8-1 8 Organic Chemistry William H. Brown & Christopher S. Foote.
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8-1
88
Organic Organic ChemistryChemistry
William H. Brown & William H. Brown & Christopher S. FooteChristopher S. FooteWilliam H. Brown & William H. Brown & Christopher S. FooteChristopher S. Foote
8-2
88
Nucleophilic Nucleophilic Substitution Substitution
and and -Elimination-Elimination
Chapter 8
Chapter 8Chapter 8
8-3
88 Nucleophilic SubstitutionNucleophilic Substitution
Nucleophilic substitution:Nucleophilic substitution: any reaction in which one nucleophile is substituted for another at a tetravalent carbon
Nucleophile:Nucleophile: a molecule or ion that donates a pair of electrons to another molecule or ion to form a new covalent bond; a Lewis base
nucleophilicsubstitution
Nucleophile
++ C NuC XNu:- :X-
leavinggroup
8-4
88 Nucleophilic SubstitutionNucleophilic Substitution An important reaction of alkyl halides
+an alcohol (after proton transfer)
an alkylammonium ion
an alkyl iodide I -
NH3
HOH
CH3I
CH3NH3+
CH3O-H
a nitrileCH3C N- C N
an alkyneCH3C CHHC C -
::
:
:
:::
:
H
::
::
::
:
a thiol (a mercaptan)HS - CH3SH
an ether
an alcohol
Reaction: + +CH3NuCH3Br Br-
RO -
HO -
Nu
CH3OH
CH3OR
: :
:
:
:
::::::
::::::
8-5
88 SolventsSolvents Protic solvent:Protic solvent: a solvent that is a hydrogen bond
donor • the most common protic solvents contain -OH groups
Aprotic solvent:Aprotic solvent: a solvent that cannot serve as a hydrogen bond donor• nowhere in the molecule is there a hydrogen bonded
to an atom of high electronegativity
8-6
88 Dielectric ConstantDielectric Constant Solvents are classified as polar and nonpolar• the most common measure of solvent polarity is
dielectric constant
Dielectric constant:Dielectric constant: a measure of a solvent’s ability to insulate opposite charges from one another• the greater the value of the dielectric constant of a
solvent, the smaller the interaction between ions of opposite charge dissolved in that solvent
• polar solvent: dielectric constant > 15• nonpolar solvent: dielectric constant < 15
8-7
88 Protic SolventsProtic Solvents
Solvent StructureDielectric Constant (25°C)
Water
Formic acid
Methanol
Ethanol
H2O 79
HCOOH
CH3OH
CH3CH2OH
59
33
24
Acetic acid CH3COOH 6
8-8
88 Aprotic SolventsAprotic Solvents
2.3Toluene
4.3Diethyl ether
9.1Dichloromethane
SolventDielectricConstantStructure
Dimethyl sulfoxide (DMSO)
Acetonitrile
Acetone
N,N-Dimethylformamide (DMF)
48.9
37.5
36.7
20.7
Polar
Nonpolar
CH3C N
CH2Cl2CH3CH2 OCH2CH3
Hexane CH3(CH2)4CH3 1.9
(CH3)2S=O
(CH3)2NCHO
(CH3)2C=O
C6H5CH3
8-9
88 MechanismsMechanisms Chemists propose two limiting mechanisms for
nucleophilic displacement• a fundamental difference between them is the timing
of bond breaking and bond forming steps
At one extreme, the two processes take place simultaneously; designated SN2• S = substitution• N = nucleophilic• 2 = bimolecular (two species are involved in the rate-
determining step)
8-10
88 Mechanism - SMechanism - SNN22• both reactants are involved in the transition state of
the rate-determining step
C Br
H
HH
HO:- + C
H
HH
HO Brδ- δ-
T ransition state with simultaneous bond breaking and bond forming
C
H
HH
HO + :Br -
8-11
88 Mechanism - SMechanism - SNN22
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8-12
88 Mechanism - SMechanism - SNN11 Bond breaking between carbon and the leaving
group is entirely completed before bond forming with the nucleophile begins
This mechanism is designated SN1 where• S = substitution• N = nucleophilic• 1 = unimolecular (only one species is involved in the
rate-determining step)
8-13
88 Mechanism - SMechanism - SNN11• Step 1: ionization of the C-X bond gives a carbocation
intermediate
C
CH3
CH3H3C
+C
H3C
H3CBr
H3C
slow, ratedetermining
A carbocation intermediate; its shape is trigonal planar
+ :Br-
8-14
88 Mechanism - SMechanism - SNN11• Step 2: reaction of the carbocation with methanol
gives an oxonium ion. Attack occurs with equal probability from either face of the planar carbocation
• Step 3: proton transfer completes the reaction
:+
+++ fastC
H3CH3C
OH3C
OCH3
HOHO
CH3CH3
H
H
CH3
H3C
CH3CH3C
:
OCH3
H
C
CH3
CH3
O
H3C
H CH3
C
H3C
H3C
O
H3C H
CH3
+
Lewis acid Nucleophile(Lewis base)
fast
Oxonium ions
C
CH3
CH3H3C
+ + :
8-15
88 Mechanism - SMechanism - SNN11
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8-16
88 Evidence of SEvidence of SNN reactions reactions1. What is the rate of an SN reaction affected by: • the structure of Nu?• the structure of RX?• the structure of the leaving group?• the solvent?
2. What is the stereochemistry of the product if the Nu attacks at a stereocenter?
3. When and how does rearrangement occur?
8-17
88 KineticsKinetics For an SN1 reaction, the rate of reaction is first
order in haloalkane and zero order in nucleophile
d[(CH3)3CBr]dt
Rate = - = k[(CH3)3CBr]
CH3CBr + CH3OH CH3COCH3 + HBr
2-Bromo-2-methyl-propane
(tert-Butyl bromide)
Methanol 2-Methoxy-2-methyl-propane
(tert-Butyl methyl ether)
CH3
CH3
CH3
CH3
8-18
88 KineticsKinetics For an SN2 reaction, the rate is first order in
haloalkane and first order in nucleophile
d[CH3Br]
dtrate = = k[CH3Br][OH-]
CH3Br + Na+OH- CH3OH + Na+Br-
Bromomethane Methanol
8-19
88 NucleophilicityNucleophilicity Nucleophilicity:Nucleophilicity: a kinetic property measured by
the rate at which a Nu causes a nucleophilic substitution under a standardized set of experimental conditions
Basicity:Basicity: a equilibrium property measured by the position of equilibrium in an acid-base reaction
Because all nucleophiles are also bases, we study correlations between nucleophilicity and basicity
8-20
88 NucleophilicityNucleophilicity
Good
Poor
Br-, I-
HO-, CH3O-, RO-CH3S-, RS-
CH3COO-, RCOO-
H2O
CH3OH, ROH
CH3COOH, RCOOH
NH3, RNH2, R2NH, R3NCH3SH, RSH, R2S
Nucleophile
Moderate
CN-, N3-
Effectiveness
8-21
88 NucleophilicityNucleophilicity Relative nucleophilicities of halide ions in polar
aprotic solvents are quite different from those in polar protic solvents
How do we account for these differences?
Increasing NucleophilicitySolvent
Polar aprotic
Polar protic F- < Cl- < Br- < I-
I- < Br- < Cl- < F-
8-22
88 NucleophilicityNucleophilicity A guiding principle is the freer the nucleophile,
the greater its nucleophilicity Polar aprotic solvents (e.g., DMSO, acetone,
acetonitrile, DMF) • are very effective in solvating cations, but not nearly
so effective in solvating anions. • because anions are only poorly solvated, they
participate readily in SN reactions, and
• nucleophilicity parallels basicity: F- > Cl- > Br- > I-
8-23
88 NucleophilicityNucleophilicity Polar protic solvents (e.g., water, methanol)• anions are highly solvated by hydrogen bonding with
the solvent• the more concentrated the negative charge of the
anion, the more tightly it is held in a solvent shell• the nucleophile must be at least partially removed
from its solvent shell to participate in SN reactions
• because F- is most tightly solvated and I- the least, nucleophilicity is I- > Br- > Cl- > F-
8-24
88 NucleophilicityNucleophilicity Generalizations• within a period, nucleophilicity increases from left to
right; that is, it increases with basicity
Increasing NucleophilicityPeriod
Period 2
Period 3
F- < OH- < NH2- < CH3
-
Cl- < SH- < PH2-
8-25
88 NucleophilicityNucleophilicity Generalizations• in a series of reagents with the same nucleophilic
atom, anionic reagents are stronger nucleophiles than neutral reagents
Increasing Nucleophilicity
ROH < RO-
H2 O < OH-
NH3 < NH2-
RSH < RS-
8-26
88 NucleophilicityNucleophilicity• when comparing groups of reagents in which the
nucleophilic atom is the same, the stronger the base, the greater the nucleophilicity
15.7
Hydroxide ion
Alkoxide ion
Carboxylate ion
Decreasing Acidity
Increasing Nucleophilicity
Conjugate acid
Nucleophile
pKa
RCOO-
RCOOH4-5
RO-
HO-
ROH
16-18
HOH
8-27
88 StereochemistryStereochemistry For an SN1 reaction at a stereocenter, the
product is almost completely racemized
C
H
Cl
Cl
-Cl-
C+
H
Cl
CH3OH
-H+ CH3O C
H
Cl Cl
C OCH3
H
R EnantiomerS Enantiomer
+
R EnantiomerA racemic mixture
Planar carbocation (achiral)
8-28
88 StereochemistryStereochemistry For SN1 reactions at a stereocenter• examples of complete racemization have been
observed, but• partial racemization with a slight excess of inversion
is more common
Approach of the nucleophile from this side is less hindered
+
R1
C
HR2
Cl-
Approach of the nucleophile fromthis side is partially blocked by chloride ion, which remains associated with the carbocation as anion pair
8-29
88 StereochemistryStereochemistry For SN2 reactions at a stereocenter, there is
inversion of configuration at the stereocenter Experiment of Hughes and Ingold
Iacetone
SN2-131+
I I131
I-+
2-Iodooctane
8-30
88 Hughes-Ingold ExptHughes-Ingold Expt• the reaction is 2nd order, therefore, SN2
• the rate of racemization of enantiomerically pure 2-iodooctane is twice the rate of incorporation of I-131
I:- CH
I
C6H13
H3C
CH
CH3
C6H13
I :I-SN2
acetone+131 131
+
(S)-2-Iodooctane (R)-2-Iodooctane
8-31
88 Structure of RXStructure of RX SN1 reactions governed by electronic factors; • the relative stabilities of carbocation intermediates
SN2 reactions governed by steric factors; • the relative ease of approach of the nucleophile to the
site of reactionGoverned byelectronic factors
Governed bysteric factors
SN1
SN2
R3CX R2CHX RCH2X CH3X
Access to the site of reaction
(3°) (methyl)(2°) (1°)
Carbocation stability
8-32
88 Effect of Effect of -Branching-Branching
1.2 x 10-51.2 x 10-3Relative Rate
Alkyl Bromide
-Branches 0 1 2 3
1.0 4.1 10x -1
Br Br Br Brβ β β β
8-33
88 Effect of Effect of -Branching-Branching
CH3CH2Br
freeaccess
Bromoethane(Ethyl bromide)
CH3CCH2Br
CH3
CH3
1-Bromo-2,2-dimethylpropane(Neopentyl bromide)
blockedaccess
8-34
88 Allylic HalidesAllylic Halides Allylic cations are stabilized by resonance
delocalization of the positive charge• a 1° allylic cation is about as stable as a 2° alkyl cation
+ +
Allyl cation(a hybrid of two equivalent contributing
structures)
CH2=CH-CH2 CH2-CH=CH2
8-35
88 Allylic CationsAllylic Cations 2° & 3° allylic cations are even more stable
As also are benzylic cations
++
A 2° allylic carbocationA 3° allylic carbocation
CH3
CH2=CH-CH-CH3 CH2=CH-C-CH3
C6H5-CH2+CH2
+
Benzyl cation(a benzylic carbocation)
The benzyl cation is also writtenin this abbreviated form
8-36
88 The Leaving GroupThe Leaving Group The more stable the anion, the better the leaving
ability• the most stable anions are the conjugate bases of
strong acids
I- > Br- > Cl- >> F- > CH3CO- > HO- > CH3O- > NH2-
OReactivity as a leaving group
Stability of anion; strength of conjugate acid
8-37
88 The Solvent - SThe Solvent - SNN22 The most common type of SN2 reaction involves
a negative Nu and a negative leaving group
• the weaker the solvation of Nu, the less the energy required to remove it from its solvation shell and the greater the rate of SN2
+ +
Transition state
negatively chargednucleophile
negatively chargedleaving group
negative charge dispersed in the transition state
XC XCNu CNuNu:-δ−δ−
:X-
8-38
88 The Solvent - SThe Solvent - SNN22Br N3
-
CH3C N
CH3OHH2 O
(CH3 )2S=O
(CH3 )2NCHO
N3 Br-
SolventType
polar aprotic
polar protic
5000
2800
1300
71
k(methanol)
k(solvent)
Solvent
+solvent
SN2+
8-39
88 The Solvent - SThe Solvent - SNN11 SN1 reactions involve creation and separation of
unlike charge in the transition state of the rate-determining step
Rate depends on the ability of the solvent to keep these charges separated and to solvate both the anion and the cation
Polar protic solvents (formic acid, water, methanol) are the most effective solvents for SN1 reactions
8-40
88 The Solvent - SThe Solvent - SNN11
water
80% water: 20% ethanol
40% water: 60% ethanolethanol
Solvent
solvolysis++
k(solvent)
k(ethanol)
1
100
14,000
100,000
CH3
CH3 CH3
CH3
CH3CCl ROH CH3COR HCl
8-41
88 Rearrangements in SRearrangements in SNN11 Rearrangements are common in SN1 reactions if
the initial carbocation can rearrange to a more stable one
2-Methoxy-2-phenylbutane2-Chloro-3-phenylbutane
++ CH3OH + Cl -
CH3OHCH3OH
HCl
OCH3
+
8-42
88 Rearrangements in SRearrangements in SNN11 Mechanism of a carbocation rearrangement
Cl ++ Cl
-
A 2° carbocation
+H +
H
A 3° benzylic carbocation
O-CH3
HOH
CH3
++ +
An oxonium ion
:
:
(1)
(2)
(3)
8-43
88 Summary of SSummary of SNN1 & S1 & SNN22Type of Alkyl Halide
CH3XMethyl
RCH2XPrimary
R2CHXSecondary
R3CXTertiary
SN2 SN1
Substitution at a stereocenter
SN2 is favored. SN1 does not occur. The methyl cationis so unstable, it is never observedin solution.
SN1 rarely occurs. Primary cations are so unstable, that they are rarely observed in solution.
SN1 is favored in protic solvents withpoor nucleophiles. Carbocation rearrangements may occur.
SN2 is favored in aproticsolvents with goodnucleophiles.
SN2 does not occur becauseof steric hindrance aroundthe reaction center.
SN1 is favored because of the ease of formation of tertiary carbocations.
Inversion of configuration.The nucleophile attacksthe stereocenter from theside opposite the leavinggroup.
Racemization is favored. The carbocationintermediate is planar, and attack of thenucleophile occurs with equalprobability from either side. There is often some net inversion of configuration.
SN2 is favored.
8-44
88 Neighboring GroupsNeighboring Groups In an SN1 reaction, departure of the leaving
group is not assisted by Nu In an SN2 reaction, departure of the leaving
group is assisted by Nu These two types are distinguished by their order
of reaction; SN2 reactions are 2nd order, and SN1 reactions are 1st order
But some reactions are 1st order and yet involve two successive SN2 reactions
8-45
88 Mustard GasesMustard Gases Mustard gases • contain either S-C-C-X or N-C-C-X
• what is unusual about the mustard gases is that they undergo hydrolysis so rapidly in water, a very poor nucleophile
ClS
Cl 2H2O HOS
OH 2HCl+ +
Bis(2-chloroethyl)sulfide(a sulfur mustard gas)
Bis(2-chloroethyl)methylamine(a nitrogen mustard gas)
ClS
Cl ClN
Cl
8-46
88 Mustard GasesMustard Gases• the reason is neighboring group participation by the
adjacent heteroatom
• proton transfer to solvent completes the reaction
:Cl-
+
+
ClS
ClA cyclic
sulfonium ion
an internal SN2 reaction
slow, ratedetermining
ClS
ClS
O-HH
ClS
O
H
H++
a secondSN2 reaction
fast +
:
:
:
8-47
88 SSNN1/S1/SNN2 Problems2 Problems Problem 1:Problem 1: predict the mechanism for this
reaction, and the stereochemistry of each product
Problem 2:Problem 2: predict the mechanism of this reaction
+ CH3OH/ H2O HClR enantiomer
Cl
+
OH
+
OCH3
+ +Na+CN- Na+Br -DMSOBr CN
8-48
88 SSNN1/S1/SNN2 Problems2 Problems Problem 3:Problem 3: predict the mechanism of this
reaction and the configuration of product
Problem 4:Problem 4: predict the mechanism of this reaction
+ +acetoneCH3S-Na+ Na+Br-
R enantiomer
Br SCH3
+acetic acidBr OCCH3CH3COH + HBr
O O
8-49
88 SSNN1/S1/SNN2 Problems2 Problems Problem 5:Problem 5: predict the mechanism of this
reaction
++
toluene(CH3 )3P P(CH3)3 Br-Br
8-50
88 Phase-Transfer CatalysisPhase-Transfer Catalysis A substance that transfers ions from an aqueous
phase to an organic phase An effective phase-transfer catalyst must have
sufficient• hydrophilic character to dissolve in water and form an
ion pair with the ion to be transported• hydrophobic character to dissolve in the organic
phase and transport the ion into it
The following salt is an effective phase-transfer catalysts for the transport of anions
(CH3CH2CH2CH2)4N+Cl-
Tetrabutylammonium chloride(Bu4N
+Cl- )
8-51
88 Phase-Transfer CatalysisPhase-Transfer Catalysis
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8-52
88 -Elimination-Elimination -Elimination:-Elimination: a reaction in which a small
molecule, such as HCl, HI, or HOH, is split out or eliminated from a larger molecule
C C
X
H
CH3CH2O-Na+
C C
CH3CH2OH
CH3CH2OH Na+X -
α +
+ +
A haloalkane Base
An alkene
8-53
88 -Elimination-Elimination Zaitsev rule:Zaitsev rule: the major product of a -elimination
is the more stable (the more highly substituted) alkene
2-Methyl-2-butene (major product)
CH3CH2O-Na+
CH3CH2OH 2-Bromo-2-methylbutane
2-Methyl-1-butene
Br+
+
1-Methyl-cyclopentene
(major product)
CH3O-Na+
CH3OH
1-Bromo-1-methyl-cyclopentane
Br
Methylene-cyclopentane
8-54
88 -Elimination-Elimination There are two limiting mechanisms for -
elimination reactions E1 mechanism:E1 mechanism: at one extreme, breaking of the R-X
bond is complete before reaction with base to break the C-H bond• only R-X is involved in the rate-determining step
E2 mechanism:E2 mechanism: at the other extreme, breaking of the R-X and C-H bonds is concerted• both R-X and base are involved in the rate-determining step
8-55
88 E1 MechanismE1 Mechanism• ionization of C-X gives a carbocation intermediate
• proton transfer from the carbocation intermediate to the base (in this case, the solvent) gives the alkene
CH3-C-CH3
Br
CH3
CH3-C-CH3
CH3
Br–
slow, ratedetermining
+(A carbocation intermediate)
+
O:
H
H3CH-CH2-C-CH3
CH3
O
H
H3CH CH2=C-CH3
CH3fast
+++ +
8-56
88 E1 MechanismE1 Mechanism
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8-57
88 E2 MechanismE2 Mechanism
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8-58
88 Kinetics of E1 and E2Kinetics of E1 and E2 E1 is a 1st order reaction; 1st order in RX and
zero order is base
E2 is a 2nd order reaction; 1st order in base and 1st order in RX
d[RX]
dt
Rate == k[RX]
d[RX]dt
Rate = = k[RX][Base]
8-59
88 Regioselectivity of E1/E2Regioselectivity of E1/E2 E1: major product is the more stable alkene E2: with strong base, the major product is the
more stable alkene• double bond character is highly developed in the
transition state• thus, the transition state of lowest energy is that
leading to the most stable (the most highly substituted) alkene
8-60
88 Stereoselectivity of E2Stereoselectivity of E2 E2 is most favorable (lowest activation energy)
when H and X are oriented anti and coplanar
CH3O:-
C C
H
X
CH3OH
C C
:X-
-H and -X are anti and coplanar(dihedral angle 180°)
8-61
88 Stereochemistry of E2Stereochemistry of E2 Consider E2 of these stereoisomers
+
3-Isopropyl-cyclohexene
1-Isopropyl-cyclohexene
(major product)
cis-1-Chloro-2-isopropyl-
cyclohexane
Cl
CH3O-Na+
CH3OH
CH3O-Na+
CH3OH
trans-1-Chloro-2-isopropyl-
cyclohexane
Cl3-Isopropyl-cyclohexene
8-62
88 Stereochemistry of E2Stereochemistry of E2• in the more stable chair of the cis isomer, the larger
isopropyl is equatorial and chlorine is axial
CH3O:-
H
H
H
H
Cl
CH3OH :Cl-
1-Isopropyl-cyclohexene
2
1
6 + +E2
8-63
88 Stereochemistry of E2Stereochemistry of E2• in the more stable chair of the trans isomer, there is
no H anti and coplanar with X, but there is one in the less stable chair
More stable chair (no H is anti and coplanar to Cl)
Less stable chair(H on carbon 6 is
anti and coplanar to Cl)
2
2
11
6 6Cl
H
H
H
H
Cl
HH
HH
8-64
88 Stereochemistry of E2Stereochemistry of E2• it is only the less stable chair conformation of this
isomer that can undergo an E2 reaction
H
Cl
HH
HCH3O:
-
CH3OH :Cl-
3-Isopropyl-cyclohexene
21
6E2
+ +
8-65
88 Stereochemistry of E2Stereochemistry of E2Problem:Problem: account for the fact that E2 reaction of the meso-dibromide gives only the E-alkene
meso-1,2-Dibromo-1,2-diphenylethane
(E)-1-Bromo-1,2-diphenylethylene
C C
Br H
C6H5C6H5
CH3O- Na+
CH3OHC6H5CH-CHC6H5
Br Br
8-66
88 Summary of E2 vs E1Summary of E2 vs E1
RCH2X
R2CHX
R3CX
Alkyl halide E1 E2
Primary
Secondary
Tertiary
E1 does not occur.Primary carbocations areso unstable, they are neverobserved in solution.
E2 is favored.
Main reaction with strong bases such as OH- and OR-.
Main reaction with weak bases such as H2O, ROH.
Main reaction with strong bases such as OH- and OR-.
Main reaction with weak bases such as H2O, ROH.
8-67
88 SSNN vs E vs E Many nucleophiles are also strong bases (OH-
and RO-) and SN and E reactions often compete
The ratio of SN/E products depends on the relative rates of the two reactions
nucleophilicsubstitution
-eliminationC CH X + Nu-
C CH Nu X-+
C C H-Nu+ X-+
8-68
88 SSNN vs E vs E
RCH2 X
CH3X
SN1 and E1 reactions of primary halides are never observed.
bases such as I- and CH3COO-.
SN2 SN1 reactions of methyl halides are never observed.The methyl cation is so unstable that it is never formed in solution.
SN2
E2 The main reaction with strong, bulky bases such as potassium tert-butoxide.
Primary cations are never formed in solution, and, therefore,
Halide Reaction Comments
Methyl
Primary The main reaction with good nucleophiles/weak
8-69
88 SSNN vs E (cont’d) vs E (cont’d)
The main reaction with bases/nucleophiles where the
R3 CX
pKa of the conjugate acid is 11 or less, as for exampleI- and CH3COO-.
R2 CHX
Main reaction with strong bases such as HO- and RO-.
Main reactions with poor nucleophiles/weak bases.
The main reaction with bases/nucleophiles where
E2
SN2
E2
SN2 reactions of tertiary halides are never observed
SN1/E1
Secondary
Tertiary
because of the extreme crowding around the 3° carbon.
SN1/E1 Common in reactions with weak nucleophiles in polarprotic solvents, such as water, methanol, and ethanol.
pKa of the conjugate acid is 11 or greater, as for exampleOH- and CH3CH2O
-.
8-70
88 Prob 8.9Prob 8.9 Draw a structural formula for the most stable
carbocation of each molecular formula.
(a) (b)
(c) (d)
C4H9+ C3H7
+
C3H7O+C8H15+
8-71
88 Prob 8.11Prob 8.11 From each pair, select the stronger nucleophile.
(a) (b)
(c)
or
or
orH2 O OH-
CH3SH CH3S-
CH3COO-
OH-
(d)
(f)
or
oror(e)
Cl-
I- in DMSO
CH3OCH3 CH3SCH3Cl-
I- in methanol
8-72
88 Prob 8.12Prob 8.12 Draw a structural formula for the product of each SN2
reaction.
acetone+
ethanol+
(b)
(a) CH3CH2 ONaCH3CH2 CH2Cl
(CH3 )3N CH3I
ethanol+
+ acetone
(d)
(c) CH2Br
H3C Cl
NaCN
CH3SNa
8-73
88 Prob 8.12 (cont’d)Prob 8.12 (cont’d)
+
+
(f)
(e)
ethanol
C-Li+
CH2Cl
CH3CH2 CH2Cl
NH3
CH3Cdiethylether
acetone+(h)
(g) +ethanol
NHO CH3(CH2)6 CH2Cl
CH3CH2 CH2Br NaCN
8-74
88 Prob 8.14Prob 8.14 Account for the fact that the rate of this reaction is 1000
times faster in DMSO than it is in ethanol.
2KCN 2KCl1,3-Dichloropropane
+ +Propanedinitrile
Cl Cl NC CN
8-75
88 Prob 8.15Prob 8.15 The following reaction involves two successive SN2
reactions. Propose a structural formula for the product.
A
+
1-Aminoadamantane Methyl 2,4-dibromobutanoate
NH2R3 N
C15H23NO2Br
Br
OCH3
O
8-76
88 Prob 8.16Prob 8.16 Which member of each pair shows the greater rate of SN2
reaction with KI in acetone?
(a) or
Cl
Cl
(b) or Br
Cl
(d)
(c) or
orBr
Br
ClCl
8-77
88 Prob 8.17Prob 8.17 Which member of each pair gives the greater rate of SN2
reaction with KN3 in acetone?
(a)Br
or
Br
(b)Br
or
Br
8-78
88 Prob 8.19Prob 8.19 Limiting yourself to a single 1,2-shift, suggest a
structural formula for a more stable carbocation.
(a)
(c)
(b)
(d)
(f)(e)
+ +
+O
++
8-79
88 Prob 8.21Prob 8.21 Draw a structural formula for the product of each SN1
reaction.
CH3CH2 OH
ClCH3OH(b)
(a)
+ methanol
ethanol
Cl+
S enantiomer
(d) methanol+
acetic acid(c) CH3COH
CH3OHBr
OCl +
8-80
88 Prob 8.24Prob 8.24 From each pair, select the compound that undergoes SN1
solvolysis in ethanol more rapidly.
(a) or or(b)Cl Cl Cl Br
(d)or(c) orClCl ClCl
(f) oror(e)Br Br
ClCl
8-81
88 Prob 8.25Prob 8.25 Account for the following relative rates on solvolysis
under SN1 conditions.
Relative rate ofsolvolysis (SN1) 10.2 109
ClOCl O Cl
8-82
88 Prob 8.26Prob 8.26 Explain why the following compound is very unreactive
under SN1 conditions.
1-Iodobicyclo[2.2.2]octane
I
8-83
88 Prob 8.27Prob 8.27 Propose a synthesis for each compound from a
haloalkane and a nucleophile.
(b) (c)(a) CNO
OCN
(d) SH
(f)
(e)
O (g)SH
8-84
88 Prob 8.29Prob 8.29 Propose a mechanism for the formation of each product.
CH3CH=CHCH2ClH2O
CH3CH=CHCH2OH + CH3CHCH=CH2
OH1-Chloro-2-butene
2-Buten-1-ol 3-Buten-2-ol
8-85
88 Prob 8.30Prob 8.30 Propose a mechanism for the formation of this product.
If the configuration of the starting material is S, what is the configuration of the product?
NCl
NOH
H2O
NaOH
8-86
88 Prob 8.31Prob 8.31 Propose a mechanism for the formation of the products
of this solvolysis reaction.
BrCH3CH2OH
warm
+OCH2CH3 + HBr
8-87
88 Prob 8.32Prob 8.32 Propose a mechanism for the formation of each product.
OSO2Ar
CH3COHH
H
H
H
+
OCCH3O
O
8-88
88 Prob 8.33Prob 8.33 Which compound in each set undergoes more rapid
solvolysis when refluxed in ethanol?Br Br
or(a)
or(b) BrCl
BrBr
or(c)
ClClor(d)
8-89
88 Prob 8.34Prob 8.34 Account for these relative rates of solvolysis in acetic
acid.
(CH3)3CBr
Br Br Br
1 10-2 10-7 10-12
8-90
88 Prob 8.35Prob 8.35 On SN1 solvolysis in acetic acid, (1) reacts 1011 times
faster than (2). Furthermore, solvolysis of (1) occurs with complete retention of configuration. Draw structural formulas for the products of each solvolysis and account for the difference in rates.
OSO2Ar OSO2Ar
(1) (2)
8-91
88 Prob 8.36Prob 8.36 Draw structural formulas for the alkene(s) formed on
treatment of each compound with sodium ethoxide in ethanol. Assume reaction by an E2 mechanism.
(c)(b)
(d)
(a) ClCl
Cl
Br
(f)(e) ClBr
8-92
88 Prob 8.37Prob 8.37 Draw structural for all chloroalkanes that undergo
dehydrohalogenation when treated with KOH to give each alkene as the major product.
(c)(b)(a)
(e)(d)
8-93
88 Prob 8.38Prob 8.38 On treatment with sodium ethoxide in ethanol, each
compound gives 3,4-dimethyl-3-hexene. One compound gives an E alkene, the other gives a Z alkene. Which compound gives which alkene?
C CEt Et
MeBr
MeH
(A)
C CEt Et
MeBr
HMe
(B)
8-94
88 Prob 8.39Prob 8.39 On treatment with sodium ethoxide in ethanol, this
compound gives a single stereoisomer. Predict whether the alkene has the E or Z configuration.
H3C
BrH C6H5
H C6H5 CH3CH2O-Na+
CH3CH2OHC6H5CH=CC6H5
CH3
1-Bromo-1,2-diphenylpropane
1,2-Diphenylpropene
8-95
88 Prob 8.40Prob 8.40 Elimination of HBr from 2-bromonorbornane gives only
2-norbornene. Account for the regiospecificity of this elimination reaction.
2-Bromonorbornane 2-Norbornene 1-Norbornene
H
H
H
H
HBr
HH H
H
H
8-96
88 Prob 8.43Prob 8.43 Arrange these haloalkanes in order of increasing ratio of
E2 to SN2 products on reaction of each with sodium ethoxide in ethanol.
(c)
(a)
CH3CCH2 CH3
CH3CH2Br
CH3CHCH2CH2Br(d)
CH3CHCH2Br(b)
CH3
Cl
CH3 CH3
8-97
88 Prob 8.44Prob 8.44 Draw a structural formula for the major product of each
reaction and specify the most likely mechanism for its formation.
80°(b) +
+ methanol(a)
CH3CCH2 CH3 NaOHH2 O
CH3OH
Cl
CH3
Br
(c) +DMSO
Cl
(R)-CH3CHCH2CH3 CH3CO-Na
+O
8-98
88 Prob 8.44 (cont’d)Prob 8.44 (cont’d)
(d)
(e)
+ methanol
R enantiomer
+ acetone
Cl
Cl
CH3O-Na
+
NaI
+(f)
(g) + ethanol
R enantiomer
Cl O
CH3CHCH2CH3
CH3CH2 ONa
HCOH
CH2=CHCH2Cl
formic acid
8-99
88 Prob 8.45Prob 8.45 Propose a mechanism for the formation of each product.
(3)(2)
(1)
+
OH
Cl
Cl
OH
OH
OH
OH
O
NaOH
CH3CH2 OH
NaOH
CH3CH2 OH
the transisomer
the cisisomer
8-100
88 Prob 8.46Prob 8.46 Show how to bring about each conversion.
(a) (b)Cl Br
Cl OH(c) (d) Br
OH
(e) (f)Br Br
BrBr
OH
OH
8-101
88 Prob 8.46 (cont’d)Prob 8.46 (cont’d) Show how to bring about each conversion.
(g) (h)Br
Br
OH
OH(i)
8-102
88 Prob 8.47Prob 8.47 Which reaction gives the tert-butyl ether in good yield?
What is the product of the other reaction?CH3
CH3
CH3CO- K
+
CH2O-K+
CH2Cl
CH3
CH3
CH3CCl
CH3
CH3
CH3COCH2
CH3
CH3
CH3COCH2 + KCl(a) +
(b) +
DMSO
DMSO + KCl
8-103
88 Prob 8.48Prob 8.48 Each ether can, in principle, by synthesized by a
Williamson ether synthesis forming bond (1) or bond (2). Which combination gives the better yield?
(2)
(2)(1)
(a) (b)
(c)
(1)
(1) (2)O-CH2 CH3
CH3 O-CCH3
CH3
CH3
CH3
CH3
CH2=CHCH2-O-CH2CCH3
8-104
88 Prob 8.49Prob 8.49 Propose a mechanism for this reaction.
ClCH2CH2OHNa2CO3, H2O
H2C CH2
O
8-105
88 Prob 8.50Prob 8.50 Each compound can be synthesized by an SN2 reaction.
Propose a combination of haloalkane and nucleophile that will give each product.
CH3OCH3(a) (b)CH3SH
CH3CH2CH2PH2(c) (d)CH3CH2CN
CH3SCH2C(CH3)3(e) (f)(CH3)3NH+ Cl -
8-106
88 Prob 8.50 (cont’d)Prob 8.50 (cont’d)
C6H5COCH2C6H5(g) (h)(R)-CH3CHCH2CH2CH3
O N3
CH2=CHCH2OCH(CH3)2(i) (j)CH2=CHCH2OCH2CH=CH2
(k) (l)N O O
H
H
Cl -
8-107
88
Nucleophilic Nucleophilic Substitution Substitution
and and -Elimination-Elimination
End Chapter 8End Chapter 8
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