Amides are the least reactive towards nucleophiles because they exhibit the greatest degree of delocalization. You met this concept in Chapter 7 and we shall return to it many times more. In an amide, the lone pair on the nitrogen atom can be stabilized by overlap with the π* orbital of the carbonyl group—this overlap is best when the lone pair occupies a p orbital (in an amine, it would occupy an sp³ orbital).

The molecular orbital diagram shows how this interaction both lowers the energy of the bonding orbital (the delocalized nitrogen lone pair), making it neither basic nor nucleophilic, and raises the energy of the π* orbital, making it less ready to react with nucleophiles. Esters are similar, but because the oxygen lone pairs are lower in energy, the effect is less pronounced. The degree of delocalization depends on the electron-donating power of the substituent and increases along the series of compounds below from almost no delocalization from Cl to com plete delocalization in the carboxylate anion, where the negative charge is equally shared between the two oxygen atoms.

The greater the degree of delocalization, the weaker the C=O bond becomes. This is most clearly evident in the stretching frequency of the carbonyl group in the IR spectra of carboxylic acid derivatives—remember that the stretching frequency depends on the force constant of the bond, itself a measure of the bond’s strength. The carboxylate anion is included because it represents the limit of the series, with complete delocalization of the negative charge over the two oxygen atoms. There are two frequencies for the anhydride and the carboxylate anion because of symmetric and antisymmetric stretching of identical bonds. Amides react as electrophiles only with powerful nucleophiles such as HO−. Acid chlorides, on the other hand, react with even quite weak nucleophiles: neutral ROH, for example. They are more reactive because the electron-withdrawing effect of the chlorine atom increases the electrophilicity of the carbonyl carbon atom.

Bond strengths and reactivity.

 You may think that a weaker C=O bond should be more reactive. This is not so because the partial positive charge on carbon is also lessened by delocalization and because the molecule as a whole is stabilized by the delocalization. Bond strength is not always a good guide to reactivity! For example, in acetic acid the bond strengths are surprising. The strongest bond is the O–H bond and the weakest is the C–C bond. Yet very few reactions of acetic acid involve breaking the C–C bond, and its characteristic reactivity, as an acid, involves breaking O–H, the strongest bond of them all! The reason is that polarization of bonds and solvation of ions play an enormously important role in determining the reactivity of molecules. In Chapter 37 you will see that radicals are relatively unaffected by solvation and that their reactions follow bond strengths much more closely.

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How electron donation and withdrawal change chemical shifts

Uneven electron distribution in aromatic rings

The benzene ring current causes large shifts for aromatic protons

Summary chart of proton NMR shifts

Chemical shifts of CH groups

CH and CH2 groups have higher chemical shift than CH3 groups

Methyl groups give us information about the structure of molecules

Proton chemical shifts tell us about chemistry

Protons on saturated carbon atoms Chemical shifts are related to the electronegativity of substituents

Regions of the proton NMR spectrum

Integration tells us the number of hydrogen atoms in each peak

The differences between carbon and proton NMR