Acyl Chlorides

Acyl chlorides — sometimes called acid chlorides — are the most reactive class of simple carbonyl derivatives. They are so reactive that they fume in moist air (reacting with water vapour) and attack skin on contact. This high reactivity, although a nuisance in the laboratory, makes acyl chlorides incredibly useful as acylating agents: they can install a –COR group onto almost any nucleophile in one step.

This lesson covers the OCR A-Level Chemistry A (H432) specification point 6.2.2: structure, preparation and reactions of acyl chlorides, including the nucleophilic addition-elimination mechanism.

1. Structure and Naming

An acyl chloride has the general formula R–COCl. The carbonyl carbon is bonded directly to a chlorine atom instead of an OH (carboxylic acid), OR (ester) or NR₂ (amide).

Key Definition — Acyl group: The R–CO– fragment derived from a carboxylic acid by removing the OH. An acyl chloride is an acyl group bonded to Cl.

Naming rules

Drop the -ic acid ending of the parent carboxylic acid and replace it with -yl chloride.

Acid	Acyl chloride	Formula
Ethanoic acid	Ethanoyl chloride	CH₃COCl
Propanoic acid	Propanoyl chloride	CH₃CH₂COCl
Benzoic acid	Benzoyl chloride	C₆H₅COCl
Butanoic acid	Butanoyl chloride	CH₃(CH₂)₂COCl

2. Why Acyl Chlorides Are So Reactive

Three factors combine to make the carbonyl carbon of an acyl chloride extraordinarily electrophilic:

Both the C=O oxygen and the Cl withdraw electron density from the carbonyl carbon.
Chloride is an excellent leaving group (it is a stable anion with a low-energy lone pair).
The C–Cl bond is polar (Cl δ–, C δ+) and relatively weak (~338 kJ mol⁻¹) compared to C=O (~745 kJ mol⁻¹).

The result is that even weakly nucleophilic species — water, alcohols, amines — react with acyl chlorides at room temperature without any catalyst. Compare this with carboxylic acid + alcohol (needs concentrated H₂SO₄ and reflux) and you can see why acyl chlorides are preferred in synthesis.

graph LR
  A[R-COCl] --> B[Strong delta+ on C]
  B --> C[Attacked by any nucleophile]
  C --> D[Nu displaces Cl-]
  D --> E[New C-Nu bond]

3. Preparation of Acyl Chlorides

You do not need a detailed mechanism, but you should know the preparation:

$R-COOH + SOCl_2 \longrightarrow R-COCl + SO_2 + HCl$

Carboxylic acid + thionyl chloride (SOCl₂) at room temperature or with gentle warming. The by-products SO₂ and HCl are both gases, so the acyl chloride is left behind and can be isolated by distillation.

OCR also accepts PCl₅ and PCl₃ as alternative reagents. All three generate HCl and so must be done in a fume cupboard.

4. Reactions of Acyl Chlorides

All the reactions below follow the same nucleophilic addition-elimination mechanism (Section 5). The pattern is always:

Nucleophile attacks the δ+ C of C=O.
C=O breaks, giving a tetrahedral intermediate.
C–Cl breaks as Cl⁻ leaves.
C=O reforms; the final product contains the new Nu group in place of the original Cl.

The only thing that changes from reaction to reaction is which nucleophile you start with.

4.1 With water — violent hydrolysis

$CH_3COCl + H_2O \longrightarrow CH_3COOH + HCl$

Vigorous exothermic reaction at room temperature.
Produces misty white fumes of HCl (visible when exposed to moist air).
No catalyst needed.

This reaction is why acyl chlorides must be stored in tightly sealed bottles and used in dry conditions — atmospheric moisture alone will hydrolyse them.

4.2 With alcohols — the fast route to esters

$CH_3COCl + C_2H_5OH \longrightarrow CH_3COOC_2H_5 + HCl$

Fast, exothermic, at room temperature.
No catalyst, no reflux needed.
Irreversible — unlike the H₂SO₄-catalysed esterification, this goes to completion.
HCl gas is evolved (misty fumes with ammonia).

Exam Tip: Acyl chloride + alcohol is the preferred way to make an ester in quantitative yield. Carboxylic acid + alcohol only gives 65–70% conversion at equilibrium.

4.3 With ammonia — amide formation

$CH_3COCl + 2NH_3 \longrightarrow CH_3CONH_2 + NH_4Cl$

One NH₃ molecule acts as a nucleophile, attacking the carbonyl and displacing Cl⁻.
A second NH₃ molecule neutralises the HCl produced, forming NH₄Cl.
Product: ethanamide CH₃CONH₂ — a primary amide.
Vigorous reaction, white smoke of NH₄Cl.

4.4 With primary amines — N-substituted amide formation

$CH_3COCl + 2CH_3NH_2 \longrightarrow CH_3CONHCH_3 + CH_3NH_3^+Cl^-$

One methylamine acts as nucleophile, the other neutralises HCl.
Product: N-methylethanamide CH₃CONHCH₃ — a secondary amide.
The N-nomenclature indicates the substituent is on nitrogen rather than on a carbon.

4.5 Summary table

Nucleophile	Product	By-product	Conditions
H₂O	Carboxylic acid R–COOH	HCl	Room temperature, violent
R'OH (alcohol)	Ester R–COOR'	HCl	Room temperature, fast
NH₃	Primary amide R–CONH₂	NH₄Cl	Room temperature, vigorous
R'NH₂ (primary amine)	Secondary amide R–CONHR'	R'NH₃⁺Cl⁻	Room temperature, fast

Notice the pattern — you replace the Cl of R–COCl with the Nu of R'–Nu–H, releasing HCl along the way (or being mopped up by excess nucleophile).

5. The Nucleophilic Addition-Elimination Mechanism

This mechanism is the most heavily examined mechanism in OCR organic chemistry. You must be able to draw it for any of the reactions above — typically water or ammonia.

Step-by-step for CH₃COCl + NH₃

Step 1 — Addition: The lone pair on the N of NH₃ attacks the δ+ C of the C=O. Two curly arrows: one from the N lone pair to C, and one from the C=O π bond onto O. A tetrahedral intermediate forms.

Step 2 — Proton loss: The N+ in the intermediate loses a proton to another NH₃ molecule (or base). This gives a neutral sp³ intermediate with an alkoxide.

Step 3 — Elimination: The C–O⁻ reforms as C=O, pushing out Cl⁻ as the leaving group. Curly arrows: one from the O⁻ lone pair to C–O π bond, and one from the C–Cl bond to form Cl⁻.

Overall: NH₃ has replaced Cl on the carbonyl carbon, giving ethanamide and HCl.

Key teaching points

The C=O breaks and reforms during the mechanism. This is why it is called nucleophilic addition-elimination — you add the nucleophile first (breaking the C=O), then eliminate the leaving group (reforming the C=O).
Compare with nucleophilic addition to aldehydes/ketones (Lesson 2): there, the C=O breaks and stays broken (the product is an alcohol). Here it reforms because the leaving group is ejected.
Be meticulous with curly arrows. OCR marks them very strictly — from a lone pair or bond to a bond-forming position, never from an atom.

graph TD
  A["Step 1: Nu attacks C=O, C=O breaks<br/>Tetrahedral intermediate with Nu+ and O-"] --> B[Step 2: Proton transfer removes Nu+ charge]
  B --> C[Step 3: Cl- leaves, C=O reforms]
  C --> D[Final product: R-CO-Nu + HCl]

6. Why Use Acyl Chlorides at All?

Acyl chlorides might seem like overkill — you can make esters from carboxylic acids + alcohols (Lesson 4), and amides by other routes. Why bother?

Complete reaction. The acyl chloride route goes to completion, not equilibrium. 100% yield possible.
Fast. Room temperature, no reflux, no concentrated acid.
Chemoselective. Acyl chlorides react with amines but not with less nucleophilic groups, so you can acylate selectively in complex molecules.
Gentler. No strong acid needed — ideal when the rest of the molecule contains acid-sensitive groups.

In industry, making amides from carboxylic acids directly is very hard (they just form a salt instead). The acyl chloride route via SOCl₂ is the standard workaround.

7. Worked Example — The Synthesis of Aspirin

Aspirin (2-acetoxybenzoic acid, or acetylsalicylic acid) is one of the most-prescribed drugs in history — around 40,000 tonnes are produced annually worldwide. Its commercial synthesis (developed by Felix Hoffmann at Bayer in 1897) uses the acyl-chloride reaction with an alcohol.

7.1 The starting material — salicylic acid

Salicylic acid (2-hydroxybenzoic acid) has both a carboxylic acid –COOH and a phenol –OH on adjacent positions of a benzene ring. The phenol –OH is the alcohol that will react with the acylating reagent.

7.2 The acylating reagent — ethanoyl chloride

Ethanoyl chloride CH₃COCl provides the acetyl group CH₃–CO– that gets installed on the phenol oxygen.

7.3 The reaction

$\text{Salicylic acid (-COOH and -OH)} + CH_3COCl \rightarrow \text{Aspirin (-COOH and -O-CO-CH_3)} + HCl$

In summary form:

Step	Salicylic acid	+ CH₃COCl	→	Aspirin	+ HCl
Functional group	Ar–OH	acyl chloride		Ar–O–CO–CH₃ (ester)	HCl gas

The phenol –OH of salicylic acid attacks the carbonyl carbon of ethanoyl chloride (nucleophilic addition-elimination).
The Cl⁻ leaves.
An ester linkage is now installed at the phenol oxygen — the salicylic acid has been acetylated.
The –COOH of salicylic acid is unchanged.

7.4 Why use the acyl chloride rather than ethanoic acid + H₂SO₄?

In principle one could acetylate salicylic acid with ethanoic acid + concentrated H₂SO₄ (Fischer esterification, Lesson 4). However:

The Fischer route only gives ~65% yield at equilibrium.
The carboxylic acid –COOH of salicylic acid would also react with H₂SO₄, giving side products.
The acyl chloride route goes to completion (~100% yield), is fast (room temperature, ~20 minutes), and avoids side reactions on the –COOH.

In practice, the most economical industrial route uses ethanoic anhydride (CH₃CO)₂O instead of CH₃COCl — anhydrides are slightly cheaper and the only by-product is harmless ethanoic acid instead of corrosive HCl. But the chemistry (nucleophilic addition-elimination) is identical, and OCR accepts ethanoyl chloride in the equation for full marks.

7.5 PAG 6 — the school-lab version

The standard PAG 6 task for an organic solid is the synthesis of aspirin: mix salicylic acid with ethanoic anhydride (or ethanoyl chloride if the lab is well-equipped), warm in a water bath for 20 minutes, add cold water to precipitate the aspirin, filter under vacuum, recrystallise from ethanol/water, dry, determine melting point, calculate % yield. Typical yields are 75–85%; published m.p. of aspirin is 138–140 °C.

8. Worked Example — Comparing the Three Routes to Ester Formation

You can make ethyl ethanoate by three different routes. Compare them:

Route	Reagents	Conditions	Yield	Speed	Reversible?
Fischer	CH₃COOH + C₂H₅OH	conc. H₂SO₄, reflux	~65%	Slow (hours)	Yes
Acyl chloride	CH₃COCl + C₂H₅OH	room temp, no catalyst	~100%	Fast (minutes)	No
Anhydride	(CH₃CO)₂O + C₂H₅OH	room temp or gentle warm	95–100%	Fast	No

The Fischer route is the cheap, scalable industrial choice when 65% yield is acceptable. The acyl chloride and anhydride routes are preferred when (a) high yield is required, (b) the molecule has acid-sensitive groups elsewhere, or (c) the alcohol is precious / scarce.

9. Worked Example — Making an Amide from Carboxylic Acid + Amine

Q: How would you make N-methylethanamide CH₃-CO-NH-CH₃ from ethanoic acid and methylamine?

Naive answer (wrong): CH₃COOH + CH₃NH₂ → CH₃CONHCH₃ + H₂O.

Why this fails: ethanoic acid is a Brønsted acid; methylamine is a base. They simply do a proton transfer:

$CH_3COOH + CH_3NH_2 \longrightarrow CH_3COO^- CH_3NH_3^+$

You get the salt (methylammonium ethanoate), not the amide. The salt is stable indefinitely at room temperature; heating it to >200 °C can drive off water to give the amide, but this is impractical for ordinary lab synthesis.

Correct approach (acyl chloride route):

Step 1: Convert the acid to the acyl chloride: CH₃COOH + SOCl₂ → CH₃COCl + SO₂ + HCl.
Step 2: React the acyl chloride with the amine: CH₃COCl + 2 CH₃NH₂ → CH₃CONHCH₃ + CH₃NH₃Cl.

The acyl chloride is electrophilic enough that the amine acts as a nucleophile (attacks C=O carbon, displaces Cl⁻) rather than as a base. One equivalent of amine forms the amide; a second equivalent neutralises the HCl that is generated.

This two-step route via the acyl chloride is the only practical lab synthesis of an amide from an acid + amine at room temperature.

Lesson 5: Acyl Chlorides