NEIGBOURING GROUP PARTICIPATION

INTRODUCTION-
• SN2 reactions follow second order rate kinetics while SN1 follows first order kinetics.
• The geometric alignment of transition state for SN2 mechanism is such that the
nucleophile attacks from the rear of the leaving group, leading to inversion of
configuration and in case of SN1 mechanism there is racemisation.
• However, there are some examples of retention of configuration in SN2 reactions,
where an atom or group (Z) close to the carbon undergoing substitution assist in the
reaction with its available pair of electrons.
• Such a group is called a neighbouring group (NG) and the assistance provided is
termed neighbouring group participation (NGP).
• NGP is often seen in nucleophilic substitution reactions, wherein a neighbouring group
aids in the removal of the leaving group to form a reactive intermediate that leads to
product formation.
• The increase of reaction rate and unexpected stereo chemical outcomes are
associated in reactions involving NGP.
• An atom having an unshared pair of electrons and is present on the β – positon to the
leaving group can act as a neighbouring group.

DEFINITION-
It is an intramolecular effect temporarily exerted by an adjacent group which
directly participates by moving within the bonding distance of the reaction centre
and then reverts back.
TWO STEP MECHANISM OF NGP-
• The mechanism for anchimeric assistance is a two step mechanism where two
consecutive SN2 reaction leads to retention of configuration.
• In the first step, the neighbouring group (Z) acts as a nucleophile, attacking the
substitution centre and expelling out the leaving group.
• In the next step, the external nucleophile (Y) attack from backside displacing the
neighbouring group and retaining the overall configuration.

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 Since the first step is slow and is rate determining, the reaction follows first order
kinetics and there is no effect of concentration of Y- on rate of reaction

IMPORTANT CHARACTERISTICS-
• Anchimeric assistance (anchimeric in Greek means “adjacent parts”) is a case of intra-
molecular catalysis where a suitably placed intra-molecular nucleophile(any group
that possesses an unshared pair of electrons or a double bond ) assists in a substitution
reaction by enhancing rate of reaction.
• Anchimeric assistance enhances rate of reactions by several order of magnitudes.
• This is because step 1 is the rate determining step and the neighbouring group Z which
is readily available within the substrate makes the attack much faster as compared to
attack by any external nucleophile Y for which, to react, the substrate has to collide
with Y- .
• Since, Z is readily available by virtue of its position its attack is much faster.

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 NGP reactions are characterized by
➢ enhanced rate and
➢ characteristic stereochemistry of retention of configuration.
➢ Neighbouring group participation can occur from any group that possesses an
unshared pair of electrons or a double bond.
➢ The electron density will accelerate the rate for departure of the leaving group.

ADDITIONAL INFORMATION-
• Important atoms and groups that can act as neighbouring groups are COO- COOR,
COAr, OCOR, OR, OH, O- , NH2, NHR, NR2, NHCOR, SH, SR, S- , SO2Ph, I, Br, and Cl.
• The effectiveness of halogens as neighbouring groups decreases in the order
I>Br>Cl.
• The chloride is a very weak neighbouring group and can be shown to act in this way
only when the solvent does not interfere.

EXAMPLES-
1) When 2-Bromopropanoic acid is reacted with low conc NaOH in presence of Ag2O, product
Lactic acid or 2-Hydroxypropanoic acid formed after acidification has retention of
configuration
Explanation-
It is a first order reaction and the rate is independent of the concentration of the nucleophile.
Carboxylate anion acts as the internal nucleophile and reactive α-lactone is formed which is
rapidly attacked by the external nucleophile hydroxide ion. The configuration is retained in
the product as there are two nucleophilic substitution reactions. The first step is slow and rate
determining step. Hence it is first order reaction

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 H2O/NaOH

2) Mustard gas (2,2-Dichlorodiethylsulphide) undergoes hydrolysis in presence of a base. It

differs from hydrolysis of alkyl halide-
(i)First order kinetics; rate not dependent upon concentration of base
(ii) Rate of hydrolysis is very fast

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Explanation-
It is a first order reaction and the rate is independent of the concentration of the nucleophile.
Sulphur atom at β-position acts as the internal nucleophile and cyclic sulphonium ion is
formed which is rapidly attacked by the external nucleophile water. The configuration is
retained in the product as there are two nucleophilic substitution reactions. The configuration
is retained in the product as there are two nucleophilic substitution reactions. The first step
is slow and rate determining step. Hence it is first order reaction. Also, due to anchimeric
assistance rate of reaction is very fast.

STEREOCHEMICAL ASPECTS-
Nucleophilic substitutions are characterised by inversion or racemisation. But due to
neighbouring group participation, there is 100% retention of configuration.
 When 3-bromo-2-butanol with the stereochemical structure (erythro form) is treated
with concentrated HBr it yields meso-2,3-dibromobutane; a similar reaction of the 3-
bromo-2-butanol(threo form) yields (±)-2,3-dibromobutane.
 This classic experiment performed in 1939 by S. Winstein and H.J. Lucas was the
starting point for a series of investigations of what are called neighbouring group
effects.

OR

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 In the reaction of the Erythro isomer there is retention of configuration.
 In the reaction of the Threo isomer, in one of the products retention at both the
carbon atoms and in other product inversion at both the carbon atoms.
 This can be explained only by NGP mechanism as shown below
 In this reaction, two nucleophilic substitutions take place.
 First step, bromine atom (NGP) attacks the carbon with protonated hydroxy group to
form bridged bromonium ion intermediate.
 Second step, external nucleophile bromide ion attacks bromonium ion at either of the
two carbon atoms. Thus, complete retention or inversion takes place depending on
which C atom is attacked.

Mechanism for formation of racemic mixture from the optically active threo isomer

Similar mechanism can be written with erythron isomer to get meso-product

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