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
Br
Br
IDENTIFY THE TWO PROCESSES THAT ARE REQUIRED TO CHANGE THE POSITION OF A PI BOND:
IDENTIFY THE TWO PROCESSES THAT ARE REQUIRED TO INSTALL A PI BOND:
254 CHAPTER 12
or
IDENTIFY THE REAGENTS NECESSARY TO ACHIEVE EACH OF THE FOLLOWING TRANSFORMATIONS
2)
1)1)
2)
3)
12.2 Changing the Carbon Skeleton
IDENTIFY THE REAGENTS NECESSARY TO ACHIEVE THE FOLLOWING C-C BOND BREAKING REACTION:
C
H
H
C C
H
H
H C C
H
H
C C
H
H
H C C
H
H
C C
H
H
H
H
H+
+
1)
2)C
H
H
C C
H
H
C
CH
H
H H
H
HC
H
H
C C
H
H
C
OH
H
H H
C
H
HO
IDENTIFY THE REAGENT NECESSARY TO ACHIEVE THE FOLLOWING C-C BOND FORMING REACTION:
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
PRODUCT STARTING
MATERIAL
COMPLETE THE FOLLOWING RETROSYNTHETIC ANALYSIS BY DRAWING THE APPROPRIATE STRUCTURES IN THE BOXES PROVIDED:
CHAPTER 12 255
Solutions
12.1.
OH
OH
O
O
HBr
OH
OH
OH
Br
OH
Br
Br
OH
Br
HBrROOR
NaOEtBr2
HBr
NMO
2) H3O+
1) MCPBA
Br2, H2O
Br2H2
Pt2) H2O2,
1) BH3 THF
NaOH
Br
+ En
+ En
+ En
+ En
+ En
hv
1) O3
2) DMS
dilute
H2SO4
OsO4
256 CHAPTER 12
12.2.
Br
Br
BrBr
Br
CH3
O
O
H
OH
O
Br
Br
Br Br
Br
Br
C
O
O
+
H2SO4, H2O
HgSO4H2
2) H2O2, NaOH
1) 9-BBN Lindlar'sCatalyst
1) O3
2) H2O
HBr
HBr
H2
Pt
NaBr2
xs Br2
1) xs NaNH2
2) H2O
2) CH3I
1) NaNH2
NH3
1) xs NaNH2
2) H2O
12.3.
a)
Br2 1) xs NaNH2
2) H2O
Br
Br
b) Br
Br 1) NaOMe
2) HBr
c)
1) HBr
2) NaOMe
d)
Br2, hv
Br
NaOMe
CHAPTER 12 257
e)
OH
OH
conc. H2SO4
1) TsCl, py
2) NaOEt
heatdilute H2SO4
f)
OH
Br
1) NaOMe
2) dilute H2SO4
g) OH
1) TsCl, py
2) NaOEt
BrHBr, ROOR
h)
OH1) TsCl, py
2) NaOEt
OH
1) HBr, ROOR
1) BH3 THF
2) H2O2, NaOH
2) NaOH (SN2)
12.4. Br 1) NaOMe
2) HBr, ROOR
1) t-BuOK
2) Br2
Br
1) xs NaNH2
2) H2O
Br
Br
12.5.
excess HBrBr Br
1) xs NaNH2
2) H2O
Br
Br
Br2
258 CHAPTER 12
12.6.
a) Br
Br2, hv
b) Br
NaOMeBr2, hv
c) Br
NaOMe 1) BH3 THF OHBr2, hv
+ En2) H2O2, NaOH
d) Br
NaOMe 1) HBr, ROORBr2, hv
2) t-BuOK+ En
12.7.
a)
1) NaNH2
2) EtI
1) NaNH2
2) MeI
b)
Br
C C HHNaNH2
C CH Na
c) O
1) O3
2) DMS
CHAPTER 12 259
12.8.
a)
Br
C C HHNaNH2
C CH Na H2
Lindlar'scatalyst
b)
Br
t-BuOK 1) O3O
H2) DMS
c)
C C HH
Br
NaNH2
C CH Na Br Brxs HBr
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:
C CH NaBr
12.10.
a)
1) NaNH2
2) I
H2
Lindlar's Catalyst
260 CHAPTER 12
b)
Na
H2
NH3 (l)
HBr, ROOR
Br
C C HHNaNH2
C CH Na
Lindlar'sCatalyst
c)
OH
OBr
Br
1) xs NaNH2 1) O3
2) H2O2) H2O
d)
Br
C C HH3CNaNH2
C CH3C Na
ROOR
Na
NH3 (l)
HBr
e)
1) HBr, ROOR
2) t-BuOK
C C HHNaNH2
C CH Na
ROOR
HBr Br
CHAPTER 12 261
f) OH H
O1) TsCl, py
2) t-BuOK
1) O3
2) DMS
12.11.
Na
NaNH2
C C HH
C CH
1) BH3 THF
Br
OH
HO
HBr
ROOR
2) H2O2, NaOH
1) TsCl, py
2) t-BuOK
H2
Lindlar's
Catalyst
12.12.
BrC CH
C C HH
NaNH2
Na
H
O
H2
HBr, ROOR
Lindlar'sCatalyst
1) O3
2) DMS
262 CHAPTER 12
12.13.
a)
Na
H2
H2O
Br2Br
OH
NH3 (l)
1) NaNH2
2) EtI
Lindlar'sCatalyst
b)
Br
C CH
C C HH
NaNH2
Na H2
O
MCPBA
Lindlar'sCatalyst
c) Br Br O
1) xs NaNH2
2) H2O
H2SO4, H2O
HgSO4
d) Br2
BrNaOEt O
hv
1) O3
2) DMS
e)
Br2
Brt-BuOK
hv
1) BH3 THF
2) H2O2, NaOH
OH
CHAPTER 12 263
f)
OH
Br Br O1) xs NaNH2
2) H2O
1) O3
2) H2O
g)
Br
OH
Br2
H2O
1) NaNH2
2) EtI
1) NaNH2
2) EtI
NH3 (l)
+ En
Na
h)
Br2 NaOEt
hvBr
1) HBr, ROOR
2) t-BuOK
1) Br2
2) xs NaNH2
3) H2O
264 CHAPTER 12
12.14.
C CH Na
Br
Na
Br
Br
C CH
C C HH
NaNH2
Na
H2
1) NaNH2
1) H2, Lindlar's Catalyst
2) HBr
2)
Lindlar'sCatalyst
HBr, ROOR
NH3 (l)
CHAPTER 12 265
12.15.
C CH Na
Br
Br
Br
C CH
C C HH
NaNH2
Na
H2
1) NaNH2
1) H2, Lindlar's Catalyst
2) HBr
2)
Lindlar'sCatalyst
HBr, ROOR
H2
Lindlar'sCatalyst
HBr, ROOR
Br
C CH Na
H2
Lindlar'sCatalyst
266 CHAPTER 12
12.16.
C CH Na
Br
Br
C CH
C C HH
NaNH2
Na
H2
1) H2, Lindlar's Catalyst
2) HBr
Lindlar'sCatalyst
HBr, ROOR
H2
Lindlar'sCatalyst
1) O3
H2) DMS
O
12.17.
OH
OH
OH
Br
Br
OH
Br
Br
OH
Br
H2
Pt
t-BuOK
H3O+
1) BH3 THF
2) H2O2, NaOH
Br2Br2
H2O
OsO4
NMO
HBr
ROOR
Br2
hv
CHAPTER 12 267
12.18.
Br
Br
Br
Br
Br
CH3
O
O
H
OH
O
Br
Br
Br Br
Br
Br
C
O
O
+
HBrHBr
xs HBr
1) xs NaNH2
2) H2O
H2SO4, H2O
HgSO4
1) 9-BBN
2) H2O2, NaOH
Br2
xs Br2
1) O3
2) H2O1) NaNH2
2) MeI
Na, NH3 (l)H2, Pt
H2
Lindlar's
Catalyst
1) xs NaNH2
2) H2O
268 CHAPTER 12
12.19.
Br
C CH
C C HH
NaNH2
Na
H2
1) H2, Lindlar's Catalyst
2) HBr
Lindlar'sCatalyst
HBr
Br
12.20.
Br
Br
C CH
C C HH
NaNH2
Na
H2
1) H2, Lindlar's Catalyst
2) HBr
Lindlar'sCatalyst
HBr, ROOR
12.21.
a) OH
OH1) TsCl, py
2) t-BuOK
1) BH3 THF
2) H2O2, NaOH
b)
HgSO4
O
1) Br2
2) xs NaNH2
3) H2O
H2SO4, H2O
CHAPTER 12 269
12.22.
1) HBr, ROOR
2) t-BuOK
12.23.
a)
OH
O
1) Br2
2) xs NaNH2
3) H2O
1) O3
2) H2O
b)
BrHC CNa
OH
O1) O3
2) H2O
c)
BrHC CNa
H
OH2
Lindlar'sCatalyst
1) O3
2) DMS
d)
1) NaOMe
2) HBr, ROOR
Br2
hv
Br
BrHC CNa
H2
Lindlar'sCatalyst
270 CHAPTER 12
12.24.
OsO4, NMO
1) NaNH2
2) EtI
1) NaNH2
2) MeI
NH3 (l)
Na
OH
OH
+En
1) MCPBA
2) H3O+
H2
Lindlar'sCatalyst
12.25.
H2
OH
OH
Na
OsO4, NMO
+En
1) NaNH2
2) EtI
1) NaNH2
2) MeI
NH3 (l)
1) MCPBA
2) H3O+
Lindlar'sCatalyst
12.26.
a) O
Br
H2SO4, H2O
HgSO4
HBr
ROOR
HC CNa
CHAPTER 12 271
b) HBr
BrHC CNa
2) H2O2, NaOHROOR
1) 9-BBN
H
O
c)
HBrBr
HC CNa
2) H2OROOR OH
1) O3 O
d) HBr
BrHC CNa H2
ROOR
H
O
2) DMS
1) O3
Lindlar'sCatalyst
e)
Br2
BrNaOMe 1) O3
O
H
O
hv 2) DMS
12.27. H2
H2
NaNH2
O
C CH
HBr
MCPBA
Na
O
Br
OH
Lindlar'sCatalyst
Lindlar'sCatalyst
1) NaNH2
2)
3) H3O+
H2
Pt OH
272 CHAPTER 12
12.28.
O
H H
H2
NaNH2
HC CNa
C CH
1) O3
OH
Na
H2
O
H H
OH
Lindlar'sCatalyst
Lindlar'sCatalyst
2) DMS
1)
2) H3O+
12.29.
HOH2 HO
OH
Br2
O
Br
Lindlar's
Catalyst
+ En
Note: You may find it helpful
to build molecular models tohelp visualize thestereochemistry of the ring-
closing step.
12.30.
a)
HgSO4H
OH2SO4, H2O
b)
2) EtI 2) DMS H
O1) NaNH2 1) O3H2
Lindlar'scatalyst
CHAPTER 12 273
c)
Br
C CH
C C HH
NaNH2
Na1) H2, Lindlar's Catalyst
2) HBr
2) H2O2, NaOH
1) 9-BBN
H
O
d)
H
O
Br
C CH
C CH
C C HH
NaNH2
Na
Na
Br
2) HBr, ROOR
1) H2,
Lindlar's Cat.
1) H2, Lindlar's Cat.
2) HBr
1) H2, Lindlar's Cat.
2) O3
3) DMS
12.31.
H2
Br2
1) MCPBA
2) H3O+
BrBr
OHHO xs NaH
O
OOO
Lindlar'sCatalyst