An Efficient Approach for the Synthesis of Triazole Conjugated Pyrazole Chalcone Derivatives

Abstract

An important intermediate, 3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxy phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde in the synthesis of target compounds was synthesized using 2,4-dihydroxyacetophenone as starting synthon by adopting two different click chemistry synthetic protocols. Later the intermediate was further converted into a new series of triazole conjugated pyrazole chalcones from various acetophenones in the presence of potassium hydroxide under microwave irradiation and conventional methods.

Synthesis, Anticancer Activity, and Molecular Docking of New 1,2,3-Triazole Linked Tetrahydrocurcumin Derivatives

“…Tetrahydrocurcumin was alkylated with propargyl bromide in the presence of potassium carbonate (K2CO3) using dimethylformamide (DMF) at room temperature in an inert atmosphere, resulting in compound 1. Various azides (3a-m) were obtained by the reaction of anilines (2a-m) with sodium azide using dichloromethane (DCM) as a solvent [51]. Click reaction was utilized for the synthesis of the tetrahydrocurcumin conjugates (4a-m) by the reaction between compound 1 and azides using copper (Ⅱ) sulfate pentahydrate (CuSO4•5H2O), monosodium ascorbate in THF (2 mL), and a mixture of t-BuOH:H2O (2 mL, v:v = 1:1) at room temperature for 12 h. The column chromatography technique was used for purification of the newly prepared compounds (4a-m) by utilizing a mixture of DCM/EtOAc and 1 H-NMR.…”

“…To this stirred mixture was added t-BuONO (1.5 eq) followed by TMSN3 (1.2 eq) dropwise. The resulting solution was stirred at room temperature for 1 h. The reaction mixture was concentrated under vacuum and extracted with DCM (10 mL × 3) to give product 3a~m [50,51]. To a solution of product 1 (1.2 eq) add aromatic azides (3a~m) (1.0 eq) in THF (2 mL) and t-BuOH-H2O (2 mL, v:v = 1:1) at room temperature and then add copper (Ⅱ) sulfate pentahydrate (20 mg) and sodium ascorbate (2 g in 10 mL H2O, 0.6 mL).…”

“…The reaction mixture must stir at room temperature till completion of the reaction (monitored by TLC). The solvent is evaporated and residue is chromatographed on silica gel using Petroleum Ether:EtOAC to offer the target 4a~m [50,51]. Yellow oil, (139.52 mg, 0.340 mmol, 47%).…”

Synthesis and Characterization of Novel Heterocyclic Chalcones from 1-Phenyl-1H-pyrazol-3-ol

“…An in-depth analysis of NMR spectral data, which were obtained through a combination of standard and advanced NMR spectroscopy techniques, such as 1 H- 13 C HMBC, 1 H- 13 C HSQC, 1 H- 13 C H2BC, 1 H- 15 N HMBC, 1 H- 15 N LR-HSQMBC, 1 H-1 H TOCSY, 1 H-1 H COSY, 1 H-1 H NOESY and 1,1-ADEQUATE experiments, provided the key information in the establishment of structural assignments and predominant configuration, due to conformations in a solvent of novel pyrazole-chalcones. The synthesis and biological activity of the related compounds has been reported in previous works, but no data on conformational analysis supported by NMR experiments were given [58][59][60][61].…”