Nitrosation of phenolic compounds: Inhibition and enhancement

The nitrosation of phenol, m-, o-, and p-cresol, 2,3-, 3,5-, and 2,6-dimeth ylphenol, 3,5-di-tert-butylphenol, 2,4,6-trimethylphenol, o-chlorophenol, a nd o-bromophenol was studied. Kinetic monitoring of the reactions was accom plished 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+/NO2H2+, follow ed by a slow proton transfer. The finding of an isokinetic relationship sup ports 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 electrophili c attack of nitrosating agents, (ii) steric hindrance of alkyl substituents , which reduces or prevents attack by nitrosating agents, and (iii) the hyp erconjugative effect of the methyl substituent, which causes electronic cha rge to flow into the aromatic nucleus, as well as the apposite electronic w ithdrawing effect induced by halogen substituents. The results show that po tential nitrosation of widespread environmental species such as chloropheno ls is negligible, but more attention should be paid to polyphenols with str ongly nucleophilic carbon atoms.