Question

Indole reacts with electrophiles at C3 rather than at C2. Draw resonance forms of the intermediate cations resulting from reaction at \(\mathrm{C} 2\) and \(\mathrm{C} 3\), and explain the observed results.

Short answer

Attack at C3 forms more stable resonance structures, favoring reaction there.

Step-by-step solution

Understanding Indole Structure

Indole is a bicyclic compound containing a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. The carbon positions on the pyrrole ring are numbered such that the nitrogen is at C1, and the adjacent positions are C2 and C3.

Drawing the Cation from Reaction at C2

When an electrophile attacks indole at C2, it forms a cation at C2. Draw the resonance structures for this intermediate by moving the pi electrons in the pyrrole ring to show the possible distributions of the positive charge. Remember that the positive charge should not be on the nitrogen to maintain aromaticity.

Drawing the Cation from Reaction at C3

Similarly, when an electrophile attacks indole at C3, it forms a cation at C3. Draw the resonance structures for this intermediate, again moving the pi electrons in the ring to show the stability of positive charge distribution while maintaining aromaticity.

Comparing the Resonance Stability

Now, compare the number and quality of resonance structures for attack at C2 versus C3. Generally, the more resonance structures there are and the more stable they are, the more stable the cation. Stability also depends on maintaining aromaticity and minimizing positive charge localization on less electronegative atoms.

Explaining the Observed Reactivity

The intermediate formed by the electrophile attack at C3 has more and better resonance structures compared to the intermediate formed by attack at C2. The positive charge after the C3 attack can delocalize better, especially through the stable benzene ring, leading to lower energy and greater stability. Consequently, the C3 position is more reactive towards electrophiles.

Key concepts

Indole Structure

Indole serves as an interesting structure in organic chemistry due to its unique combination of rings. It combines a six-membered benzene ring with a five-membered pyrrole ring which includes a nitrogen atom. This fusion forms a bicyclic system that has distinct chemical behavior.

The nitrogen in the pyrrole ring is positioned at C1, giving a strategic position to C2 and C3 for potential chemical interactions, especially electrophilic attacks. These carbon positions are key to understanding indole's reactivity patterns, particularly how it interacts with electrophiles.

• The benzene component contributes to aromatic stability.
• The pyrrole component, with its nitrogen, influences electron distribution and reactivity.

Understanding the indole structure sets the groundwork for delving into how it behaves in reactions.

Resonance Stability

Resonance stability is a powerful concept when evaluating reaction intermediates in organic chemistry. In the context of indole, the resonance structures of cations formed during reactions are essential to determining the stability of these intermediates.

Resonance involves the movement of pi electrons, enabling the positive charge to spread across different atoms. This spread reduces the energy of the system, thus rendering it more stable. For indole, these structures support the stability of cations when attacked by electrophiles at different positions, such as C2 and C3.

• More resonance structures generally mean increased stability.
• Quality of resonance structures involves considerations like maintaining aromaticity and minimizing positive charge on electronegative atoms like nitrogen.

Identifying the extent and impact of resonance thus helps predict which reaction site is most favorable.

Cation Intermediate

Cation intermediates in indole are transient species that occur during electrophilic attack. Such intermediates are key to understanding why certain reactions proceed at given positions. When indole undergoes electrophilic aromatic substitution, cations can form at C2 or C3.

Determining the stability of these cations involves examining their resonance forms. The goal is to decide which intermediate allows for better distribution and delocalization of positive charge. Cation stability influences the reaction's direction, and in indole, it provides insight into why C3 is preferred over C2.

• Cation at C3 benefits from more stable resonance forms shared with the benzene ring.
• Cation at C2 can disrupt aromaticity more easily, leading to less stable forms.

These insights emphasize the importance of resonance in predicting reaction pathways in indole chemistry.

Aromaticity

Aromaticity is a critical concept influencing the behavior of many compounds, especially those containing benzene-like rings. Indole is an aromatic compound, thanks to its fused benzene and pyrrole systems, allowing it to benefit from substantial stability.

Maintaining aromaticity during reactions is paramount because it provides significant energy stabilization. During electrophilic attacks, aromaticity needs to be preserved as much as possible, which is why certain reaction sites like C3 in indole are more favorable than others.

• Preserving aromaticity is key to stabilizing intermediates formed during the reaction.
• Aromatic systems resist changes that would disrupt their electron delocalization.

Understanding aromaticity's effect ensures a deep comprehension of how indole maintains stability across various reactions.

Electrophile Reactivity

Electrophile reactivity refers to how easily electrophiles attack specific locations in aromatic systems like indole. The reactivity at different positions on indole depends significantly on the stability of the resulting intermediates.

Electrophiles typically seek out positions that provide the most stable cation through resonance. In indole, the C3 position is more reactive toward electrophiles due to its favorable resonance structures, allowing the positive charge to distribute efficiently, particularly drawing on the aromatic benzene's stability.

• C3 attack creates more stable intermediates, enhancing reaction odds.
• C2 lacks the stabilization benefits of C3 attack, despite being accessible.

This understanding of electrophile reactivity helps predict reaction pathways, ensuring targeted and efficient synthesis involving indole.