Question

Most favourable site for protonation in the following compound is (A) I (B) II (C) III (D) IV

Short answer

The most stable conjugate base is formed by protonation at site II due to better charge delocalization through resonance structures. Inductive effects do not significantly affect the stability of conjugate bases in this case. Therefore, the most favourable site for protonation is site II (Answer: B).

Step-by-step solution

Identify acidic sites

Identify the four possible acidic sites (I, II, III, and IV) where a proton can be added in the given compound. Keep in mind that these sites have lone pair electrons or pi bond electrons (nucleophilic sites) which are capable of forming covalent bonds with the proton (or hydrogen ion, H⁺).

Analyze the resonance effect

Compare the ability of the conjugate bases to delocalize the negative charge formed after losing a proton through resonance structures. Conjugate bases with greater charge delocalization through resonance are more stable and therefore more favourable for protonation.

Look for inductive effects

In addition to resonance, identify any electron-withdrawing or electron-donating groups that can stabilize or destabilize the conjugate base through an inductive effect. Electron withdrawing groups will stabilize the conjugate base, whereas electron-donating groups will destabilize the conjugate base.

Compare conjugate base stabilities

Compare the stabilities of the conjugate bases based on resonance and inductive effects. The most stable conjugate base will correspond to the most favourable site for protonation.

Choose the most favourable site for protonation

Among the four acidic sites I, II, III, and IV, the site that forms the most stable conjugate base after protonation is the most favourable site. Select the corresponding answer (A, B, C, or D) as your solution.

Key concepts

Resonance Effect

The resonance effect plays a crucial role in determining the stability of conjugate bases and, consequently, the most favorable site for protonation. When a compound has resonance, it means the electrons can be delocalized across multiple atoms in the molecule. This delocalization can stabilize a negative charge that is present in a conjugate base after a proton is lost.

In simple terms, if a conjugate base can spread out its negative charge over several atoms through resonance structures, it is more stable. This is because the charge is not concentrated in one location. For instance:

• Look for sites where double bonds or lone pairs can create multiple resonance structures.
• Check if these structures allow for the movement of negative charges across different atoms.
• The more resonance forms a conjugate base has, the more stable it usually is.

By evaluating the resonance effect, you can predict which site in a molecule will be most favorable for protonation. Sites that lead to a conjugate base with extensive resonance are the most likely candidates for stable protonation.

Inductive Effect

The inductive effect involves the shifting of electrons within a molecule due to electronegativity differences between atoms. This effect can influence the stability of conjugate bases by either stabilizing or destabilizing the negative charge left behind after protonation.

Here's how it works:

• Electron-withdrawing groups (EWGs), like halogens or nitro groups, pull electron density away from neighboring atoms. This withdrawal can stabilize a negative charge on a conjugate base by reducing its intensity.
• Conversely, electron-donating groups (EDGs), like alkyl groups, push electron density toward neighboring atoms, which can destabilize a negative charge on a conjugate base by increasing electron density where it is not needed.

To consider the inductive effect when analyzing protonation sites, look at the groups attached to the site in question and determine if they would favor or hinder the stability of the resulting conjugate base. A site surrounded by EWGs may be more favorable for protonation due to the additional stabilization of the conjugate base.

Conjugate Base Stability

The stability of the conjugate base is the key factor in determining the most favorable site for protonation. If a site can yield a conjugate base that handles the negative charge effectively, that site will be preferential for protonation.

Evaluate stability through both the resonance and inductive effects:

• A stable conjugate base often arises from a balance of delocalizing negative charge (resonance) and electronic effects (inductive effect).
• Consider all surrounding groups and bonds to understand how they contribute to the base's stability.
• The more stable the conjugate base, the more favorable the protonation at that site becomes.

This understanding is crucial when predicting protonation in complex molecules and helps clarify why certain sites are more reactive in terms of grabbing protons.