1

Chemistry 303
Fall, 2007
Final Examination
1:30 pm January 17th, 2008
Duration: 3.0 hr
NOTE: An additional 30 min will be allowed for completion of the course evaluation forms by those who
have not done it.

KEY___________________________________

Name_____________

Lab TA_______________________________________________ (not David, Casey, nor BJ)

This is an open book examination; you may use anything that 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

p2______/30

p3.______/16

p4.______/14

p5._______/14

p6._____ _/20

p7.______/12

p8.______/10

p9._______/14

p10._______/18

p11._______/12

p12.______/18

p13_______/14

p14_______/08

Total: ___________/200
There are 00 pages in this exam; please check now to be sure you have a complete set.

Pledge:_____________________________________________________________________________

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I. (30 pts). Warm up with old stuff Consider the molecule below, which is produced by a
marine sponge. Lets analyze its bonding and reactivity. Write clear answers; explain any ambiguity
briefly. Do not forget the hydrogens. Label the features as requested; use an arrow to locate your label.
e

Br
a

b,i

h,d

CH3

k
j

H
H
c

1.
2.
3.
4.
5.
6.
7.

Which is the weakest sigma bond in the molecule (you may need your BDE tables)? Label it (a).
Which is the strongest C-C single (sigma; not part of pi) bond in the molecule? Label it (b).
Which is the strongest C-H bond in the molecule? Label it (c).
Which is the weakest pi bond? Label it (d).
Which carbon will be most reactive in an SN2 mechanism? Label it (e) and point with an arrow.
Which group or groups is (are) responsible for the !max at 230 nm in the UV spectrum? Circle it.
Which H attached to an sp3 carbon is most deshielded (downfield, to the left) in the 1H NMR
spectrum? Draw it in and label it (f).
8. Which H or group of H is most shielded (upfield, to the right)? Draw it in and label it (g)
9. Which is the shortest C-C bond in the molecule? Label it (h).
10. Which is the shortest C-C single (not part of double or triple) bond in the molecule? Label it (i).
11. Identify one group that will show a characteristic
2060 cm-1
peak in the IR spectrum.
two possibilities (only one needed)
R
H
Draw the group here and give the approx.
-1
-1
3300
cm
position (in cm ) of the peak:
___________________________________________________________________
12. Identify a second group that will
show a characteristic peak in the IR spectrum.
O
Draw the group here and give the approx.
1680 cm-1
1760 cm-1
C
position (in cm-1) of the peak here:
13. Which H is relatively acidic due to resonance stabilization of the conjugate base? Label it (j) and
explain here.
O
O
O
R
R
H
R
O
O
O
resonance stabilized conj. base

14. How many stereogenic centers are there in the molecule?

Circle best answer.

15. Which is the most polarized bond in the molecule? Label it (k).

other

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II. (16 pts). Consider the E2 reaction of structure A.

H
Br

Br

Me

H
Me

E2
X

A. (6 pts) Draw here the structure of A using the chair representation.

Then write the mechanism for the most likely E2 reaction from A using a base. Show the product
structure carefully.
X

CH3

CH3
Br

Br

H
H
Br
antiperiplanar arrangement of H and Br gives the best transition state for E2. Only
possibility is the one shown, with the axial Br. The rings cannot flip, and therefore the
other Br can not get into the axial position for a favorable E2

B. (5 pts). Obviously, two Br and several H could be involved in the E2 process, yet only one H and one
Br are in the favored mechanism. Explain, based on your structure and mechanism.
See explanation above.

C. (5 pts). The E2 mechanism is often in competition with an SN2 reaction. Considering the list of
reagents here, circle the one most likely to favor the E2 process. Put a square around the second best
choice, and give at least two reasons why your first choice is better than the next best one.

NH2

The circled base from that list is the best choice. You are looking for the least stable base and the least polarizable
base. It also helps that it is sterically hindered. The alkoxide in the square is second best, as all the others choices
are much weaker bases and/or more polarizable.

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III. (28 pts). For each of the following pairs of reactions, pick that member of the pair that will
proceed with the highest rate. Give the single most likely product from that reaction. Give the single
most important reason for the difference in rates.
A. (7 pts).
CH3

F3C

H-Br

Br

C4H4BrF3

CH3
F 3C

CF3

F 3C

H-Br

CH3
+ E isomer

F 3C

Br

C4HBrF6

F3C

CH3
alternate cation, disfavored by inductive withdrawing effect of CF3

The second substrate must proceed through a cation intermediate which is adjacent to a CF3 group. Inductive destabilization raises the energy
for this transition state.

B. (7 pts).
O

NaI

Cl

DMSO
solvent
Tertiary halide, can react by rate determining
ionization or an E2 mechanism

LiBr
Cl

O
-Cl-

DMSO
solvent

Br
Br

Polar solvent favors ionization

Absence of strong base favors SN1
Ionization is strongly favored in the second case
due to resonance stabilization of the intermediate
cation

Continued

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C. (7 pts).
Br

Br

Br

Br

Br

Br

Br2

While triple bonds are typically equally reactive as double bonds, this
triple bond is constrained in a 7-membered ring, and cannot achieve the
ideal 180o bond angles. The bond angle strain raises the energy of the
reactant, and accelerates the reaction. Or one can say the overlap in the triple
bond is weaker than normal, and therefore the HOMO is higher and the molecule
reacts more readily with an electrophile (LUMO for Br2)

dibromide

D. (7 pts).
NaSMe
I

DMSO
(solvent)

NaSMe
I

unfavorable bond angle

DMSO
(solvent)

SMe
SMe

or E2 to give

or

Both are tertiary halides, so ionization or E2 are

the only reasonable possibilities. Ionization of the cyclo
propyl iodide is disfavored by ring strain; the cation
demands a 120o bond angle, and the 3-membered ring
is restricted to 60o. Ionization ideally changes the angle from 109o to 120o.
Another way to say the same thing is to recognize that the strained ring
leads to more (s) character in the external orbitals [more (p) character in the
bonds making the ring], and therefore is a less favorable location for a
(+) charge.

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IV. (20 pts). The reaction of V with catalytic sulfuric acid in THF leads to a mixture of
hydrocarbon isomers, with molecular formua C10H12 , mainly the structures W, X, and Y. Note that the
ratio of W:X:Y changes as the reaction is allowed to continue: at the early stages, almost no Y is
detected, but at long reaction time, Y is nearly the exclusive product. Compounds W and X show UVmax
typical of a simple benzene ring while the !max for Y is shifted to longer wavelength.
H2SO4
OH

THF

Y (E/Z mix)

X (E/Z mix)

A. (06 pts). Give the most likely structures for W, X, and Y in the boxes above.
B. (06 pts). Write a mechanism for the formation of W and X.
H2SO4
OH

H 2O

H2O

H
-H2O
O

(to X)

(to W)

H+
H

H 2O

(and Z isomer)

C. (06 pts). Write a mechanism for the formation of Y.

H+
H
(and Z isomer)
X

H+

+
Y

(and Z isomer)

H2O

D. (02 pts). Give an explanation as to why Y becomes the predominant product at longer reaction time.
The protonation and elimination processes can continue on the product X, and now elimination can take a different
course, leading to the conjugated alkene, Y. The double bond adjacent to the phenyl group leads to small
additional stabilization, and therefore this isomer predominates at equilibrium. It also leads to a longer wavelength
UV absorption, with more p orbitals involved in the pi molecular orbitals.

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V. (12 pts) From time to time, we have mentioned orbital interactions in controlling reaction
rates. For SN2 reactions, the dominant interaction is HOMO of the nucleophile and LUMO of the
electrophile.
A. (6 pts) Write the mechanism for the reaction of ammonia with methyl iodide. What is the
HOMO and what is the LUMO?
H

H
H

N:

H
HOMO is the nonbonding
orbital on nitrogen

H
H N

H
H

I-

H
LUMO is the !*
orbital from the C-I bond.

B. (6 pts). It is an interesting fact that hydrazine (G) is a much stronger nucleophile than
ammonia, in the SN2 reaction. The orbital interaction argument is usually used to explain this. What is
the argument? It will be useful to draw a simple MO diagram, showing orbital interactions and relative
energy levels for the non-bonding electrons.
NH3

H2N

NH2
G

ammonia

HOMO
In hydrazine, the nucleophilic HOMO on nitrogen has adjacent to it
a filled non-bonding orbital. This is a destabilizing HOMO orbital interaction.
It can be described by the simple MO picture here. The non-bonding orbitals
on each nitrogen (in G) interact to generate two new orbitals, one of higher
energy and one of lower energy. Since there are 4 electrons involved, both
orbitals are filled. HOMO for G is now at higher energy due to the adjacent
nonbonding electron pairs.

E
O

The destabilization can also be described as electron-electron repulsion, with

the two pairs of non-bonding electrons held in proximity.

H2N

NH2

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VI. (10 pts). HCN and the trimethylammonium ion have about the same pKa (ca 9-10).
However, cyanide anion is a much poorer leaving group than trimethylamine. Why? In your answer it
would be good to include two main features that generally contribute to a good leaving group, and then
identify which of those is the main parameter responsible for the difference here.
Leaving group ability correlates with stabilization of the negative
charge that builds up as the group departs, and with the strength of
the bond to the leaving group that is broken in the process.
There is no significant diffrerence in the stability of the negative'
charge, as indicated by the pKas of the conjugate acids.
There is a huge difference in bond energy for the cyanide-carbon bond
compared to a nitrogen to carbon bond. This is reflected
in the transition state during partial bond breaking. So even though the
resulting anion (cyanide) is quite stable,displacement of cyanide in
an SN2 process is not favorable.

116 kcal/mol from BDE table

NC

H
H

I-

87 kcal/mol from BDE table (for typical

RN-CH3 bond)
H
H3N C H + IH

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VII. (14 pts). Note that treatment of W with mCPBA gives X, a single stereoisomer, and then
treatment of X with hydroxide anion produces one product, Z. From the spectral data, possible structures
for Z are isomers a-d.
CH3
mCPBA*

CH3

CH3
O

H2O

OH

H
Z

H
X

OH

HO

= mCPBA
O OH
Cl

CH3

CH3

OH

OH

CH3

OH

CH3

OH

Possible Z:
OH

H a

OH

H
b

OH

H
c

H
d

OH

A. (4 pts). Based on your knowledge of mechanism and reactivity, which is most likely structure for X?
Please draw it in the box labeled X.
B. (4 pts). Based on your knowledge of mechanism and reactivity, which is most likely structure for Z?
Please draw it in the box labeled Z.
C. (6 pts). Justify your choice by writing a detailed mechanism for conversion of X to Z. Include with
your mechanism a reason why your choice for Z forms selectively instead of one of the other isomers.
CH3

CH3
O

CH3

OH

OH

H
O

H
O

H c

OH

initially formed alkoxide will be protonated by the solvent.

CH3

CH3
H

H
OH
OH

OH
H d

The initial epoxidation is a concerted syn addition from the less hindered face of the double bond, from "below" as written. The second
step is an SN2 reaction with hydroxide anion, which must give a trans diol (either c or d). In this case, the approach of hydroxide to
give c is inhibited by the proximity (1,3-diaxial interaction) of the methyl group. Attack at the other position is favored, to give d.

The process can also be expressed with planar representations, although the steric effects may be less clear.

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VIII. (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 1-bromo-2-methylpropane selectively into M.
Suggest how you might convert 1-bromo-2-methylpropane 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.
Possibly useful reagents: HBr, AgNO3, NaH, BH3, HOOH, LDA, NaI, RCO3H, HCl, NaBr, MeI, H2O
Me
Me

Br

H
H
H
1-bromo-2-methylpropane

Me
Me

OH

Br

One possibility:

Me
Me

Br
H

O
LDA
E2

H
H
1-bromo-2-methylpropane

There are other possibilities

RCO3H

HBr

Me
Me

S N1

Br

OH

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IX. (12 pts). When (S)-2-bromopentane ( ["]D +34o ) is mixed with sodium bromide in ethyl
alcohol solution, the 1H NMR spectrum of the solution remains constant with time. However, monitoring
the solution by optical rotation shows that the rotation slowly decreases and eventually reaches zero. If
the amount of sodium bromide is doubled, the rate of decrease of the optical rotation is doubled, but,
again, the NMR spectrum remains constant.
A. (08 pts). Write a reaction mechanism here that accounts for these observation (you need not
draw transition states). Draw the structure of (S)-2-bromopentane precisely.

Br
H

Br

(S)--2-bromopentane

SN2

Br

(R)--2-bromopentane

B. (04 pts). Explain how your mechanism is consistent with the gradual decrease in optical
rotation for the solution while the NMR spectrum remains constant.

The product has equal and opposite (-) rotation compared to the reactant,
so as the reaction proceeds, the rotation of the solution drops. However, the
product is also converted back to the reactant at the same rate, so there can
never be an excess of the product. The mixture slowly approaches an
equilibrium mixture of 50:50 each, a racemic mixture with zero rotation.
The 1H NMR spectrum shows no apparent change because the two enantiomers
must have exactly the same NMR spectrum

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X. (18 pts). Radical reactions can be quite useful in making complex system under carefully
controlled conditions. For example, compound K is converted to L under the conditions shown. The
peroxide initiator reacts with the tin-hydride (nBu3SnH) to give a tin radical that starts things off.
Note the products that are formed, and write your best mechanism to account for them using
proper arrows.
O
+

nBu3SnH

Br

Initiation:

+ nBu3SnBr

RO-OR
heat

RO-H + nBu3Sn

Bu3Sn H + RO

b. propagation:
+

nBu3Sn

+ nBu3Sn-Br

Br

product

O
c. propagation:

d. propagation:

+ nBu3Sn-H

+ nBu3Sn
chain-carrying radical

H
product

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XI. (22 pts). Alcohols will generally react very rapidly with alkenes that bear an oxygen
substituent, (e.g., G) in the presence of a catalytic amount of an acid to give an adduct, H. Structure H
shows simple spectral data (Data Supplement). You can determine the structure of H either by predicting
the mechansim of the reaction or by interpreting the spectral data.

OH

H2SO4

[H]

(catalyst)

O
G

C10H22O2

A. (10 pts). Draw the structure for H and write the best mechanism for its formation. Be sure to show
the catalytic role for the acid.
H2SO4

OH

(catalyst)

O
G

[H]

C10H22O2

H
this cation favored by resonance
H

or

-H+

OH
H

O
H
H

B. (4 pts). Is your structure consistent with the number of peaks in the proton decoupled 13C NMR
spectrum? Explain.
Ce
Ca
b
Ca

H
Cd
Cc
H
H

Ce
Ca
O

b
Ca

Because of high symmetry, there are 5 non-equivalent carbons,

and five peaks in the 13C NMR spectrum

C. (5 pts). Draw your product again here and give the approx 1H NMR chemical shift
positions in ppm for each set of equivalent protons, using the peak positions from the spectrum in the
Data Sheets.

(d)H3C

Ha

(e) H3C

O
(e) H3C

Hc

Hb

Ha
Hb
Hc
Hd
He

CH3(d)
CH3 (e)
O
Hc

CH3(e)

14

2.5 ppm
4.2 ppm
3.3 ppm
0.9 ppm
1.2 ppm

D. (3 pts). Why does the presence of the oxygen substituent accelerate the reaction, compared to a
carbon atom in the same position? Explain with words and pictures in terms of mechanism.

this cation favored by resonance

H

Protonation here gives a cation which is strongly stabilized by the resonance structure which puts a (+) on
the oxygen but also creates a new bond.

END EXAM
See you in two weeks or so