Chapter 14
Ethers and Epoxides;
Thiols and Sulfides
Review of Concepts
Fill in the blanks below. To verify that your answers are correct, look in your textbook at
the end of Chapter 14. Each of the sentences below appears verbatim in the section
entitled Review of Concepts and Vocabulary.
• Ethers are often used as ____________ for organic reactions.
• Cyclic polyethers, or __________ ethers, are capable of solvating metal ions in
organic (nonpolar) solvents.
• Ethers can be readily prepared from the reaction between an alkoxide ion and an
• ______________ can be converted into epoxides by treatment with peroxy acids
or via halohydrin formation and subsequent epoxidation.
• _____________ catalysts can be used to achieve the enantioselective epoxidation
of allylic alcohols.
• Epoxides will undergo ring-opening reactions in: 1) conditions involving a
strong nucleophile, or under 2) _____-catalyzed conditions. When a strong
nucleophile is used, the nucleophile attacks at the ______-substituted position.
312
CHAPTER 14
Review of Skills
Fill in the blanks and empty boxes below. To verify that your answers are correct, look
in your textbook at the end of Chapter 14. The answers appear in the section entitled
SkillBuilder Review.
14.1 Naming an Ether
O
Cl
Cl
PROVIDE A SYSTEMATIC NAME FOR THE FOLLOWING COMPOUND
1) IDENTIFY THE PARENT
2) IDENTIFY AND NAME SUBSTITUENTS
3) ASSIGN LOCANTS TO EACH SUBSTITUENT
4) ALPHABETIZE
5) ASSIGN CONFIGURATION
14.3 Preparing Epoxides
Et
Me
Me O
Me Et
Me
IDENTIFY REAGENTS THAT WILL ACHIEVE THE FOLLOWING TRANSFORMATION:
1)
2)
CHAPTER 14
313
14.5 Drawing the Mechanism and Predicting the Product of Acid-Catalyzed Ring-Opening
O
H
Me
Et Et
H OSO
3
H
EtOH EtOH
COMPLETE THE MECHANISM BELOW BY DRAWING ALL CURVED ARROWS, INTERMEDIATES AND PRODUCTS.
14.7 Choosing the Appropriate Grignard Reaction
R Br ROH
IDENTIFY REAGENTS THAT WILL ACHIEVE EACH OF THE FOLLOWING TRANSFORMATIONS:
1)
2)
3)
R Br R
1)
2)
3)
OH
Review of Reactions
Identify the reagents necessary to achieve each of the following transformations. To
verify that your answers are correct, look in your textbook at the end of Chapter 14. The
answers appear in the section entitled Review of Reactions.
Preparation of Ethers
314
CHAPTER 14
Reactions of Ethers
Acidic cleavage
Preparation of Epoxides
RR
H H O
R R
HH
c
i
s
c
i
s
Enantioselective Epoxidation
R OH
O
R
O
H
O
R OH
CHAPTER 14
315
Thiols and Sulfides
Thiols
R
2
R
1
Br
R
2
R
1
SH
Solutions
14.1.
a) 2-ethoxypropane
14.2.
a)
OEt
316
CHAPTER 14
14.3.
Common names in parentheses:
O
O
1-methoxybutane
2-methoxybutane
(butyl methyl ether) (sec-butyl methyl ether)
Chirality center
14.4.
a)
Br
benzene
KF F
18-Crown-6
b)
Br NaF
benzene
F
15-Crown-5
14.5.
a) A Williamson ether synthesis will be more efficient with a less sterically hindered
substrate, since the process involves an S
N
2 reaction. Therefore, in this case, it is better
CHAPTER 14
317
b) In this case, it is better to start with a secondary alcohol and a primary alkyl halide,
rather than a primary alcohol and a secondary alkyl halide:
O
1) Na
14.6.
O
HO
Cl NaH
14.7. No. The Williamson ether synthesis employs an S
N
2 process, which cannot occur
14.8.
a)
OEt
1) Hg(OAc)
2
, EtOH
2) NaBH
4
d)
O
1) Hg(OAc)
2
,
2) NaBH
4
HO
318
CHAPTER 14
14.9.
dilute H
2
SO
4
14.10.
1) BH
3
THF
2) H
2
O
2
, NaOH
14.11.
a)
OHBr Br
2+ H
2
O
CHAPTER 14
319
e)
OHI
I
I+ H
2
O
(racemic mixture)
14.12.
a) 2-methyl-1,2-epoxypropane or 1,1-dimethyloxirane
b) 1,1-diphenyl-1,2-epoxyethane or 1,1-diphenyloxirane
c) 1,2-epoxycyclohexane
14.13.
14.14.
a)
O
Me
H
Me
MCPBA
320
CHAPTER 14
14.15. This process for epoxide formation involves deprotonation of the hydroxyl
group, followed by an intramolecular S
N
2 attack. The S
N
2 step requires back-side attack,
which can only be achieved when both the hydroxyl group and the bromine occupy axial
14.16.
a)
Ti[OCH(CH
3
)
2
]
4
(+)-DET
OH
O O H
O
OH
b)
14.17.
a)
MgBr O
M
e
O
Me
HOHOH
Me
+
CHAPTER 14
321
b)
O
M
e
O
NC
Me
HOH
OH
NC
Me
+
N C
e)
O
Me
Et
HSH O
Me
Et SH
H
HOH
HO
Me
Et SH
H
14.18. The reaction yields a meso compound, regardless of which electrophilic position
is attacked by hydroxide.
Me
Me
Me
m
e
s
o
322
CHAPTER 14
14.19.
O
MeMe
NaOH
H
2
OOH
HO
Me
Me
+
HO
OH
Me
Me
14.20.
a)
OH Cl O
H
+Cl
Cl
HO
b)
O
Me
H Br O
H
Me
Br
OH
Me
H
+
Br
CHAPTER 14
323
d)
O
MeEt
Me H H OSO
3
H
Me
O
H
Me
Et
H
Me
OH
Me Et
O
H
HH
Me
OH
Me Et
HO H
HOH
HOH
Me
Et
Me
324
CHAPTER 14
14.21.
O
Me
Et H
H OSO
3
HO
H
Et
Me
H
O
OH
Me
Et
H
14.22.
a)
Br
NaSH
SH
14.23.
a)
SH 1) NaOH
2) Br
S
CHAPTER 14
325
c)
SNa
I
O
4
S
O
14.24.
a)
CN
HO
1) MCPBA
2) NaCN
3) H
2
O
d)
SH
OH
1) MCPBA
2) [H
2
SO
4
], H
2
S
326
CHAPTER 14
14.25.
I
OH
1) MCPBA
2) H
3
O
+
HO
t
-BuOK
14.26.
a)
Br OH
1) Mg
2)
3) H
2
O
O
d)
Br
OH
1) Mg
2)
3) H
2
O
H
O
Na
2
Cr
2
O
7
H
2
SO
4
, H
2
O
O
CHAPTER 14
327
g)
Cl OH
1) Mg
2)
3) H
2
O
O
i)
OH
1) MCPBA
2) PrMgBr
3) H
2
O
328
CHAPTER 14
14.28.
H
2
Lindlar’s
Catalyst
HO OH
1) Na (2 eq)
2) CH
3
I(2 eq)
H
3
CO OCH
3
OsO
4
NMO
14.29.
14.30
a) (1S, 2S)-1-ethoxy-2-methylcyclohexane
b) (R)-2-ethoxybutane
14.31
a)
OHBr Br
+ CH
3
Br + H
2
O
CHAPTER 14
329
14.32
OOO
14.33
a)
O
1) Hg(OAc)
2
, EtOH
2) NaBH
4
14.34
a)
Compound A
II
330
CHAPTER 14
c)
O
OHI
O
O
H
I
+
O
H
O
I
O
H
H
O
I
– H
2
O
I
HI
14.35
HO OH H OSO
3
H
HO OH
HO
H
O
– H
2
OHOH
14.36
HO OH H OSO
3
H
HO OH
HHO OH
HO OOH
H
– H
2
O
14.37
a) Neither alkyl group (on either side of the oxygen atom) can be installed via a
Williamson ether synthesis. Installation of the tert-butyl group would require a tertiary
CHAPTER 14
331
b) Oxymercuration-demercuration can be used to prepare tert-butyl phenyl ether:
1) Hg(OAc)
2
,
2) NaBH
4
OH O
14.38 Ethylene oxide has a high degree of ring strain, and readily functions as an
electrophile in an S
N
2 reaction. The reaction opens the ring and alleviates the ring strain.
N
14.39
1) NaNH
2
2) MeI
14.40
HO Br
NaH O
332
CHAPTER 14
14.41
a)
1) NaNH
2
2)
1) NaNH
2
2) MeI
b)
Br
O
H
EtH
1) Na, NH
3
2) MCPBA
1) NaNH
2
2)
1) NaNH
2
2) EtI
+
E
n
CHAPTER 14
333
14.42
a)
2) MeMgBr
1) RCO
3
H
3) H
2
OOH
d)
2) EtCl
1) Na
OH OEt
e)
2)
1) Na
OH
O
3) H
2
O
OOH
h)
2)
1) Mg, diethyl ether
Cl
O
3) H
2
O
OH
334
CHAPTER 14
14.43
a)
OCC
H
H
H
H
HMgBr
OH
O
HOH
+
e)
Cl O
O
H
HCl O Cl
–
CHAPTER 14
335
14.44
HBr
O
Br Br + H
2
O
14.46
O
Cl
Me
CC
H
H
H
H
HMgBr
Et
O
Me
Cl
Et Me
O
14.47
a)
2) NaBH
4
1) Hg(OAc)
2
, MeOH OMe
336
CHAPTER 14
c)
2) NaBH
4
1) Hg(OAc)
2
,
OH
O
14.48
a)
OH
O O HO
OH
1) NaNH
2
2)
2) NaNH
2
3)
1) TMSCl, Et
3
N
b)
OH
O O
HO
OH
1) NaNH
2
2)
2) NaNH
2
3)
1) TMSCl, Et
3
N
CHAPTER 14
337
14.49
MCPBA
OH
1) EtMgBr
2) H
2
O
14.50
MCPBA
2) NaBH
4
C CH
OEt
Na
HI
I
OH
Et
I
1) Hg(OAc)
2
, EtOH
heat
+
+ H
2
O
1)
338
CHAPTER 14
14.51
a)
MCPBA
O
O
H
1) MeMgBr
2) H
2
O
d)
Cl
OH SOCl
2
O
Cl
1) Mg
2)
3) H
2
O
py
e)
OH O
1) NaH
2) Et
I
CHAPTER 14
339
h)
O
dilute H
2
SO
4
1) NaH
2) EtI
OH
+ En
i)
H
2
MCPBA O
Lindlar’s
Catalyst
+ En
l)
OH
H
2
MCPBA
O
Lindlar’s
Catalyst
1) EtMgBr
2) H
2
O
340
CHAPTER 14
o)
OH OOH
O
1) NaH
2)
3) H
2
O
r)
OH [H
2
SO
4
]
O
OOH
t)
MCPBA O+ En
1) Br
2
, hv
2) NaOEt
CHAPTER 14
341
14.52.
O
14.54.
O
14.56
O
Me
Me
H
HO
Me
Me
H
D
1) LiAlD
4
2) H
2
O
14.58 When methyloxirane is treated with HBr, the regiochemical outcome is
determined by a competition between steric and electronic factors, with steric factors
prevailing – the Br is positioned at the less substituted position. However, when
342
CHAPTER 14
14.59.
1) Br
2
, hv
2) NaOEt
1) MCPBA
2) PrMgBr
OH
3) H
Oconc. H
14.60
Br 1) Mg
2)
3) H
2
O
conc. H
2
SO
4
heat
O
OH
1) MCPBA
14.61 Since the Grignard reagent is both a strong base and a strong nucleophile,
substitution and elimination can both occur. Indeed, they compete with each other. As
we discussed in Chapter 8, elimination will be favored when the substrate is secondary.
Both electrophilic positions in this epoxide are secondary, and so, elimination
predominates: