Chemistry 303

fall, 2006
THIRD EXAMINATION
7:00 PM, DECEMBER 5th, 2006
Duration: 2.0 hr
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.
USE THE ARROW FORMALISM CAREFULLY FOR ALL MECHANISMS
BE SURE TO INCLUDE ALL FORMAL CHARGES
IF YOU ARE ASKED TO WRITE THE PRODUCTS FROM A PROCESS INVOLVING RACEMIZATION, BE SURE TO
DRAW BOTH STEREOISOMERS TO MAKE IT CLEAR.

Write only in the space provided for each question.

Score:
p2___________/10

p3___________/10

p6___________/08

p7___________/12 p8___________/15

Total:

p4___________/14

p5___________/12
p9 _________/16 p10 __________/10

/107

There are 10 pages in this exam; please check now to be sure you have a complete set.

Please be aware that a small number of students will be taking the exam at different times up until the morning on Wednesday. It
would be well not to discuss the exam until after that time.

Pledge:_________________________________________________________________________________

I. (10 pts). Considering the following pair of reactions, please choose the one that you predict will be faster and draw the
product(s) from that reaction (2 pts)
A.

Br

(1)
Br

Cl

NaI

Cl

Cl

NaI

(2)

A. (04 pts). Name the mechanism and draw it, including the transition state for the rate-determining step.
The substrate for eq 1 is an allylic bromide and will react faster in both an SN1 (resonance delocalized cation) and SN2
process (pi bond stabilization of the transition state. The conditions do not include a strong base, so E2 is not likely. The
solvent is fairly non-polar, so ionization is unlikely. The chloride is not underconsideration as a leaving group, since in (1)
it is attached to an sp2 orbital (strong bond) and in 2, it is secondary (hindered). Chloride is intrinsically a less good
leaving group than Br because it forms a stronger bond to carbon and is a slightly less stabile anion (weaker conj base).
Most likely SN2.
Br

Cl

!"
I

!"
Br

Cl
+ Br

Cl
TS

B. (04 pts). Then explain why your choice is the faster reaction, focusing on the single most important reason for the
difference and based on the TS picture.
!"
I

H
Cl

!"
Br

In this TS, the pi orbitals can interact with the p orbital

at the carbon undergoing substitution, stabilizing this orbital and
therefore lowering the TS energy.

II. (14 pts). Consider the molecule B. It is one of these versatile substrates that can do any of the mechanisms we have
talked about. Which mechanism occurs depends on base/nucleophile and solvent character.
H

or
OSO2Me

OSO2Me

OSO2Me

B
diastereoisomer of B

A. (02 pts). Draw next to B a diastereoisomer of B, showing clearly the arrangement at each stereogenic center (as in B).
B. Consider an E2 mechanism.
(1) (04 pts). Suggest specific conditions (specific base/nucleophile/solvent) from the following lists (one from each) which would
tend to favor E2 over the others. Explain your choices briefly.
Best base/nucleophile: NaOMe, LDA, NaBr, Na acetate, NaCN

Li N

= LDA

Best solvent: water, CH2Cl2, isopropyl alcohol, CH3CN, hexane

Base is required for E2: best- LDA (very strong, hindered so not a good nucleophile)
second best-- NaOMe
no others are acceptabletoo weak
Should avoid a polar solvent in order to minimize the chance of competing SN1/E1.
Besthexane
Second best-- CH2Cl2
No others are acceptable

(2) (04). Draw the mechanism for the E2 reaction from B, including the transition state for the rate-determining step. Draw the
structure of the product carefully. Use the sawhorse projection carefully to illustrate.

!"
OSO2Me

OSO2Me
H
Me

Ph
H

B:

H
serious
gauche
repulsion

Ph

Me
!"
:B

Me

repulsion

Ph

Z-isomer

Cont

(3) (04 pts). Structure B and its diastereoisomer need not react at the same rate. Which would have a higher rate in the E2
reaction? Explain using Newman projections.

OSO2Me

less
serious
gauche

H
Me

less
repulsion

Ph

Me

The diastereoisomer of B has less gauche

repulsion in the required conformation for
the best E2 TS, therefore it proceeds faster
compared to the E2 for B.

Ph

E-isomer

B:
diastereoisomer of B

C.

Consider the SN1 reaction for B where NaCN provides the nucleophile, dissolved in a solvent.
(1) (04 pts). Write the mechanism for the SN1 reaction of B in water/NaCN with heating to initiate reaction.

CN

OSO2Me

CN
H

H
Me

Ph

Me

H
Me

Ph
H

CN

Ph

CN
Ph

Me

(2) (06 pts). Is the reaction likely to be faster or slower if CH2Cl2 is used as solvent in place of water
(same temperature, etc)? Draw two reaction coordinate diagrams to show the relative effect of changing the solvent.
The rate determining step is the ionization of the leaving group to give the intermediate cation. This involves very strong
increase in charge as one proceeds to the intermediate, and the TS is strongly stabilized by polar solvents relative to the
effect on the reactants.

TS
TS
cation

!G#

non-polar solvent

cation

!G#

polar solvent

extent of reaction

extent of reaction

Cont

(3). (04 pts). Like many SN1 reactions, this one is complicated by rearrangement before addition of the nucleophile
(substitution with rearrangement). Consider the possible rearrangement products and draw here the mechanism for the process that
is likely to be most favorable. Explain your choice. Show the product(s) clearly,
OSO2Me
H
Me

NC H

H
H

Ph

Me

Ph
H

H
Ph

Me

Me

H
NC

Me

CN

H
Ph

CN
H
tertiary benzylic cation,
stabilized by resonance
delocalization

H
etc

Me

The same cation as before can allow migration of a H to give a very stable tertiary cation, with resonance delocalization.
Migration of the Me group would give a secondary, resonance stabilized cation, not quite as favorable.
__________________________________________________________________________________________________________
III. (08 pts). Draw the single most likely product for the following reaction, consistent with the conditions and data. Then
write a detailed mechanism and label the rate-determining step. Show all intermediates. Name the mechanism.
Br
heat

Q; C12H15N

HBr

THF solvent

NH2

Selected 1H NMR spectral data for Q:

two singlets at 1.8 (3H), 1.85 (3H)
one alkene H ( 5.4, d, J=7Hz)

THF

RDS

NH2

N
H H

NH2

SN1 mechanism

N
Q

IV. (08 pts). One can imagine cyclohexanes with heteroatoms in the ring (e.g., S and T). The usual chair
conformational analysis is used to consider conformational isomers.
O

tBu

tBu
O

OH
O

A. (04 pts). As you know, the axial form of R is disfavored by more than 5 kcal/mol. But in S, the preference for equatorial
over axial is only 1.4 kcal/mol. Please rationalize this difference by explaining why axial R is so unfavorable and then why axial S is
much less so. Draw the relevant structures carefully in the chair form.

H
H

O
O

unavoidable
gauche
interactions

reduced
gauche
interactions

B. (04 pts). Perhaps surprisingly at first glance, in T the axial conformer is actually favored compared to equatorial.
Explain.

H O
O
O

axial stabilized by H-bonding.

Not available in the equatorial

V. (12 pts). Consider the trisubstituted cyclohexanes, H and J

and the E2 reaction in the presence of strong base.
Br

A. (04 pts). Draw here the two chair forms of H (H-1 and H-2) and the two
chair forms of J (J-1 and J-2).

Me
Hb
Hc

Me

Ha

Cl

Cl

Ha
Cl

Br
Cl

Hd

H-2
Ha
Cl

Ha

Hb

Br

Hc

H-1

Br

Me
Hd

Hc

Br

Cl

Me
Hc

J-1

Br

J-2

B. (08 pts). Which of the four isomers above will react faster in the E2 process? Explain your choice carefully. Several different
elimination products are possible. Draw carefully the single most likely product from the E2 reaction and explain why it is formed
preferentially. Draw the mechanism carefully.
An axial leaving group is required for the anti-parallel TS preferred for E2, so only H-2 and J-2 are candidates.
Br is a better leaving group than Cl (weaker bond and more stable anion). So Ha is the preferred proton to pick off.
J-1 is the low energy state for that molecule and an increase of energy is necessary to move to the all axial version J-2
before the elimination can begin. On the other hand, H-2 has only two axial substituents and both have relatively small
repulsive values (0.5 compared to 1.7 for Me). Relatively little energy is necessary to achieve the axial Br conformation,
H-2.
This added energy to access J-2 means the overall activation energy for E2 from J is higher than for H.

:B
Ha
Cl
Me
Hc

Br

Me
Cl
Me
Cl

J-2

VI. (15 pts). Note the formation of X under the conditions specified.
O

BF3
CH3OH solvent

IR: 3500 cm-1 (only significant functional group absorption)

UV: no significant absorption
C5H10O2
C-13 NMR: 5 peaks
H NMR: ! 2.0 (broad s, 1H), 3.5 (s, 3H), 4.35 (d, 2H, J=7 Hz), 4.40 (d, 2H, J=7 Hz)
5.45 (1H, d of t, J=12, 7 Hz), 5.50 (1H, d of t, J=12,7 Hz

A. (02 pts). What is the structure of the product, X? [You may purchase this structure at a penalty of 7 pts]
OH

MeO

or

MeO

OH

OH
B. (08 pts). Write a careful mechanism for the formation of X
showing all intermediates (not transition states).

BF3

or

MeO

BF3

BF3

BF3

Me-O-H

HO
O

BF3

H+

+ BF3

BF3
O

-H+

O
H

C. Support your structure for X by analyzing the spectral data:

1. (02 pts). How are the IR data consistent with the structure?

Give one point.

The peak at 3500 cm-1 is consistent with the presence of the OH group
2. (03 pts) Give one key element of the H NMR data which supports your structure clearly.
presence of broad peak at 2.0 is not very definitive.

Same for singlet at 3.5 for the Ome

better:
Presence of two alkene H (5.45, 5.50)
Coupling pattern for the alkene H showing CH2- adjacent
Coupling pattern for the CH2- showing one H adjacent
Two peaks at appropriate chemical shift to be inbetween an O and a double bond (4.35, 4.40)

MeO

OH

VII. (16 pts). Consider the molecule E. It undergoes reaction in methyl alcohol solvent with silver nitrate added to give two
isomeric products, each of them a pure single compound.

H OCH3

AgNO3
F

a
E

Cl

CH3OH
(solvent)

[!]D = +4.5o

C8H18O2

[!]D = 0o

[!]D = +10.0o

A. (02 pts). In the reactant, E:

What is the absolute configuration at carbon (a)?

R
R

What is the absolute configuration at carbon (b)?

cannot tell (circle single best answer)

cannot tell (circle single best answer)

B. (02 pts). The rotation for E of +10.0o in a solution requires that: (circle all correct answers)
(1) E has one at least one stereogenic center with the R configuration.
(2) The solution of E caused rotation of polarized light to the right
(3) The concentration of E in the solution is 0.1 M
(4) The sample vial containing E was spinnng at +10 rpm
C. (04 pts). Draw the exact structure for F and for G, showing clearly the configuration at each stereogenic carbon. Explain how
your structures are consistent with the [] values (F has a positive value and E has a value of zero).

H OCH3

H OCH3
F

H3CO

OCH3

F is chiral, capable of having a non-superimposable mirror image and therefore is capable of rotating the plane of plane
polarized light. It is present as one enantiomer, so there should be a net rotation.
G has a plane of symmetry (through the central carbon-carbon bond). The stereogenic centers at the end are mirror images
of each other. The mirror image is the same structure. This is a MESO isomer, and does not rotate polarized light.
D. (06 pts). Write a mechanism for the formation of F and G which makes clear how each forms under these conditions.

H OCH3

H OCH3

Cl

H3CO

addition to either
lobe of the empty p
orbital

Ag+

H OCH3

H OCH3

H OCH3

H OCH3

HOMe

OCH3

H3CO
H

E. (02 pts). How are F and G related?

Enantiomers

OCH3
H

Diastereoisomers Stereoisomers
(circle all correct choices)

None of these

VIII. (10 pts). The reaction of an amine with nitrous acid gives the diazonium ion group, which very easily loses N2 as a
+
leaving group in a spontaneous ionization process. In the case shown here, the elements of an E1 elimination appear [N2 and H ],
along with Q [C6H10O]. However, Q is not the simple E1 product.
Spectral data for Q:
N

NH2

HONO

OH

IR: 1751 cm-1 (s)

OH

+ N2

H NMR: 1.1 ppm, 3H (d, J=7Hz)

1.5-1.7 ppm, 4H (multiplet)
2.2 ppm,
2H (t, J=7Hz)
2.5 ppm, 1H (sextet, J=7Hz)

+ H+

CH3

CH3

13

C NMR:
peaks at 16, 18, 19, 30, 33, 210
ppm
A. (05 pts). Draw the structure of the simple E1 product one might expect from P and write the (hypothetical) mechanism of
its formation. Give two elements of the spectral data that are clearly inconsistent with the structure.

OH

OH
CH3

OH

-H+

CH3

-N2

CH3

B. (05 pts). Draw the structure of Q showing clearly the configuration at the stereogenic center(s), and write the mechanism
of its formation. Show all intermediates; you need not represent transition states. Give two elements of the spectral data that are
clearly consistent with your structure.

H
O

OH
CH3

-N2

Me

H
OH

-H+

Me H
O

CH3
Me migration from
top face of fivemembered ring

-H+

resonance structure
stabilized by additional
bond

Me
O

The product structure is consistent with the presence of a C=O in a 5-membered ring (1751)
with a Me doublet (adjacent H)
with 5-non equivalent C and a C=O in the C13 NMR

10