Chemistry 303

fall, 2006
FINAL EXAMINATION
9:00 AM, JANUARY 24TH, 2007
Duration: 3.0 hr
NOTE: an additional 30 minutes will be allowed for completion of the course evaluation by those who have not done it

KEY________________________________________

Name____________________

Lab TA___________________________________________________________
(if you do not know his/her name, give day of lab sectionNot Shawn nor Bill)
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
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
WRITE SOMETHING
Write only in the space provided for each question.
Score:
p2___________/15

p3___________/15

p4___________/18

p5___________/14

p6___________/16

p7___________/18

p8___________/18

p9 __________/17

p10 __________/12

p11___________/12

p12___________/15

p13___________/20

Total:

p14__________/10 pts

/200

There are 14 pages in this exam; please check now to be sure you have a complete set.

Pledge:_________________________________________________________________________________

I. (08 pts). Considering the following pair of reactions, note that reaction (a) is much faster than (b) under
these conditions. Write the most likely mechanism for reaction (1) and explain carefully why it proceeds faster than reaction (b).
H3C

A.

H+

H3C
O

H3C

HBr

(a) NC

NC

NC

CH2Cl2 solvent

Br
Cl
HBr
(b)

CH2Cl2 solvent

NC

Br

Not catalytic in acid

The lone pair on the ether can be protonated to activate the oxygen as a leaving group. In reaction (b), the chloride is a good leaving
group for spontaneous ionization, but is not easily activated by protonation (lone pairs held tightly). In a more polar solvent,
reaction (b) might proceed rapidly spontaneously, but in the non-polar solvent, the acid activation is necessary.

__________________________________________________________________________________________
II. (22 pts). Consider reactions 1, 2, and 3 (next page)
A. The ratio Y:Z for reaction (1) is 95:5.
OH
OH

H2SO4(catalytic)
(1)

or

H2O solvent
X

i. (02 pts) What do you predict for the molecular rotation of Z?

(+)

zero

(-)

cannot tell (circle best answer)

ii. (05 pts) Write the best mechanism for this reaction and explain
carefully why Y is preferred. Show the catalytic role of the acid.
H+

OH
OH

H2SO4(catalytic)
(1)

or

H2O solvent
X

-H+

H2O

H
H O

Y is the preferred product

because the reaction goes
through the best cation, a
secondary benzylic cation
with resonance stabilization.
The cation leading to Z is
simply secondary

resonance stabilized cation

Proton in for the first step and out in the last step: catalytic in H+

cont

B. (07 pts). The ratio Y:Z for reaction (2) is also 95:5 when R = tBu in the boron reagent. This might seem surprising
until you think carefully about the parameters which influence the regioselectivity [I urge you to do so].
OH
OH
a. R2BH

(2)

or

b. NaOH, H2O2

Write the best mechanism for step (a) of this process and explain why Y is favored.
R

R
B

OH
OH
a. R2BH

(2)

or

b. NaOH, H2O2

X
R2B

Two factors influence the regio

selectivity, and they work in
opposition in this case. The
polar picture, with H being
delived to the best cation site
would lead to Z, while the steric
factors (large tBu group) favor H
addition to the benzylic position.
Hard to predict, but the given
result allows one to conclude
that the steric effects dominate.

no mechanism required

C. (08 pts). For this modified substrate (X) in eq 3, the ratio of Y:Z is now 25:75.

R is still tert-butyl.

OH
OH

a. R2BH

(3)

or

b. NaOH, H2O2
Me2N

Me2N

X'

Me2N

Y'

Z'

i. (04 pts) Explain carefully the origin of the contrasting regioselectivity between reactions (2) and (3).
ii. (04 pts) Which would be the faster reaction, step (a) of reaction (2) or step (a) of reaction (3)?
H
1

(3)

BR2
2

OH
OH

a. R2BH
or

b. NaOH, H2O2
Me2N

Me2N

X'

Y'

Me2N

!H BR
2

BR2

!+
Me2N

Me2N

Me2N

Me2N

Z'

The Me2N group pushes electron density into the

ring and to the alkene. Favors donation of
electron density from C2 and build-up of (+)
charge at C1.

Me2N

New and stable resonance structure favors the polar factors to determine the regioselectivity. Steric factors are the
same, but the now the polar factors become dominant and lead to the opposite regioselectivity.

ii. The dimethylamino group pumps electron density into the arene ring and then into the alkene, as indicated by the
resonance structure shown in the mechanism. More electron rich alkene reacts more favorably (faster) with the electron deficient
boron reagent.

III. (18 pts). Consider the stereoisomer V, where one stereocenter is labeled with deuterium.
A. (02 pts). What is the absolute configuration at C-3?

cannot tell (circle one)

Br

H D
V

B. (16 pts). Treatment of V with sodium ethoxide in ethanol gave three alkenes. Draw the mechanism
for formation of each one, and indicate clearly the location of deuterium (if any) in each. Draw the structures carefully.

Br

H
H D

D
Br

E2

Z isomer, with one D

H
:B

Br

E2

E isomer, with no D

:B
H

Br
D

E2
H

H
:B

Alternate E2, one D in product

IV. (14 pts).

A. Note the relative rates for reaction of D with water

R
R
rate
CH
2.0
3
OSO2Me
CH3CH24.0
(CH3)2CH10.0
D
(CH3)3C180.0
i. (02 pts) Draw D in its most stable conformation with R = tert-butyl.
ii. (04 pts) Write the product and the mechanism for the most likely substitution process with R = (CH3)3C-.
iii. (04 pts) Use your mechanism to rationalize why the substrate with the t-butyl group reacts 90 times faster than the one with the
Me group. Explain carefully in terms of the transition state for the rate-determining step.
H2O

[products]

R
OSO2Me

H2O

R
CH3CH3CH2(CH3)2CH(CH3)3C-

[products]

SN1

rate
2.0
4.0
10.0
180.0

H
O H

H2O

H
O

+ H+

OSO2Me

equatorial tert-butyl is favored

over any other substituent
The rate determining step in the SN1 process involves a carbon atom going from having four substituents to
having three substituents; there is relief of strain in this step. The larger tert-butyl group leads to a larger relief
of strain (relatively higher energy reactant) compared to the methyl case.

iv. (04 pts) Write the product and the mechanism for the most likely elimination process with R = (CH3)3C-. The observed product
shows a triplet (J = 5 Hz) with area 1H at ! 5.35 ppm, and no other peaks above 2 ppm.
H
SN1
OSO2Me

triplet

cont

B. (16 pts) Now, note the related reaction from C. The rate of this reaction (substitution + elimination) shows a much
bigger dependence on the substituent R, with the t-butyl group giving an enormous acceleration.
R
OSO2Me

H2O

R
CH3CH3CH2(CH3)2CH(CH3)3C-

[products]

rate
2.0
15.4
67.0
45,000

i. (10 pts) Compared to the reaction in part A, why is this process so much more sensitive to the change from isopropyl to tertbutyl? Explain carefully.
OH
H

H
OSO2Me

H2O
rearrangement

simple
E1

J = 2 Hz
H

observed elimination product

strained double bond;

no alkene H showing

The tert-butyl is now locked into the axial position and feels two gauche interactions. In particular, one of the methyl
groups on the tert-butyl has to be in the repulsive interaction; it cannot rotate into a less repulsive conformation. The
other substituents, such as isopropyl, also have the axial gauche interactions, but there is at least one accessible
conformation with just a H pointing into the gauche interaction. So the steric effect for tert-butyl is strongly amplified
in this system.
H

H
OSO2Me

vs

H
H
OSO2Me

ii. (06 pts). Note that for the elimination product in this case, with R = tert-butyl, the 1H NMR spectrum shows two alkene H,
both doublets with J = 2 Hz and nearly the same chemical shift. Draw the structure of the elimination product and show the
mechanism of its formation.
See above

V. (18 pts). Consider the formation of cation H as the exclusive product from each of three different substrates, under the same
reaction conditions. The conditions are special: SbF5 is a powerful Lewis acid with an affinity for Cl greater than silver ion; SO2 is an
exceedingly weak nucleophile and allows the observation of free cations. The 13C NMR was used to establish the structure of H.
Cl

conditions for each reaction: SbF5 in SO2 solvent, -60o

13C

NMR for cation H: 4 signals (s, 2 t, quartet)

cation
H

Cl

Cl

Structure H:

A. (06 pts). What is the structure of cation H?

Explain how your structure is consistent with the NMR data.
By symmetry, cation H has 4 non-equivalent carbons: two CH2- types (triplet)
one with no H (s, cation carbon)
one methyl group (quartet)

B. (06 pts). What is the mechanism of formation of cation H from T? If you are not sure about your mechanism, explain your
reservations or alternatives.
Cl SbF5
H

Full credit requires showing a concerted (one step)

for ionization and h migration to give the tertiary cation.
The alternate two step mechanism via a primary cation
is certain to be of higher energy

+ SbF5Cl
H

C. (06 pts). What is the mechanism of formation of cation H from V? If you are not sure about your mechanism, explain your
reservations or alternatives.

Cl
V

SbF5

CH2

c
+ SbClF5

CH3

d H

In this case, initial ionization leads to a secondary cation, c. Carbon migration is possible, as shown, to give an
unfavorable primary cation (d) and then a hydride shift to give the stable tertiary cation, H. While the primary cation is so
high energy that we tend to discount mechanisms that require them, here the system has no other choice in order to
eventually equilibration to the most stable cation, H.

VI. (18 pts). Note the series of bromides, a-e. When mixed with silver nitrate in water, substitution occurs to give the
corresponding alcohols (OH substitution for Br). Note also the very different rates for this process (monitoring the rate of
disappearance of reactant bromide).
Br
Br
Br
Br
Br
O
O
O
O
c
d
a
e
b
rel rate:

1.0

0.01

0.1

50,000

5,000

A. (06 pts) Why is (b) much less reactive than (a)? Explain with a general mechanism.
The general mechanism is ionization, SN2. Secondary leaving group and activated by silver ion.
The rate determining step is the ionization step. The question is how do the oxygens in the ring
affect the transition state for this step, and that translates into how do the oxygens affect the
stability of the resulting cation.
H

Br

H 2O

Ag+

H H
O
H

O
H

RDS

+ H+

Br
In this substrate, the oxygen is close enough to exert electron removal by the inductive
effect, due to its high electronegativity. That destabilizes the cation intermediate and slows the rate.

B. (06 pts) Why is (e) much more reactive than a, b, or c? Explain with reference to the general mechanism.
Ag+
Br

Cation has resonance stabilization which is

estimated to be strong because it creates an
additional bond for the structure. This effect
dominates over the destabilizing inductive
effect.

H
O

C. (06 pts) Why is (d) still more reactive? Explain with reference to the general mechanism.
Ag+
Br

H 2O

H H
O
H

O
H

+ H+

O
O
This intermediate forms instead of the high energy
simple cation; involves two favorable 5-membered rings
and a new sigma bond C-O. The other substrates can
form parallel intermediates but each would involve a highly strained ring.

VII. (17 pts). Consider the reaction of molecule K under the conditions specified to replace hydrogen by bromide (HBr
byproduct). Reactions of this type are typically quite unselective and give a mixture of monobromide products.
Br2, h!

monobromide substitution products + HBr

K
A. (10 pts). Draw the major product (call it M) you expect from this reaction and the mechanism by which it forms. This is a
multi-step process; draw each step carefully. Identify the product-determining step. Use the appropriate arrows appropriately.

2 Br

Br2, h!

+ H-Br

Br +
H

product determining step.

Br
Br--Br

+ Br

H
M

B. (07 pts). Also draw the product (N) expected to be the second most abundant and explain why it is not as favored as M, but
favored over other alternatives. Include in your answer a brief general discussion of what parameter(s) influence the selectivity in
this bromination reaction.
95
110

93
H

H
H

103
85

There are five different C-H bond types (assuming the benzene C-H are all
approximately the same).
Each has a different bond energy (shown on structure), depending on
hybridization, number of substituents, etc. These can be found in the BDE
table in the data sheets.

In a radical reaction, the only thing that counts is the bond energy (no polar factors, etc). This depends on
hybridization, resonance stabilization, etc. Product is determined by which bond is weaker in the productdetermining step.
H

Br
H

The tertiary C-H bond is the next weaker, compared to secondary, methyl, and aryl.

VIII. (24 pts). Organic synthesis is what most organic chemists do, and you already have the tools to plan some simple
syntheses (I hope). It requires that you recognize the standard reactions (one or more) that connect a starting material with a synthesis
target. It sometimes helps to work backward from the target to the starting material.
Please suggest how you might carry out the following conversions by writing a sequence of steps showing reagents and
reactants required. Shorter plans with fewer potential side reactions or byproducts are better.
Be specific about the reagents and products for each step; you need not write mechanisms.
Name the mechanism involved in each step (SN1, SN2, E1, E2, electrophilic addition, oxidation, radical, etc) wherever possible
Possibly useful reagents: HBr, BH3, H2O, RO-OR, RCO3H, LiNR2, NaOH, CrO3, OsO4, NaH, pyridine, HCl, NaI, SOCl2,
Pbr3, MeSO2Cl. You may use any reactants you wish, such as acetylene, EtI, etc. Just specific clearly for each step.

A. (12 pts)

OH

CN

racemic

OH

Many possibilities.

HO

CN

Bonds that need to be made to get to the product.

CN is readily available as a nucelophile in NaCN, so an SN2 reaction is a good idea.
Need a leaving group at C-1

The substitution at C2 and C3 looks like electrophilic addition of H-OH to the pi bond. Now
decide whether you need Markovnikoff addition (H+,H2O) or anti-Markovnikoff (R2BH/H2O2)
Since OH is on the best cation site, Markovnifoff addition of H2O should give the right selectivity

SOCl2

NC-

OH

Cl
chlorination
by SN2

cat H2SO4
CN

H2O

SN2

CN
HO

Electrophilic add to alkene

OR:
Reversing the sequence gets you into some trouble:

cat H2SO4
OH

H 2O

OH
HO

need to make this into a leaving group selectively,

in the presence of another -OH. Possible, but
tricky.

Electrophilic add to alkene

Short sequences with reliable (i.e., not too creative) procedures will get full credit.

cont

10

HO
O

OH

B. (12 pts)

Note: one diastereoisomer

(racemic) is desired, as
drawn

Possible bond formations to get the product. But the formation of the bond to the
-OH must occur from the side opposite the Me group

O
RCO3H

HO
CH3CH2O

SN2
reagent approaches from the
less hindered face, away from the
Me group

addition to the less hindered end, typical of SN2

Electrophilic addition to the alkene

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IX. (15 pts). Note the following reaction promoted by base to equilibrate S with its isomer T.
Treatment of T with CrO3 gives U.
OH

base

CrO3

1H

O
S

NMR
!1.2 (3H, s)
1.4 (3H, s)
4.5 (1H, d, J=2 Hz)
9.5 (1H, d, J=2 Hz)
13C

NMR: 5 different signals in broad band decoupled spectrum

IR: 1740 cm-1 (strong)

i. 07 pts) Write the structure of T and the mechanism by which it forms from S. (Note: you may want to consider part ii
simultaneously)
H
O

:B-

SN2

H+

H
O

OH

ii. (08 pts) Write the structure of U and the mechanism by which it forms from T. Explain how your structure is consistent with the
1
H NMR data and the IR data. Note: you can buy the structure of U at a penalty of 5 pts.

O
H
OH

Cr
O

-H+

H
H

H
O
Cr
O
O

!1.2 (3H, s)
1.4 (3H, s)
4.5 (1H, d, J=2 Hz)
9.5 (1H, d, J=2 Hz)

O
H
O
Cr
O
O

CH3
-H+

H3C

H
H
O

O
Cr

+
HO

OH

CH3
H3C

H
H
O

Methyl groups are in different environments due positioning above and below the ring; the assignment shown
is arbitrary. The methine attached to the ring is perturbed by the O, shows up at 4.5. The aldehyde appears
at the position typical of -CHO groups.
The IR shows a typical aldehyde C=O stretch.

12

X. (20 pts). Note that isomers T and P react under the same conditions to give different products.
Br
OH

NaH

(1)

C8H14O + NaBr + H2
U

THF
solvent

O
THF

Br
OH

NaH

(2)

C8H14O + NaBr + H2
Q

THF
solvent

A. (02 pts). How are P and T related?

conformational isomers
(circle all correct answers)

a. enantiomers

b. diastereoisomers c. stereoisomers

d.

B. (08 pts). i. Draw T in both chair forms. ii. Circle the more stable chair.
iii. Estimate the difference in energy between the two chair forms using the Table of substituent effects on the Data Handout.

Br

OH
T

Br

O
H

diaxial: -CH2Br ca 1.8 + CH2OH ca 1.8 +

1,3-diaxial ca 3-4 = 6.6-7.6 kcal/mol

diequatorial, zero torsional strain

C. The chemist who was carrying out these reactions obtained pure samples of U and Q, but realized he got them mixed up while
labeling the containers. He noted that one sample showed moderate peaks in the IR at 3500 and 1680 cm-1 while the other one showed
neither of these (and no other characteristic functional group peaks other than C-H stretch) but he was stumped to come up with exact
structures. He turned to his labmate and she used mechanistic reasoning to suggest the exact structures of U and Q.
i. (02 pts) What is the structure for U?
ii. (05 pts) Draw the mechanism of formation of U from T.
iii. (03 pts) How is your structure consistent with the IR information?

Br

SN2

OH
T

Br

Na+ H-

Br

+ BrO
U

The IR shows no significant functional group stretches; structure U has no functional groups that would give such peaks.

cont.

13

D.
i.
ii.
iii.

(10 pts).
(02 pts) What is the structure for Q?
(05 pts)Draw the mechanism of formation of Q from P.
(03 pts) How is your structure consistent with the IR data?

Br

Br
Br

E2
OH

H
P

Na+ H-

+ BrHO
Q

Neither conformation of P is favorable for the intramolecular SN2; would give a highly strained bicyclic structure.
At the same time, one conformation, with the axial -CH2O- is ideally poised for an intramolecular E2.
The IR shows a peak for 1,1-disubstituted double bond at 1680 cm-1, and peak for the -OH stretch at 3500 cm-1.

________________________________________________________________________________________________________
Thats it!
Have a good break; see you in Chem 304 for bigger and more biological things
MFS

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