Synthesis and Reactivity of Some 6-Substituted-2,4-dimethyl-3-pyridinols, a Novel Class of Chain-Breaking Antioxidants

Abstract

The synthesis and study of a series of 6-substituted-2,4-dimethyl-3-pyridinols having interesting antioxidant properties is reported. The general synthetic strategy leading to the compounds involved a low-temperature aryl bromide-to-alcohol conversion as the last step. 2,4-dimethyl-3-pyridinol (1a), 2,4,6-trimethyl-3-pyridinol (1b), and 2,4-dimethyl-6-(dimethylamino)-3-pyridinol (1d) were thus prepared from the corresponding 3-bromopyridine precursor. The methoxy derivative 2,4-dimethyl-6-(methoxy)-3-pyridinol (1c) was also prepared by an alternate route via a Baeyer-Villiger reaction on the substituted benzaldehyde precursor. Novel bicyclic pyridinols 2 and 3 required prior construction of the ring structure. Thus, 2 was prepared by the use of a 6-step intramolecular Friedel-Crafts strategy, and 3 required an 11-step sequence with a thermolytic intramolecular inverse-demand Diels-Alder reaction between a pyrimidine ring and an alkyne as the key step. Basicities of the pyridinols approached physiological pH with increasing electron density in the ring. Pyridinols 1a-d were found to be indefinitely stable to air oxidation while 2 and 3 decomposed upon extended exposure to the atmosphere. The reactivities of the pyridinols toward chain-carrying peroxyl radicals in homogeneous organic solution were examined by studying the kinetics of radical-initiated styrene autoxidations under controlled conditions. These experiments revealed that some of the newly synthesized pyridinols are the most effective phenolic chain-breaking antioxidants reported to date.

Protection of biodiesel and oil from degradation by natural antioxidants of Egyptian Jatropha

“…The effectiveness of an antioxidant can depend on a variety of factors, including the fatty acid profile of the oil or fat, the amount of naturally occurring antioxidants and storge or conditions (Knothe, 2007). Natural antioxidants such as tocopherols and tocotrienols in vegetable oils is affected by the refining process (Wijtmans et al, 2004). Antioxidants such as phenols and amines either have a hydrogen atom, phenols becom quinones or react with a radical in an addition fashion.…”

An oxysterol biomarker for 7-dehydrocholesterol oxidation in cell/mouse models for Smith-Lemli-Opitz syndrome

“…An unidentifi ed peak at retention time 5.45 min in our previously published chromatogram of a 7-DHC free radical oxidation mixture was confi rmed to be epox- tests and in studies of neuronal oxidative stress (63)(64)(65)(66), and experiments were therefore carried out with SLOS HFs to assess the potential of these antioxidants to reduce the levels of oxysterols. SLOS fi broblasts in lipid-defi cient serum were incubated for 5 days in the absence or presence of 10 M antioxidant 3 ( Fig.…”

Optimization of algal methyl esters using RSM and evaluation of biodiesel storage characteristics

“…Hence, it can be suggested that suitable additives can be added to the fuel to increase its shelf life and storage characteristics. Some additives for biodiesel storage found in literature are pyrimidinols [29], butylated hydroxytoluene, butylated hydroxyanisol, tert-butyl hydroquinone, propyl gallate, ethylenediaminetetraacetic acid, citric acid, phosphoric acid, and amino acids [30].…”