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