Bis(β‐iminoenolate)copper(II) complexes with different substituents (3 a–c) have been prepared and explored the catalytic activity for azide‐alkyne cycloaddition reaction in environmentally benign condition. Copper complexes showed highly efficient catalytic activity and produced regioselective product of 1,4‐disubstituted‐1,2,3‐triazoles in one‐pot three component reaction between benzyl chloride, sodium azide and alkynes at room temperature in water medium. The structure‐activity comparison revealed that copper complex with electron withdrawing fluoro substituent (3 c) exhibited comparatively higher catalytic activity in azide‐alkyne cycloaddition reactions and produced up to 98 % of yield with 12.5 mol % of the catalyst without addition of any other reagent.

Ten chiral methyl 2‐(2‐oxo‐2H‐benzo[e][1,3]oxazin‐3(4H)‐yl)propanoate derivatives 6a‐6j have been synthesized from optically pure amino methyl phenol 5 and 4‐nitrophenyl chloroformate. These derivatives 6a‐6j are characterized by 1H NMR, 13C NMR, FT‐IR, and HRMS spectral techniques. Optical purity of these derivatives was confirmed by chiral HPLC method. Ten synthesized ester derivatives 6a‐6j were screened for their in vitro antioxidant activity. Among the compounds 6b‐d and 6h‐j have exhibited comparable antioxidant activity with ascorbic acid as a standard. Compounds 6a and 6e‐g have shown moderate antioxidant activity. Further, the in vitro cytotoxicity of these compounds were studied through MTT cell proliferation assay in addition the effect on LDH leakage and NO release. Among the derivatives, 6j showed extremely best activity and the IC50 value (12.54 ± 0.71 μM) is very close to doxorubicin (7.2 ± 0.58 μM) as a standard. Compounds 6b, 6h, and 6i showed better inhibition next to compound 6j on the viability of HepG2 cells with an IC50 value (μM) of 56.02 ± 1.4, 41.76 ± 0.58, and 38.17 ± 0.34, respectively. Also, molecular docking studies have been carried out with STAT‐3 (PDB ID: 1BG1) and BCL‐2 (PDB ID: 4AQ3) proteins against the four active compounds 6b, 6h, 6i, and 6j. The binding energies of the tested compounds were in the range of −7.76 to −8.41 kcal/mol, which is very close to doxorubicin (−8.53 kcal/mol) as a standard. These molecular docking results are in good agreement with the in vitro studies.

An efficient, environmental friendly and substrate controlled method of synthesis of 2‐substituted benzimidazole derivatives 3 and 1,2‐disubstituted benzimidazole derivatives 4 with high selectivity has been achieved from the reaction of o‐phenylenediamine 1 and aldehydes 2 in the presence of water extract of onion and selecting suitable reaction medium. This method is widely applicable for variety of aldehydes such as aromatic/aliphatic/heterocyclic aldehydes and 1,2‐diamines to afford 2‐substituted benzimidazole derivatives 3 and 1,2‐disubstituted benzimidazole derivatives 4 in good to excellent yields (up to 96%). The developed method of water extract of onion catalysis produced 2‐substituted benzimidazoles 3 from aromatic aldehydes having electron‐withdrawing groups, whereas aromatic aldehydes bearing electron donating groups selectively furnished 1,2‐disubstituted benzimidazole 4 derivatives. The process described here has several advantages of cheap, low energy consumption, commercially available starting materials, operational simplicity and nontoxic catalyst. The use of water extract of onion makes this present methodology green and giving a useful contribution to the existing methods available for the preparation of benzimidazole derivatives. In addition, Hammett correlation of substituent constant (σ) vs percentage (%) yield has been established.