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Basicity and Effect of Substituent on Basicity

Nitrogen in amines is electron-dense because of the lone pair electrons, as shown by the red color in the electrostatic potential map to the left.

Basicity

Nitrogen in amines is electron-dense because of the lone pair electrons, as shown by the red color in the electrostatic potential map to the left. Acids are electron-poor and react easily with basic amino acids.



Among the few neutral functional groups that can be considered bases due to the presence of lone pairs of electrons on nitrogen, amines are one of them. lone electrons attacking a hydrogen atom produce a N-H bond when acidic hydrogen reacts with a base. This results in four single bonds and a positive charge on the nitrogen in the resulting ammonium salt.

The following equation shows that when a proton is transferred to an amine, ammonia and water will react, yielding an ammonium salt and a hydroxide ion:



Known also as the base dissociation constant (Kb), the equilibrium constant for this reaction is:



Using the same method as described in Section 2-8 to calculate a carboxylic acid's acid strength, we can determine an amine's base strength by defining analogous basicity constant. If Kb is larger and pKb is smaller, then proton-transfer equilibrium is more favorable and the base is stronger.

Effect of substituent on basicity

  • An amine is basic because each atom possesses two electrons that can be shared with another atom. The nitrogen atom is surrounded by an electron density created by these unshared electrons.
  • An electron-rich molecule is more basic than one with few.
  • Using a positive inductive effect, electron-donating or supplying groups like alkyl groups (-H3, etc.) will result in increased basicity, while electron removing groups like -NO2, etc. will decrease the basicity of the molecule.
  • Due to the electron density created around the nitrogen atom of the amine, its electron-releasing capabilities increase due to the electron-donating properties possessed by the attached alkyl group.
  • Alkylamines, because they release electrons more easily and more readily, are therefore more basic than ammonia.
  • Basicity – order: NH3<1<2<3
A similar releasing group is not attached to ammonia. Ammonia has much lower basicity than alkylamines. The highest basicity can be found in the aliphatic amines, i.e., tertiary amines, followed by secondary amines, and finally primary amines. This is not true. NH3 is the most basic, followed by primaries, tertiaries, and secondary amines because of their respective amines.NH3 is the most basic, followed by primaries, tertiaries, and secondary amines.



Steric hindrance

  • The number of alkyl groups in an alkyl group is greater than the number of hydrogen atoms.
  • Alkyl groups prevent hydrogen atoms from attacking them, thus decreasing the molecule's basicity.
  • Alkyl groups are a measure of basicity, and the more there are, the slower it will be.
  • As a result, amines are ordered ascendingly: tertiary amine < secondary amine < primary amine.

Salvation effect

  • It is a relatively strong base, and its aqueous solutions are fairly straightforward.
  • Aqueous and gaseous solutions have different basicity orders due to hydrogen bonding (solvation effects).
  • Hydroxide and ammonium ions can be produced by absorption of a proton by amines.
Water with ammonium salts of primary and secondary amines has a greater solvation effect due to hydrogen bonding than water with ammonium salts of tertiary amines. Water containing ammonium salts of primary and secondary amines is subjected to greater solvation effects due to hydrogen bonding, compared with water containing ammonium salts of tertiary amines. Whenever amines are dissolved in water, protonated amines are formed. The possibility of hydrogen bonds forming increases as well. A molecule's hydration energy increases if it contains more hydrogen bonds. Amines are more stable if they have higher hydration energy. Studies indicate tertiary amines are the least stable of all the amine species, followed by secondary amines and then primary amines. The most stable species are secondary amines, while the least stable are tertiary amines.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of pharmaguideline.com, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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