DAT Review · Organic Chemistry
Carbonyl Chemistry: Aldehydes, Ketones, and Carboxylic Acid Derivatives
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Scope: Nucleophilic addition to aldehydes/ketones, nucleophilic acyl substitution at carboxylic acid derivatives, reactivity trends, formation of acetals, imines, enamines, Fischer esterification, saponification, and Claisen condensation. Expect 3–5 questions. Aldehyde vs. ketone reactivity and the acid derivative reactivity ladder are core concepts.
The college version
Core Review
The Carbonyl Group
The carbonyl carbon is electrophilic due to the polarized C=O bond (O is more electronegative, pulls electron density from C). This makes the carbonyl carbon susceptible to nucleophilic attack. The reaction typically proceeds through a tetrahedral intermediate.
Aldehydes vs. Ketones: Reactivity
Aldehydes are MORE reactive than ketones for two reasons:
- Steric: Aldehydes have only one alkyl group (and one small H). Ketones have two bulkier alkyl groups that hinder nucleophilic approach.
- Electronic: Alkyl groups are electron-donating (inductive effect). Ketones have TWO electron-donating groups, making the carbonyl carbon less electrophilic. Aldehydes have only one.
Nucleophilic Addition to Aldehydes/Ketones
| Nucleophile | Product (after workup) | Notes |
|---|---|---|
| H₂O | Hydrate (gem-diol) | Equilibrium favors carbonyl, except with electron-withdrawing groups |
| ROH (1 equiv) + H⁺ | Hemiacetal | Unstable; usually proceeds to acetal |
| ROH (excess) + H⁺ | Acetal | Carbonyl protected as acetal; reversible |
| 1° Amine (RNH₂) | Imine (Schiff base) | C=NR. Water is eliminated. pH ~4–5 optimal. |
| 2° Amine (R₂NH) | Enamine | C=C-NR₂. Requires α-hydrogen. |
| Hydride (NaBH₄) | 1° or 2° Alcohol | NaBH₄ reduces aldehydes and ketones. LiAlH₄ is stronger (reduces esters, acids too). |
| Grignard (RMgX) | Alcohol (extends carbon chain) | RMgX adds R group. Formaldehyde → 1° alcohol; aldehyde → 2°; ketone → 3°. |
| Wittig (Ph₃P=CR₂) | Alkene | Converts C=O to C=C. Powerful synthetic tool. |
Acetal Formation Mechanism (Acid-Catalyzed)
- Protonation of carbonyl oxygen (activates carbonyl).
- Nucleophilic attack by ROH → tetrahedral intermediate (hemiacetal).
- Proton transfer, then loss of water → oxocarbenium ion.
- Second ROH attacks → proton loss → acetal.
Acetals serve as protecting groups for carbonyls. They are stable to base and nucleophiles but hydrolyzed by aqueous acid back to the carbonyl.
Imine and Enamine Formation
- Imine: 1° amine + aldehyde/ketone → imine (C=N-R). Loss of water. Optimal pH ~4–5 (acid catalyzes dehydration but too much acid protonates the amine, destroying the nucleophile).
- Enamine: 2° amine + aldehyde/ketone (with α-hydrogen) → enamine (C=C-NR₂). The α-proton is lost instead of the N-H.
Carboxylic Acid Derivatives — Reactivity Order
Acid chloride > Anhydride > Ester > Carboxylic acid > Amide > Carboxylate
Why this order? The better the leaving group, the more reactive the derivative. Leaving group ability: Cl⁻ > RCOO⁻ > RO⁻ > OH⁻ > NH₂⁻. Also, resonance donation from the heteroatom stabilizes the derivative (amide has strongest resonance = least reactive).
Nucleophilic Acyl Substitution
All carboxylic acid derivatives undergo nucleophilic acyl substitution — addition-elimination at the carbonyl:
- Nucleophile attacks carbonyl → tetrahedral intermediate.
- Leaving group is expelled → carbonyl reforms.
More reactive derivatives can be converted to less reactive ones: acid chloride → anhydride → ester → amide. The reverse requires special conditions.
Key Reactions of Carboxylic Acid Derivatives
Fischer Esterification: RCOOH + R'OH + H⁺ (cat.) ⇌ RCOOR' + H₂O. Acid-catalyzed, reversible. Use excess alcohol or remove water to drive equilibrium.
Saponification: RCOOR' + NaOH → RCOO⁻ Na⁺ + R'OH. Ester hydrolysis with BASE. Irreversible (carboxylate is resonance-stabilized and doesn't react further). This is how soap is made from fats (triacylglycerols).
Claisen Condensation: 2 RCH₂COOR' + NaOR' → RCH₂COCHR-COOR'. Two esters condense, driven by deprotonation of the β-ketoester product (pKa ~11). Requires at least 2 α-hydrogens on starting ester. Forms new C-C bond.
Decarboxylation of β-Keto Acids: β-keto acid + heat → ketone + CO₂. The cyclic 6-membered transition state makes this facile.
Reduction Hierarchy
| Reagent | Reduces |
|---|---|
| NaBH₄ | Aldehydes, ketones (NOT esters, acids, amides) |
| LiAlH₄ (LAH) | Aldehydes, ketones, esters, carboxylic acids, amides (everything!) |
| DIBAL-H (1 equiv, cold) | Esters → aldehydes (controlled reduction) |
Common Traps
- Confusing Claisen with Aldol: Claisen involves ESTERS and forms β-ketoesters. Aldol involves aldehydes/ketones and forms β-hydroxy carbonyls.
- NaBH₄ vs. LiAlH₄ selectivity: DAT questions test whether you know NaBH₄ won't touch esters.
- Imine formation pH: Too acidic = amine protonated (no nucleophile). Too basic = no acid catalysis for dehydration. Optimal ~pH 4–5.
- Fischer esterification is equilibrium: It doesn't go to completion without Le Chatelier tricks (excess reagent, water removal).
Eli explains
The same idea, in plain words
Explain it like I’m 10
Think of the carbonyl carbon as a magnet for things with extra electrons (nucleophiles). Aldehydes are "hungrier" than ketones because they have less stuff in the way. Carboxylic acid derivatives are like a family: acid chlorides are the most reactive (like the hot-headed sibling), and amides are the calm, stable one. Converting them goes only one way — downhill from reactive to stable, unless you really force it.
Key takeaways
- Aldehydes > ketones in reactivity (steric + electronic reasons).
- Acid chloride > anhydride > ester > amide in reactivity.
- NaBH₄ = selective (only aldehydes/ketones). LiAlH₄ = powerful (reduces nearly everything).
- Fischer esterification is acid-catalyzed and reversible. Saponification is base-promoted and irreversible.
- Claisen condensation requires 2 α-hydrogens and forms a β-ketoester.
- Which is more reactive toward nucleophilic addition: propanal or acetone? Why? Answer: Propanal (an aldehyde). Less steric hindrance (one small H vs. two CH₃ groups) and less electron donation (one alkyl group vs. two) makes the carbonyl carbon more electrophilic.
- Ethyl acetate + NaOH (aq), heat → ? Answer: Sodium acetate (CH₃COO⁻ Na⁺) + ethanol (CH₃CH₂OH). This is saponification: base-promoted ester hydrolysis. The carboxylate product is resonance-stabilized and does not react further.
- Two equivalents of ethyl propanoate + NaOEt, then H₃O⁺ → ? Answer: Ethyl 2-methyl-3-oxopentanoate (a β-ketoester). Claisen condensation: the α-carbon of one ester attacks the carbonyl of another. The product has a new C-C bond and a β-ketoester structure.
Study tools & related lessonsYou’ll learn to · Related
You’ll learn to
- Predict products of nucleophilic addition to aldehydes and ketones
- Rank carboxylic acid derivatives by reactivity toward nucleophilic acyl substitution
- Draw mechanisms for acetal/hemiacetal, imine, and enamine formation
- Apply Fischer esterification and saponification
- Recognize Claisen condensation and decarboxylation of β-keto acids
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