Trifluoromethyl group polar effect

The strong inductive effect of the three trifluoromethyl groups polarizes the bond between the carbon and hydrogen and makes the hydrogen very acidic (pKa = 7). In basic media, the compound is deprotonated, and the tris(trifluoromethyl)carbanion adds to the double bond of acrylonitrile in the sense of the Michael addition. It joins the P-position of acrylonitrile because of its lower electron density. The product is 4,4-bis(trifluoro-methyl)-5,5,5-trifluorovaleronitrile T [107],... 

However, if two trifluoromethyl groups are attached to the beta carbon, the cumulative effect of the two trifluoromethyl groups polarizes the double bond so that lower electron density is in alpha position, and the nucleophile becomes attached to the alpha carbon. The reaction product is L, ethyl 2-(P-hydroxyethylamino)-3-trifluoromethyl-4,4,4-tri-fluorobutanoate [117]. 

The trifluoromethyl group has become an important structural component of many bioactive compounds, mainly because of its polar influence and its effect on the lipophilicity of compounds. 

It has been shown that the SF5 group has a similar but often enhanced effect on the lipophilicity of compounds, and on essentially any physical or chemical property that derives from its strong polar influence. It also has the advantage of greater hydrolytic stability than a trifluoromethyl group. 

Similarly, electrophilic CHj radicals add faster to ethylene than to tetrafluo-rethylene, in which the inductive effects of the fluorine substituents make the double bond somewhat electron deficient. The reverse selectivity is shown by CH3 radicals, which are nucleophilic in character [24]. This parallels the observations in organic chemistry thatcarbonium ion formation is facilitated by replacement of hydrogens by alkyl groups and hindered by CF3 groups. There is a polarization of a electrons towards the trifluoromethyl group, whereas these electrons can be more effectively released by alkyl substituents. 

A Fluorine is very electronegative and this strong electron-withdrawing effect not only polarizes the O-H bond in the sense O but also the electron-deficient carbon of the trifluoromethyl group stabilizes the alkoxide. 

Generally the ap/om ratio is between 1.2 and 1.3 for substituents for which resonance delocalization is impossible or unimportant (17). For the equilibrium reactions, the Opltrifluoromethyl group ranges from 1.25 for the phenols to 1.34 for the anilines. These results suggest that the polar effect of the trifluoromethyl group is dominant even in reactions that are electron-rich. 

Sigma electron withdrawing groups like trifluoromethyl have no effect at C4 which is consistent with partial radical and not polar character at that site. Trifluoromethyl at C2 does provide some rate acceleration. However, the origin of this effect is not clear since the SDKIEs are similar to those of the parent molecule. 

Polyimides with low 8 values were prepared by introducing of fluorine as fluorine substitution lowered the electron polarization and close packing of the polyimide. The 8 values of polyimides with trifluoromethyl groups along with fluorene moieties were lower (2.51-2.69), and the effects of fluorine atoms on the dielectric constant were also observed in the polyimides containing fluorene (Table 7.13). 

Polar effects also appear to exist in the addition reactions of certain radicals to substituted ethylenes. It is clear from Table II that for electronegative radicals like difluoroamino or hydroxy and to a lesser extent trifluoromethyl radical and hydrogen atom, substitution with donor groups like methyl increases the rate of addition. Substitution with electronegative atoms like fluorine or chlorine has the effect of slowing the rate of addition by hydroxy or trifluoromethyl radicals but the rate of addition of methyl radicals is increased. 

The addition is facilitated by polarization of the alkenic double bond by the powerful electron-withdrawing (-1) effect of the attached trifluoromethyl group and the reaction probably occurs via the 1,1-difluoroallylic cation with solvent-assisted ionization of the initial step. ... 

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