Hanyang University
Chapter 8
Nucleophilic Substitution Reactions:
Reactions of Alkyl Halides, Alcohols and
Related Compounds
Information and Communication Materials Lab.
Contens
8.1 The General Reaction
8.2 Reaction Mechanisms
8.3 Bimolecular Nucleophilic Substitution
8.4 Stereochemistry of the SN2
8.5 Effect of substitution on the Rate of the SN2 Reaction
8.6 Unimolecular Nucleophilic Substitution
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8.7 Effect of substitution on the Rate of the SN1 Reaction
8.8 Stereochemistry of the SN1 Reaction
8.9 Leaving Group
8.10 Nucleophiles
8.11 Effect of Solvent
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Contens
8.12 Competition Between SN1 and SN2 Reaction
8.13 Intramolecular Reaction
8.14 Competing Reactions
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Mastering Organic Chemistry
▶ Learning the two mechanisms by which substitution reactions occur
▶ Recognizing nucleophiles and leaving groups and understanding
the factors that control their reactivities.
▶ Understanding the factor that control the rates of substitution
reaction
▶ Predicting which mechanism will occur for a particular reaction
▶ Predicting the products of substitution reaction
▶ Predicting the stereochemistry of the products
▶ Recognizing when a rearrangement reaction will occur
▶ Recognizing the products formed form competing reactions
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8.1 The General Reaction
※ General form
p. 258
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8.2 Reaction Mechanism
• Nucleophilic substitution reaction occur through two
path way
① The bond to the leaving group may be broken first, followed by
formation of the bond to the nucleophile.
② Breaking and formation of bond to the leaving group and
nucleophile occur simultaneously.
① is called Unimolecular nucleophilic substitution reaction (SN1)
② is called Biimolecular nucleophilic substitution reaction (SN2)
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8.3 Bimolecular Nucleophilic Substitution
HO- + CH3CH2-Cl → CH3CH2-OH + Clrate = k[EtCl][OH-]
p. 260
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8.4 Stereochemistry of the SN2 Reaction
Possibility 1 ⇒ retention
of configuration
Possibility 2 ⇒ inversion
of configuration
Possibility 3 ⇒
racemization
- Result is possibility 2.
⇒(back-side attack)
p. 261
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• Transition state of SN2 reaction
p. 262
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Examples of the SN2 reaction
p. 262
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• Mechanism of the SN2 reaction of (S)-2-chloronbutane
and hydroxide ion
p. 263
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8.5 Effent of Substituents on the Rate of
the SN2 Reaction
p. 264
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• Free energy versus reaction progress diagrams for the SN2 reactions
of (A) MeCl, (B) EtCl, and (C) I-propyl chloride with hydroxide Ion
p. 265
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- The rate of the SN2 reaction is controlled by steric factors at the
electrophilic carbon. Steric hindrance slows the reaction.
p. 266
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Stabilization
Allyl chloride, benzyl chloride and chloroacetone react considerably
faster than other primary alkyl chloride. This increase in reaction
rate is due to resonance stabilization of the transition state.
p. 266
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•
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Some alkyl chlorides. Chlorine is green, and the electrophilic carbon is blue.
p. 267
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8.6 Unimolecular Nucleophilic Substitution
rate = k[t-BuCl]
This re action follow t he first -orde r rate law. Because the
reaction follow a different rate law from the S N 2 mechanism, it
must also proceed by a different mechanism
p. 268
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• Mechanism of SN1 reaction
p. 268
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• Free energy versus reaction progress diagram For the SN1 reaction of
tert-Butyl chloride and acetate anion
p. 269
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Reactive intermediate
p. 270
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• Transition state of SN1 reaction
The transition station has a structure that is intermediate between that
of the reactant, tert-butyl chloride, and that of the product, the tertbutyl carbocation.
p. 270
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• Using the hammond postulate to predict the structure of a
transition state ⓐ exergonic reaction and ⓑ endergonic reaction.
p. 271
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8.7 Effect of Substituents on the
Rate of the SN2 Reaction
SN1 reaction, formation of the carbocation is the rate-limiting step. So
any change that make the carbocation more stable will also make the
transition state more stable , result in g in a faste r react ion .
p. 272
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p. 272
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Hyperconjugation
The sigma MO and the empty p AO are coplanar, so they overlap on a
manner similar to pi bond, even though they are not parallel.
p. 273
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Allyl chloride and benzyl chloride have much faster rate for SN1 reactions
than would be expected for primary systems.
p. 273
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8.8 Stereochemistry of the SN1 Reaction
• Mechanism and Stereochemistry of the SN1 Reaction of (s)-1chloro-1-phenylethane in Aqueous Solution.
p. 276
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• Stereochemistry of the SN1 Reaction of (s)-1-chloro-1phenylethane in Acetic Acid Containing Potassium Acetate.
p. 277
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8.9 Leaving Group
p. 279
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Role of base
OH- is much too basic to act as a leaving
group in SN1 and SN2 reaction. So replacing
the hydrogen of the alcohol with this group
produces a sulfonate ester.
p. 280
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Example of the preparation of a mesylate ester
General form of the preparation of a mesylate ester
p. 281
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Example of the preparation of a tosylate ester
General form of the preparation of a tosylate ester
p. 281, 282
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[α]=+8.5
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[α]=-13.9
The only conclusion that can be reached on the basis of these data
is that the reaction has not proceeded with complete racemization.
p. 282
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8.10 Nucleophiles
▶ Rule 1
If the nucleophilic atoms are from the same period of the periodic table,
strength as a nucleophile parallels as a base
p. 284
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▶ Rule 2
Nucleophilic strength increases down a column of the periodic table (in
solvents that can hydrogen bond, such as water and alcohols).
p. 284
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▶ Rule 3
Steric bulk decreases nucleophlilcity
p. 285
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8.11 Effect of Solvent
• EFFECT OF CHANGING SOLVENT POLARITY ON THE S N 1 REACTION
p. 287
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The rate of an SN2 reaction involving a negative nucleophile is slower
in a more polar solvent.
Therefore, the rate of an SN2 reaction
involving a negative nucleophile is faster in a more polar solvent.
p. 287
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p. 288
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8.12 Competition Between
SN1 and SN2 Reaction
▶ The SN1 path way is favored in the following circumstances:
1. The carbocation is stabilized (tertiary or resonance stabilized
carbocations are best; secondary carbocations are acceptable if
other factors are favorable; primary carbocations are not formed).
2. The solvent is polar (to stabilize the transition state).
3. only poor nucleophiles are present (the absence of a good
nucleophile slows the rate of a competing SN2 reaction).
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▶ The SN2 path way is favored in the following
circumstances:
1. the electrophilic carbon is not sterically hindered (reactions at
methyl and primary carbons are excellent; reaction at secondary
carbons are acceptable; SN2 reactions do not occur at tertiary
carbons).
2. Strong nucleophiles are present.
3. The solvint is aprotic (to make the nucleophile more reactive).
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Preferred Substitution
Mechanisms for
Various Carbon
Substrates
p. 291
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8.13 Intramolecular Reactions
p. 293
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8.14 Competing Reactions
p. 294
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p. 295
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◀ Hydride and Alkyl shift ▶
: The change from the secondary carbocation to the more stable tertiary
cabocation again makes this rearrangement favorable.
p. 295
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Mechanism of an SN1 Reaction Involving Carbocation Rearrangement
p. 296
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Impact Factor
어떤 잡지에 게재된 논문 한편이 특정년도나 기간동안 인용
된 빈도수로 그 논문이 실린잡지의 수준을 평가하는 척도
29.273
30.927
4.127
7.419
3.027
9.596
4.426
6.770
4.024
3.705
9.107
(2006년 기준 자료)
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• Assignments
•28(ⓐ~ⓔ), 29(ⓐ~ⓒ), 40(ⓐ~ⓑ), 41, 47, 51, 54