Synthesis and Biological Activity of Substituted 2-[2-(Diphenylmethylene)hydrazinyl]-5,5-dimethyl-4-oxohex-2-enoates

The synthesis of new substituted 2-[2-(diphenylmethylene)hydrazinyl]-5,5-dimethyl-4-oxohex-2-enoates is described. The synthesis from commercially available starting materials included the preparation of 5,5-dimethyl-2,4-dioxohexanoic acid via Claisen condensation of 3,3-dimethylbutan-2-one (pinacolone) and diethyl oxalate in the presence of sodium methanolate. The resulting acid reacted with (diphenylmethylene)hydrazine to form 2-[(diphenylmethylene)hydrazono]-5,5-dimethyl-4-oxohexanoic acid. The initial 5-(tert-butyl)-3-[(diphenylmethylene)hydrazono]furan-2(3H)-one was obtained by a known literary method: intramolecular cyclisation of 2-[(diphenylmethylene)hydrazono]-5,5-dimethyl-4-oxohexanoic acid under the action of propionic anhydride. 5-(tert-Butyl)-3-[(diphenylmethylene)hydrazono]furan-2(3H)-one entered the decyclization reaction under the action of primary aromatic alcohols to form substituted 2-[2-(diphenylmethylene)hydrazinyl]-5,5-dimethyl-4-oxohex-2-enoates. The presence of equimolar quantities of triethylamine was important; otherwise, the reaction proceeded with low yields. The isolation of target compounds was carried out by filtration of the resulting sediment followed by recrystallization. The structure of the compounds obtained was confirmed by the 1H and 13C NMR spectroscopy methods. The resulting substituted esters exist in a solution of deuterated chloroform in one tautomeric form, in contrast to the previously studied solutions of deuterated DMSO, where up to four tautomeric forms were observed. Analgesic and anti-inflammatory activity of new and previously synthesized compounds of this series has been studied. Analgesic activity was evaluated by the “Hot Plate” test on outbred white mice of both sexes with intraperitoneal injection. Anti-inflammatory activity was studied on a carrageenan-induced paw edema model with oral administration of the studied substances. One compound possesses both high analgesic and high anti-inflammatory effects, which causes the prospects for its use as a pharmacologically active substance.