Q30E - Organic Chemistry (Mcmurry)

Question

21-30 Electrostatic potential maps of a typical amide (acetamide) and an acyl azide (acetyl azide) are shown. Which of the two do you think is more reactive in nucleophilic acyl substitution reactions? Explain.
 

Step-by-Step Solution

Answer

Acetamide is one of the two carboxylic acid derivatives to be compared.

Acetamide:

${\mathrm{H}}_3\mathrm{C}-\stackrel{\mathrm{O}}{\stackrel{\parallel }{\mathrm{C}}}-{\mathrm{NH}}_2$

Acetyl azide:

${\mathrm{H}}_3\mathrm{C}-\stackrel{\mathrm{O}}{\stackrel{\parallel }{\mathrm{C}}}-\ddot{\mathrm{N}}=\mathrm{N}=\underset{¨}{\mathrm{N}}:$

Based on their electron-releasing or electron-withdrawing effects on the carbonyl carbon, both can be depicted as resonance hybrids of the following respective structures:

 

As a result,

Step 1: Introduction to the Concept

A nucleophilic substitution reaction occurs when an electron-rich nucleophile contacts a positively charged electrophile in order to replace a leaving group.

Step 2: Solution Explanation

By increasing electron density on the carbonyl atom, the ${\mathrm{NH}}_2$ amino group makes it less reactive.

${\mathrm{H}}_3\mathrm{C}-\stackrel{\mathrm{O}}{\stackrel{\parallel }{\mathrm{C}}}-\ddot{\mathrm{N}}=\mathrm{N}=\underset{¨}{\mathrm{N}}:$

For the acyl carbon, the guide ion N is electron withdrawing and activating: it is a resonance hybrid of the following structures.

$\begin{array}{l}\underset{\updownarrow }{\mathrm{R}-\ddot{\mathrm{N}}=\mathrm{N}=\underset{¨}{\mathrm{N}}:}\\ \mathrm{R}-\overline{\mathrm{N}}-{\mathrm{N}}^{+}\equiv \mathrm{N}\leftrightarrow \mathrm{R}-\mathrm{N}={\mathrm{N}}^{+}\equiv {\mathrm{N}}^{-}\end{array}$

As a result, acetyl amide forwards nucleophile acyl replacements are more reactive than acetyl amide. Furthermore, the amide ion is a strong base with a poor leaving group; however, protonation to acid reduces basicity and produces a better leaving group.

${\mathrm{H}}_3\mathrm{C}-\stackrel{\mathrm{O}}{\stackrel{\parallel }{\mathrm{C}}}-\ddot{\mathrm{N}}=\mathrm{N}=\mathrm{N}:\stackrel{{\mathrm{H}}_3{\mathrm{O}}^{+}}{\to }{\text{ H}}_3\mathrm{C}-\stackrel{\mathrm{O}}{\stackrel{\parallel }{\mathrm{C}}}-\underset{+}{\overset{\mathrm{H}}{\mathrm{N}}}=\mathrm{N}=\mathrm{N}:\stackrel{-{\mathrm{HN}}_3}{\to }{\text{ H}}_3\mathrm{C}-\stackrel{\mathrm{O}}{\stackrel{\parallel }{\mathrm{C}}}-$

In nucleophile acyl substitution processes, acetyl acid is more reactive than acetamide.