Synthesis and Characterization of New Functionalized 1,2,3-Triazole-Based Acetaminophen Derivatives via Click Chemistry from Expired Commercial Acetaminophen Tablets

• Published in: Reactions (Basel, Switzerland) Switzerland), 2023-09, Vol.4 (3), p.329-341
• Main Authors: Kouznetsov, Vladimir V., Calderón Lamus, Daniela, Puerto Galvis, Carlos E.
• Format: Article
• Language: English
• Subjects: 1,4-disubstituted 1,2,3-triazoles; acetaminophen; Analgesics; Aniline; Anticancer properties; Anticonvulsants; Azide; azide-alkyne cycloaddition; Chemical synthesis; Chemistry; Cu(PPh3)3Br catalyst; Huisgen reaction; molecular hybrids; Nitric oxide; NMR; Nuclear magnetic resonance; Pharmaceuticals; Pharmacology; R&D; Reagents; Research & development; Solvents; Tablets; Triazoles
• ISSN: 2624-781X; 2624-781X
• DOI: 10.3390/reactions4030020

We hereby describe an efficient method for the preparation of a series of new 1-substituted 1,2,3-triazole-based acetaminophen derivatives through a clean, good-yielding, simple, and expeditious procedure based on the O-propargylation reaction of the acetaminophen (APAP) obtained from expired commercial tablets and the CuBr(PPh3)3-catalyzed Huisgen reaction between O-propargylated APAP and diverse organoazides prepared from commercially available anilines as available starting reagents. An interesting nitric oxide-releasing 1,2,3-triazole hybrid of APAP was also obtained easily using the developed method. The structures of the designed hybrid compounds, which are expected to be pharmacologically active, were characterized by FT-IR, 1H-, and 13C-NMR and are reported for the first time. According to the in-silico ADMET prediction studies performed in this work and literature analysis, these hybrids are interesting models in search of new pharmacological nontoxic agents endowed with anti-inflammatory and anticancer properties.