You are on page 1of 22

Chemistry 303

Fall, 2011
FINAL EXAMINATION KEY
1:30 PM, January 18TH, 2012
Duration: 20 minutes reading and then 3.0 hr to write
Name_____KEY______________________________________________________
(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.
HO2C

HO2C

CO2H

CO2

O
HO2C

CO2H

H O

1 pt for drawing conjugate base of maleic acid


3 pts for identifying intramolecular H-bond
1 pt for identifying that intramolecular H-bond not possible for 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.
O2C

HO2C

CO2

CO2
O

O
H O

maleic acid: 1 pt for stabilization of acid by H-bond; 3 pts for dipole-dipole destabilization of conjugate
base
fumaric acid: 1 pt for dipole-dipole stabilization of conjugate base

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
intermediate

NMe2

least

O
N

most

O
N

NMe2

O
N

NMe2

Me

NMe2

Me
NMe2

NMe2

MeO

MeO
destabilized due to electron-electron repulsion
NMe2

NMe2

2 pts for ordering


1 pt for accurate resonance structures showing delocalization of nitrogen lone pair into ring
1 pt for effect of nitro group
1 pt for effect of methoxy group
(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

O2N
x NMe2
t-Bu

O2N

The two aromatic rings cannot be in the same plane due


to steric interactions between the amine and tert-butyl
group. Thus, there is no resonance delocalization of the
nitrogen lone pair into the bottom ring.

3 pts for non-planarity of ring system


2 pts for no delocalization of nitrogen lone pair into the bottom ring

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

Me

EtOH

Me
Me
Me

AgNO3

Br

Me

Me

Me
Me

Me

EtOH

Me

Me

AgNO3

Br

OEt

Me

Me

Me

Me

Me

OEt
Me

Me

Me

1 pt for each correct product (2 pts total)


1 pt for correct choice of faster reaction
1 pt for SN1 (cation formation is rds)
1 pt for stabilization of allylic cation
1 pt for destabilization of !-carbonyl cation

(b)

NaI
t-Bu

Cl

acetone

Cl
t-Bu

Cl

t-Bu

t-Bu

H
I

NaI
t-Bu

Cl

acetone

t-Bu

t-Bu

Cl

t-Bu

Cl
!

1 pt for each correct product (2 pts total)


1 pt for correct choice of faster reaction
1 pt for SN2 mechanism (rds is dependent on electrophile and nucleophile identity)
2 pt for starting material destabilization (transition states similar energies)
-or(1 pt for nucleophile attack on opposite face of t-Bu group (steric argument))

(c)

HO

NaH

Br
Et2O
(0.1M)

Me

OH

NaH

Me

Br

Et2O
(0.1M)

Me

Me

1 pt for each correct product (2 pts total)


1 pt for correct choice of faster reaction
1 pt for SN2 mechanism (rds is dependent on electrophile and nucleophile identity)
2 pts for intramolecular faster than intermolecular

4. Consider the following transformations of compound C.

1. BH3, Et2O

D: C11H14O

E: C11H14O

H2SO4

Ph

2. H2O2, NaOH

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

H2O
C

(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.
Ph

BH3

H2B

! H
H2B
!

H
Ph

H2O2/NaOH

Ph

HO

H2B

Ph

H
Ph

Ph
B

H
Ph

D
Ph

1 pt for correct structure of D (anti-Markovnikov)


1 pt for concerted addition of B and H
2 pts for correct direction of two arrows
1 pt for correct position of B and H relative to alcohol product
1 pt for 4-membered transition state
(no penalty for not showing di- and trihydroboration)
(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.
H+
Ph

Ph

Ph

H
H+

Ph

H2O

formation of stabilized
benzylic cation is favorable
even though it is still
secondary

Ph

OH

H2O

3 pts for correct structure of E (1 pt for wrong structure but consistent with IR data)
1 pt for Markovnikoff protonation
1 pt for cyclopropane ring opening
1 pt for cleavage of correct cyclopropane bond
1 pt for water addition to cation
1 pt for deprotonation of oxonium
(no penalty for showing E or Z alkene isomer)

(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.
H

Ph

O
Compound E will react with MnO2:
MnO2 only oxidizes allylic or benzylic alcohols because it is a mild oxidant. E contains a benzylic alcohol whereas D
contains an aliphatic alcohol.

2 pts for correct alcohol substrate


1 pt for correct product
1 pt for explanation

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

Me

Me

Cl
F

Me
N
Me

Me

NMe3

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.


2 pts all or nothing
(b) (2 pts) Identify the nucleophile and the electrophile of the reaction.
Alkyl chloride F is the electrophile; trimethylamine is the nucleophile
1 pt for each
(c) (4 pts) Carefully draw the orbitals corresponding to the HOMO of the nucleophile and LUMO of the electrophile.
Me
Me

Cl

Me

Me

HOMO: sp3 lone pair on Nitrogen

LUMO: !* CCl

1 pt for CCl antibonding as LUMO; 1 pt for correct picture


1 pt for lone pair as HOMO; 1 pt for correct picture
(d) (3 pts) Which of the thermodynamic terms above favors this reaction going toward G?
The entropy term is the only one that is favorable for the forward direction because it is positive (the products are
more disordered than the starting materials). The enthalpy, the free energy, and the Keq all favor the starting
material over the products.
3 pts for correct answer. No partial credit.
(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?
Relative to the gas phase, both the starting materials and the products will be stabilized. In aqueous solution, the
charged products will be highly stabilized by H-bonding and dipole-dipole interactions with water. The starting
materials will only be minimally stabilized in water compared to the products due to the fact that they are neutral
molecules. Thus, the Keq value will increase.
2 pts for stabilization of products
2 pts for specific molecular associations that will stabilize products (H-bonding, dipole-dipole interactions)

(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.

TSgas
!G aq < !G gas

potential energy

!G gas
TSaq

!G aq

!Gogas >0

F + NMe3
(gas)
F + NMe3
(H2O)

!Goaq < 0

G + Cl
(gas)

G + Cl
(H2O)

reaction coordinate
1 pt for single TS (SN2) for both reactions
1 pt for correct identification of activation energy ("G)
1 pt for correct identification of free energy ("Go)
1 pt for aq starting materials lower energy than gas phase starting materials
1 pt for aq products lower energy than gas phase products
1 pt for aq transition state lower energy than gas phase transition state
2 pts for "Gogas > 0 as given
2 pts for "Goaq less than "Gogas (probably negative - part (e))
2 pts for "Gaq < "Ggas transition state stabilization more significant than starting material stabilization.

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?


Diastereomers
2 pts for diastereomers
(or 1 pt for stereoisomer)
(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.
E2 mechanism
Me

Br
Me

Me

OEt
H

Me

NaOEt
+ HOEt + NaBr

EtOH
Me

Me

1 pt each for correct arrows (concerted) (3 pts total)


1 pt for E2

(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.

i-Pr
axial i-Pr: + 2.1 kcal/mol
axial Br: + 0.5 kcal/mol
axial Me: + 1.7 kcal/mol
1,3 diaxial Br/Me interaction
+ 4.3 kcal/mol

Me

i-Pr
Br

Br

Me

i-Pr/Br gauche interaction

ambiguities: + 1,3 diaxial Br/Me interaction


i-Pr/Br gauche interaction

1 pt each for well-drawn/correct chairs (2 pts total)


1 pt for correct low energy structure
2 pts for correct value of energy difference
1 pt for ambiguities

i-Pr

Br
i-Pr

Me

axial i-Pr: + 2.1 kcal/mol


axial Me: + 1.7 kcal/mol
gauche i-Pr/Br
0.5 kcal/mol
gauche i-Pr/Br

Br
Me

axial Br: +0.5 kcal/mol


gauche i-Pr/Br

+3.3 kcal/mol

1 pt each for well-drawn/correct chairs (2 pts total)


1 pt for correct low energy structure
2 pts for correct value of energy difference
1 pt for no ambiguities

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

Me

i-Pr

H
H

Br

Br

Me

There is only one available antiperiplanar beta hydrogen for E2 elimination.


1pt for E2 from correct chair conformation
1 pt for antiperiplanar beta-H

10

H
Br

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

Br
Me

i-Pr
H

Me
H

Elimination will occur from the low energy chair conformation. Two axial C-H bonds are aligned antiperiplanar to
the C-Br bond and could undergo elimination. Elimination to favor the more stable/more-substituted double bond
is faster because the transition state leading to its formation is lower in energy.
1 pt for E2 from correct chair conformation
2 pts for identifying both antiperiplanar beta C-H bonds
1 pt for more substituted double bond, more stable = lower energy transition state
(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.

Med

Mec

Hc
Hb
Mec

Hb/Hc

Med

Me
He c
He

PPM

Mea

Meb

Meb

Ha
Mea

Ha
6

possible answers:

Me
Hd a

3
PPM

Hd
2

vinyl C-H bond (Ha) is a triplet in the bottom spectra, consistent with the trisubstituted
alkene product and not the disubstituted alkene (Hb/Hc).
Hd is more downfield in the bottom structure, consistent with it being allylic whereas He is
not.

3 pts for structure matching


3 pts for consistent justification

11

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

Me
Me

Me

mCPBA

OH

(+/)-J

OH

Me

Me

Me

Me

Me
O

OH

Me

OH

OH

2 pts for correct structure


2 pts for 4 diastereomers (all or nothing). No need to draw all four isomers so long as a structure is drawn
that clearly indicates the trans geometry of the epoxide.
(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.
Me

NaSPh
K

Me

NaOH
H2O, t-BuOH

OH
SPh
OH
L

Me
O

OH

Me
O

Me
O

Me

Me
O

O
O

Me

Me
O

Me

O
OH

O
HO H

Me
O

Me
Me

OH

SPh
OH
L

1 pt for deprotonation of alcohol


3 pts for formation of terminal epoxide by SN2 process
1 pt for protonation of alkoxide 1
2 pts for nucleophilic attack of thiolate as SN2 process
1 pt for protonation of alkoxide 2

12

SPh

Me
O

O
OH

H OH
SPh

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

NaOH
I

1. O3

acetone

formula: C10H18O

2. H2O2

M
H

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).
SN2
C=C stretch: 1500-1650 cm-1
O-H stretch: broad peak at ~3200-3500 cm-1
=C-H stretch: 3150-3100 cm-1

OH

2 pts for correct structure (1 pt for wrong structure consistent with molecular formula or wrong stereochem)
2 pts for IR peaks (1 each) (consistent with proposed structure)
(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?
OH
ozonolysis followed by oxidative workup

for a carboxylic acid, a signal at ! 10-12 ppm

OH

2 pts for correct structure (1 pt for aldehyde)


2 pts for NMR signal (consistent with proposed structure)
(c) (2 pts) Label all of the stereocenters in P as (R) or (S)
H
(S)
(R)

1 pt for each stereocenter

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

3 pts for trans decalin; 2 pts for correct enantiomer

13

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?
Q
M = 120 (100%)
M+1 (0%)
M+2 (100%)

R
M = 122 (100%)
M+1 (0%)
M+2 (100%)

Because we have defined the carbon isotopes exactly,


there is no 1.1% chance of a 12C being replaced with a
13C in either molecule. M+2 is from 81Br.

1 pt for no M+1 for Q


1 pt for M+2 at (100%) for Q
1 pt for answer of YES
For R: 1 pt for M at +2 units relative to Q
For R: 1 pt for M+2 at (100%) for R
1 pt for no M+1 for R
(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.
Q
C=C stretch (1500-1650 cm-1)

R
Because frequency is proportional (Mr)-1/2, where Mr is reduced
mass, C=C stretch will decrease in frequency.

1 pt for C=C functional group


1 pt for answer of YES
2 pts for decrease in frequency based on reduced mass
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?
Q
None! There are no 13C's

R
Two. Cy and Cz are both doublets (they couple to each other), and CX is 12C

1 pt for no signals for Q


2 pts for two signals for R
1 pt for doublets

14

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.)
5 pts each 2/5 points for correct connectivity and wrong stereochemistry
3 points for correct first step and wrong second step
Me

Me OH
Br2/H2O

Br

(a)
T (racemic)
S

Me Br
(b)

OH

1. m-CPBA
2. HBr

U (racemic)

1. BH3
2. H2O2/NaOH
(c)

Me
OCH3

S
3. NaH
4. CH3I

V (racemic)

Me OH
OH

1. m-CPBA
(d)

S
2.NaOH/H2O
W (racemic)

Me OH
OH

1. OsO4
(e)

S
2. NaHSO3/H2O
X (racemic)

(f)

1. BH3
2. H2O2/NaOH

Me
O

3. PCC or Collins Reagent


Y (racemic)

15

16

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

H2SO4

Me
H

H2O

Me Me H

Me

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).
Me H
Me

Me

Me H
Me

H
H

H
H

Me H
Me

Me

Me

H
HO

H+

Me H
Me

H2O

Me

OH2

Intermediate

Me H
Me

Me

H
HO
caryolanol

2 pts for protonation of correct alkene


1 pt for formation of correct cation (more substituted)
2 pts for alkene attack of cation
1 pt for correct cation formation (more substituted)
1 pt for water attack
1 pt for deprotonation
(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).
Me H
Me
H

Me Me H

Me Me H

Me

H
H2O

Me
Me

Intermediate

clovene
although this is also a
secondary cation, it is more
stable than the intermediate
because the ring strain in the
4-membered ring has been
relieved

3 pts for common intermediate (or redoing mechanism)


2 pts for alkyl shift
1 pt for breaking correct CC bond
2 pts for elimination of CH

17

+ H+

+ H+

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): d 25.8, 112.1, 141.8
Butene 2
proton-decoupled 13C NMR (CDCl3): d 14.0, 26.7, 116.4, 134.3
Dibromide 3
1

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

Dibromide 4
1

H NMR (CDCl3): d 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.)

There are only four possible butene isomers, A-D. We can use the proton-decoupled 13C NMR spectral data to
differentiate these four isomers. From symmetry considerations alone, we can differentiate 1-butene (A) [4 unique
carbons] and isobutylene (D) [3 unique carbons] from the cis- and trans-2-butenes (B) and (C) [each with 2 unique
carbons]. Thus, butene 1 must be isobutylene (D), which shows three unique carbons in its proton-decoupled 13C
NMR spectrum. Similarly, butene 2 must be 1-butene (A), which shows four unique carbons in its protondecoupled 13C NMR spectrum. (Chemical shift assignments are not required for full credit.)

18

25.8
134.3
141.8
25.8

112.1

116.4

14.0
26.7

1 (= D)

2 (= A)

(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.
a

Br

PyHBr3
1

CH2Cl2
0 C

Br

! 1.87 (s, 3H) Ha


3.86 (s, 1H) Hb

Note: The relative integrals need to be multiplied by a factor of two to give the absolute integrals.
(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.
Br
3
2

Br

This bromination reaction produces a racemic mixture of 1,2-dibromobutane (4). The 1H NMR spectral
complications are a result of the newly created stereogenic center at C-2. The chemical shift calculations (not
required) are summarized below:
#
#
#
#

(H4) = 0.90 ppm


(H3) = 1.20 + 0.60 = 1.80 ppm
(H2) = 1.55 + 2.20 + 0.25 = 4.00 ppm
(H1) = 1.20 + 2.15 + 0.60 = 3.95 ppm

(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.
Br
Et

! 4.10-4.20 Hc

Ha ! 3.63

! 3.84 Hb
Br
4

19

The methylene protons at C-1 (Ha and Hb) are diastereotopic. Even though there is free rotation about the C-1/C-2
bond, these methylene protons are not equivalent, as nicely illustrated by the Newman projection of the most
populated (lowest energy) staggered conformation (looking down the C-1/C-2 bond), shown above, for one
enantiomer of 4. As you learned in lab, the lowest energy conformation here keeps the two bromine atoms as far
apart as possible to minimize any Br/Br dipole destabilization. The 1H NMR signal at # 3.63 ppm is due to Ha. This
signal appears at as a triplet because the two coupling constants are approximately equal (Jab ~ Jac = 10 Hz). Jab is
large, of course, because the two protons are geminally coupled. The large vicinal coupling constant (Jac = 10 Hz) is
consistent with a large dihedral angle (~180) for Ha-C-C-Hc. The 1H NMR signal at # 3.84 ppm is due to Hb. This
signal appears as a doublet of doublets with Jab = 10 Hz and Jbc = 4.5 Hz. Again, Jab is large because it is a geminal
coupling constant. The smaller vicinal coupling constant (Jbc = 4.5 Hz) is consistent with a smaller dihedral angle
(~60) for Hb-C-C-Hc. Finally, the multiplet at # 4.10-4.20 ppm is due to Hc. Thus far, Hc should be a dd with Jac =
10 Hz and Jbc = 4.5 Hz. However, as we shall see, Hc is split by two additional protons and will be more complicated
than a dd.
(3) (4 pts) Please explain why the multiplets at d 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?
The 1H multiplets at # 1.75-1.91 and 2.12-2.26 ppm are due to the C-3 methylene protons (Hd and He). These
methylene protons are also diastereotopic due to the C-2 stereogenic center. This situation can nicely be illustrated
by examining the lowest energy staggered Newman projection, looking down the C-3/C-2 bond, shown below.
CH3
Br

! 4.10-4.20 Hc

Hd ! 1.75-1.91 or 2.12-2.26

! 1.75-1.91 or 2.12-2.26 He

CH2Br
4

Alternately, you can demonstrate the diastereotopicity of Hd and He by performing the X substitution test; i.e.,
"X substn."

H3C

Hc
Br

He
X
H3C

Hc
Br

Diastereomers!

He
Hd

CH2Br

CH2Br
"X substn."

H3C

Hc
Br

X
Hd

CH2Br

You dont have enough information to assign which proton is which here, as both signals were only reported as
multiplets. Hd should be a ddq (Jde, Jcd, and Jdf), which could be reduced to a tq, if Jde ~ Jcd. He should be a dqd (Jde,
Jdf, and Jce).
(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).
The remaining signal in the 1H NMR spectrum of dibromide 4 is the 3H triplet at # 1.08 ppm. This signal must be
due to the C-4 methyl group (Hf). The signal appears as a triplet because the methyl protons are coupled to Hd and

20

He with Jdf ~ Jef ~ 7 Hz (due to rotational averaging). Note that coupling constant for the methyl hydrogens (Hf)
with Hd and He must both be 7 Hz; otherwise, the methyl signal would appear as a dd.
(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.
The signal at # 4.10-4.20 ppm has presumably already been assigned to the C-2 methine proton (Hc). This proton is
coupled to four different protons (Ha, Hb, Hd, and He) with four different coupling constants (Jac, Jbc, Jcd, and Jce).
Thus, Hc should actually appear as a doublet of doublets of doublets of doublets (dddd) with 16 lines (assuming
none of the lines overlap, which is unlikely).

21

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

22