Nucleophilic Acyl Substitution and the Reactivity Ladder
When the carbonyl carbon carries a leaving group, the tetrahedral intermediate collapses forward instead of being protonated. The result is a ladder of acid derivatives on which, under ordinary conditions, each step needs a willing leaving group with its reagents and conditions.
What a learner can do afterwards
- Orders acyl chlorides, anhydrides, esters and amides by reactivity and gives the electronic reason
- Draws the addition then elimination sequence for a stated interconversion
- Explains why an amide cannot be made into an ester directly under ordinary conditions and states what has to be done instead
- Distinguishes acid and base hydrolysis of an ester by mechanism and by the fate of the product
1 · Read
Acyl substitution runs addition then elimination as a fixed two-act play. On the unactivated route taught here, the nucleophile first attacks the carbonyl carbon to give a tetrahedral intermediate, exactly as with aldehydes. Then the intermediate collapses, reforming the carbonyl and ejecting the leaving group. Acid activation can reorder the start by protonating first, which this route sets aside.
The reactivity ladder runs acyl chlorides above anhydrides above esters above amides. Chloride leaves gladly while the amide nitrogen clings, and resonance donation from the attached heteroatom steadies the starting material against attack. Read any interconversion by asking whether the leaving group departs willingly.
An amide cannot convert directly into an ester under ordinary conditions because the traffic flows the wrong way up the ladder. Amides sit at the calm bottom while esters perch above. Hydrolyse the amide to the acid first with heat in aqueous acid, or in base followed by acidic workup since base alone strands carboxylate, then esterify with acid plus alcohol while removing water, and each step runs with a willing leaving group.
Acid hydrolysis of an ester returns the neutral acid, while base hydrolysis consumes hydroxide and leaves the carboxylate salt. Both pass through a tetrahedral motif, though in different protonation states. Only the acid route gives back the neutral acid directly; the base route needs a separate acidic workup to reach the same neutral acid.
Add, eliminate, and check each leaving group with its conditions.
The rewritten reading was written for this dataset.
2 · Watch
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