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.
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.[4]
The net reaction is:
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.[14]
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.[16][17] 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:
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 bondincalicheamicin. 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.[19]
N-organylhydroxylamines, R−NH−OH, where R is an organyl group, can be reduced to aminesR−NH2:[20]
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:
Approximately 95% of hydroxylamine is used in the synthesis of cyclohexanone oxime, a precursor to Nylon 6.[10] The treatment of this oxime with acid induces the Beckmann rearrangement to give caprolactam (3).[21] The latter can then undergo a ring-opening polymerization to yield Nylon 6.[22]
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.[23] 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.[24] 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.[24] 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.[25] 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,[26] & mutation of purified DNA in vitro.[27]
This route also involves the Beckmann Rearrangement, like the conversion from cyclohexanone to caprolactam.
Some non-chemical uses include removal of hair from animal hides and photographic developing solutions.[2] 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.[28] Similarly, Ubiquitin molecules bound to serines or threonines residues are sensitive to hydroxylamine, but those bound to lysine (isopeptide bond) are resistant.[29]
Hydroxylamine can also be used to highly selectively cleave asparaginyl-glycine peptide bonds in peptides and proteins.[32] 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.[16][17] At least two factories dealing in hydroxylamine have been destroyed since 1999 with loss of life.[33] It is known, however, that ferrous and ferric iron salts accelerate the decomposition of 50% NH2OH solutions.[34] 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.[35]
^W. C. Lossen (1865) "Ueber das Hydroxylamine" (On hydroxylamine), Zeitschrift für Chemie, 8 : 551-553. From p. 551: "Ich schlage vor, dieselbe Hydroxylamin oder Oxyammoniak zu nennen." (I propose to call it hydroxylamineoroxyammonia.)
^C. A. Lobry de Bruyn (1891) "Sur l'hydroxylamine libre" (On free hydroxylamine), Recueil des travaux chimiques des Pays-Bas, 10 : 100-112.
^Walker, John E.; Howell, David M. (1967). "Dichlorobis(hydroxylamine)zinc(II) (Crismer's Salt)". Inorganic Syntheses. Vol. 9. pp. 2–3. doi:10.1002/9780470132401.ch2. ISBN9780470132401.
^James Hale, Arthur (1919). The Manufacture of Chemicals by Electrolysis (1st ed.). New York: D. Van Nostrand Co. p. 32. Retrieved 5 June 2014. manufacture of chemicals by electrolysis hydroxylamine 32.
^Ralph Lloyd Shriner, Reynold C. Fuson, and Daniel Y. Curtin, The Systematic Identification of Organic Compounds: A Laboratory Manual, 5th ed. (New York: Wiley, 1964), chapter 6.
^Kirby, AJ; Davies, JE; Fox, DJ; Hodgson, DR; Goeta, AE; Lima, MF; Priebe, JP; Santaballa, JA; Nome, F (28 February 2010). "Ammonia oxide makes up some 20% of an aqueous solution of hydroxylamine". Chemical Communications. 46 (8): 1302–4. doi:10.1039/b923742a. PMID20449284.
^Hamer, Jan; Macaluso, Anthony (1964) [29 Feb 1964]. "Nitrones". Chemical Reviews. 64 (4): 476. doi:10.1021/cr60230a006.
^Smith, Michael and Jerry March. March's advanced organic chemistry : reactions, mechanisms, and structure. New York. Wiley. p. 1554. 2001.
^Clayden, Jonathan; Greeves, Nick; Warren, Stuart (2012). Organic chemistry (2nd ed.). Oxford University Press. p. 958. ISBN978-0-19-927029-3.
^Waugh, Robbie; Leader, David J.; McCallum, Nicola; Caldwell, David (2006). "Harvesting the potential of induced biological diversity". Trends in Plant Science. 11 (2). Elsevier BV: 71–79. doi:10.1016/j.tplants.2005.12.007. ISSN1360-1385. PMID16406304.
^ abBusby, Stephen; Irani, Meher; de Crombrugghe, Benoít (1982). "Isolation of mutant promoters in the Escherichia coli galactose operon using local mutagenesis on cloned DNA fragments". Journal of Molecular Biology. 154 (2). Elsevier BV: 197–209. doi:10.1016/0022-2836(82)90060-2. ISSN0022-2836. PMID7042980.
^Hollaender, Alexander (1971). Chemical Mutagens : Principles and Methods for Their Detection Volume 1. Boston, MA: Springer US. p. 41. ISBN978-1-4615-8968-6. OCLC851813793.
^Arciero, David M.; Hooper, Alan B.; Cai, Mengli; Timkovich, Russell (1993-09-01). "Evidence for the structure of the active site heme P460 in hydroxylamine oxidoreductase of Nitrosomonas". Biochemistry. 32 (36): 9370–9378. doi:10.1021/bi00087a016. ISSN0006-2960. PMID8369308.
^Bornstein, Paul; Balian, Gary (1977). "Cleavage at AsnGly bonds with hydroxylamine". Enzyme Structure Part E. Methods in Enzymology. Vol. 47(Enzyme Struct., Part E). pp. 132–45. doi:10.1016/0076-6879(77)47016-2. ISBN978-0-12-181947-7. PMID927171.{{cite book}}: CS1 maint: multiple names: authors list (link)
^Cisneros, L. O.; Rogers, W. J.; Mannan, M. S.; Li, X.; Koseki, H. (2003). "Effect of Iron Ion in the Thermal Decomposition of 50 mass% Hydroxylamine/Water Solutions". J. Chem. Eng. Data. 48 (5): 1164–1169. doi:10.1021/je030121p.
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).
