---
title: "Nucleophilic Acyl Substitution and the Reactivity Ladder"
description: "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 every step can be take"
canonical: https://lightmysky.com/learn/science/nucleophilic-acyl-substitution-and-the-reactivity-ladder-mt_b60fq2aQ7r
source: https://lightmysky.com/learn/science/nucleophilic-acyl-substitution-and-the-reactivity-ladder-mt_b60fq2aQ7r.md
retrieved: 2026-09-12
---

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# 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 every step can be taken downhill and none uphill.

Subject: Science · Area: Chemistry · Ages 20 to 21
Page: https://lightmysky.com/learn/science/nucleophilic-acyl-substitution-and-the-reactivity-ladder-mt_b60fq2aQ7r

## Ready when they can

- 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 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

## Lesson: One ladder, travelled downhill only

Acyl substitution runs addition then elimination as a fixed two-act play. 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.

**Example.** 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 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, then esterify, and every step runs downhill.

**Tip.** Acid hydrolysis of an ester returns the neutral acid, while base hydrolysis spends hydroxide and leaves the carboxylate salt. Both pass through the same intermediate, but the fate of the product differs.

**Recap.** Add, eliminate, and only ever walk the ladder downhill.

## Practice

8 questions on this page, each with its working shown.

## Needs first

- [Acetals, Imines and Protecting Groups](https://lightmysky.com/learn/science/acetals-imines-and-protecting-groups-mt_3dB99bKrMf)
- [Carboxylic Acids, Esters and Hydrolysis](https://lightmysky.com/learn/science/carboxylic-acids-esters-and-hydrolysis-mt_QLxUs5cOH2)

## Opens up

- [Enols, Enolates and Alpha Substitution](https://lightmysky.com/learn/science/enols-enolates-and-alpha-substitution-mt_EltcLAjnLC)
- [Chain Growth and Step Growth: Two Routes to a Polymer](https://lightmysky.com/learn/science/chain-growth-and-step-growth-two-routes-to-a-polymer-mt_LADBgarlKs)