Comprehensive Organic Chemistry: Reactivity, Aromaticity, and Functional Groups, and Synthetic Reagents

Why are aldehydes more reactive than ketones?

Less steric hindrance around the carbonyl carbon; ketones have two electron-donating alkyl groups which reduce the electrophilicity of the carbonyl carbon.

State Hückel's rule for aromaticity.

A molecule must be cyclic, planar, fully conjugated, and contain 4n + 2 π electrons.

What makes a compound aromatic?

It is cyclic, planar, fully conjugated, and has 4n + 2 π electrons.

What makes a compound antiaromatic?

It is cyclic, planar, fully conjugated, and has 4n π electrons.

Name the intermediate formed during electrophilic aromatic substitution.

The Wheland intermediate (σ-complex or arenium ion).

What is the rate-limiting step of electrophilic aromatic substitution?

Formation of the Wheland intermediate.

Why is benzene unusually stable?

It is aromatic with six delocalised π electrons.

Why are amides much less reactive than other carboxylic acid derivatives?

The nitrogen lone pair is delocalised into the carbonyl by resonance, reducing electrophilicity.

Why are acyl chlorides highly reactive?

The chlorine withdraws electron density and is an excellent leaving group.

Arrange these in order of reactivity toward nucleophiles: acid chloride, anhydride, ester, carboxylic acid, amide.

Acid chloride > Anhydride > Ester ≈ Carboxylic acid > Amide.

What mechanism do acyl chlorides undergo?

Nucleophilic addition–elimination.

What is the first step in nucleophilic addition–elimination?

Nucleophilic attack on the carbonyl carbon.

Why are carboxylic acids acidic?

Their conjugate base is resonance stabilised.

Why do basic nucleophiles often fail to react with carboxylic acids?

They deprotonate the acid instead of attacking the carbonyl.

What reaction converts a carboxylic acid into an ester?

Fischer esterification.

What catalyst is used in Fischer esterification?

Concentrated sulfuric acid (H₂SO₄).

How can the esterification reaction be reversed?

Heat with aqueous acid (acid hydrolysis).

Why are conjugated dienes more stable than non-conjugated dienes?

Delocalisation lowers the overall energy.

How does conjugation affect the central C–C bond in 1,3-butadiene?

It is shorter than a normal single bond because of partial double-bond character.

How does conjugation affect rotation about the central bond?

Rotation is restricted.

What reagent oxidises a primary alcohol to an aldehyde?

PCC.

What reagent oxidises alcohols under aqueous conditions?

PDC.

What reagent converts carboxylic acids into acid chlorides?

SOCl₂ (thionyl chloride).

What is MeMgBr?

Methylmagnesium bromide (a Grignard reagent).

What do Grignard reagents do?

Add to carbonyl compounds to form alcohols after acidic work-up.

What does a phosphorane reagent do?

Performs the Wittig reaction to form an alkene.

What is electrophilic aromatic substitution?

Replacement of a hydrogen on an aromatic ring by an electrophile.

What effect do electron-donating groups have on benzene?

They activate the ring and direct substitution to the ortho and para positions.

What effect do electron-withdrawing groups have on benzene?

They deactivate the ring and usually direct substitution to the meta position.

Why does a nitro group favour nucleophilic aromatic substitution?

It stabilises the negatively charged intermediate by resonance.

What must be shown in a full reaction mechanism?

Curly arrows, charges, intermediates, resonance forms, and the rate-limiting step where appropriate.

What should be shown when drawing a carbonyl functional group?

Hybridisation, bond angles, polarity, and oxygen lone pairs.

Why is aromatic stabilisation important?

It significantly lowers the energy of the molecule.

What are the four requirements for aromaticity?

Cyclic, planar, fully conjugated, 4n+2 π electrons.

What type of reaction do aldehydes usually undergo?

Nucleophilic addition.

Why are ketones less reactive than aldehydes?

Greater steric hindrance and electron donation from two alkyl groups.

What is resonance?

Delocalisation of electrons over multiple atoms.

What is conjugation?

Alternating single and double bonds allowing π electrons to delocalise.

What is the leaving group in acyl chloride reactions?

Chloride ion.

Why are acid chlorides more reactive than esters?

Better leaving group and more electrophilic carbonyl carbon.

What must always be restored after electrophilic aromatic substitution?

Aromaticity.

Which mechanism requires a Wheland intermediate?

Electrophilic aromatic substitution.

Which mechanism requires a tetrahedral intermediate?

Nucleophilic addition–elimination.

What is the product when a Grignard reagent reacts with an aldehyde?

A secondary alcohol (except formaldehyde, which gives a primary alcohol).

What is the product when a Grignard reagent reacts with a ketone?

A tertiary alcohol.

What is the purpose of acidic work-up after a Grignard reaction?

To protonate the alkoxide and produce the alcohol.

Which topics appear most frequently in IOC exams?

Aromaticity, electrophilic aromatic substitution, carbonyl chemistry, carboxylic acid derivatives, reaction mechanisms, conjugation, Grignard reactions, Wittig reactions, oxidation reactions.