O-Benzylhydroxylamine Hydrochloride1

(base)

[622-33-3]  · C7H9NO  · O-Benzylhydroxylamine  · (MW 123.15) (.HCl)

[2687-43-6]  · C7H10ClNO  · O-Benzylhydroxylamine Hydrochloride  · (MW 159.62)

(reagent for the preparation of N-hydroxyamides2 (including N-hydroxy peptides3 and N-hydroxy b-lactams4) and hydroxamic acids;5 derivatizing agent for ketones,6-8 aldehydes,6 and carbohydrates9)

Alternate Names: O-phenylmethylhydroxylamine hydrochloride; benzyloxyamine hydrochloride; benzyloxyammonium chloride.

Physical Data: white flakes, mp 234-238 °C (subl); hygroscopic.

Solubility: sol H2O, pyridine; slightly sol alcohol; insol ether.

Analysis of Reagent Purity: 1H NMR (DMSO-d6 + CDCl3) d 5.17 (s, 2H, CH2), 7.42 (s, 5H, C6H5), 11 (br, ex NH2).

Preparative Methods: the free base O-benzylhydroxylamine, a liquid of bp 115-119 °C/30 mmHg, is easily prepared from the commercially available hydrochloride salt.10 For many reactions, however, it is preferable to generate the free base in situ from the salt.

Handling, Storage, and Precautions: store in a cool dry place to preclude contact with moisture and oxygen; may be harmful by inhalation, ingestion, or skin absorption; avoid contact with the eyes.

N-Hydroxyamides and Hydroxamic Acids.

The ease with which an O-benzyl moiety can be converted, often through catalytic hydrogenation, to the analogous alcohol allows this reagent to be used as an O-protected equivalent of hydroxylamine. For example, it is especially suited for the preparation of N-hydroxyamides (eq 1)2 (including N-hydroxy peptides3 and N-hydroxy b-lactams),1,4,11 hydroxamic acids (eq 2),5 and N-hydroxyimides (eq 3).12

Other functional groups prepared by similar methodology include N-alkyl hydroxyureas, N-alkyl-N-hydroxycarbamates and N-alkylhydroxylamines.13

O-Benzyloximes.1

The reagent is used extensively as a derivatizing agent for preparation of O-benzyloximes of ketones,6-8 aldehydes,6 and carbohydrates (eq 4).9 Usually both syn (Z) and anti (E) isomers are formed.

Reaction with O-alkyl thiocarboxylates affords alkyl N-benzyloxycarboximidates,14 while enol esters may be converted in the presence of saturated ester functions to their respective ketoximes (eq 5).15


1. FF 1981 9, 504; 1986 12, 272; 1989 14, 28; 1992 16, 22.
2. Katoh, A.; Akiyama, M. JCS(P1) 1991, 1839 and references cited therein.
3. Akiyama, M.; Iesaki, K.; Katoh, A.; Shimizu, K. JCS(P1) 1986, 851 and references cited therein.
4. Ikeda, K.; Achiwa, K.; Sekiya, M. CPB 1989, 37, 1179 and references cited therein.
5. Karunaratne, V.; Hoveyda, H. R.; Orvig, C. TL 1992, 33, 1827 and references cited therein.
6. Ollett, D. G.; Attygalle, A. B.; Morgan, E. D. J. Chromatogr. 1986, 367, 207 and references cited therein.
7. Bodor, A.; Fey, L.; Breazu, D. RRC 1980, 25, 1367.
8. Devaux, P. G.; Horning, M. G.; Hill, R. M.; Horning, E. C. Anal. Biochem. 1971, 41, 70.
9. Andrews, M. A. Carbohydr. Res. 1989, 194, 1 and references cited therein.
10. Welch, J. T.; Seper, K. W. JOC 1988, 53, 2991.
11. Miller, M. J.; Mattingly, P. J.; Morrison, M. A.; Kerwin, J. F., Jr. JACS 1980, 102, 7026.
12. Groutas, W. C.; Brubaker, M. J.; Stanga, M. A.; Castrisos, J. C.; Crowley, J. P.; Schatz, E. J. JMC 1989, 32, 1607. N-Benzyloxyisoimides may also be formed: Hearn, M. T. W.; Ward, A. D. AJC 1977, 30, 2031.
13. Sulsky, R.; Demers, J. P. TL 1989, 30, 31.
14. Brion, J.-D.; Reynaud, P.; Kirkiacharian, S. S 1983, 220.
15. Lichtenthaler, F. W.; Jarglis, P. TL 1980, 21, 1425.

David C. Rees & Niall M. Hamilton

Organon Laboratories, Newhouse, UK



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