KEY
Massachusetts Institute of Technology
Dr. Kimberly L. Berkowski
5.13, Fall 2006 Organic Chemistry II
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
4
O
O
O
Me
2
Me
O
Cl
Me
1
O
O
5
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
O
H
HO
Et
n-Bu
Et
NR
2. workup
O
1. excess MeLi
OH
2. workup
OH
NR
or
O
n-Bu
OH
H2SO4
O
O
Na2Cr2O7
n-Bu
Me
n-Bu
EtO-, EtOH
O
n-Bu
2. workup
n-Bu
1. excess NaBH4
O
n-Bu
2. workup
1. excess EtMgBr
OMe
n-Bu
O
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, Δ
or
H2O2, Δ
CH2
Me
Me
(c)
NH2
CuCN
CN
N2 Cl
POCl3
or
(d)
P2O5
O
n-Bu
n-Bu
NH2
H+/H2O
or
-OH/H O
(e)
2
n-Bu
CN
O
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
O
OH
Me
Cl
k2
PT
HO
O
Me
Cl
k1
Me
Cl
k2
O
O
Me
O
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
N
C
Me
A
N
Me
H
H2O
Me
+
Me
O
Me
NH2
OH
Me
NH2
Me
O
O
NH2
Me
H+, H2O
H
Me
Me
OH
NH2
O
OH
C
Me
PT
OH2
Me
OH
NH3
OH
Me
H2O
Me
NH4
OH2
O
Me
NH2
B
NH2
Me
H
H
Me
Me
B
OH2
Me
(b)
NH2
PT
Me
H3O
O
Me
H+, H2O
N
Me
O
O
H
NH3
+
Me
OH
Name_______________
Me
OH
Figure by MIT OCW.
7. Provide a mechanism for the Hofmann elimination. Please show all arrow pushing.
O
NaOH
H2O
+ Br2
n-Bu
NH2
NH2
O
O
O
H
N
n-Bu
n-Bu
H
H
OH
n-Bu
n-Bu
N
Br
H
O
n-Bu
N
O
Br
O
Br
H
n-Bu
N
n-Bu
N
Br
+ OH
N
Br
O
n-Bu
C
O
n-Bu
O
N
C
HO
HO
H2N
+
n-Bu
HO
O
N
H
OH
n-Bu
H
N
HO
H
H2O + CO2 +
HNn-Bu
HO
H
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
A
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
N
MeO
N
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.
Allowed Starting Materials:
MeOH
Me
O
CN
CO2
OH
H
H
H
H
H
H
O
(a)
O
Me
Cl
1. PBr3
EtOH
2. Mg, Et2O
Me
MgBr
1. H
OH 1. PBr
H
2. H+
MgBr
3
2. Mg, Et2O Me
Me
1. CO2, Et2O
2. H+
O
O
SOCl2
Me
NH
OH
Me
from(a)
H
PCC
Me
Me
MeOH
2. KCN
+
+
B
Me
H+
MeMgBr
O
H+ workup
1. PBr3
Me
OH
Me
Me
A
Me
Cl
(b)
1. PBr3
2. Mg, Et2O
Me
O
PCC
Me
Me
OH
1. LiAlH4
CN
2. H+
Me
N
Cat.
Me
Me
Me
MeOH
NH2
1. LiAlH4
A
B
Me
N
H
Me
2. H+
Me
Figure by MIT OCW.