A Novel Computer Lab Experiment
Studies of Diels-Alder Reactions
Stanislaw Skonieczny and Mima Staikova
Department of Chemistry, University of Toronto, Toronto, Ontario,
Canada, M5S 3H6
Relationship between research and teaching
Why are research and teaching linked ?
research - an élite activity
scholars and scientists held hostage in classrooms
It is impossible to teach well without reflection, analysis, discussion.
CHM 348F (Organic Reaction Mechanisms) :
- Lectures
- “Wet” labs
- Computer labs
The Diels-Alder Reaction:
O
H
a dienophile
H
H
+
a diene
O
O
transition
state
a cyclohexene
derivative
Number of Research Papers on the Studies
of Diels-Alder Reactions
400
Number of Papers
350
300
250
200
150
100
50
0
2001
2002
2003
Year
2004
2005
Dienes:
MeO
S
O
Dienophiles:
H H
H
H
MeO
O
N
C
N
H
H
N
C
H
H
C
C
C
C
C
C
C
C
C
C
C
H H
O
O
O
H
C
N
C
H
N
C
H
N
O
O
C
N
F
OCH3
Molecular Orbitals - review
The most important orbitals in molecules for
reactivity are the two so-called frontier orbitals.
These are called the HOMO and LUMO
Energy
LUMO = lowest unoccupied molecular orbital
• lowest energy orbital available
• LUMO receives electrons
• characteristic for electrophilic component
LUMO
HOMO = highest occupied molecular orbital
HOMO
• electrons from the HOMO are donated
• most available for bonding
• most weakly held electrons
• characteristic for nucleophilic component
Molecular Orbital Analysis of Diels-Alder reaction
ethene
HOMO
LUMO
butadiene
HOMO-1
HOMO
LUMO
LUMO+1
Molecular Orbital Analysis – cont.
Therefore the reaction is said to be
a "symmetry allowed"
Molecular Orbital Analysis – cont.
LUMO
LUMO
HOMO
stabilization
HOMO
energy difference larger,
less overlap
- lower stabilization
LUMO
HOMO
energy difference smaller,
more overlap
- more stabilization
An example of a problem:
Choose the best pair (one diene and one dienophile)
and calculate the energies of HOMO and LUMO.
O
HOMO: -0.32348
LUMO:
0.1212
-0.38622
-0.34261
-0.29698
0.10006
0.19862
0.14441
0.20
0.20
0.10
0.10
0.00
0.00
- 0.10
- 0.10
- 0.20
- 0.20
- 0.30
- 0.30
- 0.40
- 0.40
LUMO
HOMO
dienes
dienophiles
O
An example of a problem:
Choose the best pair (one diene and one dienophile)
and calculate the energy difference.
O
HOMO:
-0.38622
-0.29698
LUMO:
0.10006
0.14441
E = 0.10006 – (-0.29698) = 0.39704 Hartree
= 246.76 kcal/mol
0.20
0.20
N
LUMO
H
0.10
C
C
0.10
O
C
H
0.00
N
O
0.00
N
- 0.10
C
C
- 0.10
O
N
C
C
C
- 0.20
- 0.20
- 0.30
- 0.30
- 0.40
- 0.40
HOMO
dienes
dienophiles
C
N
C
N
O
O
O
O +
O
O
O
C
O
O
C
O
exo product O
O
O
O
O
O + O
O
O
O
O
C O
O
C O
endo product
Experiment: exo product more stable by 1.9 kcal/mol
Ea lower for the endo product by 3.8 kcal/mol
E
O O
O
3.8 kcal/mol
O
O
O
O
O
O
O
O +
O
O
C O
C
O O
1.9 kcal/mol
O
O
C
O
C
O
Reaction progress
The Undergraduate Computer Lab - UCL
Chemistry Department
 CHM 138 Introductory Organic Chemistry |
 CHM 151 Chemistry: The Molecular Science
 CHM 247 Introductory Organic Chemistry ||
 CHM 348H Organic Reaction Mechanisms
 CHM 379 Biomolecular Chemistry
 CHM 415 Atmospheric Chemistry
 CHM 441F Applications of Spectroscopy to
Organic Structure Determination
 CHM 443S Physical Organic Chemistry
 CHM 447F Bio-Organic Chemistry
Linux Computer Cluster Zeus
Zeus configuration
*Main node:
AMD Athlon 64 Dual 4800+
with 4 GB memory
and 250 GB HD
*Computational nodes:
10 Dual Athlon CPUs
at 2 GHz, each
with 1 GB memory.
courtesy of Scott Browning
Foundation of the project
 WebMo Pro interactive computer
interface
Hope College, Holland, MI, US
http://www.webmo.net/index.html
CHM348
Diels – Alder Reactions
Computational Experiment
using Gaussian03 suit of programs and WebMo interface
Before you begin:
1. Read these instructions beforehand and then start working.
2. You have to complete 7 calculation jobs:
3 jobs for Geometry Optimization – 2 Reactants, 1 Product
1 job for Transition State Optimization
1 job for Transition State Vibrations
2 jobs for Molecular Orbital Calculations – one for each Reactant.
3. All energies are calculated in Hartree (Atomic Unit for Energy)
Conversion factor to kcal/mol:
1 Hartree = 627.51 kcal/mol
Building the Reactant Structures – cont.
Select the appropriate substituents in the periodic table and construct
the substituted diene and dienophile for your reaction.
Prepare a separate job for each reactant.
Job Options
Job Options for Reactant and Product
Geometry Optimization (3 jobs)
From the “Calculation” drop box select “Geometry Optimization”.
Use “Theory”, “Basis set”, “Charge”, and “Multiplicity” as shown above.
When ready, send your job for calculation with the right blue arrow.
Monitoring jobs progress
When your job is calculated (it will take some time) it will show
a “complete” status.
Use the “view button” to see and evaluate the results and to use them
for your next job preparation.
Evaluating Results
Energy
To view orbital, click here:
HOMO Energy
LUMO Energy
Comparing HOMO – LUMO orbitals
Diene - HOMO
Dienophile - LUMO
Energy
Endo Transition State
FURAN
Endo Product
Malonic Anhydride
Diels Alder Reaction
Energy
B3LYP/6-31G
-609.07
0.51 kcal/mol
-609.08
-609.09
-609.10
-609.11
1.89 kcal/mol
Reaction progress
Methodological particularities:
 calculations are performed at “research
level”
 each student has a different set of
compounds, works independently.
 project can be done in class or remotely
at each student convenience.
Benefits to the educational process:
 relates the theoretical knowledge of the students
gained in the courses to real problems, from the real
environment.
Benefits to the educational process:
 relates the theoretical knowledge of the students
gained in the courses to real problems, from the real
environment.
 facilitates the direct connection between
macroscopic description of the chemistry
phenomena and the microscopic world of molecular
interactions that drive chemical processes.
Benefits to the educational process:
 relates the theoretical knowledge of the students
gained in the courses to real problems, from the real
environment.
 facilitates the direct connection between
macroscopic description of the chemistry
phenomena and the microscopic world of molecular
interactions that drive chemical processes.
 exposes the students to various theoretical methods
and approaches in solving scientific problems as a
parallel/alternative to the experimental approaches
presented in the chemistry course.
Acknowledgments
Andrew P. Dicks
Scott Browning, Jamie Donaldson
Andrew Woolley
Frank Buries, Michael Yoo
$$ Chemistry Department, University of Toronto
$$ Instructional Technology Courseware Development Fund