Neighbouring Group Participation (NGP)
Also known as SNGP or Anchimeric Assistance.
By chemca Team • Updated Jan 2026
In certain nucleophilic substitution reactions, a group attached to the substrate (near the reaction center) acts as an internal nucleophile. This participation dramatically increases the reaction rate and leads to Retention of Configuration instead of the usual inversion.
1. Mechanism: The Double Inversion
Two-Step Intramolecular Process
The reaction proceeds in two steps, effectively performing two $S_N2$ reactions back-to-back.
Step 1: Intramolecular Attack (Cyclization)
The neighbouring group ($G$, with lone pair or $\pi$ electrons) attacks the carbon holding the leaving group ($L$) from the backside. This displaces $L$ and forms a cyclic intermediate.
Result: Inversion of configuration at the reaction center.
The neighbouring group ($G$, with lone pair or $\pi$ electrons) attacks the carbon holding the leaving group ($L$) from the backside. This displaces $L$ and forms a cyclic intermediate.
Result: Inversion of configuration at the reaction center.
$$ G-C-C-L \xrightarrow{\text{Internal Attack}} \underset{\text{Cyclic Intermediate}}{[G-C-C]^+ L^-} $$
Step 2: External Nucleophilic Attack
The external nucleophile ($Nu^-$) attacks the cyclic intermediate from the backside, opening the ring.
Result: Second Inversion of configuration.
The external nucleophile ($Nu^-$) attacks the cyclic intermediate from the backside, opening the ring.
Result: Second Inversion of configuration.
$$ [G-C-C]^+ + Nu^- \rightarrow G-C-C-Nu $$
Net Result: Inversion + Inversion = Retention of Configuration.
2. Key Features of NGP
Anchimeric Assistance
1. Rate Enhancement:
Reactions involving NGP are often thousands of times faster than comparable intermolecular $S_N2$ reactions.
Reason: The attacking group is part of the same molecule, so the effective concentration is very high (Entropic advantage). This rate enhancement is called Anchimeric Assistance.
Reactions involving NGP are often thousands of times faster than comparable intermolecular $S_N2$ reactions.
Reason: The attacking group is part of the same molecule, so the effective concentration is very high (Entropic advantage). This rate enhancement is called Anchimeric Assistance.
2. Kinetics:
It generally follows First Order Kinetics ($\text{Rate} = k[\text{Substrate}]$) because the rate-determining step (Step 1) is unimolecular (intramolecular cyclization).
It generally follows First Order Kinetics ($\text{Rate} = k[\text{Substrate}]$) because the rate-determining step (Step 1) is unimolecular (intramolecular cyclization).
3. Stereochemical Requirement:
The neighbouring group ($G$) and the leaving group ($L$) must be Anti-periplanar (trans to each other) to allow backside attack.
The neighbouring group ($G$) and the leaving group ($L$) must be Anti-periplanar (trans to each other) to allow backside attack.
3. Examples of Participating Groups
Groups with lone pairs ($-OH, -OR, -NH_2, -SR, -X, -COO^-$) or $\pi$-bonds (Phenyl, Double bond) can participate.
A. Sulfur Participation (Mustard Gas Hydrolysis):
$\beta$-chloroethyl sulfides hydrolyze extremely rapidly.
$\beta$-chloroethyl sulfides hydrolyze extremely rapidly.
$$ R-S-CH_2-CH_2-Cl \xrightarrow{-\text{Cl}^-} \underset{\text{Episulfonium Ion}}{[R-S^+(CH_2)_2]} \xrightarrow{H_2O} R-S-CH_2-CH_2-OH $$
B. Aryl Participation (Phenonium Ion):
In the acetolysis of $\beta$-phenylethyl tosylates, the phenyl ring acts as a nucleophile.
In the acetolysis of $\beta$-phenylethyl tosylates, the phenyl ring acts as a nucleophile.
$$ Ph-CH_2-CH_2-OTs \rightarrow \text{Phenonium Ion Intermediate} \rightarrow \text{Product (Retention)} $$
C. Carboxylate Ion Participation:
Hydrolysis of $\alpha$-halo carboxylates often proceeds via an $\alpha$-lactone intermediate, leading to retention.
Hydrolysis of $\alpha$-halo carboxylates often proceeds via an $\alpha$-lactone intermediate, leading to retention.
4. Comparison with Standard Mechanisms
| Feature | $S_N2$ | $S_N1$ | NGP ($S_N$GP) |
|---|---|---|---|
| Steps | 1 (Concerted) | 2 (Carbocation) | 2 (Cyclic Intermediate) |
| Stereochemistry | Inversion | Racemization | Retention |
| Rate | Standard | Standard | Enhanced (Anchimeric Assistance) |
| Reagent Order | 2nd Order | 1st Order | 1st Order |
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