Exams Organic Chemistry MIT

TUYN TP
THI HA HU C
MIT
Massachusetts Institute of Technology

Dr. Kimberly L. Berkowski
5.12, Spring 2005
Organic Chemistry
PRACTICE EXAM IIa
Books, notes, and calculators will not be allowed in the exam room.
Molecular model kits will be allowed during the exam.
You will be given a periodic table.
The exam will focus on Chapters 5-8 in McMurry as well as all topics
covered in lecture and any previous material.
This practice exam is longer than the real exam.
HAVE FUN!
Actually, not at all since Me groups

would have to leave as methyl cations.
However, does react quickly with
certain "E+" (electrophile) to form a semistable ionic species: [(CH3)6(Ph)E]+
KEY
Organic Chemistry 5.13
Friday, September 29, 2006
Prof. Timothy F. Jamison

Hour Exam #1
Name
_____________________________________________________
(Please both print and sign your name)
Official Recitation Instructor
__________________________________
Directions:
Closed book exam, no books, notebooks, notes, etc. allowed.
However, calculators, rulers, and molecular model sets are permitted.
Please read through the entire exam before beginning, in order to make sure that you have
all the pages and in order to gauge the relative difficulty of each question. Budget your
time accordingly.
Show all your work if you wish to receive partial credit.
You should have 14 pages total: 8 exam pages including this page, 4 pages of reference
information, and 2 blank pages for scratchwork.
Question:
1. _________/
2. _________/
3. _________/
4. _________/
5. _________/
Total: __________/
Grader:
10 points
25 points
25 points
25 points
15 points
_________
_________
_________
_________
_________
100 points
_________
1. (10 points total, 2 points each) For each set of compounds below, circle the one in
which the indicated hydrogen is the furthest upfield in a 1H NMR spectrum.
OMe
NO2
NMe2
6.77
6.59
A.
Both Awarded Full Credit
B.
CHCl3
CH3Cl
CH2Cl2
CH4
C.
D.
E.
CH3OCH3
CH4
H3C
CH3OCH2OCH3
CH3
(CH3)3CH
(CH3)2CH2
CH3 CH3
O
H2C = CH2
Figure by MIT OCW.
2. (25 points total) Answer the questions below about the structure that has the following
data:
EA
MW (g/mol)
13
C NMR (ppm)
IR (cm-1)
C, 66.62; H, 11.18; N, 22.20

126.20
140.3, 48.0, 24.7
2116 (strong more intense than the C-H stretches
between 2800 and 3100); no other peaks between
1500 and 4000.
1
H NMR spectrum:
6H, J=6.9 HZ
N=C=N
1H, J=6.9 HZ
11
10
ppm
Figure by MIT OCW.
a. (3 points) To what structural fragment does the signature splitting pattern in the 1H
NMR correspond? Circle your final answer.
CH3
CH3
CH
or = c-Pr etc.
CH3
Figure by MIT OCW.
b. (2 points) Which peak or peaks in the 13C NMR correspond(s) to the fragment you
identical in a, above. List the chemical shift(s) of the peak(s), and circle your final
answer(s).
49.0, 24.7
Figure by MIT OCW.

3
c. (5 points) Determine the molecular formula of this compound. Circle your final answer.
C7H14N2
d. (5 points) Calculate the Index of Hydrogen Deficiency (IHD) of this unknown

compound. Circle your final answer.
e. (10 points) Draw the structure of the unknown compound. Circle your final answer.
N=C=N
N C N
(Also full
credit)
Figures by MIT OCW.

4
3. (25 points total) Answer the questions below about the structure that has MW = 107
and the following NMR spectra:
6 H,s
2 H, J=7.9 HZ
1 H, J=7.9 HZ
10
200
180
160
5
PPM
140
120
100
PPM
80
60
40
20
Figure by MIT OCW.

5
a. (10 points) Determine the molecular formula of this compound. Circle your final
answer.
.107 - ODD # OF N
.CONSIDER 1 N:
.107 -14 = 93
93/13 = 7 + 2/13
=> C7H9N
C7H9N
b. (5 points) Calculate the Index of Hydrogen Deficiency (IHD) of this compound. Circle
your final answer.
c. (10 points) Draw the structure of the unknown compound. Circle your final answer.
Me
Me
Figures by MIT OCW.

6
4. (25 points total) An unknown compound (X) contains only carbon and hydrogen, has
MW = 112, and exhibits the spectral data below. In addition to the IR signal listed below,
there are only peaks corresponding to C-H stretches (between 3300 and 2900) and several
peaks in the fingerprint region. Please note that there are no overlapping peaks in either
the 1H NMR or the 13C NMR spectra. In other words, what you see is all there is!
IR (cm-1)
13
C NMR (ppm)
1
H NMR (ppm)
2145
77.8, 70.1, 30.2
2.45 (s)
When compound X was treated with excess n-Buli (n-butyllithium) in tetrahydrofuran and
then excess CH3I (iodomethane), a new compound (Y) with MW = 168 and 4 signals in its
13
C NMR spectrum was formed.
What are the structures of X (15 points) and Y (10 points)? (Show your work in the space
below for partial credit consideration.) Write your final answers in the boxes provided
below.
H
C
C
C
C
C
1. 4 n-BuLi
(C
CH3 )4
2. 4 CH3I
C
H
H
X
1. n-BuLi (excess), THF

2. CH3I(excess)
X (MW=112)
Y (MW=168)
Figure by MIT OCW.
5. (15 points) In one of our problem sets, cubane (C8H8) was one of the possible
answers to a structure elucidation problem. Based on the formula for the Index of
Hydrogen Deficiency, the IDH of cubane is 5. However, as you know, a cube has
six sides. In other words, it looks like cubane has 6 rings and thus that its IHD
should also be 6.
Please provide an explanation (not the formula used to calculate the IHD) for this
apparent discrepancy in the spaces below.
CHEMICALY, CAN DO 5 "HYDROGENATION" RXNS TO OBTAIN "SATURATED"
(ACYCLIC, NO T BOND) BOND :
H2
1
C8H8
H3C
H 1 H
4
H
H3C
REDRAW WITH
DISTORTED
H 3 H
H
CH2
IHD=5
H
C-C
CH3
C8H8
IHD=0
BONDS, VOILA
CUBANE IS IN
FACT A PENTACYCLIC
MOLECULES !
4
1
ALSO, CAN DRAW AS CUBE (BONDS 1-12,

ORDER 1 AT LEFT) AND SEE THAT
DRAWING 5 RING GIVES CUBANE.
6
8
3
9
5
11
12
10
Figure by MIT OCW.

8
KEY
Wednesday, October 25, 2006

Hour Exam #2
Name
_____________________________________________
(Please both print and sign your name)
_________________________________
Directions:
Calculators are not permitted for the exam. However, rulers, and molecular
model sets are permitted.
Please read through the entire exam before beginning, in order to make sure
that you have all the pages and in order to gauge the relative difficulty of each
question. Budget your time accordingly.
Show all your work if you wish to receive partial credit. You should have 8
pages total: 6 exam pages including this page and 2 blank pages for
scratchwork.
Question:
1. _________/
2. _________/
3. _________/
4. _________/
Total: __________/
Grader:
14 points (page 2)
16 points (page 3)
48 points
22 points
_________
_________
_________
100 points
_________
1. (30 points total, 2 points per box) In each box below, draw the structure of the major
product of the reaction. Indicate relative stereochemistry where appropriate. If no reaction
occurs, put a large X in the box. (Note: D = deuterium, 2H)
a.
O
H3C
H
+
H
CH3
O
O
Me
Me
O
b.
H3C
CH3
+ H3CO
Me
Me
CO2Me
CH3
Me
d.
Me
(CH3)2S
c.
CH3
O3
O
H
O
CHO
Me
O
O
e.
Me
NaBH4
OH
OH
f.
(R)
HO
Me
H
H+
EtOH
O H
(S)
CH3
g.
BF3
MgBr
OH
Ph
H
(S) Me
OE+
Figure by MIT OCW.

2
(1., continued see previous page for directions)
h.
O CH3
H3C
O
CH3
CH3
H3C
CH3 1. PhCH2OH,
Hg(OAc)2
Me
Ph
Me
2. NaBH4
CH3
i.
Me
CH3
O
Ph
j.
Me
CH3
Me
Ph
or
m.
H H
o.
SH
Br
H H
2S + 2S
(or (IS, cis)
NaOH
S Na
Me
HH
Must have "x"

in box
n. No Reaction
Me
Me
l.
[3,3]
COPE
Me
CH3
Me
Me
k.
C=N=O
1.NaOH
2. excess
EtBr
S Br
H3C
Figure by MIT OCW.
3
2. (48 points total)

a. Draw the orbitals (by shading the lobes appropriately) at each energy level for
1,3,5- hexatriene (2 points each).
b. Write the number of nodes in the box to the left of each orbital array (1 point each).
c. For the ground state of 1,3,5-hexatriene, draw the electron population for each
orbital on the line to the right of each orbital array. For each electron, clearly indicate
whether it is spin up or spin down. If there are no electrons given orbital, leave it
blank (1 point each).
# of nodes
# of Nodes
orbitals
Orbitals
electron
population
Electron
population
5
E
4
3
2
1
0
1 point per box
2 points per orbital array
1 point each
or
1 point per box
1 point each
Figure by MIT OCW.
2. (continued)
d. For each reaction shown below, indicates which energy level is used to predict the
stereochemical outcome by shading the appropriate lobes of the entire orbital
array. (The methyl groups are omitted for clarity; you do not have to draw them.)
e. In the box under each reaction arrow, write conrotatory or disrotatory, as appropriate.
f. In the box to the right of each reaction arrow, draw the major product of the reaction,
clearly indicating the relative stereochemistry.
Me
Me
heat
Me
Disrotatory
(trans)
Me
Me
h
Me
Conrotatory
(cis)
Me
Me
Me
heat
Me
Me
Disrotatory
(cis)
Me
Me
Me
h
Me
Conrotatory
(trans)
(Shade appropriate lobes)
(write "conrotatory" or disrotatory")
2 points each
1 points each
Me
(draw major product- show

stereochemistry)
3 points each
Figure by MIT OCW.
(shade appropriate lobes)

2 points each
(write conrotatory or disrotatory)

1 point per box
(draw major product show stereochemistry)

3 points per box
OH Me
H
3. (22 points total) Using retrosynthetic analysis, propose a

synthesis of the molecule to the right (A). You may use any
reagents you wish, as long as your starting materials and any
other reagent that is used to install a carbon that is found in the
final product (target molecule A) have no more than 6 carbon
atoms. For example, 1,3-butadiene and benzene would be
acceptable, but benzyl bromide (PhCH2Br) would not be.
Me
target molecule (A)

Write your synthesis in the forward direction, showing all
Steps and reagents necessary. (You may include solvents, but
you are not required to do so.) Draw a box around or circle
Your final synthesis.
Hint: Use a Diels-Alder reaction.
HO
Me
Me
Target
O
H
HO
Me
Me
O
O
Me
Me
Forward Synthesis:
O
Me
O
O
Diels- Alter
(endo)
Me
Me
HO
LiAlH4
O
O
Me
Me
HO
Intramolecular
Oxy-mercuration
1.Hg(OAc)2
2. NaBH4
Me
HO
CH3
O
Product
Figure by MIT OCW.

6
First Three Letters of Last Name:
TA Name:
Hour Exam #3
5.13 Fall 2006
KEY
Organic Chemistry II
November 15, 2006
Name______________________________________________________________
Signature___________________________________________________________
ID#________________________________________________________________
1.
Make sure your exam has 9 numbered pages plus a periodic table.
2.
Write your initials on each page.
3.
Look over the entire exam before you begin to familiarize yourself with its
length. Do what you know first, then attempt the harder problems.
4.
Show all of your work. Partial credit receives points!
1. (4 pts) When N,N-dimethylaminopyridine reacts with one equivalent of acid,

the sp2 nitrogen becomes protonated.Why don't you see protonation at the sp3
nitrogen when you know that the more p character an orbital has, the more stable
it is with a positive charge?
H
H3C N CH3
H3C
CH3
H3C
H+
CH3
H+
N
H
conjugate acid
not formed
The Sp3 Nitrogen is actually Sp2. The lone pair on nitrogen is in a P orbital
&can delocalize into the pyridine ring. The lone pair of electrons on the Nitrogen
atom in the ring are orthogonal to the ring & cannot delocalize .Those electrons
are more available for bonding and more basic.
2. (4 pts) Rank the following molecules in order of electrophilicty(1= most electrophilic )
O
CH3
Me
N
CH3
O
Me
O
Cl
Me
CH3
O
Me
CH3
Figure by MIT OCW.
3. (18 pts) Provide the missing products for each reaction. Indicate no reaction with N.R.
H3C
(a)
(b)
CH3
CH3
H3C
CH3
O
H3C
NH2
H2O2
D
NaBH4
NR
1.CH3l(excess)
2.Ag2O
3. D
CH3 1.CH3l(excess)
2.Ag2O
3. D
(c)
H3C
(d)
O
H3C
(e) H3C
O
Cl
+ HNMe2
NaBH3CN
H+
1. HNMe2,pyridine
2.LiAlH4
3. H2O
+
:N(Me)3
CH3
Me
H3C
Me
H
H3C
CH3
CH3
Figure by MIT OCW.
4. (21 pts) Provide the missing reagents for each reaction. Several steps may be needed for
some transformations.
1.LiAlH4
2. H2O
(a) H C C N
3
H 3C
(b)
H3C
H 3C
Pr
HO
OEt
1. H3O+/H2O, D
2. EtLi (2 eq.)
O
(d)
H 3C
MeMgBr
2 eq.
Pr
Me
Me
1.H2N OH,H+
2. LiAlH4
3. H2O
NH2
CH3
H3C
or 1. POCl3 2.EtMgBr
NH2
H3C
CH3
3. H3O+/H2O
1.SOCl2
2. NH3
3. NaOH, Br2
1.LiAlH4
2. PCC
OH
O
(c)
or
1. SOCl2
2.LiAl(OtBu)3H
NH2
NH2
OH
(e)
1. NaN3
(f)
H3C
Br
2. LiAlH4
3. H2O
or
1.
2.
O
N K
H2N
NH2
H3C
+
O
NH2
Figure by MIT OCW.

3
(1 2 pts) Consider the labeling experiment outlined below. What level of 18O
incorporation do you expect in the recovered anhydride (high or low)? Your
answer should include a mechanism of hydrolysis and a detailed explanation.
5.
O
O
Me
O
O
O
Me
k1
OH
*
stop at 50% conversion

of acetic anhydride
*
OH/H
*
2O
*
OH
Pt
k-1
O
+
k-1
O
*
O
k1
k2
k2
O
*
O
HO
O
*
OH
*
OH
O
O
18
O Incorporation is expected to be low in recovered anhydride.

O
OH. There fore, k2 >> k-1, or elimination of
is a better leaving group than
faster than revesal to starting material. Most of the
18
O will be found in the acetic acid product.

Figure by MIT OCW.
6. (10 pts) Provide a mechanism for the following transformation.
O
MeO
O
MeO
Me
OH
Me
O+/H
OH H3
2O
Me
Me
Me
O H
H OH2
MeO
Me
Me
Me
OH
Me
MeO
MeO H
OH
Me
PT
OH
O
Me
Me
O H
Me
+ OH2
OH2
Me
+ H3O
Me
Me
Figure by MIT OCW.
(10 pts) Under basic hydrolysis conditions, a nitrile goes through a primary
amide intermediate before becoming a carboxylate. Show the mechanism for this
reaction and explain why it is NOT a facile method for converting nitriles into
carboxylates.
7.
+ NH3
N H
N
R
OH
H OH
OH
OH
N H
O
R
OH/H2O
HO
N H
NH2
HO
O
R
OH
NH2
O
R
NH2
+ NH3
Base catalyzed hydydrolysis of nitriles is not a facile process because NH2

is not good leaving group( -OH is better!) There, fore, the reaction is slow.
Figure by MIT OCW.
6
8. (9 pts) Provide a synthesis for the following compound.
OH
Cl
HNO3
NO2
H2SO4
NO2
Cl2
AlCl3
Cl
H2, Pd
OH
Cl
H2SO4
N N
NH2
NaNO2
HCl
Cl
Cl
Cl
Figure by MIT OCW.
9. (12 pts) Provide a selective synthesis for ONE of the following compounds. Circle the
molecule that you want graded. All of the carbon atoms of the product should come from
either ethanol or compounds that contain just one carbon atom.
A
O
Me
N Me
Me
OH
Me
NH2
B
OH
Mg
PBr3
MgBr
Br
OH
1. CO2
2. H2O
O
SOCl2
Cl
LiAl(OtBu)3H
HCN
CN
OH
1. LiAlH4
2. H2O
OH
NH2
O
OR
1. H
MgBr
OH
2. H2O
OR
Jones
OH
O
MeOH
EtOH
PCC
PBr3
PBr3
EtBr
MeBr
1. NaN3
2. LiAlH4
3. H2O
OR
MeOH
PBr3
MeBr
SOCl2
OH
1. Mg
2. CO2
3. H2O
0
Et
1. NaN3
2. LiAlH4
3. H2O
OH
SOCl2
Cl
O
pyridine
O
NH2
1. H
H ,H+
2. LiAlH4
3. H2O
N
H
O
Me
NH2 +
Cl
pyridine
1. LiAlH4
N
O
2. H2O
H
N
Figure by MIT OCW.

8
EXTRA CREDIT
(5 pts) Synthesize methamphetamine (crystal meth) from benzene and any other reagents.
All the carbon atoms in the product should come from reagents that only contain one
carbon atom.
H
N
Me
1. Mg
2.CO2
Br2
FeBr3
Me
O
OH
3.H2O
1.LiAlH4
OH
2.H2O
PBr3
OH
O
1.MeLi
OH
O
2.H2O
1. Mg
2.CO2
3.H2O
Br
H2NMe
H
OH
N
1.LiAlH4
2.H2O
Figure by MIT OCW.

5.13, Fall 2006

EXAM #3 EXTRA PROBLEMS

KEY
What to expect on Exam #3:

1. ~1 Labeling experiment
2. ~2 Mechanisms
3. ~2 Syntheses
4. ~5 transformations supply missing product
5. ~5 transformations supply missing reagents
6. ~3 General questions
1. (4 points each, 8 points total) In the boxes, please provide the reagents for the illustrated
transformations. More than one step may be required.
(a)
1. KCN
2. H3O
i-Pr
or
1. Mg ,ether
2. CO2
+
3. H3O /workup
Br
O
i-Pr
OH
(b)
1. SOCl2
2. LiAl(OtBu)3H
3. workup
O
i-Pr
or
1. LiAlH4 (XS)
2. H2O
3. PCC
O
i-Pr
OH
Figure by MIT OCW.
2. (2 points each, 8 points total) Please provide the products of the following reactions. If no
reaction is expected, write NR.
(a)
O
Et
(b)
1. Excess Na BH4
Cl
O
Et
(c)
(d)
O
Et
NR
or
O
2. Workup
1. Excess MeLi
OMe
Et
2. Workup
HO
Me
Et
Me
2. Workup
1. Excess LiAlH4
NMe2
OH
2. Workup
1. Excess MeMgBr
OH
Et
Et
Et
NMe2
Figure by MIT OCW.
NAME____________________________
3. (2 points each, 16 points total) Please provide the requested products or reagents. If no
reaction is expected, write NR.
(a)
Br2,
NaOH
Me
NH2
Me
Me
NH2
H2O2,
Me
(b)
O
Me
H2N
Me
OH
N-OH
1. LiAlH4
cat. H+
NH2
2. workup
(c)
POCl3
n-Bu
n-Bu
NH2
CN
H3O+
H2O
O
nBu
OH
(d)
NH2
NaNO2
HCl
N2
CuBr
Br
Figure by MIT OCW.
Name_________________________
4. (11 points) Please provide a detailed mechanism for the illustrated conversion of acetic acid
(A) to acetyl chloride (B).
O
Me
OH
Cl
O
S
O
Cl
Me
O
S
Me
HCl
Cl
Cl
OH
Cl
Me
+ SO2
Cl
S Cl
O
OH
Cl
OH
Cl
Me
Cl
O H
Me
+ SO2
Cl
Figure by MIT OCW.
Name_______________________
5. (11 points each, 22 points total) Please provide syntheses for only two of the three indicated
compounds. All the carbon atoms should be derived from the allowed starting materials. You
may use any common reagents.
Allowed Starting Materials:

Me
Me
CO2
Me
Me
OH
Me
Pick Two:
Me
HO Me
H
N
Synthesis # 1:
D
A
O
OH
2
O
Me
1.O3
2.MeS
3.Na2Cr2O7
H2SO4
SOCl2
Cl
NH3
Me
Me
Me
KMnO4
Me OH
1.BH3, THF
2. H2O2,OH
or
H3O+/H2O
O
NH2
OH
POCl3
1.PBr3
MgBr
O
1.CO2
OH
2. H +
2.Mg
SOCl2
OH
(excess)
1.MeMgBr
2.H2O
Cl
Figure by MIT OCW.
Name__________________________
5. (Continued)

Me
Me
Me
CO2
Me
A
Pick Two:
Me
OH
Me
Me-OH
HO Me
Me
Me
H
N
Me
Me
O
1.
Synthesis #2:
C
MeOH
OH
O
2. H2NNH2
PBr3
or
TsCl, Pyridine
Br
NH2
PCC
H
N K
NH2
or 1. NaN3
2. LiAlH4
3. H3O+
or XS NH3
Cat H
1. LiAlH4
2. H2O
H
N
Figure by MIT OCW.
Name________________________________
6. (11 points) Provide a synthesis that will selectively convert A to B. Show all the key
intermediates and furnish all the important reagents. This is not a one-step process.
O
Me
A
O
Me
HNO3
H2SO4
O 2N
HO
Me
B
O
Me
H2, Pd
H2N
N2
O
Me
NaNO2, HCl
O
Me
H2SO4, H2O
HO
O
Me
Figure by MIT OCW.
Name________________________________
7. Methyl acetimidate (A) is hydrolyzed in aqueous sodium hydroxide to give mainly acetamide
and methanol (eq 1). In aqueous acid, A hydrolyzes to give primarily methyl acetate and
ammonium ion (eq 2).
a) Provide a detailed mechanism for the illustrated process. Please show all arrow
pushing.
HO-
NH
Me
N-H
Me
OMe
H2O
OMe
Me
NH2
PT
Me
OH
NH2
OMe
Me
MeOH
H OH
+ MeO
(1)
MeOH + OH
NH2
Figure by MIT OCW.
b) Provide a detailed mechanism for the illustrated process. Please show all arrow
pushing.
NH
Me
Me
H
Me
OMe
OMe
NH2
OMe
excess H
H 2O
PT
OH2
Me
Me
OMe
NH4
NH3
OMe
OH
O
Me
(2)
OMe + NH3
H2O
O
Me
OMe +
NH4
Figure by MIT OCW.
c) Briefly explain why the two reactions provide different products.
Basic conditions:
NH2 worse L.G. than
OMe . Elimination favors amide
Acidic conditions: Acid/base equilibrium favors protonation of
ntrogen making it a good
L.G. Also, NH4 is not nucleophilic + formation of ester is reversible
Figure by MIT OCW.

5.13: Organic Chemistry II
8. Synthesize the indicated compounds from the allowed starting materials shown below. All of
the carbons of the target compounds should be derived from the allowed starting materials.
8.
b)
TsCl
MeOH
NaCN
MeOTs
MeCN
1) LAH
NH2
2) H2O
HBr
EtOH
EtBr
Mg
1)
H, O
2) H3O+
EtMgBr
Na2Cr2O7
OH
EtNH2, H+
PCC
O
T
H
c)
Me
OH
Me
OH
Me
OH
KMnO4, H+
PBr3
Br
Me
Cl
Br
O
Me
Me
OH
Me
PCC
CN
SOCl2
Me
Me
LiAlH4
O
Me
NH2
Me
Me
Me
NH
Me
LiAlH4
O
1
Cl
Me
Me
Me
N
T
Figure by MIT OCW.

1 from part c
O
Cl
(d)
Me
CN
OH
O
Me
H-CN
Me
AlCl3
LiAlH4
OH
NH2
Me
NO2
H2SO4
(e)
NH2
H2/Ni cat
Br
FeBr3
HNO3
NH2
Br2(excess)
Br
Br
NaNO2
HCl
Br
Br
O
H2O, H
OH
Br
Br
Br
Br
C N
N N
CaCN
Br
Br
Br
SOCl2
Br
Br
O
Cl
Br
Br
H 2N
O
N
H
Me
4 from part c
Br
Me
Br
Figure by MIT OCW.

9. Provide the best stepwise mechanism for the illustrated process. Please show all arrow
pushing.
(9)
H
NH2
H+
O H
H
NH2
H
N
H
H 2O
H
H
N
H
H
OH
H
OH
NaBH3CN
"H "
O H
H
H
H
HO
H
H
NaBH3CN
"H
"
H2O
H
O
H
N
H
Target
Figure by MIT OCW.
10

10. (a) Provide the best mechanism. Please show all arrow pushing.
(a)
O N
benzylic cation
H
C Me
O
OH
CH3
C CH3
C
N
OH
OH
OH
OH
etc
N C
CH3
O H
or workup
Me
N
O
Target
Figure by MIT OCW.
11

(b) Provide the best mechanism. Please show all arrow pushing.
Me
H
N
OH2
H 2O
H H
Me
N
O H
O
Me
H
N
Me
O H
O
H
H
NH2
O
NH3
Me
Me
+
H
NH3
O H
Me
O
H O
H
NH3
O
H
Me
OH2
H
NH3
O H
Me
O
OH
H
OH2
NH3
OH
O H
HO
Me
workup
NH2
OH
Figure by MIT OCW.
12

11. Consider the labeling experiments outlined below:
11.Start with the mechanisms:
O H
NHMe
H2O
HO
k1
PT
O H2
OH
H 2O
k1
NHMe
NHMe
NHMe
PT
PT
HO
OH
k2
O H
OH
OH
NH2Me
Proton transfer are very fast.
O H
Acid/base equilibria favor the protonated

N (not O). Therefore, once the tetrahedral
intermediate forms, loss of NH2Me (k2) is
faster than loss of OH (k1).Very little O is
incorporated into the unreacted starting
material.
H
O
OH
OH
O H
OMe
H2O
k1
HO
O H2
PT
H2O
OH
k1
OMe
OMe
OMe
PT
PT
HO
All of the oxygens in the tetrahedral
intermediate are roughly equally basic.
Therefore, each protonated form 13
present in the same concentration ,and
k2 ~= k1. as a result, you would expect
more O incorporation into the ester starting
material than you would into the corresponding
amide.
OH
OMe
H
k2
O H
O H
OH
OH
H
O
O
OH
OH
Figure by MIT OCW.
Name_______________
13
First Three Letters of Last Name:
TA Name:
Hour Exam #4
5.13 Fall 2006
December 6, 2006
Name____________________________________________________________________
Signature_________________________________________________________________
ID#______________________________________________________________________
1. Make sure your exam has 7 numbered pages plus a periodic table.
2. Write your initials on each page.
3. Look over the entire exam before you begin to familiarize yourself with its length. Do
what you know first, then attempt the harder problems.
4. Read the instructions carefully and budget your time.
5. Show all of your work. Partial credit receives points!
1. (3pts) For each molecule, write the correct pKa value for the most acidic proton.
O O
O O
OMe
9
25
20
Figure by MIT OCW.
2. (16 pts) Fill in the correct reactants for the following transformations.
Be specific about quantities, where relevant.
1.KCN, HCN
2.LiAlH4 or CH2N2
3.H2O
4.NaNO2,HCl
O
a)
O
b)
Ph
CH3
Ph
CH3
O
d)
O
Br
Ph
1. LDA (1 eq)
Br (1 eq)
2.
O
c)
Br2
AcOH
O
CH3
Ph
MgBr2
O
H
Figure by MIT OCW.
3. (24 pts) Provide the missing products for each reaction. Indicate no reaction with
N.R.
(a)
O
Ph
Excess NaOH
CH3
(b)
Excess I2
Ph
H3O /H2O
+ HCI3
D
OMe
(c)
O
(d)
H 3C
CH3
CH3
NaOEt
EtOH
CH3
O
OEt
mCPBA
CH3
HO
(e)
H 3C
CH3
H3O+/H2O
CH3
Me
(f)
H3O+/H2O
or
HO
OH
Figure by MIT OCW.
4. (15 pts) Provide a mechanism for the following transformation.
O
H2C
O
Me
Me
OEt
OEt
1 equiv.
Me
O
O
OEt
OEt
O
OEt
OEt
O
Me
HOEt
O
OEt
OEt
O
OH O
OEt
O
H OEt
OEt
+ OEt
OEt
HOEt
O H + OEt
H
EtO
OH O
H
O
OEt
OEt
O
O
OEt
OEt
O
Figure by MIT OCW.

O
HOEt
Figure by MIT OCW.

3
5. (14 pts) Provide a mechanism (steps 1 and 3 only)
HO OH
1. H3O+/H2O
2.NaBH4(no mech)
3.H3O+/H2O
+ H
OH OH
OH2
HO
H2O
O
H3O
HO
OH2
H2O
+
NaBH4
H2O H
OH2
OH
+ H2O
Figure by MIT OCW.

H2O
H
H3O
Figure by MIT OCW.
6. (14 pts) Synthesize the target molecule from methyl acetate. Partial credit will be
given for a retrosynthetic analysis.
O
Me
Me
Me
Me
target
2 Me
methyl acetate
1.
O O
1 eq OMe
OMe
O
OMe
O O
OMe
(claisen)
2.
OMe
H3O
PBr3
1.LiAlH4
Br
OH
2. H2O
NaOMe
O O
OMe
OMe
O O
NaOMe
OMe
Br
Br
O
CO2
O O
OH
H3O /H2O
D
Figure by MIT OCW.
7. (14 pts) Synthesize the target molecule from methyl acetate and 2-butanol. Partial
credit will be given for a retrosynthetic analysis.
OH
OH
Me
Me
Me
O
Me
O
Me
OH
OMe
2-butanol
OMe
methyl acetate
target
Cl
PCC
AcOH
Cl2
OH
O
2 MeO
MeO
+
NaOMe
MeOH
NaOMe
MeOH
aOH
MeO
MeO
O
H2O
MeO
O
NaBH4
O
O
OH
MeO
HO
Figure by MIT OCW.
EXTRA CREDIT
(5 pts) Propose a reasonable mechanism for the following transformation.
O
Me
+H
Me
N
H
Me
H+, cat
Me
N
Me
Ph
OH
O
H
Ph
HNMe2
H
NMe2
H
PT
OH2
Me
Me
N
H
N
Me
O
Me
Ph
Ph
O
Ph
Me
OH
O H
Me
OH2
H 2O
Ph
Me
N
H O
Ph
Me
Me
Me
Me
Figure by MIT OCW.

5.13, Fall 2006

EXAM #4 MORE PROBLEMS

DO THESE PROBLEMS BEFORE THE OTHER
SET OF EXTRA PROBLEMS!
(they are more relevant to the exam material)
What to expect on Exam #4:

1. pKas of ketones, diketones, esters, etc.
2. ~3 Transformations supply missing reagents
3. ~10 Transformations supply missing product
4. ~2 Mechanisms
5. ~2 Synthesis
What NOT to expect on Exam #4:

1.
Determine mechanism by crossover and stereochemical experiments
(end of Fridays lecture)
2.
Neighboring Group Participation Do not work through problems
#8, 24 & 25 on the Extra Problem Set.
1. Please provide a detailed mechanism for the following transformation. Show all
arrow pushing.
O
O
O
OMe
cat. MeO
+
MeO
OMe
OH
OH
OMe
H
OMe
O
O
OMe
O
OH
O
H
OMe
O
OMe
OMe
O
OMe
H
HO
OMe
CO2Me
O
O
O
O
OMe
H
O
O
O
Figure by MIT OCW.
2. (10 points) Please provide a detailed mechanism for the following transformation.
Show all arrow pushing.
O
OMe
Me
Me
Me
Me
Me
1. MeMgBr
2. H3O+
Me
Me
Me
MgBr
Me
Me
H2O
OH
Me
OMe
Me
Me
Me
Me
Me
Me
H2O
HO
Me
OMe
Me
Me
MeO
OH
Me
Me
Me
Me
Me
PT
H2 O
Me
Me
OMe
OH2
Me
Me
Me
Me
Me
Me
Me
OR:
OMe
Me
Me
Me
MeO
Me
O
H2 O
Me
Me
H2 O
Me
Me
Me
Me
Me
Figure by MIT OCW.
Me
3. (10 points) Please provide a detailed mechanism for the following transformation.
Show all arrow pushing. Hint: This mechanism is from problem set 6.
1. NaOMe, MeOH
2. H+ workup
Me
Me
OMe
H
O
O
OMe
Me
Me
O
OMe
O
OMe
Me
Me
O
OMe
Me
Figure by MIT OCW.
4. (10 points) Diastereomers A and B provide different products upon diazotization.

Please explain why only one product is formed selectively in each reaction. Your
explanation should include a 3-dimensional mechanism for the formation of each
product from the corresponding diazonium salt.
OH
OH
NaNO2
HCl
NH2
t-Bu
t-Bu
N2
t-Bu
A
O
OH
OH
NaNO2
HCl
t-Bu
NH2
t-Bu
N2
t-Bu
In the concerted Tiffeneau-Demjanov rearrangement, the migrating bond must be antiperiplanar

to the leaving group.
(A)
H
O
H
:B
-N2
OH
product
N2
H
(B)
OH
N2 H
:B
-N2
H
product
H
H
(Bolded bonds are antiperiplanar)
Figure by MIT OCW.
5. Please provide a detailed mechanism for the following transformation. Show all
arrow pushing.
O
O
Think about common

disconnection...
cat. -OH
H2O
Me
Me
Me
retroaldol
(aldol)
H
OH
OH
OH
OH
OH
H2 O
O
H
O
OH
Me
HO
HO
H-OH
Me
H
OH
Target
Figure by MIT OCW.
6. Please provide a detailed mechanism for the following transformation. Show all arrow
pushing.
O
Cl
OH
O
O
Ar
O
O
HO
O
O
Ar
O
Ar
Figure by MIT OCW.
7. Please provide a synthesis of the indicated compound. All of the carbon atoms
should be derived from methyl acetate.
Target
O
Me
Me
methyl acetate
Me
O
+
OMe
OMe
Me
MeO
OMe
H+
1 equiv
MeO-
MeO
1. 1 equiv 2.
Br
NaOMe
(below)
1. 1 equiv
NaOMe
H3O,
2.
MeO
Br MeO
(below)
O
H3O
OMe
MeOH
PBr3
OH
1. LiAlH4
2. workup
MeBr
OH
PBr3
Br
Figure by MIT OCW.
8. Please provide a synthesis of the indicated compound. All of the carbon atoms
should be derived from isopropanol.
Target
OH
OH
Me
Me
isopropanol
OH
OH
PCC
PBr3
OH
LDA
(1 equiv.)
Br
(below)
Br
1. LiAlH4
2. workup
Target
OR:
OH
PCC
O
1. cat. -OH
2.
H2
Pd/C
1. LiAlH4
2. workup
Target
Figure by MIT OCW.
9. (12 points) Please provide a synthesis of the indicated compound. All of the carbon
atoms should be derived from methyl acetate. You will receive partial credit for a
complete retrosynthesis
Target
O
Me
Me
OMe
methyl acetate
O
+
Me
OMe
1. 1 equiv.
NaOMe
2. H+ wkup
OMe
Me
OMe
1. 1 equiv.
NaOMe
2. EtBr
O
O
O
H3O+
1. 1 equiv.
NaOMe
OMe
2. EtBr
OMe
mCPBA
Target
Figure by MIT OCW.
10. (12 points) Please provide a synthesis of the indicated compound. All of the
carbon atoms should be derived from dimethyl malonate and alcohols containing
three or fewer carbons. You will receive partial credit for a complete retrosynthesis.
Target
O
O
HO
MeO
MeO
OMe
alcohols containing
three or fewer carbons
dimethyl malonate
OH
MeOH
PCC
PCC
1. cat. H+, excess

formaldehyde
2. H+,
H
O
1. 1 equiv.
NaOMe
2.
MeO
MeO
OMe
1. NaBH4
MeO
OMe
OH
2. workup
OMe
cat. H+
MeO
Figure by MIT OCW.
10

Friday, September 30, 2005

Hour Exam #1
Name
SOLUTIONS
______________________________________________________
(please both print and sign your name)
Directions:
____________________________________
However, calculators, rulers, and molecular model sets are permitted.
Please read through the entire exam before beginning, in order to make sure that
you have all the pages and in order to gauge the relative difficulty of each
Show all of your work if you wish to receive partial credit.

You should have 11 pages total: 6 exam pages including this page, 3 pages of
reference information, and 2 blank pages for scratchwork.
Question:
Grader:
1. ________/
40 points
_______
2. ________/
30 points
_______
3. ________/
30 points
_______
100 points
_______
Total: _________/
1.
(40 points total 5 points each) The molecular formulas and 1H NMR spectra of 8
common organic solvents are provided below and on the following 2 pages. For each,
neatly draw the entire structure (i.e., not the acronym) in the box provided. In some
cases, relative integration values (circled numbers) and/or other information have been
provided.
Note: Do not represent functional groups with partial molecular formulas or other
abbreviations. For example, do not use Ph or C6H5 for a phenyl group. Draw the entire
group (including hydrogen atoms).
a. C7H8
CH3
5
Draw structure here
10
ppm
Figure by MIT OCW.
b. C3H8O
OH
6 ,d
CH3
CH3
1
Septet
Draw structure here
11
10
ppm
Figure by MIT OCW.

2
c. C3H6O
O
H3C
CH3
Draw structure here
10
ppm
Figure by MIT OCW.
d. C2H3N
CH3C
Draw structure here
10
ppm
Figure by MIT OCW.
e. C3H7NO
O
H
3 ,s
CH3
3 ,s
CH3
1 ,s
Draw structure here

11
10
Figure by MIT OCW.
f. C4H8O2
O
3
H3C
OCH2CH3
,t
Draw structure here
10
,q
ppm
Figure by MIT OCW.
g. C4H10O
CH2CH3
CH3CH2
3
2
,q
,t
Draw structure here

10
ppm
Figure by MIT OCW.

h. C4H8O
Draw structure here

11
10
5
ppm
Figure by MIT OCW.
2. (30 points total) Answer the questions below about the structure that has the following data:
EA
MS
13
C NMR
1
H NMR
C, 81.61; H, 11.06; N, 7.32

191, 176.
162.7, 136.5, 118.9, 35.1, 31.9
7.59 (t, J = 7.8, 1H), 7.14 (d, J = 7.8, 2H), 1.34 (s, 18H)
a. (10 points) Determine the molecular formula. Circle your final answer.
C13H21N
Figure by MIT OCW.
b. (5 points) Calculate the Index of Hydrogen Deficiency (IHD). Circle your final answer.
13 -21/2+1/2+1= 4
c. (2 points) How many types of carbon (chemically non-equivalent) does this compound
have? Circle your final answer.
5
d. (3 points) How many types of hydrogen (chemically non-equivalent) does this
compound have? Circle your final answer.
e. (10 points) In the space below, draw the structure of the molecule that is consistent
with all of the data provided. Circle your final answer.
N
Figure by MIT OCW.
3. (30 points total) Answer the questions below about the structure that has the following data:
EA
M+
IR
13
C NMR
1
H NMR
C, 75.69; H, 8.80
206
3430 (broad), 1705 (strong)
181.4, 140.9, 137.0, 129.5, 127.4, 45.9, 44.1, 30.3, 22.5, 18.2
11.9 (broad s, 1H), 7.21 (d, J = 7.7, 2H), 7.09 (d, J = 7.7, 2H), 3.70
(q, J = 7.0, 1H), 2.44 (d, J = 6.8, 2H), 1.84 (nonet (9 lines), J = 6.8,
1H), 1.49 (d, J = 7.0, 3H), 0.89 (d, J = 6.8, 6H)
a. (7 points) Determine the molecular formula. Circle your final answer.
C H O
13 18 2
b. (5 points) Calculate the Index of Hydrogen Deficiency (IHD). Circle your final answer.
13 -18/2+1= 5
c. (8 points) Which protons are coupled to which? Complete the tables below using the
NMR data above. Write H1, H2, etc. or none, as appropriate, in the box provided, and
list all protons to which a given proton is coupled.
Proton(s)
(ppm)
H1
11.9
H2
Coupled to
Proton(s)
(ppm)
Coupled to
none
H5
2.44
H6
7.21
H3
H6
1.84
H5, H8
H3
7.09
H2
H7
1.49
H4
H4
3.70
H7
H8
0.89
H6
d. (10 points) Draw all of the possible enantiomers and diastereomers of the unknown
compound that are consistent with all the data given. Circle your final answers.
CH3
H
H
OH
CH3
H3C
CH3
CH3
H3C
OH
Figure by MIT OCW.
e. (Extra credit 5 points total) What is the common name of this over-the-counter
pharmaceutical (3 points), and for which symptoms is it indicated (2 points)?
IBUPROFEN; PAIN

Wednesday, October 26, 2005

Hour Exam #2
Name
SOLUTIONS
_________________________________________________
(please both print and sign your name)
Directions:
____________________________________
Calculators are not permitted for this exam. However, rulers and molecular model
sets are permitted.
Please read through the entire exam before beginning, in order to make sure that
you have all the pages and in order to gauge the relative difficulty of each
Show all of your work if you wish to receive partial credit. You should have 7
pages total: 5 exam pages including this page and 2 blank pages for scratchwork.
Question:
Grader:
1. ________/
42 points (page 2)
_______
1. ________/
30 points (page 3)
_______
2. ________/
28 points
_______
100 points
_______
Total: _________/
1. (72 points total, 3points per box) in each box below, draw the structure
of the reagent or major product of the reaction, where appropriate. If no reaction occurs,
put a large X in the box. Clearly indicate the double bond geometry and relative
stereochemistry of the major product, where appropriate.
(a.)
1. NaH
2. PhCH2Br
CH3OH
OH
OH
1. NaHCO3
2. CH3l
(c.)
1. NaOH
2. CH2=CHCH2CI
t-BuSH
Me
Me
Me
OMe
O H
O
Me
O
H
m-CPBA
(draw the structure)
O O
S
NaBH4
Cl
Me
tBu
DMDO (excess)
(draw the structure)
Me
OMe
Hg(OAc)
MeOH
O
O
Me
Me
t-BuSH
Hg(OAc)2
(g-h.)
(i-n.)
Ph
OCH3
1. NaH
2. CH3l
(b.)
(d-f.)
CH3O
O3
(o.)
OH
OH
Me
O
NaBH4
Me
(CH3)2S
O
O
Me
O
O
H
H
Figure by MIT OCW.
(o).
OMe
Me
H
O
(p).
+
O
C
(q).
Me
O
O
Cy = Cydohexyl =
H O
Me
Me
H O
O
H O
Me
hv
Dis
Et
Ph
H O
O
Me
(r).
OMe
Cy
Me
Me
Ph
Et
Me
(s)
Me
hv
Dis
Ph
Ph
Et
Me
Me
(t-u)
Me
(v-w)
CO2Me
+
C N O
hv
Me
con
Dis
Me
Me
CO2Me
D
CO2Me
CO2Me
C10H12O4
CO2Me
(x)
Et
+ Me
CO2Me
Ph
MeO2C
CO2Me
C14H18O4
O
Me
Ph
or
Me
O
CO2Me
Figure by MIT OCW.
2. (28 points total) In a Nazarov Cyclization (below), treatment of a dienone with a strong
Lewis acid effects a thermal 4 electrocyclic ring closure, giving intermediate A, and an aqueous
workup affords the final product (B), the thermodynamically most stable cyclopentenone.
TiCl4
TiCl4
TiCl4
H2O
O
B
Figure by MIT OCW.

a. In the diagram below, draw the atomic orbitals (by shading the lobes appropriately) that
represent the system of C (the precursor to A) in the reaction above (2 points each).
b. Write the number of nodes in the box to the left of each orbital array (1 point each).
c. For the ground state of C, draw the electron population for each orbital on the line to the
right of each orbital array. Clearly indicate whether each electron is spin up or spin
down. If there are no electrons in a given orbital, leave the line blank (1 point each).
# of Nodes
Electron
population
Orbitals
1 point per box
1 point each
Figure by MIT OCW.

4
4. (continued)
d. (4 points each) For the example of the Nazarov cyclization below, in the indicated
boxes draw the direct product of the electrocyclic ring closure and the
cyclopentenone final product after the aqueous workup. In both cases, clearly
indicate stereochemistry and double bond geometry, as appropriate.
O TiCl4
O
Me
Me
TiCl4
Me
H
H2O
Me
Me
Me Me
direct cyclization product
Me
Me
cyclopentenone
LESS STABLE CYCLOPENTENONES (2 Pts PARTIAL CREDIT):
Me
Me
Me
Me
Me
Me
Figure by MIT OCW.
KEY

5.13, Fall 2006
PRACTICE EXAM #3
Hour exam #3 will be held on Wednesday, November 15, from 12:05

12:55.
Books, notes, and calculators will not be allowed during the exam.
Molecular model kits will be allowed during the exam. You will be
given a periodic table and blank pages.
Material Covered on Exam #3:

Everything presented in lecture related to Amines, Carboxylic
Acids, and Carboxylic Acid Derivatives
Reaction and Drill Problems
Problem Sets 5 and 6
McMurry Chapters 20, 21, 24
All 5.12 material.
The answer key will be posted on Monday
1. Rank the following acyl derivatives based on their reactivity as electrophiles toward
hydroxide ion (1 = most reactive, 5 = least reactive).
O
Me
O
NMe2 Me
O
O
O
Me
Me
O
Cl
Me
O
O
Me
OMe
3
2. In the boxes, please provide the reagents for the illustrated transformations. More
than one step may be required
O
(a)
1.
1. NaN3
2. LiAlH4
3. H2O
Me
Br
N K
or
or
Excess NH3
O
2. H2NNH2
Without Over-Alkylation
Me
NH2
1. HCN, Cat. KCN
(b)
2. LiAlH4
3. H2O
O
Me
Me
HO
Me
NH2
Me
Figure by MIT OCW.
3. Please provide the requested products. If no reaction is expected, write NR.

O
n-Bu
Cl
O
n-Bu
OMe
HO
Et
n-Bu
Et
NR
2. workup
1. excess MeLi
OH
2. workup
OH
NR
or
O
n-Bu
OH
H2SO4
Na2Cr2O7
n-Bu
Me
n-Bu
EtO-, EtOH
O
n-Bu
2. workup
n-Bu
1. excess NaBH4
n-Bu
2. workup
1. excess EtMgBr
OMe
n-Bu
1. Li(t-BuO)3AlH
n-Bu
OH
Figure by MIT OCW.
4. Please provide the requested reagents.
(a)
Br2, NaOH
H2O
O
n-Bu
n-Bu
NH2
(b)
NMe2
1. Excess MeI
2. Ag2O,
or
H2O2,
CH2
Me
Me
(c)
NH2
CuCN
CN
N2 Cl
POCl3
or
(d)
P2O5
n-Bu
n-Bu
NH2
H+/H2O
or
-OH/H O
(e)
n-Bu
CN
CN
n-Bu
OH
Figure by MIT OCW.
5. (12 points) Consider the labeling experiment outlined below:

O
H2 O
Stop the reaction at 50% conversion and examine

the recovered acyl chloride for incorporation of O
OH
Cl
O = isotopically labeled oxygen (18O)
Me
(a) Please provide the mechanism for the hydrolysis reaction shown above, including the
pathway for incorporation of O into the acyl chloride.
O
k1
Me
OH
Cl
OH
Me
Cl
k2
PT
HO
Me
Cl
k1
Me
Cl
k2
O
O
Me
OH
Me
OH
(b) What level of O incorporation ("high" or "low") you would expect to observe in the
recovered acyl chloride? Explain briefly.
Very low incorporation of labeled Oxygen into acid chloride Cl is a much better leaving group
than OH. Hydrolysis will take place much faster than label incorporation.
k2 >> k1
(c) Based on your answer to part b, do you think the results of this labeling study definitively
prove the mechanism of this reaction? Explain briefly.
No. It is impossible to definitely prove a mechanism incorporation of the label is consistent
with both SN2 and addition elimination mechanisms.
Figure by MIT OCW.
Name_______________
6. (12 points) The hydrolysis of a nitrile (A) to a carboxylic acid (C) involves initial
formation of a primary amide (B). Provide a detailed mechanism for each the following
transformations.by MIT OCW.
(a)
Me
Me
Me
C
Me
Me
A
N
Me
H2O
Me
Me
Me
NH2
OH
Me
NH2
Me
NH2
Me
H+, H2O
Me
Me
OH
NH2
O
OH
Me
PT
OH2
Me
OH
NH3
OH
Me
H2O
Me
NH4
OH2
Me
NH2
NH2
Me
Me
Me
OH2
Me
(b)
NH2
PT
Me
H3O
Me
H+, H2O
Me
NH3
+
Me
OH
Name_______________
Me
OH
Figure by MIT OCW.
7. Provide a mechanism for the Hofmann elimination. Please show all arrow pushing.
NaOH
H2O
+ Br2
n-Bu
NH2
NH2
O
H
N
n-Bu
n-Bu
OH
n-Bu
n-Bu
Br
O
n-Bu
Br
Br
H
n-Bu
n-Bu
Br
+ OH
N
Br
O
n-Bu
C
n-Bu
C
HO
HO
H2N
n-Bu
HO
N
H
OH
n-Bu
H
N
HO
H2O + CO2 +
HNn-Bu
HO
Figure by MIT OCW.
8. Provide a synthesis that will selectively convert A to B. Show all the key intermediates, and
furnish all of the important reagents.
OMe
HNO3
H2SO4
MeO
OMe
Br
OMe
OMe
NO2
OMe
Br
Br2
H2, Pd
MeO
MeO
MeO
NH2
OMe
MeO
OMe
Br
OMe
B
OMe
NH2
Br
OMe
NaNO2, 2HCl
Br
OMe
Br
Br
H3 PO2
OMe
MeO
MeO
OR
N Cl
Br
OMe
N
OMe
MeO
OMe
OMe
HNO3
H2SO4
fuming
OMe
OMe
O2N
NO2
MeO
OMe
Br
MeO
OMe
Br
OMe
H2, Pd
CuBr
Cl
N
H2N
NH2
MeO
OMe
NaNO2
HCl
OMe
MeO
Cl
N
OMe
Figure by MIT OCW.
9. Provide synthesis for the following compounds. All of the carbons in the target molecules
should be derived from the allowed starting materials. You may use any common reagents.

MeOH
Me
O
CN
CO2
OH
(a)
Me
Cl
1. PBr3
EtOH
2. Mg, Et2O
Me
MgBr
1. H
OH 1. PBr
2. H+
MgBr
2. Mg, Et2O Me
Me
1. CO2, Et2O
2. H+
O
SOCl2
Me
NH
OH
Me
from(a)
PCC
Me
Me
MeOH
2. KCN
Me
H+
MeMgBr
H+ workup
1. PBr3
Me
OH
Me
Me
Me
Cl
(b)
1. PBr3
2. Mg, Et2O
Me
PCC
Me
Me
OH
1. LiAlH4
CN
2. H+
Me
Cat.
Me
Me
Me
MeOH
NH2
1. LiAlH4
A
B
Me
H
Me
2. H+
Me
Figure by MIT OCW.
KEY
5.13, Fall 2006

PRACTICE EXAM #4
Hour exam #4 will be held on Wednesday, December 6, from 12:0512:55.
Books, notes, and calculators will not be allowed during the exam.
Molecular model kits will be allowed during the exam. You will be
given a periodic table and blank pages.
Material Covered on Exam #4:

Everything presented in lecture related to Enols and Enolates and
Carbocations
Recitation and Drill Problems
Problem Sets 7 & 8
McMurry Chapters 22 & 23
All 5.12 materials.
The answer key will be posted on Monday
(1) (1 point each, 7 points total) Please provide the pKa value for the indicated H.
O O
Me
O O
O O
Me
Me
OMe MeO
13
11
O
MeCO2H
Me3NH
4-6
9-11
OMe
Me
EtO
16-23
23-27
2
Figure by MIT OCW.
(2) (2 points for each box; 20 points total) Please provide the indicated
information. If you use a base or an acid, please specify whether a catalytic
amount, 1 equivalent, etc. is required.
(a)
(a)
O
CH3
Ph
(b)
O
Ph
1eq.
LDA
CHI3
O
Ph
CH3
Ph
(b)
excess I2
4 eq. NaOH
also acceptable:
l eq. LDA; H workup
cat. OH
(c)
O
Ph
or H
O
CH3
OH
Ph
cat. OH
(c)
(d)
Ph
OH
or H
O
Ph
H2O
Figure by MIT OCW.
1 eq. LDA
also accepted
1 eq.
OMe
O
(e)
H+
CH
2 H3CO
H3CO
cat.
OMe
CH3
CH3
(f)
CH3
CH3
CH3
CO2CH3
also accepted:
O
(g)
CH3
MeS
MeS
O
Ph
CO2CH3
O
O
O
CH3
cat.
OMe
H3CO
1 eq. LDA; H workup

Ph
Ph
(h)
(i)
O
CH3
Ph
cat.
OMe
1 equiv. of base
CH3
MeS
Me
also accepted:
O O
MeS
Me
Figure by MIT OCW.
(3) (12 points) Please provide an efficient synthesis of the indicated target
compound. All of the carbons of the target compound must come from ethyl
acetate and 1, 5-dibromopentane.
O
Me
Br
Br
EtO
Me
target compound
O
2 EtO
Me
1 equv
EtO
Br
O OEtO
Br
EtO
Br
Me
OO
Me
1 equiv. LDA
O
OO
H2O EtO
+
cat H or HO
D
Figure by MIT OCW.
compound. All of the carbons of the target compound must come from the three
illustrated alcohols.
Me
OH
OH
Me
Me
Me Me
OH
target compound
SYNTHESIS:
(1)
OH
OH
(2)
OH
(3)
PCC
PCC
PCC
}
O
1. LDA(1.1 eq.)
OLi
1.
H
OH,
2.
O
cat. NaOMe
Figure by MIT OCW.
compound. All of the carbons of the target compound must come from acetone and
diethyl malonate.
O
O
Me
Me
Me EtO
Me
OEt
target compound
O
1 eq. EtO
O
O
cat H+
EtO
1 eq. EtO
OEt
EtO2C
H+, H2O
O
EtO
EtO ,
OEt
EtO
(-H2O)
Mechanism
not
necessary
XS
,-H2O
EtO
OEt
O-
O
O
O-
O
OEt
EtO
H+
H2O
EtO2C
EtO2C
O
OEt
EtO
O
O
H
H
O
OEt
Figure by MIT OCW.
(6) (12 points) Provide a mechanism for the conversion of A to B and B to C.

Please show all arrow pushing.
O
Me
H
OH cat.
O H
CH2
H
OH
OH
OH
O
O
OH
OH
C
O
H2O
O
OH
OH cat.
OH
H OH
OH
O
H OH
HO
OH
H OH
HO
OH
OH
OH
OH
B
O
OH
H OH
O
C
Figure by MIT OCW.
(7) (12 points) Provide the best mechanism for the illustrated transformation.
Please show all arrow pushing.
OH
catalyst
OH
+ OH
OH
OH
OH
O
O
HO
H
OH
Figure by MIT OCW.
(8) (13 points) Provide the best mechanism for the illustrated reaction. Please show
all arrow pushing. Hint: RS can serve as a nucleophile and add to the carbon of
Michael acceptors.
O
Ph
O
H
OH
Me
catalytic RS
Me
Me
Ph
Me
O
Ph
Ph
Me
SR
RS
RS
OH
OH
Ph
Ph
Me
Me
SR
A
Tautomerization mech. (not necessary)
O
Ph
RSH O
O
Me
O-
Ph
OH
Me
SR
SR
Ph
Me
RS
RS
Keto
Enol
Protonated enol
Figure by MIT OCW.

9
(9) BONUS question (10 points) The process shown below is an example of a
Mannich reaction. Nature uses this reaction to synthesize alkaloids (natural
product that contain a basic nitrogen). Suggest the best mechanism for this process.
Please show all arrow-pushing.
O
Ph
O
Me Ph
H+
Me2NH
OH
Ph
Ph
H Cat.
Ph
OH
Ph
OH
Ph
Ph
OH2
NMe2
Ph
Me2NH
Ph
H
HO
OH
Ph
Ph
B (H2O or Me2NH)
H+
NMe2
Ph
Ph
NMe2
N
Ph
Ph
B
O
Ph
NMe2
Ph
Figure by MIT OCW.
10
KEY
December 19, 2005

Final Exam
Question 1
__________/10 points
Question 2
__________/15 points
Question 3
__________/30 points
Question 4
__________/10 points
Question 5
__________/10 points
Question 6
__________/15 points
Question 7
__________/10 points
Question 8
__________/12 points
Question 9
__________/10 points
Question 10
__________/12 points
Question 11
__________/12 points
Question 12
__________/12 points
Question 13
__________/12 points
Question 14
__________/14 points
Question 15
__________/16 points
TOTAL
_________/200 points
Name (printed) ________________________________

Name (signed) __________________________________
T.A
_____________________
There are 18 pages (2-19) of questions in this exam.

1
1.
(10 points total) Write an arrow-pushing mechanism for the reaction below.
Note: Aste risk(*)=13C.
O
N
H
Me
H
O
heat
Me
OH
N
H
O
R2N+H2
H
O
Me
O
H * H
OH H
N
H
CO2
IMINIUM FORMATION +3
OH2
N
Me
CO2
Aza-cope +4
O
N
Me
Me
O H
H * H
H O
N
Me
CO2
CO2
N
Me
H2O
HYDROLYSIS +3
O
O
H2O
N
Me
CO2
13
Solution must account for C in formaldyde, otherwise no more than 5 pts should be awarded.
Figure by MIT OCW.
2. (15 points total) Compound A is prepared from B and C and has the spectroscopic data listed
below. Draw the structure of A in the box provided, and write an arrow-pushing mechanism for
its formation from B and C in the space below.
2. points 2. points
Ph
OH
+
O Catalytic H
Heat
CH3
B
O
1. point
OH
Ph
H
N
O
Ph
H
O
Partial credit for another

mechanism leading to the
right molecule that doesn't
include [3.3] sigmatropic
REARR: [0-3 points].
7
O
2. points
Data for A:
1H NMR (ppm)
IR
7.05-7.15, m, 5H
1685 cm-1
5.80, t, J = 6.3, 1H
3.67, t, J = 6.5, 4H
Molecular weight
3.47. t , J = 6.5, 4H
3.22, d, J = 6.3, 2H
2.34, t, J = 7.4, 2H
273.17
2.12, t, J = 7.4, 2H
1.71, s, 3H
Ph
N
O
Ph
O
MECHANISM 8
Ph
Claisen Rearr
O
Ph
Ph
Figure by MIT OCW.
3. (30 points total, 1 point per box) For the following 15 structures, write the number of
chemically non-equivalent (number of different types) of hydrogens and carbons in the
appropriate boxes below. (Be careful to put the numbers in the correct boxes we cant read your
mind, i.e. wrong numbers will receive no credit no exceptions.)
# non-equivalent H
# non-equivalent C
CH3
a.
All
or
nothing
CH3
Cl
Br
b.
c.
CH3
CH2
CH3
d.
CH3
CH2
CH2
CH3
Me
1
Me
2
e.
Me
3
Me
Me Me
Figure by MIT OCW.

4
# non-equivalent H
f.
Me
Me
Me
3
Me
HO
2
Me
1
6 Me
H
Me
2
i.
1
Me
g.
h.
Me 1
# non-equivalent C
3 2
Me
7
Me
1
2
1
j.
6 5
7
3
4
Figure by MIT OCW.

5
# non-equivalent H
O
k.
N
Me
Me
Me
(DIASTEREOTOPICITY)
m.
restricted rotation
i.
(3 was
accepted)
# non-equivalent C
Me
Me
(Me's are diastereotopic)
n.
Me
Me
o.
(10e-,
aromatic)
Figure by MIT OCW.
4. (10 points) An alcohol (R-OH) was treated with sodium hydride and 1-bromo-2-butyne to give
compound D (molecular weight = 166.10). Using the 1H NMR data listed below, determine the
structure of the product and the starting alcohol. Draw the structures in the boxes provided.
1. NaH, THF
2. 1-bromo-2-butyne
chirality 2pts.
R-OH
OH
5.68, ddd, J= 17.0, 10.5, 8.5, 1H

5.27, dd, J=10.5, 1.5, 1H
5.19, dd, J=17.0, 1.5, 1H
4.14, d, J=15.0, 1H
3.94, d, J=15.0, 1H
3.42, d, J=8.5, 1H
1.86, s, 3H
0.91, s, 9H
Me
draw D here
draw R-OH here
H NMR data for D (ppm)
= From ROH
= From ALKYNE
Correct ether synthesis +2 pts.

CH3
Br
Me
RO
RO
H H
RO
Has : 9 H S 2,(tBu) 2pts.

2pts. 3 H IN Alkene region, All Coupled to each other
2H, S OR 2 1H IF R IS CHIRAL
WHICH IT IS IN THIS CASE
H
H
H
2pts. Add'l 1H is coupled to 1 Alkene H
H
H
H
Z
Y
Y and Z have no H directly attached.
3.42ppm
CH3
ONLY tBr and O Remain
Figure by MIT OCW.
5. (10 points) At room temperature, compound E is converted to compound F in high yield. Using
the data provided, determine the structure of F (and draw the structure in the box provided), and
write an arrow-pushing mechanism for its formation from E.
H2N
O
S
NO2
Me
23 0C
Me
Ph
or
E
H
N
H
Ph
SO2
N
Data for F :
+3
Me
Ph
Ph
coupled to *
+ 4 if not concerted
but correct arrow
pushing over all
O
Me
IR
1H NMR (ppm)
1955 CM
7.15-7.30, m, 5H
5.99, d, J = 2.0, 1H
5.25, dq, J =7.0, 2.0, 1H
1.59, d, J =7.0, 3H
Molecular
weight
+ 2 for
allene
-1
allene
130.19
CH3
C10H10 = MW
130
+ HN=N-SO2Br
Me
Ph
CORRECT
ARROW PUSHING AND STRUCTURE =10 pts
1 OF ABOVE CORRECT: 5pts
PARTIAL CREDIT FOR PARTIALLY CORRECT MECH AND/OR STRUCTURE BOTH OK.
Figure by MIT OCW.
6. (15 points) Propose a synthesis of G from H, maleic anhydride, and benzyl bromide (BnBr =
PhCH2Br). (All of the substituents on the five-membered ring in G are cis to one another, and your
synthesis must establish this relative configuration.) Your synthesis must use H, maleic anhydride,
and BnBr. You may use any other reagents in addition to these. Write your synthesis neatly in the
forward direction, and for each transformation, write the reagents necessary over the arrow.
BnO
BnO
OBn
OBn
BnO
BnO
OO
HH
BnO
BnO
OBn
OBn
OO
OO
OO
+3
+3pts
pts
HH
HH
HH
OBn
OBn
OHC
OHC
OO
+2
+2pts
pts
OO
OO
+2
+2pts
pts
HH
OO
maleic
maleicanhydride
anhydride
+6
+6pts
pts
HH
endo
endo
HH
HH
away
awayfrom
fromCH
CH2OBn
2OBn
OH
OH
(1)
(1)OO3 3
(2)
(2)Me
Me2SS
OO
OBn
OBn
OBn
OBn
G
G
(all
(allcis)
cis)
OO
BnO
BnO
LiAlH
LiAlH4 4
CHO
CHO
OO
All
CIS
AuH's are
H' s
CiS
OO
OBn
OBn
HO
HO
OH
OH
OH
OH
OH
OH
MANY POSSIBLE CORRECT SEQUENCES AFTER

MANY POSSIBLE CORRECT SEQUENCES AFTER DIELS
DIELS - ALDER
+2
+2pts
pts
NaH
NaH
BnBr
BnBr
GG
(x.s. of each)
Figure by MIT OCW.
(7) (2 points for each box; 10 points total) Please provide the indicated information. If you use a
base or an acid, please specify whether a catalytic amount, 1 equivalent, etc. is required.
cat. HO
(a)
Ph
Ph
CH3
Ph
CH3
(c)
N OH
(d)
Ph
cat. HO
or RO
+
or H
H
O
Me
OH
O
Ph
CH2N2
H2SO4
NH
H 2O
(e)
Ph
(b)
or RO
MCPBA
Figure by MIT OCW.
10
(8) (12 points) Please provide an efficient synthesis of the indicated target compound. All of the
carbon of the target compound must come from methyl acetate.
O
Me OMe
methyl acetate
Me Me
Target compound
Various routes were possible and partial credit was given depending on efficiency.
Below are the most common:
O
1 eq MeO
OMe MeOH
O O
OMe
O-
LDA
(B)
Route 2:
Route3:
(A)
OMe
A
O-
cat. MeO
OMe
OMe
OMe
O (C)
(-H2O)
O- (A)
OMe
O (C)
(A)
OMe
OMe
1 eq MeO
2. H+, H2O
O
OMe
O
(D)
O-
O O
O O
(-H2O)
H2O
B
OMe
Route 1:
cat. H+
or OH-
(C)
1 eq MeO
2. H
cat MeO
MeO
O O
1 eq MeO,
+
2. H , H2O,
(B) OMe
Figure by MIT OCW.
11
(9) (10 points) The Strecker reaction, followed by a hydrolysis reaction, is an excellent method for
synthesizing amino acids, which are the building blocks of proteins. Provide the best mechanism
for this process. Please show all arrow pushing. Note: You do NOT have to draw the mechanism
for the hydrolysis reaction.
O
R
HCN
H CN
O
R
NH3
Strecker
H2N CN
reaction
R
H
HO
O H
R
hydrolysis H2N CO2H

R
NH3
H2N
CN
H+
transfer
H
H2O NH2
R
NH3
2pts for each step !
NH2
R
H
CN
Figure by MIT OCW.
12
(10) (12 points) Provide the structure of A and the best mechanism for both of the illustrated
transformations. Please show all arrow pushing.
HO OH
1) LiAlH4
2) H
A
C8H12O
HO OH
HO OH2
OH2
O
AlH3Li
workup
OH
H
H2O
H
OH
H
POINTS
POINTS
HO
OH2
OH2
H
+
+
POINTS
H2O
* FULL CREDIT FOR ALL STEPS AND CLEAN, THROUGH MECHANISM
Figure by MIT OCW.
13
Bu3SnI
Figure by MIT OCW.
14
(12) (12 points) Provide the best mechanism for the illustrated process. Please show all arrow pushing. Your
mechanism should rationalize why the reaction proceeds with complete retention of stereochemistry.
O
HO
HO
Me PT
NH2
O
HO
HO
HO
(2) H
Me
N
Me
Cl
N O
H2O N O
Me (1) PT
NH
N
O
H+
HO N O
O
HO
NaNO2 HCl
NH2
Na -O N O
Me
O
HO
Me
N2
N OH2
inversion
inversion
Me
+4
Cl
Overall retention
H O
Me
Cl
Neighboring Group Participation
O
Me
+ 4 pts formation of HO
O
+ 10 pts if via HO
N2
Me
NH3
+8 pts if double inversion mechanism involving NO2 as nucleophile
Figure by MIT OCW.
15
(13) (10 points) Please provide a detailed mechanism for the illustrated transformation. Show all arrow
pushing. (Bn = CH2Ph)
Hint #1: Number your carbons! Hint #2: PhSH is catalystic!
OBn
cat. AIBN,
OMe
OBn
MeO
cat. PhS-H
Initiation:
NC
CN
CN
+ N2
CN
CN
PhS
+ PhS
Propagation:
OBn
PhS
OBn
PhS
OBn
PhS
O
+
MeO
OBn
PhS
OBn
PhS
O
MeO
OMe
OBn
O
MeO
+ PhS
Figure by MIT OCW.

16
(14) (10 points) Compound A is converted to B, C, and D upon heating. The reaction is accelerated by
irradiation. Provide the structures of B, C, and D, and provide the mechanisms by which they are formed
(please show all arrow pushing).
Me
O
Me Me
A
Cl
C4H9Cl
B
C3H6O
C
C7H15ClO
D
O
+ Cl
+
C
Cl
Cl
OH
Cl
Cl
OH
Figure by MIT OCW.
17
(15) (16 points total) In an amazing process, Nature transforms squalene oxide into steroids (as a single
stereoisomer!). For each of the process illustrated below, provide the best mechanism. Please show all arrow
pushing.
Me
squalene oxide
Me
Me
Me
Me
Me
Me
Me
H2O H
Me
Me
Me
Me Me
Intermediate l
HO
Me
Me Me
Me
Me
Me
Me
Me
Ianosterol, a steroid
HO
Me
Me Me
(a). (10 points) Squalene oxide into intermediate l:

Me
Me
Me
Me
Me
Me
Me
Me
H
Me
Me
Me
Me
Me
HO
Me
Me
Me
Me
Me
Me Me
Me
Me
HO
* or Show Stepwise C
HO
Me
Me
Me
Me
Me
Me
Me Me
Me
Charges
Figure by MIT OCW.
18
+2 for each step: Protonation opening of epoxide each cation Cyclization

* if no errors
-2 if show wrong connectivity after cation Cyclic.
(b) (6 points) Intermediate 1 into lanosterol:

Me
Me
+2 for deprotonation
H
H
Me
+1 for every 1,2-shift
Me Me
HO
Me
Me Me
H2O
H
Me
HO
Me H
Me
Me
Me
Me
Me
Me
HO
Me
Me
Me
Me
Me Me
Me Me
* or show stepwise C
charges !
-1 if show deprotonation in same step at alkyl shift.

-1 if show formation of double bond s deprotonation, but show arrow
-2 for every 1,3 shift
-1 for every 2 missing mech. arrows
Figure by MIT OCW.
19
Massachusetts Institute of Technology 5.13, Fall 2006

EXAM 4 EXTRA PROBLEMS
1. Provide the best mechanism for the following reaction.
Br
OH/H2O
O_
Figure by MIT OCW.
2. A useful diketone, dimedone, can be prepared in high yield by the synthesis below.
Provide structures for the intermediate A and for dimedone, and show a mechanism
for each step up to B.
O
EtO
+
Me O
Me
OEt
NaOH
EtOH
NaOH
EtOH
H3O+
Me
O
Me
Me
NaOH
O H2O
CO2Et
H3O+
dimedone
(B)
Figure by MIT OCW.
3. A biochemist, Sal Monella, has come to you to ask your assistance in testing a
promising biosynthetic hypothesis. She wishes to have two samples of methylsuccinic
acid specifically labeled with 14C as shown below. The source of the isotope, for
financial reasons, is the salt Na14CN. Outline a synthesis that will accomplish this
objective.
(a)
CH3 O
HO
OH
(b)
CH3 O
HO
* OH
O
Figure by MIT OCW.
4. In early 1999, chemists from Tohoku Univerwsity in Japan reported that they had
achieved the transformation shown below. In this equation, B: is a base strong enough
to form enolate ions. Propose a reasonable mechanism for this transformation. (L
22.87)
B:-
CO2Me
O
CO2Me
Figure by MIT OCW.

5. With the aid of three-dimensional drawings, provide a clear rationale for the products
that are observed in the following transformations. Your rationale must include the
mechanism for each transformation.
OTs
OH
H2O,
H
H
OTs
H2O,
OH
Figure by MIT OCW.

6. Please provide a detailed mechanism for the illustrated transformation.
OMe
HO
OMe
O
F3C
OH
Figure by MIT OCW.
7. Please provide a detailed mechanism that accounts for the formation of all three of the
observed products.
H
N
O
O
O
O
Me
1. NH2OH, HCl
2. PCl5,
Me
O
N
H
Me
O
N
Me
Figure by MIT OCW.

8. a). Please provide a rationale for the illustrated rate data.
Relative Rate
OSO2Ar
KOAc, AcOH
7 x 107
OAc
KOAc, AcOH
OSO2Ar
OAc
Figure by MIT OCW.

b). Please provide a mechanism to account for the formation of the products illustrated
below. In addition, explain why no other stereoisomers are generated in the reaction.
OSO2Ar
KOAc, AcOH
OAc + AcO
O
D
Figure by MIT OCW.

9. Please provide a detailed mechanism for the illustrated transformation.
HO
HO
NH2
MeCHO
H+
HO
NH
HO
Me
Figure by MIT OCW.
10. In the reaction illustrated below, the desired product from a simple Friedel-Crafts
acylation (A) was not observed. Instead, and isomeric product (B) was generated
through a more complex route that also involves Friedel-Crafts chemistry. Please
provide a detailed mechanism for this unexpected process.
CO2H
OMe O
OMe
Me
OMe
Me
HF
Me
OMe
OMe O
B
Not desired observed
OMe
OMe O
A
Desired not observed
OMe
OMe
Figure by MIT OCW.

11. Provide the best mechanism. Please show all arrow pushing.
O
(a)
O
1 equiv MeO
Ph
MeOH
Ph
(b)
O
1) HO, H2O
2)
Figure by MIT OCW.

12. Propose a synthesis for each of the following compounds, starting with benzyl
alcohol ( PhCH2OH) and with alcohol that contains three or fewer carbons.
O
(a)
O
OMe
Ph
Me Me
(b)
Me
Ph
Figure by MIT OCW.
13. Provide a mechanism for the illustrated transformation that is consistent with the
carbon-13 labeling results. Please show arrow pushing.
O
13
Me
O
H
1 equiv EtO
OEt
13
EtO
Me
Figure by MIT OCW.
14. Provide a mechanism. Please show arrow pushing.
Me
O
Me
Me
OR
Me
O
Me
Figure by MIT OCW.
15. Propose a synthesis for the molecules on the right using the starting materials on the
left and any one-carbon organic molecules.
O
Me
O
Me
Me
Me
Me Me
Me
O Me Me O
Me
Me Me
OMe
O
Me
Me Me
Me
O
O
Me
OMe
Me
Me
O
OMe Me
Me
Me
Me
Figure by MIT OCW.
16. Provide a mechanism for the illustrated reaction. Please show arrow pushing.
CO2Et
CO2Et
CO2Et
CO2Et
2 equiv of EtO
H
H2O,
Figure by MIT OCW.

17. Provide a mechanism for the conversion of A to B and of B to C. Please show arrow
pushing.
Me
H
OH/H2O
OH/H2O
(A)
(B)
(C)
Figure by MIT OCW.

18. Provide a mechanism for the illustrated reaction. Please show arrow pushing.
O
MeO
Me
O
O
MeOH
Me Me
Me
O
Figure by MIT OCW.
O
Me
Me
1 equiv
EtO
OEt
Me
O
OEt
Figure by MIT OCW.

20. Provide the best mechanism for each of the reactions illustrated below. Hint: The
mechanism for part (a) only requires three or four steps. Please show all arrow
pushing.
Me
(a)
1 equiv of
OH
O
H2O
O
O
Me
(b)
O
Me
O
O
Me
1 equiv of
MeOH
OMe
O
O
Figure by MIT OCW.
c). Succinctly explain why different pathways are observed under the different reaction
conditions.
Me
Me
Catalytic
NH2
Me
+ MeO
O
Me + MeO
Me
Me
NH2
Figure by MIT OCW.
22. Provide the best mechanism. Please show all arrow pushing. Hint:The last step is a
Michael addition reaction.
Me
OH
Me
Et
OH
Me
Et
O
Me
Figure by MIT OCW.

23. Provide a mechanism for the illustrated reaction that relies upon C1 serving as a
neighboring group. Please show ail arrow pushing.
Cl
D
Cl
O
+
F3C
OH
O
CF3
Enantiopure
A Strong acid
Enantiopure
Figure by MIT OCW.
24. Provide the best mechanism for the illustrated transformation. Please show all arrow
pushing.
Me
OOH
Me
OH
O
Me
Me
Figure by MIT OCW.
pushing
O
Me
Me
H2O
Cl
Me
Me
N
H
Figure by MIT OCW.

pushing.
Me
Me
Me
O
Me
H
H2O,
Me
Me
Figure by MIT OCW.
27. Diastereomers A and Bprovide different products upon diazotization. Please explain
why only one product is generated selectively in each reaction. Your explanation
should include three-dimensional structures (e.g., chair representations of
cyclohexane rings) of the starting materials, intermediates, and products
OH
NH2
t-Bu
NaNO2
HCl
t-Bu
A
OH
NH2
t-Bu
NaNO2
HCl
O
t-Bu
Figure by MIT OCW.
Exam 4 Extra Problems Key
Br
1.
O
OH
O
O O
2.
EtO
H
EtO
O
OEt +
Me
O O
EtO
OEt
OEt
+H
EtO
O O OEt
EtO
OEt
H
OEt
O O
O O H
+ OEt
O
EtO
O
H3O
O
CO2
+ H2O
O
A
O O
OEt
OH
Br
EtO
OEt + OH
O O
EtO
Br
+ H2O
O O
1. HO
+
O
2. H3O+
EtO
O
Figures by MIT OCW.
3.
NaCN
OEt
(a)
dil. HOAc
N C
dil. HOAc
4.
H3O
HO
C N
EtO
H3O
CH3 O
OH
HO
CH3
CH3 O
OMe
1 2
OMe
4
O
O
O
O
OMe
B H
5
4 3
1 2
OMe
O
Me
OH
CH3
O
OEt
NaCN
EtO
CH3
(b)
H O
Figures by MIT OCW.

5.
OH
OTs
O
OH2
D
H
Figures by MIT OCW.

In this "Pinacol- like" concerted process, the migrating bond must be antiperiplanar
to the LG so that the oxygen can stabilize the developing change in the TS.
OTs
HO
HO
d+
dOTs
Figures by MIT OCW.

Only the ring fusion bond is a.p.p. to the LG.
H OTs
D
OH2
H
OH
Figures by MIT OCW.

This Grob fragmentation is also concerted, so the bond that is cleared must be antiperiplanar
to the LG.(only the fusion bond is a.p.p.)
dOTs
OTs
d
OH
+
d OH
Figures by MIT OCW.

Only the bond a.p.p. to the LG is involved in these processes. The position of the oxygen determines
which product will be formed.
Figures by MIT OCW.

3

6.
O
CF3
H
OMe
OMe
H2O
HO
OMe
OMe
OMe
H2O
H
OMe
7. Each of these mechanisms proceeds through an oxime.

O
R
Me
Me
HO
H2O
OH
Me
OH
N
H2
Me
PT
R
N
H
NH2OH
OH
H2O
N
R
Me
OH
N
Me
Would likely form mixture of

OH
N
R
HO
and
Me
N
Me
(Cont.)
Figures by MIT OCW.

7. Cont.......
N
O
OH
PCl5
Ar
PCl5
N
C
Me
Ar
Me
Me
O
(The substituted alkyl
group can migrate)
N
H
N
Me
Ar
PT
Ar
N
C
H2O
Me
OH2
OH
H
N
Me
Ar
Ar
OH2
Me
H
N
Ar
Me
O
O H
H
N
O
O
Me
O
... The methyl group can also migrate.

Me
as before
Cl5P
Ar
OH2
N
Ar
Me
OH2
Me
Ar
as before
O
O
O
Me
N
H
Figures by MIT OCW.

5

7. Continued. The nitrilium ion formed after migration is very electropholic. the aryl group
is electron-rich --> electropholic aromatic substitution.
as before
H2O
N
Me
Me
O
N
Me
8.a) Both of the substitution reactions must go through a a cationic species. Formation of this
intermediate is the RDS. In the first reaction, the oxygen can facilitate ionization by donating its
lone pair into the C-LG antibonding orbital. This speeds up the reaction . (NGP!)
O
d+
(s * c-x)
dOSO2Ar
Figures by MIT OCW.

6

In the second reaction neighbouring group participation is not possible because there is no
overlap between the oxygen lone pair s *cx. The ionization step is slower.
RDS
KDS
O
O
no
KD
Overlap
Overlap
O
O
H
H
H
H
OSO
OdO2Ar
Ar
X
X
b) Both rxns proceed through the following intermediate A. the acetate ion can attack two
possible sites to give the two observed products.
OAc
(a)
O
(a)
O
OSO2Ar
D
O
(b)
O
H
O
O
(b)
O
OAc
D
The rxns essentially proceed through an " SN2 - like" pathway because of the NGP.
--> No other stereoisoness are formed.
Figures by MIT OCW.

O H
9.
NH2
HO
H2
N
Me HO
Me
HO
HO
OH
PT
H
N
HO
OH2
HO
N
HO
Me
HO
Me
HO
HO
NH
HO
NH
HO
Me
Me
H2O
10.
OMe
Me
OH
OMe
OMe
Me
OH2
OMe
OMe
OMe
OMe
C
Me
OMe
OMe
OMe
O OMe
Me
OMe
This carbon more nucleophilic

because cation formed stabilized
by OMe & Me & not destabilized
by orthoacyl group.
(cont. on next page)
Figures by MIT OCW.

10. (cont......)
OMe
OMe
Me
OMe
C
Me
OMe
Me
OMe
This species cannot aromatize,

but it can open up again to form
a more stable acylium ion. (Stabilized
by other oxygen)
OMe
C
OMe
Me
O
This intermediate can re-form

the 5-mem. ring intermediate
or close to the six-membered
ring.
OMe
OMe
Me
OMe
This one can lose H
aromatize.
to
OMe
H2O
OMe
Me
OMe
OMe
Figures by MIT OCW.

9

11.
O OMe
(a)
OMe
(1 eqvn)
O
OMe
Ph
OMe
Ph
Ph
Ph
O
O
Ph
Ph
O
O
(b)
OH
OH
H O
OMe
OH
HO
H O
HO
O
12.
O
(a)
Na2Cr2O7
Ph
Na2Cr2O7
OH
OH
Ph
OH
O
CH2N2 or
MeOH, H+
Ph
OMe
+
O
CH2N2 or
OH
MeOH, H+
OMe
2. H
1. OMe
1 eq.
Ph
2. MeI
OMe
OH
1. 1 eq. OMe
Ph
OMe
2. MeI
O
Ph
O
OMe
PCC
(b)
1. LDA, H
Ph
2. OH cat. H2O
Ph
OH
Ph
PCC
Ph
10
Figures by MIT OCW.
13.
O
13
1 equiv
Me
OEt
OEt
O OEt
O
13
C Me
13
OEt
C OEt
O
OEt
OEt
Me
OEt
O
13
EtO
13
Me
EtO
OEt
13
Me
EtO
Me
13
EtO
OEt
OEt
H
O
OEt
Me
O
13
EtO
O
Me
13
EtO
Me
RO
O
14.
H OR
OR
Cat.
Me
Me
Me
Me
O
O
Me
OR
Me
RO
Me
O
O
Me
O
H
OR
Cat.
O
Me Me
+
RO
O
H
HO
O
Me
HO
Me O
OH
Me
O
Me
Me
Product 1
RO
RO
HO
O
H
Me
O
Me
Me
O
Me
HO O Me
Me
Me
10
11
Product 2
OH
Figures by MIT OCW.
Figures by MIT OCW.
15.
cat,
(a)
OH
"aldol" & "dehydration"
(1) LDA (1 equiv)
(2) O
1 eqvn
O
(b)
O
OMe
MeO
(1) OMe
(2) MeI
1 eqvn
O
MeO
(1) OMe
(2) MeI
OMe
MeO
OMe
LAH
OH
OH
(c)
Me
MeONa
OMe
Me
(1 eq)
Me
MeOH
OMe
LiAlH4
OH
OMe
OH
Me
Me
H ,D
O
K2CO3 (1 equiv)
MeBr
Me
Me
MeBr
H2
Pd/C
OMe
Me
Me
O
OMe
Me
O
Me
PBr3
MeOH
OH (cat)
OMe
MeOH
PCC
H+
OMe
H2O , D
Me
Me
Me
Figures by MIT OCW.

12
16.
O
O
O
O
H
OEt
O
EtO
OEt
OEt
O
O
O
OEt
OEt
O
H
OEt
EtO
EtO
EtO
OEt
EtO
EtO
EtO
OEt
OEt
EtO
EtO
OEt
OEt
EtO
EtO
EtO
EtO
OEt
OEt
OEt
OEt
EtO
EtO
O O
O
O
O
O
HO
HO
H2O
H
O
O
H2O
OH
O
O
O
O
HO
O
O
OEt
O
O
OEt
HO
OEt
Figures by MIT OCW.

13
H2O
HO
O
O
OEt
acid-cat.
hydrolysis
of ester
HO
H-O
Et
O
HO
OEt
OH
OEt
O
PT
EtO
OEt
H2O
EtO
EtO
OEt
H2O
OH
EtO
17
HO
A
H
H
O
OH
O
O
HO
HO
HO
OH
OH
OH
HO
H OH
H-OH
OH
B
HO H
HO
18
OMe
(+)
OMe
O OMe
O
O
OMe H
H OMe
MeO H
HO
O
OMe
H
HO
H OMe
O
H
H
H O
O
H OMe
OMe
O
Figures by MIT OCW.

14
19.
O
Me
O
H
OEt
OEt
O
Me
OEt
O
OEt
OEt
OH
H
OH
Me
OEt
EtO
OEt
Me
O
EtO
OEt
H 2C
Me
O
OEt
O
OEt
Me
Me
Me
OEt (1 eq.)
Me
OEt
OEt
OEt
Figures by MIT OCW.
15
20.
(a)
O OH
OH
OH
O
H
OH
O
O
(b)
O OMe
OMe
O
OMe
OH
O
OMe
OMe
C
(c) Carboxylate A generated from rapid deprotonation is not reactive toward nucleophilic attack by enolates. In
contrast, B can do further condensation generating C which can be deprotonated under rxn condition.
Figures by MIT OCW.
16
21.
Me
MeO
O
H 2N
Me
MeO
MeO
O
H
MeO
MeO
H2 O
H
MeO
OH2
MeO
MeO
OH
catalytic
OH
OH
Me
H
H2O
H2O
H
OH
H2O
MeO
MeO
MeO
MeO
MeO
N
OH2
N
O
H
H2 O
O
H
H3O+
H2O
(+)
MeO
MeO
H 2N
MeO
NH2
OH
Catalyst regenerated
Figures by MIT OCW.
17
OH
22.
O
H
OH
H
OH
Et
OH
OH
Et
Et
HO
Et
O
O
OH
Et
Et
OH
H Et
Figures by MIT OCW.
18
OH
23.
enantiopure
O
F3C
Cl
Cl
enantiopure
CF3
Note
inversion
Mechanisms
O
H
O
CF3
CF3
Cl
Cl
Cl
H
Neighboring group
participation avoids a high
energy carbocation
CF3
Sn2 backside attack

inverts the stereocenter
Cl
D
H
D
O
O
D
CF3
Cl
Figures by MIT OCW.
19
24.
Me
Me
OOH
OH
Me
Me
Mechanism:
H
Me
O
Me
O
O
H
Me
Me
Via phenonium ion

Me
Me
Me
Me
O
Me
Me
O
H
Me
Me
P.T.
H+
Figures by MIT OCW.

20
25.
O
Me
N
Me
Cl
H2O
D
Me
Me
Mechanism
O
Me
O
Cl
Me
Cl
N
Me
O
Me
Me
H
O
Me
H2O
Me
P.T.
O
Me
N
H
Me
P.T.
O
N
Me
O
H
Me
Me
N
HO
Me
Figures by MIT OCW.
21
26.
O
H
H2O, D
Me
H
Me
Me
Mechanism
O
OH
H
two steps
H
OH2
H
O
H
Figures by MIT OCW.
22
27.
OH
HCl
NH2
tBu
NaNO2
tBu
A
Mechanism:
OH
NH2
HO
O
H2O - N
Cl H
OH
OH
N OH
H
N
OH
N O
H N
H N
Note: Migrating group is

antiperiplanar to
Leaving group.
H
OH
OH
N
N
N OH2
H
O
H
H+
Next page for
Figures by MIT OCW.

23
# 27 Part B
tBu
Mechanism
OH
NaNO2
NH2
HCL
O
tBu
OH
(For diazonium Formation, see part A)
NH2
Once again:
The migrating group is
anti-periplaner to the leaving
group.
H
O
OH
H
N
H
O
O
tBu
Figures by MIT OCW.
24

Exams Organic Chemistry MIT

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5.12, Spring 2005

PRACTICE EXAM IIa

Actually, not at all since Me groups

Prof. Timothy F. Jamison

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C, 66.62; H, 11.18; N, 22.20

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Figure by MIT OCW.

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d. (5 points) Calculate the Index of Hydrogen Deficiency (IHD) of this unknown

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Figure by MIT OCW.

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1. n-BuLi (excess), THF

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ALSO, CAN DRAW AS CUBE (BONDS 1-12,

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Prof. Timothy F. Jamison

Official Recitation Instructor

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(1., continued see previous page for directions)

(or (IS, cis)

Must have "x"

2. (48 points total)

2 points per orbital array

2 points per orbital array

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(Shade appropriate lobes)

(write "conrotatory" or disrotatory")

(draw major product- show

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(shade appropriate lobes)

(write conrotatory or disrotatory)

(draw major product show stereochemistry)

3. (22 points total) Using retrosynthetic analysis, propose a

target molecule (A)

Hint: Use a Diels-Alder reaction.

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First Three Letters of Last Name:

Write your initials on each page.

Show all of your work. Partial credit receives points!

1. (4 pts) When N,N-dimethylaminopyridine reacts with one equivalent of acid,

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stop at 50% conversion

O Incorporation is expected to be low in recovered anhydride.

OH. There fore, k2 >> k-1, or elimination of

is a better leaving group than

faster than revesal to starting material. Most of the

O will be found in the acetic acid product.

6. (10 pts) Provide a mechanism for the following transformation.

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Base catalyzed hydydrolysis of nitriles is not a facile process because NH2

8. (9 pts) Provide a synthesis for the following compound.

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Massachusetts Institute of Technology

5.13, Fall 2006

EXAM #3 EXTRA PROBLEMS

What to expect on Exam #3: