Hydrogen Fluoride-Trifluoromethanesulfonic Acid

Hydrogen Fluoride-Trifluoromethanesulfonic Acid. The acidity of this binary Brpnsted acid system has not been measured, but the superacidic properties are mentioned in numerous patents concerning fluorination, olefin alkylation, and hydrocarbon conversion. 

Perchloric acid (HCIO4 Ho —13.0), fluorosulfuric acid (HSO3F Ho — 15.1), and trifluoromethanesulfonic acid (CF3SO3H Ho —14.1) are considered to be superacids, as is truly anhydrous hydrogen fluoride. Complexing with Lewis acidic metal fluorides of higher valence, such as antimony, tantalum, or niobium pentafluoride, greatly enhances the acidity of all these acids. 

Trifluoromethanesulfonic acid, also known as triflic acid [1493-13-6] is widely used ia organic syntheses and has been thoroughly reviewed (93,94). It was first prepared ia 1954 via the oxidation of bis(trifluoromethylthio)mercury with hydrogen peroxide [7722-84-1] (95). Several other routes of preparation have been disclosed (96—98). The acid exhibits excellent thermal and hydrolytic stabiUty, it is not readily oxidized or reduced, nor is it prone to fluoride anion generation. 

In order to achieve high yields, the reaction usually is conducted by application of high pressure. For laboratory use, the need for high-pressure equipment, together with the toxicity of carbon monoxide, makes that reaction less practicable. The scope of that reaction is limited to benzene, alkyl substituted and certain other electron-rich aromatic compounds. With mono-substituted benzenes, thepara-for-mylated product is formed preferentially. Super-acidic catalysts have been developed, for example generated from trifluoromethanesulfonic acid, hydrogen fluoride and boron trifluoride the application of elevated pressure is then not necessary. 

Thus, the best compromises for Boc and Fmoc chemistries seem to be cyclohexyl and 2,4-dimethylpent-3-yl (Dmpn), which is of intermediate stability, and the removal of which by trifluoromethanesulfonic acid with the aid of thioanisole (see Section 6.22) leads to minimal imide formation (see Section 6.13). Points to note are that acidolysis of esters by hydrogen fluoride can lead to fission at the oxy-car-bonyl bond instead of the alkyl-oxy bond, thus generating acylium ions that can react with nucleophiles (see Sections 6.16 and 6.22), and that benzyl esters may undergo transesterification if left in methanol. The side reactions of cyclization (see Section 6.16) and acylation of anisole (see Section 6.22) caused by acylium ion formation do not occur at the side chain of aspartic acid.47-51... 

The method is particularly well-suited to the fluorination of dithioketals of aromatic ketones (Table 12). To achieve reasonable yields with dithioketals of aliphatic or alicyclic ketones, the addition of trifluoromethanesulfonic acid or hydrogen fluoride/pyridine is required. In general, dithiane derivatives give better yields than dithiolane derivatives. 

No reaction between trimethy](trifluoroniethyl)silane and sulfur dioxide occurs in the absence of an anionic initiator when one molar equivalent of tetrabutylammonium fluoride is used, clean formation of tetrabutylammonium trifluoromethanesulfinate is observed.112 Although oxidation to the corresponding sulfonate occurred readily upon treatment with 30% hydrogen peroxide, attempts to liberate the free acid from the salt proved unsuccessful. When sodium trimethylsilanolate was used as the initiator, however, the reaction sequence was successful. The overall yield of trifluoromethanesulfonic acid (31) was about 30%. 

Of course, it is possible to decrease the stability of the S-benzyl group toward acids by substitution with electron-releasing groups. Thus, in the S-p-methoxybenzyl group the benzyl cation is sufficiently stabilized to allow cleavage of the S —C bond with liquid hydrogen fluoride under fairly mild conditions while the S-2,4,6-trimethylbenzyl group can be removed with trifluoromethanesulfonic acid in trifluoroacetic acid in the persence of w-cresol. 

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