Methoxyamine
Methoxyamine is the organic compound with the formula CH3ONH2. Also called O-methylhydroxylamine, it a colourless volatile liquid that is soluble in polar organic solvent and in water. It is a derivative of hydroxylamine with the hydroxyl hydrogen replaced by a methyl group. Alternatively, it can be viewed as a derivative of methanol with the hydroxyl hydrogen replaced by an amino group. It is an isomer of N-methylhydroxylamine and aminomethanol. It decomposes in an exothermic reaction (-56 kJ/mol) to methane and azanone unless stored as a hydrochloride salt.
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Names | |
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IUPAC name
Methoxyamine | |
Other names
Methoxylamine; (Aminooxy)methane; O-Methylhydroxylamine | |
Identifiers | |
3D model (JSmol) |
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ChemSpider | |
ECHA InfoCard | 100.000.600 ![]() |
PubChem CID |
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UNII | |
CompTox Dashboard (EPA) |
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Properties | |
CH5NO | |
Molar mass | 47.057 g·mol−1 |
Appearance | Colorless liquid |
Odor | Ammoniacal |
Density | 1.0003 g/mL |
Melting point | 42 °C (108 °F; 315 K) |
Boiling point | 50 °C (122 °F; 323 K) |
Miscible | |
Vapor pressure | 297.5 mmHg at 25°C |
Refractive index (nD) |
1.4164 |
Hazards | |
Safety data sheet | Santa Cruz (HCl) |
NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
Infobox references | |
Synthesis
Methoxyamine is prepared via O-alkylation of hydroxylamine derivatives. For example, it is obtained by O-methylation of acetone oxime followed by hydrolysis of the O-methylated oxime:[1]
- (CH3)2CNOCH3 + H2O → (CH3)2CO + H2NOCH3
The other broad method involves methanolysis of hydroxylamine sulfonates:
- H2NOSO3− + CH3OH → H2NOCH3 + HSO4−
Reactions
Like hydroxylamine, methoxyamine forms oximes upon treatment with ketones and aldehydes.
Methoxyamine is used as a synthon for NH2+. It undergoes deprotonation by methyl lithium to give CH3ONHLi. This N-lithio derivative is attacked by organolithium compounds to give, after hydrolysis, amines:[2]
- H2NOCH3 + CH3Li → LiHNOCH3 + CH4
- LiHNOCH3 + RLi → RNHLi + LiOCH3
- RNHLi + H2O → RNH2 + LiOH
Uses
Methoxyamine is an orally bioavailable small molecule inhibitor with potential adjuvant activity.[3] Methoxyamine covalently binds to apurinic/apyrimidinic (AP) DNA damage sites and inhibits base excision repair (BER), which may result in an increase in DNA strand breaks and apoptosis.[3] This agent may potentiate the anti-tumor activity of alkylating agents.
Examples of drugs incorporating the methoxyamine unit are brasofensine and gemifloxacin.
References
- Review: Houben-Weyl, Methoden der organische Chemie, vol 10.1, p 1186. Patent: Klein, Ulrich; Buschmann, Ernst; Keil, Michael; Goetz, Norbert; Hartmann, Horst "Process for preparing O-substituted hydroxylammonium salts." Ger. Offen. to BASF, (1994), DE 4233333 A1 19940407.
- Bruce J. Kokko, Scott D. Edmondson "O-Methylhydroxylamine" in eEROS, 2008. doi:10.1002/047084289X.rm192m.pub2
- NCI