Nitrosation and nitrosylation

 ( Chemical Reactions ) 

Nitrosation and nitrosylation are two names for the process of converting organic compounds or into nitroso derivatives, i.e., compounds containing the functionality. The synonymy arises because the R-NO functionality can be interpreted two different ways, depending on the physico-chemical environment:

• Nitrosylation interprets the process as adding a nitric oxide NO^•. Nitrosylation commonly occurs in the context of a metal (e.g. iron) or a thiol, leading to nitrosyl iron (e.g., in nitrosylated heme = nitrosylheme) or S-nitrosothiols (RSNOs).
• Nitrosation interprets the process as adding a nitrosonium ion . Nitrosation commonly occurs with amines (–), leading to a nitrosamine.

There are multiple chemical mechanisms by which this can be achieved, including Enzyme and chemical synthesis.

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In biochemistry The biological functions of nitric oxide include S-Nitrosylation, the conjugation of NO to cysteine thiols in proteins, which is an important part of cell signalling.

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Organic synthesis Nitrosation is typically performed with nitrous acid, formed from acidification of a sodium nitrite solution. Nitrous acid is unstable, and high yields require a rapid reaction rate. NO⁺ synthon transfer is catalyzed by a strong nucleophile, such as (in order of increasing efficacy) chloride, bromide, thiocyanate, or thiourea. Indeed, (meta)stable nitrosation products ( or nitrosamines) can also nitrosate under such conditions; and the equilibria can be driven in any desired direction. Absent a driving force, thionitrosos form out of nitrosamines, which form out of nitrite esters, which form out of nitrous acid.

Some form of Lewis acid also enhances the electrophilicity of NO⁺ carriers, but the acid need not be Brønsted: nitroprusside, for example, nitrosates best in neutral-to-basic conditions. Roussin's salts may react similarly, but it is unclear if they release NO⁺ or NO^•.

In general, nitric oxide is a poor nitrosant, Traube reaction notwithstanding. But atmospheric oxygen can oxidize nitric oxide to nitrogen dioxide, which does nitrosate. Alternatively cupric ions catalyze disproportionation into NO⁺ and NO⁻., pp. 27–28, 209. Williams refers to Traube products as "Drago complexes"; note the typo on p. 27, which should refer to "2:1 complexes".

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On the carbon skeleton , such as nitrosobenzene, are typically prepared by oxidation of hydroxylamines:

RNHOH + O → RNO + H₂O

In principle, nitrosyl can substitute directly onto an aromatic ring, but the ring must be substantially activated, because NO⁺ is about 14 bel less electrophilic than nitronium. Unusually for electrophilic aromatic substitution, proton release to the solvent is typically rate-limiting, and the reaction can be suppressed in superacidic conditions.

Excess nitrosyl typically oxidizes the initially-nitroso product to a nitro compound or diazonium salt.

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Of chalcogen heteroatoms S-Nitrosothiol are typically prepared by condensation of a thiol and nitrous acid:

RSH + HONO → RSNO + H₂O

They are liable to disproportionate to the disulfide and .

Although such cations have not been isolated, nitrosating reagents likely coordinate to organic sulfide.

and sulfinic acids add twice to nitrous acid, so that the initial nitroso product (from the first addition) is reduced to a disulfonyl hydroxylamine. A variant on this process with bisulfite is Raschig's hydroxyl­amine production technique.

O-Nitroso compounds are similar to S-nitroso compounds, but are less reactive because the oxygen atom is less Nucleophile than the sulfur atom. The formation of an alkyl nitrite from an alcohol and nitrous acid is a common example:

ROH + HONO → RONO + H₂O

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Of amines N- arise from the reaction of nitrite sources with amine. Typically, this reaction occurs when the Nucleophile nitrogen of a secondary amine attacks the nitrogen of the Electrophile nitrosonium ion:

NO₂⁻ + 2 H⁺ → NO⁺ + H₂O

R₂NH + NO⁺ → R₂N-NO + H⁺

If the amine is secondary, then the product is stable, but primary amines decompose in acid to the corresponding diazonium cation, and then attack any nearby nucleophile. Nitrosation of a primary amine is thus sometimes referred to as deamination.

The stable secondary nitrosamines are carcinogens in rodents. The compounds are believed to nitrosate primary amines during the acid environment of the stomach, and the resulting diazonium ions alkylate DNA, leading to cancer.

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External links

• Nitrosation of Amines