Question

(a) Why is the acylation of pyrrole not carried out under Friedel-Crafts conditions? (b) With reference to the nitration of pyrrole, show how acetyl nitrate behaves as a nitrating agent. Which site in pyrrole is preferentially nitrated?

Short answer

Pyrrole is too reactive for Friedel-Crafts conditions due to deactivation by acid. Acetyl nitrate nitrates pyrrole at the 2-position.

Step-by-step solution

Understanding Pyrrole Reactivity

Pyrrole is a five-membered heterocyclic aromatic compound. It is highly reactive due to the electron-rich nature of the nitrogen, which donates electrons to the ring. This makes pyrrole more reactive toward electrophilic substitution reactions, but also more sensitive to strong acids and harsh conditions.

Limitations of Friedel-Crafts Acylation for Pyrrole

Friedel-Crafts acylation uses strong Lewis acids like AlCl₃ that can protonate pyrrole or react with the nitrogen lone pair, deactivating the ring. Hence, pyrrole is acylated under milder conditions typically with milder reagents such as acyl chlorides without a traditional Lewis acid catalyst.

Mechanism of Acetyl Nitrate Nitration

Acetyl nitrate (CH₃COONO₂) is used as a nitrating agent. It generates the nitronium ion ( O₂⁺ ), a strong electrophile. In pyrrole, the nitronium ion attacks the most electron-rich position, which is the 2-position (adjacent to the nitrogen). Pyrrole prefers substitutions at the C2 or C5 positions to best maintain aromatic stability.

Predicting the Favored Nitration Site

In pyrrole, nitration typically occurs at the alpha position (C2 or C5) since these positions allow for the delocalization of positive charge over the most atoms, stabilizing the reaction intermediate. Thus, the nitronium ion from acetyl nitrate will primarily substitute at these positions.

Key concepts

Electrophilic Substitution

Electrophilic substitution is a fundamental chemical reaction where an electrophile replaces a hydrogen atom in an aromatic ring. It is especially prevalent in heterocyclic compounds like pyrrole. Due to the presence of the nitrogen atom in pyrrole, the ring is electron-rich, making it more susceptible to attack by electrophiles. Electrophiles seek out areas of high electron density, which makes pyrrole an ideal candidate due to the electron donation from the nitrogen atom.

• Pyrrole's electron-rich nature stems from the lone pair of electrons on nitrogen.
• This electron donation enhances the reactivity of pyrrole toward electrophiles.
• The substitution tends to occur at specific positions to maintain the stability of the aromatic ring.

As a result, the electrophilic substitution in pyrrole generally leads to substitution at the C2 or C5 positions, both adjacent to the nitrogen atom, ensuring the resultant compound retains its aromatic nature.

Friedel-Crafts Acylation

Friedel-Crafts acylation is a process that introduces an acyl group into an aromatic ring, usually in the presence of a Lewis acid. However, when it comes to pyrrole, using traditional Friedel-Crafts conditions is problematic.

• The process typically involves strong Lewis acids like aluminum chloride (AlCl₃).
• These acids can protonate pyrrole or react with the nitrogen’s lone pair, hindering its reactivity and potentially deactivating the aromatic ring.

This incompatibility necessitates milder conditions for successful acylation of pyrrole. Instead, pyrrole is often acylated with milder reagents such as acyl chlorides and without strong acid catalysts. This avoids protonation or complex formation with the nitrogen atom, preserving the ring's aromatic integrity.

Nitration Mechanism

The nitration of pyrrole involves adding a nitro group to the ring, and acetyl nitrate is commonly used for this purpose. The key intermediate in this reaction is the nitronium ion (\( NO_2^+ \)), a strong electrophile capable of attacking electron-rich areas in an aromatic ring.

• In the presence of pyrrole, the nitronium ion targets the 2-position next to the nitrogen, as this is the most electron-rich site.
• Such positioning allows for effective delocalization of positive charge across the molecule, stabilizing the intermediate formed.

Pyrrole tends to direct nitration predominantly at the alpha positions (C2 or C5), as these positions support aromatic stability most effectively by spreading any resultant positive charge over the ring, thus stabilizing the system during the reaction. Ensuring that the nitronium ion attacks these sites aids in maintaining the ring's aromatic character, which is crucial for the stability of the nitrated product.