Acid-base catalysis: what it is, specific versus general, why protonating a carbonyl speeds a reaction up, the five reactions where it appears in A-level, IB and AP chemistry, and how enzymes use it

Acid-base catalysis is the mechanism behind most of the organic reactions in an A-level, IB or AP course, and behind a large fraction of enzyme chemistry, and it comes down to one idea: a proton added or removed at the right place makes a bad electrophile good or a weak nucleophile strong. This page gives the idea, the distinction between specific and general catalysis (which is what the exam actually tests when it gives you a rate equation), five reactions where it appears, and how an enzyme active site does the same thing at pH 7.

The idea in two sentences

Acid catalysis: the acid protonates the substrate. A protonated carbonyl (C=OH⁺) has a much larger partial positive charge on carbon, so weak nucleophiles like water and alcohols can attack it; a protonated hydroxyl (–OH₂⁺) is a good leaving group where –OH was not.

Base catalysis: the base deprotonates the nucleophile or the substrate. An alcohol becomes an alkoxide (RO⁻), a ketone becomes an enolate; both are far stronger nucleophiles than the neutral molecule.

In both cases the catalyst provides a lower-energy pathway and is regenerated in the last step, so it does not appear in the overall equation and is not used up.

Specific and general catalysis: the distinction exams test

The same two columns exist for base catalysis with OH⁻ (specific) against all bases B (general). The experimental test is the one to remember: hold the pH constant with a buffer and change the amount of buffer. If the rate changes, the buffer's own acid and base are doing the catalysis, and it is general.

Five reactions where it appears

1. Acid-catalysed ester hydrolysis and esterification. CH₃COOC₂H₅ + H₂O ⇌ CH₃COOH + C₂H₅OH, with H₂SO₄. The acid protonates the carbonyl oxygen; water attacks the activated carbon; a proton moves to the OC₂H₅ oxygen; ethanol leaves; the catalyst is returned. The same mechanism run backwards is Fischer esterification, which is why concentrated sulfuric acid is in every esterification practical. (Base-catalysed hydrolysis, saponification, is not catalysis: the OH⁻ is consumed as the carboxylate forms.)

2. Acid-catalysed iodination of propanone. CH₃COCH₃ + I₂ → CH₃COCH₂I + HI. The rate is zero order in iodine and first order in propanone and in H⁺: the slow step is the acid-catalysed conversion of the ketone to its enol, and the enol then reacts with iodine fast. This is the standard A-level rate practical, and the rate equation rate = k[CH₃COCH₃][H⁺] is the evidence for the mechanism. The product HI is itself an acid, so the reaction is autocatalytic.

3. Acid-catalysed hydration of alkenes. CH₂=CH₂ + H₂O → CH₃CH₂OH over phosphoric acid at 300 °C and 60 atm (industrial ethanol). H⁺ adds to the double bond to give a carbocation; water attacks; a proton is lost to regenerate the catalyst. Markovnikov's rule decides which carbon takes the OH in an unsymmetrical alkene.

4. Base-catalysed aldol condensation. Two molecules of ethanal with dilute NaOH: OH⁻ removes an α-hydrogen to make the enolate (the strong nucleophile), which attacks the carbonyl carbon of a second ethanal; the alkoxide picks up a proton from water and returns OH⁻. Product: 3-hydroxybutanal. Warm it and it dehydrates to but-2-enal.

5. Acid-catalysed inversion of sucrose. Sucrose + H₂O → glucose + fructose, with dilute HCl. Protonation of the glycosidic oxygen makes it a leaving group; the reaction is first order in sucrose and in H⁺, and it was followed with a polarimeter in the nineteenth century because the optical rotation changes sign (hence "inversion"). It is the classic specific-acid-catalysed reaction in the kinetics textbooks.

The mechanism in general: what the proton does

The carbonyl case is the one to be able to draw: curly arrow from the C=O lone pair to H⁺; the C=OH⁺ drawn with the positive charge on oxygen (and its resonance form with the charge on carbon, which is the reason the carbon is now so electrophilic); curly arrow from the nucleophile's lone pair to carbon and from the C=O π bond onto oxygen.

Enzymes: general acid-base catalysis at pH 7

A cell cannot use H₃O⁺ or OH⁻ at any useful concentration, so enzymes use the side chains of amino acids as general acids and bases, placed exactly where the proton needs to go.

In chymotrypsin, His57 (a general base) removes the proton from Ser195, making the serine oxygen a strong nucleophile that attacks the peptide carbonyl; His57 then acts as a general acid, giving that proton to the nitrogen so the amine can leave. Asp102 holds the histidine in the right orientation and stabilises its positive charge. Three residues, one proton moved twice: the catalytic triad. Because the proton is transferred in the slow step, this is general, not specific, catalysis, which is why enzyme rates depend on the pK_a of the residues and give the bell-shaped rate-against-pH curves in the biology syllabus.

The exam question, and the answer that scores

Explain how an acid catalyst increases the rate of hydrolysis of an ester. The acid protonates the carbonyl oxygen (1); this increases the partial positive charge on the carbonyl carbon (1), so water, a weak nucleophile, can attack it (1); protonation of the alkoxy oxygen makes the alcohol a good leaving group (1); the proton is regenerated in the final step so the catalyst is not consumed (1); the activation energy of the rate-determining step is lowered (1). Six marks, six sentences, in that order.

How we teach mechanisms

One tutor, one student, and every mechanism drawn by the student with the curly arrows explained aloud, then the rate equation matched to the slow step. Acid-base catalysis is taught as one idea applied to five reactions rather than five separate mechanisms to memorise, which is the difference between a student who can do the unseen question and one who cannot. The first 30-minute class is free: send the topic and the last test on WhatsApp or the contact page. The carbonyl test that uses the same addition-elimination pattern is in 2,4-DNPH and Brady's reagent; the definitions of strong and weak acids are in strong acids and bases; the subject page is online chemistry tutoring.

Questions parents ask

See how we teach this, 1-on-1 online →