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