Fluoride nucleophilicity

Silver(I) fluoride dispersed on the surface of calcium fluoride demonstrates improved fluoride nucleophilicity for halogen exchange. Silver(I) fluoride/calcium fluoride is considerably more active than potassium or cesium fluoride dispersed on the surface of calcium fluoride.38... 

In such hydrogen fluoride free media, which stabilize aryl cations to a lesser extent than 70% hydrogen fluoride/pyridine mixture, aryl cation deprotonation does not occur very rapidly. On the other hand, the fluoride nucleophilicity increases with the pyridine content thus, very high fluorodediazoniation yields can be reached in hydrogen fluoride free media, provided that the diazotization step is conducted under strictly controlled conditions.40,45 67 Illustrative results, obtained by the following general procedure, are listed in Table 2 and compared to those resulting from other conditions when available.40... 

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... 

Likewise, 1-bromooctane is converted by 18-crown-6 complexed KF in acetonitrile solution into 1-fluorooctane (92%) and the by-product olefin in only 8% yield. Bro-mocyclohexane, on the other hand, is converted quantitatively into cyclohexene under the same conditions [2]. Although most of the systems which can give mixtures of E-2 and Sn 2 products, do so, the sulfonates seem to most favor substitution and the fluoride nucleophile/bromide nucleofuge pair tends to favor elimination. 

Among alkyl halides alkyl iodides undergo nucleophilic substitution at the fastest rate alkyl fluorides the slowest... 

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... 

We saw m Section 8 2 that the rate of nucleophilic substitution depends strongly on the leaving group—alkyl iodides are the most reactive alkyl fluorides the least In the next section we 11 see that the structure of the alkyl group can have an even greater effect... 

In media such as water and alcohols fluoride ion is strongly solvated by hydro gen bonding and is neither very basic nor very nucleophilic On the other hand the poorly solvated or naked fluoride 10ns that are present when potassium fluoride dis solves m benzene m the presence of a crown ether are better able to express their anionic reactivity Thus alkyl halides react with potassium fluoride m benzene containing 18 crown 6 thereby providing a method for the preparation of otherwise difficultly acces sible alkyl fluorides... 

In contrast to nucleophilic substitution m alkyl halides where alkyl fluorides are exceedingly unreactive aryl fluorides undergo nucleophilic substitution readily when the ring bears an o or a p nitro group... 

The reaction is earned out by mixing the peptide and 1 fluoro 2 4 dmitrobenzene in the presence of a weak base such as sodium carbonate In the first step the base abstracts a proton from the terminal H3N group to give a free ammo function The nucleophilic ammo group attacks 1 fluoro 2 4 dmitrobenzene displacing fluoride... 

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). 

Difluoropyridines. 2,4-Difluoropyridine can be prepared (26% yield) from 2,4-dichloropyridine and potassium fluoride in sulfolane and ethylene glycol initiator (403). The 4-fluorine is preferentially replaced by oxygen nucleophiles to give 2-fluoro-4-hydroxypyridine derivatives for herbicidal apphcations (404). 

Cyanuric fluoride is readily hydrolyzed to 2,4,6-thhydroxy-l,3,5-triaziae [108-80-5] (cyanuric acid). Cyanuric fluoride reacts faster with nucleophilic agents such as ammonia and amines than cyanuric chloride. 

The presence of inorganic salts may enhance or depress the aqueous solubiUty of boric acid it is increased by potassium chloride as well as by potassium or sodium sulfate but decreased by lithium and sodium chlorides. Basic anions and other nucleophiles, notably borates and fluoride, greatly increase boric acid solubihty by forrning polyions (44). 

S-Alkylthiiranium salts, e.g. (46), may be desulfurized by fluoride, chloride, bromide or iodide ions (Scheme 62) (78CC630). With chloride and bromide ion considerable dealkylation of (46) occurs. In salts less hindered than (46) nucleophilic attack on a ring carbon atom is common. When (46) is treated with bromide ion, only an 18% yield of alkene is obtained (compared to 100% with iodide ion), but the yield is quantitative if the methanesulfenyl bromide is removed by reaction with cyclohexene. Iodide ion has been used most generally. Sulfuranes may be intermediates, although in only one case was NMR evidence observed. Theoretical calculations favor a sulfurane structure (e.g. 17) in the gas phase, but polar solvents are likely to favor the thiiranium salt structure. 

Halide ions may attack 5-substituted thiiranium ions at three sites the sulfur atom (Section 5.06.3.4.5), a ring carbon atom or an 5-alkyl carbon atom. In the highly sterically hindered salt (46) attack occurs only on sulfur (Scheme 62) or the S-methyl group (Scheme 89). The demethylation of (46) by bromide and chloride ion is the only example of attack on the carbon atom of the sulfur substituent in any thiiranium salt (78CC630). Iodide and fluoride ion (the latter in the presence of a crown ether) prefer to attack the sulfur atom of (46). cis-l-Methyl-2,3-di-t-butylthiiranium fluorosulfonate, despite being somewhat hindered, nevertheless is attacked at a ring carbon atom by chloride and bromide ions. The trans isomer could not be prepared its behavior to nucleophiles is therefore unknown (74JA3146). 

Fluorescent brightening agents, 1, 338-341 Fluoride ions nucleophilicity crown ethers and, 7, 756 Fluorides synthesis... 

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. 

When added to nonpolar solvents, the crown ethers increase the solubility of ionic materials. For example, in the presence of 18-crown-6, potassium fluoride is soluble in benzene and acts as a reactive nucleophile ... 

The range of nueleophiles whieh have been observed to partieipate in nueleophilie aromatie substitution is similar to that for S[, 2 reactions and includes alkoxides, phenoxides, sulftdes, fluoride ion, and amines. Substitutions by earbanions are somewhat less common. This may be because there are frequently complications resulting from eleetron-transfer proeesses with nitroaromatics. Solvent effects on nucleophilic aromatic substitutions are similar to those discussed for S 2 reactions. Dipolar... 

It was pointed out earlier that the low nucleophilicity of fluoride ion and its low concentration in HF solutions can create circumstances not commonly observed with the other halogen acids. Under such conditions rearrangement reactions either of a concerted nature or via a true carbonium ion may compete with nucleophilic attack by fluoride ion. To favor the latter the addition of oxygen bases, e.g., tetrahydrofuran, to the medium in the proper concentration can provide the required increase in fluoride ion concentration without harmful reduction in the acidity of the medium. 

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