Benzylic fluorides

Both methyltriethylphosphonium fluoride and methyltributylphospho-nium fluoride have been prepared The latter generates benzyl fluoride from benzyl chloride in 80% yield and ethyl fluoroacetate from ethyl bromoacetate in 53% yield Methyltnbutylphosphonium fluoride converts 1-bromododecane to a 50 50 mixture of 1-fluorododecane and 1-dodecene Methyltnbutylphosphonium fluoride also quantitatively forms styrene from 1-bromo-1-phenylethane [26] Methyl-tnbutylphosphonium fluonde is the reagent of choice for the conversion of N,N dimethylchloroacetamide to its fluoride, but it is not able to convert chloro-acetonitnle to fluoroacetomtrile Methyltnbutylphosphonium fluoride changes chloromethyl octyl ether to the crude fluoromethyl ether in 66% yield The stereoselectivity of methyltnbutylphosphonium fluoride is illustrated by the reac tions of the 2-tert-butyl-3-chlorooxiranes [27] (Table 2)... 

Polyethylene glycol (molecular weight, 300-6(W) can aid in the displacement of activated halogen by fluorine. Propionyl chloride is converted to propionyl fluoride with potassium fluoride and polyethylene glycol in acetonitrile [63] Treatment of benzyl chloride with a mixture of potassium fluoride and potassium iodide for 5 h in acetonitrile containing polyethylene glycol 200 gives benzyl fluoride in 62% yield [64],... 

The use of cesium fluoride is limited because of its cost and its availability as a truly anhydrous reagent. Its use with 18-crown-6 shows a 5 times higher rate for the formation of benzyl fluoride from benzyl bromide when compared with cesium fluonde or potassium fluoride supported on calcium fluoride [21] Either cesium fluoride or potassium fluoride supported on calcium fluoride (Procedures 5a and 5b, p 194) provides about a twofold improvement over either unsupported alkali metal fluoride [55, 69], Cesium fluoride and Aliquat 336 convert benzyl bromide to the fluoride in 94% yield. Using tetrabuty lammonium fluoride in place of Aliquat... 

Sa. Preparation of Benzyl Fluoride by Using Potassium Fluoride Supported on Calcium Fluoride (Methanol Procedure) [5-S]... 

A one-pot conversion of benzyl alcohols to benzyl fluorides by treatment of the alcohols with a combination of methanesulfonyl fluoride, cesium fluoride and 18-crown 6 ether in tetrahydrofuran has been repotted The reaction involves mesylation of the alcohols followed by cleavage of the resultant mesyl esters with a fluoride ion The reaction has been extended also to certain heterocycles bearing the N hydroxymethyl group [43] (equation 31)... 

Hexafluoropropyldiethylamine is a particularly useful reagent for conversion of secondary benzylic hydroxy esters into the corresponding secondary benzyl fluorides The reactions proceed with inversion of configuration and a high degree of stereospecificity [86, 87] (equation 53)... 

Trimethylbenzylammonium hydroxide has been converted to benzyl fluoride in 22-60% yield by treatment with 20% hydrofluoric acid followed by vacuum distillation [71, 72]... 

GL 1] [R4] [P 2] A small amoimt of side-chain fluorination was reported ]13]. Benzyl fluoride was formed to about the same extent as the meta isomer. 

It is clear that the ionizing power of the solvent used is important in many of these reductions. When 2,4,6-trimethylbenzyl chloride is heated with diphenylsi-lane in nitrobenzene at temperatures as high as 130°, no isodurene is formed.193 Not unexpectedly, the same lack of reactivity is reported for a series of benzyl fluorides, chlorides, and bromides substituted in the para position with nitro or methyl groups or hydrogen when they are heated in nitrobenzene solutions with triethylsilane, triethoxy silane, or diphenylsilane.193... 

In polar aprotic solvents, F is a good nucleophile. Benzyl bromide is a good electrophile under all conditions. The product is benzyl fluoride, PI1CH2F. 

Acetyl-3-methyl-4,5-dihydrothiophen-4-one Benzyl alcohol, Hydrogen bromide, Iron Benzyl bromide, Molecular sieve Benzyl chloride, Catalytic impurities Benzyl fluoride l,2-Bis(chloromethyl)benzene Ethylene oxide, Contaminants Furoyl chloride... 

Fluorination of toluene gives a mixture of ortho- and para- uorotoluene, as expected for an electrophilic process (B), but the partial rate factors (Table 4) [139] show a very high ortho para ratio indicating that radical processes (A) must also be involved. Furthermore, fluorination of the methyl group, giving benzyl fluoride, also occurs in increasing yield as the reaction temperature is raised. 

For example, treatment of benzyl alcohol with selenium tetrafluoride-pyridine quantitatively yields benzyl fluoride.81... 

A variety of benzyl fluorides 9 were directly prepared in one-step from the corresponding benzyl alcohols 8 by using a combination of methanesulfonyl fluoride and cesium fluoride in the presence of dibenzo-18-crown-6.167 The mesylates formed in situ are thus easily converted to the fluoro derivatives 9. 

Tetrabutylammonium difluorotriphenylstannane is an anhydrous synthetic equivalent to TBAF and converts benzyl bromide (26) to benzyl fluoride (27) 18 times faster than cesium fluoride in refluxing acetonitrile.218... 

Calcium fluoride calcined with potassium fluoride affords benzyl fluoride (4) in 81% yield from benzyl bromide (3) on refluxing in acetonitrile.2,3 This reagent has been sucessfully used in the preparation of various other organo-fluorine compounds. 

Calcium fluoride supported on cesium fluoride gives also a good conversion rate of 95% for benzyl bromide (3) to benzyl fluoride (4). The reaction is, however, carried out in tetramethylene sulfone. 

Fhiorination of aromatics. The reagent reacts with toluene to form benzyl fluoride as the major product ( 65% yield). It is also useful for fluorination of phenols- and of alkyl ethers of phenols the or/Ao-isomcr is formed as the major product. Reactions with this reagent thus differ from those with xenon difluoride, which generally favors formation of paro-isomers. 

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