Replacement of Hydrogen by Fluorine

For the past 20 years, four mam ways of replacement of hydrogen by fluorine have been used fluorination using elemental fluorine, electrochemical fluon nation, fluorination using high-valency metal fluorides, and selective electro philic fluorination... 

Formal replacement of hydrogen by fluorine takes place in the a-position of a ketone by treatment of enol acetates with triethylamine tris(hydrogen fluoride).51-55 The kinetically favored isomers are formed.51,55 Furthermore, benzylic positions bonded with an electron-withdrawing group (ketone, ester, nitrile, sulfonate) can be fluorinated electrochemically.51" 6-58 There are also various examples of the preparation of a-fluorosulfides front sulfides.51... 

Lipophilicity. In general, the replacement of hydrogen by fluorine in a molecule increases its lipophilicity, particularly with groups such as CF3 and OCF3. Lipophilicity plays a key role in the transport of molecules through plant and insect cuticles. In addition to lipophilicity, increasing the number of fluorine atoms in a... 

Steric effects. As the second smallest substituent, fluorine closely resembles hydrogen s steric requirement for binding to an active site. This makes replacement of hydrogen by fluorine a common bioisosteric replacement [11],... 

From the previous discussion on extensive fluorination (Chapter 2, Section IV) it might be assumed that, in general, it will be very difficult to effect the selective replacement of hydrogen by fluorine in preparatively useful reactions. This has been the perceived wisdom in the past but the situation is changing rapidly [56]. 

Reactions that lead to replacement of hydrogen by fluorine could, in principle, proceed by any of the processes outlined in Figure 9.6, and it is frequently difficult to make any meaningful distinction between the possibilities. 

Replacing all the hydrogens alpha to a heteroatom by fluorine atoms can block GYP450-mediated N- or O-dealkylation processes completely but the similar replacement of hydrogen by fluorine atoms on an aryl-system will have little impact upon aromatic hydroxylation beyond that of electron withdrawal. 

Direct replacement of hydrogen by fluorine. Although most organic compounds inflame or explode when mixed with fluorine in normal circumstances, direct fluorination of many compounds is possible under appropriate conditions. There are two main techniques. 

Change of residual groups - e.g. replacement of hydrogen by fluorine or increase the carbon chain length. (6,29)... 

Silver (I) fluoride-calcium fluoride Replacement of hydrogen by fluorine s. 44, 408... 

Although the initial abstraction reaction has a low activation energy,successive replacement of hydrogen by fluorine will be expected to increase the activation energy both from the concomitant strengthening of C-H bonds and adverse polar effects in the transition state. Of some relevance in this connection are the relative rates of fluorination at different sites reported for gas phase studies of 1-f1uorobutane. These are shown in Fig. 15. It is clear that introduction of fluorine deactivates both a and 3 sites. We may use this data as a basis for discussing the fluorination of polyethylene. 

The chemical properties of anionic fluorinated surfactants also differ from those of their hydrocarbon analogs by the increased acid strength of the parent acids. Replacement of hydrogen by fluorine increases the dissociation constant of carboxylic acids (Table 3.6) [19]. Perfluorinated alkanecarboxylic acids are strong... 

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