Bimolecular Displacement Mechanisms, Orientation, Aliphatic vs Aromatic Nucleophilic Substitution
Aryl halides are aromatic compounds where a halogen atom is directly attached to the benzene ring. Their general formula is Ar–X. These compounds usually do not react easily with nucleophiles such as OH⁻, OR⁻, NH₃, or CN⁻. Therefore, nucleophilic aromatic substitution is significantly less common compared to aliphatic substitution or electrophilic aromatic substitution.
Why Aryl Halides Are Less Reactive
The C–X bond in aryl halides has partial double-bond character due to resonance. This makes the bond stronger and harder to break. However, if an electron-withdrawing group (EWG) is present at the ortho or para position (e.g., NO₂, CN, SO₃H, COOH, CHO, COR), the aryl halide becomes much more reactive towards nucleophiles.
These EWGs stabilize the intermediate that forms during nucleophilic attack, making the reaction possible.
Bimolecular Displacement Mechanism (SNAr)
The nucleophilic aromatic substitution (SNAr) mechanism takes place in two major steps:
- Attack by nucleophile: The nucleophile attacks the aromatic ring, forming a negatively-charged intermediate (known as a Meisenheimer complex).
- Departure of leaving group: The halide ion leaves the ring, restoring aromaticity.
This intermediate is a real, stable species—not just a transition state. Therefore, SNAr is easier when the intermediate is stabilized by electron-withdrawing groups.
Comparison with Aliphatic SN2 Reaction
In aliphatic nucleophilic substitution (SN2), the intermediate is not stable. It exists only as a high-energy transition state with five groups temporarily attached to carbon.
In contrast, nucleophilic aromatic substitution forms a more stable anionic intermediate, making the reaction path different and more controlled.
Orientation in Nucleophilic Aromatic Substitution
The position of substituents strongly affects the reactivity of aryl halides. Electron-withdrawing groups at ortho and para positions stabilize the intermediate carbanion formed during the reaction. Therefore, these positions react faster.
For example:
- p-Chloronitrobenzene reacts faster than m-chloronitrobenzene.
- o-Chloronitrobenzene also reacts faster than the meta isomer.
Electron-donating groups, on the other hand, destabilize the intermediate and slow down the reaction.
Aliphatic vs Aromatic Nucleophilic Substitution
The three types of nucleophilic substitution differ in how charges develop:
| Reaction Type | Charge Developed | Favored By |
|---|---|---|
| SN1 (aliphatic) | Positive charge (carbocation) | Electron-releasing groups |
| SN2 (aliphatic) | No significant charge | Less dependent on electronic effects |
| SNAr (aromatic) | Negative charge (carbanion intermediate) | Electron-withdrawing groups |
Thus, SNAr is the opposite of SN1 in terms of electronic requirements. It is heavily favored when strong electron-withdrawing groups are present on the ring.
In summary, nucleophilic aromatic substitution depends strongly on substituent effects, reaction orientation, and the stability of the intermediate formed during the reaction.
Detailed Notes:
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PATH: PHARMD/PHARMD NOTES/ PHARMD FIRST YEAR NOTES/ ORGANIC CHEMISTRY/ PHARMACEUTICAL ORGANIC CHEMISTRY/ BIMOLECULAR DISPLACEMENT MECHANISMS, ORIENTATION, ALIPHATIC VS AROMATIC NUCLEOPHILIC SUBSTITUTION.