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Chemistry 303
fall, 2005
THIRD EXAMINATION
7:00 pm December 6th
Duration: 2 hr
Name________________________KEY_________________________
Lab TA__________________________________________________________
(if you do not know his/her name, give day of lab section. NOT Brow or Clay)
This is an "open book" examination; you may use anything which is not alive.
Note: if you do not know the complete or specific answer, give a partial or general answer-WRITE SOMETHING
Write only in the space provided for each question.
Score:
p2______/14

p6______/12

p3_______/13

p7_____/10

p4_______/08

p8____/11

p5_______/11

p9_____/06

p10_____/07

p11_____/10

Total: _________/102
There are 12 pages in this exam. Please check now to be sure you have a complete set.
If you are using a resonance argument in your answer, draw the relevant resonance structures.
If you are asked to analyze a structure and you have no idea what it is, do a general analysis of the data and
propose partial structures.
Please be aware that a small number of students will be taking the exam at different times up until late morning on
Wednesday. It would be well not to discuss the exam until after that time.
NOTE: You will be asked to write mechanisms; that requires you always use the arrow formalism.
Please use it precisely, carefully, and correctly. Show charges carefully. Distinguish between an
intermediate and a transition state. When you draw cyclohexanes in the chair form, be sure to indicate
the angle of the axial and equatorial substituents accurately.`

PLEDGE:________________________________________________________________

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I. (14 pts). Consider each of the following pairs of reactions.
a. Write the single most likely mechanism and product(s) for the faster reaction in each pair. Pay
attention to stereochemistry; e.g., if the product is a racemic mix, draw both isomers.
b. Give the name of the mechanism SN1 SN2 E1 E2.
c. Give the single most important reason for the difference in reaction rate.
A.
Br
H

1.

Na CN

Good nucleophile, fairly non-polar solvent, secondary bromide substrate


SN2 conditions

THF

Br

CN

2.

Na CN

The primary alkyl bromide reacts faster


in the SN2 mechanism due to less steric
crowding in the transition state.

+ NaBr

THF

OMe

OMe

________________________________________________________________________________________
B.
CN
1.
R-configuration

AgNO3
Br

CH3
2.
H

EtNH2

AgNO3

Br

Silver ion to force ionization. Moderate nucleophile present.


rate determining step is ionization. Product determining step
is nucleophile addition, SN1. E1 gets partial credit but the presence
of a moderate nucleophile favors SN1.
The rate of ionization depends on the stabilization of the resulting
cation. CN destabilizes the cation due to the inductive withdrawing effect.
CH3

EtOH

R-configuration

H
CH3
H

OEt

CH3
racemic

+
H

OEt

racemic product mixture due to planar cation intermediate


CH3
H
H

O
Et

II. ( 21 pts). Consider the following related reactions.


A. (5 pts). Using the R,S system, indicate the absolute configuration at each stereogenic center in A.
Name the most likely mechanism to operate on A under the conditions shown and draw it using the
arrow formalism, indicating the exact product(s) carefully.
For each product, indicate the configuration of each stereogenic center.
H
H
Et

H H
Cl
Me H
A

H
H
Et

MeSNa
THF solvent

H H

Strong nucleophile, low polarity solvent,


secondary halide = SN2

Me
H

SMe
R-configuration

MeS

B. (8 pts). Name the most likely mechanism to operate on A under the conditions shown and draw it using the
arrow formalism, indicating the exact product(s) carefully.
For each product, indicate the configuration of each stereogenic center.
NOTE: NMR analysis of the product mixture shows peaks in the region 5-7 ppm.
H
H
Et

Forced ionization, low polarity solvent.


NMR data suggest alkene product and confirm E1 mechanism

H H
Cl
Me H
A

AgNO3

THF
H
H
Et

H H

E1
H
Me

H
H
Et

H
H
Me

H
H
Et

H
Me
H
major

C. (8 pts). For the slightly more complicated case, B is converted to C by a multi-step process.
Draw the mechanism carefully making clear the configuration of each carbon at each step.
Name each step [SN1, SN2, E1, E2]. HINT: Note carefully the location of the Me and Et groups.
This is tough to visualize and the product is deliberately drawn to not correlate directly with B.
Do some visual gymnastics.
Indicate the configuration of all stereogenic carbons in the product using the R,S nomenclature.

O
H
Et

H
Cl

MeSNa

THF solvent

Me H
B

Me H

S-configuration

H
Et
C

H
Et
O
H
H
Me
MeS C

SMe

SN2
MeS

SN2
O H

Et
Cl
H
MeS Me H

S configuration

Et
H
MeS

O H
H
Me
Cl

R configuration

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III. (23 pts). Consider the structure D (no stereochemistry intended).
A. (2 pt) How many stereogenic centers are there?

______

Cl

B. (2 pt) Assuming only structures in their lowest energy conformation,


how many stereoisomers are possible?
______

D
CH3

C. (7 pts) Using the chair representation:


a. Draw the most stable stereoisomer of D, in its lowest conformational form. Call it D-1.
b. Draw also its ring flip (other chair) isomer, call it D-2.
[Note Table 3.2 of substituent steric effects on the last page for your reference.]
c. Explain carefully the difference in stability between D-1 and D-2, by listing gauche, eclipsing,
and 1,3-diaxial interactions, for the Cl and CH3 shown on the structure. You need not be quantitative.
g

D-1

Cl
g

H3C
g

Cl

g
D-2

H
g

CH3

1,3-diaxial
g = gauche interaction

In D-1, the Cl has three gauche interactions while the CH3 has one gauche.
In D-2, the Cl has two gauche interactions with the ring CH2 groups, and one gauche with a CH3
The CH3 has two gauche interactions with the ring CH2, and a 1,3-diaxial interaction with a CH3
A satisfactory answer would point out the gauche interactions approximately, and note the 1,3-diaxial
interaction carefully, and do not mis-identify interactions.

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D. (6 pts). Using the chair representation:
a. Draw a diastereoisomer of D-1, in its lowest conformational form. Call it D-3.
b. Draw also the ring flip (other chair) isomer of D-3, call it D-4.
c. Explain carefully the difference in stability between D-3 and D-4, taking into account gauche,
eclipsing, and 1,3-diaxial interactions, for the Cl and CH3 where relevant. You need not be quantitative.
Cis arrangement of Cl and CH3
H

H
D-3

H
g

H3C g

Cl

g
g

Cl
CH3 g g

D-4
g

g
1,3-diaxial

g = gauche interaction

D-4 is less stable than D-3 because it has a 1,3-diaxial interaction; also more gauche interactions.
Again, the grading was gentle on exactly what gauche interactions are present, but the 1,3-diaxial needed to be
specified carefully.
E. (6 pts). Which isomer (D-1, D-2, D-3, D-4) will react fastest in an E2 reaction?
Draw the mechanism here and use it to explain your choice carefully. Draw the product(s).
Specify in your answer a specific base you would choose to favor the E2. Explain your choices.

MeO
H
D-3

H
H3C
Cl

H3C

+ MeOH + Cl

We want a strong base to initiate E2; alkoxide is a good choice or the R2 N- anions.
D-3 will react faster because it is the only isomer with the Cl and H lined up (1,2-diaxial). antiparallel.

IV. (10 pts). Consider the reaction of X and Y with dimethylamine to give the product shown. Note
the kinetic expression for each reaction.
A. (4 pts). Write the mechanism for the reaction of X under these conditions.
Clearly show the transition state for the rate-determining step.
Show partial charges where relevant.
Br
X

NHMe2

NHMe2
Br

rate = k [X][NHMe2]

HH
"+
Me2HN

"Br

B. (6 pts). Write the mechanism for the reaction of Y under these conditions.
Explain the difference in the kinetic expressions.
Why is a different mechanism followed by Y?

Br Y

NHMe2
!

NHMe2
Br

rate = k [Y]

NHMe2

Br
This is an SN1 reaction, with ionization being the rate-determining step.
This is a unimolecular reaction, with the rate expression shown. The reaction
above in (A) is an SN2 process, with a bimolecular step and a rate expression
including two concentrations.
Y cannot undergo an SN2 process as the leaving group is attached to a tertiary
carbon, too hindered for SN2. However, it can ionize easily to give a tertiary,
resonance stabilized cation.

V. (11 pts).

A. (7 pts). This question is from the Chem 301 Make-up exam

First, please make an excellent, fully three-dimensional drawing of the following molecule (E) in its energy
minimum form. [chair form]
Next, explain in detail how F is formed from E. [write mechanism]

H
I

E H

H2N

NH2

I
H2N

H2N

NH2
SN2 not favorable
due to the geometry
of this chair form

Very favorable
SN2 in the diaxial form

F
(actually the enantiomer
of F; my mistake but
probably of no consequence)

B (4 pts). Finally, explain why the related compound G does not react as does E to give an analogous
product.
H

H2N

H
G

H2N

As for E, this isomer cannot


do a good SN2. It also cannot
flip to the other chair because
the other ring "locks" it.

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VI. (13 pts). Consider the following related reactions.
Perhaps surprisingly, reaction (2) is much faster than (1).
O

O
S

1.
OH

NaH

Na

CH3

+ H2

OCH3

2.

O
OH

O
S

NaH

+ Na O

O
S

+ H2

Ph

O
Ph

A. (6 pts). Write the mechanism for reaction (2), showing exactly the role of the NaH.
Name the mechanism: SN1

2.

O
O-H

NaH

+ Na O

O
Ph

Na H
SN2
O
O

O
S
Ph

O
S
Ph

+ H2

SN2 E1 E2

B. (5 pts). Explain in detail why reaction (1) is much slower. Consider transition state structure.
What mechanism is being followed: SN1 SN2 E1 E2
O

O
S

1.
OH

O
NaH

Na

CH3

+ H2

OCH3

O
S

O
S

O
S

O
CH3

!"
O

H C

H
H

Transition state requires a 180o bond angle


at the carbon undergoing substitution. This cannot
be achieved in this intramolecular case, with a 6-membered
ring transition state.

O !"

C. (2 pts bonus). In fact, it was noted that the rate-determining step for reaction (1) is bimolecular while the
RDS for reaction (2) is unimolecular. Explain.
O

O
S

1.
OH

O
S

NaH

CH3

Na

+ H2

OCH3

O
S

O
CH3

O
O
H3C

Intermolecular version is the only


reasonable way to achieve an SN2.

The intermolecular version is a normal, bimolecular SN2. Reaction 2 is an intramolecular SN2 which is
unimolecular.

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VIII. (10 pts). Consider reactions (1) and (2). Reaction (1) is much faster than reaction (2).
AgNO3

1.
Br

AgNO3

2.

H2O

Br

OH

H2O

OH

A. (4 pts). Write a careful mechanism for reaction (2), showing all intermediates (not transition states).
Identify the rate-determining step.
AgNO3

2.
Br

Step (a) is the rate determining step. The forced ionization


by Ag+ is effective with the secondary bromide.

H2O

OH
c

a
H2O
b

O H
H

B. (6 pts). Write a careful mechanism for reaction (1), showing all intermediates (not transition states).
Identify the rate-determining step. Explain carefully why (1) is faster than (2).
Alternative:
a

1.
Br
AgNO3

This ionization would give


a secondary cation, just like
the one shown in Rxn 2. Should
therefore have essentially
the same rate.

Formation of secondary cation has


extra driving force of ring opening of the
cyclopropane, release of strain energy.

Br
Ag

H2O
b

O H
H
c

O
H

Step a is the rate determining step, and is much faster than the RDS in rxn 2 because of the extra strain energy
release.

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Glossary:
Me = methyl
THF
O

Et = ethyl

Ph = phenyl