Fluorides nucleophilic reactions

Nucleophilic Reactions. The strong electronegativity of fluorine results in the facile reaction of perfluoroepoxides with nucleophiles. These reactions comprise the majority of the reported reactions of this class of compounds. Nucleophilic attack on the epoxide ring takes place at the more highly substituted carbon atom to give ring-opened products. Fluorinated alkoxides are intermediates in these reactions and are in equiUbrium with fluoride ion and a perfluorocarbonyl compound. The process is illustrated by the reaction of methanol and HFPO to form methyl 2,3,3,3-tetrafluoro-2-methoxypropanoate (eq. 4). 

Apparently the Lewis acid induced and the fluoride-induced reactions of allylsilanes with enones follow different pathways. The perpendicular approach of the nucleophilic allylsilane... 

A better route has been found using SiFgNa2 which is a by-product of the fertilizer industry. It is possible to separate quantitatively silicon and fluoride by reaction of catechol on hexafluorosilicates in basic conditions (this reaction is also a nucleophilic attack on a hexacoordinate compound). Scheme 7 illustrates the synthesis of useful products by this means [10]. 

Poirier, Wang and Westaway (1994) also investigated the relationship between transition state structure and the magnitude of the secondary a-deuterium KIE in a theoretical study of the SN2 reactions between methyl and ethyl chlorides and fluorides with several different nucleophiles (reaction (12)). 

The synthesis of polyhalide salts, R4NX , used in electrophilic substitution reactions, are described in Chapter 2 and H-bonded complexed salts with the free acid, R4NHX2, which are used for example in acid-catalysed cleavage reactions and in electrophilic addition reactions with alkenes, are often produced in situ [33], although the fluorides are obtained by modification of method I.I.I.B. [19, 34], The in situ formation of such salts can inhibit normal nucleophilic reactions [35, 36]. Quaternary ammonium chlorometallates have been synthesized from quaternary ammonium chlorides and transition metal chlorides, such as IrClj and PtCl4, and are highly efficient catalysts for phase-transfer reactions and for metal complex promoted reactions [37]. 

Fjfluoride anion is in most cases produced by irradiation of oxygen-18-enriched water (see Section 2.4) and therefore provided in aqueous solution. Its highly solvated form is a poor nucleophile [28] but a strong base [128], A number of procedures have been described for the isolation of [ F]fluoride from the target water that render it more reactive and suitable for nucleophilic reactions. 

As has been exemplified in this chapter, fluorinations with fluorine-18 can be classified into two categories (1) the nucleophilic reactions, which usually involve no-carrier-added [ F]fluoride of high-specific radioactivity as its Kf FIF-K complex and include substitutions in the aliphatic and the /lomoaromatic series and (2) the electrophilic reactions, which mainly use moderately low-specific radioactivity molecular [ F]fluorine, or other reagents prepared from it, such as acetyl [ F] hypofluorite, and include addition across double bonds, reactions with carbanions and especially fluorodehydrogenation and fluorodemetallation reactions. 

Silver ion also catalyzes nucleophilic reactions of thiol esters, including reactions of acetylhomocysteine thiolactone (12) and diethylethylphosphonothiolate (52). In the first reaction, an insoluble complex of silver ion and the substrate was first produced at pH 7.5, which then reacted with the nucleophile, in this case an amino group of a protein. In the second reaction silver ion complexes of the substrate were also postulated, on the basis that silver ion complexes with sulfur are much more stable than those with oxygen (I). The complexes postulated were 1 1 and 2 1 silver ion-substrate complexes. These complexes were suggested to react with the nucleophiles, water and fluoride ion, giving as products phos-phonic acid and phosphonyl fluoride, respectively, and silver mercaptide. It is evident that the last reaction at least must involve only the direct interaction of a silver ion with the sulfur atom of the thiol ester without chelate formation. Therefore it appears the metal ion-catalyzed reactions of thiol esters are unique, in that they involve complex formation, but not chelate formation in their catalytic mechanism. 

In the reaction illustrated in the following equation, a fluoride nucleophile replaces the chlorine of a derivative that can be viewed as both a diester and an acid chloride. The... 

Because of the presence of nitrogen in the aromatic ring, electrons in pyridine are distributed in such a way that their density is higher in positions 3 and 5 (the P-positions). In these positions, electrophilic substitutions such as halogenation, nitration, and sulfonation take place. On the contrary, positions 2, 4, and 6 (a- and y-positions, respectively) have lower electron density and are therefore centers for nucleophilic displacements such as hydrolysis or Chichibabin reaction. In the case of 3,5-dichlorotrifluoropyridine, hydroxide anion of potassium hydroxide attacks the a- and y-positions because, in addition to the effect of the pyridine nitrogen, fluorine atoms in these position facilitate nucleophilic reaction by decreasing the electron density at the carbon atoms to which they are bonded. In a rate-determining step, hydroxyl becomes attached to the carbon atoms linked to fluorine and converts the aromatic compound into a nonaromatic Meisenheimer complex (see Surprise 67). To restore the aromaticity, fluoride ion is ejected in a fast step, and hydroxy pyridines I and J are obtained as the products [58],... 

Instead to acid fluorides the reaction between trifluorovinyllithium and carbonyl compounds can lead to oc-fluoro-oc,0-unsaturated aldehydes and ketones by treating the intermediate lithium alkoholates either with a lithiumalkyl or lithium aluminium hydride, as the geminal fluoro atoms on the vinylic carbon in the alcoholates are susceptable to nucleophilic replacement by these reagents (reaction sequence (51)). Finally, rearrangement yields the a-fluoro-a,(J-unsaturated aldehydes and ketones 55). 

The CTAB-catalyzed reaction between p-nitrophenyl diphenyl phosphate and hydroxide or fluoride ion is also inhibited by phenyl, diphenyl, and p-t-butylphenyl phosphates (Bunton et al., 1969). The inhibition by these bulky anions decreases, however, with decreasing pH, and at lower pH values, where the hydroxide ion reaction becomes negligible, the reaction of p-nitrophenyl diphenyl phosphate with p-t-butylphenyl, phenyl, and inorganic phosphate ions is enhanced significantly by CTAB (Fig. 12 and Table 8). The order of the micellar rate enhancement for these nucleophilic reactions (p-t-BuC6H40P03 >C6H60P0 > HOPOf ). The cationic micellar catalysis is thus not dependent on the nucleophilicity of the anions but is explicable in terms of hydrophobic interactions between the nucleophiles and the micelle (Bunton et al., 1969). 

Benzaldehyde reacts with trimethyl(pcrfluorophenyl)silane/potassium fluoride in a fashion similar to that described by Olah for trimethyl(trifluoromethyl)silanc, togive(perfluorophenyl)-phenyl(trimethylsiloxy)methane.In the absence of potassium fluoride the reaction requires a temperature of 170 C. Other nucleophiles, such as cyanide, in place of fluoride cause trimethyl(perfluorophenyl)silane to react with ketones to produce silyl enol ethers which result from abstraction of an a-hydrogen by... 

It was found that the ring opening of phenyl-substituted epoxides, as well as of aliphatic epoxides, can be achieved in high yield in a regio- and stereoselective manner with a mixture of 1 3 of diisopropylamine and hydrogen fluoride (diisopropylamine trishydrofluoride).9 1 m-2,3-Diphenyloxirane. for example, gives pure. >w-2-fluoro-l, 2-diphenylcthanol (1). indicating a nucleophilic reaction mechanism of the SN2 type. 

The reaction of various substituted 2-fluorobenzonitriles 1 with guanidine carbonate affords quinazoline-2.4-diamines 2 in excellent yields. It is proposed that this cyclization reaction proceeds by the reversible addition of guanidine to the cyano function followed by nucleophilic displacement of fluoride. The reaction possesses considerable generality and is successful even when electron-donating groups are present at position 6 of the educt... 

The thiolates, though less sensitive to basicity, are more reactive than oxygen anions over the total accessible range of basicity, but intersect the amine line at ca. pA 12. Other reactive nucleophiles which do not fall in the amine, thiolate, or oxygen anion categories are fluoride, thiosulfate, nitrite, azide, and sulfite. Halides other than fluoride, and also thiocyanate, nitrate, sulfate, and thiourea have no reactivity towards p-nitrophenyl acetate (Jencks and Carriuolo, 1960a). The total lack of reactivity of thiocyanate, iodide, bromide, and thiourea, all very polarizable nucleophiles which are reactive to sp carbon, rules out any possibility that polarizability is at all important in nucleophilic reactions at the carbonyl carbon. In general, the order of nucleophilic reactivity to p-nitrophenyl acetate correlates well with nucleophilic reactivity to other carboxylic acid derivatives (see later). Nitrite, however, shows... 

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