Substitution reactions of fluorine

A substitution reaction of fluorine and oxygen easily proceeds on unstable CxO to form CXF as shown in equation 10. 

Addition of fluorine to a C=C bond is different from that of the other halogens in one important respect the heat of reaction exceeds the dissociation energy of an aliphatic C-C bond (80 kcl/mole) quite appreciably. Addition and substitution reactions of fluorine are so exothermic that most organic substances burn or explode if brought into direct contact without special arrangements.15 Addition of F2 to olefins has no preparative importance 48 in the aromatic series addition and substitution result simultaneously. In electrophilic addition, i.e., in most cases, chlorine reacts faster than bromine with olefins, but in nucleophilic addition bromine reacts faster than chlorine.16... 

A similar synthetic approach was used in the synthesis of polyfluorinated oxygen-and nitrogen-containing macrocycles. Substitution reaction of fluorinated pyridines... 

G.l.c. retention data over a ran of temperatures have been measured for Cr(hfa)3, Cr(tfa)3, and several other such chelates in three liquid phases and, together with other solution-phase data, have been used to show that the behaviour of these complexes in the liquid phase is determined solely by nonspecific van der Waals-type forces. " The electrophilic substitution reactions of fluorinated P-diketonato-chromium(iii) complexes have been studied under controlled conditions and the results obtained were shown to support the quasi-aromatic character of the six-membered chelate ring. Seven new tris(P-diketonato)chromium(iii) complexes have been prepared and characterized by magnetic, i.r., and electronic spectral studies. ... 

The experimental results which we will describe are primarily those obtained in this laboratory but a few experimental data exist which have been collected elsewhere. Our experimental program in fluorine atom chemistry has been motivated primarily by two facts which have also been important to studies performed by other methods (1) atomic fluorine abstraction of hydrogen atoms from appropriate molecules has been demonstrated to be an important class of reactions for chemical lasers W. In particular, the reactions of F + H2 HF + H and F + D DF + D have been investigated in great detail by various theoretical and experimental approaches (3-11) the latter reaction provides us with an example from the general class of reactions of fluorine atoms with diatomic molecules. (2) Substitution reactions of fluorine atoms with unsaturated hydrocarbons Involving the formation of C-F bonds frequently are observed to proceed through a "complex" which... 

Konno T, Takehana T, Ishihara T, Yamanaka H. The fluorine-containing 7t-allylmetal complex. The transition metal-catalyzed allylic substitution reaction of fluorinated allyl mesylates with various carbon nucleophiles. Org. Biomol. Chem. 2004 2 93-98. 

Kinetics of Nucleophilic Substitution Reactions of Polyfluoroaromatic Compounds Rodionov, P P, Furin, G G J Fluorine Chem 47. 361 34 105 ... 

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]... 

Reactions of fluorinated dipolarophiles. Electron-deficient unsaturated species generally make better dipolarophiles, therefore, fluonnated alkenes become better dipolarophiles when vinylic fluonnes are replaced by perfluoroalkyl groups For example, perfluoro-2-butene is unreactive with diazomethane, but more highly substituted perfluoroalkenes, such as perfluoro-2-methyl-2-pentene, undergo cycloadditions in high yields [5] (equation 2) Note the regiospecificity that IS observed in this reaction... 

Chlorine and iodine can be introduced into aromatic rings by electrophilic substitution reactions, but fluorine is too reactive and only poor yields of monofluoro-aromatic products are obtained by direct fluorinafion. Aromatic rings react with CI2 in the presence of FeCl3 catalyst to yield chlorobenzenes, just as they react with Bi 2 and FeBr3. This kind of reaction is used in the synthesis of numerous pharmaceutical agents, including the antianxiety agent diazepam, marketed as Valium. 

The same fluoroalkoxy substituents, however, are able to enhance substitutional reactivity of fluorinated polyphosphazenes by originating methatetical exchange reactions on polymers in the presence of new nucleophiles and under appropriate experimental conditions. Thus, a series of exchange reactions at phosphorus atoms bearing the trifluoroethoxy substituents in PTFEP have been describedbyH.R. Allcock [508] (Fig. 13),Cowie [482,483] (Fig. 14), and Ferrar [509] (Fig. 15), while surface modification of PTFEP films were reported by Allcock [514,515] (Fig. 16 or 17) and by Lora [516] (Fig. 18). 

In contrast to the cathodic reduction of organic tellurium compounds, few studies on their anodic oxidation have been performed. No paper has reported on the electrolytic reactions of fluorinated tellurides up to date, which is probably due to the difficulty of the preparation of the partially fluorinated tellurides as starting material. Quite recently, Fuchigami et al. have investigated the anodic behavior of 2,2,2-trifluoroethyl and difluoroethyl phenyl tellurides (8 and 9) [54]. The telluride 8 does not undergo an anodic a-substitution, which is totally different to the eases of the corresponding sulfide and selenide. Even in the presence of fluoride ions, the anodic methoxylation does not take place at all. Instead, a selective difluorination occurs at the tellurium atom effectively to provide the hypervalent tellurium derivative in good yield as shown in Scheme 6.12. 

In contrast to saturated hydrocarbons, the unsaturated hydrocarbons react with atomic fluorine by two pathways, i.e. (atomic fluorine addition at >C=C< double bond and hydrogen substitution by fluorine atoms. The reaction of fluorine with aromatic hydrocarbons proceeds with the formation of F-derivatives and hydrogen atoms break off ... 

Electrophilic substitution in benzo[fe]thieno- and benzo[fe]furo-[2,3-c]pyridines (2) occurs mainly at the 6-position, although when this position is blocked by Cl in a related structure 5-,7-, and 8-substituted products are formed. The usefulness of triflu-oromethanesulfonic acid as a new solvent with CFCI3 for the reaction of fluorine with aromatics has been explored. Fluorobenzene gives 1,4-difluorobenzene (31%) and 1,2-difluorobenzene (7%) instead of the addition products mainly observed when the acid is absent 1,2- and 1,3- but not 1,4-difluorobenzene undergo further substitution at appropriate acidity. 

One of the very few examples of a four-membered heterocycle with sulfur atoms substituted 1,2 was reported by Dupont workers (60JA1515,61JA3434). Its synthesis involves the high temperature reaction of fluorinated alkynes and elemental sulfur, probably via a diradical intermediate (Scheme 102). The chemistry of these 1,2-dithietenes has been reviewed (76RCR639). As discussed later, these dithietenes form complexes with a number of transition metals. 

Let us now look at some examples to illustrate what we have discussed so far to get a feeling of how structural moieties influence the mechanisms, and to see some rates of nucleophilic substitution reactions of halogenated hydrocarbons in the environment. Table 13.6 summarizes the (neutral) hydrolysis half-lives of various mono-halogenated compounds at 25°C. We can see that, as anticipated, for a given type of compound, the carbon-bromine and carbon-iodine bonds hydrolyze fastest, about 1-2 orders of magnitude faster than the carbon-chlorine bond. Furthermore, we note that for the compounds of interest to us, SN1 or SN2 hydrolysis of carbon-fluorine bonds is likely to be too slow to be of great environmental significance. 

The fluorine substitution reactions of 4-fluorophenyl ketones can be extended by using alkanc-or arenesulfinates as the sulfur nucleophile, opening access to 4-(alkyl)- or 4-(arylsulfonyl) phenyl ketones 6.14... 

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. 

Both experimental and theoretical studies have been reported of fluoro-denitration and fluoro-dechlorination reactions using anhydrous tetrabutylammonium fluoride in DMSO. The absences of ion pairing and strong solvation are critical in contributing to the reactivity of the fluorinating agent24 Quaternary ammonium salts derived from cinchona alkaloids have been shown to be effective catalysts in an improved asymmetric substitution reaction of /1-dicarbonyl compounds with activated fluoroarenes. The products may be functionalized to yield spiro-oxindoles.25... 

Kinetic studies of the substitution reaction of 2-chloro-l-methylpyridinium iodide with phenoxides are consistent with the SnAt mechanism, with rate-determining nucleophilic attack.38 The effects of a variety of ring substituents on the reactivities of 2-fluoro- and 2-chloro-pyridines in reactions with sodium ethoxide in ethanol have been examined. The results were discussed in terms of the combination of steric, inductive, and repulsive interactions.39 Substitution in 2,4,6-trihalopyridines normally occurs preferentially at the 4-position. However, the presence of a trialkylsilyl group at the 3-position has been shown to suppress reaction at adjacent positions, allowing substitution at the 6-position.40 Methods have been reported for the introduction and removal of fluorine atoms for polyfluoropyridines. Additional fluorine atoms were introduced by metallation, chlorination, and then fluorodechlorination, while selective removal of fluorine was achieved by reduction with either metals or complex hydrides or alternatively by substitution by hydrazine followed by dehydrogena-tion-dediazotization.41... 

Soloshonok and Hayashi applied chiral ferrocenylphosphine-gold(I) complexes to asymmetric aldol-type reactions of fluorinated benzaldehydes with methyl isocyano-acetate (27) and A, A/-dimethyl-a-isocyanoacetamide (95). It is noteworthy that successive substitution of hydrogen atoms by fluorine in the phenyl ring of benzaldehyde causes gradual increase of both the cis selectivity and the ee of cw-oxazolines [53]. 

The reactions of fluorine with aqueous solutions of alkaline-earth-metal chlorides give different products depending on the Group II metal. With MC12 (M = Ca, Sr, or Mg), fluorination leads directly to MF2, but with BaCl2 the compound BaF(HF2) is formed. An intermediate step in the reaction involves the formation of BaCIF followed by substitution of Cl by HF2.77... 

The replacement of the fluorine atoms by chlorine atoms led to the formation of 2,2-dimethoxy-2,3-dihydrofurans 18 as the result of a ring enlargement. As in the difluorocyclopropyl series, the cyclopropane carbon with the geminal halogen substituents reached the oxidation state of a carboxylic acid by a sequence of elimination, addition and substitution reactions of unknown order. 

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