Efficient catalyst-free synthesis of diversified bis (spirooxindoles) via one-pot, three-component reaction

Engaging Isatins in Multicomponent Reactions (MCRs) – Easy Access to Structural Diversity

“…reported the synthesis of dispirooxindole derivatives (20 examples) in excellent yields, but this time using ethylene glycol as reaction medium for the pseudo five‐component reaction between bis‐isatins, cyclic carbonyls and malononitrile (Scheme 108). The reaction, which proceeded with short reaction times, allowed the preparation of these derivatives without time‐consuming work‐up procedures and under catalyst‐free conditions [202] . A similar library (6 examples) was also reported recently by Wagh et al ., using cesium floride (10 mol%) as catalyst.…”

One‐pot, Multi‐Component Synthesis of Novel Bis‐Spiro Pyranopyrazole Derivatives in the Presence of DABCO as an Efficient and Reusable Solid Base Catalyst

“…There are a limited number of synthetic procedures for the synthesis of bis‐isatin derivatives via the condensation reaction of isatin derivatives with different di‐halides in the presence of different reagents such as NaH, or K 2 CO 3. , However, these synthetic routes have suffered from some disadvantages such as the use of toxic solvents (DMF or DMSO), low yields and difficulties encountered in the product separation ,. Thus, the extension of a simple, green procedure for synthesis of bis‐isatin compounds remains desired.…”

“…Their applications in pharmaceutical ingredients, anti‐inflammatory, antimicrobial and anticancer agents have been investigated. However, survey of literature data show that only two published manuscripts have reported the preparation of only two bis‐spiro pyranopyrazoles molecules and both of them suffered from utilizing toxic solvents such as DMSO, Furthermore, 3‐methyl‐1 H ‐pyrazole‐5‐(4 H )‐one has been used in the reported articles which limits the molecular diversity and complexity of the desired compounds. Synthesis of pyrazolone derivatives would be achieved through the in‐situ reaction of hydrazine and β ‐ketoesters;, and this would help to achieve the diversity and complexity of the final product.…”

Highly efficient, one-pot synthesis of novel bis-spirooxindoles with skeletal diversity via sequential multi-component reaction in PEG-400 as a biodegradable solvent

“…However, survey of the literature data show that the majority of these methods suffer from one or more drawbacks, such as multistep sequences, toxic solvents like DMSO and DMF, application of hazardous and toxic agents like NaH and long reaction times. [29][30][31]36 Considering the aforementioned drawbacks, producing of N-alkyl-linked bis-isatins and then obtaining the corresponding bis-spirooxindole compounds in our introduced reaction model have merits such as green solvent, non-toxic reagent, room temperature conditions, low cost, and easy work-up.…”