Acetaldoxime

[107-29-9]  · C₂H₅NO  · Acetaldoxime  · (MW 59.07) (E)

[5780-37-0] (Z)

[5775-72-4]

(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 imidazoles;⁶ thiazolidines;⁷ precursor for acetonitrile oxide, a useful 1,3-dipole for cycloadditions;⁸ 1,3-dipolar cycloaddition^5,9,10) 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.

Introduction.

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 1}H NMR^11,14 and ¹³C NMR¹⁵ have been used to establish the (E)/(Z) configurations of oximes.

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 gas^8,18 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 7).⁸

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 (eq 10).⁷

1,3-Dipolar Cycloaddition.

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

O-Functionalization.

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

Miscellaneous.

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 double bond.

Related Reagents.