Org. Synth. 1986, 64, 217
DOI: 10.15227/orgsyn.064.0217
TRIFLOROACETYL TRIFLATE
[Acetic acid, trifluoro-, anhydride with trifluoromethanesulfonic acid]
Submitted by Stephen L. Taylor, T. R. Forbus, Jr., and J. C. Martin
1.
Checked by Thomas W. Panunto and Edwin Vedejs.
1. Procedure
Caution! The volatile product reacts rapidly with water to give corrosive strong acids. It also reacts rapidly with other nucleophiles. Care should therefore be exercised to avoid inhalation of its vapors. It should be handled in a well-vented fume hood.
To a 1-L flask containing 160 g (1.13 mol) of powdered phosphorus oxide (P2O5), thoroughly mixed with an equal volume of dried fine sand (Note 1), is added a mixture of 85.5 g (0.75 mol) of trifluoroacetic acid (TFA) (Note 2) and 56.5 g (0.376 mol) of triflic acid (TfOH) at −20°C (Note 3). The stoppered flask (Note 4) is vigorously shaken for 5 min and then fitted for simple distillation, with the receiving flask cooled to −78°C, and allowed to stand at room temperature under a dry nitrogen atmosphere for 2.5 hr. The liquid is removed from the solid mixture by simple distillation at a bath temperature of 240°C (Note 5) for 3.5 hr (Note 6). The distillate is then carefully fractionally distilled (Note 7) from 5 g of powdered P2O5 (Note 8) with the receiving flasks cooled at −78°C. The colorless liquid collected at 62.5–63°C (760 mm) (Note 9), 69 g (75%) of trifluoroacetyl triflate (TFAT), is of 99% purity (Note 10), as determined by fluorine magnetic resonance (Note 11).
2. Notes
1.
In recent synthetic applications of this method the powdered
phosphorus oxide was mixed with
twice as much volume of dried fine sand. The increased volume of sand makes it easier to remove the TFAT by distillation and reduces the probability that the flask will be broken after the distillation.
2.
The
99% TFA obtained from Aldrich Chemical Company, Inc. was used without further purification.
3.
Triflic acid (TfOH), obtained from Minnesota Mining & Manufacturing Company, (3M), in kilogram quantities was used without further purification.
4.
Ground-glass joints were connected using
Teflon sleeves or a
chlorofluorocarbon stopcock grease.
5.
High temperatures are needed to distill the products from P
2O
5. The use of temperatures higher than 250°C, however, causes the round-bottomed flask to break when the temperature is lowered to near room temperature. On completion of the reaction, the P
2O
5 sand mixture can be removed from the flask by careful, slow addition of water. The checkers used an equilibrated bath of sand in a large heating mantle; the flask always broke after distillation (see
(Note 1)).
6.
The nitrogen outlet from the distillation apparatus should be well vented.
7.
An
8-mm × 1-m jacketed column packed with a coiled tantalum wire was used by the submitters. The checkers used a Vigreux column of similar size.
8.
Since the distillate contains 1–3% of the starting acids, P
2O
5 is added to prevent the reaction of
TFA and TFAT, which gives
trifluoroacetic anhydride (TFAA) and TfOH.
9.
The first fraction is TFAA, bp
38.5–41°C (760 mm).
10.
The impurity is TFAA.
11.
The reactants and products show only singlets in their fluorine magnetic resonance spectra with the following chemical shifts (downfield from
fluorotrichloromethane internal standard) δ: TFA, −76.3; TfOH, −77.3; TFAT, −73.3 and −74.8; TFAA, −75.9;
triflic anhydride, −72.6 ppm.
3. Discussion
Trifluoroacetyl triflate is probably the most powerful trifluoroacetylating agent known, as evidenced by its reactivity toward several types of nucleophiles under mild conditions. A sterically hindered base,
2,6-di-tert-butyl-4-methylpyridine,
2 may be used to scavenge the
triflic acid produced in the reactions, since it does not react with TFAT under these conditions.
Trifluoroacetylation occurs at
carbon in activated arenes such as
anthracene3 under milder conditions using TFAT than when using T FAA. Trifluoroacetate esters are formed from alcohols and phenols,
4 while ketones are acylated at
oxygen to yield enol trifluoroacetates.
3 Amines
4 give the corresponding amides on reaction with 1 equiv of TFAT or imides on reaction with 2 equiv. Some covalent halides (fluorides
5 and chlorides
3) are acylated at halogen by TFAT to yield the very volatile trifluoroacetyl halides and ionic triflates. It was recently reported that TFAT reacts with a thioketone to give a stable cation.
6 Reaction of TFAT with the
methyl ester of glutaconic acid gives
2,6-dimethoxypyrylium triflate, the first member of a new class of pyrylium salts
4 with alkoxy groups at positions-2 and -6.
The high reactivity of TFAT limits the number of solvents that can be used for its reactions. We have found that TFAT is unreactive towards saturated hydocarbons, benzene, and common halogenated solvents. It reacts only very slowly with nitromethane, but reacts relatively rapidly with ether, tetrahydrofuran, ethyl acetate, and acetonitrile.
This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
TRIFLOROACETYL TRIFLATE
Triflic acid (TfOH)
trifluoroacetic anhydride (TFAA)
Benzene (71-43-2)
ethyl acetate (141-78-6)
ether (60-29-7)
acetonitrile (75-05-8)
oxygen (7782-44-7)
carbon (7782-42-5)
anthracene (120-12-7)
Nitromethane (75-52-5)
Tetrahydrofuran (109-99-9)
fluorotrichloromethane (75-69-4)
trifluoroacetic acid (76-05-1)
Acetic acid, trifluoro-, anhydride (407-25-0)
trifluoromethanesulfonic acid,
triflic acid (1493-13-6)
triflic anhydride (358-23-6)
Trifluoroacetyl triflate (68602-57-3)
2,6-dimethoxypyrylium triflate
TFA
phosphorus oxide (1314-56-3)
2,6-Di-tert-butyl-4-methylpyridine (38222-83-2)
methyl ester of glutaconic acid
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