text 1: chapter 6 text 2: 第九章 chapter 4 alkyl halides ( 卤代烷 ): nucleophilic substitution...
TRANSCRIPT
Text 1: chapter 6
Text 2: 第九章
Chapter 4 Alkyl halides ( 卤代烷 ):
Nucleophilic substitution and elimination ( 亲核取代和消除 )
ContentsClassification and Nomenclature of Alkyl h
alidesPhysical properties of alkyl halidesPreparation of Alkyl halidesReactions of alkyl halides
• Nucleophilic Substitution Reactions
• Elimination Reactions
4.1 Classification and Nomenclature of Alkyl halides
• Halohydrocarbons ( 卤代烃 )
X
alkyl halides ( 卤代烷烃 ):
vinyl halides ( 卤代烯烃 ):
aryl halides ( 卤代芳烃 ):
C XC X
sp3 sp2 sp2
Classification of alkyl halides
Primary halides伯卤代烷 ; 1°
Secondary halides仲卤代烷 ; 2°
Tertiary halides叔卤代烷 ; 3°
R C
H
H
X R C
H
R
X R C
R
R
X
C
X
X C C
XX
a geminal dihalide偕二卤代
a vicinal dihalide邻(连)二卤代
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 ------------ fluoro- chloride---------chlorine ----------- chloro-bromide---------bromine ----------- bromo-iodide------------iodine ------------- iodo-
Br
Bromocyclohexane
( 溴代环己烷 )
cyclohexyl bromide
环己基溴
CH3CH2CHCH3
Br
fluoroethane ( 氟乙烷 )ethyl fluoride ( 乙基氟 )
2-chloro-2-methylpropanet-butyl chloride ( 叔丁基氯 )
CH3CH2 F (CH3)3CCl
2-bromobutane(2- 溴 丁烷 )sec-butyl bromide( 仲丁基溴 )
CHCl3trichloromethane
chloroform ( 氯仿 )
CF3CF2CF3
perfluoropropane
全氟丙烷
Cl H
H CH3
(1R,3R)-1-chloro-3-methylcyclopentanetrans-1-chloro-3-methylcyclopentane(1R,3R)-1- 甲基 -3- 氯环戊烷trans- 1- 甲基 -3- 氯环戊烷
Cl
3-(chloromethyl)pentane3- 氯甲基戊烷
CH2Cl2dichloromethane( 二氯甲烷 )methylene dichloride
perchloromethanetetrachloromethanecarbon tetrachloride( 四氯化碳 )
CCl4
Common uses of alkyl halides
• 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)
reading material: text 1: 6-3
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)
1) Free-radical halogenation ( 自由基卤代 ) 6-6A
(Reading material: text 1 6-6, p 220-223)
+ Cl2
Cl
+ HClhv
H3C C H
CH3
CH3
H3C C Br
CH3
CH3
+ Br2 + HBrhv
Allylic halogenation ( 烯丙位卤化 ) 6-6B
N
O
O
Br
NBSN-bromosuccinimideN- 溴代丁二酰亚胺
N
O
O
Br + HBr N
O
O
H + Br2
Allylic radical is resonance-stableilized. 烯丙基自由基稳定.
Important reactions !!
HH
H
NBS, CCl4
HBr
Hhv or initiator
3) From alcohol ( 醇的取代 )
4) From other halides (halogen exchange, 主要用于制备碘代烷 )
2) From alkenes ( 烯烃加成 )
CH3CH2CH2CH CH3
BrCH3CH2CH2CH CH2
CH3COOH+ HBr 84%
CH3CH2CH2CH2OHH2SO4 CH3CH2CH2CH2Br H2O+ HBr + 95%
RCl (Br ) NaIacetone+ 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 )
Reactive intermediates( 反应活性中间体 )
C : Zheterolysis
C + Z
ÒìÁÑ
carbocation; carbonium ion£¨ ̼正Àë×Ó£©
C + Z
carbanion£¨ ̼负Àë×Ó£©
+ :
: +
C : Zhomolysis
C . + Z.¾ùÁÑ
Carbon radical or free radical
1) Nucleophilic substitution reactions ( 亲核取代反应 ):
X = F , Cl, Br, IC X+
_
Carbon-halogen bond lengths
Bond Bond Length (Å)
CH3F 1.39
CH3Cl 1.78
CH3Br 1.93
CH3I 2.14
Structure of alkyl halides
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.
Nu: Nucleophiles 亲核试剂X: Cl, Br, I , reactivity: I>Br>Cl
C
H
C
X
+ Nu- C
H
C
Nu
+ X-
For examples:
R X + CN R CN + X
R X + OH R OH + X
R X + R'O Na+ R O R' + NaX
R X + I R I + X
R X + H2O ROH + HX
R X +
NH3 RNH2 + HX RNH3+X
OH -RNH2
RNH2 R2NH + HX R2NH2+X OH - R2NH
R2NH R3N + HX R3NH+XOH -
R3N
R X + P(C6H5)3 [ 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
C
H
C
X
+ C C + X-B:- B +H
2) Elimination reactions ( 消除反应 ):
B: base, OH - , CH3O - , CH3CH2O -
X: Cl, Br, I
1,2-elimination, β-elimination
CH3CH2CHCH3
Br
CH3CH2ONa
CH3CH2OHCH3CH CHCH3
CH3CH2CH CH2
81%
19%
Most Nu are also basic and can engage in either substitution or elimination, depending on the alkyl halide and the reaction conditions.
CH3CHCH3
Br
CH3CH2ONa
CH3CH2OHCH3CHCH3
OEt+ CH3CH CH2
21% 79%
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 u
sually 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。
3) Formation of organometallic compounds
( 形成有机金属化合物 ) (T2: p234; T1 p 420 10-8, 9 )
R X + Mgether(ÃÑ)
R MgX
organomagnethium compound“Grignard reagent” ( 格利雅试剂 , 格氏试剂 )
Important reagents in organic synthesis !!!
R M
M: Li, Na; Mg; B, Al, Ga; Si, Ge, Sn, Pb; P, As, Sb; etc.
C M +
活性顺序: RI £¾RBr £¾RCl £¾RF
organolithium compound 有机锂化合物
R X +ether(ÃÑ)
RNa + NaX2 Na
R X +ether(ÃÑ)
RLi + LiX2 Li
R R +ether(ÃÑ)
RNa + RX NaX
Wurtz reaction ( 武慈反应 )
ether(ÃÑ)2RLi + CuI R2CuLi + LiI
+ RCu + LiXR2CuLi + R'X R R'
4) Reduction of alkyl halides to alkanes ( 还原反应 )
Reductive agents ( 还原剂 ) : LiAlH4, NaBH4
CH3(CH2)8CH2Br CH3(CH2)8CH3
reactivity: RI > >RBr RCl
primary secondary tertiary halides> >
CH3(CH2)6CH2XNaBH4
¶þ̧ Ê´¼¶þ¼×ÃÑCH3(CH2)6CH3
1. LiAlH4
2. H2O
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)
CH3 C Br
CH3
CH3
+NaOHH2O
CH3 C OH
CH3
CH3
NaBr+
¦Í = K CH3 C Br
CH3
CH3
CH3Br + NaOHH2O
CH3OH + NaBr
¦Í = K CH3Br OH
Experimental facts:
SN1 : first-order nucleophilic substitution
( 单分子亲核取代反应 )
SN2 : second-order nucleophilic substitution
( 双分子亲核取代反应 )
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 )
¦Í = K CH3Br OH
HO C Br
H
HH
+
CHO
H
H
H
Br+
transition state ( 过渡态 , TS)nucleophile substrate ( 底物 )
product ( 产物 )
CH3Br + NaOHH2O
CH3OH + NaBr
fast
Mechanism
C Br
H H
H
HO δ–δ–
slow
LNu C
C LNu
C LNu
C LNu
:
::::
The reaction-energy diagram ( 反应能线图 )
TS
E
HO C Br
H
HH CHO
H
H
H
C Br
H H
H
HO
Eact
reaction coordination
δ– δ–
exothermic reaction放热反应
Characteristics of SN2
(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。 )
(1) second-order reaction ( 二级反应 ) ν= k[RX][Nu]
(4) stereochemistry: inversion of configuration ( 构型转化 ) Walden inversion ( 瓦尔登转化 )
I* C I
C6H13
CH3
H
+ CI
C6H13
CH3
H
* + I
racemization ( 外消旋化 )
inversion of configuration ( 构型转化 )Walden inversion ( 瓦尔登转化 )
optically pure
HO +
C6H13
Br
HH3C
C6H13
HO
H
CH3
( R ) ( S )
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 。
H3C
Br
ClH
HO +CH3
HO
Cl
H
( R ) ( R )
Factors affecting SN2 reactions Nu, Substrate, Solvent, TemperatureA. The effect of nucleophile
CH3O- + CH3Irapid
CH3OCH3 + I-
methoxide ion (¼×Ñõ»ùÀë×Ó£©
CH3OH + CH3Ivery slow
CH3OCH3 + I-
H
+
methanol
• A base is always a stronger nucleophile than its conjugate acid.
CH3O- CH3OH
HO- HOH
CH3COO- CH3COOH
RO- ROH
RS- RSH
>
>
>>
>
• 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
basicity ≠ nucleophilicity
But:
O
H3C
H3CCH3
CH3 CH2 O
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 )
R3P, HS-, I-, -CN, HO-, CH3O- , R2NH
F-, H2O, CH3OH
Br-, Cl-, NH3, CH3OH, CH3SCH3, CH3COO-
strong
moderate
weak
weakstrong
strong
B. The effect of the structure of the substarate ( 底物结构的影响)
Relative rates of reactions of alkyl halides in SN2 reactions
Methyl
Substituent Compound relative rate
CH3X 30
1o CH3CH2X 1
2o
3o
(CH3)2CHX 0.02
Neopentyl ÐÂÎì »ù (CH3)3CCH2X 0.00001
(CH3)3CX 0
General order of reactivity in SN2 reaction
CH3- > 1° > 2°> 3 °
R---X(L)
R-: steric effectsCH3
H3CCH3
Br
CH3
HCH3
Br
CH3
HH
Br
H
HH
Br
Leaving group effects
A good leaving group must be
electron withdrawing; stable after leaving; (usually weak base) polarizable, to stablize the TS
O S
O
O
R O S
O
O
O RI-, Br-, Cl-,
HOH, ROH, NR3, etc.
CH3 OH+Br- Br CH3 + OH-×
CH3 OH + H+ CH3 O
H
H
Br-
Br CH3 + H2O
F HO RO NH2 NHR CN
poor leaving group
C. Solvent effects on SN2 reactions
Protic solventProtic solvent ( 质子性溶剂 )
Aprotic solvent ( 非质子性溶剂 )
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 ):
Apolar solvent ( 非极性溶剂 ):
H2O, ROH, acetone( 丙酮 ), acetonitrile( 乙腈 ), etc.
Hexane, carbon tetrachloride
Polar Aprotic Solvents (极性非质子溶剂)
O
H N
CH3
CH3
S
O
H3C CH3
N,N-Dimethylformamide (DMF)N,N- 二甲基甲酰胺
Dimethyl sulfoxide (DMSO) 二甲亚砜
acetonitrile乙腈
O
H3C CH3
acetone丙酮
CH3CN
in protic solvents: I- > Br- > Cl- > F-
SH- > CN- > I- > OH- > N3- > Br- > CH3CO2
- > Cl- > F- > H2O
O
H
HO
H H
HO
HH
OH
X-
in aprotic solvents: I- < Br- < Cl- < F-
Generally, polar solvents are required in the nucleophilic substitution reaction.
Relative Nucleophilicity
CH2Cl CH2FKF, 18-crown-6
CH3CN+ Cl-
O
O
O
OO
O
18-crown-6
O
O
O
OO
O
K+
F-
Factors affecting SN2 reactions
Nu
Substrate
Solvent
Temperature
R
L
Strong Nucleophiles are needed.
less steric hindrance
good leaving groups are required.
Higher temperature can increase the rate.
Wide variety, polar aprotic
2) SN1: First-order nucleophilic substitution ( 单分子亲核取代 )
(CH3)3C Br + CH3OH (CH3)3C OCH3+ HBr-boil
CH3 C Br
CH3
CH3
+NaOHH2O
CH3 C OH
CH3
CH3
NaBr+
¦Í = K CH3 C Br
CH3
CH3
CH3 C
CH3
CH3
Brslow
CH3 C
CH3
CH3
Br¦Ä ¦Ä
CH3 C
CH3
CH3
+ Br
step 1
TS 1 carbocation
intermediate
CH3 C
CH3
CH3
+ OHfast
CH3 C
CH3
CH3
OH¦Ä ¦Ä CH3 C
CH3
CH3
OH
step 2
TS 2
Mechanism of SN1
rate-limiting step
Eact1
Eact2
TS 1
TS 2
£¨CH3£©3CBr
£¨CH3£©3C
BrOH
Br£¨CH3£©3COH
E
reaction coordination
The reaction-energy diagram ( 反应能线图 )
rate-limiting step
CH3+
(CH3)3C+
H
H
H planar
sp2S
Vacant p orbital
methyl cation tert-butyl cation
H3C
H3C
CH3 planar
sp2sp3
Vacant p orbital
+ +
The structure of carbocations
Stereochemistry
C
R1
R2 R3
Nu
C
R2
R3
R1
Nu C
R2R3
R1Nu
racemization( 外消旋化 )
Factors affecting SN1 reactions
Nu
Substrate
Solvent
Temperature
R
L
No effects, weak ones are OK.
Good leaving groups are required. Similar as SN1.
Higher temperature can increase the rate.
Stability of carbocation, or Substituent effects
Good ionizing solvents needed, protic solvents
The relative stabilities of carbocations
How a methyl group helps stabilize the positive charge of a carbocation?
CH3+RCH2
+ >R2CH+ >R3C+ >
(most stable) (least stable)
benzylic > allylic >
CH2
CH2
benzylic cation allylic cation
C HH
H
.
sp2
+CH2CH3
C CH
H
HH
H
.
sp2 sp3
.
CH3C
H3CH C
H3C
H3CCH3
+CH2(CH3)2
+CH2(CH3)3
+CH3
hyperconjugation超共轭效应 , σ-p
electron-donating of alkyl group烷基的给电子效应
stable
Rearrangement ( 重排 ) of carbocation
stable
H3C C
CH3
H3C
CH CH3
Br
-Br-
H3C C
CH3
H3C
CH CH3SN1
H3C C
CH3
H3C
CH CH3
Nu
Nu-
H3C C
H3C
CH CH3
CH3
Nu-
H3C C
H3C
CH CH3
CH3Nu
H3C C
CH3
H3C
CH Ph
Br
-Br-
H3C C
CH3
H3C
CH PhSN1
H3C C
H3C
CH Ph
CH3
H3C C
CH3
H3C
CH Ph
Nu
Nu-
Characteristics of SN1
(2) multi-step reaction ( 多步反应 )
(3) having a carbocation intermediate.
( 反应经过碳正离子中间体。 )
(1) first-order reaction ( 一级反应 ) ν= k[RX]
(4)stereochemistry: racemization ( 外消旋化 )
(5) rearrangement ( 重排 )
C CCH
H H
Nu
X ¦Ä
¦Ä
H
H
Allylic halides 烯丙基卤
SN1
SN2
stablized TS
stable intermediateCH3CH CHCH2Br Br CH3CH CHCH2 CH3CH CH CH2
CH3CH = CHCH2OH
OH-
CH3CH CH = CH2
OH
OH-
CH3CH CH CH2
¦Ä ¦Ä
SN2 SN1
kineticsRate = k[R–X][Nu], second-order
Rate = k[R–X], first-order
Mechanism Bimolecular, Concerted, TS Two Steps, intermediate, carbocation, rearrangements
StereochemistryStereospecific ( 立体专一的 )(inversion)
Loss of Stereochemistry (racemization)
Substrate (R-)Sterics (methyl >1°> 2°, No 3°)
Cation Stability(benzylic > allylic > 3° > 2°)(No 1° or methyl)
Leaving GroupModerately Important(same trend as SN1)
Very Important(– I > –Br > –Cl, H2O > -OH)
Nucleophile
Strong/Moderate Requiredstrong: RS–, I–, R2N–, R2NH, RO–, HO–, CN–
moderate: RSH, Br–, RCO2–
Not important
Solvent wide variety, (especially polar aprotic) Polar protic
离子对机理
R Xk1
k -1R+X
k2
k -2R X
k3
k -3R + X
分子骨架
构型转化
紧密离子对
骨架构型转化
典型 SN2
溶剂分割离子对
部分外消旋化
碳正离子
外消旋化
典型 SN1
But :C C
+ Cl-CH3
Cl
NaOH-H2OH
OH
CH3
H
C
CH3
OHH
+
inversion56.5%
retention43.5%
??
4.6 Elimination reactions ( 消除反应 )
C
H
C
X
+ C C + X-B:- B +H
B: base, OH - , RO - , etc.X: Cl, Br, I, HOH, OTs, etc.
1,2-elimination, β-elimination
Dehydrohalogenations ( 脱卤化氢 )
alkene
CH3
CH3C CH3
Br
H3C
H3C
H
H
+ H-BrCH3CH2OH
CH3
CH3C CH3
Br
H3C
H3C
H
H
+ H-BrCH3CH2ONa
CH3CH2OH
Rate = k[R–X][B], second-order
Rate = k[R–X], first-order
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
CH3 C
CH3
CH3
Brslow
CH3 C
CH3
CH3
Br¦Ä ¦Ä
CH3 C
CH3
CH3
+ Br
step 1
TS 1 intermediatestep 2
rate-limiting step
CH3
CH2C CH3
CH3CH2OH
H
H3C
H3C
H
H
+ CH3CH2OH2fast
CH3CH2OH + H+
fast step 3
E1 compete with SN1Rearrangement exist.
2) The E2 mechanism
C CH
X
B-
-
Transition statesingle-step, concertedH-C-C-X: anti-coplanar( 反式共平面 )anti elimination
CH3
CH2C CH3
Br
CH3CH2O HCH3
CH2C CH3
Br
CH3CH2O H
H3C
H3C
H
H
+ CH3CH2OH + Br
slow
fast
B is far from X, stable TS
H
Br
Stereochemistry of elimination:Anti elimination( 反式消除 ) for the E2 reaction.
Stereochemistry of elimination:Anti elimination( 反式消除 ) for the E2 reaction.
Br
H ++B
C C
Br
HB
The orbitals are aligned. B is far away from L.
H
X
H
XAnti coplanarstaggered conformation
XH H
X
Syn coplanar
eclipsed conformation
X
H
XH
Br
H
HKOC(CH3)3
HOC(CH3)3
KOC(CH3)3 BrH
HHOC(CH3)3
(2)
k1 > k2
cis-1,4- trans-1,4-(1)
Br
HH
D
H
D
NaOCH3
syn elimination
problem 6-38
C CBr
PhPh
H
CH3
H
H
Ph CH3
Ph
H
Ph
CH3
Ph
C C
Br
PhPh
H
CH3H
NaOCH3
NaOCH3
trans
cis
diastereomers cis-trans isomers
Positional orientation of elimination( 消除反应的定位方向 )
CH3CH2CHCH3
Br
CH3CH2ONa
CH3CH2OHCH3CH CHCH3 CH3CH2CH CH2+
81% 19%
Saytzeff rule: (Zaitsev, 扎衣切夫规则 )
In elimination reactions, the most highly substituted alkene u
sually 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 ?
Saytzeff product Hoffman prduct
原因:取代基多的烯烃能量更低。
The competition of SN2 with E2
H C
C X
+ Nu H + X-
H C
CNu
b
SN2
a
E2
Nu-
b
a
+ X-
CH3CH2ONa + CH3CH2BrCH3CH2OH
55oCCH3CH2OCH2CH3 + CH2=CH2
SN2 (90%) E2 (10%)
CH3CH2ONa + CH3CH2OH
55oC SN2 (21%) E2 (79%)(CH3)CHOC2H5 + CH2=CHCH3CH3CHCH3
Br
SN1 (9%) E2 (91%)CH3CH2ONa + CH3CH2OH
25oC(CH3)3COCH2CH3 +CH2=C(CH3)2
CH3CH2ONa +CH3CH2OH
55oCE1+E2 (100%)
CH2=C(CH3)2 + CH3CH2OH
CH3
majorminor
CH3CCH3
CH3
Br
CH3CCH3
Br
(a)
(b)
(c)
(d)
CH3CH2CH2Br + CH3O-CH3OH
50oCCH3CH2CH2OCH3 + CH3CH=CH2
SN2 major E2 minor
CH3CH2CH2Br + (CH3)3CO-(CH3)3COH
50oCCH3CH2CH2OC(CH3)3 + CH3CH=CH2
SN2 minor E2 major
(e)
(f)
Factors affecting the relative rates of E2 and SN2 reaction
E2 SN2
Structure of substratesecondary and tertiary alkyl halide
primary alkyl halide
Basicity of nucleophilestronger sterically hindered base
Stronger basic nucleophile
Temperature high temperature low temperature
E2 E1
Mechanism ConcertedTwo Steps
(carbocation rearrangements.)
Rate Equation Rate = kr[R–X][Base] Rate = kr[R–X]
Stereochemistry Stereospecific
(anti coplanar TS)Not Stereospecific
SubstrateAlkene Stability
(3° > 2° > 1°)
Cation Stability
(benzylic > allylic > 3 ° > 2 °
BaseStrong Base Required
(RO–, R2N–)Not Important: Usually Weak(ROH, R2NH)
Leaving GroupModerately Important
(same trend as SN1)
Very Important
(same trend as SN1)
Solvent Wide Range of Solvents Polar Protic
Product RatioSaytzeff 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
yesBimolecularReaction
yes
yes
no
* Under conditions that favor a unimolecular reaction (weak Nu/base and polar protic solvent), mixtures of
SN1 and E1 are usually obtained.
SN2
methyl or 1°
Is Nuc/Base bulky?
noWhat kind of substrate?
SN2+E2
E23°
2°
1°
mostly SN1*
mostly E1*Is Nuc/Base bulky?
UnimolecularReaction
UnfavorableReaction
Is Nuc/Base strong?
What kind of substrate?
2°, 3°, orstabilized 1°
no
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, inc
luding stereochemistry.3. Draw the mechanisms and energy profiles of SN1, SN2, E1,
and E2 reactions, 4. Predict and explain the rearrangement of cations in first-or
der 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 second-order.
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