Hydroxylamine

The compound is in a form of a white hygroscopic crystals. Hydroxylamine is almost always provided and used as an aqueous solution. It is consumed almost exclusively to produce Nylon-6. The oxidation of NH₃ to hydroxylamine is a step in biological nitrification.

Hydroxylamine

Names
IUPAC name Azinous acid
Preferred IUPAC name Hydroxylamine (only preselected)
Other names Aminol Azanol Hydroxyammonia Hydroxyamine Hydroxyazane Hydroxylazane Nitrinous acid
Identifiers
CAS Number	7803-49-8 Y
3D model (JSmol)	Interactive image
3DMet	B01184
ChEBI	CHEBI:15429 Y
ChEMBL	ChEMBL1191361 N
ChemSpider	766 Y
ECHA InfoCard	100.029.327
EC Number	232-259-2
Gmelin Reference	478
KEGG	C00192 Y
MeSH	Hydroxylamine
PubChem CID	787
RTECS number	NC2975000
UNII	2FP81O2L9Z Y
CompTox Dashboard (EPA)	DTXSID7041043
InChI InChI=1S/H3NO/c1-2/h2H,1H2 Y Key: AVXURJPOCDRRFD-UHFFFAOYSA-N Y InChI=1/H3NO/c1-2/h2H,1H2 Key: AVXURJPOCDRRFD-UHFFFAOYAD
SMILES NO
Properties
Chemical formula	NH2OH
Molar mass	33.030 g·mol−1
Appearance	Vivid white, opaque crystals
Density	1.21 g cm−3 (at 20 °C)
Melting point	33 °C (91 °F; 306 K)
Boiling point	58 °C (136 °F; 331 K) /22 mm Hg (decomposes)
Solubility in water	Soluble
log P	−0.758
Acidity (pKa)	6.03 ([NH3OH]+)
Basicity (pKb)	7.97
Structure
Coordination geometry	Tricoordinated at N, dicoordinated at O
Molecular shape	Trigonal pyramidal at N, bent at O
Dipole moment	0.67553 D
Thermochemistry
Heat capacity (C)	46.47 J/(K·mol)
Std molar entropy (S⦵298)	236.18 J/(K·mol)
Std enthalpy of formation (ΔfH⦵298)	−39.9 kJ/mol
Hazards
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H200, H290, H302, H312, H315, H317, H318, H335, H351, H373, H400
Precautionary statements	P201, P202, P234, P260, P261, P264, P270, P271, P272, P273, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P312, P314, P321, P322, P330, P332+P313, P333+P313, P362, P363, P372, P373, P380, P390, P391, P401, P403+P233, P404, P405, P501
NFPA 704 (fire diamond)	2 1 3
Flash point	129 °C (264 °F; 402 K)
Autoignition temperature	265 °C (509 °F; 538 K)
Lethal dose or concentration (LD, LC):
LD50 (median dose)	408 mg/kg (oral, mouse); 59–70 mg/kg (intraperitoneal mouse, rat); 29 mg/kg (subcutaneous, rat)
Safety data sheet (SDS)	ICSC 0661
Related compounds
Related hydroxylammonium salts	Hydroxylammonium chloride Hydroxylammonium nitrate Hydroxylammonium sulfate
Related compounds	Ammonia Water Hydrazine Hydrogen peroxide N,O-Dimethylhydroxylamine N,N-Diethylhydroxylamine Hydroxylamine-O-sulfonic acid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

Hydroxylamine was first prepared as hydroxylammonium chloride in 1865 by the German chemist Wilhelm Clemens Lossen (1838-1906); he reacted tin and hydrochloric acid 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 ZnCl₂(NH₂OH)₂ (zinc dichloride di(hydroxylamine)), known as Crismer's salt, releases hydroxylamine upon heating.

Hydroxylamine or its salts (salts containing hydroxylammonium cations [NH₃OH]⁺) can be produced via several routes but only two are commercially viable. It is also produced naturally as discussed in a section on biochemistry.

From nitric oxide

NH₂OH is mainly produced as its sulfuric acid salt, hydroxylammonium hydrogen sulfate ([NH₃OH]⁺[HSO₄]⁻), by the hydrogenation of nitric oxide over platinum catalysts in the presence of sulfuric acid.

2 NO + 3 H₂ + 2 H₂SO₄ → 2 [NH₃OH]⁺[HSO₄]⁻

Raschig process

Another route to NH₂OH is the Raschig process: aqueous ammonium nitrite is reduced by HSO−3 and SO₂ at 0 °C to yield a hydroxylamido-N,N-disulfonate anion:

[NH₄]⁺[NO₂]⁻ + 2 SO₂ + NH₃ + H₂O → 2 [NH₄]⁺ + N(OH)(SO−3)₂

This anion is then hydrolyzed to give hydroxylammonium sulfate [NH₃OH]₂SO₄:

N(OH)(SO−3)₂ + H₂O → NH(OH)(SO−3) + HSO−4
2 NH(OH)(SO−3) + 2 H₂O → [NH₃OH]₂SO₄ + SO2−4

Solid NH₂OH can be collected by treatment with liquid ammonia. Ammonium sulfate, [NH₄]₂SO₄, a side-product insoluble in liquid ammonia, is removed by filtration; the liquid ammonia is evaporated to give the desired product. The net reaction is:

2 NO−2 + 4 SO₂ + 6 H₂O + 6 NH₃ → 4 SO2−4 + 6 [NH₄]⁺ + 2 NH₂OH

A base then frees the hydroxylamine from the salt:

[NH₃OH]Cl + NaOCH₂CH₂CH₂CH₃ → NH₂OH + NaCl + CH₃CH₂CH₂CH₂OH

Other methods

Julius Tafel discovered that hydroxylamine hydrochloride or sulfate salts can be produced by electrolytic reduction of nitric acid with HCl or H₂SO₄ respectively:

HNO₃ + 3 H₂ → NH₂OH + 2 H₂O

Hydroxylamine can also be produced by the reduction of nitrous acid or potassium nitrite with bisulfite:

HNO₂ + 2 HSO−3 → N(OH)(OSO−2)₂ + H₂O → NH(OH)(OSO−2) + HSO−4
NH(OH)(OSO−2) + [H₃O]⁺ → [NH₃OH]⁺ + HSO−4 (100 °C, 1 h)

Hydrochloric acid disproportionates nitromethane to hydroxylamine hydrochloride and carbon monoxide via the hydroxamic acid.^{[citation needed]}

A direct production of hydroxylamine from molecular nitrogen is also possible in water plasma.

Hydroxylamine reacts with electrophiles, such as alkylating agents, which can attach to either the oxygen or the nitrogen atoms:

R−X + NH₂OH → R−O−NH₂ + HX
R−X + NH₂OH → R−NH−OH + HX

The reaction of NH₂OH with an aldehyde or ketone produces an oxime.

R₂C=O + [NH₃OH]Cl → R₂C=N−OH + NaCl + H₂O (in NaOH solution)

This reaction is 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 an inorganic acid then restores the original aldehyde or ketone.

Oximes such as dimethylglyoxime are also employed as ligands.

NH₂OH reacts with chlorosulfonic acid to give hydroxylamine-O-sulfonic acid:

HO−S(=O)₂−Cl + NH₂OH → NH₂−O−S(=O)₂−OH + HCl

When heated, hydroxylamine explodes. A detonator 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:

4 NH₂OH + O₂ → 2 N₂ + 6 H₂O

Absent air, pure hydroxylamine requires stronger heating and the detonation does not complete combustion:

3 NH₂OH → N₂ + NH₃ + 3 H₂O

Partial isomerisation to the amine oxide H₃N⁺−O⁻ contributes to the high reactivity.

Conjugate oxoacids

Hydroxylamine yields via oxidation to azinic acid.^{[citation needed]} Further attempted oxidation yields nitric acid, and finally orthonitrate.

More hydroxyl radicals substitute the hydrogen atoms to yield azonous acid & azorous acid.

 

Substituted derivatives of hydroxylamine are known. When the hydroxyl or an amine hydrogen is substituted, such a molecule is called (respectively) an O- or N-hydroxylamine. In general N-hydroxylamines are more common. Examples are N-tert-butylhydroxylamine or the glycosidic bond 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, R−NH−OH, where R is an organyl group, can be reduced to amines R−NH₂:

R−NH−OH (Zn, HCl) → R−NH₂ + ZnO

Synthesis

Amine oxidation with benzoyl peroxide is the most common method to synthesize hydroxylamines. Care must be taken to prevent over-oxidation to a nitrone. Other methods include:

• Hydrogenation of an oxime
• Alkylating a precursor hydroxylamine
• Amine oxide pyrolysis (the Cope reaction)

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 (3). The latter can then undergo a ring-opening polymerization to yield Nylon 6.

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 by acting as a DNA nucleobase amine-hydroxylating agent. In is thought to mainly act via hydroxylation of cytidine 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 & 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 capsids, & mutation of purified DNA in vitro.

An alternative industrial synthesis of paracetamol developed by Hoechst–Celanese involves the conversion of ketone 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.

In biological nitrification, the oxidation of NH₃ to hydroxylamine is mediated by the ammonia monooxygenase (AMO). Hydroxylamine oxidoreductase (HAO) further oxidizes hydroxylamine to nitrite.

Cytochrome P460, an enzyme found in the ammonia-oxidizing bacteria Nitrosomonas europea, can convert hydroxylamine to nitrous oxide, a potent greenhouse gas.

Hydroxylamine can also be used to highly selectively cleave asparaginyl-glycine 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 of photosynthesis on account of its similar structure to water.

With a theoretical decomposition energy of about 5 kJ/g, hydroxylamine is an explosive, and aqueous solutions above 80% can be easily detonated by detonator or strong heating under confinement. 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 salts accelerate the decomposition of 50% NH₂OH solutions. Hydroxylamine and its derivatives are more safely handled in the form of salts.

It is an irritant to the respiratory tract, skin, eyes, and other mucous membranes. It may be absorbed through the skin, is harmful if swallowed, and is a possible mutagen.

• Amine
• Amino acid