Nucleophilic Addition Reactions
High-Yield Summary
- Nucleophile attacks the carbonyl carbon → tetrahedral alkoxide intermediate. No good leaving group (aldehydes/ketones) → simply protonated to an alcohol = addition. Good leaving group present (acid derivatives) → substitution instead.
- Aldehydes > ketones in reactivity toward nucleophiles — one alkyl/aryl group (vs. two) means less steric hindrance and a greater partial positive charge on the carbonyl carbon.
- Water adds → geminal diol (two OH on one carbon). 1 equivalent alcohol → hemiacetal (from aldehyde) / hemiketal (from ketone); 2nd equivalent + acid catalyst (via oxocarbenium ion) → acetal / ketal (two OR groups, no OH).
- Primary amine + carbonyl → imine (C=N, water eliminated). Secondary amine + carbonyl → enamine (C=C-NR₂) — no N-H left to lose, so a proton leaves from the α-carbon instead.
- Cyanide (CN⁻) adds → cyanohydrin (OH + CN on same carbon); the nitrile hydrolyzes (acid or base) to a carboxylic acid, giving an α-hydroxy carboxylic acid.
Amine Type → Product
| Amine | Product |
|---|---|
| Primary amine (R-NH₂) | Imine (C=N) — loses a proton from N |
| Secondary amine (R₂NH) | Enamine (C=C-NR₂) — loses a proton from the α-carbon (no N-H available) |
Hemiacetal/Hemiketal → Acetal/Ketal (2nd Equivalent, Acid-Catalyzed)
- 1Acid protonates the hemiacetal/hemiketal's -OH, converting it into a better leaving group.
- 2That group leaves as water, generating a resonance-stabilized oxocarbenium ion.
- 3A second alcohol molecule attacks the oxocarbenium ion.
- 4Result: a carbon bearing two -OR groups — an acetal (from an aldehyde) or a ketal (from a ketone).
Key Terms
- Geminal diol
- Two -OH groups on the same carbon; forms when water adds across a carbonyl.
- Hemiacetal / Hemiketal
- Carbon bonded to one -OH and one -OR group, from 1 equivalent of alcohol addition to an aldehyde/ketone; distinguished from acetal/ketal by the retained OH.
- Oxocarbenium ion
- Resonance-stabilized cation formed when a hemiacetal/hemiketal's protonated OH leaves as water; attacked by the second alcohol equivalent to form the acetal/ketal.
- Cyanohydrin
- Product of CN⁻ addition to a carbonyl; carries both -OH and -CN on the same carbon, hydrolyzable to an α-hydroxy carboxylic acid.
Common MCAT Trap
- Don't mix up hemiacetal (1 OR + 1 OH, no acid catalyst needed) with acetal (2 OR, no OH, requires acid catalysis and a second alcohol equivalent) — the retained OH is the tell.
- The imine-vs-enamine outcome depends only on primary vs. secondary amine — both mechanisms proceed through the same charged tetrahedral intermediate up to that point.
- Addition vs. substitution isn't about the nucleophile — it's about whether the substrate has a leaving group after nucleophilic attack (aldehydes/ketones don't; acid derivatives do).
Quick Recall
Why are aldehydes more reactive than ketones toward nucleophilic addition?
What forms when a secondary amine reacts with a ketone, and why not an imine?
What is the key structural difference between a hemiacetal and an acetal?
What does hydrolyzing a cyanohydrin's nitrile group produce?