Acylation (A-level only) — AQA A-Level Chemistry
Test yourself on Acylation (A-level only) with AQA A-Level practice questions.
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Acylation (A-level only) explained
All three are relatives of the carboxylic acid with the -OH replaced.
Read the full explanation
An acyl chloride is RCOCl, the chlorine bonded to the carbonyl carbon, named -oyl chloride, as in ethanoyl chloride. An acid anhydride is two acyl groups sharing a single oxygen, (RCO)₂O, and is what is left when two acid molecules lose one molecule of water between them, hence ethanoic anhydride. An amide has nitrogen on the carbonyl carbon, RCONH₂, named -amide; if an alkyl group replaces one of the hydrogens on the nitrogen the name gains an N- prefix, as in N-methylethanamide. Reactivity falls along the series acyl chloride, anhydride, ester, amide, because the group leaving the carbonyl carbon becomes harder to displace.
The nucleophilic addition–elimination reactions of water, alcohols, ammonia and primary amines with acyl chlorides and acid anhydrides.
In each of these reactions the nucleophile's lone pair attacks the δ⁺ carbonyl carbon, and the chloride ion or a carboxylate is then eliminated, so the carbonyl group survives and only the group attached to it changes. Ethanoyl chloride gives, with water, ethanoic acid; with an alcohol, an ester; with ammonia, ethanamide; and with a primary amine, an N-substituted amide. Hydrogen chloride is released each time, as misty fumes. With ammonia or an amine two moles are needed per mole of acyl chloride, because the second mole takes up the HCl as an ammonium salt. Ethanoic anhydride gives exactly the same organic products, but ethanoic acid instead of HCl, and reacts less violently.
The industrial advantages of ethanoic anhydride over ethanoyl chloride in the manufacture of the drug aspirin.
Aspirin is made by acylating the -OH group of 2-hydroxybenzoic acid; the -COOH on the ring is left alone. Either ethanoyl chloride or ethanoic anhydride will do the job, but industry chooses the anhydride. It is cheaper to buy, it is much less readily hydrolysed by moisture in the air so it can be stored and handled safely, and it reacts far less violently with water if there is a spill. The by-product matters just as much: the anhydride releases ethanoic acid, which is a weak acid that can be recovered and reused, while the acyl chloride releases hydrogen chloride, a corrosive and toxic gas that would need scrubbing. Against that, the anhydride has the poorer atom economy of the two.
Students should be able to outline the mechanism of nucleophilic addition–elimination reactions of acyl chlorides with water, alcohols, ammonia and primary amines.
The mechanism has two stages, which is why it is called addition-elimination. First, addition: a lone pair on the attacking atom, the oxygen of water or an alcohol, or the nitrogen of ammonia or an amine, moves to the δ⁺ carbonyl carbon, and at the same time the electron pair of the C=O bond moves onto the oxygen. That gives a tetrahedral intermediate with a negative charge on oxygen and a positive charge on the attacking atom. Second, elimination: the electron pair on the negative oxygen comes back down to reform the C=O, and the electrons of the C-Cl bond leave with the chlorine as Cl⁻. Finally the attacking atom loses H⁺, which the chloride takes, and the final product is left.
Required practical 10 Preparation of: a pure organic solid and test of its purity a pure organic liquid.
The solid preparation, typically aspirin, is purified by recrystallisation: dissolve the crude solid in the minimum volume of hot solvent, filter hot to take out insoluble impurities, cool so the product crystallises while the soluble impurities stay in solution, filter under reduced pressure, wash the crystals with a little cold solvent and dry them. Purity is tested by melting point: a pure sample melts sharply at the value in the data book, and an impure one melts lower and over a range. The liquid preparation, typically an ester, is distilled, then shaken in a separating funnel with sodium carbonate solution to remove acid, venting the carbon dioxide, dried with an anhydrous salt and redistilled over the right boiling range.
Your focus
- Draw and name an acyl chloride, an acid anhydride and a primary amide given the parent carboxylic acid.
- Deduce the parent acid from the structure of an acyl chloride, an anhydride or an amide.
- Place acyl chlorides, anhydrides, esters and amides in order of reactivity towards nucleophiles.
Show all 15 objectives
- Predict and draw the organic product of an acyl chloride or anhydride with water, an alcohol, ammonia or a primary amine.
- Write balanced equations that account for both moles of ammonia or amine used per mole of acyl chloride.
- State the observation expected when ethanoyl chloride is added to water and explain what causes it.
- Give three properties of ethanoic anhydride - its cost, how readily moisture hydrolyses it, and the by-product it releases - and state the consequence of each for a factory making aspirin.
- Identify which functional group of 2-hydroxybenzoic acid reacts when aspirin is made, and draw the product.
- Compare the two routes on atom economy and explain which one wins on that measure.
- Draw the full mechanism for ethanoyl chloride with water, an alcohol, ammonia or a primary amine, arrow by arrow.
- Draw the tetrahedral intermediate for a given acyl chloride reaction, with both formal charges in place.
- Explain why this mechanism is named addition-elimination rather than substitution.
- Describe the full recrystallisation procedure for an impure organic solid and give the reason for each step.
- Interpret a measured melting point to decide whether a sample is pure, referring to both the value and the range.
- Justify each stage used to purify an organic liquid, naming the species removed at each stage.
Acylation (A-level only) exam tips
Marking Points
- one mark for the acyl chloride drawn with chlorine bonded to the carbonyl carbon
- one mark for the anhydride drawn as two C=O groups joined through a single oxygen atom
- one mark for the amide drawn with nitrogen bonded to the carbonyl carbon
- one mark for the correct IUPAC name, ending -oyl chloride, anhydride or -amide as appropriate
- one mark for the correct organic product with each named nucleophile
- one mark for hydrogen chloride given as the inorganic product with an acyl chloride
- one mark for ethanoic acid, not hydrogen chloride, when ethanoic anhydride is used
- one mark for two moles of ammonia or amine per mole of acyl chloride, the second forming the salt
- one mark for the anhydride being cheaper or less corrosive than the acyl chloride
- one mark for the anhydride reacting less vigorously with water, so it is safer to store and handle
- one mark for ethanoic acid rather than hydrogen chloride as the by-product
- one mark for identifying the -OH group of 2-hydroxybenzoic acid as the group that is acylated
- one mark for the structures of the reacting species drawn correctly, with the lone pair shown on the attacking atom
- one mark for a curly arrow from that lone pair to the carbonyl carbon
- one mark for a curly arrow from the C=O bond to the oxygen
- one mark for the tetrahedral intermediate drawn with the negative charge on oxygen
- one mark for the arrows that reform the C=O bond and release the chloride ion, followed by loss of H⁺
- one mark for dissolving the crude solid in the minimum volume of hot solvent
- one mark for a sharp melting point at the literature value as the test of purity
- one mark for washing the organic liquid with sodium carbonate solution, with carbon dioxide released
- one mark for drying the liquid with an anhydrous salt before redistillation
- one mark for collecting the distillate over the correct boiling range
Examiner Tips
- 💡Always draw the bond to the carbon of a carbon-containing functional group; the bond to an oxygen there is penalised even when the rest is right.
- 💡An N- prefix in an amide name tells you the group is on the nitrogen, not on the carbon chain.
- 💡Identify the atom that attacks: O of water, O of the alcohol, N of ammonia or of the amine. The product is that atom joined to the acyl group.
- 💡Observations count: ethanoyl chloride with water gives steamy fumes, and with ammonia gives a white solid.
- 💡Give industrial reasons in pairs: a property and the consequence for a factory, such as 'less easily hydrolysed, so it can be stored'.
- 💡Name the by-product in every comparison; that is usually where the mark is.
- 💡Every curly arrow must start from a lone pair or from a bond; an arrow starting anywhere else is penalised each time it appears.
- 💡Draw the intermediate as a separate structure with both charges on it; AQA gives a mark for the intermediate and its lone pair alone.
- 💡Learn the order of the liquid purification: distil, wash, separate, dry, redistil. Questions often ask you to justify one step in that sequence.
- 💡When justifying a melting point measurement, say both things AQA wants: sharp, and matching the data book value.
Common Mistakes
- bonding the chlorine to the carbonyl oxygen instead of the carbon
- drawing an anhydride with an O-O link, which is a peroxide
- naming CH₃COCl as ethanol chloride or as ethyl chloride
- drawing the bond from the carbon chain to the O of -COCl, which AQA marks as an ambiguous structure
- drawing the ester with the alkyl group of the acyl chloride on the single-bonded oxygen
- giving an amine rather than an amide as the product with ammonia
- writing only one mole of ammonia and leaving free HCl alongside the amide
- writing HCl as a product of a reaction in which the reagent was an anhydride
- claiming the anhydride gives the better atom economy, when its larger by-product makes it worse
- saying the -COOH group on the ring is esterified, rather than the -OH group
- describing hydrogen chloride as a useful by-product without any qualification
- arguing the anhydride is chosen because it is more reactive, when the opposite is the point
- starting the curly arrow at the attacking atom's symbol or at a negative sign rather than at its lone pair
- attacking the carbonyl oxygen, which carries the δ⁻ charge, instead of the carbon
- showing the chloride leaving in the same step as the nucleophile attacking, which is the wrong mechanism
- leaving the charges and the lone pair off the intermediate
- forgetting the final loss of H⁺, so the product is drawn still carrying a positive charge
- using more hot solvent than the minimum, so much of the product stays dissolved on cooling and the yield falls
- washing the crystals with hot solvent, which redissolves them
- saying impurities raise the melting point, when they lower it and widen the range
- failing to vent the separating funnel, when carbon dioxide from the carbonate raises the pressure
- keeping the aqueous layer and discarding the organic layer after the wash