An aziridinium ion intermediate in the nitrosation of a hexetidine model.
The nitrosation chemistry of 1,3,5-trimethyl-5-aminohexahydropyrimidine (2) has been investigated as a model for the behavior of the antimicrobial agent hexetidine (1) under similar conditions. The reaction of 2 with sodium nitrite in glacial acetic acid gives 4-methyl-4-[(methylnitrosamino)methyl]-3-nitroso-1,3-oxazolidine (4) as the major nitrosamine. This compound arises from a molecular rearrangement which proceeds through the diazotization of the primary amino group followed by intramolecular displacement of nitrogen to generate an aziridinium ion. The N-nitrosooxazolidine 4 forms from the nitrosation of an imidazolidine produced from the aziridinium ring hydrolytic opening. The N-nitrosooxazolidine 4, an isomer, 5-methyl-5-[(methylnitrosamino)methyl]-3-nitroso-1,3-oxazolidine (14), which is not formed in the nitrosation of 2, and an analog 4-methyl-4-[[(2-ethylhexyl)nitrosamino]methyl]-3-nitroso-1,3-oxazolidine (22) have been independently synthesized. The N-nitrosooxazolidine 22 which would be formed from hexetidine is not present in its nitrosation mixture, suggesting the absence of reactive aziridinium ions in that case. The dissimilar nitrosation chemistry of 2 and 1 are discussed.
Loeppky
R N
RN
Department of Chemistry, University of Missouri, Columbia 65211.
Bae
J Y
JY
D001388:Aziridines / Q000737:chemistry*; D006590:Hexetidine / Q000737:chemistry*; D008956:Models, Chemical; D009602:Nitrosamines / Q000737:chemistry*; D015538:Nitrosation; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship
D001388:Aziridines; D009602:Nitrosamines; D010080:Oxazoles; D011743:Pyrimidines; C064210:oxazolidine; D006590:Hexetidine