It’s useful to be able to compare leaving group ability quantitatively. This is impossible to do exactly, but a good guide is the pKa of the conjugate acid (Chapter 8). If X⁻ is the leaving group, the lower the pKa of HX, the better X⁻ is as a leaving group. If we go back to the example of ester formation from acyl chloride plus alcohol, there’s a choice of Me−, EtO−, and Cl⁻. HCl is a stronger acid than EtOH, which is a much stronger acid than methane. So Cl⁻ is the best leaving group and EtO− the next best. These observations apply only to reactions at the car bonyl group.

●Leaving group ability, The lower the pKa of HX, the better the leaving group of X− in carbonyl substitution reactions.

The most important substituents in carbonyl reactions are alkyl or aryl groups (R), amino groups in amides (NH2), alkoxy groups in esters (RO−), carboxylate groups (RCO2 −) in anhydrides, and chloride (Cl−) in acyl chlorides. The order of leaving group ability is then:

We can use pKa to predict what happens if we react an acyl chloride with a carboxylate salt. We expect the carboxylate salt (here, sodium formate or sodium methanoate, HCO₂Na) to act as the nucleophile to form a tetrahedral intermediate, which could collapse in any one of three ways. We can straightaway rule out loss of Me− and we might guess that Cl− is a better leaving group than HCO₂ − as HCl is a much stronger acid than a carboxylic acid, and we’d be right. Sodium formate reacts with acetyl chloride to give a mixed anhydride.

مواضيع ذات صلة

Strength of nucleophile and leaving group ability are related and pKa is a guide to both

Factors other than leaving group ability can be important

Using base strength to predict the outcome of substitution reactions of carboxylic acid derivatives

Amines react with acyl chlorides to give amides

?How do we know that the tetrahedral intermediate exists

?Why are the tetrahedral intermediates unstable

Acid chlorides and acid anhydrides react with alcohols to make esters

The product of nucleophilic addition to a carbonyl group is not always a stable compound

Oxidation of alcohols

?Secondary and tertiary alcohols: which organometallic, which aldehyde, which ketone

Making primary alcohols from organometallics and formaldehyde

Making carboxylic acids from organometallics and carbon dioxide