a.
Rank by acidity. The most acidic compound is 1, while the least acidic compound is 5.
O
O
O
O
O
OH
1
OCH3
4
2
5
OH
3
b.
Rank by rate of hydrolysis. The carboxylic acid derivative that hydrolyzes the fastest in
basic conditions is 1, while the carboxylic acid derivative that hydrolyzes the slowest in basic
conditions is 5.
O
O
S
O
O
3
c.
S
4
O
O
N
H
S
1
2
5
Rank by basicity. The most basic compound is 1, while the least basic compound is 5.
CN
5
N
4
NH2
N
2
3
NH2
1
2.
Similar to a Wittig reaction, a sulfur ylide can also react with a carbonyl. The sulfur
ylide is generated by reacting butyl lithium with a sulfonium salt. When the sulfur ylide reacts
with cyclohexanone, however, an epoxide is formed.
a.(10) Draw the mechanism for this reaction.
O
BuLi
(H3C)2S CH2
(H3C)2S CH3
O
(H3C)2S
epoxide
O
O
(H3C)2S CH2
CH3SCH3
b.(5) Draw the organic products formed when the sulfur ylide shown reacts with
cyclohexanone.
O
CH3SCH3
3.
Indicate the reagents that would allow the following interconversions to occur. Each
reaction may require more than one step. Draw the steps above the appropriate letter. (6 points
each)
O
Br
A
O
OH
B
H
C
O
O
E
1) Mg
2) CO2
1) LAH
2) PDC
__________
A
__________
B
O
D
1) cyclohexane amine
2) LDA 3) CH3Br
4) H+, H2O
__________
C
cannot use LDA
directly on aldehyde
H
acetone
NaOCH3
cyclohexanone
NaOCH3
__________
D
(Aldol)
__________
E
(Robinson)
4.
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
a.(6)
O
O
CoASH
S
choline
CoA
acetyl-CoA
O
acetyl choline
Given the structure of acetyl choline, draw the structure of choline.
HO
N
b.(6) Does acetyl-CoA react faster or slower with choline than an ester under similar
conditions? Why?
Acetyl-CoA reacts faster than an ester. A thiol ester reacts faster because the thiolate leaving
group is more stable than the alkoxide leaving group with an ester.
c.(6)
N
Draw the structure of the product if acetyl-CoA reacts with 1-butanamine.
O
N
H
Reaction of an amine with a thiol ester would generate the amide shown.
5.
Indicate the preferred products for the following reactions. Assume proper work-up for
each step. (7 points each)
a.
1) CH3I, excess
2) Ag2O, !
NH2
Hoffman elimination
b.
H 2N
Cl
1) NaNO2, HCl
2) HBF4
F
Cl
c.
O
NaOCH3
OCH3
O
O
O
Dieckmann cyclization
d.
P(Ph)3
1) BuLi
2)
H
O
H
e.
1) BuLi, -78˚C
2) CH3Br
O
O
f.
OH
HO
1)
(1 equiv.)
O
H
O
O
H+
2) NaCN
3) H+, H2O, !
H
OH
CO2H
g.
H2O2
N
Cope elimination
h.
H
N
N
O
H+
i.
1) Br2, NaOH, !
2) CH3OH, H+
O
O
O
j.
O
O
!
O
OH
N
H
NH2
k.
O
F3C
O
CH3ONa
O
O
O
l.
O
OH
O
O
H
CH3ONa
Aldol reaction
6.
Indicate how to synthesize the product shown using the starting material supplied. You
can use any organic or inorganic reagents you desire, but you must use the indicated starting
material. (15 points each)
a.
O
O
N
1) LAH
2) H+
O
N
HO
H+
O
1) SOCl2
O
KMnO4
2)
H
N
b.
OH
O
O
O
OH
O
O
(CH3)2CuLi
LAH
EtONa
7.
A starting material (A) has a molecular formula of C6H12O2 and the 1H NMR is shown.
When A is reacted with sodium ethoxide, a new product B is obtained which displays two peaks
in a IR at 1718 and 1746 cm-1 (in addition to other peaks). Compound B is then reacted with
sodium ethoxide followed by benzyl bromide to generate compound C. Compound C is then
heated in acidic aqueous conditions to produce compound D. Indicate the structures for
compounds A-D. (7 points each)
1) NaOCH2CH3
NaOCH2CH3
A
H+, H2O, !
C
B
2)
O
O
O
__________
Compound A
O
Br
O
O
__________
Compound B
D
O
O
O
__________
Compound C
__________
Compound D