Preparation of New Spiropyrazole, Pyrazole and Hydantoin Derivatives and Investigation of Their Antioxidant and Antibacterial Activities.

Abstract

In this study, the synthesis of new spiropyrazoles, pyrazole and hydantoin heterocycles is reported by three component reactions of parabanic acids, hydrazine derivatives, and phenacyl bromides in the presence of triphenylphosphine as a nucleophile and triethylamine as a base in good to high yields (69–91 %). Evaluation of the synthesized compounds revealed a good to excellent antioxidant activities (37.6–96.2 %) using DPPH inhibitory potency. Among these compounds, hydantoin derivatives displayed higher antioxidant activities (93.7–96.2 %) comparing with spiropyrazoles and pyrazoles. The obtained results showed that Cl and Br substituents on the phenyl ring increased antioxidant activities of the related heterocycles. The antibacterial activities of the synthesized compounds were examined against two Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) and two Gram‐positive (Staphylococcus aureus and Bacillus subtilis) bacteria. Among the synthesized heterocycles, 2‐[1,3‐dimethyl‐2,5‐dioxo‐4‐(2‐oxo‐2‐phenylethyl)imidazolidin‐4‐yl]hydrazine‐1‐carbothioamide exhibited the excellent antibacterial activity against both Gram‐positive and Gram‐negative bacteria.

[3+2]-Cycloaddition of Nitrile Imines to Parabanic Acid Derivatives—An Approach to Novel Spiroimidazolidinediones

“…At the same time, the fragmentation of the molecule apparently occurs only when two aromatic fragments are present in the structure of the thioparabanic acid (no formation of a by-product was observed when products 4f and 4g were obtained). An analogous influence of the nature of substituents on the tendency to fragmentation was previously observed in the formation of spiro compounds from 5-arylidene thiohydantoins and thiosemicarbazides [24]. The structure of product 7 was proposed based on a match between the spectral data obtained by us and those described in the literature [25].…”

Regioselective Cycloaddition of Nitrile Imines to 5-Methylidene-3-phenyl-hydantoin: Synthesis and DFT Calculations

“…The decrease in the yield of the compound 7l is presumably due to the side reaction of pyrazole 9a formation ( Scheme 4 ). Apparently, the pyrazole derivative 9a is formed as a result of cleavage of the imidazolone fragment of the spiro compound 7l , accompanied by aromatization of the pyrazole fragment, similarly to that described in [ 28 , 29 ]. However, it should be noted that an increase in the reaction time does not lead to a significant increase in the yield of the side product 9a .…”

Synthesis, crystal structure and Hirshfeld surface analysis of 2-[(4-hydroxyphenyl)amino]-5,5-diphenyl-1H-imidazol-4(5H)-one

“…Hydantoins or imidazolidine-2,4-diones are heterocyclic compounds characterized by the presence of an imidazole ring and keto groups in positions 2 and 4. Hydantoin-containing compounds exhibit a broad spectrum of pharmacological and biological activities such as an anticancer (Cao et al, 2022), antibacterial (Ghasempour et al, 2021;El Moutaouakil Ala Allah et al, 2024), antidiabetic (Sergent et al, 2008), antiinflammatory (Lin et al, 2021), antimicrobial (Shaala & Youssef, 2021), anticonvulsant (Byrtus et al, 2011) and anti-HIV (Romine et al, 2011) activities. Thiohydantoins, sulfur analogues of hydantoins, undergo replacement of one or both carbonyl groups with thiocarbonyl groups (Johnson & Scott, 1913;Wyzlic et al, 1996;Cromwell & Stark, 1969).…”