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Nitrosation and nitrosylation are two names for the process of converting organic compounds or
metal complex A coordination complex is a chemical compound consisting of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or ...
es 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 nitrosyl radical 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 Nitrosamines (or more formally ''N''-nitrosamines) are organic compounds produced by industrial processes. The chemical structure is , where R is usually an alkyl group. Nitrosamines have a nitroso group () that are "probable human carcinogens", ...
. There are multiple chemical mechanisms by which this can be achieved, including
enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...
and chemical synthesis.


In biochemistry

The biological functions of
nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...
include S-nitrosylation, the conjugation of NO to
cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
thiols in proteins, which is an important part of
cell signalling In biology, cell signaling (cell signalling in British English) is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in both prokaryotes and eukary ...
.


Organic synthesis

Nitrosation is typically performed with
nitrous acid Nitrous acid (molecular formula ) is a weak and monoprotic acid known only in solution, in the gas phase, and in the form of nitrite () salts. It was discovered by Carl Wilhelm Scheele, who called it " phlogisticated acid of niter". Nitrous ac ...
, formed from acidification of a
sodium nitrite Sodium nitrite is an inorganic compound with the chemical formula . It is a white to slightly yellowish crystalline powder that is very soluble in water and is hygroscopic. From an industrial perspective, it is the most important nitrite sa ...
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 The term chloride refers to a compound or molecule that contains either a chlorine anion (), which is a negatively charged chlorine atom, or a non-charged chlorine atom covalently bonded to the rest of the molecule by a single bond (). The pr ...
, bromide, thiocyanate, or
thiourea Thiourea () is an organosulfur compound with the formula and the structure . It is structurally similar to urea (), with the oxygen atom replaced by sulfur atom (as implied by the '' thio-'' prefix). The properties of urea and thiourea differ s ...
. Indeed, (meta)stable nitrosation products ( alkyl nitrites or
nitrosamines Nitrosamines (or more formally ''N''-nitrosamines) are organic compounds produced by industrial processes. The chemical structure is , where R is usually an alkyl group. Nitrosamines have a nitroso group () that are "probable human carcinogens", ...
) 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 Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...
is a poor nitrosant, Traube-type reactions notwithstanding. But atmospheric oxygen can oxidize nitric oxide to
nitrogen dioxide Nitrogen dioxide is a chemical compound with the formula . One of several nitrogen oxides, nitrogen dioxide is a reddish-brown gas. It is a paramagnetic, bent molecule with C2v point group symmetry. Industrially, is an intermediate in the s ...
, which does nitrosate. Alternatively cupric ions catalyze disproportionation into NO+ and NO.


On the carbon skeleton

Nitroso compounds, such as nitrosobenzene, are typically prepared by
oxidation Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
of
hydroxylamines Hydroxylamine (also known as hydroxyammonia) is an inorganic compound with the chemical formula . The compound exists as hygroscopic colorless crystals.Greenwood and Earnshaw. ''Chemistry of the Elements.'' 2nd Edition. Reed Educational and Prof ...
: :RNHOH + → RNO + H2O In principle, NO+ can substitute directly onto an aromatic ring, but the ring must be substantially activated, because NO+ is about 14 bel less electrophilic than NO. Unusually for
electrophilic aromatic substitution Electrophilic aromatic substitution (SEAr) is an organic reaction in which an atom that is attached to an aromatic ring, aromatic system (usually hydrogen) is replaced by an electrophile. Some of the most important electrophilic aromatic substitut ...
, proton release to the solvent is typically rate-limiting, and the reaction can be suppressed in superacidic conditions. Excess NO+ typically oxidizes the initially-nitroso product to a nitro compound or diazonium salt.


Of chalcogen heteroatoms

''S''-nitrosothiols are typically prepared by
condensation Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor ...
of a
thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...
and
nitrous acid Nitrous acid (molecular formula ) is a weak and monoprotic acid known only in solution, in the gas phase, and in the form of nitrite () salts. It was discovered by Carl Wilhelm Scheele, who called it " phlogisticated acid of niter". Nitrous ac ...
: :RSH + HONO → RSNO + H2O They are liable to disproportionate to the
disulfide In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inorg ...
and
nitrogen oxide Nitrogen oxide may refer to a binary compound of oxygen and nitrogen, or a mixture of such compounds: Charge-neutral *Nitric oxide (NO), nitrogen(II) oxide, or nitrogen monoxide * Nitrogen dioxide (), nitrogen(IV) oxide * Nitrogen trioxide (), o ...
s. Although such cations have not been isolated, nitrosating reagents likely coordinate to sulfides with no hydrogen substituent.
Sulfinate Sulfinic acids are oxoacids of sulfur with the structure RSO(OH). In these organosulfur compounds, sulfur is Molecular geometry, pyramidal. Structure and properties Sulfinic acids RSO2H are typically more acidic than the corresponding carboxyl ...
s and sulfinic acids add twice to
nitrous acid Nitrous acid (molecular formula ) is a weak and monoprotic acid known only in solution, in the gas phase, and in the form of nitrite () salts. It was discovered by Carl Wilhelm Scheele, who called it " phlogisticated acid of niter". Nitrous ac ...
, 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 nucleophilic than the sulfur atom. The formation of an alkyl nitrite from an alcohol and nitrous acid is a common example: :ROH + HONO → RONO + H2O


Of amines

''N''-
Nitrosamine Nitrosamines (or more formally ''N''-nitrosamines) are organic compounds produced by industrial processes. The chemical structure is , where R is usually an alkyl group. Nitrosamines have a nitroso group () that are "probable human carcinogens", ...
s arise from the reaction of
nitrite The nitrite polyatomic ion, ion has the chemical formula . Nitrite (mostly sodium nitrite) is widely used throughout chemical and pharmaceutical industries. The nitrite anion is a pervasive intermediate in the nitrogen cycle in nature. The name ...
sources with amino compounds. Typically, this reaction occurs when the nucleophilic
nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...
of a secondary
amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...
attacks the nitrogen of the electrophilic
nitrosonium The nitrosonium ion is , in which the nitrogen atom is bonded to an oxygen atom with a bond order of 3, and the overall diatomic species bears a positive charge. It can be viewed as nitric oxide with one electron removed. This ion is usually o ...
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 Deamination is the removal of an amino group from a molecule. Enzymes that catalysis, catalyse this reaction are called deaminases. In the human body, deamination takes place primarily in the liver; however, it can also occur in the kidney. In s ...
. 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.


References


External links


Nitrosation of Amines
{{Nitric oxide signaling Chemical reactions Nitrogen cycle Organic reactions