44 - Organic Chemistry

Question

Rank the nitrogen atoms in each compound in order of increasing basicity. Isoniazid is a drug used to treat tuberculosis, whereas histamine causes the runny nose and watery eyes associated with allergies. 

Step-by-Step Solution

Answer

For isoniazid:

The increasing order of basicity is 2 < 3 <1.

 

For histamine

The increasing order of basicity is 3 < 2 < 1.

Factors that affect the basicity of amines

• Hybridization: If the percentage of s-character increases, then basicity decreases.

 

• Inductive effect: If a nitrogen atom is attached to an electron-donating group, then basically increases.

 

• Resonance: If a lone pair on nitrogen is involved in delocalization through resonance, then basicity decreases.

 

• Aromaticity: If a lone pair on nitrogen participates in delocalization to get an aromatic character, then basically decreases.

 

Increasing order of N atom basicity

(a)

The structure of the isoniazid is shown below:

 

• Isoniazid has three nitrogen atoms they are labeled as 1,2,3.
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                         Nitrogen atoms in isoniazid

• The lone pair electron on nitrogen-1 is localized and it is  $s{p}^3$ hybridized. So, nitrogen-1 is the most basic.

 

• The lone pair electron on nitrogen-2 is delocalized with the adjacent carbonyl group through resonance which leads to a decrease in electron density on the nitrogen and makes it least basic.

 

• The lone pair on nitrogen-3 is not participating in the aromatic pi system (i.e., localized). However, nitrogen-3 is  $s{p}^3$ hybridized (increasing percent of s character leads to a decrease in basicity).

 

 

• So, nitrogen-3 is less basic than nitrogen-1 and more basic than nitrogen-2.

 

 

Therefore, the increasing order of basicity is 2 < 3 <1.

 (b)

 

The structure of histamine is shown below.

 

• It has three nitrogen atoms they are labeled as 1,2,3.

 

         Nitrogen atoms in histamine

• The lone pair electron on nitrogen-1 is localized and it is  $s{p}^3$ hybridized. So, nitrogen-1 is the most basic.

 

• The lone pair on nitrogen-2 is not participating in delocalization to get the aromatic character (i.e., localized). However, nitrogen-2 is  $s{p}^2$ hybridized (increasing percent of s character leads to decrease in basicity.) So, nitrogen-2 is less basic than nitrogen-1.

 

• The lone pair on nitrogen-3 is participating in delocalization to get the aromatic character. It leads to a decrease in electron density on the nitrogen-3 and makes it least basic.

 

 

Therefore, the increasing order of basicity is 3 < 2 < 1.