Hydroxylamine

Hydroxylamine (also known as hydroxyammonia) is an inorganic compound with the chemical formula . The compound exists as hygroscopic colorless crystals. Hydroxylamine is almost always provided and used as either an aqueous solution 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 of Ammonia| to hydroxylamine is a step in biological nitrification.

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 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 (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 most stable conformation of hydroxylamine has the NOH anti to the lone pair on nitrogen, seeming to minimize the repulsion between the nitrogen and oxygen lone pairs.

Production

Hydroxylamine or its salts (salts containing hydroxylammonium cations ) 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

is mainly produced as its sulfuric acid salt, hydroxylammonium sulfate (), by the hydrogenation of nitric oxide over platinum catalysts in the presence of sulfuric acid.

Raschig process

Another route to is the Raschig process: aqueous ammonium nitrite is reduced by Bisulfite| and Sulfur dioxide| at 0 °C to yield a hydroxylamido-N,N-disulfonate anion:

This ammonium hydroxylamine disulfonate anion is then hydrolyzed to give hydroxylammonium sulfate:

Other methods

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

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

: (100 °C, 1 h)

Hydrochloric acid disproportionates nitromethane to hydroxylamine hydrochloride and carbon monoxide 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, , a side-product insoluble in liquid ammonia, is removed by filtration; the liquid ammonia is evaporated to give the desired product.

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

In aqueous solution, hydroxylamine is predicted to coexist with a tautomer, the amine oxide (ammonia oxide). The solvated ammonia oxide form has variously been estimated to be less stable by 0.9–3.5 kcal·mol<sup>−1</sup>. It is absent from the gas phase, where the predicted stability gap is 27.6 kcal·mol<sup>−1</sup>.

Functional group

80px|thumb|left|class=skin-invert-image|Secondary N,N-hydroxylamine schema

Hydroxylamine derivatives substituted in place of the hydroxyl or amine hydrogen are (respectively) called O- or Nhydroxylamines. In general Nhydroxylamines are more common. Examples are N'tertbutylhydroxylamine or the glycosidic bond in calicheamicin. N,ODimethylhydroxylamine 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.

Norganylhydroxylamines, , where R is an organyl group, can be reduced to amines :

Oximes such as dimethylglyoxime are also employed as ligands.

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 is a common method to synthesize hydroxylamines. Care must be taken to prevent over-oxidation to a nitrone. Other methods include:

Hydrogenation of an oxime
Amine oxide pyrolysis (the Cope reaction) or rearrangement

Uses

:400px|thumb|left|class=skin-invert-image|Conversion of cyclohexanone to caprolactam involving the [[Beckmann rearrangement.]]

Approximately 95% of hydroxylamine is used in the synthesis of cyclohexanone oxime, a precursor to Nylon 6. The latter can then undergo a ring-opening polymerization to yield Nylon 6.

:400px|thumb|class=skin-invert-image|Synthesis of paracetamol, with a Beckmann Rearrangement as the final step

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 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. 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, and mutation of purified DNA in vitro.

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).

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.

Safety and environmental concerns

Hydroxylamine is a skin irritant but is of low toxicity.

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:

Absent air, pure hydroxylamine requires stronger heating and the detonation does not compete 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 salts accelerate the decomposition of 50% 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.

References

External links

Calorimetric studies of hydroxylamine decomposition
Chemical company BASF info
MSDS
Deadly detonation of hydroxylamine at Concept Sciences facility