Benzyl fluoride, hydrolysis

It is interesting to note that the hydrolysis of unhindered benzoyl chlorides is not catalyzed by acids, but benzoyl fluoride is acid catalyzed and follows Kq (Bevan and Hudson, 1953). Similarly, acid catalysis of benzyl fluoride hydrolysis which follows occurs (Swain and Spalding, 1960), but no acid catalysis of benzyl chloride hydrolysis is known. Furthermore, benzyl halide reactions show non-linear pa correlations (Hudson and Klopman, 1962 Hill and Fry, 1962 Swain and Langsdorf, 1951). Although much less work has been carried out on benzoyl halides, it would appear then that nucleophilic reactions with benzoyl halides resemble, in many respects, nucleophilic reactions with benzyl systems, including the considerable uncertainty as to the S l or bimolecular nature of these reactions (Thornton, 1964). 

Bevan and Hudson86 have reported that the hydrolysis of benzoyl fluoride is acid-catalysed and follows the [H30+], whereas other unhindered benzoyl halides do not. A parallel situation is found with the benzyl fluoride and chloride. Satchell87 has likewise demonstrated the hydrolysis of acetyl fluoride and chloride to be acid-catalysed. 

In the hydrolysis of benzyl chloride, the leaving group is chloride anion. When benzyl fluoride is hydrolyzed in alkaline or neutral media, the leaving group is fluoride anion, which is a worse leaving group than chloride anion because the carbon-fluorine bond is much stronger than the carbon-chlorine bond 443 kJ (106 kcal/mol) vs. 328 kJ (78 kcal/ mol), respectively. 

Rate of Hydrolysis in 10% Aq. Acetone at 50° (1(q x 106 sec"1) Concentration of HCIO4 Benzyl Chloride Benzyl Fluoride... 

Catalysis by protonic acids accounts for the hydrolysis of fluorides, such as trityl fluoride [31], or elimination of hydrogen fluoride from various systems (Chapter 6), frequently being autocatalytic. The hydrolysis of benzyl fluoride is roughly proportional to the Hammett acidity function [32], which is consistent with the scheme indicated in Figure 5.14 [1, 33]. Indeed, the decomposition of benzyl fluoride, on storage, may be violent [34]. 

Phenols with an appropriate leaving group in the benzylic position such as fluoride may form QMs by spontaneous hydrolysis, possibly catalyzed by a basic amino acid residue as shown in Scheme 10.2c. Evidence for this process was obtained with 4-(fluoromethyl)phenyl phosphate involving initial enzymatic hydrolysis of the phosphate followed by nonenzymatic formation of a QM.11 Similarly, several lines of evidence demonstrate nonenzymatic QM formation from 4-trifluoromethylphenol under physiologic conditions.12... 

E-2-bromomethyleneglutaric esters (>70%) have been obtained from the corresponding 2-bromo-2-bromomethylglutarates using a 25% excess tetra-n-butyl-ammonium fluoride in HMPA [24], A similar procedure converts dimethyl 2-bromo-2-bromomethylsuccinate into dimethyl Z-2-bromomethylenefumarate [25], whereas methyl 2,2-bis(bromomethyl)ethanoate yields the 2-bromomethyl-propenoate when reacted with aqueous sodium hydroxide in the presence of benzyl-triethylammonium chloride [26]. No hydrolysis of the ester is evident at 0°C, but becomes apparent at 25 °C. 

Johnson and McCants (161) were the first to show that the alkaline hydrolysis of alkoxysulfonium salts, obtained by 0-alkylation of sulfoxides, proceeds with inversion of configuration at sulfur. This method was employed to interconvert (/ )- and (5)-benzyl p-tolyl sulfoxides 37 as shown in Scheme 21. In contrast to the hydroxide anion, the chloride, bromide, and iodide anions as well as the nitrogen atom of pyridine react with chiral ethoxydiarylsulfonium salts, not at sulfur but at the a-carbon atom of the ethoxy group, yielding the starting sulfoxide with retained configuration (284). On the other hand, the nucleophilic attack of the fluoride anion is directed at sulfur as in the case of the hydroxide anion (285). 

The selective alkylation of a chemically distinct phenohc site on a perfluorinated aromatic has been achieved following a polymer assisted solution phase protection of an alternative o-hydroxybenzoic acid unit as the dioxin-4-one (19) (Scheme 2.45) [66]. A diverse set of 22 different alkyl and benzyl bromides were then attached to the free phenol using cesium fluoride as the base, followed by treatment with Amberlyst 15 and Amberlyst A-21 as the work-up. Subsequent hydrolysis of the dioxin-4-one group with NaOH proceeded smoothly and was quenched... 

Tnfluoromethyl groups are very resistant to hydrolysis, unless they are allylic or benzylic, or vicinal to a carbon linked to hydrogen. In the last case, elimination of hydrogen fluoride leads to the formation of a difluoromethylene group which is key to additional reactions... 

Many carbamates have been used as protective groups. They are, for the most part, arranged in this chapter in order of increasing complexity of structure. The most useful compounds (not necessarily the simplest structures) are /-butyl (BOC), readily cleaved by acidic hydrolysis benzyl (Cbz or Z), cleaved by catalytic hydro-genolysis 2,4-dichlorobenzyl, stable to the acid-catalyzed hydrolysis of benzyl and /-butyl carbamates 2-(biphenylyl)isopropyl, cleaved more easily than /-butyl carbamate by dilute acetic acid 9-fluorenylmethyl, cleaved by 3-elimination with base isonicotinyl, cleaved by reduction with zinc in acetic acid 1-adamantyl, readily cleaved by trifluoroacetic acid allyl, readily cleaved by Pd-catalyzed isomerization or by nucleophilic addition to the tt-allylpalladium complex and trimethylsilylethyl, cleaved with fluoride. 

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