Trifluoroperacetic acid (trifluoroperoxyacetic acid, TFPAA) is an organofluorine compound, the peroxy acid analog of trifluoroacetic acid, with the condensed structural formula CF3COOOH. It is a strong oxidizing agent for organic oxidation reactions, such as in Baeyer–Villiger oxidations of ketones. It is the most reactive of the organic peroxy acids, allowing it to successfully oxidise relatively unreactive alkenes to epoxides where other peroxy acids are ineffective. It can also oxidise the chalcogens in some functional groups, such as by transforming selenoethers to selones. It is a potentially explosive material and is not commercially available, but it can be quickly prepared as needed. Its use as a laboratory reagent was pioneered and developed by William D. Emmons.
Properties At standard ambient temperature and pressure, trifluoroperacetic acid is a colourless liquid with a boiling point of 162 °C. It is soluble in acetonitrile, dichloromethane, diethyl ether, and sulfolane, and readily reacts with water. Like all peroxy acids, it is potentially explosive and requires careful handling. It is not commercially available, but can be made in the lab and stored for up to several weeks at −20 °C. Some preparative methods result in mixtures containing residual hydrogen peroxide and trifluoroacetic acid, and heating such a mixture is extremely hazardous; the hydrogen peroxide can be decomposed using manganese dioxide for safety before heating.
Preparation Trifluoroperacetic acid can be easily prepared by an Organic Syntheses process of treating trifluoroacetic anhydride with a concentrated (90%) aqueous solution of hydrogen peroxide:
CF3COOCOCF3 + H2O2 → CF3COOOH + CF3COOH As the anhydride will form trifluoroacetic acid in contact with water, an excess of the anhydride also serves to remove the solvent from the peroxide reactant:
CF3COOCOCF3 + H2O → 2 CF3COOH A more dilute hydrogen peroxide solution (30%) can be used to form trifluoroperacetic acid for some reactions from trifluoroacetic acid.
CF3COOH + H2O2 → CF3COOOH + H2O In order to avoid the danger of handling pure or highly concentrated solutions of hydrogen peroxide, hydrogen peroxide – urea can be used to give the peracid. This method involves no water, so it gives a completely anhydrous peracid, which is an advantage when the presence of water leads to side reactions during certain oxidation reactions.
CF3COOCOCF3 + H2O2·CO(NH2)2 → CF3COOOH + CF3COOH + CO(NH2)2 In cases where a pH buffering agent is needed for a synthesis and where the presence of water is tolerated, another approach has been developed. Reacting trifluoroacetic anhydride with sodium percarbonate, 2Na2CO3·3H2O2, yields trifluoroperacetic acid and sodium carbonate, obviating the need for an additional buffer.
3 CF3COOCOCF3 + 4 Na2CO3·3/2H2O2 → 6 CF3COOOH + 4 Na2CO3 + 3 H2O Trifluoroperacetic acid can also be generated in situ, allowing it to react promptly with the target substrate rather than pre-synthesizing a batch of the reagent for later use.
History and uses
Trifluoroperacetic acid is primarily used as an oxidising agent. In September 1953, the Journal of the American Chemical Society published work by William D. Emmons and Arthur F. Ferris reporting that this reagent, generated in situ, was capable of oxidising aniline to nitrobenzene. Over the following two years, Emmons reported a preparative method for this reagent and published six further manuscripts in this journal on its applications. Emmons is remembered in part as the pioneer and developer of trifluoroperacetic acid as a laboratory reagent, which has since become useful as a reagent for many different types of synthetic reactions. One example is the formation of the hypervalent iodine compound (bis(trifluoroacetoxy)iodo)benzene, (CF3COO)2IC6H5 which is used to carry out the Hofmann rearrangement under acidic conditions. The hypervalent compound is accessible in two ways, and which is chosen usually depends on what materials are available: it can be prepared from its acetate analogue by an exchange reaction, or by reacting iodobenzene with a combination of trifluoroperacetic acid and trifluoroacetic acid:
Baeyer–Villiger oxidation
Trifluoroperacetic acid is one of the strongest reagents used for Baeyer–Villiger oxidations, as a consequence of its high acidity relative to similar peracids and peroxides. This reaction converts ketones to either straight-chain esters or lactones, and is named for Adolf von Baeyer and Victor Villiger, who first reported it 1899. The reaction is believed to proceed via a Criegee intermediate and demonstrates good regioselectivity and chemoselectivity for the position of oxygen atom insertion, along with retention of stereochemistry at the adjacent position, as can be seen in the following example. The disodium phosphate (Na2HPO4) is added as a pH buffer to prevent the highly acidic trifluoroacetic acid byproduct from causing hydrolysis or transesterification of the ester product.
Epoxidation The Prilezhaev reaction involves the conversion of an alkene to an epoxide using a peracid as the oxidant and was first reported in 1909. The reaction has been used as the final step of the synthesis of scopine, a tropane alkaloid. In this approach, a [4+3] cycloaddition mediated by diiron nonacarbonyl is used to construct the bicyclic skeleton, the hydroxyl functional group is then introduced by diastereoselective reduction of the ketone with diisobutylaluminum hydride, and the preparation completed with a Prilezhaev trifluoroperacetic acid epoxidation.
The high reactivity of trifluoroperacetic acid relative to other peroxy acids allows it to successfully oxidize relatively electron-poor alkenes such as 1-hexene and α,β-unsaturated esters such as methyl methacrylate, substrates that are generally resistant to peroxy-acid epoxidation. Including additional buffered trifluoroacetic acid in the mixture gives a vicinal hydroxy–trifluoroacetate structure instead of an epoxide, which can be converted to the diol by treatment with acidic methanol, such as in the following conversion of 1-dodecene to 1,2-dodecanediol.
In the case of an allyl alcohol compound with a proximate carbonyl functional group, the epoxide can undergo a ring-expansion reaction to form a dioxolane. The process below was used as part of the total synthesis of neosporol, a natural product:
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