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Can the guanidinium ion react with inorganic nitrite under mild basic metalworking conditions ($\mathrm{pH\ 8 - 10}$ and temperature $\lt \pu{70^\circ C}$) to give stable N-nitrosamines?

Usually, the carcinogenic nitrosamines are generated from secondary amines. But guanidinium ion is not a secondary amine. Guanidinium ion is a mesomerism-stabilized system, and the nitroso group could be also stabilized by mesomerism therefore. So I'm afraid that it can build nitrosamines readily. But is this possible under basic conditions as mentioned above?

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    $\begingroup$ What do you mean by this? "Give" how? What reactants would the guanidine be reacting with to "give" the N-nitroso-substituted derivatives? Just itself and oxygen from the air? With some other NO donor? $\endgroup$
    – Curt F.
    Apr 11, 2021 at 18:12
  • $\begingroup$ Nitrosoguanidine may be precipatated from cold water and dried at 40C according to this ref prepchem.com/synthesis-of-nitrosoguanidine $\endgroup$
    – Waylander
    Apr 11, 2021 at 18:35

1 Answer 1

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By definition, N-nitrosamines are aliphatic or aromatic derivatives of secondary amines, which have a nitroso group ($\ce{–NO}$) attached to nitrogen. In general, N-nitroso compounds are usually formed by the interaction of a nitrosating agent ($\ce{NOX}$) derived from either nitrite salts or nitrogen oxides with an amino substance such as secondary and tertiary amines, secondary and tertiary amides, peptides, substituted ureas, guanidines, and urethanes. Some important N-nitroso compounds are shown below:

N-nitroso compounds

As structures indicated, resonance in the framework has nothing to do with $\ce{-N-N=O}$ function (e.g., 1-Methyl-3-nitro-1-nitrosoguanidine is stable at room temperature and commercially available). Nonetheless, guanidine derivatives interact with $\ce{NOX}$ to give stable nitroso-guanidine derivatives (which are type of N-nitrosamides). With $\ce{NOX}$ derived from nitrite salts, the formation of N-nitroso derivatives of guanidine rarely occurs above $\mathrm{pH \ 4}$, but increases steadily with increasing acidity i.e. decreasing $\mathrm{pH}$, a maximum at $\mathrm{pH \ 2.5-3.5}$ where the yield is inversely proportional to the basicity of the amino substance (Ref.1).

Examples of nitrosamines and nitrosamides

On the other hand, guanidines do not react with $\ce{NOX}$ derived from nitrogen oxides in aqueous media (Ref.2,3). Note that $\ce{NOX}$ derived from nitrogen oxides worked best with strongly basic amino substances (e.g., aliphatic amines and heterocyclic amines) under non-aqueous or neutral and alkaline aqueous conditions (Ref.2,3).


References:

  1. Sidney S. Mirvish, "Formation of N-nitroso compounds: Chemistry, kinetics, and in vivo occurrence," Toxicology and Applied Pharmacology 1975, 31(3), 325-351 (DOI: https://doi.org/10.1016/0041-008X(75)90255-0).
  2. B. C. Challis, "Nutrition and nitrosamine formation," Proceedings of the Nutrition Society 1985, 44(1), 95-100 (DOI: https://doi.org/10.1079/PNS19850015) (PDF).
  3. Brian C. Challis, Soterios A. Kyrtopoulos, "The chemistry of nitroso-compounds. Part 11. Nitrosation of amines by the two-phase interaction of amines in solution with gaseous oxides of nitrogen," J. Chem. Soc., Perkin Trans. 1 1979, 299-304 (DOI: https://doi.org/10.1039/P19790000299).
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