Carbonyl Chemistry

How to amplify electrophilicity of carbonyl group

Protonate the C=O before adding the nucleophile

Do aldehydes and ketones react via the same mechanism

Yes

Are aldehydes or ketones more reactive?

Aldehydes as the alkyl groups in ketones are much bulkier than the H atoms and alkyl groups also weak electron donors

Aldehyde/Ketone + Water

Diol

Alcohols + aldehydes/ketones

Hemiacetals

During acetal formation, to favour acetal formation…

add excess of diol/alcohol or remove water

During acetal formation, to favour aldehyde/ketone formation (reverse reaction)…

add excess water

Aldehyde/Ketone + Amine

Imine + water

How to test for a methyl adjacent carbonyl?

Iodoform test:

• Add I₂ in NaOH solution

• Positive result forms a carboxylic acid and iodoform - yellow precipitate (CHI₃)

How to distinguish between an aldehyde and ketone?

Fehlings test:

• Add Cu²⁺ (Fehling’s A) in sodium tartrate & NaOH solution (Fehling’s B)

• Positive result reduced Cu²⁺ to Cu⁺ and the aldehyde is oxidised to a carboxylic acid - froms a red precipitate

How to test for a specific halide group

Silver Nitrate test:

• Add AgNO₃

• The Ag⁺ ions react with the halide to from AgX

• Precipitate forms: White for Cl, Cream for Br, Yellow for I

Why are acyl chlorides very reactive?

Cl is an electronegative substituent → strongly withdraws electron density

Cl is a larger atom → minimal interaction between Cl lone pairs and C=O (no resonance stabilisiation)

Cl is a good leaving group as it is very stable

Why are amides very unreactive?

NR₂ is a moderately electronegative substituent → less electron withdrawing than other substituents

N atom is similar in size to C atom → strong interaction between N lone pairs and C=O (very strong resonance stabilisation)

What is a leaving group

A substituent that is good at accepting a negative charge

What conditions does acyl chloride hydrolysis react under?

Mild conditions, no heating, neutral pH

Why is the esterification of acyl chlorides irreversible?

Cl^- is a poor nucleophile

Basic ester hydrolysis

Base, H₂O, H⁺ (acid workup)

Acidic ester hydrolysis

H⁺, H₂O

Why can amides be synthesised from amines + carboxylic acids

Amines are basic so react with a carboxylic acid to form an ammonium salt

Tautomers

Isomers of the same compound which interconvert by migration of a H⁺ and a double bond

When can enolisation occur?

When there are protons alpha to the carbonyl

What are the consequences of enolisation

One issue is the racemisation of chiral centres next to a carbonyl group

What is an aldol

A molecule containing both a hydroxyl and carbonyl group

Self-Aldol reactions

The electrophile and nucleophile derive from the same carbonyl compound

Cross-Aldol reactions

The electrophile should be unable to undergo enolisation and a better electrophile than the nucleophile

Why should asymmetrical ketones generally be avoided?

The are two potential enols/enolates that can be formed. To avoid this, use aldehydes or ketones where one side is non-enolisable.

What is an enol?

A molecule containing a hydroxyl group bonded to a carbon involved in a C=C