Chemistry 213
Clark College
Exam 2 Review SOLUTION
1. Road map. Provide the intermediates for the synthesis of Buproprion, better known by the trade
names Wellbutrin® or Zyban®. [18]
O
1) Cl
AlCl3
2) H2O
Cl2
FeCl3
A
A:
B
HBr
C
OH
HO
H+
H2N
D
E
TEA
H3O+
F
B:
O
O
Cl
C:
D:
O
O
O
Br
Br
Cl
Cl
E:
F:
O
O
O
HN
HN
Cl
Cl
Exam 2 Review
Spring 2008
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Chemistry 213
Clark College
2. Flutamide (Eulexin®) is a drug that is used in the prevention and treatment of prostate cancer by
reducing the amount of testosterone and androsterone in target cells. Propose a synthesis of
flutamide from (trifluoromethyl)benzene.
CF3
CF3
O2N
The CF3 group is a meta director, so we can add one
nitro group in the correct location. Once it is reduced
to the amine (in preparation for the amide), it is a o/p
director, and the second nitro group can be added.
O
N
H
CF3
CF3
CF3
CF3
O
HNO3 O2N
H2
H2SO4
Ni
EtO
NH
NH2
NO2
2
CF3
*I added the nitro before making the
amide, as the amine activates this ring
O2N
more and will make the reaction easier!
HNO3
H2SO4
O
N
***Remember, if you use the acid chloride to make the amide H
you MUST use a non-nucleophilic base like TEA or pyridine!
And no SN2 reactions on an sp2- hybridized carbon!
3. Synthesize the following molecule from benzene.
CH3
O
F
To put the fluoride on, we will have to go through
the diazonium salt. That begins with a nitro group
that gets converted to the amine, so we have
control over the placement of the other groups.
CH3
CH3Cl
HNO3
H2SO4
AlCl3
NO2
meta director
CH3
H2
Ni
NO2
NH2
O
1)
CH3
Cl
AlCl3
2) H2O
O
NH2
o/p director
***You must reduce the nitro group
before you add the ketone group, or
that will be reduced to an alcohol!
1) NaNO2,
HCl, 0°C
2) HBF4, !
CH3
O
Exam 2 Review
Spring 2008
F
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Chemistry 213
Clark College
4. Complete the following Diels-Alder reaction, provide a mechanism, and give a product that is
consistent with the following observation: an IR of the product shows a broad peak centered at
3000 cm-1. [8]
OH
O
O
O
OH
O
OH
O
Heat
O
C10H12O4
OH
O
H
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
O
H+
O
O
5. Each of the following compounds can be hydrolyzed back to butanoic acid when treated with acid
and water. Which will react the most rapidly? Completely explain your answer. [10]
O
O
O
O
O
N
O
H
The anhydride will react most rapidly. The leaving group on the carbonyl is the acetate ion, which is a
weak base stabilized through resonance. Compared with the methoxide ion and the methylamide ion, it
is the weakest base of the three leaving groups and is therefore the best leaving group.
6. Provide the mechanisms for the following reactions.
O
OH
O
O
Cl
H
Exam 2 Review
N
H
CH3
O
O
OH
H
O
HO
O
O
O
H
O
Cl
N CH H
CH3
3
N
HH
H
Spring 2008
Cl
N CH
3
H
H
O
HO
OH
O
N
H
CH3NH3+Cl-
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Chemistry 213
Clark College
7. Determine the structure of Compound A below. Then, give the structures of the two starting
materials that, when heated in the presence of acid, will form compound A. [13]
Compound A
C7H14O2
6H, d
3H, t
2H, d
2H, q
1H, m
Spectrum obtained from http://www.aist.go.jp/RIODB/SDBS/cgi-bin/cre_index.cgi, SDBS Spectral Database of Organic
Compounds, (accessed April 25, 2007).
O
OH
H+
heat
HO
O
O
Compound A
8. What is the correct IUPAC name for the following molecule?
O
OEt
a. E-ethyl-3-methyl-2-pentenoate
b. Z-3-methyl-2-pentenoic acid, ethyl ester
c. Ethyl Z-3-methyl-3-penten-5-oate
d. Ethyl E-3-methyl-2-pentenoate
Exam 2 Review
Spring 2008
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Chemistry 213
Clark College
9. Which of the following is the correct product for the following reaction?
O
O
CH3OH
H+
H3CO
O
H3CO
O
O
OCH3
HO
OH
H3CO
H3CO
OH
O
10. What statement best explains why an amide can’t be synthesized directly from the carboxylic acid?
a. The amine will deprotonate the carboxylic acid proton and will no longer be a nucleophile
11. Nomenclature.
a. Name the following molecules using the IUPAC naming system.
O
O
F
Br
OH
N
O
O
O
O
O
O
Cl
H
H3C
O
Cl
NH2
H
N
HN
F
CH3
O
i) N, N–dimethyl–3–bromobutanamide
ii) Z-4-fluoro-3-heptenoic acid
iii) Propyl benzoate
iv) (3R, 4S)-3-chloro-4-methylcyclopentanone
v) 4-methyl-3-oxopentanal
vi) 3,4-dimethyl-6-oxoheptanoyl chloride
vii) 3-fluoro-5-methoxyaniline
viii) R-N,4-dimethylpentan-2-amine
ix) N-ethyl-3-methylbutan-2-amine
b. Draw the following molecules from the IUPAC names.
i)
O
Cl
3,3–dimethylhexanoyl chloride
O
OH
HO
O
ii) 2–methyl–1,4–butanedioic acid
H
N
OH
iii) trans-3-(ethylamino)cyclohexanol
Exam 2 Review
Spring 2008
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Chemistry 213
Clark College
12. Fill in the blanks I.
O
O
OH
OH
O
N
H
pyridine
O
O
O
O
H+
H
N
O
N
OH
1) NaBH4
2) H3O+
O
O
OH
O
O
O
SOCl2 or PCl3
pyr or TEA
Cl
1) DIBALH, -78°C
2) H2O
EtO
O
Cl
O
H
O
1) (CH3CH2)2CuLi
-78°C
2) H2O
H
N
O
O
OEt
N
H+, heat
HO
H
N
OH
O
O
O
O
O
HCl
H 2O
O
O
O
Cl
Exam 2 Review
OH HO
Give both organic products.
N H
pyridine
O
N
O
Spring 2008
Page 6 of 8
Chemistry 213
Clark College
13. More fill in the blanks.
NH2
NH2
NH2
H2N
1) NaNO2
HCl, 0°C
2) CuCN
3) H2, Pt
I
N
Excess Et-I
1) NaNO2
HCl, 0°C
2) HBF4, !
F
O
O
Br
NH2
1) NaN3
2) LiAlH4
O
Br
1)
N K+
NH2
O
2) N2H4, !
14. Road Maps. Give the identities of the compounds in the following synthetic pathways.
O
OH
O
HBr
H2O2 Br
O
NH3
H2N
DMSO
OH
NH2
Br
O
H2N
Exam 2 Review
Spring 2008
NH
OH S
Py OCl
rid 2
ine
heat H N
2
Pyridine
O
Cl
NH2
Page 7 of 8
Chemistry 213
O
Clark College
1) BrMg
2) H3O+
H
O
OH
H2CrO4
O
HO
O
Cl
SOCl2
pyr
O
O
OH
1) Hg(OAc)2,
H2O
2) NaBH4
O
OH
H+
O
CH3NH2
DMSO
O
H+
O
N H
Exam 2 Review
N
Spring 2008
C12H21N
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