Nef reaction template

NaOH turns 2-nitropropane into its nitronate; in cold strong acid it is protonated twice on oxygen, water adds to carbon and loss of water and HNO gives acetone.

Mechanism step by step

A nitronate salt poured into strong acid gives a ketone or aldehyde and N₂O

1. Nitronate formation – Hydroxide removes the acidic α-H (pKa ≈ 8 in water): the nitronate anion
2. O-Protonation – In strong acid the nitronate takes a proton on oxygen: the nitronic acid (aci-nitro form)
3. Second protonation – A second proton on oxygen gives a very electrophilic iminium-like carbon
4. Water adds to carbon – Water attacks the C=N⁺ carbon
5. Proton transfers, − H₂O – Loss of a proton and of water from N(OH)₂ gives a 1-nitroso alcohol
6. Fragmentation – Loss of the O–H proton breaks the C–N bond: acetone and nitroxyl (HNO), which gives N₂O + H₂O

Key points

• Primary nitroalkanes give aldehydes, secondary give ketones; tertiary nitroalkanes have no α-H, form no nitronate and do not react.
• The nitronate must go into strong acid (pH < 1); in weaker acid oximes and other by-products form.
• Nitroalkanes are acyl anion equivalents (umpolung): a Henry or Michael reaction followed by the Nef reaction makes carbonyl compounds.
• Milder variants: oxidative (KMnO₄, Oxone, O₃ on the nitronate) and reductive (TiCl₃, which goes through the oxime).

Drawn with 101 atoms, 19 arrows, 10 shapes – every one editable in MolDraw.

Sources

• Kürti & Czakó, Strategic Applications of Named Reactions in Organic Synthesis, Elsevier 2005 Textbook
• Smith, March's Advanced Organic Chemistry, 8th ed., Wiley 2020, ch. 16 Textbook