Nitroaldol addition
Henry (nitroaldol) reaction
How the Henry (nitroaldol) reaction works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: Nitroalkane, aldehyde, cat. base (NaOH, Et₃N). Conditions: MeOH or THF, 0–25 °C. Bonds formed: C–C σ bond; O–H; bonds broken: α C–H; C=O π. Stereochemistry: Two new stereocentres (syn/anti mixture); reversible. Rate and selectivity: Nitro pKa ≈ 10 makes the nitronate easy to form.
At a glance
Step 1: Base removes the acidic α-H
Base deprotonates the acidic alpha carbon of a nitroalkane (strongly acidified by the electron-withdrawing nitro group), forming a stabilized nitronate anion.
Step 2: Nitronate carbon attacks the aldehyde
The nitronate carbon attacks an aldehyde's carbonyl carbon — a standard aldol-type addition, just with a nitro group instead of a carbonyl stabilizing the nucleophile.
Step 3: Protonation; optional dehydration
Protonation gives a β-nitro alcohol, which can be dehydrated further (an aza-analog of the aldol condensation) to a nitroalkene.
Abbreviations and terms
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- MeOH
- Methanol. Polar protic solvent (also a nucleophile in solvolysis).
- Et3N
- Triethylamine. Common tertiary-amine base that scavenges HCl.
- NaOH
- Sodium hydroxide. Strong aqueous base and nucleophile.
- pKa
- Acid-dissociation constant (–log). Lower pKa = stronger acid; used to judge which proton a base removes.
How it compares with related reactions
| Henry (nitroaldol) reaction | Acid-catalyzed hydration of an alkene | Br₂ addition to an alkene (vicinal dihalide) | |
|---|---|---|---|
| Reagents | Nitroalkane, aldehyde, cat. base (NaOH, Et₃N) | Dilute H₂SO₄ or H₃PO₄ (H₃O⁺), H₂O | Br₂ |
| Conditions | MeOH or THF, 0–25 °C | 25–100 °C; heat and excess water favour the alcohol | CH₂Cl₂ or CCl₄, 25 °C, dark |
| Stereochemistry | Two new stereocentres (syn/anti mixture); reversible | Planar carbocation: racemic; Markovnikov regiochemistry | Anti addition via bromonium; trans product (racemic) |
| Rate / selectivity | Nitro pKa ≈ 10 makes the nitronate easy to form | Protonation of the alkene is rate-determining | Bromonium formation rate-limiting; fast |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Henry (nitroaldol) reaction?
Nitroalkane, aldehyde, cat. base (NaOH, Et₃N). Conditions: MeOH or THF, 0–25 °C.
Which bonds are formed and which are broken?
Formed: C–C σ bond; O–H. Broken: α C–H; C=O π.
What is the stereochemical outcome?
Two new stereocentres (syn/anti mixture); reversible
What controls the rate or the selectivity?
Nitro pKa ≈ 10 makes the nitronate easy to form
Study guides that help with this reaction
- Carbonyl chemistry: addition, acyl substitution and enolates
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go