SYNTHESIS OF 1-(4-HYDROXYPHENYL)-5-OXOPYRROLIDINE-3-CARBOXYLIC ACID DERIVATIVES AND EVALUATION OF THEIR ANTIBACTERIAL ACTIVITY

Abstract

A novel series of 1,4-disubstituted pyrrolidinone derivatives with nitroso, azo, hydrazone, azole, triazine moieties has been prepared from 1-(4-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid and its hydrazide, prepared by the known methods. The reaction of 1-(4-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid with sodium nitrite at room temperature afforded a nitroso group-containing compound 1-(4-hydroxy-3-nitrosophenyl)-5-oxopyrrolidine-3-carboxylic acid. The interaction of this acid with phenyldiazonium chlorides at 0 °C gave red-color compounds – azo dyes. Hydrazone-type derivatives with an azomethine fragment in the molecule were prepared by condensation of hydrazide with aromatics and carboaldehydes. Heterocyclic compounds – pyrazole, pyrrole and triazine derivatives – were synthesized by the condensation of hydrazides with the diketones 2,4-pentanedione, 2,5-hexanedione and 1,2-diphenyl-1,2-ethanedione, respectively. The reactions were carried out in 2-propanol and catalyzed by hydrochloric acid to form 3,5-pyrazole derivative, and by acetic acid to obtain a compound with a 2,5-pyrrole fragment. For the formation of 1,2,4-triazine moiety, the reaction of acid hydrazide was performed in refluxing acetic acid with the addition of a large excess (10 equiv) of ammonium acetate.

The structure of the synthesized compounds was confirmed by data of ¹H, ¹³C NMR, IR spectroscopy and elemental analyses.

Moreover, in this work, the antibacterial activity of the synthesized derivatives was tested. The results of this investigation have revealed that 1-(4-hydroxyphenyl)-N¢-[(5-nitrothiophen-2-yl)methylidene]-5-oxopyrrolidine-3-carbo-hydrazide exhibits the highest antibacterial activity.

DOI: http://dx.doi.org/10.5755/j01.ct.65.1.8715