Synthesis, Interaction with Arylamines, and Antimicrobial Activity of 4-Arylhydrazones of 1-Aryl-5-methyl-5-ethoxycarbonylpyrrolidine-2,3,4-triones

As reported previously, 1-substituted 4-acyl-5-arylpyrrolidine-2,3-diones possess antiinflammatory [1], analgesic [2], antiviral [3], nootropic [2], and antibacterial activity [4]. In continuation of the search for biologically active compounds in the class of substituted pyrrolidine-2,3-diones, we have attempted at introducing a substituent, whose structure is significantly different from that of acyl group, into position 4. The aim was to study how this structural change will modify the chemical properties and antibacterial activity of pyrrolidine-2,3-diones. In this context, we have studied the reactions of 1-aryl5-methyl-5-ethoxycarbonylpyrrolidine-2,3-diones (I – V) with aryldiazonium salts. The results showed that treatment of compounds I – V with aryldiazonium chloride in an ethyl alcohol – dioxane mixture leads to the formation of 4-arylhydrazones of 1-Aryl-5-methyl-5-ethoxycarbonylpyrrolidine-2,3,4-triones (VI – XX). Compounds VI – XX appear as red or orange crystalline substances soluble in ethanol, DMF, and DMSO and insoluble in water. The yields, melting points, and empirical formulas of the synthesized compounds are listed in Tables 1 and 2. The 1 H NMR spectra of compounds VI – XX contain (i) a triplet and a quadruplet from protons of the ethoxy group at = 1.18 – 1.25 and 4.22 – 4.25 ppm, respectively; (ii) a singlet due to the methyl group in position 5 of the heterocycle (1.71 – 1.76 ppm); (iii) signals from aromatic protons (7.00 – 7.77 ppm); and a signal due to protons of the NH group (12.90 – 13.21 ppm). The IR spectra of compounds VI – XX display absorption bands due to lactam and ketone carbonyl groups in the regions of 1710 – 1716 cm –1 , ester carbonyls at 1740 cm –1 , azomethine group at 1653 – 1662 cm –1 , and a band due to the stretching vibrations of NH bonds in the region of 3192 – 3200 cm –1 .