Trifluoromethanesulfonic Acid1


[1493-13-6]  · CHF3O3S  · Trifluoromethanesulfonic Acid  · (MW 150.09)

(one of the strongest organic acids; catalyst for oligomerization/polymerization of alkenes and ethers; precursor for triflic anhydride and several metal triflates; acid catalyst in various reactions)

Alternate Name: triflic acid.

Physical Data: bp 162 °C/760 mmHg, 84 °C/43 mmHg, 54 °C/8 mmHg; d 1.696 g cm-3.

Solubility: sol water and in many polar organic solvents such as DMF, sulfolane, DMSO, dimethyl sulfone, acetonitrile; sol alcohols, ketones, ethers, and esters, but these generally are not suitable inert solvents (see below).

Analysis of Reagent Purity: IR;2 19F NMR.3

Preparative Methods: best prepared by basic hydrolysis of CF3SO2F followed by acidification.2

Purification: distilled with a small amount of Tf2O.4

Handling, Storage, and Precautions: is a stable, hygroscopic liquid which fumes copiously on exposure to moist air. Transfer under dry nitrogen is recommended. Contact with cork, rubber, and plasticized materials will cause rapid discoloration of the acid and deterioration of the materials. Samples are best stored in sealed glass ampules or glass bottles with Kel-FTM or PTFE plastic screw cap linings. Use in a fume hood.

Reaction with P2O5.

Trifluoromethanesulfonic acid (TfOH) reacts with an excess of Phosphorus(V) Oxide to give Trifluoromethanesulfonic Anhydride (eq 1),5 while treatment with a smaller amount of P2O5 (TfOH:P2O5 = 6:1) and slower distillation leads to trifluoromethyl triflate (eq 2).6

The synthetic utility of trifluoromethyl triflate as a trifluoromethanesulfonylating agent is severely limited, because the reagent is rapidly destroyed by a fluoride-ion chain reaction in the presence of other nucleophiles.7

Dehydration of a 2:1 mixture of CF3CO2H and TfOH with P2O5 affords trifluoroacetyl triflate (eq 3),8 which is a very reactive agent for trifluoroacetylations at O, N, C, or halogen centers (eq 3).8a

Protonation and Related Reactions.

TfOH is one of the strongest monoprotic organic acids known. The acid, and its conjugate base (CF3SO3-), have extreme thermal stability, are resistant to oxidation and reduction, and are not a source of fluoride ions, even in the presence of strong nucleophiles. They do not lead to sulfonation as do Sulfuric Acid, Fluorosulfuric Acid, and Chlorosulfonic Acid in some reactions. TfOH is therefore effectively employed in protonation reactions.

The strong protonating property of TfOH is used to generate allyl cations from suitable precursors in low-temperature ionic Diels-Alder reactions. 3,3-Diethoxypropene and 2-vinyl-1,3-dioxolane add to cyclohexa-1,3-diene in the presence of TfOH to give the corresponding Diels-Alder adducts, the latter in high yield (eq 4).9

An intramolecular Diels-Alder reaction with high stereoselectivity occurs involving allyl cations by protonation of allyl alcohols (eq 5).10

Alkynes and allenes are protonated with TfOH to give vinyl triflates (eqs 6 and 7),11 which are precursors to vinyl cations.

A convenient synthesis of pyrimidines is developed by protonation of alkynes with TfOH in the presence of nitriles (eq 8).12

Triflic acid catalyzes the transformation of a-hydroxy carbonyl compounds to ketones (eq 9).13

Oximes undergo Beckmann rearrangement with TfOH in the presence of Bu4NReO4 to give amides in high yield (eq 10).14

TfOH protonates nitroalkenes, even nitroethylene, to give N,N-dihydroxyiminium carbenium ions, which react with arenes to give arylated oximes. This overall process provides a route to a-aryl methyl ketones from 2-nitropropene (eq 11)15 and constitutes a versatile synthetic method for the preparation of a-arylated ketones, otherwise difficult to synthesize by the conventional Friedel-Crafts reaction.

TfOH catalyzes the removal of N-t-butyl groups from N-substituted N-t-butylcarbamates to give carbamate-protected primary amines (eq 12).16

The methyl group attached to the phenolic oxygen of tyrosine is smoothly cleaved by TfOH in the presence of Thioanisole (eq 13).17 This deblocking method was successfully applied to the synthesis of a new potent enkephalin derivative.

1,3,4-Oxadiazoles are prepared in good yields from silylated diacylhydrazines (formed in situ) by acid-catalyzed cyclization using TfOH (eq 14).18

TfOH protonates naphthalene at room temperature to give a complex mixture of products.19 TfOH promotes aldol reaction of silyl enol ethers with aldehydes and acetals, leading to new C-C bond formation (eq 15).20 TfOH competes well with other reagents employed for the aldol reaction, while Methanesulfonic Acid does not afford any product.

Cyclization of 3- and 4-arylalkanoic acids to bicyclic ketones is effected by TfOH via the corresponding acid chlorides (eq 16).21

Allylic O-methylisoureas are cyclized with TfOH containing Benzeneselenenyl Trifluoromethanesulfonate to 5,6-dihydro-1,3-oxazines (eq 17).22

Tscherniac amidomethylation of aromatics with N-hydroxymethylphthalimide in TfOH proceeds smoothly at room temperature to give the corresponding a-amido-methylated products (eq 18).23

TfOH catalyzes the amination24 and phenylamination25 of aromatics via the corresponding aminodiazonium ion generated from Azidotrimethylsilane and Phenyl Azide respectively (eq 19).

Electrophilic hydroxylation of aromatics is carried out by protonation of Bis(trimethylsilyl) Peroxide with TfOH in the presence of the substrate (eq 20).26

Phenol and 2,3,5,6-tetramethylphenol are protonated with TfOH under irradiation to afford rearranged products (eqs 21 and 22).27

Other Applications.

TfOH is the starting material for the preparation of the electrophilic reagent Trimethylsilyl Trifluoromethanesulfonate. The latter is prepared by reacting TfOH with Chlorotrimethylsilane28 or more conveniently with Me4Si (eq 23).29

Functionalized silyl triflates can also be prepared using TfOH (eq 24).30

Reaction of aromatic compounds with Bis(pyridine)iodonium(I) Tetrafluoroborate in the presence of TfOH is an effective method to form the monoiodo compounds regioselectively (eq 25).31

Ionic hydrogenation of alkenes with trialkylsilanes is possible in the presence of the strong acid TfOH, even at -75 °C (eq 26).32

Hydroxycarbonyl compounds can be selectively reduced to carbonyl compounds by means of TfOH in the presence of trialkylboranes (eq 27).33

The triphenylmethyl cation is nitrated with Nitronium Tetrafluoroborate in the presence of TfOH (eq 28).34

Sterically hindered azidophenyltriazines decompose in TfOH at 0 °C to give isomeric triflates (eq 29).35

Benzoyl triflate prepared from TfOH and Benzoyl Chloride is a mild and effective benzoylating agent for sterically hindered alcohols36 and acylative ring expansion reactions.37 The applications of TfOH in Koch-Haaf carboxylation,38 Fries rearrangement,39 and sequential chain extension in carbohydrates40 are also documented. Recent applications of TfOH in cyclization reactions have been published.41-43

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Lakshminarayanapuram R. Subramanian, Antonio García Martínez, & Michael Hanack

Universität Tübingen, Germany

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