Displacement of fluoride ion

The formation of ethyl cyano(pentafluorophenyl)acetate illustrates the intermolecular nucleophilic displacement of fluoride ion from an aromatic ring by a stabilized carbanion. The reaction proceeds readily as a result of the activation imparted by the electron-withdrawing fluorine atoms. The selective hydrolysis of a cyano ester to a nitrile has been described. (Pentafluorophenyl)acetonitrile has also been prepared by cyanide displacement on (pentafluorophenyl)methyl halides. However, this direct displacement is always aecompanied by an undesirable side reaetion to yield 15-20% of 2,3-bis(pentafluoro-phenyl)propionitrile. 

Streitweiser et al.597 have also measured second-order rate coefficients for hydrogen exchange of fluorobenzenes with sodium methoxide in methanol, Table 182. Nucleophilic displacement of fluoride ion by methoxide ion accompanies... 

The reaction of the carbanion derived from diethyl methylphosphonate with perhalogenated aromatics may result in substitution of halide to yield perhaloaryl(hetaryl)methylphosphonates, which can be converted into tris- or bis-(perhaloaryl)methanes. Displacement of fluoride ion has been reported in the reaction of dimethoxycarbene with l-fluoro-2,4-dinitrobenzene and with hexafluorobenzene. The hydrodehalogenation of halogenated aryl ketones may be facilitated using hydrogen over a Pt/C catalyst. " ... 

In contrast to their hydrocarbon analogues, many unsaturated fluorocarbons react with anionic transition metal nucleophiles to yield products arising from net displacement of fluoride ion. This synthetic approach has been successful in producing a host of fluorovinyl and fluoroaryl complexes (95-110). 

The known reactions of fluorinated olefins, arenes, and heterocycles with metal carbonyl anions, to afford fluorovinyl or fluoroaryl complexes resulting from net displacement of fluoride ion (see Section II1,G), prompted us to attempt such substitution reactions with OFCOT, in order to generate the required metal-substituted heptafluorocyclooctatetraenes. 

The unique feature of type (95) is that the double bond is very much activated to nucleophilic attack but reactions proceed with allylic displacement of fluoride ion, often producing an intermediate that is highly reactive towards further attack by nucleophiles, including intramolecular processes. For example, the furan derivative (99) may be obtained directly from (37) (Scheme 60, and also see Scheme 66, later). Other nucleophiles give products of di- and polysubstitution [126] (Scheme 61). The bicyclobutylidine system (41a) is electronically very similar to the tetramer (37), but (41a) is particularly reactive, as a consequence of strain (Scheme 62, [111]). 

Scheme 4.20. Synthesis of poly(aryl amines) via aromatic nucleophilic displacement of fluoride ion.

The reaction of the fluoro compound 16 (X = F)92is the first example of the displacement of fluoride ion in S l reactions at an sp3 carbon atom. 

It is the aim of this chapter to develop a model for the very broad spectrum of reactivity of fluorine-containing systems towards nucleophiles. Substiment effects of fluorine and fluorocarbon groups on the SnI process were considered earlier, in a more general discussion of carbocations (see Chapter 4, Section VI) effects on the Sn2 process will now be examined. Then the broader principles of displacement of fluorine, as fluoride ion, from carbon in different environments will be discussed to emphasise why, for example, nucleophilic displacement of fluoride ion from perfluoroalkenes occurs extremely rapidly while, in contrast, perfluoroalkanes are characterised by extreme inertness. 

The presence of C—H bonds in a perfluoiinated system can, of course, have a profound effect, but the subsequent increase in reactivity usually stems from an elimination-addition rather than direct nucleophilic displacement of fluoride ion (see below). 

Ring closure could also be effected via displacement of fluoride ion by a carbanion (20) already having formed a link with the appropriate hetero-... 

Reaction with neutral methanol at room temperature is very revealing. Remarkably, [23] reacted exothermically, while [20] reacted over a period of days, in each case giving the corresponding bis(methylether) by vinylic displacement of fluoride ion. Diene [19], however, required added base to promote the corresponding reaction with methanol. This dramatic difference in... 

DFP is stable and in the absence of moisture can be stored for considerable periods without decomposition. Hydrolysis in neutral aqueous solution occurs slowly. The reaction is catalyzed by both acid and base. At pH>7, hydrolysis is proportional to the hydroxide ion concentration and at high pH is extremely rapid. The product is always diisopropyl phosphoric acid (equation 38), except under more forcing conditions which eventually produce phosphate (and propan-2-ol). The hydrolysis is strongly catalyzed by the addition of a-effect nucleophiles such as hypochlorite, peroxide, hydroxylamine, hydroxamic acid and their substituted derivatives . Under basic conditions, such nucleophiles (HOX) are present as the anion and are responsible for the rapid initial displacement of fluoride ion from DFP to give intermediate 36 shown in equation 39. Displacement of OX by hydroxide ion regenerates the catalytic OX anion. The reaction with hydrogen... 

Papers dealing with the chemistry of polstfluorocyclohexadienones and related compounds, e.g. the pyrolysis of pentafluorophenyl prop-2-enyl ether to afford the tetrahydroindenone (44), via the intramolecular Diels-Alder adducts (45) and (46), are dealt with in Chapter 6. The kinetics of the alkaline hydrolysis of hydroxybenzotrifluorides suggest the participation of phenolate anions in the displacement of fluoride ion to give difluoroquinone methide intermediates, e.g. (47). ... 

The reactivity of the thiocarbonyl group toward alkyl halides has been evaluated by the CNDO method (80). A much higher energy transition state for the displacement of fluoride ion than of chloride ion is indicated. The demarcation is in keeping with the significantly different softness of the two halogens. 

When pentafluoropyridine and heptafluoro-quinoline and -isoquinoline react with hydrogen diloride or bromide in suipholane, replacement of fluorine ortho and para to the nitrogen by halogen occurs. The order of reactivity is heptafluoroquinoline > heptafluoroisoquinoline > pentafluoropyridine traces of water lead to a considerable rediKtion in the reaction rate and to the formation of hydroxy-daivatives. The proposed mechanism for these reactions, involving nucleophilic displacement of fluoride ion from the protonated heterocycle, is illustrated for heptafluoroquinoline in Scheme 52. No evidence for initial attack at the 4-position was obtained, mid 2,4-dichloro-pentafluoroquinoline was obtained in high yield. 

Chemical properties of fluorine-containing thiazoles are represented only by reactions of nucleophilic substitution. Thus, nucleophilic displacement of fluoride ion in 4,5-dichloro-2-fluorothiazole by cyano, hydroxy and methoxy anions as weU as by diethylamine produced the respective 2-substituted dichlorothiazoles [83]. 

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