Chirality — the chiral centre

A carbon atom is a chiral centre (an asymmetric carbon, marked with a *) when it is attached to four different groups. That molecule then has no plane of symmetry and it is not superimposable on its mirror image.

The two non-superimposable mirror images are enantiomers (optical isomers). They are a type of stereoisomer: same structural formula, different arrangement of bonds in space.

• Enantiomers have identical melting point, boiling point, density and ordinary chemical reactivity.
• They differ in one physical property: they rotate the plane of plane-polarised light in opposite directions — one clockwise (+), one anticlockwise (−), by an equal angle.
• They also behave differently towards other chiral species (enzymes, receptors) — which is why one enantiomer of a drug can be therapeutic and the other useless or harmful.

Exam habit: to prove chirality, don't just say "four different groups" — say the molecule has no plane of symmetry and is non-superimposable on its mirror image.

Spot the chiral molecule

Your turn — how many chiral centres?

Racemic mixtures

A racemic mixture (racemate) is a 50 : 50 mixture of the two enantiomers. It is optically inactive: the rotation caused by one enantiomer is exactly cancelled by the equal and opposite rotation caused by the other.

Why do so many lab syntheses give a racemate? Whenever a chiral centre is created from a planar (trigonal) intermediate — a C=O carbon, or a carbocation — the nucleophile can attack from either face with equal probability. Equal amounts of the two enantiomers form, so the product is optically inactive.

Contrast: enzymes are chiral catalysts and have a chiral active site, so biological syntheses usually give a single enantiomer.

Why is the racemate inactive?

Aldehydes and ketones: the polar C=O bond

Oxygen is much more electronegative than carbon, so the C=O bond is strongly polar: C^δ+=O^δ−. The δ+ carbon is therefore open to attack by nucleophiles — and because C=O is a double bond, the nucleophile adds rather than substitutes.

• Aldehydes (RCHO) have the C=O at the end of the chain — suffix -al (ethanal, propanal).
• Ketones (RCOR′) have the C=O inside the chain — suffix -one (propanone, butan-2-one).
• Both are made by oxidising alcohols with acidified potassium dichromate(VI): a primary alcohol → aldehyde (distil off immediately) → carboxylic acid (reflux); a secondary alcohol → ketone (which resists further oxidation).

Key difference: an aldehyde can be oxidised further (to a carboxylic acid) because the carbonyl carbon still carries an H atom. A ketone carbon has no H there, so it is not oxidised by mild oxidising agents — and that single fact powers every test on the next screens.

Nucleophilic addition — HCN and NaBH₄

1. With HCN (in the presence of KCN): the nucleophile is the cyanide ion, :CN⁻. Its lone pair attacks the δ+ carbonyl carbon; the C=O π electrons shift onto the oxygen to give an intermediate alkoxide (RO⁻), which then takes a proton from HCN (regenerating CN⁻).

2. With NaBH₄ (a reducing agent, in aqueous or alcoholic solution): the nucleophile is the hydride ion, :H⁻. Same two steps — attack, then protonation by water.

• aldehyde + 2[H] → primary alcohol (CH₃CHO → CH₃CH₂OH)
• ketone + 2[H] → secondary alcohol (CH₃COCH₃ → CH₃CH(OH)CH₃)

Stereochemistry link: the carbonyl group is planar. CN⁻ (or H⁻) attacks from above or below that plane with equal probability, so where a chiral centre is formed the product is a racemic mixture and is optically inactive. Ethanal + HCN is the classic example.

The HCN product

Telling carbonyls apart

Step 1 — is there a carbonyl at all? Add 2,4-dinitrophenylhydrazine (2,4-DNPH, Brady's reagent). An orange/yellow crystalline precipitate forms with any aldehyde or ketone (a condensation reaction), and with nothing else. Filter the crystals, recrystallise them, take the melting temperature and compare with a database — that identifies the exact carbonyl compound.

Step 2 — aldehyde or ketone? Use a mild oxidising agent. Only the aldehyde is oxidised (to a carboxylic acid / carboxylate).

• Tollens' reagent — ammoniacal silver nitrate, [Ag(NH₃)₂]⁺, warmed gently in a water bath. The aldehyde reduces Ag⁺ to Ag: a silver mirror coats the tube. Ketone → no change.
• Fehling's (or Benedict's) solution — a blue Cu²⁺ complex in alkali. The aldehyde reduces Cu²⁺ to Cu⁺: the blue solution gives a brick-red precipitate of Cu₂O. Ketone → stays blue.

Detail worth a mark: Fehling's works with aliphatic aldehydes but not with benzaldehyde; Tollens' works with both. And an acidified dichromate(VI) test (orange → green) also distinguishes them, but it is less specific.

Reading the test results

The iodoform (triiodomethane) test

Warm the compound with iodine in aqueous sodium hydroxide (alkaline aqueous iodine). A pale-yellow precipitate of triiodomethane, CHI₃, with a distinctive antiseptic smell, is a positive result.

It is positive for a very specific fragment:

• a methyl ketone, CH₃CO– (e.g. propanone, butan-2-one) — and ethanal, CH₃CHO, which also has CH₃CO–;
• a methyl secondary alcohol, CH₃CH(OH)– (e.g. propan-2-ol) — and ethanol, CH₃CH₂OH — because the alkaline iodine oxidises them to the corresponding CH₃CO– compound first.

Exam trap: the test does not distinguish aldehyde from ketone — ethanal is positive and propanal is negative. It tells you whether the CH₃CO– (or CH₃CH(OH)–) group is present. Pair it with Tollens' to nail the structure.

Positive or negative?

Which test does each compound pass?

Tap a compound, then tap the box that describes how it behaves. (Tollens' = warm ammoniacal silver nitrate; iodoform = warm I₂ / NaOH(aq).)

Carboxylic acids — why they are acidic

The –COOH group loses a proton to give the carboxylate ion, RCOO⁻. That ion is stabilised because the negative charge is delocalised over both oxygen atoms (the two C–O bonds become identical and intermediate in length). A stabilised anion means the equilibrium lies further right — so carboxylic acids are much more acidic than alcohols or phenols.

Electron-withdrawing groups increase acidity. Chloroethanoic acid (ClCH₂COOH, pK_a ≈ 2.87) is a stronger acid than ethanoic acid because the electronegative Cl pulls electron density away from the COO⁻ group, spreading the negative charge further and stabilising the anion. Add more Cl atoms and the acid gets stronger still.

Reactions of the –COOH group:

• with a reactive metal (Na): salt + H₂ — 2CH₃COOH + 2Na → 2CH₃COONa + H₂
• with a base/alkali (NaOH): salt + water — CH₃COOH + NaOH → CH₃COONa + H₂O
• with a carbonate (Na₂CO₃) or hydrogencarbonate: salt + water + CO₂ effervescence
• with LiAlH₄ in dry ether: reduced all the way to the primary alcohol (NaBH₄ is too weak to do this)
• with an alcohol + conc. H₂SO₄ catalyst: an ester (see next screen)

Your turn — gas from a carboxylic acid

Esterification and hydrolysis

Making an ester (esterification): warm a carboxylic acid with an alcohol and a few drops of concentrated sulfuric acid as catalyst. The reaction is reversible and reaches equilibrium, so yields are moderate — distil the ester off to shift it right.

Hydrolysis — breaking the ester back down:

• Acid hydrolysis (reflux with dilute H₂SO₄): the reverse of the equation above. It is reversible and incomplete — you get the carboxylic acid + the alcohol.
• Alkaline hydrolysis / saponification (reflux with NaOH(aq)): CH₃COOC₂H₅ + NaOH → CH₃COO⁻Na⁺ + C₂H₅OH. This goes to completion (irreversible) because the carboxylate salt formed will not react back with the alcohol. Acidify afterwards if you want the free acid.

Uses: esters are volatile with sweet, fruity smells (flavourings, perfumes) and are good solvents. Alkaline hydrolysis of a vegetable-oil triester (triglyceride) gives soap (the sodium salts of long-chain acids) + glycerol (propane-1,2,3-triol).

Your turn — percentage yield

Your turn — atom economy

Acyl chlorides — the reactive derivative

An acyl chloride (RCOCl, e.g. ethanoyl chloride CH₃COCl) is the most reactive carboxylic acid derivative. The carbonyl carbon is bonded to two electronegative atoms (O and Cl), so it is very δ+ — and Cl⁻ is an excellent leaving group. They react vigorously with any species carrying a lone pair, by nucleophilic addition–elimination, releasing steamy fumes of HCl every time.

• + water → carboxylic acid: CH₃COCl + H₂O → CH₃COOH + HCl
• + alcohol → ester: CH₃COCl + C₂H₅OH → CH₃COOC₂H₅ + HCl (fast, and not reversible — a far better route to an ester than esterification)
• + ammonia → primary amide: CH₃COCl + 2NH₃ → CH₃CONH₂ + NH₄Cl
• + primary amine → N-substituted amide: CH₃COCl + 2CH₃NH₂ → CH₃CONHCH₃ + CH₃NH₃⁺Cl⁻
• + phenol → an aryl ester (phenol is too weak a nucleophile to be esterified by a carboxylic acid, so you must use the acyl chloride)

Amides: RCONH₂. Made from an acyl chloride + ammonia (or by dehydrating an ammonium carboxylate). Hydrolysed on refluxing with acid (→ carboxylic acid + ammonium salt) or with alkali (→ carboxylate salt + ammonia gas).

Choosing the reagent

Hydrolysing an ester

Explaining acid strength

Match the reagent to the result

Tap an item on the left, then its partner on the right.

The big ideas to know

You've now covered Topic 17: Organic Chemistry II of the Edexcel A-level Chemistry (9CH0) specification. Press Finish to see your score.