Alkyl Halides
and Nucleophilic
Substitution
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Interesting Alkyl Halides
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Reactions of Alkyl Halides
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General Features of a Substitution Reaction
Three components are necessary in any substitution reaction.
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When a neutral nucleophile is used, the substitution product
bears a positive charge.
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Nucleophiles
Basicity is a
thermodynamic
property
Nucleophilicity is a
kinetic
property
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• Steric hindrance decreases nucleophilicity but not basicity.
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But what is the order of bond making and bond breaking? In
theory, there are two possibilities.
[1] Bond making and bond breaking occur at the same time.
This is an example of an SN2 (substitution nucleophilic bimolecular)
mechanism.
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[2] Bond breaking occurs before bond making.
This is an example of an SN1 (substitution nucleophilic unimolecular)
mechanism.
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SN2 Reaction
CH3Br + OH–
Rate = k[CH3Br][OH-]
CH3OH + Br–
a second-order reaction
All SN2 reactions proceed with backside attack of the nucleophile,
resulting in inversion of configuration at a stereogenic center.
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The SN2 reaction is a key step in the laboratory synthesis of
many important drugs.
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• The rate of an SN1 reaction is affected by the type of alkyl halide
involved.
• This trend is exactly opposite to that observed in SN2 reactions.
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The Hammond Postulate
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• The strong nucleophile favors an SN2 mechanism.
• The weak nucleophile favors an SN1 mechanism.
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• A better leaving group increases the rate of both SN1 and SN2
reactions.
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In addition to substitution, an alkyl halide can undergo an
elimination reaction
The E2 Reaction
The Regioselectivity of the E2 Reaction
The major product of an E2 reaction is the most stable
alkene
The greater the number of substituents, the more stable is
the alkene (The Zaitsev Rule)
Potential Energies of Pentene Isomers
Consider the regioselectivity of the E2 reaction
The alkene with the bulkiest groups on opposite sides of
the double bond will be formed in greater yield, because it
is the more stable alkene
The E1 Reaction
Elimination from Cyclic Compounds
In an E2 reaction, groups to be eliminated must be trans
to one another (anti-coplanar)
Competition Between Substitution and
Elimination
Alkyl halides can undergo SN2, SN1, E2 and E1
1) decide whether the reaction conditions favor SN2/E2 or SN1/E1
•SN2/E2 reactions are favored by a high
concentration of nucleophile/strong base
•SN1/E1 reactions are favored by a poor
nucleophile/weak base
2) decide how much of the product will be the substitution product
and how much of the product will be the elimination product
Apakah mekanisme reaksi yang berkaitan dengan reaksi
berikut, substitusi SN1 atau SN2? Jelaskan alasan Saudara
1.(CH3)3CBr + CH3OH  (CH3)3COCH3 + HBr
2.CH3CH2I + NaCN  CH3CH2CN + NaI
H
H
c.
+
+ HBr
CH3OH
OCH3
Br
d.
H
H
+
Br
CH3O-Na+
+ NaBr
OCH3