Reaction of Nicotine and Sodium Nitrite: Formation of Nitrosamines and Fragmentation of the Pyrrolidine Ring

Stephen S. Hecht, Chi hong B. Chen, Raphael M. Ornaf, Eugenia Jacobs, John D. Adams, Dietrich Hoffmann

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Abstract

The reaction of nicotine and sodium nitrite was investigated in order to provide insight on the formation of potentially carcinogenic tobacco-specific nitrosamines. Reaction at 25 °C resulted in the formation of N-nitrosonor-nicotine (3), 4-(N-methyl-N'-nitrosamino)-l-(3-pyridyl)-l-butanone (4), and 4-(N-methyl-N'-nitrosamino)-4-(3-pyridyl)butanal (5) in yields of 0.1-2.8%, with most of the nicotine being unreacted. When the reaction was carried out at 90 °C, with a fivefold excess of NaNO2, 75-85% of the nicotine reacted. The nitrosamines 3 and 4 were formed in higher yield [up to 13.5 (3) and 4.3% (4)], but 5 was not observed. Both 4 and 5 gave secondary products under these conditions; 4 was nitrosated further to give 4-(N-methyl-N-nitrosamino)-2-oximino-l-(3-pyridyl)-l-buta-none (6), and 5 gave rise to l-methyl-5-(3-pyridyl)pyrazole (7). The major products resulting from fragmentation of the pyrrolidine ring were cis- and (rarcs-3-(3-pyridyl)acrylonitrile (8a,b), N-methylnicotinamide (9), and nicotinic acid (10). The nitrosamines 3-5 and the fragmentation products 8a, 8b, and 9 most probably arise via cyclic iminium salts.

Original languageEnglish (US)
Pages (from-to)72-76
Number of pages5
JournalJournal of Organic Chemistry
Volume43
Issue number1
DOIs
StatePublished - Jan 1 1978

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