Hydroxylamine was first prepared as hydroxylamine hydrochloride in 1865 by the German chemist Wilhelm Clemens Lossen (1838-1906); he reacted tin and hydrochloric acid in the presence of ethyl nitrate. 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).
NH2OH can be produced via several routes. The main route is via the Raschig process: aqueous ammonium nitrite is reduced by HSO3− and SO2 at 0 °C to yield a hydroxylamido-N,N-disulfonate anion:
Solid NH2OH can be collected by treatment with liquid ammonia. Ammonium sulfate, (NH 4) 2SO 4, a side-product insoluble in liquid ammonia, is removed by filtration; the liquid ammonia is evaporated to give the desired product.
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: 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.
The hydroxylamine-O-sulfonic acid, which should be stored at 0 °C to prevent decomposition, can be checked by iodometric titration.[clarification needed]
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
The high reactivity comes in part from the partial isomerisation of the NH2OH structure to ammonia oxide (also known as azane oxide), with structure NH3+O−.
N-hydroxylamine 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. In general N-hydroxylamines are the more common. Similarly 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.
The most common method for the synthesis of substituted hydroxylamines is the oxidation of an amine with benzoyl peroxide. Some care must be taken to prevent over-oxidation to a nitrone. Other methods include:
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.
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. In the semiconductor industry, hydroxylamine is often a component in the "resist stripper", which removes photoresist after lithography.
Safety and environmental concerns
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.
^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.
^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.)
^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.
^Smith, Michael and Jerry March. March's advanced organic chemistry : reactions, mechanisms, and structure. New York. Wiley. p. 1554. 2001.
^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 (Cambridge, England). 46 (8): 1302–4. doi:10.1039/b923742a. PMID20449284.
^Clayden, Jonathan; Greeves, Nick; Warren, Stuart (2012). Organic chemistry (2nd ed.). Oxford University Press. p. 958. ISBN978-0-19-927029-3.
^Nuyken, Oskar; Pask, Stephen (25 April 2013). "Ring-Opening Polymerization—An Introductory Review". Polymers. 5 (2): 361–403. doi:10.3390/polym5020361.
^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.