( E )-3-Aryl-2-cyanoprop-2-entioamides, prepared by Knoevenagel condensation between aromatic aldehydes and cyanothioacetamide, react with sodium nitrite in acetic acid to form (2 E ,2′ E )-2,2′-(1,2,4-thiadiazole-3,5-diyl)bis[3-arylacrylonitriles]. A possible mechanism and limitations of the reaction are discussed. Molecular docking was carried out in order to search for possible protein targets for the obtained 1,2,4-thiadiazoles. One of the compounds showed a pronounced antidote effect against the herbicide 2,4-D in a laboratory experiment on sunflower seedlings and under field conditions.

Aminomethylation of 1,6-diamino-4-aryl-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles under the action of excess of formaldehyde in ethanol has led to the formation of 7-aryl-3-(hydroxymethyl)-5-oxo-1,2,3,5-tetrahydro[1,2,4]triazolo[1,5-a]pyridine-6,8-dicarbonitriles. Bioavailability parameters of the obtained compounds have been predicted in silico and the possible protein targets have been predicted via the protein-ligand docking.

Electrochemical oxidation of (Е)-3-aryl-2-cyanoprop-2-enethioamides in a undivided cell in the presence of KBr in an aqueous or aqueous-organic medium has led to the formation of (2Е,2′E)-2,2′-(1,2,4-thiadiazole-3,5-diyl)bis[3-arylacrylonitriles] in 37–76% yield. A plausible reaction mechanism has been discussed. In laboratory experiments, (2E,2′E)-2,2′-(1,2,4-thiadiazol-3,5-diyl)bis[3-(4-methoxyphenyl)acrylonitrile] has revealed pronounced antidote effect against herbicide 2,4-D on sunflower seedlings and no pronounced growth-regulating properties.

This work aimed to synthesize new derivatives of 2-hydrazinylpyridine-3-carbonitrile and to investigate their biological activity as safeners for the 2,4-D herbicide. The new 2-hydrazinylnicotinonitriles were obtained in high yields (up to quantitative) under mild conditions (25 °C, dioxane) by treating 4,6-diaryl-2-bromo-3-cyanopyridines with hydrazine hydrate. The latter were synthesized by brominating 2-(3-oxo-1,3-diarylpropyl)malononitriles, the Michael adducts, which are readily available from 1,3-diarylpropenones (chalcones) and malononitrile. An unusual side product of the bromination/carbocyclization was isolated and characterized; it consisted of co-crystals of 3-benzoyl-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile and 3-benzoyl-5-bromo-4-hydroxy-4-phenyl-2,6-di-(p-tolyl)cyclohexane-1,1-dicarbonitrile at a ~4:6 ratio. The new 2-hydrazinylnicotinonitriles react with halogen-containing aromatic aldehydes to form the corresponding hydrazones. The biological activity of the new nicotinonitriles was examined for their function as 2,4-D antidotes. It was found that, under laboratory conditions, eight of the synthesized compounds exhibited a notable antidote effect against 2,4-D on sunflower seedlings.

Oxidation of (Е)-3-aryl-2-cyanothioacrylamides under the action of the Et₂S(O)–HCl system leads to the formation of (2Е,2′E)-2,2′-(1,2,4-thiadiazole-3,5-diyl)bis[3-arylacrylonitriles] in 54–91% yields. Structure of the obtained compounds was confirmed by the two-dimensional NMR spectroscopy data. A plausible reaction mechanism was discussed. Two compounds showed a pronounced antidote effect against 2,4-D herbicide in a laboratory experiment on sunflower seedlings in the absence of growth-stimulating activity.