Nitrosation by alkyl nitrites. Part 7. Comparison with thionitrites: reactions with phenols

Abstract

Both isopentyl nitrite (IPN) and S-nitroso-N-acetylpenicillamine (SNAP) react with phenol in the pH range 2-9 to give overwhelmingly 4-nitrosophenol. For IPN the reaction is first order in both IPN and phenol and the measured rate constant is much reduced by the addition of isopentyl alcohol, suggesting that reaction occurs by prior hydrolysis of IPN to nitrous acid. When allowance is made for the nitrous acid ionisation we find no acid catalysis in the pH range 3.62-5.25 but acid catalysis at higher acidities. The corrected rate constant also increases with pH at pH values greater than 6. There is no bromide ion catalysis at pH 4 but a substantial kinetic primary hydrogen isotope effect (using [*H,]phenol) of 4.0 at pH 2.55 which decreases towards 1 as the pH is increased. All of these results are consistent with rapid and reversible hydrolysis of IPN, and phenol nitrosation results from the nitrous acid produced. All of the experimental features parallel those found in the nitrous acid nitrosation of phenol. The kinetic pattern for the reaction of SNAP with phenol is quite different, showing autocatalytic features. We have obtained an EPR spectrum from the photolysis of SNAP, characteristic of RS', and for the phenoxy radical derived from the reaction mixture of SNAP with 2,6-di-tert-butyl-4-methylphenol at pH 7. We propose a radical mechanism for the reaction of SNAP with phenol involving hydrogen-atom abstraction by the RS' radical and subsequent reaction of the phenoxy radical with nitric oxide formed by homolysis of SNAP.

Inhibition of Lipid Peroxidation in Synaptosomes and Liposomes by Nitrates and Nitrites

“…Nitrosothiols are NO donors, which undergo homolysis to NO and disulfide, usually requiring trace metal ion catalysis, or photochemical initiation (76). Spin-trapping in the reactions of phenol with either a nitrosothiol or i-pentyl nitrite gave evidence for a thiyl radical intermediate from the nitrosothiol, but no alkoxyl radical intermediate from the nitrite, an observation echoed in study of mixed solutions of nitrosothiols and nitrites (71,77). Nitrosothiols, argued to be acting via NO release, have been shown to act as antioxidants in a variety of systems (40).…”

“…It is a mistake to consider these chemical species collectively, since the chemical reactivity of nitrites and nitrates is very different. The organic nitrite functional group is relatively labile toward hydrolysis, which is susceptible to acid catalysis, and provides an effective nitrosating agent, reacting with a variety of nucleophiles and readily undergoing transnitrosation (20,70,71). Conversely, the organic nitrate functional group is hydrolytically stable, undergoing denitration only in strong alkali, and represents a poor nitrating agent (19).…”

“…The reduction of an organic nitrite to NO is a more facile 1ereduction, and much larger fluxes of NO can be detected from nitrites in neutral, aqueous solution, even in the absence of added thiols (30). There is a body of work on the heterolytic reactions of nitrites, but there exist little data on NO release from homolytic reactions (71). Comparison of nitrites (RONO) with nitrosothiols (RSNO) is useful.…”

Organic Nitrites and NO: Inhibition of Lipid Peroxidation and Radical Reactions

“…The chemistry of nitrites includes heterolytic and homolytic reactions, in addition to oxidation of hemoglobin (73). In several elegant mechanistic studies on nitrite hydrolysis, the sole N-containing product has reasonably been presumed to be inorganic nitrite; therefore, there has been no attempt to detect other products (28,(73)(74)(75). Nitrites are excellent nitrosating agents: the nitrosation of different substrates (alcohols, thiols, and amines) by alkyl nitrites (especially tertiary alkyl nitrites) occurs at rates several order of magnitudes higher than competing hydrolysis (76).…”

Importance of phenols structure on their activity as antinitrosating agents: A kinetic study

“…The hindered 2,6-dimethoxyphenol was nitrosated by dissolution in an ethanolic hydrochloric acid solution, to which sodium nitrite was gradually added. [ 30b ] Nitrosation of anisole was performed with sodium nitrite in a mixture of dichloromethane and trifluoroacetic acid. [ 30c ] The product had a λ max at 350 nm.…”