Synthesis and Antioxidant Evaluation of Urea, Carbamate, and Triazole Derivatives of (2-(6-Methoxynaphthalen-2-yl) propanoyl) glycinoyl azide

In this study, a novel series of compounds, derived from the drug naproxen, was synthesized, this series includes carbamates, ureas, semicarbazides, and 1,2,4-triazole derivatives, and the synthesis was achieved through a multi-step synthetic approach. Initially, hydrazide (1) was prepared by reacting naproxen amino acid ester with hydrazine hydrate, followed by its conversion to naproxen glycine azide (2) through treatment with sodium nitrite in hydrochloric acid. Azide (2) was then subjected to thermal decomposition via Curtius rearrangement to yield isocyanate (3). Isocyanate (3) was subsequently reacted with various reagents, such as water, alcohol, amine, concentrated hydrochloric acid, hydrazine, and naproxen hydrazide, resulting in the formation of symmetrical urea (4), carbamates (5a-e), ureas (6a-d), hydrochloride salt (7) semicarbazides (8), and (11). Furthermore, compound (9) was synthesized by refluxing semicarbazide (8) with acetyl chloride, and both compounds (9 and 11) were subsequently converted into 1,2,4-triazol-5-one derivatives (10 and 12) through a cyclization reaction. In a parallel line of research, nucleophilic substitution reactions were performed on hydrazide (1) using acetyl chloride, aryl sulfonyl chloride (benzene or toluene), and terephthaloyl chloride, yielding substituted hydrazide derivatives (13, 15a-b, and 16), respectively. Diamide compounds (13, 16) were further cyclized with ammonium acetate to produce 1,2,4-triazole derivatives (14, 17). The progression of these chemical reactions were monitored using thin-layer chromatography (TLC), and synthesized compounds were identified using IR, 1H NMR, and 13C NMR spectroscopy. The antioxidant properties of these compounds were extensively assessed, contributing to the development of novel derivatives with potential applications in pharmacology and medicinal chemistry.