Nitrosation of Phenolic Compounds:  Inhibition and Enhancement

Abstract

The nitrosation of phenol, m-, o-, and p-cresol, 2,3-, 3,5-, and 2, 6-dimethylphenol, 3,5-di-tert-butylphenol, 2,4,6-trimethylphenol, o-chlorophenol, and o-bromophenol was studied. Kinetic monitoring of the reactions was accomplished by spectrophotometric analysis of the products at 345 nm. At pH > 3, the dominant reaction was C-nitrosation through a mechanism that appears to consist of an attack on the nitrosatable substrate by NO(+)/NO(2)H(2)(+), followed by a slow proton transfer. The finding of an isokinetic relationship supports the idea that the same mechanism operates throughout the series. The observed sequence of nitrosatable substrate reactivities is explained by (i) the preferred para-orientation of the hydroxyl group for the electrophilic attack of nitrosating agents, (ii) steric hindrance of alkyl substituents, which reduces or prevents attack by nitrosating agents, and (iii) the hyperconjugative effect of the methyl substituent, which causes electronic charge to flow into the aromatic nucleus, as well as the opposite electronic withdrawing effect induced by halogen substituents. The results show that potential nitrosation of widespread environmental species such as chlorophenols is negligible, but more attention should be paid to polyphenols with strongly nucleophilic carbon atoms.

Tyrosine Nitration by Simultaneous Generation of ⋅NO and O⨪2 under Physiological Conditions

“…This conclusion is further supported by a recent study (38) demonstrating that once 2-NOphenols are formed, they are stable, and therefore 3-nitrosotyrosine cannot be the source for dityr formation.…”

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

“…Casado et al ,[192223] have shown unambiguously that the reaction with nitrous acid occurs by the first of these mechanisms. However, other nitrosating agents, like nitrososulfonamides[21] and alkyl nitrites,[24] in basic media, present a different behavior.…”

“…[19] In fact, the halogenated phenols studied (1a-e and 1g) reacted very slowly with MeNMBS and the absorbance-time data deviated significantly from the best-fitting first order integrated equation. Kinetic constants estimated from the available data were in the order of 10 -4 M -1 .s -1 , which was the magnitude of the basic hydrolysis constant of MeNMBS determined in our laboratory, so a competition between the two reactions should be expected.…”

“…[17] A mechanism is proposed, in which the quinone monoxime tautomer of a nitrosophenol reacts with nitrous acid to produce an intermediate nitrosating agent, which undergoes an attack by the amine to produce N -nitrosamine and regenerate the catalyst,[18] although it has been stressed that catalytic activity is only observed when the nitrosating agent concentration significantly exceeds the concentration of phenol, which is rare in vivo or in environmentally significant situations. [19] It has also been observed that the introduction of a nitroso group in phenols brings about a loss in their antioxidant activity. [14]…”

“…This and other N -methyl- N -nitrosobenzenesulfonamides have been used before as nitrosating agents in the study of the transnitrosation of amines[20] and phenols. [21] In addition, we expect to collect more evidence on the mechanism of nitrosophenol formation, as there has been some discussion on whether the reaction occurs directly at the carbon atom[192223] or the previous formation of an O -nitroso intermediate is involved. [2124] The nitrosation of OH-blocked ‘phenols,’ such as anisole, is possible when the mechanism involves the nitrosonium ion polar reaction,[25] but it will not be observed when the reaction follows the oxidative pathway via the phenoxy radicals, because the formation of those are hindered, as observed by Daiber et al .…”