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AAT Bioquest

What are the important factors that affect the basicity of amines?

Posted May 17, 2024


Answer

The three main factors that affect the basicity of amines include:

  • Aromaticity: Aromatic amines are typically less basic compared to their aliphatic counterparts; this is because the lone pair of electrons on the nitrogen atom is delocalized into the aromatic ring. This stabilizes the lone pair and makes it less available for donation to accept a proton, thus decreasing basicity. 
  • Resonance: Amines can exhibit resonance when attached to electron-withdrawing groups or when part of a conjugated system. Resonance delocalizes the lone pair of electrons into adjacent π-systems, reducing the availability of the lone pair for protonation. This results in decreased basicity.
  • Hybridization: The hybridization of the nitrogen atom in an amine affects its basicity. The greater the s-character in the hybrid orbital of the nitrogen atom, the more electronegative it is and thus the more stable the lone pair. This results in decreased basicity. The basicity of nitrogen peaks with sp3-hybridized nitrogen and reaches its lowest point with sp-hybridized nitrogen; the order based on basicity is sp3 > sp2 > sp. 
Additional resources

5 Key Basicity Trends of Amines

Intracellular pH

Weak Base pH Calculator