6.

1 Writer the following as net ionic reactions and designate the nucleophile, substrate, and leaving
group in each reaction.
(a) CH3I+CH3CH2ONa
(b) NaI+CH3CH2Br

CH3OCH2CH3+NaI
CH3CH2I+NaBr

(c) 2CH3OH+CH33CCl

CH33COCH3+CH3OH2++Cl-

(d) CH3CH2CH2Br+NaCN

CH3CH2CH2CN+NaBr

(e) C6H5CH2Br+2NH3

C6H5CH2NH2+NH4Br

ANSWER
aCH3I+CH3CH2O-

CH3OCH2CH3+I-

nucleophileCH3CH2OsubstrateCH3I
leaving groupIbI-+CH3CH2Br

CH3CH2I+Br-

nucleophile IsubstrateCH3CH2Br
leaving groupBrCH33COCH3+CH3OH2++Cl-

c2CH3OH+CH33CCl
nucleophileCH3OH
substrate CH33CCl
leaving groupCldCH3CH2CH2Br+CN-

CH3CH2CH2CN+Br-

nucleophile CNsubstrate CH3CH2CH2Br

leaving groupBrC6H5CH2NH2+NH4++Br-

eC6H5CH2Br+2NH3
nucleophile NH2substrate C6H5CH2Br
leaving groupBr-

6.2 Use chair conformational structures (Sect.4.12) and show the nucleophilic substitution reaction that
would take place when trans-1-bromo-4-tert-butylcyclohexane reacts with iodide ion. (Show the most
stable conformation of the reactant and the product.)

Answer:
I
Br

C(CH3)3

I
C(CH3)3

6.3 SN2 reactions that involve breaking a bond to a stereocenter can be used to relate configurations of
molecules because the stereochemistry of the reaction is known,
(a) Illustrate how this is true by assigning configurations to the 2-chloro-butane enantiomers based on
the following date. [The configuration of (--)-2-butanol is given in Section 5.7C.]

OH-

(+)-2-Chlorobutane

(-)-2-Butanol

S N2

[ ]D25 = +36.000

[ ]D25 = -13.520

Enantiomerically pure

Enantiomerically pure

(b) When optically pure (+)-2-chlorobutane is allowed to react with potassium iodide in acetone in an
SN2 reaction, the 2-iodobutane that is produced has a minus rotation. What is the configuration of
(--)-2-iodobutane? Of (+)-2-iodobutane?
Answer,
(a)
Et

Et
C

HO

OH

H
Me

H
Me

An inversion of configuration
(b)
CH3

CH3
I

CH2CH3
R-(-)-2-iodobutane

CH2CH3
S-(+)-2-iodobutane

6.4 Keep in mind that carbocations have a trigonal planar structure, (a) write a structure for the
carbocation intermediate and (b) write structures for the alcohol (or alcohols) that you would expect
from the following reaction:
I

C(H3C)3

CH3

Answer:
(a) Structure of the carbocation intermediate:

(b) Structures of the alcohols would be:

H2 O
SN1

CH3

C(H3C)3

OH
OH

C(H3C)3

CH3

6.5 What product(s) would you expect from the methanolysis of the cyclohexane derivative given as
the reaction in Problem 6.4?
I

CH3

(H3C)3C

Answer:
CH3

OCH3

CH3

(H3C)3C

The product is
following:

the reaction is as
CH3

OCH3
CH3

(H3C)3C

OCH3

(H3C)3C

CH3OH

CH3

(H3C)3C

OCH3

(H3C)3C

6.6 The relative rates of ethanolysis of four primary alkyl halides are as follows: CH3CH2Br, 1.0;
CH3CH2CH2Br, 0.28; (CH3)2CHCH2Br, 0.030; (CH3)3CCH2Br, 0.00000042.
(a). Are each of these reactions likely to be SN1 or SN2?
(b) Provide an explanation for the relative reactivities that are observed.
Answer:
(a) All the reactions are likely to be SN2.
(b) For particles (molecules and ions) to react, their reactive centers must be able to come within
bonding distance of each other. Large and bulky groups can often hinder the formation of the
required transition state. So the relative rates of the above alkyl halides are from high to low.
O

6.7 Classify the following solvents as being protic or aprotic: formic acid, H
O
H3C

CH3 ;acetonitrile, H3C

N ; formamide, H

OH; acetone,

O
C

NH2 ; sulfur

CH3

dioxide, SO2 ;
HOCH2CH2OH.

NH3 ; trimethylamine, H3C

ammonia,

CH3 ;

ethylene glycol,

Answer:
O

Protic: H

OH, H

NH2, NH3, HOCH2CH2OH.

Aptotic: H3C

CH3

CH3, H3C

N, H3C

CH3, SO2.

6.8 Would you expect the reaction of propyl bromide with sodium cyanide (NaCN), that is,
CH3CH2CH2Br + NaBr
CH3CH2CH2CN + NaBr
to occur faster in DMF or in ethanol? Explain you answer.
O
CH3

C
N

CH3

DMF
Answer: The reaction occurs faster in DMF than in ethanol. Because it dont solvate anions to any
appreciable extent. These naked anions are highly reactive both as base and nucleophiles. This is the
opposite of their strength as nucleophiles in alcohol or water solutions.
The rates of SN2 reactions generally are vastly increased when they are carried out in polar
aprotic solvents. The increase in rate can be as large as a millionfold.
6.9 Which would you expect to be the stronger nucleophile in a protic solvent:
(a). CH3CO2- or CH3O-?
CH3O- is the stronger nucleophile.
(b). H2O or H2S?
H2S is the stronger nucleophile.
(c). (CH3)3P or (CH3)3N?
(CH3)3P is the stronger nucleophile in a protic solvent.

6.10 When tert-butyl bromide undergoes solvolysis in a mixture of methanol and water, the rate of
solvoysis (measured by the rate at which bromide ions from in the mixture) increases when the
percentage of water in the water increased.
(a) Explain this occurrence.
(b) Provide an explanation for the observation that the rate of the SN2 reaction of ethyl chloride
with potassium iodide in methanol and water decreases when the percentage of water in the
mixture is increased.

Answer:
(a) Because water is the most effective solvent for promoting ionization. It made the intermediate
more stable.
(b) Because the charge of the transition state is more dispersed than the charge in the starting
material. Increasing the polarity of the solvent will increase the stability of the starting
material. Therefore, it will decrease the rate of the reaction.

6.12 Starting with (S)-2-bromobutane, outline syntheses of each of the following compounds.
(b) (R)- CH3CHCH2CH3

(a) (R)- CH3CHCH2CH3

OCCH3

OCH2CH3

O
(c) (R)- CH3CHCH2CH3

(d) (R)- CH3CHCH2CH3

SCH3

SH

Answer:
CH3

CH3
H
(a)

Br

H3CH2CO

CH3CH2O

CH3
(b)

O
Br

CH3CO

Br

Br

CH3

H3CCO

H
CH3

CH3

CH3

CH3
H

Br

(c)
H

HS

HS

H
CH3

CH3

CH3

CH3
(d)

Br

CH3

CH3

Br

H
CH3

CH3S

H3CS

H
CH3

Br

6.13 Show how you might use a nucleophilic substitution reaction of propyl bromide to synthesize
each of the following compounds. (You may use any other compounds that are necessary.)
(a) CH3CH2CH2OH
(b) CH3CH2CH2I
(c) CH3CH2OCH2CH2CH3
(d) CH3CH2CH2SCH3
(e) CH3COOCH2CH2CH3
(f) CH3CH2CH2N3
CH3

(g) H3C

CH2CH2CH3 Br

CH3

(g) CH3CH2CH2CN
(h) CH3CH2CH2SH
Answers:

(a) OH + CH3CH2CH2

(b) I + CH3 CH2CH2

CH3CH2CH2OH + Br

Br

Br

CH3CH2CH2I + Br

(c) CH3CH2O + CH3CH2CH2

(d) CH3S + CH3CH2CH2

Br

Br

CH3CH2CH2SCH3 + Br

(e) CH3CO

CH3CH2OCH2CH2CH3 + Br

+ CH3CH2 CH2

Br

CH3COCH2 CH2CH3 + Br

(f) N3 + CH3CH2CH2

Br

(g) (CH3)3N + CH3CH2CH2

CH3CH2CH2N3 + Br

Br

(CH3)3NCH2CH2CH2 Br

(h) CN + CH3CH2 CH2

Br

CH3CH2CH2CN + Br

(i) SH + CH3CH2CH2

Br

CH3CH2 CH2 SH + Br

6.14 Which alkyl halide would you expect to react more rapidly by an SN2 mechanism? Explain your
answer.
(a) CH3CH2CH2Br or (CH3)2CHBr
(b) CH3CH2CH2CH2Cl or CH3CH2CH2CH2I
(c) (CH3)2CHCH2Cl or CH3CH2CH2CH2Cl
(d) (CH3)2CHCH2CH2Cl or CH3CH2CH(CH3)CH2Cl
(e) C6H5Br or CH3CH2CH2CH2CH2CH2Cl
Answer:
(a) 1-Bromopropane. Because it is less hindered.
(b) 1-Iodobutane. Because I- is a good leaving group.
(c) 1-Chlorobutane. Because it is less hindered.
(d) 1-Chloro-3-methylbutane. Because the carbon bearing the leaving group is less hindered than in
1-Chloro-2-methylbutane.
(e) 1-chlorohexane. Phenyl halides are unreactive in SN2.
6.15 Which SN 2 reaction of each pair would you expect to take place more rapidly
in a protic solvent?

(a) (1) CH3CH2 CH2 Cl + CH3 CH2 O(2) CH3CH2CH2Cl + CH3CH2OH

CH3CH2CH2OCH2CH3 + ClCH3CH2CH2 OCH2CH3 + HCl

(b) (1) CH3CH2CH2Cl + CH3CH2O-

CH3CH2 CH2 OCH2CH3 + Cl-

(2) CH3CH2 CH2 Cl + CH3 CH2 S-

CH3CH2 CH2 SCH2CH3 + Cl-

(c) (1) CH3CH2CH2Br + (C6H5)3N

CH3 CH2 CH2N(C6H5)3+ + Br-

(2) CH3CH2CH2Br + (C6H5)3P

CH3 CH2 CH2P(C6H5)3+ + Br-

(d) (1) CH3CH2CH2Br (1.0M) + CH3O- (1.0M)

CH3CH2CH2 OCH3 + Br-

(2) CH3CH2 CH2 Br (1.0M) + CH3O- (2.0M)

CH3CH2 CH2 OCH3 + Br-

Answer:
(a) (1) ,(b) (2) ,(c) (2) ,(d) (2) are expected to take place more rapidly in a protic solvent in
each pair.
6.16 Which SN1 reaction of each pair would you expect to take place more rapidly? Explain your
answer.
(a)

(1)(CH3)3CCl +H2O
(2)(CH3)3CBr + H2O

(CH3)3COH + HCl
(CH3)3COH + HBr

(1)(CH3)3CCl +H2O
(2)(CH3)3CBr + CH3OH

(CH3)3COH + HCl
(CH3)3COH + HBr

(b)

(C)

(1) (CH3 )3CCl (1.0M) + CH3 CH2O- (1.0M)

(CH3)3COCH2CH3 + Cl-

(2)(CH3)3 CCl (2.0M) + CH3CH2O- (1.0M)

(CH3)3COCH2 CH3 + Cl-

(1) (CH3 )3CCl (1.0M) + CH3 CH2O- (1.0M)

(CH3)3COCH2CH3 + Cl-

(2)(CH3)3 CCl (1.0M) + CH3CH2O- (2.0M)

(CH3)3COCH2 CH3 + Cl-

(d)

(e)

(1)(CH3)3CCl +H2O
(2)C6H5Cl + H2O

(CH3)3COH + HCl
C6H5 OH + HCl

Answer:
(a) Reaction2 will be more rapidly. Because bromide ion is better leaving group than chloride ion
(b) Reaction1 will be more rapidly. Because H2O and ethanol are both solvent and nucleophile, and the
water is stranger polar protic solvent than ethanol.
(c) Reaction2 will be more rapidly. Because the substrate has bigger concentration.
(d) The two reactions have same reaction rate. Because the Nu has no effect on the reaction.
(e) Reaction1 will be more rapidly. Because (CH3)3C+ is more stable.

6.17 With methyl, ethyl, or cyclopentyl halides as your organic starting materials and using any needed
solvents or inorganic reagents, outline syntheses of each of the following. More than one step may be
necessary and you need not repeat steps carried out in earlier parts of this problem.
(a) CH3I

(b) CH3CH2I

(c) CH3OH

CH3CN (h) CH3CH2CN (i) CH3OCH3

(d) CH3CH2OH

(e) CH3SH

(f) CH3CH2SH (g)

(j) CH3OCH2CH3 (k) Cyclopentene

Answer:
(a) CH3I

CH3Br

I-

CH3I

Br-

(b) CH3CH2I

CH3CH2 Br

I-

CH3CH2I

Br-

(c) CH3OH

CH3I + OH-

CH3 OH

+ I-

(d) CH3CH2OH

+ I-

CH3CH2OH

CH3CH2I + OH(e) CH3SH

CH3I + SH-

CH3 SH

CH3OH

+ I-

(f) CH3CH2SH

CH3 CH2 I + SH-

CH3 CH2 SH

CH3OH

+ I-

(g) CH3CN

CH3 I + CN-

CH3 CN

CH3OH

+ I-

(h) CH3CH2CN

CH3CH2I + CN(i)

CH3OH

+ I-

CH3OCH3

2 CH3ONa +H2

2 CH3OH + 2 Na
CH3I
(j)

CH3 CH2 CN

CH3

O-

50o C
CH3OH

CH3OCH3 +I-

CH3OCH2CH3

CH3CH2I +CH3O-

50oC
CH3 OH

CH3CH2OCH3 +I-

(k) Cyclopentene

CH3CH2ONa
CH3CH2 OH

NaI

CH3CH2OH

6.18 Listed below are several hypothetical nucleophilic substitution reactions. None is synthetically
useful because the product indicated is not formed at an appreciable rate. In each case provide an
explanation for the failure of the reaction to take place as indicated.
(a)

CH3CH2CH3+OH-

CH3CH2OH+CH3

(b) CH3CH2CH3+OH-

CH3CH2 CH2OH+ H-

+ OH-

(c)

CH2CH3CH2 CH2OH

Br

CN

+CN-

(d)
(e) NH3+CH3OCH3
(f) NH3+CH3O

H2+

+BrCH3NH2+CH3OH
CH3NH3++H2O

Answer
(a) Alkanide ion (CH3-) is very powerful base and its virtually never acting as leaving groups.
Therefore, reaction (a) is not feasible.
(b) Hydride ion (H:-) is very powerful base and its virtually never acting as leaving groups. Therefore,
reaction (b) is not feasible.
(c) Alkanide ion (R:-) is very powerful base and its virtually never acting as leaving groups.
Therefore, reaction (c) is not feasible.
(d) Tertiary alkyl bromide cant be the substrate for the SN2 reaction.
(e) CH3O- is a strongly basic ion and rarely acts as leaving group. Therefore, reaction e is not feasible.
(f) CH3O H2+ only appear in a strong acid and NH3 cant exist in a strong acid.
6.19 You have the task of preparing styrene (C6H5CH=CH2) by dehydrohalogenation of either
1-bromo-2-phenylethane or 1-bromo-1-phenylethane use KOH in ethanol. Which halide would you
choose as your starting material to give the better yield of the alkene? Explain your answer.
Answers:
1-Bromo-1-phenylethane will be used as the starting material, because a 1 alkyl bromide gives
mainly SN2 except with a hindered strong base and then gives mainly E2. A 2 alkyl bromide gives
mainly E2 with strong bases.
6.20 Your task is to prepare isopropyl methyl ether. CH3OCH(CH3)2, by one of the following reactions.
Which reaction would give the better yield? Explain your choice.
(1)

CH3ONa + (CH3)2CHI

(2)

(CH3)2CHONa + CH3I

CH3OCH (CH3)2
CH3OCH (CH3)2

Answer: The second reaction would give the better yield because the desired reaction is an SN2
reaction, and the substrate is a methyl halide. Use of reaction (1) would result in considerable
elimination by an E2 pathway.
6.21 Which product (or products) would you expect to obtain from each of the following reactions? In
each part give the mechanism (SN1, SN2, E1, or E2) by which each product is formed and predict the
relative amount of each product (i.e., would the product be the only product, the major product, a minor

product, etc.?)
SN2

(a)

major product
50 C
CH3CH2OH

CH3CH2 CH2 CH(OCH2 CH3 )CH3 + Br-

50 C
CH3CH2OH

CH3CH2CH2CH=CH2

50 C
CH3CH2CH2CH2 CH2 Br + (CH3)3 CO- (CH ) COH
3 3

CH3CH2CH2CH=CH2

CH3CH2 CH2 CH2CH2Br + CH3CH2Ominor product

CH3CH2 CH2 CH2CH2Br + CH3CH2O(b)

E2

major product

minor product
CH3CH2 CH2 CH2CH2Br + (CH3)3CO-

(c)

50 C
(CH3)3 COH

CH3CH2CH2CH2CH2OC(CH3)3 + Br-

E2

the only product

(CH3)3CBr + CH3O-

50C
CH3OH

H3C

CH2

CH3

(d)

E1

the only product

(CH3)3CBr + (CH3)3CO-

50C
(CH3 )3COH

H3C

C
CH3

CH2

(e)

SN 2

the only product

Cl

(f)

50C
acetone

+ I-

(H3 C)3C

S N1

(H3C)3C

the only product

Cl

50C
CH3OH

CH3

(H3C)3C

(g)

CH3
(H3C)3 C

OCH3
CH3 + (H3C)3C
OCH3

E1

3-Chloropentane + CH3O-

50C
CH3OH

CH3CH2CH=CHCH3

3-Chloropentane + CH3O-

50C
CH3 OH

CH3CH(OCH3 )CH2CH2CH3 + Cl-

(h)

SN 1

3-Chloropentane + CH3CO2-

3-Chloropentane + CH3CO2 -

(i)

50C
CH3CO2H
50C
CH3CO2H

CH3CH2CH(O2 CCH3 )CH2CH3 + Cl-

CH3CH=CHCH2CH3

E2

major product
HO- + (R)-2-bromobutane

25C

+ H2O + Br

minor product
HO- + (R)-2-bromobutane

25C

OH

SN1

(j)

CH3

25 C

(S)-3-Bromo-3-methylhexane

H3CH2C

CH2CH2CH3

CH3OH
OCH3

(k)

(+)-

SN 2
50C

(S)-2-Bromooctane + I-

(R)-2-Iodooctane + Br-

CH3OH
6.22

Write conformational structures for the substitution products of the following

deuterium-labeled compounds:
(a)
Cl

I-

H
D

CH3 OH

(b)

Cl

ICH3OH

(c)
Cl
H

ICH3OH

(d)
Cl

CH3

The answer:

H2O
CH3OH

(a)
Cl
D

I-

H +

H
D

CH3OH

Cl-

H
I

(b)
Cl

I-

+ Cl

CH3OH
H

(c)
H

Cl
H

I
CH3 OH

Cl-

D
D

(d)
Cl

CH3

CH3

CH3

H 2O
CH3OH

OCH3

OH

OH
OCH3
H

CH3

CH3

+
D

6.23 Although ethyl bromide and isobutyl bromide are both primary halides. Ethyl bromide undergoes
SN2 reactions more than 10 times faster than isobutyl bromide does. When each compound is treated
with a strong base/ nucleophile (CH3CH2O-), isobutyl bromide gives a greater yield of elimination
products than substitution products, whereas with ethyl bromide this behavior is reversed. What factor
account for these results?
Answer: The reason ethyl bromide undergoes SN2 reactions faster than isobutyl bromide is
steric effect.
This steric hindrance causes isopropyl bromide to react more slowly in SN2 reactions and to
give relatively more elimination (by an E2) when a strong base is used.
6.24 Consider the reaction of I- with CH3CH2Cl. (a) Would you expect the reaction to be SN1 or SN2?

The rate constant for the reaction at 60C is 5*10-5L mol-1 s-1 . What is the reaction rate if [I-]=0.1mol
L-1 and [CH3CH2Cl]=0.1 mol L-1? (c) If

[I-]=0.1mol L-1 and

[CH3CH2Cl]=0.2mol L-1? (d) If

[I-]=0.2mol L-1 and [CH3CH2Cl]=0.1 mol L-1? (e) If [I-]=0.2mol L-1 and [CH3CH2Cl]=0.2 mol L-1?
Answer: Because the substrate is the primary alkyl halide, the reaction would be SN2.
V=k*[I-][CH3CH2Cl]
(b) v =5*10-5*0.1*0.1=5*10-7
(c) v =5*10-5*0.1*0.2=1*10-6
(d) v =5*10-5*0.2*0.1=1*10-6
(e) v =5*10-5*0.2*0.2=2*10-6
6.25 Which reagent in each pair listed here would be the more reactive nucleophile in a protic solvent?
(a) CH3NH- or CH3NH2
O

(e) H2O or H3O+

(b) CH3O- or CH3CO

(f) NH3 or NH4

(g) H2S or HSO

(c) CH3SH or CH3OH

(h) CH3CO or OH-

(d) (C6H5) 3N or (C6H5) 3P

Answer:
(a) CH3NH-

(b) CH3O-

(c) CH3SH

(d) (C6H5) 3P

(e) H2O

(f) NH3

(h) OH-

(g) HS

6.26 write mechanisms that account for the products of the following reaction
(a)

_
HOCH2CH2 Br

OH
H2O

(b)

_
OH
H2NCH2CH2CH2CH2Br
H2 O
N
H

ANSWER:
(a)

OHO

O
H

Br

Br

(b)
Br
H2N

N
H

OH-

6.27 Many SN2 reactions of alkyl chlorides and alkyl bromides are catalyzed by the addition of sodium
or potassium iodide. For example, the hydrolysis of methyl bromide takes place much faster in the
presence of sodium iodide. Explain.
Answer: Because Alkyl chlorides and bromides are also easily converted to alkyl iodides by
nucleophilic substitution reactions.
RCl- + I-

RI +Cl-

RBr + I-

RI + Br-

The effect of the leaving group in SN2 reaction:

RI> RBr> RCl> RF
That is why many SN2 reactions of alkyl chlorides and alkyl bromides are catalyzed by the addition of
sodium or potassium iodide take place much faster in the presence of sodium iodide.
Iodide ion is a good nucleophile and a good leaving group.
6.28 Explain the following observations: When tert-butyl bromide is treated with sodium methoxide in
a mixture of methanol and water, the rate of formation of tert-butyl alcohol and tert-butyl methyl ether
does not change appreciably as the concentration of sodium methoxide is increased. However,
increasing the concentration of sodium methoxide causes a marked increase in the rate at which
tert-butyl bromide disappears from the mixture.

Answer:
tert-Butyl alcohol and tert-butyl methyl ether are formed via an SN1 mechanism. The rate of the

reaction is independent of the concentration of methoxide ion. However, A cpompetetion reaction of

this reaction is the E2 elimination reaction that is associated with the concentration of the methoxide
ion. This mechanism will cause the disappearance of the tert-butyl bromide.
The mechanism is as follows:

CH3

O-

CH3

Br

CH3

CH3OH + CH2

C(CH3)2 + Br-

6.29 (a) Consider the general problem of converting a tertiary alkyl halide to an alkene, for example,
the conversion of tert-butyl chloride to 2-methylpropene. What experimental conditions would you
choose to ensure that elimination is favored over substitution?
(b) Consider the opposite problem, that of carrying out a substitution reaction on a tertiary alkyl halide.
Use as your example the conversion of tert-butyl chloride to tert-butyl ethyl ether. What experimental
conditions would you employ to ensure the highest possible yield of the ether?
Answer:
(a.) It is hard to influence the relative partition between SN1 and E1 products, E2 reaction should be
chosen to ensure that elimination is favored, because SN2 reaction is hard to take place as the
result of the steric hindrance. So high temperature, bulky strong base are required. In the
conversion of tert-butyl chloride to 2-methylpropene, a base of C2H5ONa solved in C2H5OH and
a high temperature should be offered.
(b.) Because of the steric hindrance, SN2 reaction couldnt take place, so the only way to ensure the
substitution is to ensure the SN1 reaction. We should use a neutral nucleophile at low temperature.
For example, when (CH3)3CCl and C2H5OH are mixed at a low temperature, they can produce
C(CH3)3OC2H5.

6.30 1-Bromobicyclo[2,2,1]heptane is extremely unreactive in either SN2 or SN1 reactions. Provide

explanations for this behavior.
Answer: 1-Bromobicyclo[2,2,1]heptane

Br

First it is one kind of bicycloalkane, so the ring strain in structure baffles the nucleophile attacking to
the substrate from back. So it is unreactive in SN2. Second, it is hard for the bridge carbon atom
forming carbocation, because the sp2 hybridization should be in one plane. So it is unreactive in SN1.

6.32 Starting with an appropriate alkyl halide, and using any other needed reagents, outline syntheses
of each of the following. When alternative possibilities exist for a synthesis you should be careful to
choose the one that gives the better yield
(a) Butyl sec-butyl ether
(b)

CH3CH2SC(CH3)

(c) Methyl neopentyl ether

(g) (S)-2-Pentanol
(h) (R)-2-Iodo-4-methylpentane
(i) (CH3)3CCHCH2

(d) Methyl phenyl ether

(j) cis-4-Isopropylcyclohexanol

(e) C6H5CH2CN

(k) (R)-CH3CH(CN)CH2CH3

(f) CH3CO2CH2CN
Answer:

(l) trans-1-Iodo-4-methylcyclohexane

(a)

OH

NaOH
Cl

Butyl sec-butyl ether

(b)

Cl

(c)

(d)

O
+

(e)

Cl

CN-

CN

(f)
O

Cl

+
ONa

(g)

OH
+

NaOH

NaCl

Cl

(h)

(i)

Br

Cl

I-

CH3CH2ONa

I
+

Br-

(j)

HO

+ OH-

Cl-

cis-4-Isopropylcyclohexanol

Br

(k)

CN

Br

CN-

Cl-

(R)-CH3 CH(CN)CH2CH3

(l)

I-

trans-1-Iodo-4-methylcyclohexane
Br

--

6.33 Give structures for the products of each of the following reactions:
(a)
H

NaI(1mol)

acetone

C5H8FI

NaBr

Br

acetone
(b) 1,4-Dichlorohexane(1mol) + NaI(1 mol)

C6H12ClI +NaCl

(C) 1,2-Dibromoethane(1mol) + NaSCH2CH2SNa

- H2
Et2O

(d)

4-Chloro-1-butanol +NaH

(e)

- NH3
CH 3I
liq.NH
3 C3H3Na
Propyne + NaNH3

C4H8S2 +2NaBr

heat
Et2O

C4H8ClONa

C4H6 + NaI

Answers:
(a) C5H8FI
I

C4H8O + NaCl

Br-

(b) C6H12ClI

Cl
I

4-Chloro-1-iodo-hexane
(c) C4H8S2
S

(d) C4H8ClONa

O-Na+
Cl
C4H8O

(e) C3H3Na

H3C

CNa

C4H6

H3C

CH3

6.34 When tert-butyl bromide undergoes SN1 hydrolysis, adding a common ion(e.g.,NaBr) to the
aqueous solution has no effect on the rate. On the other hand, when (C6H5)2CHBr undergoes SN1
hydrolysis, adding NaBr retards the reaction .Given that the (C6H5CH)2CH+ cation is known to be
much more stable than the (CH3)3C+ cation (and we shall see why in section 15.12A), provide an
explanation for the different behavior of the two compounds.
Answer:

Br-

Br

H 2O

Ph

Ph

Br
Ph

OH

Br-

Ph
Ph

H2O

OH
Ph

The rate determining step of the SN1 reaction is the formation of the carbocation, in the hydrolysis
of tert-butyl bromide, the carbocation intermediate is relative unstable comparing with the
diphenyl methyl cation. Which means that diphenyl methyl cation could combine with the
bromine anion, a reversible reaction takes place easier than the first reaction. Therefore, increasing
the concentration of bromine anion will increase the reaction speed of the reverse one, and retard
the hydrolysis reaction.

6.35 When the alkyl bromides ( listed here ) were subjected to hydrolysis in a mixture of ethanol and
water ( 80% C2H5OH/ 20% H2O ) at 55, the rates of the reaction showed the following order:
(CH3)3CBrCH3BrCH3CH2Br(CH3)2CHBr
Provide an explanation for this order of reactivity.
Answer:
The relative reactivity of the substrates towards SN2 is as follows:
CH3XCH3CH2X(CH3)2CHX
The relative reactivity of the substrates towards SN1 is as follows:
(CH3)3CBr(CH3)2CHBr CH3CH2Br CH3Br
Combine those two mechanisms, the relative reactivity of the substrates towards the nucleophilic
substitution reaction is:
(CH3)3CBrCH3BrCH3CH2Br(CH3)2CHBr
6.36 The reaction of 1 alkyl halides with nitrite salts produces both RNO2 and RONO. Account for
this behavior.
Answer:
The nucleophilic sites for the NO2- are:

N
-

O R

X-

N
O

transition state
-O

N
O

-O

-O

N+
O

N+
O

X-

6.37 What would be the effect of increasing solvent polarity on the rate of each of the following
nucleophilic substitution reaction?
(a)

Nu: + RLRNu+ + :L-

(b)

RL+ R+ + :L

Answer:

+
The transition state for the reaction (a) should be: Nu

L , in which the charge is

developing. The more polar the solvent, the better it can solvate the transition state, thus lowing
the free energy of the activation and increasing the reaction rate.

+
The transition state for the reaction (b) should be: R

+
L , in which the charge is becoming

dispersed. A polar solvent is less able to solvate this transition state than it is to solvate the reactant.
The free energy of activation, therefore, will become somewhat larger as the solvent polarity
increases, and the rate will be slower.
6.38 Competition experiments are those in which two reactants at the same concentration (or one
reactant with two reactive sites) compete for a reagent. Predict the major product resulting from each of
the following competent experiment.
Answer:
(1)
CH3

CH3

Cl

H2
C

H2
C

H2
C

Cl

+ I--

Cl

H2
C

H2
C

H2
C

-+ Cl

CH3

CH3

In the solvent DMF, I is more reactive than in water or methanol as no hydrogen bonds is formed. So
it carries out a reaction SN2. The carbon atom 1 is bearing a bulky group which has a dramatic
inhibiting effect.
(2)
CH3

CH3

Cl

H2
C

H2
C

Cl

+ H 2O

CH3

acetone

HO

H2
C

H2
C

Cl

+ HCl

CH3

H2O is a neutral molecule, and it can only carry out a reaction SN1. The tertiary carbocation is more
stable than the primary carbocation.

CH3

CH3

Cl

H2
C

H2
C

Cl

acetone

+ H 2O

HO

H2
C

H2
C

Cl

+ HCl

CH3

CH3

6.39 In contrast to SN2 reactions, SN1 reactions show relatively little nucleophile selectivity. That
is, when more than one nucleophile is present in the reaction medium, SN1 reaction show only a
slight tendency to discriminate between weak nucleophiles and strong nucleophiles, whereas SN2
reactions show a marked tendency to discriminate.
(a) Provide an explanation for this behavior.
(b) Show how your answer accounts for the fact that CH3CH2CH2CH2Cl reacts with 0.01 M
NaCN in ethanol to yield primarily CH3CH2CH2CH2CN, whereas under the same conditions
(CH3) 3CCl reacts to give primarily (CH3) 3COCH2CH3.
Answer:
(a) Reaction of alkyl halides by an SN1 mechanism are favored by the use of substrates that can
from relatively stable carbocation, by the use of weak nucleophiles, and by the use of highly
ionizing solvent. SN1 mechanism, therefore, are important in solvolysis reactions of tertiary
halides, especially when the solvent is highly polar. If we want to favor the reaction of an
alkyl halide by an SN2 mechanism, we should use a relatively unhindered alkyl halide, a
strong nucleophile, a polar aprotic solvent, and a high concentration of the nucleophile. So
they have different behavior.
(b) CH3CH2CH2CH2Cl and 0.01 M NaCN in ethanol use SN2 reactions, and CH3CH2CH2CH2Cl
show a marked tendency to NaCN. So the product is primarily CH3CH2CH2CH2CN. Whereas
(CH3) 3CCl show slight tendency to NaCN. Because in 0.01 M NaCN in ethanol solution,
ethanol is much more than NaCN. So the product is primarily (CH3) 3COCH2CH3.

6.40 In the gas phase, the homolytic bond dissociation energy (Section 10.2A) for the carbon-chlorine
bond of tert-butyl chloride is +328KJ mol-1; the ionization potential for a tert-butyl radical is +715KJ
mol-1; and the electron affinity of chlorine is 330KJ mol-1. Using these data, calculate the enthalpy
change for the gas phase ionization of tert-butyl chloride to a tert-butyl cation and a chloride ion (this is
the heterolytic bond dissociation energy of the carbon chlorine bond).
Answer:

Cl

C(CH3)3

C(CH3)3

Cl + e

Cl

C(CH3)3

C(CH3)3
C(CH3)3

Cl

Cl

+ 328 KJ / mol

+ 715 KJ / mol

- 330 KJ / mol

C(CH3)3

Cl

+ 713 KJ / mol

+328KJ

+715KJ

-330KJ

6.41 The reaction of chloroethane with water in the gas phase to produce ethanol and hydrogen
chloride has a H= + 26.6KJmol-1and a S= + 4.81JK-1mol-1at 25
(a) Which of these terms, if either, favors the reaction going to completion
Solution: The entropy term is slightly favorable.
(b) Calculate Gfor the reaction. What can you now say about whether the reaction will
proceed to completion?
Solution: G=H-TS=26.6-298*4.81*10-3 = 25.17 > 0

So, chloroethane with water in the gas phase will produce ethanol and hydrogen chloride at 25
(c) Calculate the equilibrium constant for the reaction
Solution: G = - RT ln K K= 3.84*10-5
(d) In aqueous solution the equilibrium constant is very much larger than the one you just
calculated. How can you account for this fact?
Answer: The equilibrium is very much more favorable in aqueous solution because solvation of
the products takes place and thereby stabilizes them.
6.42 When (S)-2-bromopropanoic acid [ (S)-CH3CHBrCO2H] reacts with concentrated sodium hydroxide
the product formed (after acidification) is (R)-2-hydroxypropanoic acid [(R)-CH3CHOHCO2H, commonly
known as (R)-lactic acid]. This is, of course, the normal stereochemical result for an SN2 reaction.
However, when the same reaction is carried out with a low concentration of hydroxide ion in the
presence of Ag2O

(where Ag

acts as a Lewis acid), it takes place with overall retention of

configuration to produce (S)-2-hydroxypropanoic acid. The mechanism of this reaction involves a

phenomenon called neighboring group participation. Write a detailed mechanism for this reaction that
accounts for the net retention of configuration when Ag and a low concentration of hydroxide are
used.
Answer: at the first condition, there exists sodium hydroxide, a strong base and a good nucleophile.
So SN2 reaction takes place. But at the second condition, there exists Ag+, the reaction takes place in
the following way:
O
O

H
H3C

OH

O
H
H3C

OH-

Br
H

CH3

Ag+

6.43 The phenomenon of configuration inversion in a chemical reaction was discovered in1896 by
Paul von Walden. Waldens proof of configuration inversion was base on the following cycle:

HO2CCH2 CHClCO2 H
(-)-Chlorosuccinic acid

Ag2O

KOH

H2 O

PCl5

HO2 CCH2CH(OH)CO2H
(-)-Malic acid

HO2CCH2CH(OH)CO2 H
(+)-Malic acid

KOH
PCl5

Ag2O
H2 O
HO2CCH2CHClCO2H
(+)-Chlorosuccinic acid

(a) Basing your answer on the preceding problem, which reaction of the Walden cycle are likely
to take place with overall inversion of configuration and which are likely to occur with overall
retention of configuration? (b) Malic acid with a negative optical rotation is now known to
have the (s) configuration. What are the configuration of the other compounds in the Walden
cycle? (c) Walden also found that when (+)-malic acid is treated with thionyl chloride
(rather PCl5), the product of the reaction is (+)-chlorosuccinic acid. How can you explain this
result? (d) Assuming that the reaction of (-)-malic acid and thionyl chloride has the same
steteochemistry, outline a Walden cycle based on the vse of thionyl chloride instead of PCl5.
ANSWER:
(a) The reaction of the Walden cycle are likely to take place with overall inversion of
configuration:

HO2CCH2CH(OH)CO2 H
(-)-Malic acid

KOH
PCl5

HO2CCH2 CHClCO2 H
(+)-Chlorosuccinic acid

KOH
HO2CCH2 CHClCO2 H
(-)-Chlorosuccinic acid

PCl5

HO2CCH2CH(OH)CO2H
(+)-Malic acid

The reaction which are likely to occur with overall retention of configuration:

HO2CCH2 CHClCO2 H
(-)-Chlorosuccinic acid

HO2CCH2CHClCO2H
(+)-Chlorosuccinic acid
(b)

HO2CCH2CHClCO2H
(-)-Chlorosuccinic acid

is (S)

Ag2O
H2O

Ag2O
H2O

HO2CCH2CH(OH)CO2H
(-)-Malic acid

HO2CCH2CH(OH)CO2H
(+)-Malic acid

HO2CCH2CH(OH)CO2H
(+)-Malic acid
is (R)

HO2 CCH2CHClCO2H
(+)-Chlorosuccinic acid

is (R)

(c)The type of reaction is the retention of the configuration.

HO2CCH2 CH(OH)CO2H
(+)-Malic acid

SOCl2

HO2 CCH2 CHClCO2H

(+)-Chlorosuccinic acid

(d) The new cycle is

HO2 CCH2 CHClCO2H

(+)-Chlorosuccinic acid
KOH

thionyl chloride

HO2CCH2CH(OH)CO2H
(-)-Malic acid

HO2CCH2CH(OH)CO2 H
(+)-Malic acid

thionyl chloride

KOH
HO2CCH2CHClCO2H
(-)-Chlorosuccinic acid

6.44 (R)-(3-Chloro-2-methylpropyl ) methyl ether ( A ) on reaction with azide ion (N3-) in aqueous
ethanol gives ( S )-( 3-azido-2-methylpropyl ) methyl ether (B). Compound A has the structure
ClCH2CH(CH3)CH2OCH3.
( a ) Draw wedge-dashed wedge-line formulas of both A and B.
( b ) Is there a change of configuration during this reaction?
Answer:
A

CH2Cl

CH2N3

C
H

CH3
CH2OCH3

CH3
CH2OCH3

There is no change of configuration during this reaction.

t-BuO- in
cis-4-Bromocyclohexanol
6.46

t-BuOH

racemic C6 H10O
(compound C)

Compound C has infrared absorption in the 1620 to 1680 cm- and in the 3590 to 3650 cm- regions.
Draw and label the (R) and (S) enantiomers of produce C
Answer