Henry reaction (nitroaldol addition)

Ready to scaleAdditionnitroaldol

OBenzaldehyde+N+OO−Nitromethanen-BuNH2 (10 mol%)AcOHON+O−β-Nitrostyrene70–80 %
OBenzaldehyde+N+OO−Nitromethanen-BuNH2 (10 mol%)AcOHON+O−β-Nitrostyrene70–80 %

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 %).

CompoundRoleEquivMW (g/mol)ρ (g/mL)Safety
Benzaldehyde100-52-7 · C7H6OAldehyde acceptor. reactant 1.0 106.12 1.050 Irritant (GHS07)WarningSDS
Nitromethane75-52-5 · CH3NO2Nitroalkane — limiting reagent in this template. reactant 1.0 61.04 1.130 Flammable (GHS02)Irritant (GHS07)WarningSDS
n-Butylamine109-73-9 · C4H11NPrimary amine catalyst — typically 5–20 mol%. catalyst10 mol% 0.1 73.14 0.730 Flammable (GHS02)Corrosive (GHS05)Irritant (GHS07)DangerSDS
Acetic acid64-19-7 · C2H4O2Glacial acetic acid — proton shuttle + Mannich buffer. solvent — 60.05 1.040 Flammable (GHS02)Corrosive (GHS05)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 — Acute Toxic (GHS06)Irritant (GHS07)Danger

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