Late Stage Halogenation of Flavonoid Derivatives via In-Situ Oxidation of Halide Ion Andreana Muhammad, Ade Danova, Elvira Hermawati
Institute Technology of Bandung
Abstract
Halogenation reactions employing Oxone and halogen sources, NaX /X = F, Cl, Br, I, offer a more environmentally friendly alternative to traditional oxidative methods in electrophilic aromatic substitution /EAS. This methodology is categorized as in situ halogenation, in which electrophilic halogen species are generated directly within the reaction mixture. Such halogenation reactions can be applied to a variety of secondary metabolites, including flavonoids. Flavonoid derivatives are recognized for their extensive range of significant biological activities, such as antioxidant, anti-inflammatory, anticancer, antimicrobial, neuroprotective, and antidiabetic effects. Structural modification of flavonoids, including halogenation, has the potential to enhance their biological activity, rendering these compounds promising candidates for novel drug development. This study aimed to synthesize halogenated flavonoid derivatives via in situ halogenation of flavonoids using Oxone and halide ions. In this investigation, naringenin was successfully hydrolyzed from its glycoside form with a yield of 86.4%, and hesperetin was hydrolyzed from its glycoside form with a yield of 77.3%. Additionally, seven halogenated flavonoid derivatives were successfully synthesized: 6,8-dichloro naringenin, 6,8 dibromo naringenin, 6,8 dichloro hesperetin, 6,8 dibromo hesperetin , 6,8,2 tribromo hesperetin, 6,8 dibromo acacetin, and 6,8 diiodide acacetin. Structural characterization of the compounds was conducted using 1H NMR and 13C NMR spectroscopy and high-resolution mass spectrometry/HR-MS.
