Chemistry 303

Fall, 2011
FINAL EXAMINATION
1:30 PM, January 18TH, 2012
Duration: 20 minutes reading and then 3.0 hr to write
Name___________________________________________________________
(Official Name)
This is an open book examination; you may use anything that is not alive or 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.
You need not draw transition states as part of a mechanism unless expressly instructed to do so.
USE THE ARROW FORMALISM CAREFULLY FOR ALL MECHANISMS. SHOW ALL INTERMEDIATES.
BE SURE TO INCLUDE ALL FORMAL CHARGES.
Write only in the space provided for each question.
Score:
p2___________/ 10

p3___________/ 10

p4___________/ 18

p5___________/ 18

p6___________/ 15

p7___________/ 12

p8___________/ 6

p9___________/ 14

p10__________/ 10

p11__________/ 12

p12__________/ 15

p13__________/ 14

p14__________/ 30

p15__________/ 16

Lecture Total:

Lab question _________/26

/200

There are 19 pages in this exam; please check now to be sure you have a complete set. The last page is Table 3.2 from the
text, related cyclohexane conformational data, and a glossary of definitions.
Pledge:_________________________________________________________________________________

1. Fumaric acid is an intermediate in the Krebs cycle and is involved in the production of energy in the form of ATP from
the breakdown of carbohydrates, fats, and proteins. Fumaric acid and its closely related isomer maleic acid have several
unique properties that significantly alter their relative properties in living organisms and in the laboratory. For example,
consider the aqueous pKa values for the two compounds.
HO2C

HO2C

CO2H

CO2H

fumaric acid

maleic acid

pKa1: 3.02
pKa2: 4.38

pKa1: 1.92
pKa2: 6.23

(a) (5 pts) Provide the single best reason why the most acidic proton (pKa1) on maleic acid is approximately 12.5 times
more acidic than the corresponding proton on fumaric acid.

(b) (5 pts) Interestingly, the second proton to be deprotonated on maleic acid (pKa2) is approximately 70 times less acidic
than the corresponding second proton on fumaric acid. Provide the single best reason to explain this data.

2. (5 pts) (a) Label the following molecules in order of basicity (most, least, intermediate), and defend your choice. You must draw
pictures to receive credit.
O2N

Me

MeO
NMe2

NMe2

NMe2

(b) (5 pts) Now consider molecules A and B. Contrary to what you might expect at first glance, the basicity of A is approximately the
same as the basicity of B. Provide the single best reason why. Explain your choice with carefully drawn pictures.
O2N

O2N
NMe2
t-Bu

O2N

NMe2
t-Bu

3. (18 pts) For each of the following pairs of reactions, (i) draw the product(s) of each reaction and (ii) circle which
member of the pair would be FASTER. (iii) Explain briefly the most important reason for your choice.
O

(a)
Me

AgNO3

Br

EtOH

Me
Me
Me

AgNO3

Br

EtOH

Me

(b)

NaI
t-Bu

Cl

t-Bu

Cl

acetone

NaI

(c)

HO

acetone

NaH
Br
Et2O
(0.1M)

Me

OH

NaH

Me

Br

Et2O
(0.1M)

4. Consider the following transformations of compound C.

D: C11H14O

1. BH3, Et2O

Ph

2. H2O2, NaOH

H2SO4
H2O

E: C11H14O
select IR data:
3432, 3083, 1644,
1610 (phenyl) cm1

(a) (6 pts) Predict the structure of D and draw the best mechanism for step (1) of its formation. Include a carefully
rendered drawing of the rate-determining transition state of the reaction.

(b) (8 pts) Predict the structure of E that is consistent with the IR data provided, and indicate the single best mechanism
for its formation.

(c) (4 pts) Compounds D and E were both treated with MnO2, but only one of the two underwent reaction. Predict which
compound reacted with MnO2; draw the structure of the resulting product; and briefly rationalize your choice.

5. Consider the following reaction in the gas phase and the provided data:

Me

Me

Cl
F

Me
N
Me

Cl

!H0 = +6.36 Kcal/mol

!S0= +0.00115 Kcal/K*mol
T = 25C
!G0 = +6.02Kcal/mol
Keq = 3.85*105

(a) (2 pts) Draw the product G in the box provided above.

(b) (2 pts) Identify the nucleophile and the electrophile of the reaction.

(c) (4 pts) Carefully draw the orbitals corresponding to the HOMO of the nucleophile and LUMO of the electrophile.

(d) (3 pts) Which of the thermodynamic terms above favors this reaction going toward G?

(e) (4 pts) The equilibrium constant for this reaction in aqueous solution is much larger than the one provided for the gas
phase. How can you account for this fact?

potential energy

(f) (12 pts) On one plot, draw reaction coordinate diagrams for the gas phase and aqueous reactions. Be sure that your
diagrams account for the relative energies of the starting materials, products, and activation energies between the two
conditions. Label !Gogas, !Ggas, !Goaq and !Gaq.

reaction coordinate

6. Consider the following data regarding the reactions depicted below:

Me

Me

Me
NaOEt

(i)
Br
Me

EtOH

Me

Me
Me
100%

Me

Me

Me
0%

Me

Me
NaOEt

(ii)
Br
Me

EtOH

Me

Me

Me
25%

Me

Me

75%

(a) (2 pts) What type of isomers are H and I?

(b) (4 pts) What elimination mechanism is most likely for reactions (i) and (ii)? Draw the curved arrow mechanism that
accounts for the product generated in (i). Note: you do not need to draw a 3-dimensional picture of H for your mechanism.

(c) (12 pts) Draw the chair conformations of H and of I (4 total). Circle the lowest energy chair conformation for each
molecule and calculate how much lower in energy each is relative to the higher energy form (note: the back page of the
exam has useful data for doing this). Show your work and if necessary, identify any ambiguities in your estimate.

(d) (2 pts) Why does reaction (i) give only one product? Explain your answer using 3-dimensional pictures.

(e) (4 pts) Why does reaction (ii) favor the indicated product? Explain your answer using 3-dimensional pictures.

(f) (6 pts) Assign the 1H NMR spectra below to the two products of reactions (i) and (ii). Describe one diagnostic feature
of the spectra that justifies your answer.

PPM

3
PPM

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7. In 1990 the Sharpless lab at MIT devised an elegant synthesis of L-hexose derivatives beginning from the allylic
alcohol J shown below.
(a) (4 pts) Draw the product (K) of epoxidation of J with mCPBA and indicate how many stereoisomers are possible for
the product.

Me
O

Me

mCPBA

O
OH
(+/)-J
K

(b) (8 pts) If K is subjected to a reaction containing a sulfur nucleophile, what's known as a Payne reaction can occur. The
product of the Payne reaction is depicted below. Provide a mechanism for the formation of product L.
NaSPh
K

NaOH
H2O, t-BuOH

Me
O

Me
O

OH
SPh
OH
L

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8. The following reaction sequence can be used to provide P from M.

NaOH
I

acetone

1. O3

N
formula: C10H18O

2. H2O2

one step
(next semester)

(a) (4 pts) Draw the structure of N and describe the two most diagnostic features of N that would show up in an IR
spectrum (not the fingerprint region).

(b) (4 pts) Draw the structure of O. About where would you expect the most downfield (highest ppm) signal to be in the
1
H NMR spectrum of O?

(c) (2 pts) Label all of the stereocenters in P as (R) or (S)

(d) (5 pts) Draw the structure of P in its lowest energy chair form (make sure that you draw the correct enantiomer of P).

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9. Labeling molecules with unnatural isotopes can change their spectral properties. Consider the following pair of
molecules, one of which has ONLY 12C carbons (Q), and the other of which has TWO 13C labeled carbons (R) and ONE
12
C carbon.
Br

Br

12C

H3

12C

13C

H
12C

H3

12C

H
13C

H
R

(a) (6 pts) If the molecular ion of Q is set to 100% in the mass spectrum, what percentage is M+1 for Q? M+2? Would
the mass spectrum be different in a predictable way in R? If so, how?

(b) (4 pts) Q has an absorption peak at 1637 cm1 in the IR. What functional group does this correspond to? Would this
stretching frequency shift in a predictable way for R? If so, how? Briefly explain your answer.

For part (c), use the labeling scheme Cx-Cz shown below:
Br
H

Cy
CxH3

Cz
H

(c) (4 pts) How many signals would you observe in the proton-decoupled 13C NMR spectrum for Q? What splitting
patterns would they have and why? How many signals would you observe in the proton-decoupled 13C NMR spectrum
for R? What splitting patterns would they have and why?

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10. (30 pts) Provide the necessary reagents to convert 1-methylcyclohexene (S) into the target compounds TY. (Hint:
More than one step may be required in some of the conversions.)
Me OH

Me

Br

(a)
T (racemic)
S

Me Br
OH
(b)

S
U (racemic)

Me
OCH3
(c)

S
V (racemic)

Me OH
OH
(d)

S
W (racemic)

Me OH
OH
(e)

S
X (racemic)

Me
O
(f)

S
Y (racemic)

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11. Caryophyllene is obtained from the oil of cloves. When it is treated with aqueous acid, two products are obtained,
caryolanol and clovene.
Me H
Me

Me
H

Me H
Me

H2SO4
H2O

Me

Me Me H
Me

H
HO

caryophyllene

caryolanol

clovene

(a) (8 pts) Draw the best arrow-pushing mechanism for the formation of caryolanol (you do not need to account for the
stereochemical outcome of the reaction).

(b) (8 pts) Draw the best arrow-pushing mechanism for the formation of clovene (you do not need to account for the
stereochemical outcome of the reaction).

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Lab-Related Question (26 pts)

Bromination of butene isomers (C4H8) 1 and 2 gives dibromides 3 and 4, respectively.

PyHBr3
1

3
CH2Cl2
0 C
PyHBr3

4
CH2Cl2
0 C

Proton-decoupled 13C NMR spectra of butene isomers 1 and 2 and the 1H NMR spectra of dibromides 3 and 4 are
summarized below:
Butene 1
proton-decoupled 13C NMR (CDCl3): " 25.8, 112.1, 141.8
Butene 2
proton-decoupled 13C NMR (CDCl3): " 14.0, 26.7, 116.4, 134.3
Dibromide 3
1

H NMR (CDCl3): " 1.87 (s, 3H), 3.86 (s, 1H)

Dibromide 4
1

H NMR (CDCl3): " 1.08 (t, J = 7 Hz, 3H), 1.75-1.91 (m, 1H), 2.12-2.26 (m, 1H),
3.63 (t, J = 10 Hz, 1H), 3.84 (dd, J = 10 Hz, J = 4.5 Hz, 1H),
4.10-4.20 (m, 1H)

(a) (4 pts) Deduce the structures of butene isomers 1 and 2. Indicate how the proton-decoupled 13C NMR spectra of
butenes 1 and 2 support your structural assignments. (Hint: There are only four possible butene isomers. Draw the
four possible isomers.)

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(b) (3 pts) Deduce the structure of dibromide 3. Draw your proposed structure for dibromide 3, and label the hydrogens
on your proposed structure. Support your structural assignment by assigning the 1H NMR signals to the appropriate
hydrogens.

(c) You should be able to deduce the structure of dibromide 4, based on your proposed structure of butene 2. (There are
no rearrangements here THINK SIMPLE!) Of course, we eventually want you to assign all of the 1H NMR signals for
dibromide 4 and to explain the splitting patterns. However, we suspect that you may find the 1H NMR spectrum of
dibromide 4 more complicated than expected. So, a little guidance is in order. (Hint: Chemical shift calculations are not
required, but may prove helpful for your spectral analyses.)
(1) (1 pt) Draw the structure for dibromide 4, based on your proposed structure for butene 2.

(2) (10 pts) Draw the lowest energy staggered Newman projection looking down the carbon-carbon bond, connecting
the two bromine-substituted carbon atoms of dibromide 4. Label the hydrogens on these two carbon atoms. Now,
assign the 1H NMR signals to these labeled hydrogens and explain the observed splitting patterns. Does the magnitude
of the observed coupling constants support your lowest energy conformational assignment? Explain.

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(3) (4 pts) Please explain why the multiplets at " 1.75-1.91 and 2.12-2.26 ppm appear as separate 1H multiplets,
rather than as one 2H multiplet. Which two protons in dibromide 4 give rise to these two multiplets?

(4) (2 pts) Please assign the remaining signal in the 1H NMR spectrum of dibromide 4, and explain the observed
splitting pattern. Dont forget the label(s).

(5) (2 pts) The signal at " 4.10-4.20 ppm is reported simply as a multiplet (m), although perhaps mess might
be a more apt description. The proton, giving rise to this mutiplet, should already be labeled in your Newman
Projection from Part 2 above. What should be the actual multiplicity of this signal (e.g., dd, td, etc.)? Explain.

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Typical gauche interactions: 0.9 kcal/mol

Typical 1,3-diaxial interactions: approx 2.0 kcal/mol
Glossary:
Me = methyl
Et = ethyl
OMe = methoxy

Ph = phenyl

t-Bu = tert-butyl

THF

Me
Me
LDA = lithium disopropylamide

Li

N
Me
Me

Ts = tosylate =

Me

O
O
DMSO
Me

O
DMF
Me

NMe2

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