Conventional Route for Synthesis of Novel Heterocyclic 2-(Substituted-2-oxo-2H-chromen-3-yl)-3-(4-(2-(substituted-phenyl)-4,5-diphenyl-4,5-dihydro-1H-imidazol-1-yl)phenyl)-2-methylthiazolidin-4-one Derivatives and Their Antimicrobial Activity

Authors: Tandrani Ghosh; Sadhana Sing; Rishi kumar Vishnoi; Krishna Srivastavaa
Conventional Route for Synthesis of Novel Heterocyclic 2-(Substituted-2-oxo-2H-chromen-3-yl)-3-(4-(2-(substituted-phenyl)-4,5-diphenyl-4,5-dihydro-1H-imidazol-1-yl)phenyl)-2-methylthiazolidin-4-one Derivatives and Their Antimicrobial Activity
DOI
10.25125/ijoer-may-2026-6
DIN
IJOER-MAY-2026-6
Abstract

Conventional routes were achieved for the synthesis of methylthiazolidin-4-one derivatives starting through reaction of substituted salicylaldehyde and acetoacetic ester, which gives acetyl-coumarin. Upon further reaction with benzene-1,4-diamine, it was converted into imine, subsequently cyclized into a thiazole-amine in the presence of thioglycolic acid. The final derivatives were cyclized by a three-component one-pot reaction of amine, substituted aldehyde, and ketone, yielding 2-(8-fluoro-2-oxo-2H-chromen-3-yl)-3-(4-(2-(4-hydroxy-3-methoxyphenyl)-4,5-diphenyl-4,5-dihydro-1H-imidazol-1-yl)phenyl)-2-methylthiazolidin-4-one derivatives. The structures of the novel synthesized derivatives were established by elemental analysis, UV, FT-IR, ¹H-NMR, and mass spectra. The obtained derivatives displayed excellent to moderate antimicrobial activity. 

Keywords
Benzil thioglycolic acid coumarin acetoacetic ester substituted salicylaldehyde benzene-1 4-diamine acetic acid.
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Introduction

Imidazole [1-6] molecule or more commonly known as 1,3-diazole belongs to a five-membered heterocyclic moiety bearing three carbon atoms, two nitrogen atoms, and four hydrogen atoms with two double bonds. It is amphoteric in nature and displays both acidic and basic properties. Since this molecule is amphoteric in nature, it greatly improves the solubility of its derivative molecules. The presence of positive charge on either of the two nitrogen atoms makes it amenable to exist in two tautomeric forms. It also goes by the name of glyoxaline as it was manufactured by using glyoxal and ammonia. Imidazole is an important molecule naturally as it is the edifice of many biologically significant compounds such as histidine [7], purines, and pyrimidines. Derivatives of imidazole [8-12] depict antiviral, antibacterial, anti-inflammatory, antitumor, antidiabetic, and antiallergic activities. Some of the most significant commercially available drugs are clemizole (antihistaminic agent), etonitazene (analgesic), enviroxime (antiviral), astemizole (antihistaminic agent), omeprazole, pantoprazole (antiulcer), thiabendazole (antihelmintic), nocodazole (antinematodal), metronidazole, nitroso-imidazole (bactericidal), megazol (trypanocidal), azathioprine (anti-rheumatoid arthritis), dacarbazine (Hodgkin's disease), tinidazole, ornidazole (antiprotozoal and antibacterial), etc. Thiazolidinone [13,14] heterocyclic compounds have a propensity to be engaged as drug motifs as most of them possess unique biological properties and have shown immense results in combating/curing various diseases. The pursuit of cheap, effective, and safe alternatives to expensive drugs is the reason behind the endless efforts of synthesizing various molecules. Thiazolidinone is a significant pharmacophore possessing tremendous biological [15-30] activities such as anticancer, antibacterial, antifungal, antiviral, antidiabetic, anticonvulsant, antioxidant, sedative, anti-inflammatory, antihypertension, and antituberculosis. The variations of substituents at positions 2, 3, and/or 5, and the substitution of carbon at the second position, are responsible for the varied alterations in the structure and properties of the various thiazolidinone derivatives. Coumarins [31-33] are low molecular weight compounds bearing simple structure and high bioavailability, with excellent solubility in most organic solvents. These are compounds with negligible toxicity and various biological activities [34-37], and therefore they are amongst the pioneering scaffolds in the synthesis of new drug molecular synthons. They express profound pharmacological diversity such as anticoagulant, antimicrobial, anti-inflammatory, neuroprotective, antidiabetic, anticonvulsant, and antiproliferative activities.

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Conclusion

All synthesized derivatives (4a-n) of 2-(substituted-2-oxo-2H-chromen-3-yl)-3-(4-(2-(substituted-phenyl)-4,5-diphenyl-4,5-dihydro-1H-imidazol-1-yl)phenyl)-2-methylthiazolidin-4-one were evaluated for antimicrobial activity. Compounds 4i, 4j, and 4k demonstrated the most promising antimicrobial activity. Exclusively, compound 4i displayed broad-spectrum antibacterial and antifungal potency, suggesting that incorporation of halogen substituents, especially bromine and fluorine, may create potentially more active compounds. These findings indicate that the synthesized thiazolidinone-coumarin-imidazole hybrids may serve as potential lead molecules for the development of new antimicrobial agents.

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