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).

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 non-metal 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⁻

Nitrosyl as a ligand

Linear and bent metal nitrosyls

Main article: Metal nitrosyl

Nitric oxide can serve as a ligand in complexes. The resulting complexes are called metal nitrosyls, and can bond to a metal atom in two extreme modes: as NO⁺ and as NO⁻. It is generally assumed that NO⁺ coordinates linearly, the M−N−O angle being 180°, whereas NO⁻ forms a bent geometry, with an M−N−O angle of approximately 120°. However, the results of many studies have shown that the ionic descriptions of the NO ligand do not correlate with metal-NO geometry. A more realistic description of electron-counting in metal-nitrosyl chemistry is given by the Enemark-Feltham notation.

Organonitroso compounds

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, which is prepared by the following sequence:

(CH₃)₃CNH₂ → (CH₃)₃CNO₂

(CH₃)₃CNO₂ → (CH₃)₃CNHOH

(CH₃)₃CNHOH → (CH₃)₃CNO

(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-nitroso-anilines 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.

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:

NO₂⁻ + H⁺ $\overrightarrow{\leftarrow}$ HONO

HONO + H⁺ $\overrightarrow{\leftarrow}$ 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.

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 NO₂⁻ (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 NO₂⁻ to form NO. Ascorbate and pH 5 thus favor nitrosylation of heme iron, forming nitrosyl-heme, 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: nitrosyl-heme is thus considered a benefit for the meat industry and for consumers.

• 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. 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 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).

See also

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