We have seen how pKa gives us a guide to leaving group ability: it is also a good guide to how strong a nucleophile will be. These two properties are the reverse of each other: good nucleophiles are bad leaving groups. A stable anion is a good leaving group but a poor nucleophile. Anions of weak acids (HA has high pKa) are bad leaving groups but good nucleophiles towards the carbonyl group.

● Guide to nucleophilicity in general, the higher the pK_a of AH the better A⁻ is as a nucleophile.

But just a moment—we’ve overlooked an important point. We have sometimes used anions as nucleophiles (for example when we made acid anhydrides from acid chlorides plus car boxy late salts, we used an anionic nucleophile RCO2 −) but on other occasions we have used neutral nucleophiles (for example when we made amides from acid chlorides plus amines, we used a neutral nucleophile NH3). Anions are better nucleophiles for carbonyl groups than are neutral compounds so we can choose our nucleophilic reagent accordingly. For proper comparisons, we should use the pKa of NH₄⁺ (about 10) if we are using neutral ammonia, but the pKa of RCO₂H (about 5) if we’re using the carboxylate anion. Ammonia is a good nucleophile and we don’t usually need its anion but carboxylic acids are very weak nucleophiles and we often use their anions. You will see later in this chapter that we can alter this with acid catalysts. So, this reaction works badly in either direction. We don’t make or hydrolyse esters this way.

While amines react with acetic anhydride quite rapidly at room temperature (reaction com plete in a few hours), alcohols react extremely slowly in the absence of a base. On the other hand, an alkoxide anion reacts with acetic anhydride extremely rapidly—the reactions are often complete within seconds at 0 °C. We don’t have to deprotonate an alcohol completely to increase its reactivity: just a catalytic quantity of a weak base can do this job. All the pKas you need are in Chapter 8.

مواضيع ذات صلة

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