Oxalic Acid

(free acid)

[144-62-7]  · C2H2O4  · Oxalic Acid  · (MW 90.04) (dihydrate)

[6153-56-6]  · C2H6O6  · Oxalic Acid  · (MW 126.08)

(mild Brønsted acid; chelating5 and quenching23-25 agent; catalyst for hydrolysis,6-9 protection-deprotection,10-21 dehydration-elimination,28-33 decarboxylation,34 and condensation35-40 reactions)

Alternate Name: ethanedioic acid.

Physical Data: anhydrous acid: hygroscopic, exists in rhombic and monoclinic forms; mp (rhombic) 189.5 °C; pKa1, 1.46; pKa2, 4.40. Anhydrous acid has substantial vapor pressure; begins to sublime at slightly below 100 °C; sublimes rapidly at 125 °C. Dihydrate: monoclinic crystals, mp 101 °C.1

Solubility: anhydrous acid: v sol H2O, alcohol; sl sol ether; insol benzene.

Purification: crystallized from distilled water;43 see below for drying.

Form Supplied in: readily available as the dihydrate; anhydrous form also available.

Analysis of Reagent Purity: by titration of reductive capacity; impurity tests known.42

Preparative Methods: preparation of the anhydrous acid may be accomplished by refluxing the dihydrate in carbon tetrachloride with removal of water;2 alternatively, the hydrate may be heated in an oven at 98 °C for several hours.3 The latter process may be harmful to the oven.

Handling, Storage, and Precautions: the dihydrate should be stored in a cool area at 50-70% relative humidity to prevent caking. Oxalic acid and its solutions are corrosive and highly toxic; ingestion of oxalic acid and its salts can cause death. Use of gloves, aprons, and goggles when handling the material is strongly recommended. A review of oxalic acid as a hazardous material, with extensive references, is available.4 Use in a fume hood.

Introduction.

Oxalic acid is the simplest of the dicarboxylic acids and is typical of its class with respect to the preparation of its simple salts and esters. Several of its simple derivatives are important reagents in organic chemistry (see Diethyl Oxalate, Oxalyl Chloride); these will not be discussed here. Oxalic acid has been widely used in inorganic chemistry as a precipitant and chelating agent; a review of metal oxalato complexes may be consulted for these uses.5 Oxalic acid is utilized extensively in synthetic organic chemistry as a mild Brønsted acid for various acid-catalyzed processes. It is particularly useful in cases where the reactants or products contain potentially acid-labile functionality. In many cases it furnishes a degree of selectivity which would otherwise be difficult to attain.

Protections/Deprotection and Hydrolyses.

Aqueous oxalic acid is an excellent reagent for the hydrolysis of enol ethers to ketones.6 Hydrolysis of the enol ethers obtained by Birch reduction of aromatic ethers, by mineral acid, typically gives the conjugated ketone. In contrast, use of oxalic acid provides the ketone without concomitant migration of the double bond.7-9 In the example shown (eq 1),9 hydrolysis and closure of the hydroxy acid to the lactone occurred simultaneously.

Oxalic acid may be used for both incorporation and removal of acetal and ketal functionalities. Ketones and aldehydes may be reacted with ethylene glycol or methanol in the presence of oxalic acid (anhyd) to effect conversion to the ketals and acetals, respectively.10,11 Dimethylmethoxymethyl ethers have been prepared by stirring alcohols with 2-methoxypropene in the presence of oxalic acid.12 Ketalization of progesterone with oxalic acid proceeds without isomerization of the double bond, whereas use of p-Toluenesulfonic Acid results in migration to the 5,6-position.13 Cleavage of acetals to regenerate the carbonyl group may be accomplished in aqueous solution.14-17 Acid-sensitive functionality is well tolerated by this method (eq 2).16 A two-phase system of methylene chloride and water has also been used.18

A particularly mild method for deacetalization is the use of oxalic acid and moist silica gel.19 Cleavage of b-hydroxy ketals to the corresponding hydroxy ketones may be effected without accompanying dehydration (eq 3),20 and vinylsilanes have not undergone protodesilylation under these conditions.21 Vinylogous phosphoramides have been hydrolyzed to ketophosphonates using this method.22

Oxalic acid is a frequently used mild acid quench for a variety of reaction types, including oxidations with Dimethyl Sulfoxide activated with 1,3-Dicyclohexylcarbodiimide23,24 and Phenyl Dichlorophosphate (Pfitzner-Moffatt oxidation),25 as well as organometallic reactions and anion additions. Oxalic acid in methanol has been used to effect protodesilylation26 and protodestannylation27 of dihydropyridine compounds.

Heating alcohols with anhydrous oxalic acid28 or refluxing in aqueous oxalic acid29 effects dehydration to alkenes, often with results superior to other methods. Appropriately disposed hydroxy ketones have been cyclodehydrated to cyclic ethers (eq 4).30-32 Elimination of amines from Mannich adducts with oxalic acid in ethanol, to yield unsaturated ketones, has also been reported.33

b-Ketoesters may be decarboxylated by aqueous oxalic acid in dioxane (eq 5).34

Oxalic acid has been used as an acidic agent in a number of condensation processes, including condensation of allylic alcohols with aromatic rings35 and condensations with carbonyl groups.36 Oxalic acid can itself serve as a reaction partner in such processes, for example in condensations between aromatic amines and aldehydes,37 and between phenols.38 Oxalic acid has been utilized as a bifunctional condensation partner in the synthesis of heterocyclic systems.39 Palladium-catalyzed hydroxycarboxylation of alkenes and alkynes by oxalic acid provides alkanoic and alkenoic carboxylic acids, respectively.40

Oxalic acid is frequently used for the characterization of amines as their oxalate salts.41

Related Reagents.

Acetic Acid; Hydrochloric Acid; Methanesulfonic Acid; Pivalic Acid; Sulfuric Acid; p-Toluenesulfonic Acid; Trifluoroacetic Acid.


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Gregory S. Hamilton

Scios Nova, Baltimore, MD, USA



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