Amines and carbonyl compounds team up to form imines and enamines through nucleophilic addition. This dance of electrons involves forming a tetrahedral intermediate, proton transfer, and dehydration. The pH plays a crucial role, with acidic conditions favoring imine formation.

Oximes and 2,4-dinitrophenylhydrazones are crystalline derivatives of aldehydes and ketones. These reactions showcase nucleophilic addition followed by dehydration. The resulting solids are handy for characterizing and purifying carbonyl compounds in the lab.

Nucleophilic Addition of Amines to Aldehydes and Ketones

Formation of imines and enamines

• Imines form when a primary amine (nucleophile) adds to an aldehyde or ketone (electrophile) (acetone)
  • Nucleophilic addition of the amine to the carbonyl carbon forms a tetrahedral intermediate
  • Proton transfer from the amine to the alkoxide yields a carbinolamine intermediate (aminoalcohol)
  • Dehydration of the carbinolamine results in the imine product ($R_2C=NR'$) (N-ethylideneethylamine)
• Enamines form when a secondary amine adds to an aldehyde or ketone (cyclohexanone)
  • Nucleophilic addition of the amine to the carbonyl carbon forms a tetrahedral intermediate
  • Proton transfer from the amine to the alkoxide yields a carbinolamine intermediate
  • Dehydration of the carbinolamine results in the enamine product ($R_2C=CR-NR'R''$) (1-morpholinocyclohexene)
    • The double bond is conjugated with the nitrogen lone pair enabling resonance stabilization

pH dependence of imine formation

• Imine formation is favored under acidic conditions (pH < 7)
  • Protonation of the carbinolamine oxygen makes it a better leaving group, facilitating dehydration
  • Acid catalysis increases the reaction rate by promoting the dehydration step (rate-determining step)
• Under basic conditions, the reaction equilibrium shifts toward the starting materials (Le Chatelier's principle)
  • Deprotonation of the carbinolamine nitrogen stabilizes the intermediate, disfavoring dehydration
  • The reaction rate is slower in the absence of acid catalysis

Crystalline derivatives of aldehydes and ketones

• Aldehydes and ketones react with hydroxylamine ($NH_2OH$) to form oximes
  • Nucleophilic addition of hydroxylamine to the carbonyl carbon forms a tetrahedral intermediate
  • Proton transfer and dehydration yield the oxime product ($R_2C=NOH$) (acetophenone oxime)
  • Oximes are usually crystalline solids, useful for characterization and purification (melting point, TLC, column chromatography)
• Aldehydes and ketones react with 2,4-dinitrophenylhydrazine (2,4-DNP) to form 2,4-dinitrophenylhydrazones
  • Nucleophilic addition of 2,4-DNP to the carbonyl carbon forms a tetrahedral intermediate
  • Proton transfer and dehydration yield the 2,4-dinitrophenylhydrazone product ($R_2C=NNHAr$, where $Ar$ is the 2,4-dinitrophenyl group)
  • 2,4-Dinitrophenylhydrazones are usually highly crystalline solids with sharp melting points, useful for characterization and purification (recrystallization, derivatization)

Reaction Mechanisms and Related Concepts

• Imine and enamine formation are examples of condensation reactions, where two molecules combine to form a larger molecule with the loss of a small molecule (water in this case)
• The dehydration step in imine and enamine formation is an elimination reaction
• Tautomerism can occur between imines and enamines, where the double bond shifts between carbon-nitrogen and carbon-carbon