Chemistry 303

fall, 2001

THIRD EXAMINATION
7:30 pm December 3rd
Duration: 2.5 hr
Name_______________KEY____________________________________________
Lab TA__________________________________________________________
(if you do not know his/her name, give day of lab section. NOT Hooley)
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 only in the space provided for each question.

WRITE SOMETHING
Score:
1___________/21
2___________/21
3___________/34
4___________/08
5___________/16

Total:

/100

There are 10 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 afternoon on
Tuesday. It would be well not to discuss the exam until after that time.
NOTE: You will be asked to write mechanisms and use the arrow formalism. Please use it
precisely, carefully, and correctly. Show charges carefully. Distinguish between an
intermediate and a transition state. A "good" mechanism is short and proceeds through lower
energy intermediates/transition states.
NOTE: you may buy structures A, B, or C (Problem I) at a price of 4 pts each.
you may also buy structure T (Problem III) at a price of 10 pts.
Just ask the proctor.

PLEDGE:_________________________________________________________________

I. (21 pts) Consider the following reaction of X, and the products indicated.

Cl
X

A C 6H10 major product

B C6H10 minor product
C C7H14O minor product

Na :OMe
ether

CH3

Note: you may purchase the structures of

A, B, or C at a cost of 4 pts each

A. (1 pt) What is the most likely mechanism for the formation of A, the major product?
SN2

SN1

E2

E1 none of these

(circle single best answer)

B. (1 pt) What is the configuration at the carbon bearing the methyl group in X ?

cannot tell

C. (1 pt) What is the configuration at the carbon bearing the Cl substituent in X ?

cannot tell

D. (1 pts) Draw carefully the enantiomer of X .

E. (1 pts) Draw carefully one diastereoisomer of X .

same connectivity, non-superimposable, non-mirror
images of X

mirror image of X

Cl

or

Cl
CH3

Cl

CH3

CH3
cis isomers

F. (4 pts) Using the arrow formalism carefully, write the mechanism for the process giving A, showing clearly
the structure of the major product.
H anti (trans) to the Cl is removed in an anti-parallel transition state for the E2

H
Na :OMe

Cl

+ MeOH + BrMe A

Me

G. (2 pts) Draw a careful representation for the transition state for this process, showing clearly all partial
bonds and partial charges.
H

Me

H
H

Cl

Cl

Me

Cl

OMe
or

Me
H

OMe

4 partial bonds, 2 being broken and 2 being formed. 2 partial (-) charges, from electrons leaving the OMe, and

arriving at the Cl
H. (3 pts) There is an isomer of A which could be formed by the same mechanism, shown as B.
Please draw here the structure of B and indicate why it is less preferred than the major product.
This would require a syn E2 elimination; higher
energy than the anti parallel transition state.

Cl

HO-

Me B

Me

I. (3 pts) There is also another minor product, C, obtained as a single enantiomer. What is the structure of
C? Write the mechanism for its formation.

Na :OMe

Cl
CH3

S N2

OMe
CH3

J. (4 pts) The first two products, A and B, are obviously isomers.

1. (1 pt) Can you use Mass Spectrometry to differentiate them?
Explain, if necessary.

yes

no

Since the compounds have the same molecular formula, a mass measurement is not sufficient to distinguish
them. However, you could use the fragmentation pattern differences, in principle, so a "yes" answer is
allowed, with proper explanation.

methyl

2. (3 pts) 1H NMR will certainly be helpful. Each isomer contains a methyl group. Please explain how
the chemical shift and pattern of peaks for the methyl group in A will differ from that for the
group in B.
In A, the methyl group is adjacent to one H, and will therefore appear about 1 ppm at a doublet with J ca. 6-7 Hz.
In B, the methyl group is on a double bond, and therefore the signal is a little more downfield, perhaps about 1.8
ppm. It has no H on the adjacent carbon, so it should be a singlet. However, there can be allylic coupling to the
H on the double bond, with a small J value, and it could appear as a doublet. Either answer is acceptable.

II. (21 pts) Consider each of the following pairs of reactions.

4
Please decide which reaction is faster for each pair and write the product(s) for that reaction. Give the single
most important reason why you think that one is faster. You probably have to draw the mechanism to make your
point. Give the name of the mechanism. If you have trouble deciding which mechanism is operating, specify a
reasonable mechanism, and then indicate which example would be faster by that mechanism. For each of the
faster reactions, indicate clearly which is the nucleophile and which is the electrophile.
Br
A.

H
NaH

HO

1.

deprotonation

Br

S N2

+ Br-

C4H 8O

FASTER

rate-determining step is the internal SN2

HO
2.

NaH

C3H 6O

Br

The corresponding product here would be:

The S N2 transition state would involve more bond angle strain compared to the TS leading to
the five-membered ring, therefore this process is slower.
The nucleophile is the R-O

and the electrophile is the carbon bearing the Br leaving group

NOTE: an E2 mechanism is also not completely crazy, to give a different product with the correct formula. If you
did this, you should have gotten some partial credit. It does not normally happen with this base (NaH), but you
don't know that.

________________________________________________________________________________________
B.

Br2, H2O
1.

CH2 Cl2 solvent

Br

Br

Br--Br
H2O
CF3

Br2, H2O

2.

Nucleophiles:

CH2 Cl2 solvent

Ph
and H 2O

This cation intermediate is stabilized

by resonance interaction with the
phenyl group

In this reaction, the

intermediate cation would
be destabilized by the inductive
withdrawing effect of the CF3 group

Electrophiles:

Br

Br

Br2 or HOBr and

OH2
Br

Ph

etc

OH

Br

_________________________________________________________________________________________
Primary carbon undergoing substitution: SN2

C.
Br

CH3 OH

Br

(CH3)2 NH

N is a better electron donor than O (better base)

N
H

The rate-determining step involves the addition of the nucleophile to the electrophile; better
nucleophile, higher rate.
The MeOH is smaller than Me2NH and for that reason might react faster, but the electronic effect is very strong.
Partial credit for a well-reasoned argument that MeOH would be faster.
Nucleophile: Me2 NH. Electrophile: -CH2Br

III. (34 pts) An Orgo student planned a synthesis of W from U , and figured that one of our
5
standard substitution mechanisms would be perfect. He simply heated U in acetic acid and expected W would
form in a fast, favorable reaction. The reaction was fast but, unfortunately, W was only a minor product. The
main product was an isomer, T. Another minor product, S , was also observed. Dr. Gingrich appeared and
asked cryptically "Aren't you forgetting that the rate-determining step is not necessarily the product-determining
step?" and then went off to have a cigarette. Note: you may buy the structure of T at any time for 10 pts
penalty.
Spectral data for T: IR: 1743(s), 1676(m)
CH3 CO2H
O

heat

1H

+ T + S
(major) (minor)

NMR(CDCl3): 1.71(s,3H); 1.77(s,3H),

2.05(s,3H), 4.57(d, J=6Hz, 2H), 5.34(t,
J=6Hz, 1H) ppm
13C NMR(CDCl ): 18.0, 21.0, 25.8, 61.4,
3
118.6, 139.0, 171.0 ppm

W
(minor)

A. (6 pts) Draw the mechanism which leads to W . Show any intermediates. What is the general name of this
mechanism? Why was this reaction expected to have a particularly favorable rate-determining step?

S N1

CH2

cation intermediate especially stabilized by

resonance. Also: tertiary and great leaving
group

I
O
O
H
O
O
oxonium
ion intermediate H

-H +

O
O

Acetic acid can be a

nucleophile using the lone pair
on the carbonyl oxygen (best,
but not shown here) or using
the a lone pair from the -OH
group (shown)

B. (5 pts) Draw the structure for T and correlate it with the 1H NMR data. That is, make clear which H (or set
of equivalent H) give rise to which of the 5 peaks. Make clear which H are coupled to which other H.
Indicate any ambiguous assignments.

a
H3 C

H3 C
b HH
d

e
O

CH3 c

a or b at 1.71 and 1.77 (ambiguous)

c at 2.05, s, no coupling
d at 4.57, coupled to e, J= 6 Hz, d
e at 5.34, coupling to d, J= 6 Hz, , t

no coupling, singlets

O
continued....

III, cont. C. (5 pts). Write the best mechanism for the formation of T, showing all intermediates.
Explain why this is the major product, in preference to W .

SN1

resonance stabilized

CH2

I
intermedidate

O
intermediate

O
H

-H

The cation intermediate has (+) charge at

both ends of the allyl system. The nucleophile
can add to either end. The preferential formation
of T is based on minimizing steric repulsion as the
nucleophile approaches the cation, and the formation
of the more stable alkene (same factors stabilize the
transition state a bit).

T
+ H+

D. (6 pts) The only spectral data collected for S were the mass spectum [m/z 69(5.6%), 68(100%)]
and the UV spectrum [ max 223, 21,500]
1. Write the structure for S .

S
2. Explain how this structure is consistent with the UV spectrum.
Two conjugated double bonds give an observable pi-pi* absorption at ca 220 nm, with
a high .

3. Write a mechanism for the formation of S . What is the name of this mechanism?
H

SN1
I

-I

+ H+

E. (4 pts). Compared to the rate of formation of W, is the rate of formation of T: higher

?
circle single best answer and explain your choice briefly.
SAME

lower

same

Prob III, cont.

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F. (8 pts). Now draw carefully two reaction coordinate diagrams, one for the conversion of U to W ,
and a second one for the conversion of U to T. On the diagrams, take care to make the energy levels qualitatively
correct between the two so that the energy of transition states and intermediates can be compared between the two;
the reactants start at the same energy.
Draw structures of intermediates but not transition states.
Use these diagrams to explain what Henry meant by "the rate-determining step is not necessarily the
product-determining step."
Identify the activation energies in the product-determining step for formation of W and for T. Your
diagram should make clear their relative magnitude.

G# for the ratedetermining step

O
H
O
G# for the productdetermining step

extent of reaction

G# for the ratedetermining step

O
H
O

G# for the productdetermining step

extent of reaction

In this diagram, the

product-determining step is of lower
G# compared to that for W, while
the G# for the rate-determining
steps are the same. Therefore, the
formation of T is dominant.

IV. (8 pts). Consider the following conversion of M to N .

H Br

Na :CN

CN

(no stereochemistry implied)

H
N

A. (1 pts) Identify clearly the stereogenic centers in M with a circle.

B. (7 pts) The conversion of M to N is a multi-step process and leads to a single enantiomer of N .
Draw the best mechanism here, showing all intermediates (but not transition states).
Label each step as SN2, S N1, E2, or E1 where relevant.
Draw clearly the exact structure (stereochemistry) of the product N .
H

Br
H

H
O

:CN

inversion here

Br
H

S N2

M
S N2

SN2 at the less hindered carbon, with the better leaving group

H
H
O
N

cis configuration of the epoxide due to the inversion

in the SN2 process

V. (16 pts) The following substitution reaction was studied in an effort to prepare one
enantiomer of E. The desired pure enantiomer of E has a molecular rotation []D = +68 o.
H
I

CN

CH3
D
[]D = +45o

H H
H
NC
N
CH3
H 3C
E
[]D = see conditions

CH3 -NH2
in a solvent

A. (4 pts) When the reaction was run in hexane (100 mL) as a solvent the rate was very low, and the product had
[]D = +68 o. Draw carefully the primary mechanism which must be operating in hexane solution. Show the
structure of the main enantiomer of E that is formed. Name the mechanism.
H 3C

H
CN

CH3
D
[]D = +45o

S N2
in a solvent

H
N

NC

CH3
E
CH3 -NH2

Since the optical rotation is exactly that of

the desired enantiomer, the reaction
must have proceeded with perfect
inversion (or retention). That implies a
pure SN2 process (we have no retention
mechanism).

B. (5 pts) When the reaction was run in DMSO as solvent (100 mL) with everything else the same, the rate was
much higher but the product had []D = +18 o. Use a mechanistic analysis with words and pictures to explain
why the change in solvent to DMSO resulted in a higher rate and a lower molecular rotation for the product.
The spectral data in all cases were completely consistent with the general structure E.
H 3C

H
CN

S N2

CH3
D
[]D = +45o

H
N

NC

H
CH3
E

CH3 -NH2

S N1

CN
CH3

E + enantiomer
(50:50)

H
The reaction is faster because the more polar
solvent favors the SN2 transition state, but it
also (even more strongly) favors the ionization
pathway, SN1. Both mechanisms operate,
and the rotation is less than the maximum
because of partial racemization.

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C. (4 pts) In an effort to increase the [] value, the reaction was tried again in DMSO, but this time
with ten times less solvent (e.g., with 10 mL instead of 100 mL). Everything else was the same.
Rewardingly, the []Dwas now higher, at +51 o. Please explain in terms of your mechanism analysis in part B.
The SN2 reaction is bimolecular, and very sensitive to concentration effects--more
concentrated, faster due to more frequent collisions between the reactants. Rate is
proportional to the product of the concentrations.
The SN1 is unimolecular, related only to the conc of one reactant
Therefore at higher concentrations, the rate of SN2 is relatively faster than the SN1,
and the rotation is closer to a pure SN2 result.

D. (3 pts) When the methylamine was replaced as nucleophile by aniline (Ph-NH2), reaction with D in DMSO
gave a product (F) for which []D = 0o. Explain why this nucleophile gives a product with []D = 0o.
H H
H
N

NC
F

Aniline is a weaker nucleophile (base) because the non-bonding electron pair is held
more tightly compared to methylamine. This is a resonance effect:
H

H
N

N
H

etc (two more strucutres delocalizing the electron

pair into the benzene ring.

A weaker nucleophile will slow down the SN2 process, but will not affect the rate of
the SN1. The rate of the SN1 depends only on the ionization of the halide. In this
case, the SN2 is slowed sufficiently so that only the SN1 operates, and complete
racemization is observed.

_________________________________________________________________________________________
End Exam 3

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