Sodium Tungstate Dihydrate (Na₂WO₄·2H₂O): A Mild Oxidizing and Efficient Reagent in Organic Synthesis

Key words

oxidation - sodium tungstate - inorganic reagents - organic synthesis

Thaís do Nascimento Pinheiro received her pharmacy degree from the Federal University of Rio Grande do Norte in 2020. Currently, she is an MSc pharmaceutical sciences student at the same institution under the supervision of Prof. A. K. Jordão and Prof. E. G. Barbosa. Her work involves the synthesis and biological evaluation of novel nitroxides. Euzebio Guimarães Barbosa received his PhD in chemistry from Campinas University (UNICAMP) in 2011 under the supervision of Prof. Marcia Miguel Castro Ferreira. Currently he is a professor at the Federal University of Rio Grande do Norte. His research interests focus on medicinal chemistry and computer-aided drug design. Alessandro Kappel Jordão received his PhD in chemistry from the Fluminense Federal University (UFF) in 2010 under the supervision of Prof. Vitor Francisco Ferreira and Prof. Anna Claudia. Currently he is a professor at the Federal University of Rio Grande do Norte. His research interests focus on the synthesis of heterocyclic compounds.

Sodium tungstate dihydrate (Na₂WO₄·2H₂O) is a simple, cheap, commercially available, and water-soluble colorless crystalline solid inorganic material. It is synthesized when excess tungstic acid is added to aqueous sodium hydroxide, dehydrates at 100 °C, and is insoluble in ethanol. The aqueous solution is slightly alkaline (pH 8–9).[1] The solid can be stored in a hermetically closed flask in a dry place. This compound is usually used as an oxidizing agent in chemistry,[2] affording the corresponding peracid in conjunction with hydrogen peroxide, under mild conditions, that can oxidize amines and sulfur-containing substrates (Scheme [1]).[3] Sodium tungstate dihydrate is the most common hydrated form and can also be used as an efficient catalyst for epoxidation of alkenes and oxidation of alcohols into the corresponding carbonyl compounds. For example, Payne and Williams described the first use of sodium tungstate dihydrate for epoxidation of α,β-unsaturated acids.[4] In addition, it can be used to form heterocycles. Table [1] presents a series of recent applications of this reagent.

Scheme 1 Peracid formation in the presence of sodium tungstate dihydrate (Na₂WO₄·2H₂O)

Table 1 Recent Applications of Sodium Tungstate Dihydrate (Na₂WO₄·2H₂O)

(A) Cunha et al. synthesized a series of 4-substituted 1,2,3-1H-1,2,3-triazole linked nitroxyl radicals derived from TEMPOL (4-hydroxy-2,2,6,6-tetramethyl­piperidinyl-1-oxy). This class of stable radicals was prepared from 4-hydroxy-2,2,6,6-tetramethylpiperidine with sodium tungstate dihydrate and hydrogen peroxide in 70% yield.[5]
(B) Kuhn et al. demonstrated that a primary amine such as methyl l-leucinate could be oxidized with H2O2 in the presence of sodium tungstate dihydrate to form the corresponding oxime in excellent yield.[6]
(C) Reddy et al. reported the preparation of nitrones by oxidation of bicyclic amines with urea hydrogen peroxide (UHP) at room temperature in methanol in the presence of catalytic sodium tungstate dihydrate.[7]
(D) Eleven 1,4-epoxy cycloadducts were prepared in yields of 54–66% by the sequential selective oxidation and intramolecular 1,3-dipolar cycloaddition of methyl 2-(allylaryl)glycinates with an excess of aqueous hydrogen peroxide in the presence of catalytic amounts of sodium tungstate dihydrate.[8]
(E) Sodium tungstate dihydrate as a catalyst was disclosed by Kauthale et al. in the development of a green protocol for the synthesis of triaryl-substituted imidazoles via one-pot three-component condensation of aldehydes, benzil, and ammonium acetate in ethanol with excellent yields and short reaction times.[9]
(F) Narode et al. published a review of strategies for the synthesis of (S)-Apremilast®.[10] One synthetic approach consists of eight steps, with the last being an oxidation in the presence of sodium tungstate dihydrate and 30% hydrogen peroxide to obtain (S)-Apremilast® in 91% yield with 99.7% ee.[11]
(G) Synthesis and studies of the biological activities of novel trifluoromethylpyridine amide derivatives containing sulfur moieties was reported by Guo et al. Sixteen sulfoxide-containing compounds were chemoselectively obtained by oxidation using sodium tungstate dihydrate in good yields.[12]
(H) Wang et al. reported the use of a combination of Na2WO4 and the acidic ionic liquid [BSTma]HSO4 for the one-pot conversion of cyclohexanol into ε-caprolactam. The first step involves oxidation of cyclohexanol to cyclohexanone, followed by reaction with hydroxylamine and subsequent Hoffmann rearrangement.[13]
(I) Yada et al. described a tungsten-catalyzed epoxidation of alkenes.[14] This study allowed the catalytic conditions to be optimized.
(J) Ma and Chen published the tungstate-catalyzed decarboxylative bromination of 3-hydroxy-2-methylquinoline-4-carboxylic acid to furnish 4-bromo-2-methylquinolin-3-ol.[15]

In summary, sodium tungstate dihydrate enables a variety of diverse reactions and functionalizations that include alkene epoxidation, sulfur oxidation, and preparation of nitroxides and nitrones. In the presence of a combination of Na₂WO₄ acidic ionic liquid catalyst, lactams are synthesized from cyclic alcohols. The supported reagent offers additional advantages such mild reaction conditions, increase in reagent stability, ease of workup, and the ability to recycle.

Conflict of Interest

The authors declare no conflict of interest.

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Publication History

Received: 19 July 2022

Accepted after revision: 09 August 2022

Accepted Manuscript online:
16 August 2022

Article published online:
01 September 2022