Chapter 12
Synthesis
Review of Concepts
Fill in the blanks below. To verify that your answers are correct, look in your textbook at
the end of Chapter 12. Each of the sentences below appears verbatim in the section
entitled Review of Concepts and Vocabulary.
•
•
•
•
•
The position of a halogen can be moved by performing __________ followed by
______________.
The position of a π bond can be moved by performing ___________ followed by
______________.
An alkane can be functionalized via radical ________________.
Every synthesis problem should be approached by asking the following two
questions:
1. Is there any change in the ____________________?
2. Is there any change in the identity or location of the _________________?
In a _________________ analysis, the last step of the synthetic route is first
established, and the remaining steps are determined, working backwards from the
product.
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 12. The answers appear in the section entitled
SkillBuilder Review.
12.1 Changing the Identity or Position of a Functional Group
IDENTIFY THE TWO PROCESSES THAT ARE REQUIRED TO CHANGE THE POSITION OF A HALOGEN:
Br
Br
IDENTIFY THE TWO PROCESSES THAT ARE REQUIRED TO CHANGE THE POSITION OF A PI BOND:
Br
IDENTIFY THE TWO PROCESSES THAT ARE REQUIRED TO INSTALL A PI BOND:
Br
254
CHAPTER 12
IDENTIFY THE REAGENTS NECESSARY TO ACHIEVE EACH OF THE FOLLOWING TRANSFORMATIONS
or
1)
1)
2)
2)
3)
12.2 Changing the Carbon Skeleton
IDENTIFY THE REAGENT NECESSARY TO ACHIEVE THE FOLLOWING C-C BOND FORMING REACTION:
H H
H H
+
H C C C C
H H H
H C C C C
H H
H H
C C C H
H H H
IDENTIFY THE REAGENTS NECESSARY TO ACHIEVE THE FOLLOWING C-C BOND BREAKING REACTION:
H
H H H
H C C C C
H H H
C H
H
1)
H H H
2)
H H H
H
O
H C C C C
H
+
O
C H
12.3 Approaching a Synthesis Problem by Asking Two Questions
IDENTIFY THE TWO QUESTIONS TO ASK WHEN APPROACHING A SYNTHESIS PROBLEM:
1) __________________________________________________________________________________________________?
2) __________________________________________________________________________________________________?
12.4 Retrosynthetic Analysis
COMPLETE THE FOLLOWING RETROSYNTHETIC ANALYSIS BY DRAWING THE APPROPRIATE STRUCTURES IN THE BOXES PROVIDED:
PRODUCT
STARTING
MATERIAL
CHAPTER 12
255
Solutions
12.1.
O
Br
H
O
OH
1) O3
2) DMS
Br
+ En
OH
HBr
HBr
ROOR
OsO4
NMO
OH
+ En
1) MCPBA
Br
Br2
hv
2) H3O+
NaOEt
OH
Br2, H2O
OH
dilute
H2SO4
+ En
Br2
1) BH3 THF
OH
2) H2O2,
NaOH
Br
H2
Pt
Br
+ En
Br
+ En
OH
256
CHAPTER 12
12.2.
Br
O
CH3
HBr
O
Br
H 2SO4, H2O
Br
HBr
1) xs NaNH2
H
HgSO4
H2
1) 9-BBN
2) H2O2, NaOH
2) H2O
Lindlar's
Catalyst
H2
1) NaNH2
2) CH3I
1) xs NaNH2
2) H2O
Pt
Br2
Na
Br
NH3
Br
1) O3
2) H2O
Br
xs Br2
Br
O
O
+
OH
Br
C
Br
Br
O
Br
12.3.
a)
Br
Br2
1) xs NaNH2
Br
2) H2O
b)
Br
Br
1) NaOMe
2) HBr
c)
1) HBr
2) NaOMe
d)
Br
Br2, hv
NaOMe
257
CHAPTER 12
e)
conc. H2SO4
heat
OH
dilute H2SO4
OH
1) TsCl, py
2) NaOEt
f)
Br
1) NaOMe
2) dilute H2SO4
OH
g)
OH
Br
HBr, ROOR
1) TsCl, py
2) NaOEt
h)
1) BH3 THF
2) H2O2, NaOH
OH
1) TsCl, py
OH
2) NaOEt
1) HBr, ROOR
2) NaOH (SN2)
12.4.
Br
1) t-BuOK
2) Br2
1) NaOMe
2) HBr, ROOR
Br
Br
1) xs NaNH2
2) H2O
Br
12.5.
Br2
Br
1) xs NaNH2
2) H2O
Br
excess HBr
Br
Br
258
CHAPTER 12
12.6.
a)
Br
Br2, hv
b)
Br
Br2, hv
NaOMe
c)
Br
Br2, hv
1) BH3 THF
NaOMe
2) H2O2, NaOH
OH
+ En
d)
Br
Br2, hv
NaOMe
1) HBr, ROOR
2) t-BuOK
12.7.
a)
1) NaNH2
2) MeI
1) NaNH2
2) EtI
b)
H C C H
NaNH2
H C C
Na
Br
c)
1) O3
2) DMS
O
+ En
CHAPTER 12
259
12.8.
a)
NaNH2
H C C H
Na
H C C
H2
Br
Lindlar's
catalyst
b)
t-BuOK
Br
1) O3
O
2) DMS
H
c)
H C C H
NaNH2
H C C
Na
Br
xs HBr
Br
Br
12.9. The alkyl halide is a tertiary substrate and does not readily undergo SN2. Under
these conditions, the acetylide ion functions as a base, rather than a nucleophile, giving
an E2 reaction, instead of SN2:
Br
H C C
Na
12.10.
a)
1) NaNH2
2)
H2
I
Lindlar's Catalyst
260
CHAPTER 12
b)
H C C H
H2
NaNH2
Lindlar's
Catalyst
H C C
HBr, ROOR
Na
Br
Na
NH3 (l)
c)
Br
O
Br
1) xs NaNH2
1) O3
2) H2O
2) H2O
OH
d)
H3C C C H
HBr
NaNH2
H3C C C
Br
Na
ROOR
Na
NH3 (l)
e)
H C C H
1) HBr, ROOR
2) t-BuOK
HBr
ROOR
Br
NaNH2
H C C
Na
CHAPTER 12
261
f)
OH
H
1) TsCl, py
1) O3
2) t-BuOK
2) DMS
O
12.11.
H C C H
NaNH2
Br
HO
1) TsCl, py
HBr
2) t-BuOK
ROOR
H C C
Na
H2
Lindlar's
Catalyst
OH
1) BH3 THF
2) H2O2, NaOH
12.12.
H C C H
NaNH2
H C C
HBr, ROOR
Na
Br
H2
Lindlar's
Catalyst
O
1) O3
H
2) DMS
262
CHAPTER 12
12.13.
a)
H2
Lindlar's
Catalyst
1) NaNH2
2) EtI
Br2
Br
H2O
Na
OH
NH3 (l)
b)
H
C
C
H
NaNH2
H
C
C
H2
Na
Br
Lindlar's
Catalyst
MCPBA
O
c)
Br
Br
O
H2SO4, H2O
1) xs NaNH2
2) H2O
HgSO4
d)
Br2
hv
NaOEt
Br
1) O3
O
2) DMS
e)
Br2
hv
Br
t-BuOK
1) BH3 THF
2) H2O2, NaOH
OH
CHAPTER 12
263
f)
Br
Br
1) xs NaNH2
1) O3
2) H2O
2) H2O
O
OH
g)
1) NaNH2
1) NaNH2
2) EtI
2) EtI
Na
NH3 (l)
Br
Br2
H2O
+ En
OH
h)
Br2
hv
Br
NaOEt
1) HBr, ROOR
2) t-BuOK
1) Br2
2) xs NaNH2
3) H2O
264
CHAPTER 12
12.14.
H C C H
NaNH2
1) H2, Lindlar's Catalyst
2) HBr
H C C
Na
Br
H2
Lindlar's
Catalyst
H C C
HBr, ROOR
Na
Br
1) NaNH2
2)
Br
Na
NH3 (l)
CHAPTER 12
12.15.
H C C H
NaNH2
1) H2, Lindlar's Catalyst
2) HBr
H C C
Na
Br
H2
Lindlar's
Catalyst
H C C
Na
HBr, ROOR
Br
H2
Lindlar's
Catalyst
HBr, ROOR
H C C
Br
1) NaNH2
2)
H2
Lindlar's
Catalyst
Br
Na
265
266
CHAPTER 12
12.16.
H C C H
NaNH2
H C C
1) H2, Lindlar's Catalyst
Na
Br
2) HBr
H2
Lindlar's
Catalyst
H C C
Na
HBr, ROOR
Br
H2
Lindlar's
Catalyst
1) O3
O
2) DMS
H
12.17.
Br2
Br
hv
H2
t-BuOK
Pt
HBr
Br
H3O
ROOR
1) BH3 THF
2) H2O2, NaOH
OsO4
OH
OH
OH
+
NMO
Br2
Br2
H2O
OH
OH
Br
Br
Br
267
CHAPTER 12
12.18.
O
CH3
Br
O
H
H 2SO 4, H2 O
HgSO4
HBr
HBr
1) 9-BBN
Br
2) H2O2, NaOH
Br
Br
Br
1) xs NaNH 2
Br2
2) H2O
xs HBr
xs Br2
Br
Br
Br
1) xs NaNH 2
2) H2 O
1) O 3
1) NaNH2
2) MeI
Br
Br
Br
2) H2 O
O
O
+
OH
H2
Lindlar's
Catalyst
H 2, Pt
Na, NH 3 (l)
C
O
268
CHAPTER 12
12.19.
H C C H
NaNH2
1) H2, Lindlar's Catalyst
2) HBr
Na
H C C
Br
H2
Lindlar's
Catalyst
HBr
Br
12.20.
H C C H
NaNH2
1) H2, Lindlar's Catalyst
2) HBr
H C C
Na
Br
H2
Lindlar's
Catalyst
HBr, ROOR
Br
12.21.
a)
1) TsCl, py
1) BH3 THF
2) t-BuOK
2) H2O2, NaOH
OH
1) Br2
2) xs NaNH2
b)
OH
3) H2O
H2SO4, H2O
HgSO4
O
CHAPTER 12
269
12.22.
1) HBr, ROOR
2) t-BuOK
12.23.
a)
1) Br2
1) O3
2) xs NaNH2
3) H2O
2) H2O
OH
O
b)
O
1) O3
HC CNa
Br
OH
2) H2O
c)
Br
H2
HC CNa
1) O3
Lindlar's
Catalyst
2) DMS
O
H
d)
Br2
hv
Br
1) NaOMe
2) HBr, ROOR
HC CNa
Br
H2
Lindlar's
Catalyst
270
CHAPTER 12
12.24.
1) NaNH2
1) NaNH2
2) EtI
2) MeI
Na
NH3 (l)
H2
Lindlar's
Catalyst
1) MCPBA
2) H3O+
OsO4, NMO
OH
+En
OH
12.25.
1) NaNH2
1) NaNH2
2) EtI
2) MeI
Na
NH3 (l)
H2
Lindlar's
Catalyst
OsO4, NMO
1) MCPBA
2) H3O+
OH
+En
OH
12.26.
a)
HBr
ROOR
HC CNa
Br
H2SO4, H2O
HgSO4
O
271
CHAPTER 12
b)
HBr
1) 9-BBN
HC CNa
Br
ROOR
H
2) H2O2, NaOH
O
c)
HBr
Br
ROOR
O
1) O3
HC CNa
OH
2) H2O
d)
HBr
HC CNa
H2
Br
ROOR
Lindlar's
Catalyst
1) O3
2) DMS
O
H
e)
Br
Br2
NaOMe
1) O3
2) DMS
hv
O
O
H
12.27.
HBr
H2
Br
Lindlar's
Catalyst
NaNH2
H C C
MCPBA
H2
Na
O
Lindlar's
Catalyst
1) NaNH2
2) O
3) H3O+
H2
OH
Pt
OH
272
CHAPTER 12
12.28.
H2
Lindlar's
Catalyst
2) DMS
NaNH2
O
H
2) H3O
H
H
Na
H C C
OH
1) HC CNa
H
O
1) O3
+
H2
OH
Lindlar's
Catalyst
12.29.
H2
Lindlar's
Catalyst
HO
HO
OH
Br2
Note: You may find it helpful
to build molecular models to
help visualize the
stereochemistry of the ringclosing step.
Br
O
+ En
12.30.
a)
H2SO4, H2O
HgSO4
O
H
b)
1) NaNH 2
2) EtI
H2
Lindlar's
catalyst
O
1) O3
2) DMS
H
273
CHAPTER 12
c)
H C C H
NaNH2
Na
H C C
1) H2, Lindlar's Catalyst
Br
2) HBr
1) 9-BBN
2) H2O2, NaOH
O
H
d)
H C C H
NaNH2
Na
H C C
1) H2, Lindlar's Cat.
Br
2) HBr
1) H2,
Lindlar's Cat.
2) HBr, ROOR
Na
H C C
1) H2, Lindlar's Cat.
Br
2) O3
3) DMS
H
O
12.31.
1) MCPBA
2) H3O
HO
+
xs NaH
OH
H2
Lindlar's
Catalyst
Br2
O
Br
O
O
Br
O