Inhibition of nitrosation by steric hindrance

The nitrosation of piperidine, 2-methylpiperidine, 4-methylpiperidine, 2,6-dimethylpiperidine, and 2-ethylpiperidine in acid medium was studied. Kinetic monitoring of the reactions was accomplished by spectrophotometric analysis of the nitrosamine formed at lambda = 249 nm. In each case, the value of the rate constant of the determining step R(2)NH + N2O3 --> R(2)NNO + HNO2 was calculated observing the following sequence of reactivities: piperidine approximate to 4-methylpiperidine > 2-methylpiperidine approximate to 2-ethylpiperidine > 2,6-dimethylpiperidine. In the case of 2,6-dimethylpiperidine, no nitrosation was observed. The results are interpreted in terms of the steric hindrance of the alkyl groups to attack of the secondary amine group by dinitrogen trioxide. The results open the possibility of blocking the undesirable mechanisms of formation of N-nitroso compounds.