Acceleration of N-nitrosation reactions by electrophiles

Abstract

Selected mechanisms by which electrophiles can facilitate N-nitrosamine formation are reviewed. Special attention is given to a recently discovered reaction in which nitrogen in its lowest (ammonia) oxidation state is efficiently converted to N-nitroso compounds by oxidation in the presence of secondary amines; an electrophilic transition metal centre (E+) makes this reaction possible by initially N-coordinating the ammonia (E+ + NH3----E-NH3+). Other mechanisms considered include: the conversion of nitrite under nonacidic conditions via nitro complexes to nitrosatively active transition metal nitrosyl intermediates (E+ + NO(2-)----E-NO(2-)----E-NO2+); catalysis of N-nitrosamine formation in nitrite-amine mixtures by electrophilic carbon centres that initiate the reaction by attack on the amine (E+ + R2NH----E-NR2); and coordination of nitrite by carbon electrophiles to form activated O-bound species (E+ + ONO(-)----E-O-NO) capable of performing the required N-nitrosation. The findings suggest that acceleration of N-nitrosamine-forming reactions by electrophiles may be a critical factor to consider in attempting to rationalize, predict and control the distribution of carcinogenic N-nitroso compounds in vivo and in the environment.