Henry reaction (nitroaldol addition)
Ready to scaleAdditionnitroaldol
Base-catalysed addition of a nitroalkane to an aldehyde to give a β-nitro alcohol that dehydrates under Knoevenagel-Henry conditions to the conjugated nitroalkene. Default example here is the textbook β-nitrostyrene prep — yellow needles, mp 58 °C, recrystallised from EtOH.
Conditions
Knoevenagel-Henry variant: glacial acetic acid (or 80 % aq. AcOH for milder conditions) with n-butylamine (5–20 mol%). Run at 20–25 °C in the dark for the slow variant, or at reflux (~118 °C glacial) for the faster Knoevenagel variant.
Workup
Pour onto cold water, filter the yellow nitrostyrene, recrystallise from boiling EtOH. Slow cooling gives larger needles; seeding the cooling solution with a previously-isolated crystal accelerates onset. Classical alternative (Worrall, Org. Synth. Coll. Vol. 1, 413): NaOH in MeOH at 0–5 °C — fast (≤1 h to first crop) but lower yield (~50 %).
| Compound | Role | Equiv | MW (g/mol) | ρ (g/mL) | Safety |
|---|---|---|---|---|---|
| Benzaldehyde100-52-7 · C7H6OAldehyde acceptor. | reactant | 1.0 | 106.12 | 1.050 | WarningSDS |
| Nitromethane75-52-5 · CH3NO2Nitroalkane — limiting reagent in this template. | reactant | 1.0 | 61.04 | 1.130 | WarningSDS |
| n-Butylamine109-73-9 · C4H11NPrimary amine catalyst — typically 5–20 mol%. | catalyst10 mol% | 0.1 | 73.14 | 0.730 | DangerSDS |
| Acetic acid64-19-7 · C2H4O2Glacial acetic acid — proton shuttle + Mannich buffer. | solvent | — | 60.05 | 1.040 | DangerSDS |
| β-Nitrostyrene102-96-5 · C8H7NO2(E)-β-Nitrostyrene. Yellow crystalline needles, mp 58 °C; recrystallises cleanly from boiling EtOH or MeOH. The parent Knoevenagel-Henry condensation product — Worrall's Org. Synth. 1929 prep is the classical undergraduate preparation of this compound. | product | — | 149.15 | — | Danger |