1.
Rank the following compounds in the trend requested. (15 points each)
a.
Rank by rate of reaction of carbonyl with nucleophile. The carbonyl that reacts the
fastest with a nucleophile is 1, while the carbonyl that reacts the slowest is 5.
O
O
H
4
H
3
O
O
O
H
Cl3C
H
2
1
5
b.
Rank by boiling point. The compound with the highest boiling point is 1, while the
compound with the lowest boiling point is 5.
Br
N
N
1
H
N
NH2
4
2
5
3
c.
Rank by acidity. The most acidic carboxylic acid is 1, while the least acidic carboxylic
acid is 5.
Br
O
Br
O
OH
OH
OH
OH
O
O
O
OH
O 2N
O
5
3
4
2
1
2.
Nepetalactone is the common name for the structure shown. It is the active ingredient in
catnip. Draw the structures of the compounds obtained in the following scheme. (7 points each)
H
O
O
Nepetalactone
H
CH3NH2
!
H
HO
O
OH
(1 equiv.)
N
H
H
H+
O
H
O
N
H
H
O
O
LAH
H
H
N
H
H+, !
N
H
H
O
O
3.
In parts a-c compare the two esters shown. Indicate which of the two esters would have a
faster rate of hydrolysis for each pair. Include a short description of why the chosen ester would
have a faster rate. (7 points each)
a.
O
F3C
O
O
O
B
A
A is more reactive. The carbonyl is more
electrophilic due to the electron withdrawing
substituent.
b.
O
NO2
O
O
O
B
A
B is more reactive. The leaving group with the para
nitro group is a more stable anion.
c.
O
O
O
O
A
B
A is more reactive. The leaving group is more
stable. The anion of the leaving group for B is less
stable due to the extra donating methyl groups.
d.
Many carbonyl reactions occur in biochemical reactions. Acid chlorides and anhydrides
are too reactive, however, under the aqueous biological conditions. Your body will therefore use
reactions on other carbonyl derivatives. One example is the formation of acetylcholine, a
neurotransmitter. Acyl adenylate (adenylate is a biological part of the leaving group labeled as
Ad in the scheme below) reacts with a primary thiol of coenzyme A (labeled CoA) to form acetyl
coenzyme A, which then reacts with choline to form acetylcholine.
O
O
P Ad
O
O
acyl adenylate
O
CoASH
S
HO
CoA
N
acetyl choline
choline
Acetyl coenzyme A
Draw the structure of acetyl choline.
O
O
N
4.
Indicate the preferred product for the following reactions. Assume proper work-up for
each step. (7 points each)
a.
O
!
O
NH
NH2
H3CO
b.
O O
Cl
O
Cl
N
O
NH2
S
S
c.
1) NaH
O
Br
2)
NH2
NH
3) NH2NH2
O
d.
CH3I
NH2
N
excess
e.
Br
NH2
Br
1) NaNO2, HCl
2) CuCN
3) H+, H2O
Br
Br
O
OH
Br
Br
f.
O
CH3CO3H
O
O
g.
O
HO
O
H+, H2O
H
OH
h.
O
(Ph)3P
H
i.
NH2
N
O
H
H+
j.
1) H2O2
2) SOCl2
O
O
3)
O
OH
H
O
O
k.
O
OH
OCH3
MgBr
l.
N
1) H2O2
2) !
5.
Propose a synthesis of the products shown using the starting material indicated. You may
use any other organic or inorganic reagents, but you must begin with the starting material shown.
(15 points each)
a.
O
H+/H2O
O
EtLi (2 equiv)
N
H
O
N
OH
O
b.
1) Mg
Br 2) formaldehyde
TsCl
OH
OTs
CH3NH2
N
H
O
Cl
O
N
6.
The compound A, with molecular formula C12H17N1O1, was hydrolyzed under acidic
conditions to yield two products B and C. The 1H NMR for these products are shown below (in
the 1H NMR for compound B, the signal at 2.58 ppm is a heptet and the signal at 1.20 ppm is a
doublet). If the products were washed in D2O then the singlets at 11.88 ppm for compound B
and 3.40 ppm for compound C disappear. When compound B is reacted with first thionyl
chloride followed by ammonia and then finally phosphorus oxychloride, product D is obtained.
When compound C is reacted with acidic sodium nitrite followed by potassium iodide,
compound E is obtained. Draw the structures of compounds A-E. (7 points each)
H+/H2O
A
B
C
+
!
1) SOCl2
2) NH3
3) POCl3
1) NaNO2, HCl
2) KI
E
D
O
N
H
A
O
NH2
HO
B
C
I
NC
D
E