What Is Dakin Oxidation?
Aromatic aldehydes or ketones containing ortho- or para-hydroxyl or amino groups react with hydrogen peroxide under alkaline conditions to produce phenols. It is a variant of the Baeyer-Villger reaction. This reaction offers a concise route to valuable aromatic building blocks and finds application in natural product synthesis and the pharmaceutical industry.
It is worth mentioning that potassium persulfate (Oxone) can be used to oxidize aromatic aldehydes (including m-hydroxybenzaldehyde) to carboxylic acids or esters, but oxidation of ortho- or para-hydroxyl (or methoxy) substituted benzaldehyde mainly produces Dakin reaction products.
- Reagents: Hydrogen peroxide (H2O2), Base (e.g., sodium hydroxide, potassium hydroxide)
- Reactants: Aromatic aldehydes
- Products: Phenols
- Reaction type: Oxidation reaction
- Related reactions: Baeyer-Villiger oxidation (BVO), Cannizzaro reaction
Fig 1. Dakin oxidation reaction and its mechanism. [1]
Mechanism of Dakin Oxidation
The Dakin oxidation proceeds through a two-step process, mechanistically related to the Baeyer-Villiger oxidation (BVO).
Baeyer-Villiger Oxidation
The reaction begins with the nucleophilic attack of a peroxyacid, typically generated in situ from hydrogen peroxide and a base, on the carbonyl carbon of the aldehyde. This forms a cyclic tetrahedral intermediate. Subsequent rearrangement leads to a cleavage of the C-O bond of the original aldehyde and the formation of an aryl formate ester.
Hydrolysis
The resulting aryl formate ester is then readily hydrolyzed under basic reaction conditions to yield the final product, a phenol, and the corresponding carboxylic acid (R'COOH).
Improvements in reaction conditions
Dakin's original protocol used strong alkaline conditions and high temperatures. However, modern variants have explored milder reaction conditions using alternative catalysts and oxidants. For example, Bishwajit Saikia et al. reported a green Dakin reaction strategy without the use of any transition metal catalysts, ligands, bases, toxic or hazardous reagents, additives/promoters, and organic solvents, which was carried out under aerobic conditions in pure "water extract of banana" (WEB) at room temperature in a very short reaction time. [2]
Many different reagents have also been reported to improve the reaction yield. The commercial reagent urea-hydrogen peroxide complex (UHP) can also be used for this reaction. The characteristics of this reagent are low price, stability, easy operation, and the reaction can be carried out in the solid state with excellent yield.
Application Examples of Dakin Oxidation
- Example 1: Takumi Abe et al. developed a one-pot method for the preparation of indole[2,1-b]quinazoline from indole-3-carboxaldehyde via Dakin oxidation. The Dakin oxidation of indole-3-carbaldehyde (1a) first produces formate 8, followed by oxidation to isatoic anhydride 10a via isatin 9. Then, 10a reacts with 1a to form amide 11, which is converted to tryptanthrin (2a) through oxidation of 11 to 12 followed by intramolecular cyclization. [3]
- Example 2: The Dakin oxidation is particularly useful for the preparation of catechols, a class of dihydroxybenzenes with significant biological activity. For instance, the flavin catalyst undergoes organocatalytic Dakin oxidation of electron-rich aromatic aldehydes to phenols under mild alkaline conditions. Catechols are easily prepared and the oxidation of 2-hydroxyacetophenone was achieved. [4]
Fig 2. Synthetic examples via Dakin oxidation reaction.
Related Products
| CAS No. | Structure | Product | Inquiry |
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| 118276-06-5 |  | 3,5-Difluoro-4-hydroxybenzaldehyde | Inquiry |
| 121-32-4 |  | Ethyl vanillin | Inquiry |
| 123-08-0 |  | p-Hydroxybenzaldehyde | Inquiry |
| 1243395-68-7 |  | 4-Hydroxy-2-(trifluoromethyl)benzaldehyde | Inquiry |
| 13677-79-7 |  | Gallic Aldehyde | Inquiry |
| 139-85-5 |  | Protocatechualdehyde | Inquiry |
| 15174-69-3 |  | 4-Hydroxy-3-methylbenzaldehyde | Inquiry |
| 1620-98-0 |  | 3,5-Di-tert-butyl-4-hydroxybenzaldehyde | Inquiry |
| 16414-34-9 |  | Benzaldehyde,3-bromo-4,5-dihydroxy- | Inquiry |
| 178686-24-3 |  | 3-ETHOXY-4-HYDROXY-5-NITROBENZALDEHYDE | Inquiry |
| 18278-34-7 |  | 4-Hydroxy-2-Methoxybenzaldehyde | Inquiry |
| 1849-76-9 |  | Akos b028976 | Inquiry |
References
- Li, Jie Jack, et al. Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications Sixth Edition, 2021, 137-139.
- Saikia, Bishwajit, et al. Green Chemistry, 2015, 17(9), 4533-4536.
- Abe, Takumi, et al. Tetrahedron Letters, 2014, 55(38), 5268-5270.
- Chen, Shuai, et al. Organic letters, 2012, 14(11), 2806-2809.
