The reaction between dithiomalondianilide (N,N’-diphenyldithiomalondiamide) and alkyl 3-aryl-2-cyanoacrylates in the presence of morpholine in the air atmosphere leads to the formation of alkyl 6-amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]- pyridine-5-carboxylates in 37–72% yields. The same compounds were prepared in 23–65% yields by ternary condensation of aromatic aldehydes, ethyl(methyl) cyanoacetate and dithiomalondianilide. The reaction mechanism is discussed. The structure of ethyl 6-amino-4-(4-methoxyphenyl)-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxylate was confirmed by X-ray crystallography. Two of the prepared compounds showed a moderate growth-stimulating effect on sunflower seedlings. Three of the new compounds were recognized as strong herbicide safeners with respect to herbicide 2,4-D in the laboratory and field experiments on sunflower.

The Michael addition reaction between dithiomalondianilide (N,N′-diphenyldithiomalondiamide) and arylmethylidene Meldrum’s acids, accompanied by subsequent heterocyclization, was investigated along with factors affecting the mixture composition of the obtained products. The plausible mechanism includes the formation of stable Michael adducts which, under the studied conditions, undergo further transformations to yield corresponding N-methylmorpholinium 4-aryl-6-oxo-3-(N-phenylthio-carbamoyl)-1,4,5,6-tetrahydropyridin-2-thiolates and their oxidation derivatives, 4,5-dihydro-3H-[1,2]dithiolo[3,4-b]pyridin-6(7H)-ones. The structure of one such product, N-methylmorpholinium 2,2-dimethyl-5-(1-(2-nitrophenyl)-3-(phenylamino)-2-(N-phenylthiocarbamoyl)-3-thioxopropyl)-4-oxo-4H-1,3-dioxin-6-olate, was confirmed via X-ray crystallography.

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.

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.

2-Amino-4-arylbuta-1,3-diene-1,1,3-tricarbonitriles obtained by Knoevenagel condensation between aldehydes and malononitrile dimer reacted with cyanoacetohydrazide in the presence of bases to afford N’-arylidene-2-cyanoacethydrazides instead of the expected heterocyclization products of the pyridine series.

A series of previously undescribed 3-amino-4,5,6,7-tetrahydrothieno[2,3- b ]pyridines was prepared in 44–79% yields through alkylation of N -methylmorpholinium 3-cyano-4-(4-methoxyphenyl)-6-oxo-1,4,5,6-tetrahydropyridine-2-thiolate followed by Thorpe–Ziegler cyclization in the presence of KOH. An in silico predictor analysis was conducted to determine the bioavailability parameters and potential protein targets for the new compounds. Under laboratory experimental conditions on sunflower seedlings, some of the synthesized compounds demonstrated a moderate antidote effect against the herbicide 2,4-D.