Triethylammonium (E)-2-Oxo-1-(2-oxoindolin-3-ylidene)-2-phenylethane-1-thiolate: S-Alkylation and Antidote Activity against Herbicide 2,4-D

Abstract

Triethylammonium (E)-2-oxo-1-(2-oxoindolin-3-ylidene)-2-phenylethane-1-thiolate, readily obtained from phenacyl thiocyanate and isatin, undergoes efficient S-alkylation with alkyl halides in refluxing DMF. When ethyl 4-chloroacetoacetate is employed, the reaction affords (E)-3-[2-oxo-1-{(2-oxopropyl)thio}-2-phenylethylidene]indolin-2-one via in situ Krapcho decarboxylation of the intermediate β-keto ester; the structure was confirmed by X-ray crystallography. Quantum chemical calculations (ωB97X-3c/CPCM) reveal that the (E)-isomer of the starting thiolate is thermodynamically favored by ~18 kJ/mol over the (Z)-form in EtOAc. In silico ADMET profiling and protein-ligand docking studies indicate favorable bioavailability parameters and potential interactions with targets such as stromelysin-1 (MMP-3), FABP4, and PPAR-γ, suggesting possible anti-inflammatory and antidiabetic applications. Under laboratory conditions, the starting thiolate exhibits significant protective (antidote) activity against the herbicide 2,4-D in sunflower seedlings, increasing hypocotyl and root lengths by up to 126 and 154%, respectively.