1.
Rank the following compounds in the trend requested. (15 points each)
a.
Rank by rate of nucleophilic acyl substitution with a common nucleophile. The acid
derivative that reacts the fastest is 1, while the acid derivative that reacts the slowest is 5.
O
O
O
O
O
4
O
CH3
O
Cl
O
O
2
3
1
5
b.
Rank by equilibrium with the hydrated form. The carbonyl with the greatest percentage
of the hydrated form at equilibrium is 1, while the carbonyl with the least amount of hydrated
form at equilibrium is 5.
O
H
F3C
O
N
H
H
1
c.
O
O
O
3
2
4
5
Rank by acidity. The most acidic compound is 1, while the least acidic compound is 5.
O
O
OH
OH
1
4
SH
3
Cl
OH
2
5
2.(21) Pethidine, the common name of the active ingredient in the narcotic analgesic Demerol,
was subjected to two successive exhaustive methylations with Hofmann eliminations, and then
reacted as shown in the scheme below. Indicate the structure for compounds A, B and C.
O
1) CH3I, excess
2) Ag2O, H2O, !
O
1) CH3I, excess
2) Ag2O, H2O, !
A
B
1) NaOH
2) SOCl2
3) LiAl(OCH2CH3)3H
C
N
Pethidine
O
O
O
O
H
O
N
__________
A
3.
___________
B
__________
C
Consider the compound shown.
O
O
H
N
O
O
O
CF3
O
a.(7) When this compound is reacted with methanol, one carbonyl will react first preferentially
to form a new ester compound. Draw the compound that is formed preferentially after the first
carbonyl reacts with methanol.
O
O
H
N
O
O
O
HO
CF3
O
b.(12) Draw all products obtained when the initial compound shown is hydrolyzed completely
in acidic aqueous conditions.
O
OH
HO
OH
O
O
H 2N
O
OH
HO
c.(8) When heated under acidic conditions, one of the products shown in part b will react in an
intramolecular fashion to form a new compound. Draw this new product formed.
O
NH
4.
Indicate the preferred product for the following reactions. Assume proper work-up for
each step. (7 points each)
a.
O
O
Cl
N(CH3)2
HO
N(CH3)2
O
1 equiv.
b.
O
NH2
N
H+
c.
NH2
CN
1) NaNO2, HCl
2) CuCN
F
F
d.
O
CH3CH=PPh3
e.
1) SOCl2
2) NH3
3) POCl3
O
CN
OH
f.
O
MgBr
1)
CN
2) H+, H2O
g.
O O
O
H+, H2O
HO
OH
h.
O
OH
CH3CH2MgBr
Cl
i.
H
N
O
NH2
Cl
HO
O
HO
1 equiv.
j.
O
H+, H2O, !
HO
O
CN
k.
O
O
1) CH3NH2
2) LAH
O
H
N
HO
l.
O
O
NH2
S
!
SH
HN
m.
H2O2, !
N
n.
1) H+, H2O, !
O
Li
2)
CN
3) H+
2 equiv.
5.
Shown below are the two active ingredients in the pain relievers aspirin and Tylenol.
O
H
N
O
CO2H
O
HO
acetylsalicylic acid
(aspirin)
acetominophen
(Tylenol)
a.(15) Propose a method to synthesize acetominophen (active ingredient in Tylenol) starting
with benzene and using any other organic or inorganic reagents you desire.
HNO3
H2SO4
NO2
NH2
Sn, HCl
1) NaNO2, HCl
2) H2SO4
OH
HNO3
H2SO4
OH
O
O
N
H
OH
OH
Sn, HCl
Cl
1 equiv.
H 2N
O2N
b.(8) Which pain reliever can be stored in the medicine cabinet for a longer period of time?
Why?
Tylenol. Aspirin has an ester functional group which can be more easily hydrolyzed with water
in the air than the amide functional group in Tylenol.
c.(8) Which pain reliever can be sold as a liquid version (dissolved in water) for easier
administration to children? Why?
Tylenol. Similar to reasons stated in part b, the amide group in Tylenol will not be hydrolyzed as
easily as the ester in aspirin. Aspirin would hydrolyzed readily if stored in water.
6.(28) The starting material A (C8H14O4) has a strong absorbance in the IR at 1730 cm-1 and the
1
H NMR is shown below. Upon reaction with first base and then thionyl chloride, compound B
(C4H4O3) is obtained which has an IR absorbance at 1787 and 1841 cm-1. Compound B was then
reacted with aniline to form compound C, which was subsequently reacted with one equivalent
of borane to synthesize compound D. Indicate the structures of compounds A-D above the
appropriate letter.
NH2
1) NaOH
2) SOCl2
A
(C8H14O4)
B
(C4H4O3)
C
O
O
O
O
O
O
O
D
H
N
HO
O
B
C
D
4
6
4
H
N
HO
O
O
A
BH3•THF
1 equiv.