TiO₂ Nanoparticle Catalyzed Rapid Synthesis of Spiroxindole‐Pyrrolidine in Aqueous Medium and Evaluation of their Antimicrobial Properties

Abstract

We report TiO2 nanoparticle as a reusable heterogeneous catalyst for rapid synthesis of Spiroxindole‐Pyrrolidine by reacting of 3‐aryl‐1‐(pyridin‐2‐yl)‐prop‐2‐en‐1‐one, isatins and benzylamines via 1,3‐dipolar cycloaddition reaction using water as reaction media. The reaction proceeded with excellent regio and diastereoselective product formation along with good yields within 30 minutes. Structure of the product was unambiguously confirmed by single crystal X‐ray diffraction study. Synthesized Spiroxindole‐Pyrrolidine derivatives were evaluated for antimicrobial activity and found that all the compounds performed well against standard streptomycin drug.

Recent Developments on 1,3-Dipolar Cycloaddition Reactions by Catalysis in Green Solvents

“…More recently, TiO2 nanoparticles (TiO2 NP) in aqueous media was proposed as a reaction system to prepare spirooxindole-pyrrolidines 107 via 1,3-dipolar cycloaddition between substituted isatins 104, benzylamines 105, and pyridyl enones 106 with excellent regio-and diastereoselectivity, very good yields (80%-94%), and very short reaction time (Scheme 22) [70]. The effect of substituents on isatin substrates was evaluated observing that the halogen groups gave spirooxindoles in high yields, while a methoxy group on the benzylamine substrates produced the final products in low yield in contrast to fluoro-functionalized benzylamines.…”

“…More recently, TiO2 nanoparticles (TiO2 NP) in aqueous media was proposed as a reaction system to prepare spirooxindole-pyrrolidines 107 via 1,3-dipolar cycloaddition between substituted isatins 104, benzylamines 105, and pyridyl enones 106 with excellent regio-and diastereoselectivity, very good yields (80%-94%), and very short reaction time (Scheme 22) [70]. A plausible mechanism of reaction was proposed that includes an initial immobilization of the reagents on the TiO 2 NP surface, facilitating the proximity of the substrate to react.…”

Nanoparticle‐Catalysed 1,3‐Dipolar Cycloadditions

“…As can be seen in Scheme 2 both di-spiroindolizidine bisoxindoles 1 and spiroxindole-pyrrolidine 2 skeletons were obtained at room temperature in EtOH or water (1: 10 examples, 83-97 % yield; 2: 16 examples, 80-94 % yield). The initial condensation between tetrahydroisoquinoline (or benzylamine) and isatine provide the precusor of the azomethine ylide intermediate whose subsequent cycloaddition onto the appropriate dipolarophile gives the target molecules 1 [52] and 2 [53] as single stereoisomers. Curiously enough, these reactions occur in the absence of a basic agent, in contrast with both uncatalysed [54] and metal-catalysed [55] azomethine ylide cycloadditions.…”

Green Protocols in Heterocycle Syntheses via 1,3-Dipolar Cycloadditions

“…The use of Lewis acids, such as Ceric Ammonium Nitrate (CAN) or TiO 2 , in the formation of spirooxindoles in water has been investigated, giving excellent results (Scheme 18) (Ramesh et al, 2016, 2018). The 1,3-dipolar cycloaddition was performed with 1 mol% of CAN in 2 h, while the reaction was complete after 30 min when heterogeneous TiO 2 nanoparticles were used.…”