Chapter 8 Alkyl Halides8.1 IUPAC Nomenclature of Alkyl Halides8.2 Classes of Alkyl Halides8.3 Preparation of Alkyl Halides8.3.1 Addition of HX or X2 to Alkenes, Alkynes8.3.2 Preparation of Alkyl Halides from Alcohols and HX8.3.3 Exchange between Halides8.3.4 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 radicals8.3.5 Allylic Bromination of Alkenes 8.4 Reactions of Alkyl Halides 8.4.1The sites of reactions of alkyl halides8.5 Nucleophilic Substitution8.5.1 Nucleophilic Substitution8.5.2 A Mechanism for the SN2 Reaction8.5.3 Stereochemistry of SN2 Reactions

8.5.4 A Mechanism for the SN1 Reaction8.5.5 Stereochemistry of SN1 Reactions8.5.6 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 Reactions8.6.1 Dehydrohalogenation of Alkyl halides8.6.2 Dehydration of Alcohols8.6.3 Mechanisms of Elimination Reactions A. The E2 reaction B. The E1 Reaction8.6.4 Stereochemistry of Elimination Reactions8.6.5 Nucleophilic Substitution Versus Elimination 1.The structure of the substrate 2. The basicity of the reagent 3. The temperature of the reaction

R HR X : Halogen-substiuted organic compounds.

HCl

ClCl

Trichloro-ethylene(solvent)

C CF

F

F Br

Cl

H

Halothane( 氟烷 )(a anesthetic)( 麻醉剂 )

C

Cl

F

FCl

Dichlodifloro-methane

a refrigerant

C

H

H

HBr

a. Halogen: as a functional groupFor simple alkyl groups: P218P218

Bromomethanea fumigant

( 薰剂 )

Common nameCommon name

8.1 IUPAC Nomenclature of Alkyl Halides

Subsitutivenames

Ex. CH3FMethyl floride

( 甲基氟 )

ClAlkyl + halide

Pentyl chloride( 戊基氯 )

IH

Cyclohexyliodide

( 环己基碘 )b. Halogen as a substituent.For branched alkyl groups:

4,5-Dichloro-2-methylheptane(2- 甲基 -4,5- 二氯庚烷 )

• Number: begin at the end nearer the first substituent, regardless of X- or R-.

CH3CHCH2CHCHCH2CH3

ClCH3

Cl1 2 3 4 5 6 7

• Properly numbered from either end, list them in alphabetical order.

CH3CHCH2CH2CHCH3

CH3

Br6 5 4 3 2 1

(2- 甲基 -5- 溴己烷 )

2-Bromo-5-methylhexane

CH3

ClH3C

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 )

CH3CCH2Br

CH3

CH3

1-Bromo-2,2-dimethylpropane

RCHR'

X

Secondary Alkyl halides( 仲卤代烃 )

CH3CHCH2CH3

Br

R3CX Tertiary alkyl halides( 叔卤代烃 )

cis-1,4-Dimethylchlorocyclohexane

2-Bromobutane

Models of 1,2-dibromoethane

8.3 Preparation of Alkyl Halides8.3.1 Addition of HX or X2 to Alkenes, Alkynes

H2C CHCH2Cl BrCH2CH2CH2Cl+ HBr PhCOOCPh

O OEx.

8.3.2 Preparation of Alkyl Halides from Alcohols and HX P222, 7.3P222, 7.3Ex.

Reagents: HBr, HCl, PX3, PX5, SOCl. (Thionyl chloride) ( 亚硫酰氯 )

HX: HI > HBr > HCl >> HFAlcohols: 3°> 2° > 1° > Methanol

The order of reactitivity:

OH + HBrheat Br + H2O

(73%)

8.3.3 Exchange between Halides Ch.P 178Ch.P 178

CH3C

CH3

CH2CH3

Cl + NaIZnCl2, CS2

r.tCH3C

CH3

CH2CH3

I + NaCl

(96%)

Ex.

8.3.4 Halogenation of Alkanes

R H + X2h or heat

R X + HX

Common reagents: Cl2 or Br2.Reactivity: F2 > Cl2 > Br2 >I2

A. Chlorination of Methane:CH4

Cl2h or heat CH3Cl

Cl2h CH2Cl2

Cl2h CHCl3

Cl2h CCl4

Chloro-methane

Dichloro-Methane

Chloroform( 氯仿 )

Tetrachloromethane

Carbontetrachloride

( 四氯化碳 )

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

A species that bears a unpaired electron.

Methane chlorinationis a homolytic cleveage.Heterolytic cleavage ( 异裂 ):

A B A + B

A B A + BPolar breaking:cation and anion

Radical reaction:The reaction is promoted by light or by heat.Chain initiation ( 链的引发阶段 )

Step 1 Dissociation of a chlorine mole..

Chain propagation ( 链的增长阶段 )

Step 2 Radicals react with a mole.

Cl Cl h 2 Cl

Cl + H CH3 Cl H + CH3

Cl Cl + CH3 Cl CH3 + Cl

The radical reacts with the mole. of product

Cl Cl + CH2Cl Cl CH2Cl + Cl

Cl + H CH2Cl Cl H + CH2Cl

P219,7.2P219,7.2

initiatorinitiator

H3C + CH3 H3C CH3

Cl + Cl Cl Cl

Chain termination ( 链的终止阶段 )Step 3 The reactions between the radicals.

CH3Cl + Cl CH3

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 of higher alkanes:CH3CH2CH2CH3 + Cl2

h35°

CH3CH2CH2CH2Cl + CH3CHCH2CH3

Cl28% 72%

Primary < Secondary < Tertiary

C

H

H

R C

R

H

R C

R

R

R

Increasing the stability of alkyl radicals

The reaction gives a mixture of isomers:

CH3CHCH3

CH3

h 25°/

Cl2 CH3CHCH2Cl

CH3

+ CH3CCH3

CH3

Cl(63%) (37%)Primary hydrogen 9 63%Tertiary hydrogen 1 37%

Reactivity for different type of hydrogens in mole.:

The rate of the reactivity for the hydrogen: Tertiary hygrogenPrimary hydrogen

=63% / 937%

≈5.0

C

H

H

R H C

R

H

R H C

R

R

R H

Primary < Secondary < Tertiary1.0 3.5 5.0

Increasing the reactivity

Brominationis higher selective:

CH3CHCH2CH2CH3 + Br2h60°

CH3

CH3CCH2CH2CH3 + HBr

CH3

Br(76%)

8.3.5 Allylic Bromination of Alkenes

H H BrN

O

O

Br

+ N

O

O

Hh¦Í,CCl4

NBS

Mechanism of the reaction:

H H

Br+

H

+ HBrBr2

H Br

+ Br

Allylic radical

N

O

O

Br h¦Í N

O

O

Br+

HBr + N

O

O

Br Br2 + N

O

O

H

Stability of radicalsvinylic < methyl < 1°< 2°< 3°< allyic

CC

HH

X

7.4 Reactions of Alkyl Halides The sites of reactions of alkyl halides :

δ+ δ-

A polar covalent bondreadily broken

Nucleophilicsubstitution

Nu:-

BB:Elimination

8.5 Nucelophilic SubstitutionPaul Walden made a remarkable discovery:

HOCCH2CHCOH

O O

OH

PCl5

Et2OHOCCH2CHCOH

O O

Cl(–)-Malic acid ( 苹果酸 ) [α]D = -2.3°

(+)-Chlorosuccinic acid ( 卤代琥珀酸 )

(+)-Malic acid [α]D = +2.3°

(–)-Chlorosuccinic acid

AgO, H2O

HOCCH2CHCOH

O O

OH

PCl5

EtherHOCCH2CHCOH

O O

Cl

AgO, H2O

Inversion in configurationInversion in configuration

P225,7.5P225,7.5

                         

    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 mentioned almost in all textbooks on organic chemistry published throughout the world. 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. 

Paul Walden 1863-1957

The reaction of alkyl halides with sodium hydroxide:

8.5.1Nucelophilic Substitution( 亲核取代反应 )P226P226General type of the reaction:

Nu + C L C Nu + L

Ex. The reaction of ROH with HXHX + R OH

heat R X+ H2O

R O H

H

1.

+ X

2.

HO + H3C Br CH3OH +BrX and HO are nuclophiles( 亲核试剂 )

Nucleophiles: A species with an unshared electron pair. A Lewis base.

A reagent attacks a sp3-hybridized carbonwith partially positive charge,displacinga substituent. A nucleophilic substitution reaction

( 亲核取代反应 )

Substrates: like alkyl halides ( 卤代烷 ), a sp3-hybridized carbon with a leaving group.

The leaving group: a substituent departs from central carbon with a pair of bonding electrons.

C X C CX

X H2C CHCH2 X C C X

Ex. CH3ONa + CH3CH2Br CH3OCH2CH3 + NaBr

CH3CHCH3

Br

+ NaIacetone

CH3CHCH3

I

+ NaBr

Functional groups transformation by nucleophilic substitution reactions of alkyl halides

P227, Table 7.1P227, Table 7.1

8.5.2 A Mechanism for the SN2 Reaction(Substitution nucleophilic bimolecular)

Mechanism of nucleophlicsubstitution

SN1

SN2

Hydrolysis of methyl bromide:

HO + H3C Br CH3OH +BrH2O

Hydroxide ion in aqueous solution( 水溶液 ).

Reaction rate = k[CH3Br][-OH]In a single step process without intermediate.

Second-order reaction kinetics( 二级反应 )

C BrH

H

HO + HO C Br

H

H

H

H

CH

H

HHO

- - +BrC BrH

H

HO + HO C Br

H

H

H

H

CH

H

HHO

- - +Br

• The nucleophile approaches the central C from back side – the side opposite the bond to the leaving group

An transition state

Alkali( 碱 )

P228,7.7P228,7.7

CNu + L C LNu CNu

+ L

HO C Br

△G

C + BrHH

HHO

BrCH

H

HOH- +

En

ergy

Reaction progress

++

Ch.P188, ( 五 )Ch.P188, ( 五 )

• 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 inversionof conjugation( 构型翻转 ) at carbon that bears the leaving group.Walden inversion:

C

HCH3(CH2)5

H3CBr

(S)-(+)-2-Bromooctane (R)-(-)-2-Octanol

NaOHEtOH-H2O

CHO

H(CH2)5CH3

CH3

+δ- δ-

+

P229P229

8.5.4 A Mechanism for the SN1 Reaction(Substitution Nucleophilic Unimolecular)

In the hydrolysis of tert-butyl bromide: P232,7.8P232,7.8

ClH

H3CH + OH + ClH

H3C H

OH

An inversion of configuration

Reaction rate = k[CH3)3C-Br]

A first-order reactionA first-order reaction

(CH3)3C Br + H2O CH3)3C OH + HBr

Like an umbrella in the gale

Edward Davies Hughes(1906-1963)

Sir Christopher (Kelk) Ingold1893-1970 **

 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 Incorporation 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 symmetryof benzene's ground state and gave a quantitative description of its firstexcited 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.

C

CH3

CH3

H3C Br slow(rate-determing step) C

CH3

CH3

H3C Br+

C

CH3

CH3

H3C + OH

H

fast C

CH3

CH3

H3C OH

H

Step 3 The transfer of a proto to a mole. of water to produce a neutral alcohol.

Step 2 The carbocation reacts rapidly with water as nucleophile to produce an alkyloxonium ion.

C

CH3

CH3

H3C OH

H+ O

H

H

fast C

CH3

CH3

H3C OH

A fast acid-base reaction

FIGURE 2 A reaction energy diagram for an SN1

ΔG1 > ΔG2

++++

A carbocationis intermediateA carbocationis intermediate

C + Br

T1T2

△ G2

++

△G1

++

(CH3)3CBr + H2O

(CH3)3COH + HBr

Reaction progress

En

ergy

8.5.5 Stereochemistry of SN1 Reactions

(R)-(-)-2-Bromooctane (R)-(-)-2-Octanol (S)-(+)-2-Octanol

CH

H3C

CH3(CH2)5

Br H2OEtOH

CH

H3C

CH3(CH2)5

OH C+

HCH3

(CH2)5CH3

HO

(17%) (83%)

Nu Nu

Inversion of conjugationInversion of conjugation

Retention of conjugationRetention of conjugation

( 构型翻转 ) ( 构型保留 )

More than 50%More than 50% Less than 50%Less than 50%

For an optically active alkyl halide:

NuNu

Racemic productRacemic product

+P234 P234

8.5.6 Factors Affecting the Rate of SN1 Reactions and SN2 reactions1. Structure of substrates

SN2 reactions:The order of reactivity:

Tertiary < Secondary < Primary < Methyl Relative reactivity <1 500 40,000 2,000,000

Increasing SN2 reactivity

C

CH3

H3C

CH3

CH2 X

Neopentyl halides

is very unreactive.

CR

R'

R''

X

Nu

CR

R'

R''

X

Nu

The steric hindranceof alkyl group.

Nucleophile carriesout a back-side

displacementP230 P230

CH

H

HBr C

HH

CH3

Br

CHH3C

CH3

BrC

CH3

H3C

CH3

Br

FIGURE 3 Space-filling models of alkyl bromide, showing how substituents shield the C atom that bears the leaving group.

SN1 reactionsCH3 R2CH RCH CHCH2 CH2 R3CRCH2

Methyl< Primary Secondary< = Allyl =Benzyl < Tertary

Carbocation stabilityLessstable

Morestable

Reactivity for SN1 reactions

2. Nucleophiles The rates of SN2 reactions depends on both the concentration and identity of the attackingNucleophile:The nucleophile is usually a Lewis base

Ch. P195Ch. P195

Increasing the concentration of a nucleophileincreases the rate of an SN2 reaction.

> HO >> > ROH > H2ORO RCOO

• Negatively charged nucleophiles are usually more reactive than neutral ones.

HO > H2O > ROHRO

• nuclophilicity is also related to polarizability ( 可极化度 ).

>RS RO I > Br > Cl > F,

• Nucleophilicity roughly parallels basicity when comparing nucleophiles that have the same attacking atom.

The stronger the nucleophilicity of a reagent,the more rapid the reaction. The stronger the nucleophilicity of a reagent,the more rapid the reaction.

Distortion

3. The leaving group The leaving group affects both SN2 reactions and SN1 reactions. The best leaving groups should be the weakest bases. The best leaving groups should be the weakest bases.

The weak bases stabilize a negative chargemost effectively

FHO , NH2 , OR- - Cl Br I TsO

Relativereactivity << 1 1 200 10,000 30,000 60,000

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 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.

ROH + CH3 S

O

O

Cl RO S

O

O

CH3 + HCl

The best leaving groups: P326,8.14P326,8.14

p-Toluenesulfonateion( 对甲基苯磺酸根负离子 )

CH3 S

O

O

O CH3 S

O

O

O

Methylsulfonateion( 甲磺酸根负离子 )

TsO-

MsO-

Tosylate:

R OTs + Nu R Nu + OTs

Basicity: OH >> H2O-

R OHH

R OH

HBr

R Br + H2O

Transformationof leaving groups.

Transformationof leaving groups.

4. The solventSN1 reactions: P320, 8.12P320, 8.12

Dielectric constant (ε)( 介电常数 ) is a parameterto measure the polarity of solvent.

The polar solvent with a higher dielectric constant.

Polar solvents favor the dissociation of alkylhalides to form carbocations. Polar solvents favor the dissociation of alkylhalides to form carbocations.

C+

OHH

OH

H

O

H

H

OH H

O

H

H

O

H

H

Solvent mole. orient aroundthe carbocation.

H2O40% H2O/60%EtOH

80% H2O/20%EtOH

EtOH

1 100 14,000 100,000Relativereactivity:

C

CH3

CH3

H3C Cl + ROH C

CH3

CH3

H3C OR + HCl

Lessreactivity

morereactivitySolvent reactivity

SN2 reaction:Protic solvents: containing –OH, –NH groups.

worst solvents for SN2 reactions. They all have active hydrogen atoms that allowthem to form hydrogen bonds with nuclophiles,so that decrease the nucleophilicity of reagents.

Nu HO R

HO R

HO

R

HOR

Nu HO R

HO R

HO

R

HOR

In contrast to protic solvent,polar aprotic solvents increasethe rates of SN2 reactions.Ex.

H C

O

NCH3

CH3N,N-Dimethyl formamide(DMF)(N,N- 二甲基甲酰胺 )

CH3 S CH3

O

Dimethyl sulfoxide(DMSO)( 二甲亚砜 )

P

O

N

N

NCH3

CH3

CH3

CH3

CH3

H3C

HMPAor

HMPT

CH3CH2CH2CH2 Br + N3- CH3CH2CH2CH2 N3 + Br-

Solvent CH3OH H2O DMSO DMF CH3CN HMPARelativereactivity 1 7 1,300 2,800 5,000 200,000

Solvent reactivityLessreactive

Morereactive

8.6 Elimination ReactionsIonic reactions

1. Nucleophilic substitutions2. Elimination reactions

The Eliminaiton Reaction:

C C

Y L

Elimination

-YLC C

The atoms or the groups are removed from adjacent C atoms in a molecule isβElimination or 1,2-Elimination.

8.6.1 Dehydrohalogenation of Alkyl halides

P124, 4.9P124, 4.9

The loss of a hydrogen and a halogen fromadjacent C atoms of an alkyl halide to yield an alkene.

C C

H

+ B

X

C C + H B + XC C

H

+ B

X

C C + H B + X

CH3CHCH3

Br

EtONaEtOH, 55

°°CH3CH CH2 + NaBr + EtOHEx.

(79%) The reaction is carried out in the presentof a stronger base.

KOC(CH3)3- ROH:

2EtOH + 2Na 2EtONa + H22EtOH + 2Na 2EtONa + H2

αβ

The base attacks the β–H, X: leaving group

is used to primaryalkyl halides

EtONa-EtOH KOH-EtOH

C CH3

CH3

H3C

OH

H2SO4

HeatCH2 + H2OC

CH3

CH3

The regioselectivity of the elimination:H2C C

CH3

CH2CH2+ CHCH3C

CH3

CH3(29%) (71%)The elimination follows Zaitsev’s rule:

βelimination predominates in the directionthat leads to the more highly substituted alkene.

βelimination predominates in the directionthat leads to the more highly substituted alkene.8.6.2 Dehydration of Alcohols P126P126

The loss of a hydrogen and a hydroxyl groupfrom adjacent C atoms of an alcohol by acid-catalyst:

(82%)

C C

H

Br

H

H

CH3

C

H

H

CH3EtOKEtOH, 70

°°

The reaction also follows Zaisev’s rule:CH3

OH

H2SO4

Heat

CH3+

CH3

2-Methyl-cyclohexanol

1-Methyl-cyclohexene

3-Methyl-cyclohexene

(84%) (16%)Questions: For dehydration of alcohols, why the acid must be used? Which group is leaving group?

Questions: For dehydration of alcohols, why the acid must be used? Which group is leaving group?8.6.3 Mechanisms of Elimination ReactionsA. The E2 reaction (Elimination bimolecular):

C CH

X

C2H5O+-

-

+

C C + C2H5OH + Br

C2H5O

C CH

XTransition state

P236,7.9P236,7.9

R X C2H5ORate = kAt the same time,1. C-H bond breaking2. C=C πbond formation3. C-X bond breaking

take place.

Central C atom: sp3-hybrid sp2-hybridReactivity 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 Cl 80%C2H5OH20%H2O

(CH3)3C OH + (CH3)3C OC2H5

H2C C(CH3)2

(83%)

(17%)

Substitution

Elimination

Rate = k[(CH3)3C Cl]For the elimination:

Step 1 Alkyl halide dissociates by heterolytic cleavage of C － X bond.

C

CH3

CH3

H3C Cl C

CH3

CH3

H3CSlow + Cl

Step 2 EtOH acts at a base to remove a proton from the carbocation to give the alkene.

CH3CH2OH

C

CH3

CH3

CH

H

H

Fast CH3CH2OH

H+ H2C C

CH3

CH3

Step1 is rate-determining one.

P239,7.10P239,7.10

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 ReactionsThe E2 Reaction: In the transition state of the E2 reaction,

H C C X

With a periplanar ( 全平面的 ) geometry.

C CH

X

B-

-

The two conformations that permit this relationship:

XH H

X

Syn periplanarBond are eclipsed

H

X

H

XAnti periplanarBond are staggered

β- H and X are on the opposite side.

H

Br

Anti elimination( 反式消除 ) for the E2 reaction.Anti elimination( 反式消除 ) for the E2 reaction.

Br

H ++B

C C

Br

HB

Br

H

HKOC(CH3)3

HOC(CH3)3

KOC(CH3)3 BrH

HHOC(CH3)3

(1) (2)k1 > k2cis-1,4- trans-1,4-

Derek Harold Richard Barton1918-1997

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, Bartonwent 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 Substances Naturelles in Gif-sur-Yvette (France, 1977-85), and in 1986 he became Dow Distinguished Professor of Chemical Invention at Texas A. and M. University. He received many honors besides the Nobel, including the 1995 Priestley Medal (USA) and the 1995 Lavoisier Medal (France); an unusual honor for a chemist was his appointment (1989) by the Governor of Kentucky as a Kentucky Colonel.

In 1950 Barton published a 4-page paper in Experientia entitled "The Conformation of the Steroid Nucleus", in which he analyzed how molecular shape affects chemical behaviour. The paper was developed using cyclohexane ring

8.6.5 Nucleophilic Substitution Versus Elimination P239, 7.11P239, 7.11

NuC

C

H

X (b)

SN2C

C

H

Nu+ X

(a)E2

C

C+ Nu H + X

Substitution

Elimination

The three factors that affect the relative rates of E2 and SN2 reaction:1.The structure of the substrate

SN2 E2(90%) (10%)

For primary alkyl halide,the substitution is highlyfavored.

CH3CH2O Na + CH3CH2Br C2H5OH55 C°

CH3CH2OCH2CH3 + CH2 CH2-NaBr

E2

SN2

CH3CHCH3

Br

CH3CH2O Na + C2H5OH55 C°

CH3CHCH3

OCH2CH3

+ CH3CH CH2

-NaBr

SN2 E2 (21%) (79%)

For secondary alkyl halide,elimination reaction is highlyfavored.

CH3CH2O

As crowding at the central C atom decreases,

the rate of nucleo-philic attack by theLewis base increases.

How about tertiary halide in the presenceof a stronger Lewis base? Ex.CH3CH2O Na + C CH3

CH3

H3C

Br

C2H5OH25 C°

-NaBrC CH3

CH3

H3C

OCH2CH3

+ CH2CCH3

CH3

(9%) (91%)2. The basicity of the reagent

E2 SN2(1%) (99%)

E2 SN2(1%) (99%)

C

CH3

CH3

H3C O + CH3(CH2)15CH2CH2 Br (CH3)3COH40 C°

CH3O + CH3(CH2)15CH2CH2 Br CH3OH

65 C°CH3(CH2)15CH CH2

+CH3(CH2)15CH2CH2 OCH3

CH3(CH2)15CH2CH2 OC(CH3)3CH3(CH2)15CH CH2 +

E2 SN2(85%)(15%)

E2 SN2(85%)(15%)

• The elimination reaction is favored in thepresence of a stronger sterically hindered base. • Increasing the nucleophilicity of the reagent favors the SN2 reaction.

Less basicity than hydroxide:CH3CH(CH2)5CH3

Cl

KCNDMSO

CH3CH(CH2)5CH3

CN2-Chlorooctane 2-Cyanooctane(70%)

（ 2- 氰基辛烷）3. The temperature of the reaction Increasing the temperature of the reactionfavors E2 reaction.

Problems to Chapter 8P2467.22(c), (d)7.23(b)7.297.30(b), (c), (f)7.327.33(a)7.347.35(b)7.397.427.457.467.47

7.487.497.517.527.537.557.567.58

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.

CH3CHCH2

OHTsCl

CH3CHCH2

OTsCH3CH2OH

CH3CHCH2

OCH2CH3

[α]D = + 33.0° [α]D = + 31.1° [α]D = - 19.9°

K

CH3CHCH2

O K+

CH3CH2BrCH3CHCH2

OCH2CH3

[α]D = + 23.5°