Acetyl chloride will react with an alcohol in the presence of a base to give an acetate ester and we get the same product if we use acetic anhydride.

In each case, a substitution (of the black part of the molecule, Cl⁻ or AcO⁻, by cyclohexanol) has taken place—but how? It is important that you learn not only the fact that acyl chlorides and acid anhydrides react with alcohols but also the mechanism of the reaction. In this chapter you will meet a lot of reactions, but relatively few mechanisms—once you understand one, you should find that the rest follow on quite logically. The fi rst step of the reaction is, as you might expect, addition of the nucleophilic alcohol to the electrophilic carbonyl group—we’ll take the acyl chloride fi rst. The base is important because it removes the proton from the alcohol once it attacks the carbonyl group. A base commonly used for this is pyridine. If the electrophile had been an aldehyde or a ketone, we would have got an unstable hemiacetal, which would collapse back to starting materials by eliminating the alcohol. With an acyl chloride, the alkoxide intermediate we get is also unstable. It collapses again by an elimination reaction, this time losing chloride ion, to form the ester. Chloride is the leaving group here—it leaves with its negative charge.

With this reaction as a model, you should be able to work out the mechanism of ester forma tion from acetic anhydride and an alcohol. Try to write it down without looking at the acyl chloride mechanism above, and certainly not at the answer below. Here it is, with pyridine as the base. Again, addition of the nucleophile gives an unstable intermediate, which undergoes an elimination reaction, this time losing a carboxylate anion to give an ester.

We call the unstable intermediate formed in these reactions the tetrahedral intermediate because the trigonal (sp2) carbon atom of the carbonyl group has become a tetrahedral (sp3) carbon atom.

●Tetrahedral intermediates Substitutions at trigonal carbonyl groups go through a tetrahedral intermediate and then on to a trigonal product.

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

pKa is a useful guide to leaving group ability

?How do we know that the tetrahedral intermediate exists

?Why are the tetrahedral intermediates unstable

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