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 (
alkyl nitrites 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-type reactions notwithstanding. But atmospheric oxygen can oxidize nitric oxide to
nitrogen dioxide, 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 of
hydroxylamines: :RNHOH + [O] → 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, 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 of a
thiol and
nitrous acid: :RSH + HONO → RSNO + H2O They are liable to disproportionate to the
disulfide and
nitrogen oxides. Although such cations have not been isolated, nitrosating reagents likely coordinate to
sulfides with no hydrogen substituent.
Sulfinates 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
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-
Nitrosamines arise from the reaction of
nitrite sources with
amino compounds. Typically, this reaction occurs when the
nucleophilic nitrogen of a secondary
amine attacks the nitrogen of the
electrophilic 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. ==References==