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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 Lab Problem__________/26

p10.______/15 p11.______/22 p12._____/18

Total: ___________/200

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

Pledge:____________________________________________________________________________

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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).

Et3N

Et3N

Cl

SH

Cl

SH

B. (8 pts).

N

O

O OH

NO

O

O

O OH

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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.

OH

SS

Me S

O

O

Cl

Et3N

SS

OH

SS

S

O

O

Cl

Et3N

O

SS

S

O

O

MeH

I

J K

Me

0o0o

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.

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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

(-H2O)O

I

O O

O

OH O

OI

O

O

OH+

iodate ester

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

OH

OH

X Y 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

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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

Va. O3

b. reduceH

H

O

O

+

O

O

Wa. O3

b. reduce

O

+

O

HH

O

O

M

Recall that catalytic hydrogenation is a process

which adds a molecule of H2 to an alkene to

produce an alkane:

H2

catalyst

H

H

C10H20

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.

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

35% aqueous H2SO4 OH

R S T

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….

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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.

PPO

PPO

PPO

PPO =

VU C10H18O

C10H16O+

enzyme

H2O

enzyme

OH

enzyme

O P O P O

O

O

O

O

(a) (b)

(c)

NAD+W

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)

H2O

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

Continued….

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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

CH3

X

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.

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VII. (17 pts). Alcohols react with thionyl chloride (SOCl2) to produce alkoxy sulfinyl chlorides:

R OSCl

SOCl2

pyridineR-OH

O

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.

HOSOCl2

pyridine

LM

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 (circle single best answer,

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

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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

N

OO

MeS

Me

O

HN

Me

O

O

O

120 oC

23 hours

(DMSO)

R S

Me

N

T

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 OH

OH

HO OH

HO

H+

heat

O

O

OH OH

OH

D

+ H2O

O OH

OH

HO OH

HO

G-1 G-2

H+

A. (05 pts). Draw the two chair

conformations of G-1 and

circle the more stable isomer.

OO

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

stepsM

Br

O

NC

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XI. (26 pts; Lab related problem). In 1905, Höring 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.

AnCH CHCH3

Br Br

AnCH CHCH3

OH Br

CaCO3

H2O/acetone

!

X Y

+ Z

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

Compound Z: 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

1H NMR (CDCl3): # 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).

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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: Don’t worry about how compound Z was

formed.)

F. (02 pts). Are the 13

C 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.