ORGANIC CHEMISTRY
Chapter 6
6.15 Organic Synthesis:
Functional Group Transformations
Using SN2 Reactions
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
SN2 reactions are highly useful in organic
synthesis because they enable use to convert
one functional group into another ——
functional group transformation (functional
group interconversion).
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
NaI
NaOH
NaOCH3
O
NaO C CH3
RX
R= Me, 1° NaONO
2
or 2°
X= Cl, Br NaCN
or I
NaN3
RI
ROH
Alkyl iodide
Alcohol
ROCH3 Ether
O
RO C CH3 Ester
CH3ONO2 Methyl nitrate
RCN
Nitrile
RN3
Alkyl azide
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Chapter 6
NaSH
RSH
NaSCN
RSCN Alkyl thiocyanate
NaCH(CO2CH3)2
R X
NaC C CH3
NH3
Thiol
RCH(CO2CH3)2
Dimethyl alkylmalonate
RC C CH3
Alkyne
RNH3Br
Alkylammonium bromide
N(CH3)3
P(CH3)3
R(CH3)3NBr
Alkyltrimethylammonium bromide
R(CH3)3PBr
Alkyltrimethylphosphonium bromide
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Chapter 6
R X
AgNO3
EtOH
R ONO2 + AgX
Room Tempt.
CH2Cl
AgCl
CH2 CHCH2Cl
(CH3)3CCl
(CH3)2CHCl
AgNO3
heat
instantly
AgCl 2 or 3 miniums
EtOH
CH3CH2CH2Cl
AgCl
CH2 CHCl
Cl
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
6.16 Elimination Reactions of
Alkyl Halides
卤代烃的消除反应
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
Another characteristic of alkyl halides is that
undergo elimination reactions. In an
elimination reaction the fragments of some
molecule (YZ) are removed (eliminated) from
adjacent atoms of the reactant. This
elimination leads to the introduction of a
multiple bond:
C C
Y Z
Elimination
YZ
C C
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
6.16A Dehydrohalogenation (脱卤化氢 )
RCH2CH2 X
RCH2CH X
KOH, EtOH
KOH, EtOH
RCH CH2
RC CH
X
Reactivity： R3CX > R2CHX > RCH2X
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Chapter 6
CH3CH2 CH CH3 KOH, EtOH CH3CH CHCH3
81%
Br
+
CH3
CH3CH2 C
Br
CH3CH2CH CH2
19%
CH3 KOH, EtOH CH3CH C(CH3)2
+
71%
CH3CH2C CH2
CH3
29%
Zaitsev (Saytzeff) rule: base-induced elimination reactions
generally give the more highly substituted alkene product.
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ORGANIC CHEMISTRY
Chapter 6
CH2 CHCH2CHCH(CH3)2
KOH, EtOH
Br
CH2 CH CH CHCH(CH3)2
Conjugated diene
H
β
C
2
α
C
1
X
β elimination
1,2-elimination
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
6.16B Bases Used in Dehydrohalogenation
KOH / EtOH
EtONa / EtOH
(CH3)3COK / (CH3)3COH
EtOH + Na
EtOH + NaH
(CH3)3COH + K
EtONa + H2
EtONa + H2
(CH3)3COK + H2
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
Dehalogenation (脱卤素 )
C C
Zn or Mg, Ni
C
C
+ ZnX2
X X
RCH
CH2Br
CH2Br
Zn
RCH
CH2
+ ZnBr2
CH2
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
6.16C Mechanisms of
Dehydrohalogenations
Bimolecular elimination — E2 reaction
Unimolecular elimination — E1 reaction
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Chapter 6
6.17 The E2 Reaction
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
A mechanism for the E2 reaction
EtONa + CH3CHCH3
Br
CH2 CHCH3 + EtOH + NaBr
Rate ∝ [ CH3CHBrCH3 ] [EtONa]
Rate k [ CH3CHBrCH3 ] [EtONa]
EtO
H
C
β
H
C
α
H
CH3
H
EtO
Br
H
C
H
H
C
CH3
H
Br
Transition state
H
CH3
C
H
+ EtOH + Br
C
H
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Chapter 6
6.18 The E1 Reaction
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(CH3)3C
Chapter 6
Br + OH
(CH3)2C
CH2 + Br
+ H 2O
Rate ∝ [ (CH3)3CBr ]
Rate k [ (CH3)3CBr ]
(CH3)3C
OH
slow
Br
β
H CH2
fast
(CH3)3C
+ Br
HO H + CH2
C(CH3)2
(CH3)2C
α
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
The E1cb Reaction(单分子共轭碱消除反应)
(Elimination, unimolecular, conjugate base)
B
H
slow
ZCH CH2
ZCH CH2 Br
fast
ZCH
Br
CH2 + Br-
Z — strong electron withdrawing groups
( –NO2, –CN, C=O )
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Chapter 6
6.19 Substitution versus
Elimination
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
6.19A SN2 versus E2
E2
C
+ Nu H + X
C
(a)
(a)
H C
Nu
C
X
(b)
(b)
H C
SN2
Nu C
+ X
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ORGANIC CHEMISTRY
Chapter 6
C2H5O Na + CH3CH2Br
C2H5O Na + CH3CHCH3
Br
C2H5OH
55°C
C2H5OCH2CH3 + CH2 CH2
S N2
E2
(10%)
(90%)
C2H5OH
CH3CHCH3 + CH2 CHCH3
OC2H5
SN2
E2
(21%)
(79%)
55°C
C2H5OH
CH3
C2H5O Na + CH3CCH3
Br
25°C
C2H5OH
55°C
CH3
CH3CCH3
CH3
+ CH2
OC2H5
SN2 (9%)
CH3
CH2
CCH3
E2 (91%)
CCH3 + C2H5OH
E1 + E2
(100%)
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of Chemistry,
Xiamen University
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Chapter 6
CH3O Na + CH3(CH2)15CH2CH2 Br
CH3OH
65°C
CH3(CH2)15CH2CH2 OCH3 + CH3(CH2)15CH2
E2 (1%)
SN2 (99%)
CH3
CH3 C O + CH3(CH2)15CH2CH2 Br
CH3
CH3(CH2)15CH2CH2 OC(CH3)3
SN2 (15%)
CH2
(CH3)3COH
40°C
+ CH3(CH2)15CH2
CH2
E2 (85%)
Department of Chemistry, Xiamen University
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Chapter 6
6.19B Tertiary Halides: SN1 versus E1
The two type respond in similar ways to factors
affecting reactivities.
It is usually difficult to influence the relative
partition between SN1 and E2 products.
Reaction temperature ↓, SN1 ↑
Reaction temperature ↑,E1↑
Department of Chemistry, Xiamen University
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Chapter 6
6.20 Overall Summary
Department of Chemistry, Xiamen University
ORGANIC CHEMISTRY
Chapter 6
RCH2X
(primary)
Mostly SN2 substitution
R2CHX
(secondary)
SN2 with nonbasic nucleophiles
E2 with strong base
R3CX
(tertiary)
Mostly E2
SN1 and E1 in nonbasic solvents
Department of Chemistry, Xiamen University