Hydroxylamine (also known as hydroxyammonia) is an inorganic compound with the chemical formulaTemplate:Chem2. The compound exists as hygroscopic colorless crystals.<ref name="synth">Greenwood and Earnshaw. Chemistry of the Elements. 2nd Edition. Reed Educational and Professional Publishing Ltd. pp. 431–432. 1997.</ref> Hydroxylamine is almost always provided and used as an aqueous solution or more often as one of its salts such as hydroxylammonium sulfate, a water-soluble solid.
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.<ref>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 hydroxylamine or oxyammonia.)</ref> 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).<ref>C. A. Lobry de Bruyn (1891) "Sur l'hydroxylamine libre" (On free hydroxylamine), Recueil des travaux chimiques des Pays-Bas, 10 : 100-112.</ref><ref>L. Crismer (1891) "Préparation de l'hydroxylamine cristallisée" (Preparation of crystalized hydroxylamine), Bulletin de la Société chimique de Paris, series 3, 6 : 793-795.</ref> The coordination complexTemplate:Chem2 (zinc dichloride di(hydroxylamine)), known as Crismer's salt, releases hydroxylamine upon heating.<ref>Template:Cite book</ref>
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. <ref>Template:Cite book</ref>
Production
Hydroxylamine or its salts (salts containing hydroxylammonium cationsTemplate:Chem2) 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 Template:Chem2 can be collected by treatment with liquid ammonia. Ammonium sulfate, Template:Chem2, a side-product insoluble in liquid ammonia, is removed by filtration; the liquid ammonia is evaporated to give the desired product.<ref name="synth" />
The net reaction is:
This reaction can be 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 aqueous acid then restores the original aldehyde or ketone.<ref>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.</ref>
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.<ref>Template:Cite journal</ref>
NTemplate:Nbhorganylhydroxylamines, Template:Chem2, where R is an organyl group, can be reduced to aminesTemplate:Chem2:<ref>Smith, Michael and Jerry March. March's advanced organic chemistry : reactions, mechanisms, and structure. New York. Wiley. p. 1554. 2001.</ref>
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:
Approximately 95% of hydroxylamine is used in the synthesis of cyclohexanone oxime, a precursor to Nylon 6.<ref name=Ullmann/> The treatment of this oxime with acid induces the Beckmann rearrangement to give caprolactam.<ref name="Clayden-2012">Template:Cite book</ref> The latter can then undergo a ring-opening polymerization to yield Nylon 6.<ref name="Pask-2013">Template:Cite journal</ref>
Laboratory 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.
High concentrations of hydroxylamine are used by biologists to introduce mutations by acting as a DNA nucleobase amine-hydroxylating agent.<ref name="Waugh2006">Template:Cite journal</ref> 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.<ref name="Busby1982a">Template:Cite journal</ref> 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.<ref name="Busby1982a" /> 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 effects Ernst Freese noted hydroxylamine was unable to induce reversion mutations of its C:G to T:A transition effect and even considered hydroxylamine to be the most specific mutagen known.<ref name="Hollaender1971">Template:Cite book</ref> 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,<ref name="Hong1971">Template:Cite journal</ref> and mutation of purified DNA in vitro.<ref>Template:Cite web</ref>
Some non-chemical uses include removal of hair from animal hides and photographic developing solutions.<ref name="RubberBible87th"/> 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.<ref>Template:Cite journal</ref> Similarly, Ubiquitin molecules bound to serines or threonines residues are sensitive to hydroxylamine, but those bound to lysine (isopeptide bond) are resistant.<ref>Template:Cite journal</ref>
Hydroxylamine can also be used to highly selectively cleave asparaginyl-glycine peptide bonds in peptides and proteins.<ref>Template:Cite book</ref> 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.<ref name=":0">Template:Cite journal</ref><ref name=":1">Template:Cite book</ref> In air, the combustion is rapid and complete:
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.<ref>MSDS Sigma-Aldrich</ref>
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).
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