Class of functional groups with a –N=O group attached
In
organic chemistry, nitroso refers to a
functional group in which the
nitric oxide (−N=O) group is attached to an organic
moiety. As such, various nitroso groups can be categorized as C-nitroso compounds (e.g., nitroso
alkanes; R−N=O), S-nitroso compounds (
nitrosothiols; RS−N=O), N-nitroso compounds (e.g.,
nitrosamines, RN(−R’)−N=O), and O-nitroso compounds (
alkyl nitrites; RO−N=O).
Nitrosoarenes typically participate in a
monomer–dimer equilibrium. The azobenzene N,N'-dioxide (Ar(–O)N+=+N(O–)Ar) dimers, which are often pale yellow, are generally favored in the solid state, whereas the deep-green monomers are favored in dilute solution or at higher temperatures. They exist as
cis and trans isomers.[4]
Due to the stability of the nitric oxide
free radical, nitroso organyls tend to have very low C–N
bond dissociation energies: nitrosoalkanes have BDEs on the order of 30–40 kcal/mol (130–170 kJ/mol), while nitrosoarenes have BDEs on the order of 50–60 kcal/mol (210–250 kJ/mol). As a consequence, they are generally heat- and light-sensitive. Compounds containing O–(NO) or N–(NO) bonds generally have even lower bond dissociation energies. For instance,
N-nitrosodiphenylamine, Ph2N–N=O, has a N–N bond dissociation energy of only 23 kcal/mol (96 kJ/mol).[6] Organonitroso compounds serve as a
ligands giving
transition metal nitroso complexes.[7]
C-nitroso compounds are used in organic synthesis as synthons in some well-documented chemical reactions such as hetero Diels-Alder (HDA), nitroso-ene and nitroso-aldol reactions.[8]
Nitrosation vs. nitrosylation
Nitrite can enter two kinds of reaction, depending on the physico-chemical environment.
Nitrosylation is adding a
nitrosyl ionNO− to a metal (e.g. iron) or a thiol, leading to nitrosyl iron Fe−NO (e.g., in nitrosylated heme = nitrosylheme) or S-nitrosothiols (RSNOs).
Nitrosation is adding a
nitrosonium ionNO+ to an amine –NH2 leading to a
nitrosamine. This conversion occurs at acidic pH, particularly in the stomach, as shown in the equation for the formation of N-phenylnitrosamine:
NO−2 + H+ ⇌ HONO
HONO + H+ ⇌ H2O + NO+
C6H5NH2 + NO+ → C6H5N(H)NO + H+
Many primary alkyl N-nitroso compounds, such as CH3N(H)NO, tend to be unstable with respect to hydrolysis to the alcohol. Those derived from secondary amines (e.g., (CH3)2NNO derived from
dimethylamine) are more robust. It is these N-nitrosamines that are carcinogens in rodents.
Nitrosyl in inorganic chemistry
Nitrosyls are non-organic compounds containing the NO group, for example directly bound to the metal via the N atom, giving a metal–NO moiety. Alternatively, a
nonmetal example is the common reagent
nitrosyl chloride (Cl−N=O). Nitric oxide is a stable
radical, having an unpaired electron. Reduction of nitric oxide gives the nitrosyl
anion, NO−:
Nitric oxide can serve as a
ligand forming
metal nitrosyl complexes or just metal nitrosyls. These complexes can be viewed as adducts of NO+, NO−, or some intermediate case.
Nitroso compounds react with
primary amines in acidic environments to form
nitrosamines, which human metabolism converts to mutagenic
diazo compounds. Small amounts of nitro and nitroso compounds form during meat
curing; the toxicity of these compounds
preserves the meat against
bacterial infection. After curing completes, the concentration of these compounds appears to degrade over time. Their presence in finished products has been tightly regulated since several food-poisoning cases in the early 20th century,[9] but consumption of large quantities of processed meats can still cause a slight elevation in
gastric and
oesophageal cancer risk today.[10][11][12][13]
The effects of nitroso compounds vary dramatically across the gastrointestinal tract, and with diet. Nitroso compounds present in stool do not induce nitrosamine formation, because stool has neutral
pH.[15][16]Stomach acid does cause nitrosamine compound formation, but the process is inhibited when amine concentration is low (e.g. a low-protein diet or no fermented food). The process may also be inhibited in the case of high
vitamin C (ascorbic acid) concentration (e.g. high-fruit diet).[17][18][19] However, when 10% of the meal is fat, the effect reverses, and ascorbic acid markedly increases nitrosamine formation.[20][21]
See also
Nitrosamine, the functional group with the NO attached to an amine, such as R2N–NO
^E.Bosch (2014). "Structural Analysis of Methyl-Substituted Nitrosobenzenes and Nitrosoanisoles". J. Chem. Cryst. 98 (2): 44.
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10.1007/s10870-013-0489-8.
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^Beaudoin, D.; Wuest, J. D. (2016). "Dimerization of Aromatic C-Nitroso Compounds". Chemical Reviews. 116 (1): 258–286.
doi:
10.1021/cr500520s.
PMID26730505.
^Kirby, G. W. (1977). "Electrophilic C-nitroso-compounds". Chemical Society Reviews. 6: 2.
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10.1039/CS9770600001 (Tilden lecture).
^Luo, Yu-Ran (2007). Comprehensive Handbook of Chemical Bond Energies. Boca Raton, FL: Taylor and Francis.
ISBN9781420007282.
^Lee, Jonghyuk; Chen, Li; West, Ann H.; Richter-Addo, George B. (2002). "Interactions of Organic Nitroso Compounds with Metals". Chemical Reviews. 102 (4): 1019–1066.
doi:
10.1021/cr0000731.
PMID11942786.
^Bianchi, P.; Monbaliu, J. C. M. (2022). "Three decades of unveiling the complex chemistry of C-nitroso species with computational chemistry". Organic Chemistry Frontiers. 9: 223–264.
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^Combet, E; El Mesmari, A; Preston, T; Crozier, A; McColl, K. E. (2010). "Dietary phenolic acids and ascorbic acid: Influence on acid-catalyzed nitrosative chemistry in the presence and absence of lipids". Free Radical Biology and Medicine. 48 (6): 763–771.
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