Amine-hydrogen fluoride reagents

Amine-Hydrogen Fluoride and Ether-Hydrogen Fluoride Reagents... 

A polymeric form of the reagent from hydrogen fluoride and poly(4-vinylpyndine) is especially easy to handle [I0 Other tertiary amines can also be employed [II], and a two-phase mixture of hydrogen fluoride-melamine-pentane hydrofluorinates cyclohexene to fluorocyclohexane m 98% yield [12]... 

Various sources of fluoride ion have been investigated, of which highly nucleophilic tetraalkylammonium fluorides ate the most effective Thuf, fluoro alkyl halides and N (fluoroalkyl)amines are efficiently synthesized by treatment of the corresponding trifluoromethanesulfonic esters with tetrabutylammonium fluoride trihydrate in aprotic solvents [5fl] (equation 34) The displacement reactions proceed quantitatively at room temperature within seconds, but tail with hydrogen fluoride-pyridine and give reasonable yields only with hydrogen fluo ride-alkylamine reagents... 

The two most widely accepted hydrogen fluoride systems, besides pure hydrogen fluoride, are 70% hydrogen fluoride/pyridine (Olah s reagent)10 11-31-33 and tricthylaminetris(hydrogen fluoride).9 32 33-316 Tetrahydrofuran. various other amines, amides, carbamic acids and esters. 

Benzhydrylamines are better suited than benzylamines as acid-labile linkers for amines. The MBHA linker ( methylbenzhydrylamine ), which is usually used to prepare peptide amides (see Section 3.3), can also be used as a linker for amines (Entry 1, Table 3.21). Hydrogen fluoride is, however, required as the cleavage reagent. Easier to cleave are alkoxy-substituted benzhydrylamines (Entries 2-5, Table 3.21), which can be prepared from the corresponding benzhydryl chlorides [263] or by reductive alkylation [410] or solvolysis [411] of the Rink amide linker. In the case of benzhydrylamines linked to polystyrene as benzyl ethers, treatment with TFA can lead to the release of the linker into solution (acidolysis of the benzylic C-O bond, see Figure 3.18). 

Summarizing, it can be stated that hydrogen fluoride/pyridine and hydrogen fluoride/amine mixtures are useful for the synthesis of simple secondary and tertiary alkyl fluorides, but probably arc not suitable for fluorination reactions in complex multifunctional structures due to the highly acidic properties of these reagents. 

The reaction of 2//-azirines (e.g.. 1) with hydrogen fluoride in pyridine [pyridinium poly(hy-drogen fluoride). Olah s reagent] gives /f,/f-difluoro amines (e.g., 7) or a-fluoro ketones (e.g., 5) (Table 10). In some cases, pyrazines (e.g.. 9) are the main reaction products (Table IQj 31-35 2//-Azirines arc more reactive than aziridines towards pyridinium poly(hydrogcn... 

Another highly effective and convenient hydrogen fluoride/amine reagent for the hydrofluorination of alkenes is the solution of 14% melamine in 86% hydrogen fluoride (Table... 

Table 17 indicates some limitations of the amine hydrofluorides in the reaction with glycidic esters. In the least-substituted case (entry 1) the yield is low. On the other hand, the fully substituted glycidic esters (entries 8 and 9) do not react at all with the amine hydrofluoride, probably due to steric hindrance. This type of epoxide gives better results with other fluorination reagents, e.g. they can be opened to the fluorohydrins in good yield with hydrogen fluoride in the presence of the boron trifluoride-diethyl ether complex (sec Section 1.1.4.3.2.1.2.).37... 

Another highly effective and convenient hydrogen fluoride/amine reagent for the hydrofluorination of alkenes is the solution of 14% melamine in 86% hydrogen fluoride (w/w)46,47 (Table 3). The two-phase mixture of this reagent with pentane or carbon tetrachloride is a suitable system for repeated use47 (Table 4). 

Tertiary amine trishydrofluorides are stable complexes, very convenient for the delivery of hydrogen fluoride. They can be distilled in vacuo, and are suitable reagents for the nucleophilic replacement reactions of chlorine by fluorine under mild homogeneous conditions. The reaction of COCl, with Et3N.3HF [680] in dry ethanenitrile at room temperature proceeds quantitatively according to ... 

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