Hydroxylamine

Hydroxylamine is an inorganic compound with the formula NH2OH. The pure material is a white, unstable crystalline, hygroscopic compound. However, hydroxylamine is almost always provided and used as an aqueous solution. It is used to prepare oximes, an important functional group. It is also an intermediate in biological nitrification. The oxidation of NH3 is mediated by the enzyme hydroxylamine oxidoreductase (HAO).

Production
NH2OH can be produced via several routes. The main route is via Raschig synthesis: aqueous ammonium nitrite is reduced by HSO4− and SO2 at 0°C to yield a hydroxylamido-N,N-disulfate anion:
 * NH4NO2 +  2 SO2  +  NH3  +  H2O → 2 NH4+ + N(OH)(OSO2)22&minus;

This anion is then hydrolyzed to give (NH3OH)2SO4:
 * N(OH)(OSO2)22− + H2O → NH(OH)(OSO2)&minus; + HSO4&minus;
 * 2 NH(OH)(OSO2)− + 2 H2O →

Solid NH2OH 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.

Hydroxylammonium salts can then be converted to hydroxylamine by neutralization:
 * (NH3OH)Cl + NaOBu → NH2OH + NaCl + BuOH

Hydroxylamine can also be produced by the reduction of nitrous acid or potassium nitrite with bisulfite:
 * HNO2 +  2 HSO3−  →  N(OH)(OSO2)22−  +  H2O → NH(OH)(OSO2)−  +  HSO4−
 * NH(OH)(OSO2)− + H3O+ (100 °C/1 h) → NH3(OH)+ + HSO4−

Reactions
Hydroxylamine reacts with electrophiles, such as alkylating agents, which can attach to either the oxygen or the nitrogen:
 * R-X +  NH2OH  →  R-ONH2  + HX
 * R-X +  NH2OH  →  R-NHOH  + HX

The reaction of NH2OH with an aldehyde or ketone produces an oxime.
 * R2C=O +  NH2OH∙HCl, NaOH  →  R2C=NOH  +  NaCl  + H2O

This reaction is useful in the purification of ketones and aldehydes. Oximes, e.g., dimethylglyoxime, are also employed as ligands.

NH2OH reacts with chlorosulfonic acid to give hydroxylamine-O-sulfonic acid, a useful reagent for the synthesis of caprolactam.
 * HOSO2Cl +  NH2OH  →  NH2OSO2OH  +  HCl

The hydroxylamine-O-sulfonic acid, which should be stored at 0 °C to prevent decomposition, can be checked by iodometric titration.

Hydroxylamine (NH2OH), or hydroxylamines (R-NHOH) can be reduced to amines.


 * NH2OH (Zn/HCl) → NH3
 * R-NHOH (Zn/HCl) → R-NH2

Hydroxylamine explodes with heat:


 * 4 NH2OH + O2 → 2 N2 + 6 H2O

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. Some non-chemical uses include removal of hair from animal hides and photography developing solutions.

The nitrate salt, hydroxylammonium nitrate, is being researched as a rocket propellant, both in water solution as a monopropellant and in its solid form as a solid propellant.

This has also been used in the past by biologists to introduce random mutations by switching base pairs from A to G, or from C to T. This is to probe functional areas of genes to elucidate what happens if their functions are broken. Nowadays other mutagens are used. 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.

In the semiconductor industry, hydroxylamine is often a component in the "resist stripper" which removes photoresist after lithography.

Safety
Hydroxylamine may explode on heating. The nature of the explosive hazard is not well understood. 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.

Functional group
Substituted derivatives of hydroxylamine are known. If the hydroxyl hydrogen is substituted, this is called an O-hydroxylamine, if one of the amine hydrogens is substituted, this is called an N-hydroxylamine. Smilarly to ordinary amines, one can distinguish primary, secondary and tertiary hydroxylamines, the latter two referring to compounds where two or three hydrogens are substituted, respectively. Examples of compounds containing a hydroxylamine functional group are N-tert-butyl-hydroxylamine or the glycosidic bond in calicheamicin. N,O-Dimethylhydroxylamine is a coupling agent, used to synthesize Weinreb amides.