Chemistry 303

Fall, 2009
Final Examination
1:30 pm January 14th, 2010
Duration: 3.0 hr
Name______________________________________________

This is an open book examination; you may use anything that is not alive nor 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.
USE THE ARROW FORMALISM CAREFULLY FOR ALL MECHANISMS
BE SURE TO INCLUDE ALL FORMAL CHARGES

p2.______/16

p3.______/16

p4.______/23

p5._______/14

p6.______ /16

p7.______/20

p8.______/23

p9._______/17

p10.______/15 p11.______/22

p12._____/18

Lab Problem__________/26

Total: ___________/200
There are 14 pages in this exam; please check now to be sure you have a complete set.

Pledge:____________________________________________________________________________

I. (16 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. (8 pts).

Cl
Et3N

SH

Cl
Et3N

SH

B. (8 pts).

O OH

O OH

II. (16 pts). Note the reaction of H to give the methyl sulfonate ester, I, a fairly conventional transformation for
you by now. Surprisingly to the person planning this experiment, compound J, under the same conditions, leads to K.
O
O

Me S Cl
S
OH

O
Et3N
0o

S
O

O
S Me
O

OH

Me S Cl
O
Et3N
0o

A. (10 pts). Write the best mechanism for the conversion of J to K. Show all intermediates and use the arrow formalism
carefully. Where possible, identify each step that is one of our standard mechanisms [SN2, SN1, E1, E2, electrophilic addn. to
alkene; write the name of the mechanism under the reaction arrow].

B. (06 pts). Explain with words and pictures why H undergoes the simple formation of the methyl sulfonate ester without
complication while J gives a different product type.

III. (23 pts). An oxidation process we did not talk about in lecture is shown here in general form (Sorrell, p 343).
The overall result is the conversion of a 1,2-diol to a pair of ketones (or aldehydes).

OH

OH

HIO4

O
I

(-H2O)

OH
O
iodate ester

O
I

OH

Consider the set of diastereomeric 1,2-diols, X, Y, and Z. Only two of these isomers undergo the reaction with HIO4 under the
usual conditions; the other one is relatively inert.

OH

OH

OH

OH
Y

OH
OH
Z

A. (09 pts). Choose one of the isomers that does undergo the reaction successfully; draw the intermediate iodate ester in the
chair representation and draw the product(s).

B. (06 pts). Identify the isomer which does not react readily. Explain your choice carefully, including a chair representation.

C. (08 pts). Suggest a method for the preparation of diol Z from trans-4-tert-butylcyclohexanol, Q. You need not draw a
mechanism, just draw the intermediates and the reagents for each step.
OH
Q

IV. (14 pts). The molecules !-terpinene (V) and "-terpinene (W) are isomeric C10H16 compounds that are constituents
of many plants. Upon catalytic hydrogenation, they both afford cis-1-isopropyl-4-methylcyclohexane, M. Upon ozonolysis
(followed by reduction), each isomer yields different products:

V and W

H2

catalyst

a. O3
b. reduce

a. O3
b. reduce

Recall that catalytic hydrogenation is a process

which adds a molecule of H2 to an alkene to
produce an alkane:
H
H2

C10H20

catalyst

O
H

+
O

O
O

O
H

A. (02 pts). How many double bonds are in V and in W?

one____

two____

three_____

cannot tell_____

B. (06 pts). Draw the structure of V and explain how the ozonolysis results and the hydrogenation result are consistent with it.
If you see ambiguities, explain.

C. (06 pts). Draw the structure of W and explain how the ozonolysis results and the hydrogenation result are consistent with it.
If you see ambiguities, explain.

V. (28 pts). Consider the fairly standard hydration reaction shown here, by which R is converted selectively to S.
35% aqueous
H2SO4

OH

A. (06 pts). Write the best mechanism for the formation of S; show all intermediates and proton transfers in detail with nice
arrows. Draw the other possible regioisomer from this reaction and explain why it is not preferred. Your mechanism should
make clear the role of acid as catalyst.

B. (06 pts). In another experiment, using a higher concentration of sulfuric acid (70%), the major product was a hydrocarbon
with the molecular formula, C14H24. This was done in the dark ages, pre-NMR, and the structure was proposed to be T based
heavily on a likely mechanism. Please write the "likely mechanism" which would account for the formation of T from R.

C. (04 pts). Give the single most important reason why the change in conditions from a 30% aqueous sulfuric acid solution
to a 70% aqueous sulfuric acid solution can lead to the observed change in product type, from the alcohol S to the hydrocarbon
dimer.

Continued.

D. (12 pts). Spectroscopy later showed some issues with this structural assignment for the product in the 70% aq.
acid. First, while there was not a really clear peak for the C=C stretch (consistent with T), there was a weak peak at 3065 cm-1.
The 1H NMR spectrum showed key methyl peaks at: # 0.65 (d, J=7 Hz, 3H) and 0.92 (s, 3H), and a pattern at # 5.50 (td, J=6, 1
Hz, 1H) .
1. (04 pts). Explain why the (partial) 1H NMR data are incompatible with T (give two elements of inconsistency).

2. (08 pts). Catalytic hydrogenation showed that the new product had one double bond and the same carbon skeleton as T.
Propose a mechanistically reasonable alternative structure that is compatible with the spectral data and draw the mechanism for
its formation.

________________________________________________________________________________________________________
VI. (31 pts). As we learned in lecture, terpenoid natural products are derived from isoprene (C5) units which combine in
the presence of enzymes. The fundamental building block is the pentenyl phosphate shown here which can react with itself to
make the somewhat unusual intermediate (U). Compound U is then processed by the organism through two more steps via alcohol
V to give the observed product, W.
(a)

PPO

enzyme

(b)

PPO

H2O

PPO
PPO =

H2O
U

enzyme

enzyme
V

OH
C10H18O

W
C10H16O
IR: 1620, 1630, 1690 cm-1
1H

NMR: ! 1.4 (s,6H);

1.95 (s,3H); 2.2 (s,3H);
5.3 (m,2H),
5.9 (dd, J=17,10 Hz, 1H)
6.2 (broad s, 1H)

O P O P O
O

NAD+
(c)

A. (08 pts). Write the best mechanism to rationalize the formation of U (tough but not crazy!).

Continued.

B. (06 pts). Write the best mechanism to rationalize the formation of V from U (easier).

C. (05 pts). Draw the structure of W. Explain carefully how the structure is consistent with the NMR pattern at ! 5.9 ppm and
the IR peaks which are listed.

D. (06 pts). The methyl pyridinium ion X is a good stand-in for NAD+. Write a mechanism for the conversion of V
to W, assisted by X and a little base, B:.

N X
CH3

E. (06 pts). Note that the spectrum for W shows a single peak for two methyl groups at # 1.4. In contrast, the 1H NMR
spectrum for V shows two methyl singlets in that region, at # 1.41 and 1.45 (each 3H). Explain the difference in pattern based on
the structures of V and W.

VII. (17 pts).

Alcohols react with thionyl chloride (SOCl2) to produce alkoxy sulfinyl chlorides:

R-OH

SOCl2

R OSCl

pyridine

A. (10 pts). However, under the same conditions, substrate L leads to an alkene, M. Write the best mechanism to rationalize
the formation of M.

SOCl2

HO

pyridine
M

B. (03 pts). Explain in one sentence the primary driving force leading to the carbon skeletal changes represented by M.

C. (04 pts). How many stereogenic centers are in M?

zero one

two

three four

Would you expect M to have non-zero optical rotation? Explain briefly.

(circle single best answer,

VIII. (15 pts). Consider the following interesting reaction in which the aziridine R is converted to S simply on
heating in DMSO. Note that under the same conditions, the related structure T shows no reaction.

Me
Me

(DMSO)

H
N

Me

N
Me

120 oC
23 hours

Me

A. (12 pts). Write the best mechanism for the conversion of R to S; show all intermediates and use arrows carefully.

B. (03 pts). Considering your mechanism, explain why T is much less reactive than R.

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IX. (22 pts). Consider the conversion of the isomers G-1 and G-2 into D by warming with trifluoroacetic
acid in THF, with a drying agent added to remove the water as it forms.
O

HO

OH
OH

HO
OH
G-1

H+ HO

OH
OH

HO
OH
G-2

OH
O

H+
heat
OH

O
+ H2O

D OH

A. (05 pts). Draw the two chair

conformations of G-1 and
circle the more stable isomer.
O

B. (07 pts). Note that in an aqueous acid solution, the isomer G-1 is converted into an equilibrium mixture of G-1 and G-2.
Explain with a mechanism.

C. (10 pts). Write the best mechanism to rationalize the conversion of G-1 to D, using the chair representation.

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X. (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 bromocyclopentane selectively into M.
Suggest how you might convert bromocyclopentane 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. You can receive partial credit for a
reasonable partial synthesis, either in the forward direction or in the reverse direction, working backwards from the product.
Possibly useful reagents: HBr, AgNO3, NaH, BH3, HOOH, LDA, NaCN, NaI, RCO3H, HCl, NaBr, MeI, H2O, Br2, OsO4

Br

NC
steps

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XI. (26 pts; Lab related problem). In 1905, Hring reported the reaction of anethole dibromide (X, a molecule
you made in the lab this semester) in aqueous acetone in the presence of CaCO3 (to pick up the HBr that was released). The main
product was the bromohydrin, Y.
CaCO3
AnCH CHCH3
AnCH CHCH3
+
Z
H2O/acetone
Br
Br
!
OH Br

Y
An = 4-CH3O C6H4
Undetected by Hring, his reaction also produced a minor product, Z. Spectral data for compound Z are summarized below:
Compound Z:
1

Mass spectrum: m/z = 166 (0.5%), 165 (11%),164 (M, 100%)

IR (neat): 2817 (w), 2719 (w), 1724 (s), 1602 (m), 1242 (s), and 820 (m) cm-1

H NMR (CDCl3):

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# 1.42 (d, J = 7 Hz, 3H); 3.60 (qd, J = 7 Hz, J = 1.5 Hz, 1H); 3.78 (s, 3H); 6.85 (d, J = 9 Hz, 2H)
7.17 (d, J = 9 Hz, 2H); 9.67 (d, J = 1.5 Hz, 1H).

C NMR (CDCl3): # 14.6, 53.0, 55.2, 114.0, 125.2, 130.4, 158.8, 200.8

A. (03 pts). What are the three most important pieces of information about compound Z that can be deduced from the mass
spectral data? Explain.

B. (02 pts). What is the molecular formula of compound Z? Carefully explain how you deduced the molecular formula of Z.

C. (01 pt). How many degrees of unsaturation are present in the molecular formula for compound Z?

D. (03 pts). Assign the peaks at 2817, 2719, 1724, and 1602 cm-1 in the IR spectrum of compound Z.

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E. (15 pts). Deduce the structure of compound Z. Draw your proposed structure for compound Z, and label each
unique hydrogen. Under this structure, please indicate your chemical shift assignments for all of the 1H NMR resonances. Also,
carefully explain the splitting patterns and make coupling constant assignments. (Hint: Dont worry about how compound Z was
formed.)

F. (02 pts). Are the 13C NMR spectral data consistent with your proposed structure for compound Z? Briefly explain. Please
assign the peak at ! 200.8 ppm. The rest of the peak assignments are not required.

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