Substitution fluorination

As noted, these zinc reagents find extensive application in the preparation of fluorinated styrenes [113, 114], aryl-substituted fluorinated propenes [114],fluor-inateddienes [115,116], and tnfluorovinyl ketones [117], as illustrated in equations 83-88... 

The use of nitrogen anions in this process has not been well investigated. Nitrogen anion (36) readily substituted fluorine in perfluoroazaaromatics and the products could be rationalized on the basis of kinetic and thermodynamic control. With tetafluoropyridazine and CsF as a source of F, none of the expected 4,5-isomer was obtained. For 4,5 substitution a less... 

Hales JM, Hagan DJ, Van Stryland EW, Schafer KJ, Morales AR, Belfield KD, Pacher P, Kwon O, Bredas JL (2004) Resonant enhancement of two-photon absorption in substituted fluorine molecules. J Chem Phys 121 3152-3160... 

The solubility and thermal stability of polymers are usually improved and the surface energy is decreased by substituting fluorine atoms for the hydrogen atoms in the isopropylidene units connecting phenylene units in the main chain. 

Second, the effect of substituting fluorine by other atoms or groups... 

However, phenyllithium does not substitute fluorine or methoxy and methyl-lithium affords a mixture of fluorinated and methylated anions (Scheme 14) ... 

Figure 13.3. Illustration of increase in dielectric constant increment owing to orientational polarization of nonsymmetrically substituted fluorine atoms.

Chlorine monofluoride substitutes fluorine for bromine atoms in haloalkanes and halo esters.28104... 

Unlike bromine trifluoride (vide infra), chlorine monofluoride is capable of substituting fluorine for chlorine without catalysts in compounds eliminating chlorine via the intermediate formation of stable carbocations. Chlorine is easily replaced by fluorine at — 50 to — 10 C in /m-butyl chloride and at the secondary carbon atom in 1.2-dichloropropane and 1,2,3-tri-chloropropane.107... 

Bromine trifluoride is used to selectively substitute fluorine for bromine in brominated alkanes and esters. The reactions are carried out by gradual addition of bromine trifluoride to a solution of the substrate in CFC-113 or CFC-112 at 10-20nC. The bromine-fluorine exchange in mono-bromohaloalkanes is nonstereoselective and accompanied, in some eases, by skeletal rearrangements, hydride shifts, and halogen migrations. All three fluorine atoms in bromine trifluoride are involved in the fluorination reaction. Chlorine atoms in the substrate molecules remain intact.109... 

Diethyl phenylmalonate and its sodium salt undergo substitutive fluorination by perfluoro-1-fluoropiperidinc (1) and perfluorinated polymers. The fluorination product is diethyl fluoro(phenyl)malonate, perfluoro-l-fluoropiperidine being a more efficient fluorinating agent than the N-F containing fluoropolymers 5. 

Arsenic(III) fluoride, like antimony(III) fluoride (see Section 12.1.), is used to substitute fluorine for chlorine, bromine and iodine not only at carbon but also at other atoms, such as phosphorus, boron or metals. Chlorophosphanes undergo oxidative fluorination with arsenic(III) fluoride [or antimony(III) fluoride] to trifluoro-A5-phosphanes 1. 

Electrochemical oxidation of pentafluoroaniline (1) at a platinum anode at a potential of +1.5 to 1.6 V (vs SCE) using an acctonc/water/potassium acetate electrolyte leads to decafluoro-diphenyldiazene (3) and octafluorophenazine (2) in 18% and 6% yield, respectively. The phenazine heterocycle is formed by a sequence of oxidation/substitution steps in which nitrogen radical intermediates substitute fluorine atoms. The low yield in this reaction is due to a laborious workup.203 204... 

Thermal decomposition of aryl azides under a nitrogen atmosphere leads to nitrenes which are able to substitute fluorine in polyfluorinated naphthalenes, albeit with a poor yield (4%). Since no substitution product was isolated when oxygen was present during this reaction, the intermediacy of a triplet nitrene was proposed, which is completely trapped by oxygen.207... 

Frickel225 has provided a comprehensive review of the chemistry of the retinoids which shows that most of the literature relates to molecular modifications aimed at pharmaceutical purposes. It has been rare to find a retinoid designed to include a polar element at a side chain location, although some work has been done on substituting fluorine into the side chain. Dawson Hobbs226 updated Frickel s review to 1994 and noted some additional work... 

The one-electron molecular-orbital energies resulted from the calculations when the oxygen atom of the cluster is replaced by substitution fluorine was show in Fig. 5 on the right side. 

For zirconia with water bridge type and anion nitrogen, orbital connected with nitrogen appear in the forbidden gap. Thus, zirconia with anion nitrogen and water on surface must be deep donor. The one-electron molecular-orbital energies resulted from the calculations when the oxygen atom of the cluster is replaced by substitution fluorine was show in Fig. 11 on the right side. 

Syntheses of heterocyclic compounds with perfluorinated side chains are mainly performed by substitutional fluorinations of the available fragments or by the introduction of a perfluoroalkyl group in the heterocycle. The development of convenient approaches and direct perfluoro-alkylation methods is a current challenge. 

In the syntheses of heterocyclic compounds with perfluoroalkyl groups, the key methods are based on two types of chemical transformations. The first type involves the introduction of the perfluoroalkyl group on the heterocyclic system, namely, substitutional fluorination of fragments already available in the system or direct introduction of the perfluoroalkyl group onto the heterocycle. 

In contrast to chlorine, bromine, and iodine, which deactivate aromatic rings for electrophilic substitutions, fluorine exerts an even higher activation of the ring than does hydrogen, as has been shown by measurements of the rates of bromination of durene (1,2,4,5-tetramethylben-zene) and its 3-halo derivatives [35]. 

In aromatic systems, oxazolines can have three different functions (Fig. 4). Firstly, they can be used as protecting groups for carboxylic acids. Secondly, they activate even electron-rich aromatic systems for nucleophilic substitution. Fluorine or alkoxy groups in the ortho position can be substituted by strong nucleophiles such as Grignard reagents. Thirdly, when biaryl compounds with axial chirality are synthesized in these reactions, oxazolines can induce the formation of only one atropisomer with excellent selectivity. These three qualities were all used in the synthesis of 20, a precursor of the natural product isochizandrine [10]. 

More unusual reactions are those aimed at substituting fluorine by oxygen or even... 

In view of possible industrial products, cleavage of the cyclobutane ring is the most interesting reaction. The pyrolysis of substituted fluorinated cyclobutanes may yield four unsaturated products however, cleavage A seems to be favored. 

The effect of substituting fluorine for hydrogen in the methylene halides is to increase the rate of carbanion formation and presumably to stabilize the carbanion and decrease the pK. The effect of fluorine substitution on the acidity of other carbon acids is not so clear. In some cases fluorine substitution leads to a smaller increase in rate than expected from the inductive effect and in other cases results in a decrease in the rate of carbanion formation and an increase in pK values. The results shown in Table 6 were obtained for the rate coefficient (k) for methoxide ion catalysed carbanion formation per hydrogen atom by following the appearance of the MeOH absorbance in the IR spectrum when the esters were allowed to exchange in MeOD [167]. The acidity of the nitro-paraffins in Table 7 is mostly increased by chlorine substitution (p/T... 

Prior structure-activity studies with diclofenac analogs indicate that methyl or chlorine substituents on the lower aniline ring of the inhibitor in the ortho position are required for potent inhibition of COX (44). Analogs with halogen substitutions (fluorine or chlorine) at the 5 position of the phenylacetic acid ring demonstrate an even higher potency for COX inhibition (44). 

We prepared a number of derivatives of benzoyltrifluoroacetone bearing substituents on the meta and para positions of the benzene ring and converted these to the corresponding europium tetrakis chelates. Schimitschek (33) has studied the nine BTFA derivatives obtained by substituting fluorine, chlorine, or bromine at the ortho, meta, or para position of the ring. Table I shows that substituents can have a considerable effect on the laser threshold of these compounds although the... 

Indeed, onium salts improve dramatically the results for the substitutive fluorination of 3,4-dichloronitrobenzene in sulfolane at 120°C, as shown from the relative initial rates (ref. 17) ... 

Because of the high lattice energy of inorganic fluorides, substitutive fluorination with alkaline fluorides in aprotic solvents is always a two-phase reaction which is very dependent on the origin and the preparation of the solid reagent. 

A series of symmetrically substituted fluorine derivatives of BAPTA (see Figure 3.3A) has been synthesized.One of these chelators is 5F-BAPTA (Figure 3.5A), which has a binding constant for Ca, of 1.4 x 10 M and a F NMR chemical shift, 8, that in the free ligand is different from that in the complex with Ca + (ASca2+ 6 ppm). The rate of Ca + dissociation, koft, is 5.7 X 10 s , which gives the rate of association, kon, as 8 x 10 M " s according to... 

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