Fluondes

Methyl fluonde Pentyl chloride 1 Ethylbutyl bromide Cyclohexyl iodide... 

Alkyl fluonde (slowest rate of elimination strongest carbon-halogen bond)... 

The order of alkyl halide reactivity in nucleophilic substitutions is the same as their order m eliminations Iodine has the weakest bond to carbon and iodide is the best leaving group Alkyl iodides are several times more reactive than alkyl bromides and from 50 to 100 times more reactive than alkyl chlorides Fluorine has the strongest bond to car bon and fluonde is the poorest leaving group Alkyl fluorides are rarely used as sub states m nucleophilic substitution because they are several thousand times less reactive than alkyl chlorides... 

Using the relationship from the preceding section that the effective electronega tivity of carbon m a C—H bond increases with its s character (sp < sp < sp) the order of hydrocarbon acidity behaves much like the preceding methane ammonia water hydrogen fluonde series... 

Schiemann reaction (Section 22 17) Preparation of an aryl fluonde by heating the diazonium fluoroborate formed by addition of tetrafluorobonc acid (HBF4) to a diazonium ion Schiffs base (Section 17 10) Another name for an imine a compound of the type R2C=NR ... 

Fluonde Ion as Nucleophile and a Leaving Group in Aromatic Nucleophilic Substitution Reactions Vlasov V M J Fluorine Chem 6i. 193-216 77... 

Anhydrous hydrogen fluonde Yield based on fluonne The compound is commercially available The compound has considerable vapor pressure... 

Anhydrous hydrogen fluonde The compound is commercially available... 

The hydrofluonnation of alkenes also occurs in the gas phase, generally at somewhat higher temperatures [J]. Huoroethane is obtained m yields as high as 98% at 100 to 160 C by reaction in the presence of minor amounts of higher ot-olefms [6], and 2-fluoropropane is prepared in greater than 90% yield at <.80 "C from hydrogen fluonde and propene in the presence of activated carbon [7]... 

Alkyl and aryl isocyanates react with anhydrous hydrogen fluonde to give carbamyl fluorides [J, 55], the more conveniently handled pyridinium poly(hydro-gen fluoride) reagent can also be used, although the yields tend to be poorer [9] (equation 10). 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

The high reactivity of N-H bonds has also been exploited to produce N-F denvatives without significant substitution on neighbonng C-H bonds, Diethyl-phosphoramidates of ammonia, alkylammes, and a,polar solvents to produce difluoroamine [57], N,N-difluoroalkylamines, and a,to-bis(At,7V-difluoroamino)alkanes [52] Acetamide undergoes fluonnation to give modest yields of N,N difluoroacetatnide and acetyl fluonde when fluorinated... 

During electrochemical fluorination retention of important functional groups or atoms in molecules is essential. Acyl fluorides and chlorides, but not carboxylic acids and anhydrides (which decarboxylate), survive perfluorination to the perfluorinated acid fluorides, albeit with some cyclization in longer chain (>C4) species [73]. Electrochemical fluorination of acetyl fluoride produces perfluoro-acetyl fluoride in 36-45% yields [85]. Electrochemical fluorination of octanoyl chloride results in perfluorinated cyclic ethers as well as perfluorinated octanoyl fluonde. Cyclization decreases as initial substrate concentration increases and has been linked to hydrogen-bonded onium polycations [73]. Cyclization is a common phenomenon involving longer (>C4) and branched chains. a-Alkyl-substituted carboxylic acid chlorides, fluorides, and methyl esters produce both the perfluorinated cyclic five- and six-membered ring ethers as well as the perfluorinated acid... 

Lead tetrafluoride, generated in situ from lead dioxide and hydrogen fluonde, can replace benzylic hydrogen by fluonne [3] Under sirmlar conditions phenol is simultaneously oxidized to 4,4-difluoro-2,5-cyclohexadienone [4 (equations 3 and 4)... 

Only cohalt tnfluoride without calcium fluonde was used... 

These reactions liberate carbonyl fluonde and fluorotnmethylsilane and thus require no hydrolysis A fluorinated erythromycin derivative is obtained from fluorination of 3 O raycarosyl-8 9-anhydroerythronolideB 6,9 hemiacetal, an enol ether [iS] (equation 16)... 

The tnmethylsilyl enol ether of 1 mdanone (3 2 mmol) in 2 mL of methylene chlonde is added to a mixture of xenon difluonde (4 mmol) and a catalytic amount of pyndimum poly (hydrogen fluonde) m 5 mL of methylene chlonde The mixture IS stured at 0 C for 2 h and poured into dilute sodium bicarbonate solution, tlie organic layer is separated and dned After concentration and column chromatogra phy (silica gel, hexanes), 2-fluoro-1 -mdanone (mp, 59 C) is obtamed in 87% yield... 

Chlorine monofluoride can be tamed by reacting it with cyanunc fluoride to form the trimer (CF2NC1)3 The trimer reacts with 1,1-dichloro 2,2,2 tri fluoroethanesulfenyl chloride to form a mixture of 1 chloro-l,2,2,2-tetra-fluoroethanesulfenyl chlonde and perfluoroethanesulfenyl chloride In the same Way, tnfluoroacetyl bromide yields trifluoroacetyl fluonde[14] (equation 16)... 

Early workers using anhydrous tetrabuCylammonium fluonde (TBAF) may have actually used mixtures of TBAF and tetrabutylammonium bifluoride It IS known that excessive drying at 77 °C in a vacuum below 2 torr (1 torr = 133 322 Pa) produces the bifluoride salt [20] TBAF can be obtained by drying commer... 

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)... 

In contrast, l,l,3,3-tetrachloro-],3-dihydroisobenzofuran and anhydrous hydrogen fluoride form 2-tnfluoromethylben2oyl fluonde [36] (equation 27)... 

Anhydrous hydrogen fluonde, potassium fluonde, and sodium fluonde have all been used to promote the chlorine-fluonne exchangein tetmchloropyrukizine All three fliionne sources replace the chlonne in position 3 first Both sodium and potassium... 

A second variable is the amount of residual moisture present in the extremely hygroscopic potassium fluonde Solvents are often used to remove this moisture hy azeotropic distillation When the reaction mass is anhydrous, the solvent is... 

The conversion of octachloronaphthalene to octafluoronaphthalene with potassium fluoride and either 18-crown-6, dibenzo-18-crown-6, cis,j>m,cis-dicyclohexano-18-crown-6, cis,anti,cis-dicyclohexano-l 8-crown-6, or irons,syn,trails-dicyclohexano-18-crown-6 demonstrates that 18-crown-6 or dibenzo-18-crown-5 increases the yield and selecuvity and decreases the reaction time [55] Treatment of 3,4-dichloro-],2,5-thiadiazole with potassium fluonde in sulfolane with and without 18-crown-6 present shows that less severe conditions can be used with either 18-crown-6 or dibenzo-18-crown-6 to form 3,4-difluoro-l,2,5-thiadiazole (equation 34)... 

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... 

Although both cuprous and cupric fluorides have been studied in the past, an active fluorine donor can be formed from cupric oxide and hydrogen fluonde. This donor, in combination with 2,2 -bipyridine, effectively displaces the halogen of... 

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