5-Aryl-2-(3,5-dialkyl-4-hydroxyphenyl)-4,4-dimethyl-4H-imidazole 3-Oxides and Their Redox Species: How Antioxidant Activity of 1-Hydroxy-2,5-dihydro-1H-imidazoles Correlates with the Stability of Hybrid Phenoxyl–Nitroxides

Abstract

<jats:p>Cyclic nitrones of the imidazole series, containing a sterically hindered phenol group, are promising objects for studying antioxidant activity; on the other hand, they can form persistent hybrid phenoxyl–nitroxyl radicals (HPNs) upon oxidation. Here, a series of 5-aryl-4,4-dimethyl-4H-imidazole 3-oxides was obtained by condensation of aromatic 2-hydroxylaminoketones with 4-formyl-2,6-dialkylphenols followed by oxidation of the initially formed N-hydroxy derivatives. It was shown that the antioxidant activity of both 1-hydroxy-2,5-dihydroimidazoles and 4H-imidazole 3-oxides increases with a decrease in steric volume of the alkyl substituent in the phenol group, while the stability of the corresponding HPNs generated from 4H-imidazole 3-oxides reveals the opposite tendency.</jats:p>

Development of a 2nd Generation Process for 3‐Ethyl‐4‐Hydroxy‐5‐Methylbenzonitrile – A Key Building Block of S1P1 Receptor Modulator Cenerimod – through a Non‐Classical Nitrile Formation Using Hydroxylamine‐O‐sulfonic Acid (HOSA)

“…Therefore, we envisioned to telescope 5 directly into the Duff reaction after completion of the Sandmeyer hydroxylation. As a mixture of AcOH/H 2 O can be employed for Duff reactions (vide infra), [14][15][16] we used this solvent combination for the initial screening optimizations of the Sandmeyer step (Table 1). Indeed, dosing of aq.…”

A Novel Class of Potent Anti-Tyrosinase Compounds with Antioxidant Activity, 2-(Substituted phenyl)-5-(trifluoromethyl)benzo[d]thiazoles: In Vitro and In Silico Insights

“…Interestingly, the coupling of 2-amino-4-(trifluoromethyl)benzenethiol with 3-bromo-4-hydroxybenzaldehyde ( p ) in the presence of Na 2 S 2 O 3 in DMF at 80 °C afforded the oxidized benzothiazole compound 1p , instead of 2-bromo-4-(5-(trifluoromethyl)-2,3-dihydrobenzo[ d ]thiazol-2-yl)phenol ( 1p′ ). On the other hand, compound 1m was synthesized by coupling 2-amino-4-(trifluoromethyl)benzenethiol with 4-hydroxy-3,5-dimethylbenzaldehyde ( m ), the latter of which was prepared from 2,6-dimethylphenol using Duff formylation conditions (hexamethylenetetramine and acetic acid) [ 50 ], in the presence of Na 2 S 2 O 5 in DMF at 80 °C [ 49 ]. The corresponding 3,5-dihydroxyphenyl compound 1n was obtained by refluxing 2-amino-4-(trifluoromethyl)benzenethiol and 3,5-dihydroxybenzaldehyde ( n ) in the presence of a weak acid and its sodium salt (e.g., CH 3 CO 2 H and NaOAc).…”