[107-29-9] · C2H5NO
· Acetaldoxime · (MW 59.07)
(acetaldehyde equivalent; acetylation of arenes via diazonium
salts;1 synthesis of aldoximes;2
rearrangement into acetamide;3,4
synthesis of heterocycles, e.g. 2-isoxazolines,5
precursor for acetonitrile oxide, a useful 1,3-dipole for
cycloadditions;8 1,3-dipolar cycloaddition5,9,10)
Alternate Name: acetaldehyde oxime.
Physical Data: (E) and (Z) mixture
bp 114-115 °C; mp 47 °C.
Solubility: sol most organic solvents, e.g. THF,
CHCl3, benzene, xylene,
diethyl ether, 1,2-dichloroethane.
Form Supplied in: widely available commercially.
Commercial samples, which had been refrigerated for several
months, showed (Z):(E) ratios of 10-20:1.2
Analysis of Reagent Purity: 1H
NMR. Preparative Method: reaction of freshly
distilled Acetaldehyde with Hydroxylamine
hydrochloride in the presence of a base (eq 1).3,11
Handling, Storage, and Precautions: the oxime
is preferably freshly prepared. The freshly prepared solid
compound decomposes slowly on standing. Use in a fume hood.
Unsymmetrical oximes, like acetaldoxime, occur as a mixture
of (E) and (Z) isomers across the carbon-nitrogen
double bond (often referred to as syn and anti
isomers, respectively). The position of the equilibrium changes
with the conditions. A frequently reported equilibrium is
situated around 40% (E) in the pure state and 46% (E)
in aqueous acid,12 but the position
of the equilibrium is independent of the temperature and the
concentration of the acid.13
(Z)-Acetaldoxime can be prepared by slow crystallization
of a freshly distilled mixture of (E)/(Z) isomers.13
and 13C NMR15 have
been used to establish the (E)/(Z) configurations
Acetylation of Arenes via Diazonium Salts.
The reaction of acetaldoxime with aromatic diazonium salts
affords oximes of acetophenones, which are hydrolyzed in acid
medium to give aryl methyl ketones (eq 2).1
a-Alkylation of Acetaldoxime.
Deprotonation of acetaldoxime with 2 equiv of n-Butyllithium
at -78 °C generates the dianion which reacts with
Benzyl Bromide or 1-iodopropane to give excellent
yields of a-alkylated (Z)-oximes
(eqs 3 and 4).2 a,a-Dialkylation
by further alkylation in similar way has been achieved (eq
4).2 It is generally known that
ketone oximes can be deprotonated and alkylated regiospecifically
syn to the oxime hydroxy group.16,17
It is essential to perform the deprotonation and alkylation
at -78 °C as otherwise no a-alkylated
oximes are isolated, the major byproducts being nitriles.16
Rearrangement into Acetamide.
Heating of acetaldoxime in xylene in the presence of 0.2
mol % Nickel(II) Acetate3
or silica gel4 as catalyst caused
isomerization into acetamide (eq 5).
Synthesis of Heterocycles.
Chlorination of acetaldoxime with N-Chlorosuccinimide5
or Chlorine gas8,18
in chloroform affords acetohydroxamic acid chloride, which
suffers dehydrochlorination with Triethylamine
to give Acetonitrile N-Oxide. The latter
1,3-dipole undergoes 1,3-dipolar cycloaddition to alkenes
giving 2-isoxazolines in a one-pot procedure (eq 6).5
This reaction is also suitable for the construction of more
complex molecules such as the conversion of a 6-ethylideneolivanic
acid derivative into the corresponding spiroisoxazoline (eq
The cyclocondensation of acetaldoxime with biacetyl monooxime
yields 1-hydroxy-2,4,5-trimethylimidazole 3-oxide,19
originally believed to be 4-hydroxy-3,4,6-trimethyl-1,2,5-oxadiazine.20
The reaction is preferably performed in liquid sulfur dioxide
in the presence of catalytic amounts of hydrogen chloride
(eq 8),6 and works as well with
other a-oximino ketones (eq 9).21
Upon reaction of acetaldehyde oxime with 2,2-dimethylthiirane,
ring expansion to 3-hydroxy-2,5,5-trimethylthiazolidine occurs
Acetaldoxime cycloadds very slowly to Methyl Acrylate
and Acrylonitrile, giving 2:1 adducts as mixtures
of regioisomers and stereoisomers (eq 11).10
The palladium-catalyzed cycloaddition of the reagent to 1,3-butadiene
yields an isoxazolidine via the intermediacy of a nitrone
which undergoes 1,3-dipolar cycloaddition (eq 12).9
Addition Reactions Across the Carbon-Nitrogen Double Bond.
Cyanotrimethylsilane adds to acetaldoxime to
give the cyanated adduct (eq 13),22
while allylboronates behave similarly to afford the adduct,
which disproportionates and can subsequently be cleaved to
the alkenic hydroxylamine (eq 14).23
a-Bromo aldoximes are difficult
to obtain. Direct a-bromination
of aldoximes with a variety of brominating agents was not
successful, but smooth bromination of the O-silylated
derivative was accomplished (eq 15).24
Functionalization at the oxygen atom has been accomplished
with organogermanium25 and organoarsenium26
reagents (eq 16), while O-alkylation has been performed
with the sodium salt of acetaldoxime and an a-bromo
ketone.27 Lithium Aluminum
Hydride readily effected hydrogenolysis of the N-O
bond to afford the corresponding 1,2-diol (eq 17).27
Thermal decomposition of alkyl peresters or peroxides in
H-donor solvents, e.g. cycloalkanes or ethers, in the presence
of acetaldoxime afforded C-1 alkylated products.28
The reaction involves carbon radical addition to the carbon-nitrogen
Acetaldehyde; Acetaldehyde N-t-Butylimine;
Acetonitrile N-Oxide; Formaldoxime;
- 1. Beech, W. F. JCS 1954,
- 2. Gawley, R. E.; Nagy, T. TL 1984,
- 3. Field, L.; Hughmark, P. B.; Shumaker,
S. H.; Marshall, W. S. JACS 1961, 83,
- 4. Chattopadhyaya, J. B.; Rama Rao, A.
V. T 1974, 30, 2899.
- 5. Larsen, K. E.; Torssell, K. B. G. T
1984, 40, 2985.
- 6. Rogic, M. M.; Tetenbaum, M. T.; Swerdloff,
M. D. JOC 1977, 42, 2748.
- 7. Sokolov, V. V.; Ogloblin, K. A.; Potekhin,
A. A. KGS 1980, 1569 (CA 1981,
94, 121 393).
- 8. Corbett, D. F. JCS(P1) 1986,
- 9. Baker, R.; Nobbs, M. S. TL 1977,
- 10. Grigg, R.; Jordan, M.; Tangthongkum,
A.; Einstein, F. W. B.; Jones, T. JCS(P1) 1984,
- 11. Karabatsos, G. J.; Taller, R. A.
T 1968, 24, 3347.
- 12. Somin, I. N.; Gindin, V. A. ZOR
1974, 10, 2473.
- 13. Holloway, C. E.; Vuik, C. P. J. TL
- 14. Lichter, R. L.; Dorman, D. E.; Wasylishen,
R. JACS 1974, 96, 930.
- 15. Hawkes, G. E.; Herwig, K.; Roberts,
J. D. JOC 1974, 39, 1017.
- 16. Kofron, W. G.; Yeh, M. K. JOC
1976, 41, 439.
- 17. Jung, M. E.; Blair, P. A.; Lowe,
J. A. TL 1976, 1439.
- 18. Mukerji, S. K.; Sharma, K. K.; Torssell,
K. B. G. T 1983, 39, 2231.
- 19. Wright, J. B. JOC 1964,
- 20. Diels, O.; Van der Leeden, R. CB
1905, 38, 3363.
- 21. Ertel, H.; Heubach, G. LA
- 22. (a) Nagai, Y.; Ojima, I.; Inaba,
S. Jpn. Patent 76 125 218, 1975/76 (CA
1977, 86, 140 239). (b) Ojima, I.; Inaba,
S.; Nakatsugawa, K.; Nagai, Y. CL 1975, 331.
- 23. Hoffmann, R. W.; Eichler, G.; Endesfelder,
A. LA 1983, 2000.
- 24. Hassner, A.; Murthy, K. TL
1987, 28, 683.
- 25. Singh, A.; Rai, A. K.; Mehrotra,
R. C. JOM 1973, 57, 301.
- 26. Kaufmann, J.; Kober, F. JOM
1974, 71, 49.
- 27. Gravestock, M. B.; Morton, D. R.;
Boots, S. G.; Johnson, W. S. JACS 1980, 102,
- 28. Citterio, A.; Filippini, L. S
Norbert De Kimpe
University of Gent, Belgium