1

Chemistry 303
Fall, 2008
Final Examination
1:30 pm January 15th, 2009
Duration: 3.0 hr
Name______________________________________________
Lab TA_______________________________________________ (not Anna, David, Brent)
This is an open book examination; you may use anything that is not alive nor connected to the Web.
Note: if you do not know the complete or specific answer, give a partial or general answer
We love to give partial credit.
If there seems to be more than one good answer, explain your thinking.
If you invoke resonance delocalization as part of your answer, draw the relevant resonance structures.
If you draw a chair cyclohexane, be sure to orient the bonds carefully.
If you do not know a structure and need to write a mechanism, write a general mechanism for partial
credit.
USE THE ARROW FORMALISM CAREFULLY FOR ALL MECHANISMS
BE SURE TO INCLUDE ALL FORMAL CHARGES

p2______/14

p3.______/26

p4.______/23

p5._______/24

p6._____ _/15

p7.______/16

p8.______/18

p9._______/10

p10._______/08

p11._______/24

p12.______/22

Total: ___________/200
There are 13 pages in this exam; please check now to be sure you have a complete set.

Pledge:____________________________________________________________________________

2
I. (14 pts). Note the pKa values shown below (measured in water).
A. (8 pts). Why is the axial carboxylic acid less acidic than the equatorial isomer? Explain carefully

HO2C

pKa 8.23

pKa 7.79
CO2H

O
O
H
H H
H
H O H O
O
C

The stability of the carboxylate anion is very sensitive

to H-bonding with the solvent. Water strongly stabilizes
the anion. However, in the case with the axial CO2-, the water
solvation is less due to steric crowding, amplified gauche
interactions.

O
H
H
H
O
C
H O H less crowded, more effective stabilization.
O

more acidic due to

better stabilization of the
carboxylate anion

B. (6 pts). Suppose the pKa could be measured in benzene. Would you expect the difference in pKa's
to be larger or smaller or exactly the same? Explain your choice.
In an aprotic solvent, the solvation is much less. In the extreme, the gas phase, there would be no solvent
molecules around the carboxylate anion and the stability would depend simply on the intrinsic electronic
stabilization (inductive, resonance, etc). This is not sensitive to the steric features, so one would predict
that the axial and equatorial would show similar pKas; the difference in pKas would be less.

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II. (26 pts). The reaction of Br2 in water with Z-2-butene produces a racemic mixture. The
enantiomers can be separated. One of the enantiomers, A, reacts with HBr to give a dibromide,
(represented as C) which is racemic. No trace of the meso isomer (D) of the dibromide was detected.
Think carefully as to why A (single enantiomer) leads to C as a racemic mixture under these conditions.
Br2
Me

Me

H2O

HO

Me
H

Br

HBr
CH2Cl2

H
Me A Br

Me
H

racemic

H
Me C Br

+ enantiomer

A. (08 pts). Write a careful mechanism for the formation of A, using the arrow formalism and
showing all intermediates. You need not show transition states.
H2O
H
H
H
H
H
H
H
H
O
Me
Me
O
Me
Me
H
Me
Me
H
-BrH
Br
Me
Me
Br
Br
A
Br-Br
B. (04 pts). Draw the enantiomer of A here
and label each stereogenic carbon as (R) or (S).

C. (04 pts). Draw the meso isomer D here and

label each stereogenic carbon as (R) or (S)

HO S H
Me
S
Me
Br
H

Br R Me
H
S
H
Br
Me
D

Br
H
Me

Br
H
Me

.
D. (10 pts). Write a careful mechanism for the formation of C, using the arrow formalism and
showing all intermediates. You need not show transition states. Make clear why two enantiomers form,
but not the meso isomer.

HO
H
Me

Me
H
Br

H+

H
HO
H
Me

Me
H
Br

a
H
Me

Br b

Br

H
Me

Br

Me
H

H
Br
Me
from (a)

Me
H

Br

H
Br
Me
from (b)

Protonation followed by ionization leads to the symmetrical bromonium ion (same as first intermediate in addition of Br2).
The Br- then adds as a nucleophile at either end of the bromonium ion, by backside attack, to give a 50:50 mixture
of enantiomers.
The alternative mechanism of direct SN2 substitution of Br for -OH (activated by H+) would give the meso isomer.
The alternative mechansim of ionization without participation of the Br gives a planar secondary cation; then reaction
with Br- would produce all three stereoisomers: A, its enantiomer, and D.

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III. (23 pts). Consider the reaction shown below, where E is isomerized into F with ZnCl2 in THF.
Ph
Ph

ZnCl2

F (spectra at the end of the exam)

THF

O
E

A. (12 pts). Draw here the structure of F. Explain carefully how your structure is consistent with the
H NMR data: approximate chemical shifts, areas, and coupling constants.

O
Hb Ha
F

In the 1H NMR, Ha appears at the typical aldehyde H position, around 10 ppm, as doublet with
coupling to Hb.
Hb appears at 4.8 ppm, perturbed by two !"aryl rings and an !-C=O
no calculation necessary.
The phenyl H appear as overlapping peaks in the arene region, around 7 ppm,
with area 10H

B. (03 pts). Point out two key features of the IR spectrum in the region 1500-4000 cm-1 that support
your structure.
The two most significant features of the IR spectrum are the C=O stretch at 1720 cm-1,
consistent with the aldehyde C=O; and the C-H stretches at around 2700/2800 cm-1 for the
unique aldehyde C-H.

C. (08 pts). Write a careful mechanism for the formation of F from E under these conditions.
Obviously, the role of the ZnCl2 is important in your analysis.
Lewis acid catalysis by Zn(II)

O
H
H

ZnCl2

ZnCl2
O

ZnCl2
H
H

(a)

O
+ ZnCl2

H H

regeneration of
the Zn(II) catalyst

(b)
ZnCl2
O
H
OR
H
(c)

Equivalent answers:
ZnCl2
O
H
+ H

(a) concerted hydride shift

(b) hydride shift from intermediate
cation.
(c) elimination from intermediate
cation and re-protonation

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IV. (16 pts). Consider the reaction of F under hydroboration conditions. Two regioisomeric
products are possible, G and H.
MeO
OH
a. R2BH
MeO
or
G
H
b. H2O2, HOL

A. (04 pts). Draw in the box above the structure (G or H) of the isomer you expect to be preferred in
this process.
B. (12 pts). Write a careful mechanism for the hydroboration stage of this process and explain why one
isomer is preferred over the other (include the transition state for the product determining step). You
need not write the mechanism for the peroxide stage.
MeO

BR2
H

!"
BR2

MeO

MeO

!+ H

BR2

H
product of the first
stage

TS

OH

MeO

H2O2
NaOH
(several
steps)

Imagine the extreme picture for the transition state, with a full cation:
MeO

BHR2

MeO

!+

MeO

BHR2

vs

H
BR2
!"

The methoxy group can stabilize this cation (or partial cation) by resonance donation of an electron pair.
no direct stabilizing
effect of the methoxy
group.

V. (08 pts). Predict the most likely substitution product from the following conditions and explain
your choice with a mechanism. Note that the major product shows two different methyl signals in the 1H
NMR spectrum.
I
H-I
Br

HO
Me

Me

HI
CH2Cl2
solvent

H
HO

Br

Br

Me

Br

I
Me
two Me signals
in the NMR

one Me signal
in the NMR
The acid activates the -OH as a leaving group. It cannot simply ionize (primary cation), but
can undergo substitution with rearrangment. Rearrangement is verified by the observation of two
different Me groups in the product by NMR.

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VI. (07 pts). Note the application of the ozonolysis protocol to the substrates below.
Considering the first step in this process, the rate determining step, which substrate would react faster?
Explain your choice and write the end product(s) from that reaction.
a. O3
O

b. Me2S
a
O:

a. O3

Faster first step, the rate determining step.

b. Me2S

O
O
:O

!+
O:
TS

O
O
O
:O
!" !+

O
OO O
Product of the
first step

OO

Me2S
O

ozonide
no mechanism required

The reaction is driven by donation of electrons from the electron rich double bond to the electrophilic ozone, arrow (a).
The transition state for the first step shows partial development of a (+) charge on the carbon
next to the oxygen. This is strongly stabilized by resonance donation from the oxygen lone pair.

VII. (08 pts). Rationalize the following reaction. This is a little tricky. Show a typical reaction of an
alkyne under these conditions and then see if you can get further to the observed product.

H+

H2O

H O

H
-H+

H O

H
Phenyl stabilized
cation

H
H+

-H+

H
resonance-stabilized
cation (oxygen donation
and phenyl delocalization)

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VIII. (16 pts). Consider the conversion of Q to R upon heating in acidic water. Write the best
mechanism for this process, showing all intermediates along the way.
O
1

4
2

6
5

8
7

H+
9

H2O

H+
H

OH
H

7 8

4
3

5
1
2

HO
OR:
H
OH
-H+

OH

OH

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IX. (18 pts). We have not emphasized doing organic synthesis yet, but this requires nothing
more than recognizing the standard reactions (one or several steps) that connect a starting material with a
synthesis target. Proper sequencing of steps can lead to contrasting structures. For example, consider the
conversion of L selectively into M.
Suggest how you might convert L to M, through a series of one or more intermediate molecules. Draw
the series with an arrow connecting one to the next, and above the arrow draw the reagents that will
bring about this conversion. You may choose any of the reagents we discussed in class. Shorter
sequences are better. Sequences that proceed through very unfavorable intermediates (e.g., primary
cations, high energy anions, etc) will get very little credit.
Possibly useful reagents:
HBr, AgNO3, NaH, BH3, HOOH, Tosyl Chloride, CrO3, LDA, SOCl2, NaI, RCO3H, OsO4, HCl,
NaSMe, NaBr, MeI, H2O, NaOH
For each step, identify the reaction as: SN1, SN2, E1, E2, electrophilic addn. to alkene/alkyne, or
oxidation.
(if ambiguous, explain)

steps?
OH

L
(SN2)

HO

O
H

HBr
Br

LiNR2
(E2)

OsO4

HO

(electrophilic
addition to an
alkene)

OH

CrO3

One possibility....
HO
M

O
H

(oxidation)

9
X. (18 pts). Consider the following reaction.
A. (06 pts). Write the most likely mechanism and the structure of K.

Br

NH2
J-5

Na2CO3

Na2CO3

NH2

THF solvent

NH

C5H11N
K

Br

+ HCO3
+ NaBr

B. (12 pts). Now consider the parallel reaction with related substrates. Below each substrate is given the
relative rate of the reaction with that substrate. There is a large dependence of rate on the structure.
Br
relative rate:

J-2
0.07

NH2

NH2 Br

Br
J-3
0.001

J-4
100

NH2

Br

NH2
J-5
1.0

1. (04 pts). Rationalize the difference in rate for J-2 compared to J-3.

Br
J-2

NH2

NH

vs

Br

NH2

NH

J-3

The cyclization of J-2 is disfavored by ring strain (enthalpy) to the same degree roughly as J-3.
However, J-2 has fewer degrees of freedom and can more likely get properly oriented for the
cyclization (entropy). Therefore, the cyclization of J-2 is faster.

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Continued next page
2. (04 pts). Rationalize the difference in rate between J-4 and J-5.
Br
J-4

NH2

vs

NH

Br

NH2

NH

J-5

The cyclization of J-4 is faster. This reaction suffers to a small degree from developing eclipsing
interactions in the transition state, but the bond angles are nearly ideal on the way to the product. J-5
has somewhat more favorable enthalpy (lack of strain), but less favorable entropy, parallel with the argument
in part 1. It would be hard to predict this result, but given the numbers, this must be the analysis.

3. (04 pts). Rationalize the difference in rate between J-2 and J-5.

Br
J-2

NH2

NH

vs

Br

NH2
J-5

NH

The cyclization of J-5 is faster, in spite of strong entropy factors favoring J-2. The bond angle
strain and eclipsing in J-2 is an overwhelming enthalpy problem and dominates the rate.

11
XI. (24 pts). Think about the general oxidation of alcohols with CrO3 and the isomers X and Y.
Evidence for the rate-determining step can be gleaned by studying relative rates of oxidation.
Me

Me
OH

Me

OH

Me

OH

Chair version of X

OH

H
Chair version of Y

A. (06 pts). In the boxes above, draw the structures of X and Y using the chair template, in their
most stable conformation.
B. (10 pts). Write the multi-step mechanism for the oxidation of X with CrO3.

H
HO
X

O
Cr

a
O

(-H+)

H
O
O
O Cr
O

:B
b

+ BH
O
+ reduced chromium
species

C. (04 pts). Suppose isomer Y is more reactive than X in this process. Which step would be the likely
rate-determining step? Explain.
Step (a) is the formation of the chromate ester, increasing the steric size of the OH substituent. The
transition state for this step will be particularly sensitive in the case of the axial OH (X) due to the usual
gauche interactions of that substituents. These interactions get worse on the way to the TS. Therefore,
the barrier for X is larger than the barrier for Y. This is consistent with the rate relationship stipulated in
this problem, where X is overall less reactive than Y.

D. (04 pts). Suppose isomer X is more reactive than Y. Which step would likely be the rate-determining
step? Explain.
Step (b) is the elimination of the chromate ester, leading to the ketone. There is general relief of strain in
this process, but particularly strongly for X, where the axial repulsions are relieved. Therefore, the axial
isomer should feel a greater relief of stain and have a lower barrier to this step, a higher rate. If this step
is the rate-determining step, X will be more reactive than Y.

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XII. (10 pts). A special oxidizing process for the conversion of cyclopentanol to
cyclopentanone involves triphenylmethyl chloride and silver nitrate. Consider the byproducts shown, and
write the best mechanism for this process.
a
OH
H

+ Ph3C-Cl + AgNO3

+ AgCl

+ Ph3CH + HNO3

b
Ph3C + AgCl

d -H+

+ Ph3CH

stabilized by donation from oxygen

lone pair.

XIII. (12 pts). In reaction with a metal oxide such as MnO2, butenyl alcohol, T, is rapidly
oxidized to the aldehyde but n-butyl alcohol, U, is quite unreactive. Write the mechanism for oxidation of
butenyl alcohol with MnO2, and explain carefully why this substrate is much more reactive.
H H
OH

O
Mn
O

H H

O
Mn

-H+

H H

O
O

:B
H

O
Mn

O
O

:B

MnO2
The C-H bond is broken in the rate-determining step. As the bond is stretched and broken,
the system is stabilized by overlap with the pi bond. To put it another way, the C-H is
weakened by interaction with the adjacent pi bond. This is revealed clearly in the bond
energy tables, comparing this bond (allylic C-H) with the simple alkyl C-H in n-butane.

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doublet
J = 2Hz
(area 1H)

Structure F, problem III

overlapping peaks
(area 10H together)

1H

NMR at 400 MHz

doublet
J = 2Hz
(area 1H)

Structure F, problem III