Nitrosation of phenolic compounds: inhibition and enhancement

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.