Development of New Multicomponent Reactions in Eco-Friendly Media-Greener Reaction and Expeditious Synthesis of Novel Bioactive Benzylpyranocoumarins

Abstract

Multicomponent cyclocondensation of hydrazine derivatives, ethyl acetoacetate, aromatic aldehydes, and 4-hydroxycoumarin has been reported. The optimization details of the developed novel protocol are recorded. The novel procedure features short reaction time, moderate yields, and simple workup. In addition, BMIM[triflate] was chosen as a green solvent. The structures of the obtained benzylpyrazolyl coumarins were determined and confirmed by 1H NMR, 13C NMR, IR, and elemental analysis. The MIC values of benzylpyrazolyl coumarin derivatives were determined by the microbroth dilution method using 96-well plates. However, the derivatives 5a, 5b, 5d, and 5g possess the strongest activities. Compound 5b was the most active derivative against Candida albicans. Moreover, the antioxidant activity determination of these coumarins derivatives 5(a–g)–6(a–g) were studied with the DPPH and compared with gallic acid (GA)and butylated hydroxytoluene (BHT). Molecular modelling studies using DFT (density functional theory) calculations showed that there two tautomers A and B in which A is more stable than B. The benzylpyrazolyl coumarin derivatives 5e and 6f exhibited the most cytotoxic effect on the promising cytotoxic activity with IC50 values 4.45 μg/mL against MDA-MB-231 and 4.85 μg/mL against MCF7, respectively.

Potassium dihydrogen phosphate‐catalyzed synthesis of benzylpyrazolyl coumarin and pyrano [2,3‐c] pyrazole derivatives via cascade—One‐pot—Multicomponent reaction

“…Thus, the hybrid resulting from both the motifs might exhibit promising biological properties. These compounds exhibited various biological activities like antifungal, antibacterial, and antioxidant properties [4]. In general, the benzylpyrazolyl coumarin derivatives have been prepared from a 4‐component reaction of 4‐hydroxy coumarin, ethyl acetoacetate, aldehyde, and phenylhydrazine/hydrazine hydrate.…”

“…In general, the benzylpyrazolyl coumarin derivatives have been prepared from a 4‐component reaction of 4‐hydroxy coumarin, ethyl acetoacetate, aldehyde, and phenylhydrazine/hydrazine hydrate. Many reported methods include the use of metallic nanoparticles [5a, b], ionic liquid [4], gl. AcOH [6], Ca(OTf) 2 [7], melamine‐modified chitosan material [8], taurine [9], and graphene‐oxide nanoparticles [10].…”