The Schmidt reaction uses catalytic acid and hydrazoic acid to convert carboxylic acids, aldehydes, ketones, olefins, and 3° alcohols to amines, nitriles, amides, imines, and imines respectively. In the case of aldehydes, hydrazoic acid attacks the carbonyl group, to form a tetrahedral azidoalkanol intermediate. Water is expelled as nitrogen forms a double bond to carbon, followed by removal of a proton and expulsion of nitrogen gas to make a carbon-nitrogen triple bond.

Lab Tips:

• Note that hydrazoic acid is both toxic and explosive, especially in large amounts. It is handled either as a solution in an inert solvent (e.g. CHCl₃) or generated in situ by adding NaN₃ to the acidic reaction mixture.
• A possible side reaction for aldehydes is the formation of formamide.
• If sulfuric acid is used, aromatic aldehydes are preferred as aliphatic aldehydes are unstable in this acid.
• Lewis acids (TiCl₄, TFA, CH₃SO₃H) are effective catalysts when alkyl azides are used.
• Unsymmetrical ketones can result in a mixture of amide products since either R group is able to migrate to the nitrogen atom.

• Reagents: Hydrazoic Acid or Alkyl Azide, Acid Catalyst (H₂SO₄, TFA, PPA, etc.)
• Reactant: Carboxylic Acid, Aldehyde, Ketone, Olefin, or 3° Alcohol
• Product: Amine, Nitrile, Amide, or Imine
• Type of Reaction: Azide Nucleophilic Addition
• Bond Formation: C-N or C=N, and C≡N

Mechanism

Original Paper

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