Investigation of the conditions of recycling of N-arylitaconimides with phenylhydrazine using HPLC mass spectrometry

Abstract

Pharmaceutical preparations with the ability to act on several targets at once are increasingly used as anti-cancer, anti-inflammatory drugs, and are used in the treatment of atherosclerosis and human immunodeficiency virus. As a rule, their active substances are complex heterocyclic compounds containing several pharmacophore centers. One of the effective methods of synthesis of such compounds is cyclization.

Using this synthetic approach, we obtained a pair of regioisomeric products of the reaction of N-arylitaconimide, a universal precursor for a number of heterocyclic systems, and phenylhydrazine. The resulting 2-(5-oxo-1-phenylpyrazolidine-4-yl)-N-arylacetanilides and 2-(3-oxo-1-phenylpyrazolidine-4-yl)-N-arylacetanilides can combine anti-inflammatory, antibacterial, analgesic, anti-tuberculosis properties of pyrazole-containing compounds and anti-cancer activity associated with the presence of an acetanilide fragment in the molecule.

However, the possibility of further studying the biological activity and using the obtained systems as medicinal compounds is directly related to the simplicity and accessibility of their synthesis. Therefore, the improvement of methods for obtaining promising compounds is an urgent task. Evaluating the effectiveness of the method requires tracking the composition of the reaction mixture, the conversion rate of reagents, and selectivity, for which the method of liquid chromatography in combination with mass spectrometry is very convenient. In this regard, the purpose of this study is to select the conditions for the synthesis of 2-(5-oxo-1-phenylpyrazolidine-4-yl)-N-arylacetanilides and 2-(3-oxo-1-phenylpyrazolidine-4-yl)-N-arylacetanilides, namely, the choice of temperature regime and reaction media, using HPLC-MS.

It was found that the reaction of N-arylitaconimides with phenylhydrazine at room temperature does not lead to the formation of 5-oxopyrazolidine-4-ylacetanilide and 3-oxopyrazolidine-4-ylacetanilide. It was found that as the temperature of the reaction increases, the degree of conversion of the starting materials increases. However, when using weakly polar solvents such as diethyl ether, hexane, benzene, toluene, dioxane, the conversion of the starting compounds into reaction products remains low or absent.

It was revealed that the interaction of reagents in an alcoholic medium during boiling leads to the formation of 5-oxopyrazolidine-4-ylarylacetanilide and 3-oxopyrazolidine-4-ylacetanilide. The maximum concentration of the starting substances into the reaction products over a period of 60 minutes is observed during boiling in butanol.