Electronegativity and Induction

Various effects on N acids (resonance, hybridization, sterics, and induction)  

If a benzene ring can stabilize a negative charge on oxygen via resonance, it should also stabilize a negative charge on N or C. In fact, the pKaS of various anilines are between 18 and 28, whereas typical alkyl amines are in the range of 38 to 42 (Table 5.5A). 

Another case where resonance influences carbon acidities is the comparison of toluene to diphenylmethane and lastly triphenylmethane (pK s = 41.2,33.0, and 31.5, respectively). The large shift between toluene and diphenylmethane is due to additional resonance stabilization of the conjugate base. However, the third additional phenyl ring has little effect. Several factors are involved to account for this small change. One is that the phenyl rings cannot all be planar with the anionic carbon, which is required for full resonance stabilization (examine the trityl radical discussed in Chapter 2), and instead a propeller twist develops in the anion. This is an example of a steric inhibition of resonance. A second factor is called a resonance saturation effect. Once the charge on the conjugate base is stabilized via resonance, the additional resonance is not as effective at stabilization. 

Competitive resonance effects can be found. In general, C-H bonds alpha to ketones are more acidic than when alpha to ester carbonyls, which are more acidic relative to amide carbonyls, all three of which are more acidic than C-H bonds near carboxylates. The resonance stabilization gained by ionization of the C-H bond is increasingly lower in this series because the O, N, or 0 heteroatom on the ester, amide, or carboxylate, respectively, is increasingly involved in resonance with the carbonyl in the acid prior to ionization of the C-H bond. In such cases, we must consider the role of resonance in stabilizing the HA compound as well as A . 

Similar resonance effects influence the acidities of ammonium and amine acids. The most interesting examples are relevant to biological chemistry, and a discussion of these is left to the next section. 

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Steric and inductive effects determine the rate of formation of the pentacovalent siUcon reaction complex. In alkaline hydrolysis, replacement of a hydrogen by alkyl groups, which have lower electronegativity and greater steric requirements, leads to slower hydrolysis rates. Replacement of alkyl groups with bulkier alkyl substituents has the same effect. Reaction rates decrease according to ... 

Indolmycin, biosynthesis of, 864 Inductive effect. 37, 562 alcohol acidity and. 604 carboxylic acid strength and. 758 electronegativity and, 37 electrophilic aromatic substitution and, 562... 

The F s are very electronegative and, by their inductive effects, they delocalize electron density from the N atom. The N in NFj has less electron density than the N in NH, NF, is a weaker base than NH,. The CH, group, on the other hand, is electron-donating and localizes more electron density on the N of CH,NH, making CHjNHj a stronger base than NH,. 

The bond polarization due to electronegative substituents should propagate along the carbon chain and decrease with the inverse cube of the distance. Much smaller inductive effects are thus expected in /I and y position. Table 3.2 shows, however, that the observed ft and y effects do not correlate at all with substituent electronegativities and that the influence of other effects must therefore be involved. 

The influence of fluorine substituents on the stability of alkyl radicals derives from the same complex interplay of inductive and resonance effects that affects their structure. Simple orbital interaction theory predicts that substituents of the -X type (that is, electronegative substituents bearing lone pairs) should destabilize inductively by virtue of their group electronegativities, and stabilize by resonance to the extent of their ability to delocalize the odd electron. 

Tuning of selectivity in the metallation of m-anisic acid has been realized by an appropriate choice of base.67 The results obtained with LTMP have indicated that the regiochemistry of the lithiation of m-anisic acid is thermodynamically controlled. Resonance and inductive effects favour removal of the H(2) proton. In contrast, superbases such as n-BuLi-r-BuOK are not significantly influenced by or//m-directing groups and preferentially attack H(4), the inductively activated aromatic position next to the most electronegative heteroatom and/or the most acidic position available. 

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