Aqua/Mechanochemical Mediated Synthesis of Novel Spiro [Indole–Pyrrolidine] Derivatives

Abstract

Spirocyclic scaffolds are found in many pharmacologically active natural and synthetic compounds. From time to time, efforts have been made to develop new or better processes for the synthesis of spirocyclic compounds. Spiro [Indole–pyrrolidine] Derivatives are readily synthesized in high to excellent yields by the Michael condensation of 3-dicyanomethylene-2H-indol-2-ones (produced via the Knoevenagel condensation of indole-2,3-dione with malononitrile) with isothiocyanate derivatives under aqueous and mechanochemical conditions. The advantages of this protocol are that the reactions are solvent-free, occur at ambient temperature, require short reaction times, have experimental simplicity, and produce excellent yields. These environmentally friendly reaction media are useful alternatives to volatile organic solvents.

Mechanochemically‐Assisted Passerini Reactions: A Practical and Convenient Method for the Synthesis of Novel α‐Acyloxycarboxamide Derivatives

“…Thus, we found that liquid‐assisted mechanochemical activation was efficient and valuable in our work with respect to yields and experimental simplicity [28] . Other mechanochemically activated multicomponent reactions (MCRs) have afforded various novel spiro‐[ indole‐pyrrolidine], thiophene, and 4H‐pyran derivatives [29,30,31] …”

“… [28] Other mechanochemically activated multicomponent reactions (MCRs) have afforded various novel spiro‐[ indole‐pyrrolidine], thiophene, and 4H‐pyran derivatives. [ 29 , 30 , 31 ]…”

Unlocking New Avenues: Solid-State Synthesis of Molecularly Imprinted Polymers

“…Examples of mechanochemical reactions include ball milling, sonication, and grinding of solid reactants to produce new compounds with unique properties. Such reactions have been reported for the synthesis of various inorganic [8] or organic molecules [9,10] or supramolecular structures [11,12], such as co-crystals, polymorphs, metal-organic frameworks, covalent-organic frameworks, and coordination polymers, with a plethora of scientific and industrial applications.…”

3-[N,N-Bis(sulfonyl)amino]isoxazolines with Spiro-Annulated or 1,2-Annulated Cyclooctane Rings Inhibit Reproduction of Tick-Borne Encephalitis, Yellow Fever, and West Nile Viruses

“…Spiroheterocyclic motifs are present in a number of approved drugs and natural compounds [ 1 , 2 , 3 , 4 ] ( Figure 1 ). Such an interest in spirocyclic structures echoed in the field of synthetic organic chemistry, giving rise to a number of elegant preparative approaches to compounds of this type [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ].…”