Rn. Loeppky et Jy. Bae, AN AZIRIDINIUM ION INTERMEDIATE IN THE NITROSATION OF A HEXETIDINE MODEL, Chemical research in toxicology, 7(6), 1994, pp. 861-867
The nitrosation chemistry of 1,3,5-trimethyl-5-aminahexahydropyrimidin
e (2) has been investigated as a model for the behavior of the antimic
robial agent hexetidine (1) under similar conditions. The reaction of
2 with sodium nitrite in glacial acetic acid gives ethylnitrosamino)me
thyl]-3-nitroso-1,3-oxazolidine (4) as the major nitrosamine. This com
pound arises from a molecular rearrangement which proceeds through the
diazotization of the primary amino group followed by intramolecular d
isplacement of nitrogen to generate an aziridinium ion. The N-nitrosoo
xazolidine 4 forms from the nitrosation of an imidazolidine produced f
rom the aziridinium ring hydrolytic opening. The N-nitrosooxazolidine
4, an isomer, ethylnitrosamino)methyl]-3-nitroso-1,3-oxazolidine (14),
which is not formed in the nitrosation of 2, and an analog exyl)nitro
samino]methyl]-3-nitroso-1,3-oxazolidine (22) have been independently
synthesized. The N-nitrosooxazolidine 22 which would be formed from he
xetidine is not present in its nitrosation mixture, suggesting the abs
ence of reactive aziridinium ions in that case. The dissimilar nitrosa
tion chemistry of 2 and 1 are discussed.