Hydroxylamine
Encyclopedia
Hydroxylamine is an inorganic compound
with the formula
NH2OH. The pure material is a white, unstable crystal
line, hygroscopic compound. However, hydroxylamine is almost always provided and used as an aqueous solution. It is used to prepare oxime
s, an important functional group. It is also an intermediate in biological nitrification
. The oxidation of NH3 is mediated by the enzyme
hydroxylamine oxidoreductase (HAO).
is reduced by HSO4− and SO2 at 0 °C to yield a hydroxylamido-N,N-disulfate anion:
This anion is then hydrolyzed to give (NH3OH)2SO4:
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:Cl + NaOBu → NH2OH + NaCl + BuOH
Hydroxylamine can also be produced by the reduction of nitrous acid
or potassium nitrite
with bisulfite
:
The reaction of NH2OH with an aldehyde or ketone produces an oxime
.
This reaction is useful in the purification of ketones and aldehydes. Oximes, e.g., dimethylglyoxime
, are also employed as ligand
s.
NH2OH reacts with chlorosulfonic acid to give hydroxylamine-O-sulfonic acid, a useful reagent for the synthesis of caprolactam
.
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 amine
s.
Hydroxylamine explodes with heat:
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 G to A, 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.
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.
in calicheamicin
. N,O-Dimethylhydroxylamine
is a coupling agent, used to synthesize Weinreb amides.
Inorganic compound
Inorganic compounds have traditionally been considered to be of inanimate, non-biological origin. In contrast, organic compounds have an explicit biological origin. However, over the past century, the classification of inorganic vs organic compounds has become less important to scientists,...
with the formula
Chemical formula
A chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....
NH2OH. The pure material is a white, unstable crystal
Crystal
A crystal or crystalline solid is a solid material whose constituent atoms, molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions. The scientific study of crystals and crystal formation is known as crystallography...
line, hygroscopic compound. However, hydroxylamine is almost always provided and used as an aqueous solution. It is used to prepare oxime
Oxime
An oxime is a chemical compound belonging to the imines, with the general formula R1R2C=NOH, where R1 is an organic side chain and R2 may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substituted oximes form a closely related family of compounds...
s, an important functional group. It is also an intermediate in biological nitrification
Nitrification
Nitrification is the biological oxidation of ammonia with oxygen into nitrite followed by the oxidation of these nitrites into nitrates. Degradation of ammonia to nitrite is usually the rate limiting step of nitrification. Nitrification is an important step in the nitrogen cycle in soil...
. The oxidation of NH3 is mediated by the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
hydroxylamine oxidoreductase (HAO).
Production
NH2OH can be produced via several routes. The main route is via Raschig synthesis: aqueous ammonium nitriteAmmonium nitrite
Ammonium nitrite, NH4NO2, is the ammonia salt of nitrous acid. It is used as a rodenticide, microbiocide and agricultural pesticide, and is acutely toxic to both humans and aquatic organisms.-Preparation:...
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−
This anion is then hydrolyzed to give (NH3OH)2SO4:
- N(OH)(OSO2)22− + H2O → NH(OH)(OSO2)− + HSO4−
- 2 NH(OH)(OSO2)− + 2 H2O →
Solid NH2OH can be collected by treatment with liquid ammonia. Ammonium sulfate
Ammonium sulfate
Ammonium sulfate , 2SO4, is an inorganic salt with a number of commercial uses. The most common use is as a soil fertilizer. It contains 21% nitrogen as ammonium cations, and 24% sulfur as sulfate anions...
, , a side-product insoluble in liquid ammonia, is removed by filtration; the liquid ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
is evaporated to give the desired product.
Hydroxylammonium salts can then be converted to hydroxylamine by neutralization:Cl + NaOBu → NH2OH + NaCl + BuOH
Hydroxylamine can also be produced by the reduction of nitrous acid
Nitrous acid
Nitrous acid is a weak and monobasic acid known only in solution and in the form of nitrite salts.Nitrous acid is used to make diazides from amines; this occurs by nucleophilic attack of the amine onto the nitrite, reprotonation by the surrounding solvent, and double-elimination of water...
or potassium nitrite
Potassium nitrite
Potassium nitrite is a salt with chemical formula 2.It is a strong oxidizer and may accelerate the combustion of other materials. Like other nitrite salts such as sodium nitrite, potassium nitrite is toxic if swallowed, and laboratory tests suggest that it may be mutagenic or teratogenic...
with bisulfite
Bisulfite
Bisulfite ion is the ion HSO3−. Salts containing the HSO3− ion are termed bisulfites also known as sulfite lyes...
:
- 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
Oxime
An oxime is a chemical compound belonging to the imines, with the general formula R1R2C=NOH, where R1 is an organic side chain and R2 may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substituted oximes form a closely related family of compounds...
.
- R2C=O + NH2OH∙HCl , NaOH → R2C=NOH + NaCl + H2O
This reaction is useful in the purification of ketones and aldehydes. Oximes, e.g., dimethylglyoxime
Dimethylglyoxime
Dimethylglyoxime is a chemical compound described by the formula CH3CCCH3. This colourless solid is the dioxime derivative of the diketone diacetyl . DmgH2 is used in the analysis of palladium or nickel. Its coordination complexes are of theoretical interest as models for enzymes and as catalysts...
, are also employed as ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
s.
NH2OH reacts with chlorosulfonic acid to give hydroxylamine-O-sulfonic acid, a useful reagent for the synthesis of caprolactam
Caprolactam
Caprolactam is an organic compound with the formula 5CNH. This colourless solid is a lactam or a cyclic amide of caproic acid. Approximately 2 billion kilograms are produced annually...
.
- 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 amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
s.
- 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
Hydroxylammonium nitrate
Hydroxylammonium nitrate or hydroxylamine nitrate is an energetic chemical with the chemical formula NH3OHNO3. It is the salt of hydroxylamine and nitric acid. It is related to ammonium nitrate, but has a higher oxygen content...
, is being researched as a rocket propellant, both in water solution as a monopropellant
Monopropellant
Monopropellants are propellants composed of chemicals or mixtures of chemicals which can be stored in a single container with some degree of safety. While stable under defined storage conditions, they react very rapidly under certain other conditions to produce a large volume of energetic gases...
and in its solid form as a solid propellant
Solid rocket
A solid rocket or a solid-fuel rocket is a rocket engine that uses solid propellants . The earliest rockets were solid-fuel rockets powered by gunpowder; they were used by the Chinese in warfare as early as the 13th century and later by the Mongols, Arabs, and Indians.All rockets used some form of...
.
This has also been used in the past by biologists to introduce random mutations by switching base pairs from G to A, 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
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
-glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
peptide bonds in peptides and proteins. It also bonds to and permanently disables (poisons) heme-containing enzymes
Hemoprotein
A hemeprotein , or heme protein, is a metalloprotein containing a heme prosthetic group- an organic compound that allows a protein to carry out a function that it cannot do alone....
. It is used as an irreversible inhibitor of the oxygen-evolving complex
Oxygen evolving complex
The oxygen-evolving complex, also known as the water-splitting complex, is a water-oxidizing enzyme involved in the photooxidation of water during the light reactions of photosynthesis. Based on a widely accepted theory from 1970 by Kok, the complex can exist in 5 states: S0 to S4. Photons trapped...
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 ironIron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
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 bondGlycosidic bond
In chemistry, a glycosidic bond is a type of covalent bond that joins a carbohydrate molecule to another group, which may or may not be another carbohydrate....
in calicheamicin
Calicheamicin
The calicheamicins are a class of enediyne antibiotics derived from the bacterium Micromonospora echinospora, with calicheamicin γ1 being the most notable. It was isolated originally from a rock collected by a Scripps Research Institute chemist while hiking in Waco, Texas. It is extremely toxic to...
. N,O-Dimethylhydroxylamine
N,O-dimethylhydroxylamine
N,O-Dimethylhydroxylamine is used in amide coupling reactions to form Weinreb amides for use in the Weinreb ketone synthesis.It was identified as a microbial degradation product of the herbicide linuron formed in the presence of extracts of Bacillus sphaericus ATCC 12123 by characterization of its...
is a coupling agent, used to synthesize Weinreb amides.
Further reading
- Hydroxylamine
- Walters, Michael A. and Andrew B. Hoem. "Hydroxylamine." e-Encyclopedia of Reagents for Organic Synthesis. 2001.
- Schupf Computational Chemistry Lab
- 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).