Copper(II) Acetate1


[142-71-2]  · C4H6CuO4  · Copper(II) Acetate  · (MW 181.64)

(oxidizes carbanions,2 radicals3 and hydrocarbons;4 for oxidative coupling and solvolytic cleavage of Si-C,5 Bi-C, Pb-C, and Sb-C bonds; rapid radical scavenger; catalyst for cyclopropanation of alkenes with diazo esters;6 Lewis acid catalyst)

Alternate Name: cupric acetate.

Physical Data: blue crystals, mp 130-140 °C (dec); d 1.92-1.94 g cm-3.7

Solubility: sol H2O (6.79 g/100 mL, 25 °C); sol AcOH, pyridine; insol ether.

Form Supplied in: widely available; the anhydrous salt can be prepared from the usually available monohydrate Cu(OAc)2.H2O [6046-93-1] by heating to 90 °C until constant weight7,8 or by refluxing Cu(OAc)2.H2O in acetic anhydride and washing the insoluble product with Et2O.9

Analysis of Reagent Purity: iodometric titration;10 atomic absorption spectroscopy.11

Purification: recrystallize (as monohydrate) from warm dil HOAc.57

Handling, Storage, and Precautions: must be stored in the absence of moisture; is decomposed on heating to hydrogen and CuIOAc.7 Irritating to skin, eyes, and respiratory system. May be dissolved in a combustible solvent for incineration.

Oxidation of Carbanions.

Oxidative coupling of terminal alkynes to diynes (eq 1) with Cu(OAc)2 and Pyridine can be carried out in MeOH or in benzene/ether.2 The reaction requires the presence of copper(I) salt; the rate-determining step corresponds to the formation of the CuI acetylide.12

While a-sulfonyl lithiated carbanions are oxidatively coupled with Copper(II) Trifluoromethanesulfonate (eq 2), Cu(OAc)2 oxidizes them to the corresponding (E)-a,b-unsaturated sulfones (eq 3).13

Other carbanions can be coupled oxidatively by Cu(OAc)2, as shown in the synthesis of b-lactams (eq 4).14

In the presence of 1,4-Diazabicyclo[2.2.2]octane in DMF, the complex of Cu(OAc)2 and 2,2-bipyridyl catalyzes the oxygenation of a-branched aldehydes with O2 to ketones.15

Carbon-Hydrogen Bond Oxidations.

Ortho hydroxylation of phenols with O2 is catalyzed by a complex of Cu(OAc)2 and Morpholine (soluble in EtOH).16 In the absence of O2, ortho acetoxylation of phenols can be induced with equimolar amounts of Cu(OAc)2 in AcOH (eq 5).17

Allylic hydrogens are replaced by acyloxy groups by reaction of peroxy esters in the presence of catalytic amounts of copper salts, including Cu(OAc)2.18 The reaction probably proceeds via the formation of an allylic radical, which reacts quickly with CuII to form a CuIII intermediate that generates the most substituted alkene, probably via a pericyclic transition state (eq 6).19 Allylic oxidation can be enantioselective when performed in AcOH and Pivalic Acid in the presence of Cu(OAc)2 and an L-amino acid.20

Allylic oxidation of cyclohexene and related alkenes can be achieved with catalytic amounts of Palladium(II) Acetate, Cu(OAc)2, hydroquinone, and O2 as oxidant in AcOH, leading to allylic acetates.21 Methyl glyoxylate adducts of N-Boc-protected allylic amines cyclize, in the presence of catalytic Pd(OAc)2 and an excess of Cu(OAc)2 in DMSO at 70 °C, to 5-(1-alkenyl)-2-(methoxycarbonyl)oxazolidines (eq 7).22

Methyl substituted benzene derivatives are oxidized in boiling AcOH to the corresponding benzyl acetates (eq 8) with sodium, potassium, or Ammonium Peroxydisulfate, Cu(OAc)2.H2O, and NaOAc.4 The peroxydisulfate radical is responsible for the primary oxidation, whereas Cu(OAc)2 prevents dimerization of the intermediate benzylic radical by oxidizing it to benzyl acetate. The benzylic acetoxylation of alkyl aromatics can also be carried out with O2 using Pd(OAc)2 and Cu(OAc)2 as catalysts.23

Cycloalkanes are transformed into the corresponding cycloalkenes by treatment with t-Butyl Hydroperoxide in pyridine/AcOH solution containing Cu(OAc)2.H2O. When FeIII salts are used instead of Cu(OAc)2.H2O, the major product is the corresponding cycloalkanone.24 Cyclohexanone is the main product of cyclohexane oxidation with H2O2, Cu(OAc)2.H2O in pyridine, and AcOH (GoCHAgg system).25 Cu(OAc)2 also catalyzes the oxidation of secondary alcohols by Lead(IV) Acetate.26

Carbon-Metal Bond Oxidations.

In MeOH and under O2 atmosphere, a catalytic amount of Cu(OAc)2 promotes the cleavage of the Si-C bond of (E)-alkenylpentafluorosilicates to give alkenyl ethers (eq 9). The reaction is highly stereoselective and leads to the (E)-enol ethers. In the presence of H2O the corresponding aldehydes are obtained.5

In the presence of Cu(OAc)2, 1,4-additions of alkylpentafluorosilicates to a,b-unsaturated ketones take place on heating (eq 10).5 This reaction proceeds probably by initial one-electron oxidation with formation of an alkyl radical (eq 11), which then adds to the enone.

The monophenylation of 1,n-diols with Triphenylbismuth Diacetate27 is greatly accelerated by catalytic amounts of Cu(OAc)2.28 This reaction can be enantioselective in the presence of optically active pyridinyloxazoline ligands as cocatalysts (eq 12).29 Reaction of alcohols (ROH) with Triphenylbismuthine and Cu(OAc)2 gives the corresponding phenyl ethers (PhOR) and benzene.30 The treatment of Ph5Sb with a catalytic amount of Cu(OAc)2 in toluene at 20 °C gave 100% yields of Ph3Sb, Ph-Ph, and PhH.31 Cu(OAc)2 catalyzes the arylation of amines by diaryliodonium salts,32 aryl halides,33 Ph3Bi(OCOCF3)2,34 and aryllead triacetates.35

Fast Radical Scavenging and Oxidation.

Rates of oxidative decarboxylation by Pb(OAc)4 of primary and secondary carboxylic acids to alkenes36 are enhanced in the presence of catalytic amounts of Cu(OAc)2 or Cu(OAc)2.H2O. This effect is attributed to the fact that the rate of one-electron-transfer oxidation of alkyl radicals by CuII salts (eq 13) approaches a diffusion-controlled rate.3 Oxidative decarboxylation of carboxylic acids can also be carried out with (Diacetoxyiodo)benzene in the presence of a catalytic amount of anhydrous Cu(OAc)2.37

The case of radical oxidation with Cu(OAc)2 has been exploited by Schreiber38 in the fragmentation of a-alkoxyhydroperoxides, as in eq 14.38b

In an electrochemical system containing Manganese(III) Acetate, acetic acid is added to butadiene to generate an allylic radical intermediate that is oxidized with Cu(OAc)2.H2O to the corresponding allylic cation, leading to g-vinyl-g-butyrolactone (eq 15),39 a precursor in the industrial synthesis of sorbic acid.

b-Oxoesters are oxidized with Mn(OAc)3 to the corresponding radicals that can add intermolecularly40 or intramolecularly (eq 16)41 to generate alkyl radicals. In the presence of Cu(OAc)2 the latter are rapidly quenched and oxidized to give alkenes. Radical arylation with alkyl iodides can be induced with Dibenzoyl Peroxide; the yield of the reaction can be improved using a catalytic amount of Cu(OAc)2.H2O,42 which minimizes hydrogen abstraction by the intermediate radical but introduces a competitive electron-transfer oxidation of the intermediate radical. The oxidative addition of disulfides to alkenes (Trost hydroxysulfenylation43) can be promoted by catalytic amounts of Cu(OAc)2.44

Reoxidant in Palladium-Catalyzed Reactions.

Cu(OAc)2 has been used as a reoxidant in the Wacker oxidation (CH2=CH2 + O2 -> CH3CHO)45 and in the Pd(OAc)2-catalyzed alkenylation of aromatic compounds with alkenes46 (eq 17).47 Pd(OAc)2 and Cu(OAc)2 are effective catalysts for the reactions of nitrosobenzenes with carbon monoxide, dioxygen, and alcohols that give the corresponding N-alkylcarbamates.48

Enantioselective Cyclopropanation.

Cu(OAc)2 has been used as procatalyst in the asymmetric cyclopropanation49 of alkenes with alkyl diazoacetates with optically pure imines as cocatalyst (eq 18).6

Cu(OAc)2 as Lewis Acid.

Decarboxylation of L-tryptophan into L-tryptamine proved most effective in HMPA in the presence of Cu(OAc)2.50 In boiling MeCN and under Cu(OAc)2.H2O catalysis, aldoximes are converted smoothly into nitriles.51 In the presence of various Lewis acids including Cu(OAc)2, cyclodeca-1,2,5,8-tetraene is rearranged to cis,syn-tricyclo[,4]deca-5,8-diene (eq 19).52

The Michael reaction of O2NCH2CO2R (R = Me, Bn) with R1COCH=CHR2 (R1 = Me, Et, R2 = H; R1 = R2 = Me) is catalyzed by Cu(OAc)2 and gives R1COCH2CHR2CH(NO2)CO2R in dioxane at 100 °C.53 Knoevenagel condensation of t-butyl malonate with Paraformaldehyde to give di-t-butyl methylidenemalonate can be achieved in the presence of KOH and Cu(OAc)2.54 Lithium imine anions of a-amino esters undergo Cu(OAc)2-catalyzed reactions with a,o-dihalogenoalkanes to give the corresponding o-halogenoalkylimines.55 Cu(OAc)2 catalyzes the coupling of PhYbI with n-BuI, giving n-BuPh and Ph-Ph.56

Acyl hydrazides are converted to the corresponding carboxylic acids by bubbling oxygen through a THF or MeOH solution containing the hydrazide and a catalytic amount of Cu(OAc)2 (eq 20).58

Synthesis of Ynamines.

Phenylacetylene reacts with dimethylamine under Cu(OAc)2 catalysis to produce N,N-dimethyl-2-phenylethynylamine (eq 21).59 The reaction is effected by bubbling oxygen through a benzene solution of the reagents and Cu(OAc)2; in the absence of oxygen, 1,4-diphenylbutadiyne is the sole product. This may be suppressed by adding a reducing agent, such as hydrazine, to the reaction mixture.

Related Reagents.

Copper(I) Acetate; Copper(II) Acetate-Iron(II) Sulfate; Iodine-Copper(II) Acetate; Lead(IV) Acetate-Copper(II) Acetate; Manganese(III) Acetate-Copper(II) Acetate; Sodium Hydride-Copper(II) Acetate-Sodium t-Pentoxide; Zinc-Copper(II) Acetate-Silver Nitrate.

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Pierre Vogel

Université de Lausanne, Switzerland

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