CHEMISTRY 850
Exam I
Saturday, October 20, 2012
NAME (Print)
Question
Max Points
Score
1
12
2
8
3
12
4
10
5
14
6
10
_________
7
12
_________
8
24
_________
9
16
_________
10
8
11
8
_________
12
14
_________
13
16
14
36
BONUS
_________
_________
8
Exam Total
_________
1
1)
Draw the detailed arrow pushing mechanism for each step. (12 pts.)
O
O
2. MeI
1. Me2NH, CH2=O
3. NaOH
Cat. HCl
O
O
H
H
H
O
H
H
NH
Me
OH
H
N
N
N
I
O
O
O
N
OH2
+H
N
N
H
OH
2
O
2)
Compounds containing a vinyl ether functional group are rather unstable upon exposure to
acid, and will decompose to aldehydes. Provide a mechanism that accounts for this
instability. (8 pts.)
HCl
OMe
O
H2O
H
H
OMe
H
OMe
OMe
OMe
+ H+
OH
OH2
H2O
H
OMe
H
O
OH
O
H
H2O
3)
Indicate the pKa for the protons shown in the compounds. (2 points if within 2 units, 1 point
if within 3 units) (12 pts.)
O
H3C CN
H3C NO2
25
4)
10
H
O
H
H
N
H
~20 ~9
8
N
N
H
8.8
Write the product that would be expected from the following reaction. Can you think of
anything that might go wrong with this reaction? (10 pts.)
O
O
H
H
H
O
H
Ph3P
Problem with this reaction:
The product from this reaction is also an aldehyde which could react with another molecule
of the Wittig reagent.
3
5)
Predict the product and show the mechanism for each step. (14 pts, 4 pts. for the product
prediction)
Li, NH3
O
EtI
tBuOH
e
e
OH
O
O
OH
tBuO H
H
O
O
Et
6)
I
The Wittig reactions of unstabilized phosphorus ylides give cis olefins via a phosphaoxetane
intermediate. However, the corresponding arsenic ylide gives an epoxide with the same
aldehyde. The first step in the reactions of both ylides is a [2+2] cycloaddition. Provide a
mechanism to account for the formation of the epoxide from the arsaoxetane. (Show the
stereochemistry of the expoxide.) (10 pts., 2 pts. for stereochemistry.)
Ph3P CHCH2CH3
Ph3As CHCH2CH3
Ph3As O
H3CH2C
H3CH2C
H3CH2C
H3CH2C
Ph
Ph
Ph3As O
PhCHO
Ph3As
Ph
Ph3P O
PhCHO
mech?
Ph
H3CH2C
O
Ph3As
Ph
4
CH2CH3
epoxide
O
Ph
O
H3CH2C
Ph
7)
Consider the hydrolysis of acetals A and B:
O
OMe
O
HCl
HCl
or
H2O
O
B
A
H2O
a) Which of the two molecules will hydrolyze faster? (2 pts.)
B
b) Draw the oxonium ion intermediate formed from each acetal. (4 pts.)
O
O
OH
A'
B'
c) Can you use structures of the oxonium ions to account for which is faster? (2 pts.)
A’ is not stable because of severe ring strain, so the hydrolysis of A will be very slow.
B’ does not have such problem.
d) Can you use stereoelectronics to predict which is faster? (Use orbital interactions to
illustrate.) (4 pts.)
As shown in the pictures on the right side, for molecule B
there is an interaction of the lone pair on the back oxygen and
the front C—O σ* bond, which will weaken the C—O bond to
facilitate the hydrolysis of the acetal. However, in molecule A
there is no such interaction. Thus B will hydrolyze faster than
A.
O
O
C—O σ∗
B
O
OMe
C—O σ∗
A
5
8)
Suggest a synthesis of each molecule shown below. (24 pts.)
a. Start from molecules with 8 carbons or less.
CHO
HO
O
CHO
1) EtNH2,
H+
4) HCl, H2O
2) LDA
CHO
CHO
3)
HO
or
O
CHO
1) Et2NH, H+
HO
b. Synthesize the following molecule from the starting materials provided in the box.
MeO
MeO
O
N
NH2
O
S
O
P2S5
S
NH2
NH2
MeO
HOAc, Br2
MeO
N
MeO
S
Br
O
O
c. Start from pyridine
1) H2O2
N
2)HNO3, H2SO4
3) PCl3
4) NH3
NO2
N
NH2
6
9)
Show a detailed mechanism (including all steps) to account for the following reactions. (16
pts.)
N
H
NH2
HOAc
N
+
HN
O
N
+ H+
H+
HN
NH2 O
HN
HN
HN H
HN
H2O
N
N
H
N
H+
HN
HN
HN
HN
H2N
HN
H
H2N
H2N
H+
N
N
N
N
+ H+
HN
10)
HN
HN
H3N
H
N
N
N
Pyrrole can act as a nucleophile and undergo many different reactions. It has two different
carbon sites that can react. Predict the product of the following reaction and explain the
regioselectivity. (8 pts.)
N
H
N
H
E+
H
N
H
E
N
H
E
E+
N
H
E
N
H
O
N
H
E
E
N
H
2-position is favored because of more stable carbocation intermediate.
7
N
H
E
11)
LDA is a commonly used non-nucleophilic base to make enolates form carbonyl compounds.
However, the first step shown below does not give enolate 2 which is needed for the second
step. Suggest a method for making enolate 2 and show a mechanism to account for its
formation. (8 pts.)
LDA
O
O
H
THF
E
H
2
1
O
EX
n-BuLi
3
H
O
mech:
O
O
+
H
n-Bu
12)
Li
Provide the product of the reaction shown below under both conditions and explain the
stereochemistry in each case by showing a mechanism. (14 pts., 4 pts. for product prediction)
nPr
OH
KH
nPr
nPr
H2SO4
nPr
nPr
THF, rt
nPr
SiMe3
left side:
H
H
O
O
nPr
nPr
nPr
nPr
nPr
nPr
nPr
O
SiMe3
SiMe3
nPr
nPr
nPr
O
Me3Si
Me3Si
right side:
H
OH2
OH
nPr
nPr
nPr
nPr
nPr
SiMe3
OH2
SiMe3
nPr
SiMe3
H2O
8
nPr
nPr
13)
Polyethylene terephthalate (PET) is made by the condensative polymerization of terephthalic
acid (PTA) and ethylene glycol.
Polybutylene terephthalate (PBT) is made by the
condensative polymerization of dimethyl terephthalate (DMT) and 1,4-butanediol.
Attempted reaction of terephthalic acid (PTA) with 1,4-butanediol will not afford polymeric
PBT. (16 pts.)
O
H2O
O
OH
HO
HO
O
O
O
OH
O
O
O
O
ethylene
glycol
terephthalic acid
PTA
O
n
polyethyleneterephthalate
PET
O
CH3OH
O
OCH3
O
O
O
OH
HO
CH3O
O
O
O
O
O
dimethyl terephthalate
n
1,4-butanediol
polybutyleneterephthalate
DMT
PBT
(a) Identify the structure of the byproduct formed during attempted polymerization of
terephthalic acid (PTA) with 1,4-butanediol that interferes with formation of PBT polymer.
O
O
H
O
H O
O
OH
H
O
(b) Why does reaction of dimethyl terephthalate (DMT) with 1,4-butanediol lead to polymer
PBT formation?
There is no acid that catalyzes cyclization of the diol to THF in this case.
(c) Why is there no need to use dimethyl terephthalate (DMT) for the synthesis of PET
polymer?
Cyclization rules:
Relative reaction rate with respect to ring size: 5 > 6 > 3
Formation of ethylene oxide (3-membered-ring) from PTA and ethylene glycol is much
slower than THF formation from PTA and 1,4-butanediol.
9
14)
Indicate the missing products/reactants/reagents for the following reactions. (36 pts).
Me
O
NH2OH·HCl
N O
Ph
Me
Ph
K2CO3
Br
O
O N
NH2OH·HCl
Me
NaOEt
Ph
O
S
O
Cl
N
H
N
NaH
O
Me3Si
Br2
OMe
Br
OMe
FeBr3
O
OSiMe3
OLi
PhCH2Br
MeLi (1 eq)
Me2CuLi
Ph
Me3SiCl
1) POCl3
N
H
O
2) EtSH
N
SEt
1) n-BuLi
SiMe3
Me3Si
SiMe3
2) EtI
3) NaOH
AcCl (excess)
O
O
AlCl3
O
O
1) NaH
OMe
O
Br
O
O
OMe
2) nBuLi
10
Bonus question. (8 pts).
Who won the Nobel Prize in chemistry for 2012? Robert J. Lefkowitz, Brian K. Kobilka
In which University(ies) was the work done?
Howard Hughes Medical Institute and Duke University Medical Center, Durham, NC, USA &
Stanford University School of Medicine, Stanford, CA, USA
Describe the nature of the work for which the award was given.
Studies of G-protein–coupled receptors
11