Chemistry 303

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

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

Cl

SN2

Et3N:

+ Cl

S:
S H

This substrate has fewer degrees of freedom (conformational freedom) with regard to the
ideal trajectory for the SN2 reaction. Therefore it is favored by entropy factors. The enthalpy
factors should be about the same. Better transition state for the SN2, which is assumed to be
the rate-determining step.

B. (8 pts).

Ar
O

O OH

O H

O OH

This reaction is initiated by electron donation

from the pi bond of the alkene unit to the oxygen
of the peroxy group. The electrons flow out from
C2 of the alkene unit. The amino group can
donate electron density into the ring and out to
the alkene unit as shown in this resonance
structure:

N
H

The nitro group has the reverse effect, removing

electron density from the alkene by inductive and
resonance effects. This slows the epoxidation

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

Et3N
0o

Me S Cl

O
S Me
O

Et3N
0o

OH

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].

O
Me S Cl
O

:NEt3
:S

Et3N
OH

0o

SN2

S Me
O
(activated by alkene-allylic activation)
Could be SN1

[no detailed mechanism

necessary]

concerted rearrangement

+ HNEt3

O
S Me
O

Could be E1

:NEt3
:S

E2

ambiguous configuration
(not relevant)

S
H

O
S Me
O

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.
The double bond in J activates the methane sulfonate leaving group. In the extreme case, an SN1 mechanism would involve an
allylic cation instead of a simple secondary cation (from H)

:S

:S

vs

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

OH

OH

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).
OH

OH

OH
OH
Y

OH

OH
No possible
cyclic iodate ester

O
O
O

OH

I O
O OH

B. (06 pts). Identify the isomer which does not react readily. Explain your choice carefully, including a chair representation.
See above. The trans diaxial isomer X cannot form the cyclic iodate ester. The oxygens cannot be connected to the
same iodate unit; they are too far apart.
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

OH2

H3O+

OH

OsO4

E1

OH

Z
reagent approach from less hindered
direction.

MeSO2Cl

K OtBu
E2

SO2Me
H

OSO2Me

good leaving group

cannot have a trans-diaxial elimination, E2

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

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

b. reduce

+
O

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

one____

two___X_

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.

cat. H2

O3

O
O

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.

O
O3

O3

W'
cat. H2

cat. H2

observed

not observed

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.
H
:O

H+

+ H+ (catalytic in acid)

OH

not observed

OH
H

alternative regioselectivity,
via secondary cation
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.

H+
R

-H+
T

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.
With lower water concentration, the rate of water addition to the intermediate cation decreases, and now the reaction
with another alkene is preferred.

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).
In T, the two methyl groups would be singlets (possibly with small J due to long range coupling; these data show a
doublet for one Me with J = 7 Hz.
The data also show an H in the region for alkene-H (5-6 ppm), which is not present in T.
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.
H
H

H+

hydride
transfer

methyl
doublet

This trisubstituted double bond is apparently preferred

over T, a tetrasubstituted double bond. Presumably the tetrasubstituted double bond has steric repulsion that is larger than
the intrinsically small electronic stabilization of more substituted
double bonds.

vinyl H
________________________________________________________________________________________________________
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

H2O

PPO

U
O

PPO =

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!).

SN1

PPO

PPO

funny
ring closure

PPO

PPO

B:

Continued.

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

PPO

H2O

OH

O
H

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.

Hb

conj C=O and two alkenes--three IR peaks between 1600-1700 cm-1

Hc

Ha shows up in the 1H NMR at ! 5.9; coupled to Hb with J=17 and to Hc with J=10 Hz

Ha

O
W

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:.

H
H

:B

N X
CH3

H-B
N:
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.

*
OH

V has a stereogenic center, so

the C-4 methyl groups are
diastereotopic, chemically different

O
W
No asymmetry, the gem-dimethyl
groups at C-4 are equivalent

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

HO

SOCl2
pyridine

Cl

rearrangement
stereogenic
center

-H+

B. (03 pts). Explain in one sentence the primary driving force leading to the carbon skeletal changes represented by M.
The rearrangements are driven by elimination of bond angle strain, as the four-membered ring enlarge
to five-membered rings. All intermediate cations are tertiary, so equivalent in energy except for the relief of bond angle
strain.

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.

The precursors to M are achiral, therefore M has to form as a racemic mix unless there is an asymmetric environment
Zero optical rotation

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)

Me

120 oC
23 hours

H
N

Me
Me

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

anion leaving group stabilized by delocalization with C=O group, and

ring opening driven by relief of bond angle strain from the
three-membered ring.
O

O
S

O H
N

Me
Me

H
N

direct H
transfer to N

Me

S
The proton abstraction need not be
intramolecular as shown, but this is
pretty neat. Typical Swern-type oxidation
mechanism

O
Me

Me

nucleophile attack at the

benzylic carbon; favored by
interaction in the transition
state of the pi electrons of
the phenyl group
Or: SN1 via cation

O
H

O
O

OH
N

H
O

Me

O
O
N

Proton transfer to O or to N,
with eventual rearrangement
to the more stable structure
with H on N.

Me

N
Me
O
Me

Me

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

O H

Me

poor leaving group; no special stabilization.

Very slow reaction.
N

Me

O
Me

Me

10

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

H+ HO

OH
OH

HO

OH
G-1

heat

OH
G-2

A. (05 pts). Draw the two chair

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

OH

O
G-1

+ H2O

D OH

HO

OH
HO
HO

OH
O

H+

OH

OH

OHOH

OH

O
OH

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.

OH

OH
H+

HO
HO
G-1

HO
HO

OH
HO:

OH
O

HO
HO

OHO
H
H

OH
O

+ HO
HO
G-2

OH
favorable delocalized
carbocation

OH
H+

OH

HO
HO

OH

H
O H

OH

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

OH
HO
HO
G-1

OH
H+

HO
HO

OH
HO:

HO
HO

OHO
H
H

O:

OH
H
O:

H
OH
O
OH

OH

OH

OH
O

OH
O

OH

11

ring flip

OH

OH

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

Possibilities:

Br

NC
steps

CrO3

strong, hindered base

[e.g., LDA or KOtBu

pretty obvious precursor of M

NC
O

RCO3H

NaCN

HO
HO-Br
or
Br2/H2O

Br
HO

NaCN

NC

Br

CrO3

NaCN

12

XI. (26 pts; Lab related problem). By now, you are all too familiar with Hrings 1905 synthesis of
anethole 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):

13

# 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.
i) molecular weight (= 164 g/mole) from the parent ion
ii) approximate number of carbons (10) from the M+1 ion
iii) absence of Br from the small M+2 ion [alternately, the mw of Z is 80 g/mole
79
(- H Br) less than Y]
B. (02 pts). What is the molecular formula of compound Z? Carefully explain how you deduced the molecular formula of Z.
164
- 120
- 12
32

mw of Z
10 C!s (from mass spectrum)
1
12 H!s (from H NMR)
missing mass (most likely due to two O!s)

Therefore, the molecular formula of Z = C10H12O2

(The presence of two O!s is consistent with the presence of a methoxy oxygen in the starting material X or major
-1
product Y. Also, the presence of the second O can be deduced from the presence of a C=O stretch at 1724 cm in the
IR spectrum of Z.)
C. (01 pt). How many degrees of unsaturation are present in the molecular formula for compound Z?
$ = [2(10) + 2 12]/2 = 5
(Five degrees of unsaturation suggests the presence of a benzene ring, which accounts for four of the five degrees
of unsaturation. The fifth and last degree of unsaturation must be due to the C=O group indicated by the IR spectrum
of Z.)
D. (03 pts). Assign the peaks at 2817, 2719, 1724, and 1602 cm-1 in the IR spectrum of compound Z.
-1

2817 & 2719 cm aldehydic C-H stretches

-1

1724 cm C=O stretch (unconjugated aldehyde or possibly ketone)

-1

1602 cm C=C stretch (probably aromatic C=C stretch)

13

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.)
Let!s start with the 3H resonance at # 1.42 ppm, which is most reasonably due to a methyl group. Note that this
resonance is a doublet with J = 7 Hz, suggesting that the methyl group is attached to a methine (CH) group. There is a
1H resonance at # 3.60 ppm, which is split into the expected quartet with the same J = 7 Hz.

! 1.42 H3C

C H ! 3.60

Jab = 7 Hz

a
b
Furthermore, note that the resonance at # 3.60 ppm is further split into a doublet with J = 1.5 Hz (i.e., a quartet of
doublets). The resonance which shares this 1.5 Hz coupling is the 1H doublet at # 9.67 ppm. The chemical shift of the
# 9.67 ppm resonance suggests that it is due to an aldehydic hydrogen. This supposition is supported by the
magnitude of the coupling constant (J = 1.5 Hz, see you coupling constant table) and by the IR analysis in Part D,
above. Thus, we have deduced the presence of the following structural fragment:

! 1.42 H3C
a

! 3.60
CH
b

O
H ! 9.67

Jab = 7 Hz
Jbc = 1.5 Hz

To what is the carbon bearing Hb attached? There are only three possibilities: (i) the other methyl group (singlet at
# 3.78 ppm), (ii) the benzene ring, or (iii) the other oxygen atom (from the molecular formula of Z). It can!t be the
methyl group (why?). This leaves the following two possibilities:

C H3

OCH3
O

CH

C H3 H

CH
C H3 H

The observed chemical shift of the methyl singlet (# 3.78 ppm) is much more compatible with attachment to an
oxygen atom (structure A) than to a benzene ring (structure B); i.e.,

ArOCH3
! (CH3) = 0.90 + 2.95
= 3.85 ppm

ArCH3
! (CH3) = 0.90 + 1.45
= 2.35 ppm

Thus, A is the most reasonable preliminary structure for Z.

What is the aromatic substitution pattern in Z? All lines of evidence point to 1,4- or

para-disubstitution:

(i) the aromatic ring was para(1,4)-disubstituted in the anthole dibromide (X) starting material
1
(ii) the 2H doublets at # 6.85 & 7.17 ppm with J = 9 Hz in the H NMR spectrum are only consistent with para(1,4)disubstitution (in particular, note the magnitude of the coupling constant)
13
(iii) the C NMR spectrum of Z exhibits only four signals for the aromatic carbons at # 114.0, 125.2, 130.4, &
158.8 ppm ortho(1,2)- or meta(1,3)-disubstitution would require six aromatic carbon signals
-1
(iv) there is an aromatic =C-H bending absorption at 820 cm in the IR spectrum of Z, which is consistent with
para(1,4)-disubstitution.

14

Thus, compound Z must have the following structure. The full H NMR spectral assignments are shown below:

OCH3 ! 3.78
Hy

Hy ! 6.85

Hx

Hx ! 7.17
b

! 3.60 C H
! 1.42 H3C
a

Jab = 7 Hz
Jbc = 1.5 Hz
Jxy = 9 Hz

Hc ! 9.67
O

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.
13

13

The C NMR spectral data for Z are consistent with the proposed structure in that there are 8 signals in the C NMR
spectrum & 8 different carbons in the proposed structure. (Also, please see the comments about the number of
aromatic carbons in Part E, above.)

OCH3
2
3
4
5

H3C

CH

Z
13

The peak at # 200.8 ppm in the C NMR spectrum of Z must be due to the aldehydic carbonyl carbon. (Only
13
aldehyde & ketone carbonyl carbons but not ester carbonyl carbons show up in this region of the C NMR
spectrum.)

15