Structural formula of nitroso group

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., nitrosoalkanes; 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).

Synthesis

Nitroso compounds can be prepared by the reduction of nitro compounds^[1] or by the oxidation of hydroxylamines.^[2] Ortho-nitrosophenols may be produced by the Baudisch reaction. In the Fischer–Hepp rearrangement aromatic 4-nitrosoanilines are prepared from the corresponding nitrosamines.

Properties

Structure of 2-nitrosotoluene dimer^[3]

Nitrosoarenes typically participate in a monomer–dimer equilibrium. The dimers, which are often pale yellow, are often 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]

When stored in protic media, primary and secondary nitrosoalkanes isomerize to oximes.^[5]

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]

Reactions

Many reaction exists which make use of an intermediate nitroso compound, such as the Barton reaction and Davis–Beirut reaction, as well as in the synthesis of indoles, for example: Baeyer–Emmerling indole synthesis, Bartoli indole synthesis. In the Saville reaction, mercury is used to replace a nitrosyl from a thiol group.

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 ion NO⁻ 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 ion NO⁺ 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:

  ${\displaystyle {\ce {NO2- + H+ <=> HONO}}}$

  ${\displaystyle {\ce {HONO + H+ <=> H2O + NO+}}}$

  ${\displaystyle {\ce {C6H5NH2 + NO+ -> C6H5N(H)NO + H+}}}$

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

Linear and bent metal nitrosyls

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⁻:

${\displaystyle {\ce {NO + e- -> NO-}}}$

Oxidation of NO yields the nitrosonium cation, NO⁺:

${\displaystyle {\ce {NO -> NO+ + e-}}}$

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.

In human health

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 20^th 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]}

For example, during the 1970s, certain Norwegian farm animals began exhibiting elevated levels of liver cancer. These animals had been fed herring meal preserved with sodium nitrite. The sodium nitrite had reacted with dimethylamine in the fish and produced dimethylnitrosamine.^[14]

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
• Nitrosobenzene
• Nitric oxide
• Nitroxyl

References