Chapter 8 Nucleophilic Substitution

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Chapter 8Nucleophilic Substitution
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8.1Functional Group Transformation By
Nucleophilic Substitution
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Nucleophilic Substitution

R

Y
R
X

• nucleophile is a Lewis base (electron-pair
  donor)
• often negatively charged and used as Na or K
  salt
• substrate is usually an alkyl halide

4
Nucleophilic Substitution
Substrate cannot be an a vinylic halide or
an aryl halide, except under certain conditions
to be discussed in Chapter 23.
X
5
Table 8.1 Examples of Nucleophilic Substitution
Alkoxide ion as the nucleophile

gives an ether
6
Example
(CH3)2CHCH2ONa CH3CH2Br
Isobutyl alcohol
(CH3)2CHCH2OCH2CH3 NaBr
Ethyl isobutyl ether (66)
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Table 8.1 Examples of Nucleophilic Substitution
Carboxylate ion as the nucleophile

..

O
R'C
..
gives an ester
..


X
R
O
R'C
..
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Example

CH3(CH2)16C
OK
CH3CH2I
acetone, water

KI
O
CH3(CH2)16C
CH2CH3
Ethyl octadecanoate (95)
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Table 8.1 Examples of Nucleophilic Substitution
Hydrogen sulfide ion as the nucleophile

gives a thiol
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Example
KSH CH3CH(CH2)6CH3
Br
ethanol, water
KBr
CH3CH(CH2)6CH3
SH
2-Nonanethiol (74)
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Table 8.1 Examples of Nucleophilic Substitution
Cyanide ion as the nucleophile


gives a nitrile


X
R
12
Example
NaCN

DMSO

NaCN
Cyclopentyl cyanide (70)
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Table 8.1 Examples of Nucleophilic Substitution
Azide ion as the nucleophile

gives an alkyl azide



X
R
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Example
NaN3 CH3CH2CH2CH2CH2I
2-Propanol-water
CH3CH2CH2CH2CH2N3 NaI
Pentyl azide (52)
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Table 8.1 Examples of Nucleophilic Substitution
Iodide ion as the nucleophile


gives an alkyl iodide


X
R
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Example
acetone

NaBr
CH3CHCH3
NaI is soluble in acetone NaCl and NaBr are not
soluble in acetone.
I
63
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8.2Relative Reactivity of Halide Leaving Groups
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Generalization

• Reactivity of halide leaving groups in
  nucleophilic substitution is the same as for
  elimination.

most reactive
RI
RBr
RCl
RF
least reactive
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Problem 8.2
A single organic product was obtained when
1-bromo-3-chloropropane was allowed to react
with one molar equivalent of sodium cyanide in
aqueous ethanol. What was this product?
BrCH2CH2CH2Cl NaCN

• Br is a better leaving group than Cl

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Problem 8.2
A single organic product was obtained when
1-bromo-3-chloropropane was allowed to react
with one molar equivalent of sodium cyanide in
aqueous ethanol. What was this product?
BrCH2CH2CH2Cl NaCN