Chapter 4
Alkyl halides (卤代烷):
Nucleophilic substitution and
elimination (亲核取代和消除)
Text 1: chapter 6
Text 2: 第九章
Contents
Classification and Nomenclature of Alkyl
halides
Physical properties of alkyl halides
Preparation of Alkyl halides
Reactions of alkyl halides
•
Nucleophilic Substitution Reactions
•
Elimination Reactions
4.1 Classification and Nomenclature of
Alkyl halides
• Halohydrocarbons (卤代烃)
alkyl halides
(卤代烷烃):
vinyl halides
(卤代烯烃):
aryl halides
(卤代芳烃):
X
C
sp3
X
C
sp2
X
sp2
Classification of alkyl halides
Primary halides
伯卤代烷; 1°
Secondary halides
仲卤代烷; 2°
H
R
C
Tertiary halides
叔卤代烷; 3°
R
H
X
R
H
C
R
X
R
R
C
X
X
a geminal dihalide
偕二卤代
C
C
C
X
X
a vicinal dihalide
邻（连）二卤代
X
Nomenclature of alkyl halides
Common name:
“alkyl halide” (某基卤)
IUPAC name:
“haloalkane” (卤代烷),
-X is treated as a substituent
fluoride----------fluorine -----------chloride---------chlorine ----------bromide---------bromine ----------iodide------------iodine -------------
fluorochlorobromoiodo-
CH3CH2
F
fluoroethane (氟乙烷)
ethyl fluoride (乙基氟)
Br
Bromocyclohexane
(溴代环己烷)
cyclohexyl bromide
环己基溴
(CH3)3CCl
2-chloro-2-methylpropane
t-butyl chloride (叔丁基氯)
CH 3CH 2CHCH 3
Br
2-bromobutane
(2-溴 丁烷)
sec-butyl bromide
(仲丁基溴)
H
Cl
CH3
H
Cl
(1R,3R)-1-chloro-3-methylcyclopentane
trans-1-chloro-3-methylcyclopentane
(1R,3R)-1-甲基-3-氯环戊烷
trans- 1-甲基-3-氯环戊烷
CH2Cl2
CHCl 3
dichloromethane
trichloromethane
(二氯甲烷)
chloroform (氯仿)
methylene dichloride
CF3CF2CF3
perfluoropropane
全氟丙烷
3-(chloromethyl)pentane
3-氯甲基戊烷
CCl4
perchloromethane
tetrachloromethane
carbon tetrachloride
(四氯化碳)
Common uses of alkyl halides
reading material: text 1: 6-3
• solvents (溶剂): CHCl3, CH2Cl2, ClCH2CH2Cl
• reagents (试剂):
• anesthetics (麻醉剂): CF3CHClBr
• refrigerants (致冷剂) :
CF2Cl2 (Freon-12，氟里昂-12)
CHClF2 (Freon-22)
• pesticides (农药): DDT,
• poly(vinyl chloride) (聚氯乙烯), Teflon（特氟隆，聚四
氟乙烯）
4.2 Physical properties of alkyl halides
• Solubilities（溶解性）:

very poor in water;

Miscible with each other and with other relatively nonpolar
solvents.(彼此互溶, 与其它非极性溶剂互溶.)
• Boiling point (bp, 沸点):
 monohalides (一卤代烷): 规律与烷烃相似.
• Density (d, 密度):

R-F, R-Cl, < 1; R-Br, R-I, > 1.

多卤代烷大于1.

随碳链增长, 同类型卤代烷密度降低.
• 一卤代烷具有不愉快的气味, 有毒.
• 在铜丝上燃烧时产生绿色火焰, 可用于鉴定卤素.
4.3 Preparation of alkyl halides (6-6)
(Reading material: text 1 6-6, p 220-223)
1) Free-radical halogenation (自由基卤代) 6-6A
+ Cl2
CH3
H3C C H
CH3
+ Br2
Cl
hv
+
hv
HCl
CH3
H3C C Br + HBr
CH3
Allylic halogenation (烯丙位卤化) 6-6B
H
H
H
NBS, CCl4
H
hv or initiator
H
N Br + HBr
N H
N Br
O
O
O
O
O
Br
+ Br2
O
NBS
N-bromosuccinimide
N-溴代丁二酰亚胺
Allylic radical is resonance-stableilized. 烯丙
基自由基稳定．
Important reactions !!
2) From alkenes (烯烃加成)
CH3COOH
CH3CH2CH2CH CH2 + HBr
CH3CH2CH2CH CH3
Br
84%
3) From alcohol (醇的取代)
CH3CH2CH2CH2OH + HBr
H2SO4
CH3CH2CH2CH2Br +
H2O
95%
4) From other halides (halogen exchange, 主要用于制备碘代烷)
RCl (Br ) +
NaI
acetone
RI
+ NaCl(Br)
4.4 Reactions of alkyl halides
•
Nucleophilic substitution (亲核取代反应)
•
Elimination (消除反应):
dehydrohalogenation (脱卤化氢)
•
Formation of organometallic compounds (形成
有机金属化合物)
C:Z
homolysis
¾ùÁÑ
C.
+
Z.
Carbon radical or free radical
C+
C: Z
heterolysis
+ : Z
carbocation; carbonium ion
£¨ ̼正Àë×Ó£©
ÒìÁÑ
C:  +
carbanion
£¨ ̼负Àë×Ó£©
Z+
Reactive
intermediates
(反应活性中间
体)
1)
Nucleophilic substitution reactions
(亲核取代反应):
Structure of
alkyl halides
_
+


C
X
X = F , Cl, Br, I
Carbon-halogen bond lengths
Bond
CH3F
CH3Cl
Bond
Length (Å)
1.39
1.78
CH3Br
CH3I
1.93
2.14
In a nucleophilic sibstitution, a
nucleophile(Nuc:- or Nu )
replaces a leaving group (X-)
from a carbon, using its lone
pair of electrons to form a new
bond to the carbon atom.
C C
H
+ Nu-
C C
X
+ X-
H Nu
Nu: Nucleophiles 亲核试剂
X: Cl, Br, I，
reactivity: I>Br>Cl
For examples:
R
X +
OH
R
X +
R'O Na+
R
X + CN
R
X +
I
R
OH
+
X
R' +
R
O
R
CN
+
X
R
I
+
X
NaX
R
X +
H2O
NH3
R
X +
RNH2
R2NH
R
X + P(C6H5)3
ROH
+
HX
RNH2 + HX
R2NH
+ HX
R3N + HX
+
RNH3 X
OH +
R2NH2 X
+
R3NH X
RNH2
OH -
OH -
R2NH
R3N
[ RP(C6H5)3]+X -
任何具有亲核性的试剂或中间体都可能与卤代烃反应，SH, carbanion, etc
2) Elimination reactions (消除反应):
C C
+ B:-
C C
+ B H + X-
H X
B: base, OH－, CH3O－, CH3CH2O－
X: Cl, Br, I
1,2-elimination, β-elimination
CH 3CH 2CHCH 3
Br
CH3CH2ONa
CH3CH2OH
CH3CH CHCH 3 81%
CH3CH2CH CH2 19%
Positional Orientation of elimination 消去反应的取向
Saytzeff rule: (扎衣切夫规则)
In elimination reactions, the most highly substituted alkene
usually predominates.
在β-消去中，主要得到双键碳上取代基较多的烯烃，也称扎
衣切夫烯烃。
CH 3CHCH 3
Br
CH3CH2ONa CH CHCH
3
3
CH3CH2OH
OEt
21%
+ CH3CH CH2
79%
Most Nu are also basic and can engage in either substitution
or elimination, depending on the alkyl halide and the reaction
conditions.
3) Formation of organometallic compounds
(形成有机金属化合物) (T2: p234; T1 p 420 10-8, 9 )
R
M

+
C
M
M: Li, Na; Mg; B, Al, Ga; Si, Ge, Sn, Pb; P, As, Sb; etc.
R
X
+
Mg
ether(ÃÑ)
R
MgX
organomagnethium compound
“Grignard reagent” (格利雅试剂, 格氏试剂)
活性顺序：
RI £¾RBr £¾RCl £¾RF
Important reagents in organic synthesis ！！！
R
X + 2 Li
ether(ÃÑ)
RLi
+
LiX
organolithium compound 有机锂化合物
R
X + 2 Na
ether(ÃÑ)
RNa +
RX
RNa +
ether(ÃÑ)
NaX
R R + NaX
Wurtz reaction (武慈反应)
2RLi
+
CuI
R2CuLi
ether(ÃÑ)
+ R'X
R2CuLi
+ LiI
R
R' +
RCu + LiX
4) Reduction of alkyl halides to alkanes (还原反应)
Reductive agents (还原剂)：LiAlH4, NaBH4
CH3(CH 2)8CH2Br
reactivity:
1. LiAlH4
2. H2O
CH3(CH 2)8CH3
RI ＞ RBr ＞ RCl
primary ＞ secondary ＞ tertiary halides
CH3(CH 2)6CH2X
NaBH4
¶þ¸Ê´¼¶þ¼×ÃÑ
CH3(CH 2)6CH3
Testing of RX
Physical methods:
IR, 1H NMR, MS
在铜丝上燃烧时产生绿色火焰.
Chemical methods:
Reaction with AgNO3 / EtOH solution.
R
X + AgNO3
R
ONO2 + AgX
4.5 Nucleophilic substitution reactions
(text 1: p 225-247; text 2: p 237-246)
Experimental facts:
CH3Br
H2O
+ NaOH
¦Í = K CH3Br
CH3
CH3
C Br
CH3
+ NaOH
¦Í = K CH3
CH3OH
+ NaBr
OH
H2O
CH3
C Br
CH3
CH3
CH 3
C OH
CH 3
+ NaBr
SN2：second-order nucleophilic substitution
(双分子亲核取代反应)
SN1：first-order nucleophilic substitution
(单分子亲核取代反应)
20世纪30年代英国伦敦大学教授英果(C. Ingold)
1) SN2：Second-order nucleophilic substitution
(双分子亲核取代反应)
CH3Br
+ NaOH
H2O
¦Í = K CH3Br
Mechanism
H
HO
CH3OH
δ
+ H
slow
H
nucleophile
substrate (底物)
–
H
C
C
H
fast
H
product (产物)
H
δ–
Br
H
transition state (过渡态, TS)
H
HO
OH
HO
C Br
+ NaBr
+ Br
Nu
C
C
Nu
C
：L
C
：L
：
Nu
Nu
：L
：L
TS
–
HO
E
–
H
C
δ
H
δ
Br
H
Eact
H
HO
exothermic reaction
放热反应
C Br
H
H
H
HO
C
H
H
reaction coordination
The reaction-energy diagram (反应能线图)
Characteristics of SN2
(1) second-order reaction (二级反应) ν= k[RX][Nu]
(2) concerted reaction (协同进行，一步完成。)
(3) having a transition state, no intermediate.
(反应中经过一个过渡态，没中间体。)
(4) stereochemistry: inversion of configuration (构型转化)
Walden inversion (瓦尔登转化)
C6H13
I*
+
CH 3
C
H
optically pure
C6H13
I
I* C
+ I
CH 3
H
racemization (外消旋化)
inversion of configuration (构型转化)
Walden inversion (瓦尔登转化)
C6H13
HO
C6H13
Br
+
HO
CH 3
H
H3C
H
（S）
（R）
H3 C
HO
+
CH 3
Br
H
Cl
（R）
HO
H
Cl
（R）
瓦尔登转变是指骨架构型转变，不是指R转为S, 或S转为R。
Nu,
Substrate,
Solvent,
Temperature
Factors affecting SN2 reactions
A. The effect of nucleophile
CH3O- + CH3I
rapid
CH3OCH3 + I-
methoxide ion
(¼×Ñõ»ùÀë×Ó£©
CH3OH + CH3I
methanol
very slow
+
CH3OCH3
H
• A base is always a stronger
nucleophile than its conjugate acid.
+
IHO- > HOH
CH3O- > CH3OH
RO- > ROH
RS- > RSH
CH3COO- > CH3COOH
• In a group of nucleophiles in which the nucleophilic
atom is the same, nucleophilicities parallel basicities.
(一般情况下, 含有相同亲核性原子的亲核试剂, 其碱性
越强, 亲核能力越强.)
Order of basicity and nucleophilicity:
RO－ > HO－ >> RCOO－> ROH > HOH
But:
basicity ≠ nucleophilicity
H3 C
CH3 CH2 O

O
H3 C
CH3
basicity:
nucleophilicity:
>
<
Steric hindrance
(空间位阻)
Strong Nu :
less electronegative,
large valence shell,
more polarizable,
soft base,
less steric hindrance (位阻小)
strong
R3P, HS-, I-, -CN, HO-, CH3O- , R2NH
moderate
Br-, Cl-, NH3, CH3OH, CH3SCH3, CH3COO-
weak
F-, H2O, CH3OH
strong
weak
strong
B. The effect of the structure of the substarate
(底物结构的影响）
R---X(L)
Relative rates of reactions of alkyl halides in SN2 reactions
Substituent
Compound
Methyl
1o
2o
Neopentyl ÐÂÎì »ù
3o
relative rate
CH3X
CH3CH2X
(CH3)2CHX
(CH3)3CCH2X
(CH3)3CX
General order of reactivity in SN2 reaction
CH3- > 1° > 2°> 3 °
30
1
0.02
0.00001
0
H
Br
H
CH3
CH3
Br
H
H
H
Br
H
CH3
CH3
H3C
Br
CH3
R-: steric effects
Leaving group effects
A good leaving group must be



electron withdrawing;
stable after leaving; (usually weak base)
polarizable, to stablize the TS
I-,
Br-,
Cl-,
O

O
S
HOH, ROH, NR3, etc.
O
O
R

O
S
O
O
R
Br- +
CH3
CH3
OH
×
Br
CH3
+
OH + H
CH3 + OHO H
H
BrBr
CH3 + H2O
poor leaving group
F
HO
RO
NH2
NHR
CN
C. Solvent effects on SN2 reactions
Protic solvent (质子性溶剂)
H2O, ROH, HCOOH, NH3, etc.
Aprotic solvent (非质子性溶剂)
hexane, acetone(丙酮), acetonitrile(乙腈), etc.
Polar solvent (极性溶剂):
H2O, ROH, acetone(丙酮), acetonitrile(乙腈), etc.
Apolar solvent (非极性溶剂):
Hexane, carbon tetrachloride
Polar Aprotic Solvents （极性非质子溶剂）
O
CH3CN
acetonitrile
乙腈

O
H


O
H3C
acetone
丙酮
N
CH3
CH3
N,N-Dimethylformamide
(DMF)
N,N-二甲基甲酰胺
CH3
H3C
S

CH3
Dimethyl sulfoxide
(DMSO)
二甲亚砜
Generally, polar solvents are required in the
nucleophilic substitution reaction.
H
H
H
X-
O
H
O
Relative Nucleophilicity
H
O
H
in protic solvents:
I- > Br- > Cl- > F-
H
H
O
SH- > CN- > I- > OH- > N3- > Br- > CH3CO2- > Cl- > F- > H2O
in aprotic solvents: I- < Br- < Cl- < FO
CH2Cl
KF, 18-crown-6
CH3CN
O
CH2F
O
+
K
+ ClO
O
O
18-crown-6
F-
Factors affecting SN2 reactions
Nu
Strong Nucleophiles are needed.
R less steric hindrance
Substrate
L good leaving groups are required.
Solvent
Wide variety, polar aprotic
Temperature Higher temperature can increase the rate.
2)
CH3
SN1: First-order nucleophilic substitution
(单分子亲核取代)
CH3
C Br
CH3
+ NaOH
(CH3)3C Br + CH3OH
H2O
boil
¦Í = K CH3
CH3
CH 3
C OH
CH 3
+ NaBr
(CH3)3C OCH3+ HBr-
CH3
C Br
CH3
Mechanism of SN1
step 1
CH3
rate-limiting step
CH3
C Br
CH3
slow
CH3
CH3
C
CH3
+
OH
fast
CH3
CH3
CH3
C + Br
CH3
carbocation
intermediate
TS 1
step 2
CH3
CH3
C
Br
¦Ä ¦Ä
CH3
CH3
¦Ä
¦Ä
C
OH
CH3
TS 2
CH 3
CH 3
C OH
CH 3
E
TS 1
rate-limiting step
TS 2
Eact2
Eact1
£¨CH 3£©3C
Br
OH
£¨CH 3£©3CBr
£¨CH 3£©3COH Br
reaction coordination
The reaction-energy diagram (反应能线图)
The structure of carbocations
CH3+
methyl cation
(CH3)3C+ tert-butyl cation
Vacant p orbital
H
Vacant p orbital
H3C
+
H
planar
H
+
CH3
planar
H3C
sp2
S
sp2
sp3
Stereochemistry
R1
racemization
(外消旋化)
C
R2 R3
Nu
R1
Nu
R1
C
C
R2
R3
R3
R2
Nu
Factors affecting SN1 reactions
Nu
No effects, weak ones are OK.
R
Stability of carbocation,
or Substituent effects
L
Good leaving groups are required.
Similar as SN1.
Substrate
Solvent
Good ionizing solvents needed, protic solvents
Temperature Higher temperature can increase the rate.
The relative stabilities of carbocations
benzylic > allylic > R3C+ > R2CH+ > RCH2+ > CH3+
(most stable)
(least stable)
CH2
CH2
benzylic cation
allylic cation
How a methyl group helps stabilize the positive
charge of a carbocation?
H
.
C
.
H
H
H
C
+CH
H
sp2
sp3
+CH CH
2
3
3
H3C
C
H
C
H
sp2
H3C
H
H
C
H3C
H3C
.
+CH (CH )
2
3 2
+CH (CH )
2
3 3
CH 3
hyperconjugation
超共轭效应, σ-p
electron-donating
of alkyl group
烷基的给电子效
应
Rearrangement (重排) of carbocation
CH3
H3C C CH CH3
H3C Br
-BrSN1
CH3
H3C C CH CH3
H3C
Nu-
CH3
H3C C CH CH3
H3C Nu
CH3
H3C C CH Ph
H3C Br
-BrSN1
stable
CH3
H3C C CH Ph
H3C
Nu-
CH3
H3C C CH Ph
H3C Nu
CH3
H3C C CH CH3
H3C
stable
Nu-
Nu CH3
H3C C CH CH3
H3C
CH3
H3C C CH Ph
H3C
Characteristics of SN1
(1) first-order reaction (一级反应)
ν= k[RX]
(2) multi-step reaction (多步反应)
(3) having a carbocation intermediate.
(反应经过碳正离子中间体。)
(4)stereochemistry:
racemization (外消旋化)
(5) rearrangement (重排)
Allylic halides 烯丙基卤
SN1
CH3CH
CHCH2Br
Br
CH3CH
CHCH2
CH3CH
CH
CH2
stable intermediate
¦Ä
CH3CH
CH
OH-
OH-
¦Ä
CH2
CH3CH = CHCH2OH
CH3CH
OH
Nu
¦Ä
SN2
H
H
H
C
C
C
H
H
X
¦Ä
stablized TS
CH = CH2
SN2
kinetics
Rate = k[R–X][Nu],
second-order
SN1
Rate = k[R–X], first-order
Mechanism
Bimolecular, Concerted, TS
Stereochemistry
Stereospecific (立体专一的)
(inversion)
Two Steps, intermediate,
carbocation,
rearrangements
Loss of Stereochemistry
(racemization)
Substrate (R-)
Sterics
(methyl >1°> 2°, No 3°)
Cation Stability
(benzylic > allylic > 3° >
2°)(No 1° or methyl)
Leaving Group
Moderately Important
(same trend as SN1)
Very Important
(– I > –Br > –Cl, H2O > -OH)
Nucleophile
Solvent
Strong/Moderate Required
strong: RS–, I–, R2N–, R2NH,
RO–, HO–, CN–
moderate: RSH, Br–, RCO2–
wide variety,
(especially polar aprotic)
Not important
Polar protic
But：
H
Cl
C H
C
NaOH-H2O
OH
CH3
OH
CH3
C H
+
inversion
56.5%
+ Cl-
CH3
retention
43.5%
？？
离子对机理
R
X
k1
k -1
+
R X
k2
k -2
k3
R
X
k
R
+
-3
分子骨架
紧密离子对
溶剂分割离子对
碳正离子
构型转化
骨架构型转化
部分外消旋化
外消旋化
典型SN2
典型SN1
X
4.6 Elimination reactions
(消除反应)
C C
H X
+ B:-
C C
+ B H + X-
alkene
B: base, OH－, RO－, etc.
X: Cl, Br, I, HOH, OTs, etc.
1,2-elimination, β-elimination
Dehydrohalogenations (脱卤化氢)
CH3
H3C
C
CH3
CH3CH2OH
H3C
H3C
Br
H
+
H-Br
+
H-Br
H
Rate = k[R–X], first-order
CH3
H3C
C
Br
CH3CH2ONa
CH3
CH3CH2OH
H3C
H3C
Rate = k[R–X][B], second-order
H
H
Mechanisms of Elimination
 E1 reaction： Unimolecular Elimination
First-order Elimination
单分子消除
 E2 reaction： Bimolecular Elimination
Second-order Elimination
双分子消除
1) The E1 mechanism
rate-limiting step
step 1
CH3
E1 compete with SN1
Rearrangement exist.
CH3
C Br
CH3
slow
step 2
CH3
CH3
C
Br
¦Ä ¦Ä
CH
3
CH3
CH3
C
CH3
+
Br
intermediate
TS 1
CH3
H2C
C
H
CH3CH2OH
CH3 fast
H3C
H
+
H3C
H
CH3CH2OH2
fast step 3
CH3CH2OH + H+
2) The E2 mechanism
CH3CH2O
H
H2C
slow
CH3
C
CH3CH2O
H
H2C
CH3
CH3
C
CH3
Br
Br
fast
H
H3C
+ CH3CH2OH + Br
Transition state
single-step, concerted
H-C-C-X: anti-coplanar
(反式共平面)
anti elimination
H
H3C
-
B
H
C
C
X
-
B is far from X, stable TS
Stereochemistry of elimination:
Anti elimination(反式消除) for the E2 reaction.
B
H
+
H
B H
C C
Br
Br
The orbitals are aligned.
B is far away from L.
Br
H
H
X
X
X
H
Anti coplanar
staggered conformation
X
H
X
H
Syn coplanar
eclipsed conformation
X
H
Br
H
KOC(CH3)3
KOC(CH3)3
HOC(CH3)3
HOC(CH3)3
Br
H
H
H
(1)
(2)
cis-1,4-
trans-1,4-
k1 > k2
Br
H
H
H
NaOCH3
D
D
syn elimination
problem 6-38
H
H
Br
C
C
Ph
Br
H
C
Ph
CH3
Ph
CH3
NaOCH3
CH3
Ph
H
C
Ph
H
trans
Ph
Ph
NaOCH3
H
cis
diastereomers
Ph
CH3
cis-trans isomers
Positional orientation of elimination
(消除反应的定位方向)
CH 3CH 2CHCH 3
Br
CH3CH2ONa
CH3CH2OH
CH3CH CHCH 3 + CH3CH2CH CH2
81%
Saytzeff product
19%
Hoffman prduct
Saytzeff rule: (Zaitsev, 扎衣切夫规则)
In elimination reactions, the most highly substituted alkene
usually predominates.
在β-消去中，当有两种β-H时，总是从含H最少的β-C上消去
H，即得到双键碳上取代基较多的烯烃—扎衣切夫烯烃。
why ?
原因：取代基多的烯烃能量更低。
The competition of SN2 with E2
a
a
H
+ Nu
E2
C
-
Nu
C
b
X
b
SN2
H
C
Nu
C
+ X-
H + X-
(a)
(b)
CH3CH2ONa + CH3CH2Br
CH3CH2OH
55oC
CH3CH2OCH2CH3 + CH2=CH2
SN2 (90%)
E2 (10%)
CH3CH2ONa + CH3CHCH3 CH3CH2OH (CH3)CHOC2H5 +
55oC
SN2 (21%)
Br
CH2=CHCH3
E2 (79%)
CH3
(c)
CH3CH2ONa + CH3CCH3
Br
CH3CH2OH (CH ) COCH CH +CH =C(CH )
3 3
2
3
2
3 2
o
25 C
SN1 (9%)
E2 (91%)
minor
major
CH3
(d)
CH3CH2ONa + CH3CCH3
Br
CH3CH2OH
55oC
CH2=C(CH3)2
E1+E2 (100%)
+
CH3CH2OH
(e)
(f)
-
CH3CH2CH2Br + CH3O
CH3OH
CH3CH2CH2OCH3 + CH3CH=CH2
o
50 C
-
CH3CH2CH2Br + (CH3)3CO
SN2 major
(CH3)3COH
o
50 C
E2 minor
CH3CH2CH2OC(CH3)3 + CH3CH=CH2
SN2 minor
E2 major
Factors affecting the relative
rates of E2 and SN2 reaction
E2
SN2
Structure of substrate
secondary and tertiary
primary alkyl halide
alkyl halide
Basicity of nucleophile
stronger sterically
hindered base
Stronger basic
nucleophile
Temperature
high temperature
low temperature
E2
E1
Mechanism
Concerted
Two Steps
(carbocation rearrangements.)
Rate Equation
Rate = kr[R–X][Base]
Rate = kr[R–X]
Stereochemistry
Stereospecific
(anti coplanar TS)
Not Stereospecific
Substrate
Alkene Stability
(3° > 2° > 1°)
Cation Stability
(benzylic > allylic > 3 ° > 2 °
Base
Strong Base Required
(RO–, R2N–)
Not Important:
Usually Weak(ROH, R2NH)
Leaving Group
Moderately Important
(same trend as SN1)
Very Important
(same trend as SN1)
Solvent
Wide Range of Solvents
Polar Protic
Product Ratio
Saytzeff Rule: The most highly substituted alkene usually
predominates.
Hofmann Product: Use of a sterically hindered base will result
in formation of the least substituted alkene (Hofmann product).
Predicting the Products: Substitution versus Elimination
Start
Bimolecular
Reaction
Is Nuc/Base
bulky?
no
What kind of
substrate?
methyl
or 1°
SN2
yes
Is Nuc/Base
strong?
yes
3°
E2
SN2+E2
1°
Unfavorable
Reaction
mostly E1*
2°
no
yes
What kind of
substrate?
2°, 3°, or
stabilized 1°
Unimolecular
Reaction
Is Nuc/Base
bulky?
no
mostly SN1*
* Under conditions that favor a unimolecular reaction
(weak Nu/base and polar protic solvent), mixtures of
SN1 and E1 are usually obtained.
Essential problem-solving skills
1. Correctly name RX, and identify them as 1°, 2°, or 3°.
2. Predict the products of SN1, SN2, E1, and E2 reactions,
including stereochemistry.
3. Draw the mechanisms and energy profiles of SN1, SN2, E1,
and E2 reactions,
4. Predict and explain the rearrangement of cations in firstorder reactions.
5. Predict which substitutions and eliminations will be faster,
based on differences in substrats, base/nucleophile,
leaving group, or solvent.
6. Predict whether a reaction will be first-order or secondorder.
7. When possible, predict predominance of substitution or
elimination.
8. Use the Saytzeff rule to predict major and minor
elimination pfoducts.
Assignments
• text 1: 6-43, 44, 45, 46, 51, 53, 55, 56
• 6-59, 60, 61, 63, 66
• text 2(selected): p 254: 6, 7, 8, 10,11, 13,
14, 15