Hydroxylamine and its N-substituted derivatives are pyramidal at nitrogen, with bond angles very similar to those of amines. The conformation of hydroxylamine places the NOH anti to the lone pair on nitrogen, seeming to minimize lone pair-lone pair interactions. [7]
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.
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.[12]
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.[15]
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.[8] The treatment of this oxime with acid induces the Beckmann rearrangement to give caprolactam.[18] The latter can then undergo a ring-opening polymerization to yield Nylon 6.[19]
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.[20] 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.[21] 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.[21] 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 and even considered hydroxylamine to be the most specific mutagen known.[22] 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,[23] and mutation of purified DNA in vitro.[24]
Some non-chemical uses include removal of hair from animal hides and photographic developing solutions.[25] 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.[26] Similarly, Ubiquitin molecules bound to serines or threonines residues are sensitive to hydroxylamine, but those bound to lysine (isopeptide bond) are resistant.[27]
Hydroxylamine can also be used to highly selectively cleave asparaginyl-glycine peptide bonds in peptides and proteins.[30] 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.[31][32] In air, the combustion is rapid and complete:
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% Template:Chem2 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]
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).
↑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.)
↑C. A. Lobry de Bruyn (1891) "Sur l'hydroxylamine libre" (On free hydroxylamine), Recueil des travaux chimiques des Pays-Bas, 10 : 100-112.
↑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.
.png){kind=link}
