, easy isolation of products, and excellent yields.

A simple, efficient and green one-pot, four-component synthesis of highly substituted polyhydronaphthalenes in aqueous media is described. The method has such advantages as short reaction times, high yields, mild reaction conditions, operational simplicity and environmentally benign.

An efficient and simple synthesis of some 2-amino-3-cyano-4H-pyran derivatives was developed by the one-pot and three-component reaction of aldehydes, ethyl acetoacetate, and malononitrile in the presence of ammonia as catalyst at room temperature. The reaction is rapid and clean, and gives the products in high yields.