Copper(II) Sulfate

CuSO4.5H2O

[7758-99-8]  · CuO4S  · Copper(II) Sulfate  · (MW 249.68)

(Lewis acid catalyst for alcohol dehydration,1 acetonide formation,6 acetal exchange;9 reagent for formation of copper carbenoids,15 intramolecular cyclopropanations;21 redox catalyst with potassium permanganate for oxidation of alcohols25 and alkenes28)

Physical Data: 110 °C, -4H2O; 150 °C, -5H2O; heating above 560 °C causes decomposition to CuO; d 2.28 g cm-3.

Solubility: sol H2O and methanol; slightly sol ethanol; insol acetone and ether; anhyd form sol H2O, practically insol methanol and ethanol.

Form Supplied in: blue solid, widely available. Drying: for certain applications, copper(II) sulfate must be used as an anhyd reagent; dehydration of CuSO4.5H2O can be accomplished by heating in an open porcelain dish at 275 °C for two days in a drying oven, stirring the sample several times during the drying period to break up any lumps; during this time the deep blue crystals are converted to an off-white powder.

Handling, Storage, and Precautions: CuSO4.5H2O can be stored and handled in the laboratory using normal laboratory methods; anhyd CuSO4 is a powerful desiccant and must be stored out of contact with moisture, but can be weighed and transferred in the laboratory if atmospheric exposure is minimized; copper(II) sulfate is a strong irritant to the skin and mucous membranes.

Introduction.

The principal uses of CuSO4 in organic synthesis stem from the chemical properties of Cu2+. Firstly Cu2+ functions as a Lewis acid towards electron donor functions and can thus promote a variety of acid-catalyzed processes. Secondly Cu2+ reacts readily with diazo compounds to give carbenoid intermediates useful in subsequent addition reactions. Thirdly Cu2+ functions as an effective redox catalyst in several mixed oxidizing systems.

Lewis Acid Catalysis.

Complexation of oxygen by Cu2+ makes an oxygen-containing functional group a much better leaving group. As such, the Cu2+ functions as a typical Lewis acid; however, anhyd CuSO4 can be used effectively to promote a variety of reactions that would be adversely affected by significant amounts of water. The dehydration of alcohols by anhyd CuSO4 is an excellent general method for the preparation of alkenes.1 The alcohol (neat or in an inert solvent) is heated with 0.75-1.0 equiv of CuSO4.1-3 The copper sulfate can be used alone or supported on silica gel.4 The method works well for benzylic, allylic, tertiary, and secondary alcohols, but is unsuitable for primary alcohols, which give the bis-ether rather than the alkene. The product mixtures are similar to those obtained in proton-catalyzed eliminations and suggest that carbocation intermediates are involved in the reaction. The method is mild and suitable for the formation of sensitive alkenes (eq 1).5 See also Copper(II) Trifluoromethanesulfonate, Phosphoric Acid, Potassium Hydrogen Sulfate, and Sulfuric Acid.

Anhyd copper sulfate is also an excellent catalyst for the formation of acetonides from glycols and acetone (eq 2).6,7 Either 2,2-Dimethoxypropane or 2-Methoxypropene can sometimes improve the efficiency. The regiochemistry of the copper-catalyzed process is different from that found in the proton-catalyzed reaction.

Acetonides can also be produced directly from epoxides and acetone using anhyd CuSO4,8 and acetal exchange can be used to deprotect ethylene glycol acetals under very mild conditions (eq 3).9 Anhyd CuSO4 has also been used as a Lewis acid catalyst for the removal of trityl protecting groups10 and for Friedel-Crafts acylation of alkenes.11

Complexation of nitrogen by Cu2+ has been used to advantage in several cases. The selective hydrolysis of a-aminodiesters is guided by chelation to nitrogen and activation of the vicinal ester group (eq 4).12 Cycloreversions of 2-azanorbornenes to give primary amines are catalyzed efficiently by copper sulfate (eq 5).13 Copper sulfate (or other Cu2+ sources) facilitates the preparation of Diimide from Hydrazine by complexation with nitrogen.14 See also Copper(II) Acetate.

Copper Carbenoids.

Copper(II) catalysts (as well as other copper species) promote the decomposition of diazo compounds and produce copper carbenoids as reactive intermediates. This is particularly useful for a-diazo carbonyl compounds, which then can add to unsaturated systems to give cyclopropanes.15 In addition, chiral ligands can be attached to the copper, yielding cyclopropanes in high optical purities.16,17

Because intramolecular alkene additions are particularly favored with copper catalysts,18 and because the low coordinating ability of the sulfate counterion is thought to contribute to an increased electrophilicity of the copper carbenoid when copper sulfate is used as the catalyst,19 anhyd CuSO4 has been used in a variety of intramolecular cyclopropanations (eqs 6 and 7, for example).20,21

In the absence of double bonds, intramolecular insertion reactions into C-H bonds are observed (eq 8).22 Recently, intramolecular insertion into the B-H bond of a carborane has been found to occur readily.23 Anhyd CuSO4 has also been used effectively to promote the formation of sulfur ylides in the reactions of diazo compounds and sulfides.24 See also Copper(I) Acetylacetonate.

Redox Catalyst.

Solid mixtures of CuSO4 and oxidizing agents are useful for the oxidation of alcohols. For example, it was found that a solid mixture of Potassium Permanganate and copper sulfate pentahydrate oxidized secondary alcohols to ketones in high yields; however, primary alcohols were not oxidized under the same conditions.25 This selectivity is quite unusual since under homogeneous conditions potassium permanganate vigorously oxidizes both primary and secondary alcohols. This selectivity is reversed by admixture of a solid base (either CuCO3, Copper(II) Hydroxide, or Potassium Hydroxide) to the KMnO4-CuSO4.5H2O oxidant (eq 9).26

These results are rationalized on the basis of the heterogeneous oxidation which takes place on the surface of the solid oxidant. In the absence of an admixed base, secondary alcohols produce ketones which diffuse away from the oxidant surface. Primary alcohols produce carboxylic acids which are bound to the oxidizing surface, effectively blocking further reaction. Inclusion of the heterogeneous base results in neutralization of the acid product and reexposure of the oxidant surface; thus the normal selectivity is restored.

In these oxidations the use of hydrated CuSO4 is mandatory. In fact, it was found that addition of catalytic amounts of water to the solid oxidant creates a more reactive oxidant for the synthesis of lactones from hydroxyaldehydes (eq 10).27 Small quantities of aqueous t-butanol added to the solid oxidant permit the direct conversion of alkenes to a-hydroxy ketones and a-diketones (eq 11).28 Normally, alkenes are inert to the solid oxidant. These differences are attributed to the formation of a thin aqueous phase on the surface of the oxidant (&OOmega; phase) which facilitates phase transfer between the bulk liquid and the surface.

Copper sulfate in combination with ascorbic acid and oxygen has been used as a source of hydroxyl radicals to study the oxidation of dopamine.29 Furthermore, copper sulfate has been used as a catalyst in the Ullmann reaction.30 In both these cases, however, the copper sulfate merely serves as a source of Cu2+ which is reduced to a copper(I) species that is thought to be the key player in the process.

Related Reagents.

Potassium Permanganate-Copper(II) Sulfate.


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Robert V. Hoffman

New Mexico State University, Las Cruces, NM, USA



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