Nucleophilic Substitution

and Elimination Reactions

Self-Study Material

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by Daniel Berger
 Nucleophilic Aliphatic Substitution

R R
Nu + R C X Nu C R + X
R R

nucleophile leaving group

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 Nucleophilic Aliphatic Substitution
leaving group nucleophile

R R
Nu + R C X Nu C R + X
R R

in reverse
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Nucleophilic Substitution
in Synthesis
 The nucleophile
attacks the alkyl
halide 180o away
from the halogen The SN2 Mechanism
H3C
HO + H C Br
CH3CH2

(R)-2-bromobutane
The configuration
at carbon is inverted

CH3 CH3
δ− δ−
HO C Br HO C H + Br
H CH2CH3 CH2CH3

Transition state with (S)-2-butanol

simultaneous bond breaking
and bond forming

5 On the web
 slow rate- CH3
H3C limiting step
1. H C Br methanol
C
H CH2CH3
+ Br
CH3CH2

A planar carbocation

The SN1 Mechanism

H3C CH3 CH3OH CH3 CH3OH H3C CH3
2. O C H
fast
C fast H C O
H CH2CH3 H CH2CH3 CH2CH3 H

HOCH3 CH3OH

H3C CH3
a racemic H3C CH3

3. O C H mixture H C O
CH2CH3 CH2CH3
(S)-2-methoxybutane (R)-2-methoxybutane

On the web
 Whether a reaction is SN1 or SN2
1. Structure of nucleophile
– Also affects side reactions
2. Structure of alkyl halide substrate
3. Structure of leaving group

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 What makes a good nucleophile
• Negative charge
– OH- > H2O
• Polarizability C N O F
– Less electronegative P S Cl
– Larger
• Basicity nucleophilicity Br
– Brønsted Bronsted basicity I
– Lewis

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 Common nucleophiles and their
electrophilicities

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 Side reactions in the SN1 mechanism

NaI
Basicity of nucleophile

Br I

H2O
+
Br OH

NaOH
Br
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 Whether a reaction is SN1 or SN2
1. Structure of nucleophile
– Also affects side reactions
2. Structure of alkyl halide substrate
3. Structure of leaving group

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 Structure of Alkyl Halide
R H H H
Governed by
electronic factors R R R R R H H H

SN1 Increasing stability of carbocation intermediate

R3CX R2CHX RCH2X CH3X

(tertiary) (secondary) (primary) (methyl)

Increasing ease of access to site of reaction SN2

R R R H
Governed by
RC X
RH C X H C X H C X steric factors
R H H

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 Steric Hindrance of SN2
CH3

CH3CH2Br CH3CCH2Br
CH3

Rate = 1 Rate = 10-30

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 Whether a reaction is SN1 or SN2
1. Structure of nucleophile
– Also affects side reactions
2. Structure of alkyl halide substrate
3. Structure of leaving group

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 Leaving Group Ability
Correlates with Acid Strength
reactivity as a leaving group

O
I > Br > Cl >> F > CH3CO > HO > CH3O > H2N

strength of conjugate acid

Protonated leaving groups are good, because the conjugate

acids of neutral molecules are more acidic.
(In other words, the leaving groups are less basic.)

15 On the web
 Nucleophilic substitution will not
occur with a poor leaving group!

good leaving groups poor leaving groups

– – – – – –
TsO ≥ X ≈ RS > HOR ≈ HNR2 CN > OR > NR2

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 Summary: SN1 vs. SN2 Reactions
Type of Alkyl Halide SN2 SN1
methyl CH3X Favored. Does not occur
because of cation
instability.
primary RCH2X Favored. Rarely occurs
because of cation
instability.
secondary R2CHX Favored in aprotic Favored in protic
solvents with good solvents with poor
nucleophiles nucleophiles
tertiary R3CX Does not occur Favored because of
because of sterics. cation stability.
stereocenter Inversion Racemization
 β-Elimination
H2 O
C C C C C C + HB
B
H OH2 H

E1
X
C C C C
C C
B
+ HB
H X H

E2 C C C C + HB + X
H X
B

18 On the web
E2 Mechanism
E1 Mechanism
SN2 vs. E2
 Substitution vs. elimination

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