Hydroxylamine (also known as hydroxyammonia) is an
inorganic compound
An inorganic compound is typically a chemical compound that lacks carbon–hydrogen bondsthat is, a compound that is not an organic compound. The study of inorganic compounds is a subfield of chemistry known as ''inorganic chemistry''.
Inorgan ...
with the
chemical formula
A chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, such as pare ...
. The compound exists as
hygroscopic
Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption (chemistry), absorption or adsorption from the surrounding Natural environment, environment, which is usually at normal or room temperature. If water mol ...
colorless
crystal
A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macros ...
s.
[Greenwood and Earnshaw. ''Chemistry of the Elements.'' 2nd Edition. Reed Educational and Professional Publishing Ltd. pp. 431–432. 1997.] Hydroxylamine is almost always provided and used as an
aqueous solution
An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, also known as sodium chloride (NaCl), in water ...
or more often as one of its salts such as
hydroxylammonium sulfate, a water-soluble solid.
Hydroxylamine and its salts are consumed almost exclusively to produce
Nylon-6. The
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
to hydroxylamine is a step in biological
nitrification
''Nitrification'' is the biological oxidation of ammonia to nitrate via the intermediary nitrite. Nitrification is an important step in the nitrogen cycle in soil. The process of complete nitrification may occur through separate organisms or ent ...
.
History
Hydroxylamine was first prepared as
hydroxylammonium chloride in 1865 by the German chemist
Wilhelm Clemens Lossen (1838-1906); he reacted
tin and
hydrochloric acid
Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...
in the presence of
ethyl nitrate. It was first prepared in pure form in 1891 by the Dutch chemist
Lobry de Bruyn and by the French chemist Léon Maurice Crismer (1858-1944). The
coordination 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 chemical bond, bound molecules or ions, that are in turn known as ' ...
(zinc dichloride di(hydroxylamine)), known as Crismer's salt, releases hydroxylamine upon heating.
Structure
Hydroxylamine and its ''N''-substituted derivatives are pyramidal at nitrogen, with bond angles very similar to those of amines. The conformation of hydroxylamine places the NOH anti to the lone pair on nitrogen, seeming to minimize lone pair-lone pair interactions.
Production
Hydroxylamine or its
salts
In chemistry, a salt or ionic compound is a chemical compound consisting of an assembly of positively charged ions ( cations) and negatively charged ions (anions), which results in a compound with no net electric charge (electrically neutral). ...
(salts containing hydroxylammonium
cations
An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
) can be produced via several routes but only two are commercially viable. It is also produced naturally as discussed in a section on
biochemistry
Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...
.
From nitric oxide
is mainly produced as its
sulfuric acid
Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid (English in the Commonwealth of Nations, Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen, ...
salt
In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...
, hydroxylammonium sulfate (), by the
hydrogenation
Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to redox, reduce or Saturated ...
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 ...
over
platinum
Platinum is a chemical element; it has Symbol (chemistry), symbol Pt and atomic number 78. It is a density, dense, malleable, ductility, ductile, highly unreactive, precious metal, precious, silverish-white transition metal. Its name origina ...
catalyst
Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...
s in the presence of sulfuric acid.
:
Raschig process
Another route to is the
Raschig process:
aqueous
An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, also known as sodium chloride (NaCl), in wat ...
ammonium nitrite
Ammonium nitrite is a chemical compound with the chemical formula . It is the ammonium salt of nitrous acid. It is composed of ammonium cations and nitrite anions . It is not used in pure isolated form since it is highly unstable and decomposes i ...
is
reduced by
and
at 0 °C to yield a hydroxylamido-''N'',''N''-disulfonate
anion
An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...
:
:
This ammonium hydroxylamine disulfonate anion is then
hydrolyzed
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysi ...
to give
hydroxylammonium sulfate:
:
Other methods
Julius Tafel discovered that hydroxylamine
hydrochloride or
sulfate
The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...
salts can be produced by
electrolytic reduction of
nitric acid
Nitric acid is an inorganic compound with the formula . It is a highly corrosive mineral acid. The compound is colorless, but samples tend to acquire a yellow cast over time due to decomposition into nitrogen oxide, oxides of nitrogen. Most com ...
with
HCl or
respectively:
:
Hydroxylamine can also be produced by the reduction of
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 ...
or
potassium nitrite
Potassium nitrite (distinct from potassium nitrate) is the inorganic compound with the chemical formula . It is an ionic salt of potassium ions K+ and nitrite ions NO2−, which forms a white or slightly yellow, hygroscopic crystalline powder that ...
with
bisulfite:
:
: (100 °C, 1 h)
Hydrochloric acid
Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...
disproportionates
nitromethane
Nitromethane, sometimes shortened to simply "nitro", is an organic compound with the chemical formula . It is the simplest organic nitro compound. It is a polar liquid commonly used as a solvent in a variety of industrial applications such as in ...
to
hydroxylamine hydrochloride and
carbon monoxide
Carbon monoxide (chemical formula CO) is a poisonous, flammable gas that is colorless, odorless, tasteless, and slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the si ...
via
the hydroxamic acid.
A direct lab synthesis of hydroxylamine from
molecular nitrogen in
water plasma was demonstrated in 2024.
Isolation of hydroxylamine
Solid can be collected by treatment with
liquid ammonia.
Ammonium sulfate
Ammonium sulfate (American English and international scientific usage; ammonium sulphate in British English); (NH4)2SO4, is an inorganic salt with a number of commercial uses. The most common use is as a soil fertilizer. It contains 21% nitrogen a ...
, , a side-product insoluble in liquid ammonia, is removed by filtration; the liquid
ammonia
Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...
is evaporated to give the desired product.
The net reaction is:
:
Base, such as sodium butoxide, can be used to free the hydroxylamine from
hydroxylammonium chloride:
:
Reactions
Hydroxylamine is a base with a
pKa of 6.03:
:
Hydroxylamine reacts with
alkylating agent Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting ...
s usually at the
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. ...
atom:
:
The reaction of with an
aldehyde
In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...
or
ketone
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
produces an
oxime
In organic chemistry, an oxime is an organic compound belonging to the imines, with the general Chemical formula, formula , where R is an organic Side chain, side-chain and R' may be hydrogen, forming an aldoxime, or another organic functional g ...
.
:
This reaction can be useful in the purification of ketones and aldehydes: if hydroxylamine is added to an aldehyde or ketone in solution, an oxime forms, which generally precipitates from solution; heating the precipitate with aqueous acid then restores the original aldehyde or ketone.
reacts with
chlorosulfonic acid to give
hydroxylamine-''O''-sulfonic acid:
:
It
isomer
In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...
izes to the
amine oxide .
Functional group

Hydroxylamine derivatives
substituted in place of the hydroxyl or amine hydrogen are (respectively) called ''O''- or ''N''hydroxylamines. In general ''N''hydroxylamines are more common. Examples are ''N'tert''butylhydroxylamine or the
glycosidic bond
A glycosidic bond or glycosidic linkage is a type of ether bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate.
A glycosidic bond is formed between the hemiacetal or hemiketal group o ...
in
calicheamicin.
''N'',''O''Dimethylhydroxylamine is a precursor to
Weinreb amides.
Similarly to amines, one can distinguish hydroxylamines by their degree of substitution: primary, secondary and tertiary. When stored exposed to air for weeks, secondary hydroxylamines degrade to
nitrones.
''N''organylhydroxylamines, , where R is an
organyl group, can be reduced to
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 ...
s :
:
Oximes such as
dimethylglyoxime are also employed as
ligand
In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
s.
Synthesis
The hydrolysis of N-substituted oximes, hydroxamic acids, and nitrones easily provides hydroxylamines.
Alkylating of hydroxylamine or N-alkylhydroxylamines proceeds usually at nitrogen. One challenge is dialkylation when only monoalkylation is desired.
:
For O-alkylation of hydroxylamines, strong base such as
sodium hydride is required to first deprotonate the OH group:
:
:
Amine oxidation with
benzoyl peroxide
Benzoyl peroxide is a chemical compound (specifically, an organic peroxide) with structural formula , often abbreviated as (BzO)2. In terms of its structure, the molecule can be described as two benzoyl (, Bz) groups connected by a peroxide ...
is a common method to synthesize hydroxylamines. Care must be taken to prevent over-oxidation to a
nitrone. Other methods include:
*
Hydrogenation
Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to redox, reduce or Saturated ...
of an
oxime
In organic chemistry, an oxime is an organic compound belonging to the imines, with the general Chemical formula, formula , where R is an organic Side chain, side-chain and R' may be hydrogen, forming an aldoxime, or another organic functional g ...
*
Amine oxide pyrolysis (the
Cope reaction)
Uses
:
Approximately 95% of hydroxylamine is used in the synthesis of
cyclohexanone oxime, a precursor to
Nylon 6.
[ The treatment of this oxime with acid induces the Beckmann rearrangement to give caprolactam.] The latter can then undergo a ring-opening polymerization to yield Nylon 6.
Laboratory uses
Hydroxylamine and its salts are commonly used as reducing agents in myriad organic and inorganic reactions. They can also act as antioxidants for fatty acids.
High concentrations of hydroxylamine are used by biologists to introduce mutations
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...
by acting as a DNA nucleobase
Nucleotide bases (also nucleobases, nitrogenous bases) are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nuc ...
amine-hydroxylating agent. In is thought to mainly act via hydroxylation of cytidine
Cytidine (symbol C or Cyd) is a nucleoside molecule that is formed when cytosine is attached to a ribose ring (also known as a ribofuranose) via a β-N1-glycosidic bond. Cytidine is a component of RNA. It is a white water-soluble solid that is ...
to hydroxyaminocytidine, which is misread as thymidine, thereby inducing C:G to T:A transition mutations. But high concentrations or over-reaction of hydroxylamine ''in vitro'' are seemingly able to modify other regions of the DNA & lead to other types of mutations. This may be due to the ability of hydroxylamine to undergo uncontrolled free radical chemistry in the presence of trace metals and oxygen, in fact in the absence of its free radical affects Ernst Freese noted hydroxylamine was unable to induce reversion mutations of its C:G to T:A transition effect and even considered hydroxylamine to be the most specific mutagen known. Practically, it has been largely surpassed by more potent mutagens such as EMS, ENU, or nitrosoguanidine, but being a very small mutagenic compound with high specificity, it found some specialized uses such as mutation of DNA packed within bacteriophage
A bacteriophage (), also known informally as a phage (), is a virus that infects and replicates within bacteria. The term is derived . Bacteriophages are composed of proteins that Capsid, encapsulate a DNA or RNA genome, and may have structu ...
capsids, and mutation of purified DNA ''in vitro''.
:
An alternative industrial synthesis of paracetamol developed by Hoechst– Celanese involves the conversion of ketone
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
to a ketoxime with hydroxylamine.
Some non-chemical uses include removal of hair from animal hides and photographic developing solutions. In the semiconductor industry, hydroxylamine is often a component in the "resist stripper", which removes photoresist after lithography.
Hydroxylamine can also be used to better characterize the nature of a post-translational modification onto proteins. For example, poly(ADP-Ribose) chains are sensitive to hydroxylamine when attached to glutamic or aspartic acids but not sensitive when attached to serines. Similarly, Ubiquitin molecules bound to serines or threonines residues are sensitive to hydroxylamine, but those bound to lysine (isopeptide bond) are resistant.
Biochemistry
In biological nitrification, the oxidation of to hydroxylamine is mediated by the ammonia monooxygenase (AMO). Hydroxylamine oxidoreductase (HAO) further oxidizes hydroxylamine to nitrite.
Cytochrome
Cytochromes are redox-active proteins containing a heme, with a central iron (Fe) atom at its core, as a cofactor. They are involved in the electron transport chain and redox catalysis. They are classified according to the type of heme and its ...
P460, an enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
found in the ammonia-oxidizing bacteria '' Nitrosomonas europea'', can convert hydroxylamine to nitrous oxide
Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or factitious air, among others, is a chemical compound, an Nitrogen oxide, oxide of nitrogen with the Chemical formula, formula . At room te ...
, a potent greenhouse gas
Greenhouse gases (GHGs) are the gases in the atmosphere that raise the surface temperature of planets such as the Earth. Unlike other gases, greenhouse gases absorb the radiations that a planet emits, resulting in the greenhouse effect. T ...
.
Hydroxylamine can also be used to highly selectively cleave asparaginyl-glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...
peptide bonds in peptides and proteins. It also bonds to and permanently disables (poisons) heme-containing enzymes. It is used as an irreversible inhibitor of the oxygen-evolving complex
The oxygen-evolving complex (OEC), also known as the water-splitting complex, is a water-oxidizing enzyme involved in the photo-oxidation of water during the light reactions of photosynthesis. OEC is surrounded by 4 core proteins of photosystem I ...
of photosynthesis on account of its similar structure to water.
Safety and environmental concerns
Hydroxylamine is a skin irritant but is of low toxicity.
A detonator
A detonator is a device used to make an explosive or explosive device explode. Detonators come in a variety of types, depending on how they are initiated (chemically, mechanically, or electrically) and details of their inner working, which of ...
can easily explode aqueous solutions concentrated above 80% by weight, and even 50% solution might prove detonable if tested in bulk. In air, the combustion is rapid and complete:
:
Absent air, pure hydroxylamine requires stronger heating and the detonation does not complete combustion:
:
At least two factories dealing in hydroxylamine have been destroyed since 1999 with loss of life. It is known, however, that ferrous and ferric iron
Iron is a chemical element; it has symbol Fe () and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, forming much of Earth's o ...
salts accelerate the decomposition of 50% solutions. Hydroxylamine and its derivatives are more safely handled in the form of salt
In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...
s.
It is an irritant to the respiratory tract
The respiratory tract is the subdivision of the respiratory system involved with the process of conducting air to the alveoli for the purposes of gas exchange in mammals. The respiratory tract is lined with respiratory epithelium as respirato ...
, skin, eyes, and other mucous membranes
A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
. It may be absorbed through the skin, is harmful if swallowed, and is a possible mutagen
In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...
.MSDS
Sigma-Aldrich
See also
*
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 ...
*
Amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
References
Further reading
Hydroxylamine* Walters, Michael A. and Andrew B. Hoem. "Hydroxylamine." ''e-Encyclopedia of Reagents for Organic Synthesis.'' 2001.
* M. W. Rathke A. A. Millard "Boranes in Functionalization of Olefins to Amines: 3-Pinanamine" ''Organic Syntheses'', Coll. Vol. 6, p. 943; Vol. 58, p. 32. (preparation of hydroxylamine-O-sulfonic acid).
External links
Calorimetric studies of hydroxylamine decompositionDeadly detonation of hydroxylamine at Concept Sciences facility
{{Authority control
Functional groups
Inorganic amines
Photographic chemicals
Rocket fuels
Reducing agents
Nitrogen oxoacids