Nitroso

Structural formula of nitroso moiety

Nitroso refers to a functional group in organic chemistry which has the NO group 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, R¹N(−R²)−N=O), and O-nitroso compounds (alkyl nitrites; RO−N=O).

Organonitroso compounds

Nitrosobenzene ((C₆H₅NO) is prepared by reduction of nitrobenzene to phenylhydroxylamine (C₆H₅NHOH), which is then oxidized.^[1] Nitrosoarenes typically participate in a monomer-dimer equilibrium. The dimers, which are often pale-yellow, are often favored in the solid state, whereas the deeply colored monomers are favored in dilution solution or at higher temperatures. They exist as cis- and trans-isomers.^[2]

Structure of 2-nitrosotoluene dimer.^[3]

Nitroso compounds can be prepared by the reduction of nitro compounds or by the oxidation of hydroxylamines. A good example is (CH₃)₃CNO, known formally as 2-methyl-2-nitrosopropane, or t-BuNO.^[4] (CH₃)₃CNO is blue and exists in solution in equilibrium with its dimer, which is colorless, m.p. 80–81 °C.

In the Fischer–Hepp rearrangement aromatic 4-nitrosoanilines are prepared from the corresponding nitrosamines. Another named reaction involving a nitroso compound is the Barton reaction.

Organonitroso compounds serve as a ligands for transition metals.^[5]

2-Methyl-2-nitrosopropane.

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 to 40 kcal/mol, while nitrosoarenes have BDEs on the order of 50 to 60 kcal/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.^[6]

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:

  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

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 hyponitrite anion, NO⁻:

NO + e⁻ → NO⁻

Oxidation of NO yields the nitrosonium cation, NO⁺:

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 food

Nitrosyl-heme

In foodstuffs and in the gastro-intestinal tract, nitrosation and nitrosylation do not have the same consequences on consumer health.

• In cured meat: Meat processed by curing contains nitrite and has a pH of 5 approximately, where almost all nitrite is present as NO⁻
  ₂ (99%). Cured meat is also added with sodium ascorbate (or erythorbate or vitamin C). As demonstrated by S. Mirvish, ascorbate inhibits nitrosation of amines to nitrosamine, because ascorbate reacts with NO⁻
  ₂ to form NO.^[7][8] Ascorbate and pH 5 thus favor nitrosylation of heme iron, forming nitrosylheme, a red pigment when included inside myoglobin, and a pink pigment when it has been released by cooking. It participates to the "bacon flavor" of cured meat: nitrosylheme is thus considered a benefit for the meat industry and for consumers.^[9]
• In the stomach: secreted hydrogen chloride makes an acidic environment (pH=2) and ingested nitrite (with food or saliva) leads to nitrosation of amines, that yields nitrosamines (potential carcinogens). Nitrosation is low if amine concentration is low (e.g., low-protein diet, no fermented food) or if vitamin C concentration is high (e.g., high fruit diet). Then S-nitrosothiols are formed, that are stable at pH 2.
• In the colon: neutral pH does not favor nitrosation. No nitrosamine is formed in stools, even after addition of a secondary amine or nitrite.^[10] Neutral pH favors NO⁻ release from S-nitrosothiols, and nitrosylation of iron. The previously called NOC (N-nitroso compounds) measured by Bingham's team in stools from red meat-fed volunteers^[11] were, according to Bingham and Kuhnle, largely non-N-nitroso ATNC (apparent total nitroso compounds), e.g., S-nitrosothiols and nitrosyl iron (as nitrosyl heme).^[12]

See also

• Nitrosamine, the functional group with the NO attached to an amine, such as R₂N–NO
• Nitrosobenzene
• Nitric oxide
• Nitroxyl

References