KEY

Massachusetts Institute of Technology 5.13, Fall 2006

Dr. Kimberly L. Berkowski 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 O O O O O

Me NMe2 Me O Me Me Cl Me O Me OMe

4 2 1 5 3

2. In the boxes, please provide the reagents for the illustrated transformations. More
than one step may be required

O
1.
(a) 1. NaN3 N K Excess NH3
2. LiAlH4 or or
3. H2O O
2. H2NNH2

Me Br Without Over-Alkylation Me NH2

1. HCN, Cat. KCN

(b)
2. LiAlH4
O 3. H2O
HO NH2
Me Me Me Me

Figure by MIT OCW.

3. Please provide the requested products. If no reaction is expected, write “NR”.

O 1. Li(t-BuO)3AlH O

2. workup
n-Bu Cl n-Bu H

O HO Et
1. excess EtMgBr

2. workup n-Bu Et
n-Bu OMe

O 1. excess NaBH4
NR
2. workup
n-Bu OMe

O
O 1. excess MeLi

2. workup n-Bu Me
n-Bu OH

NR
or
O EtO-, EtOH O

n-Bu OH n-Bu O

O
Na2Cr2O7

n-Bu OH H2SO4
n-Bu OH

Figure by MIT OCW.

4. Please provide the requested reagents.

(a) Br2, NaOH

H2O
O
n-Bu NH2

n-Bu NH2
1. Excess MeI
(b) 2. Ag2O, Δ
or
NMe2 H2O2, Δ

Me Me CH2

(c)
CuCN
N2 Cl CN

(d) POCl3
or
P2O5
O
n-Bu CN
n-Bu NH2

H+/H2O
(e)
or
-OH/H O
2
O
n-Bu 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
Me Cl
O = isotopically labeled oxygen (18O)

(a) Please provide the mechanism for the hydrolysis reaction shown above, including the
pathway for incorporation of O into the acyl chloride.

O
O
O OH HO O
k1 PT k1
Me Cl Me Cl Me Cl
Me Cl
OH k2 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 O
C
N H+, H2O

Me NH2
Me
A B

H
Me Me N Me NH2
H
C N PT
Me Me OH2 Me OH
H2O

Me NH2 Me NH2
H3O + H OH2
Me O Me O

(b) Me O Me O
H+, H2O
Me NH2 Me OH
B C

H Me OH Me OH
Me O PT
NH2 NH3
Me OH2 Me OH
Me NH2
H2O
H NH3
Me O Me O
NH4 +
Me OH Me OH

Name_______________ Figure by MIT OCW.

7. Provide a mechanism for the Hofmann elimination. Please show all arrow pushing.

O
NaOH
+ Br2 n-Bu NH2
H2O
n-Bu NH2

O O O
H H H
OH
n-Bu N n-Bu N n-Bu N
Br Br
H

O O O
Br Br H
n-Bu N n-Bu N n-Bu N + OH
Br

O
n-Bu
n-Bu O n-Bu H
O N
O C N C N
HO H

HO H OH

HO

H2N n-Bu H2O + CO2 + HNn-Bu

+

HO 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 OMe
Br Br

HNO3 MeO OMe MeO OMe

H2SO4
A B
OMe OMe OMe
Br Br
H2, Pd Br2

MeO OMe MeO OMe MeO OMe

NO2 NH2 NH2

NaNO2, 2HCl

OMe OMe
Br Br Br Br
H3 PO2

MeO OMe MeO OMe

N Cl
OR N

OMe OMe OMe

HNO3 O2N NO2 H2N NH2
H2SO4 H2, Pd
fuming
MeO OMe MeO OMe MeO OMe
NaNO2
HCl
OMe Cl OMe Cl
Br Br N N N N
CuBr

MeO OMe MeO 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:

H
O H
MeOH CO2 CN
Me OH H
H H H

O
(a)
O
Cl Me
1. H H OH 1. PBr MgBr
1. PBr3 3
EtOH Me MgBr
2. Mg, Et2O 2. H+ Me 2. Mg, Et2O Me
1. CO2, Et2O
2. H+
O O
SOCl2

(b) Cl Me Me OH
Me NH
Me

Me
H
OH PCC 1. PBr3
Me + MeMgBr MeOH
Me 2. Mg, Et2O
O
from(a)
H+ workup
Me O
PCC
Me Me
OH Me
A
1. PBr3 1. LiAlH4
MeOH Me CN
2. KCN 2. H+ Me NH2 B

H+ Me N 1. LiAlH4 Me N H
A + B Me
Cat. 2. H+ Me
Me Me

Figure by MIT OCW.