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Chapter 8 Alkyl Halides
8.1 IUPAC Nomenclature of Alkyl Halides
8.2 Classes of Alkyl Halides
8.3 Preparation of Alkyl Halides
8.3.1 Addition of HX or X2 to Alkenes,
Alkynes
8.3.2 Preparation of Alkyl Halides from
Alcohols and HX
8.3.3 Exchange between Halides
8.3.4 Halogenation of Alkanes
A. Chlorination of Methane
Substitution reaction
B. Mechanism of Methane Chlorination
Homolytic breaking
Heterolytic breaking
Radical reactions
Chain reactions
Stability of alkyl radicals
8.3.5 Allylic Bromination of Alkenes
8.4 Reactions of Alkyl Halides
8.4.1The sites of reactions of alkyl halides
8.5 Nucleophilic Substitution
8.5.1 Nucleophilic Substitution
8.5.2 A Mechanism for the SN2 Reaction
8.5.3 Stereochemistry of SN2 Reactions
8.5.4 A Mechanism for the SN1 Reaction
8.5.5 Stereochemistry of SN1 Reactions
8.5.6 Factors Affecting the Rate
of SN1 Reactions and SN2 reactions
1. The structures of substrates
2. The Nucleophile
3. The leaving group
4. The solvent
8.6 Elimination Reactions
8.6.1 Dehydrohalogenation of Alkyl halides
8.6.2 Dehydration of Alcohols
8.6.3 Mechanisms of Elimination Reactions
A. The E2 reaction
B. The E1 Reaction
8.6.4 Stereochemistry of Elimination
Reactions
8.6.5 Nucleophilic Substitution Versus
Elimination
1.The structure of the substrate
2. The basicity of the reagent
3. The temperature of the reaction
Halogen-substiuted organic
R H
X : compounds.
F
H
Cl
Cl
Cl
Cl C
H
F
Cl
Trichloroethylene
(solvent)
Br C H
H
Dichlodifloro- Bromomethane
a fumigant
methane
(薰剂)
a refrigerant
F
F
Cl
C
C H
F
Br
Halothane(氟烷)
(a anesthetic)(麻醉剂)
8.1 IUPAC Nomenclature of Alkyl Halides
a. Halogen: as a functional group P218
For simple alkyl groups:
Common name
Alkyl + halide
H
I
Cl
Ex. CH3F
Methyl floride
Pentyl chloride
(甲基氟)
(戊基氯)
Cyclohexyl
iodide
(环己基碘)
b. Halogen as a substituent. Subsitutive
For branched alkyl groups:
names
• Number: begin at the end nearer the
first substituent, regardless of X- or R-.
• Properly numbered from either end, list
them in alphabetical order.
CH3
Cl
CH3
CH3CHCH2CHCHCH2CH3
1
2
3
4
Cl
5
6
7
CH3CHCH2CH2CHCH3
6
5
4
3
2
Br
1
4,5-Dichloro-2-methylheptane
(2-甲基-4,5-二氯庚烷 ) 2-Bromo-5-methylhexane
(2-甲基-5-溴己烷)
8.2 Classes of Alkyl Halides
According to the type of the carbon
that bears the functional group.
RCH2X Primary alkyl halides (伯卤代烃)
CH3
RCHR' Secondary Alkyl halides
CH3CCH2Br
(仲卤代烃)
X
CH3CHCH2CH3
CH3
1-Bromo-2,2-dimethyl
propane
CH3
H3C
Cl
Br
2-Bromobutane
R3CX
Tertiary alkyl halides
(叔卤代烃)
cis-1,4-Dimethyl
chlorocyclohexane
Models of 1,2dibromoethane
8.3 Preparation of Alkyl Halides
8.3.1 Addition of HX or X2 to Alkenes,
Alkynes
O O
Ex.
H2C
CHCH2Cl + HBr
PhCOOCPh
BrCH2CH2CH2Cl
8.3.2 Preparation of Alkyl Halides from
Alcohols and HX
P222, 7.3
Ex.
OH + HBr
heat
Br + H2O
(73%)
Reagents: HBr, HCl, PX3, PX5,
SOCl. (Thionyl chloride) (亚硫酰氯)
The order of reactitivity:
HX: HI > HBr > HCl >> HF
Alcohols: 3°> 2° > 1° > Methanol
8.3.3 Exchange between Halides
CH3
CH3
Ex.
H3C
C
Cl + NaI
ZnCl2, CS2
r.t
H3C
CH2CH3
8.3.4 Halogenation of Alkanes
R H + X2
h or heat
Cl2
h
CH2Cl2
Chloro- Dichloromethane Methane
CH2CH3
(96%)
Carbon
tetrachloride
A. Chlorination of Methane:
Cl
+ NaCl
I
R X + HX
Common reagents: Cl2 or Br2.
Reactivity: F2 > Cl2 > Br2 >I2
2
CH4 h or heat
CH3Cl
C
Ch.P 178
Cl2
h
(四氯化碳)
CHCl3
Cl2
h
CCl4
Chloroform Tetrachloro
methane
(氯仿)
Substitution reaction:
The reaction in which a atom
or a group in mole. is replaced by another one.
B. Mechanism of Methane Chlorination
Two ways for the breaking of a covalent
bond:
Homolytic cleveage(均裂):
Reactive intermediates:
radicals or free radicals
Methane chlorination
A species that bears
is a homolytic cleveage. a unpaired electron.
A B
A + B
Heterolytic cleavage (异裂):
A B
A + B
Polar breaking:
cation and anion
Radical reaction:
The reaction is promoted by light or by heat.
Chain initiation (链的引发阶段)
initiator
Step 1 Dissociation of a chlorine mole..
Cl Cl
h
2 Cl
P219,7.2
Chain propagation (链的增长阶段)
Step 2 Radicals react with a mole.
Cl H + CH3 The radical
Cl + H CH3
reacts with
Cl CH3 + Cl
Cl Cl + CH3
the mole.
of product
Cl + H CH2Cl
Cl Cl + CH2Cl
Cl H + CH2Cl
Cl CH2Cl + Cl
Chain termination (链的终止阶段)
Step 3 The reactions between the radicals.
Cl + CH3
H3C + CH3
Cl + Cl
Cl CH3
H3C CH3
Cl Cl
Chain reactions:
The chain initiation is rate-determing step,
to product the radical.
The reaction whose mechanisms invole a
series of steps with each step producing
a reactive intermediate that cause
the next step to occur.
Halogenation hof
higher
alkanes:

CH3CH2CH2CH3 + Cl2
35 °
H
CH3CH2CH2CH2Cl + CH3CHCH2CH3
H
28%
R
R C
R C
R C
H
R
R
Cl
72%
Primary < Secondary < Tertiary
Increasing the stability of alkyl radicals
The reaction gives a mixture of isomers:
CH3CHCH3
CH3
CH3
CH3
Cl2
h / 25 °
CH3CHCH2Cl + CH3CCH3
Primary hydrogen
Tertiary hydrogen
(63%)
(37%) Cl
9
1
63%
37%
The rate of the reactivity for the hydrogen:
Tertiary hygrogen = 37% ≈5.0
Primary hydrogen
63% / 9
Reactivity for different type of hydrogens
H
R
H
in mole.:
R C H
R C H
R C H
H
R
R
Bromination Primary < Secondary < Tertiary
1.0
3.5
5.0
is higher
selective:
Increasing the reactivity
CH3
CH3
CH3CHCH2CH2CH3 + Br2
h
60 °
CH3CCH2CH2CH3 + HBr
Br (76%)
8.3.5 Allylic Bromination
of
Alkenes
O
NBS
N Br
H H
Br
O
h¦Í
,CCl4
O
+
Mechanism of the reaction:
O
N
O
O
H
+ Br
+ Br
+ HBr
Allylic radical
O
HBr +
O
O
N Br h¦Í
H H
N H
N Br
O
Br2 +
H Br
Br2
+ Br
Stability of radicals
O
vinylic < methyl
N H
< 1°< 2°< 3°
O
< allyic
7.4 Reactions of Alkyl Halides
The sites of reactions of alkyl halides :
A polar covalent bond
readily broken
Nucleophilic
substitution
δ+
C
H
Elimination
C
H
:B
δ-
X
Nu:
8.5 Nucelophilic Substitution
Paul Walden made a remarkable discovery:
O
O
O
O
PCl5
HOCCH2CHCOH Et O HOCCH2CHCOH
2
OH
(–)-Malic acid
Cl
(+)-Chlorosuccinic acid
(苹果酸)
[α]D = -2.3°
(卤代琥珀酸)
AgO, H 2O
AgO, H 2O
O
P225,7.5
O
PCl5
HOCCH2CHCOH Ether
Cl
(–)-Chlorosuccinic acid
O
O
HOCCH2CHCOH
OH
(+)-Malic acid
Inversion in configuration
[α]D = +2.3°
Born 14 July 1863; died 24 January 1957.
Paul Walden was a Latvian chemist who, while
teaching at Riga, discovered the Walden inversion,
a reversal of stereochemical configuration that
occurs in many reactions of covalent compounds
(1896). Due to this discovery, Walden's name is
Paul Walden mentioned almost in all textbooks on organic
chemistry published throughout the world.
1863-1957
Walden revealed autoracemization and put the
foundations to electrochemistry of nonaqueous
solutions. Walden is also known for Walden's rule,
which relates the conductivity and viscosity of
nonaqueous solutions.
8.5.1Nucelophilic Substitution(亲核取代反应)
General type of the reaction:
Nu +
C
C L
P226
Nu + L
Ex. The reaction of ROH with HX
HX + R OH
heat
1.
R
X + H2O
2.
H
O H +
R
X
The reaction of alkyl halides with sodium
hydroxide:
HO + H3C Br
X
and HO
CH3OH +Br
are nuclophiles(亲核试剂)
Nucleophiles: A species with an unshared
electron
pair.
A
Lewis
base.
A reagent attacks a sp3-hybridized carbon
with partially positive charge,displacing
a substituent.
A nucleophilic substitution reaction
(亲核取代反应)
The leaving group: a substituent departs
from central carbon with a pair of
bonding electrons.
Substrates: like alkyl halides (卤代烷), a
sp3-hybridized carbon with
a leaving group.
C
X
C
C
X
X
H2C
CHCH2 X
C
C X
Functional groups transformation
by nucleophilic substitution reactions
of alkyl halides
Ex.
CH3ONa + CH3CH2Br
CH3CHCH3 + NaI
Br
P227, Table 7.1
acetone
CH3OCH2CH3 + NaBr
CH3CHCH3 + NaBr
I
8.5.2 A Mechanism for the SN2 Reaction
(Substitution nucleophilic bimolecular)
SN1
Mechanism of nucleophlic
substitution
SN2
Hydrolysis of methyl bromide:
Hydroxide ion in aqueous solution(水溶液).
HO + H3C Br
H2O
CH3OH +Br
Reaction rate = k[CH3Br][-OH] Alkali(碱)
In a single step process without intermediate.
Second-order reaction kinetics P228,7.7
(二级反应)
HH
H
HO +
H
H
C
Br
-
HO
C
H
H
-
Br
HO
C
H
+ Br
H
An transition state
• The nucleophile approaches the central C
from back side – the side opposite the bond
to the leaving group
Nu
L
C
+
Nu
C
L
+
+
Energy
△G +
OH +
H
H
C Br
H
H
HO C
L
Ch.P188, (五)
HO C Br
-
C
Nu
H
H
Reaction progress
+
Br
• The formation
of a bond of
C-Nu and the
breaking of C-L
occur at the same
time.
• The breaking of
a bond is assisted
by the formation
of a bond .
8.5.3 Stereochemistry of SN2 Reactions
The substitution by SN2 mechanism is
stereoselective and proceeds with inversion
of conjugation(构型翻转) at carbon that bears
the leaving group.
P229
Walden inversion:
H
H
CH3(CH2)5
H3C
C Br
NaOH
EtOH-H2O
(S)-(+)-2-Bromooctane
+
δ-
HO C
(CH2)5CH3
CH3
(R)-(-)-2-Octanol
δ-
+
Like an umbrella in the gale
An inversion of configuration
Cl
H
H3C
H
+
OH
H3C
H
H
OH
+ Cl
8.5.4 A Mechanism for the SN1 Reaction
(Substitution Nucleophilic Unimolecular)
In the hydrolysis of tert-butyl bromide: P232,7.8
(CH3)3C
Br + H2O
CH3)3C OH + HBr
Reaction rate = k[CH3)3C-Br]
A first-order reaction
Edward Davies Hughes
(1906-1963)
Sir Christopher (Kelk) Ingold
1893-1970 **
Ingold was one of the founders of the electronic theory of organic chemistry
and made many contributions to reaction mechanisms and molecular
spectroscopy. Orientation and relative rates of aromatic nitration were used,
in his early work, to test the theory. Studies of aliphatic substitutions and
eliminations, often with his long-time collaborator E. D. Hughes, led to I
ncorporation into the standard language of chemistry of such words as
nucleophile, electrophile, inductive and mesomeric (resonance) effects,
and such symbols as SN1, SN2, E1, E2, BAC2 and others.
His monumental book "Structure and Mechanism in Organic Chemistry"
(1953) was for years an authoritative text in the field. His forays into
molecular spectroscopy first demonstrated the hexagonal symmetry
of benzene's ground state and gave a quantitative description of its first
excited state; he was the first to show that the first excited state of
acetylene is bent. Ingold sought to unite physical, organic and inorganic
chemistry. His papers were models of exposition, clarity and precision.
The vigorous and sometimes vitriolic manner with which he dealt with
opponents, in print, contrasted markedly with his personal kindness and
courtesy. Ingold received many awards including the Davy (1946)
and Royal (1952) Medals of the Royal Society and the first James
Flack Norris Award in Physical Organic Chemistry of the ACS (1965).
Mechanism of the reaction:
Step1 The alkyl halide dissociates to a carbocation
and a halide.
CH3
CH3
H3C
slow
C Br (rate-determing step) H3C C + Br
CH3
CH3
Step 2 The carbocation reacts rapidly with water as
nucleophile to produce an alkyloxonium ion.
CH3
CH3
H3C
+
C
O
H fast
H3C
H
C O
CH3
CH3
H
H
Step 3 The transfer of a proto to a mole. of water
to produce a neutral alcohol.
A fast acidCH3
CH3
H
base
reaction
H fast
H C C OH
HC C O
3
CH3
H
+ O
3
H
CH3
FIGURE 2 A reaction energy diagram
for an SN1
T1
T2
+
+
△ G2
+
+
△G1
+
+
C + Br
ΔG1 > ΔG2
+
+
A carbocation
is intermediate
(CH3)3CBr + H2O
(CH3)3COH + HBr
Reaction progress
8.5.5 Stereochemistry of SN1 Reactions
For
an optically active
alkyl halide:
H
H
H3C
H2O
C Br
EtOH
CH3(CH2)5
H3C
C OH
+
CH3(CH2)5
H
HO C CH3
(CH2)5CH3
(R)-(-)-2-Bromooctane (R)-(-)-2-Octanol (S)-(+)-2-Octanol
(17%)
(83%)
Inversion of
conjugation
Retention of
conjugation
(构型翻转)
(构型保留)
Nu
Nu
Nu
+
More than 50%
Racemic product
Nu
P234
Less than 50%
8.5.6 Factors Affecting the Rate
of SN1 Reactions and SN2 reactions
1. Structure of substrates
SN2 reactions:
The order of reactivity:
Tertiary < Secondary < Primary < Methyl
Relative
500
40,000
2,000,000
reactivity <1
Increasing SN2 reactivity
CH3
H3C
R
The steric hindrance
R' C X of alkyl group.
C CH2 X
CH3
Nu
Neopentyl halides
is very unreactive.
R''
P230
Nucleophile carries
out a back-side
displacement
H
H C Br
H
H3C
H C Br
H
H C Br
CH3
CH3
H3C C Br
CH3
CH3
FIGURE 3 Space-filling models of alkyl
bromide, showing how substituents
shield the C atom that bears the
leaving group.
SN1 reactions
CH3
RCH2
R2CH
RCH
CHCH2
CH2
R3C
Methyl < Primary < Secondary = Allyl = Benzyl < Tertary
Less
stable
Carbocation stability
Reactivity for SN1 reactions
2. Nucleophiles
More
stable
Ch. P195
The rates of SN2 reactions depends on both
the concentration and identity of the attacking
Nucleophile:
The nucleophile is usually a Lewis base
Increasing the concentration of a nucleophile
increases the rate of an SN2 reaction.
The stronger the nucleophilicity of a reagent,
the more rapid the reaction.
• Nucleophilicity roughly parallels basicity when
comparing nucleophiles that have the same
attacking atom.
RO > HO >> RCOO > ROH > H2O
• Negatively charged nucleophiles are usually more
reactive than neutral ones.
HO > H2O
RO > ROH
• nuclophilicity is also related to polarizability
(可极化度).
Distortion
RS > RO , I > Br > Cl > F
3. The leaving group
The leaving group affects both SN2 reactions
and SN1 reactions.
The best leaving groups should be the weakest
bases.
The weak bases stabilize a negative charge
most effectively
I TsO
Br
HO , NH2 , OR
Cl
F
Relative
1
200 10,000 30,000 60,000
reactivity << 1
The greater the extent of charge stabilization by
the leaving group, the lower the energy of the
transition state for SN2 reaction and the more
rapid the reaction.
The best leaving groups:
O
S
CH3
P326,8.14
O
CH3 S
O
O
O
O
p-Toluenesulfonate
Methylsulfonate
ion(对甲基苯磺酸根负离子)
ion( 甲磺酸根负离子)
TsO
MsO
O
O
Tosylate:
ROH + CH3
S
Cl
RO S
O
CH3 + HCl
O
Transformation
of leaving
R OTs + Nu
R Nu + OTs
groups.
Basicity: OH >> H2O
R OH
H
H Br
R O
H
R Br + H2O
4. The solvent
P320, 8.12
SN1 reactions:
Dielectric constant (ε)(介电常数) is a parameter
to measure the polarity of solvent.
The polar solvent with a higher dielectric constant.
Polar solvents favor the dissociation of alkyl
halides to form carbocations.
Solvent mole. orient around
H H H H
the carbocation.
CH
CH
O
H
H
O
3
O
+
C
O
H H
O
O
H
H
H
H
H3C
C Cl + ROH
CH3
3
H3C
C OR + HCl
CH3
EtOH 40% H2O/ 80% H2O/ H2O
60%EtOH 20%EtOH
Relative
reactivity: 1
100
14,000 100,000
more
Less Solvent reactivity
reactivity
reactivity
SN2 reaction:
Protic solvents: containing –OH, –NH groups.
worst solvents for SN2 reactions.
They all have active hydrogen atoms that allow
them to form hydrogen bonds with nuclophiles,
so that decrease the nucleophilicity of reagents.
O
R
In contrast to protic solvent,
H
O
polar
aprotic
solvents
increase
O
R
R
H Nu H
the rates of SN2 reactions.
H
O
Ex.
R
CH3
O
O
H C N
CH3
CH3
O
CH3 S
CH3
N
P
N
CH3
N
CH3
H3C CH3
CH3
N,N-Dimethyl formamide Dimethyl sulfoxide
(DMF)(N,N-二甲基甲酰胺) (DMSO)(二甲亚砜)
HMPA
or
HMPT
CH3CH2CH2CH2 Br + N3
CH3CH2CH2CH2 N3 + Br
Solvent CH3OH H2O DMSO DMF CH3CN HMPA
Relative
1
7
1,300 2,800 5,000 200,000
reactivity
Less
reactive
Solvent reactivity
More
reactive
8.6 Elimination Reactions
1. Nucleophilic substitutions
Ionic reactions
2. Elimination reactions
The Eliminaiton Reaction:
C
C
Y
L
Elimination
-YL
C
C
P124, 4.9
The atoms or the groups are removed
from adjacent C atoms in a molecule is
βElimination or 1,2-Elimination.
8.6.1 Dehydrohalogenation of Alkyl halides
The loss of a hydrogen and a halogen from
adjacent C atoms of an alkyl halide to yield
an alkene.
Ex.
CH3CHCH3
EtONa
°
EtOH, 55°
CH3CH
CH2 + NaBr + EtOH
(79%)
Br
The reaction
is carried out in the present
of a stronger base.
EtONa-EtOH
KOH-EtOH
KOC(CH3)3- ROH:
2EtOH + 2Na
is used to primary
alkyl halides
2EtONa + H2
H
C
β
C
α
+ B
C
C
+ HB + X
X
The base attacks the β–H, X: leaving group
The
regioselectivity
of
the
elimination:
H
CH3 H
H C
C C
CH3
EtOK
°
EtOH, 70 °
H Br H
H2C
CH3
CH3
C
+
C
CH2CH2 CH3
(29%)
CHCH3
(71%)
The elimination follows Zaitsev’s rule:
βelimination predominates in the direction
that leads to the more highly substituted
alkene.
8.6.2 Dehydration of Alcohols P126
The loss of a hydrogen and a hydroxyl group
from adjacent C atoms of an alcohol by
acid-catalyst:
CH3
H3C
C
OH
H2SO4
CH3 Heat
CH3
CH3
C CH2 + H2O
(82%)
The reaction also follows Zaisev’s rule:
CH3
OH
2-Methylcyclohexanol
CH3
H2SO4
Heat
CH3
+
P236,7.9
1-Methyl3-Methylcyclohexene cyclohexene
(84%)
(16%)
Questions: For dehydration of alcohols,
why the acid must be used?
Which group is leaving group?
8.6.3 Mechanisms of Elimination Reactions
A. The E2 reaction (Elimination bimolecular):
C2H5O
-
+
+
C2H5O H
H
C
C
C
X
C
X
-
C C + C2H5OH + Br
Rate = k R X C2H5O
At the same time,
1. C-H bond breaking
2. C=C πbond formation
3. C-X bond breaking
take place.
Central C atom: sp3-hybrid
sp2-hybrid
Reactivity of the E2 reaction:
RF < RCl < RBr < RI
The lower strength of C-X, the higher reactivity.
B. The E1 Reaction(Elimination unimolecular)
(CH3)3C OH + (CH3)3C OC2H5
(CH3)3C Cl
80%C2H5OH
20%H2O
(83%) Substitution
H2C C(CH3)2
(17%)
Elimination
For the elimination:
Rate = k[ (CH3)3C Cl ]
P239,7.10
Step 1 Alkyl halide dissociates by heterolytic
cleavage of C－X bond.
CH3
H3C
C Cl
CH3
Slow
CH3
H3C
C + Cl
CH3
Step 2 EtOH acts at a base to remove a proton
from the carbocation to give the alkene.
H
CH3CH2O
H CH3
H C
C
Fast
CH3CH2O
H
H
+ H2C
H CH3
Step1 is rate-determining one.
C
CH3
CH3
Reactivity of the E1 reaction:
RCH2X < R2CHX < R3CX
Incresing rate of the E1 reaction
The similar mechanism for the dehydration
of alcohols.
8.6.4 Stereochemistry of Elimination
Reactions
The E2 Reaction:
In the transition state of the E2 reaction,
-
B
H C
H
C
C
X
-
C X
With a periplanar (全平面的)
geometry.
The two conformations that permit this
relationship:
X
H
X
H
Syn periplanar
Bond are eclipsed
H
H
X
X
Anti periplanar
Bond are staggered
B
H
+
H
B H
C
C
Br
Br
Br
β- H and X are on the opposite side.
Anti elimination(反式消除) for the E2 reaction.
Br
H
H
cis-1,4-
KOC(CH3)3
HOC(CH3)3
(1)
k 1 > k2
KOC(CH3)3
Br
H
HOC(CH3)3
(2)
H
trans-1,4-
conformations determined from electron
diffraction studies by the Norwegian
physical chemist Odd Hassel.
Thus conformational analysis, which ever
after changed the way organic chemists think
about structure, synthesis and chemical
reactivity, came into being. Barton and
Hassel shared the 1969 Nobel Prize in
Chemistry for their seminal work.
In a long and distinguished career, Barton
went on to make major contributions
to organic photochemistry
(the Barton Reaction), and to the invention
of new reactions and their application to
natural products synthesis.
A native of England, Barton's initial
positions were at Imperial College (London),
Harvard, Birkbeck College (London) and
Glasgow University. He became Professor
at Imperial College, London (1955-1978),
then Director of the Institut de Chemie des
Derek Harold Richard Barton Substances Naturelles in Gif-sur-Yvette
(France, 1977-85), and in 1986 he became
1918-1997
Dow Distinguished Professor of Chemical
In 1950 Barton published a 4-page Invention at Texas A. and M. University.
paper in Experientia entitled "The He received many honors besides the Nobel,
Conformation of the Steroid
including the 1995 Priestley Medal (USA)
and
the 1995 Lavoisier Medal (France);
Nucleus", in which he analyzed
an unusual honor for a chemist was his
how molecular shape affects
chemical behaviour. The paper was appointment (1989) by the Governor of
developed using cyclohexane ring Kentucky as a Kentucky Colonel.
8.6.5 Nucleophilic Substitution Versus
Elimination
P239, 7.11
C
(a)
H C
Nu
C X
E2
C
+ Nu H + X
(b)
H C
SN2 Nu C
Elimination
+ X
Substitution
The three factors that affect the relative
rates of E2 and SN2 reaction:
1.The structure of the substrate
CH3CH2O Na + CH3CH2Br C2H5OH
CH3CH2OCH2CH3 + CH2 CH2
55 °C
-NaBr
For primary alkyl halide,
the substitution is highly
favored.
SN2
(90%)
E2
(10%)
CH3CHCH3 + CH3CH CH2
CH3CH2O Na + CH3CHCH3 C2H5OH
°
55 C
Br
-NaBr
OCH2CH3
S N2
For secondary alkyl halide,
elimination reaction is highly (21%)
favored.
As crowding at the
E2
(79%)
central C atom decreases,
E2of nucleothe rate
philic attack by the
Lewis base increases.
CH3CH2O
SN2
How about tertiary halide in the presence
of a stronger Lewis base?
Ex.
CH3
CH3CH2O Na + H3C
C
Br
CH3
C H OH
CH3 2 255°C
-NaBr
CH3
C
H3C C CH3 +
CH3
OCH2CH3
2. The basicity of the reagent
(9%)
CH2
(91%)
CH3O + CH3(CH2)15CH2CH2 Br CH3OH CH3(CH2)15CH CH2
65 °C
+
E2
SN 2
CH3(CH2)15CH2CH2 OCH3
(1%)
(99%)
CH3
H3C
C O + CH3(CH2)15CH2CH2 Br
(CH3)3COH
40 °C
E2 SN2
(85%)(15%)
CH3
CH3(CH2)15CH CH2 + CH3(CH2)15CH2CH2 OC(CH3)3
• The elimination reaction is favored in the
presence of a stronger sterically hindered
base.
• Increasing the nucleophilicity of the reagent
favors the SN2 reaction.
Less basicity than hydroxide:
CH3CH(CH2)5CH3 KCN CH3CH(CH2)5CH3
DMSO
Cl
2-Chlorooctane
CN
2-Cyanooctane(70%)
（2-氰基辛烷）
3. The temperature of the reaction
Increasing the temperature of the reaction
favors E2 reaction.
Problems to Chapter 8
P246
7.22(c), (d)
7.23(b)
7.29
7.30(b), (c), (f)
7.32
7.33(a)
7.34
7.35(b)
7.39
7.42
7.45
7.46
7.47
7.48
7.49
7.51
7.52
7.53
7.55
7.56
7.58
Additional Problems:
1* Among the Walden cycles carried out by
Kenyon and Phillips is the following series
of reactions reported in 1923. Explain the
results, and indicate where Walden inversion
is occurring.
OH
OTs
CH3CHCH2
TsCl
[α]D = + 33.0°
CH3CHCH2
CH3CH2OH
[α]D = + 31.1°
OCH2CH3
CH3CHCH2
[α]D = - 19.9°
K
O K+
CH3CHCH2
CH3CH2Br
OCH2CH3
CH3CHCH2
[α]D = + 23.5°