SYNTHESIS OF 1-(4-HYDROXYPHENYL)-5-OXOPYRROLIDINE-3-CARBOXYLIC ACID DERIVATIVES AND EVALUATION OF THEIR ANTIBACTERIAL ACTIVITY
Keywords:pirolidinonai, hidrazonai, azolai, 1, 2, 4-triazinai, kondensacija, antibakterinis aktyvumas
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.