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

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.

Relationship between research and teaching

The Diels-Alder Reaction:

a diene

+H

O

a dienophile

H

O

H

O

transition state

a cyclohexene derivative

CHM 348F (Organic Reaction Mechanisms) :

- Lectures- “Wet” labs- Computer labs

Number of Research Papers on the Studies of Diels-Alder Reactions

0

50

100

150

200

250

300

350

400

2001 2002 2003 2004 2005

Year

Nu

mb

er o

f P

aper

s

S

MeO

O

MeO

O

Dienes:

Dienophiles:

C

C

H H

HHC

C

H C

HH

N

C

C

C C

HH

NN

C

C

H C

CH

N

N

C

C

H C

HC

N

N

O

OCH3

O

O

O

O

F

The most important orbitals in molecules for reactivity are the two so-called frontier orbitals. These are called the HOMO and LUMO

Molecular Orbitals - review

HOMO

LUMO

EnergyLUMO = lowest unoccupied molecular orbital

• lowest energy orbital available • LUMO receives electrons • characteristic for electrophilic component

HOMO = highest occupied molecular orbital

• electrons from the HOMO are donated • most available for bonding  • most weakly held electrons • characteristic for nucleophilic component

ethene                                             

  HOMO LUMO

butadiene                                                                                                

  HOMO-1 HOMO LUMO LUMO+1

Molecular Orbital Analysis of Diels-Alder

reaction

Molecular Orbital Analysis – cont.

Therefore the reaction is said to be a "symmetry allowed"

HOMO

LUMO

stabilizationHOMO

LUMO

HOMO

LUMO

energy difference larger,less overlap

- lower stabilization

energy difference smaller,more overlap

- more stabilization

Molecular Orbital Analysis – cont.

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 -0.38622 -0.34261 -0.29698

LUMO: 0.1212 0.10006 0.19862 0.14441

HOMO

LUMO

dienes dienophiles

0.20

0.10

0.00

- 0.10

- 0.20

- 0.30

- 0.40

0.20

0.10

0.00

- 0.10

- 0.20

- 0.30

- 0.40

O

An example of a problem:

Choose the best pair (one diene and one dienophile) and calculate the energy difference.

HOMO: -0.38622 -0.29698

LUMO: 0.10006 0.14441

O

E = 0.10006 – (-0.29698) = 0.39704 Hartree

= 246.76 kcal/mol

0.20

0.10

0.00

- 0.10

- 0.20

- 0.30

- 0.40

0.20

0.10

0.00

- 0.10

- 0.20

- 0.30

- 0.40

dienes dienophiles

C

C

C C

CC

N

N N

N

O

O

O

C

C

H C

CH

N

N

LUMO

HOMO

O

C

CO

O

O

O O

O

O

+

OO

O

O

O

O

O

O

O

CC

OO

O

exo product

endo product

Experiment: exo product more stable by 1.9 kcal/mol

Ea lower for the endo product by 3.8 kcal/mol

O O

O

O

+

E

Reaction progress

O O

O

O

+

OO

O

O

O

CC

OO

O

O

O

O

O

O

C

CO

O

O

3.8 kcal/mol

1.9 kcal/mol

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 Linux Computer Cluster ZeusZeus

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.

courtesycourtesy of Scott Browningof Scott Browning

Foundation of the project 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

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.

Building the Reactant Structures – cont.

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.

Job Options for Reactant and Product

Geometry Optimization (3 jobs)

Job Options

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.

Monitoring jobs progress

Evaluating Results

Energy

HOMO Energy

LUMO Energy

To view orbital, click here:

Diene - HOMO

Dienophile - LUMO

Comparing HOMO – LUMO orbitals

Diels Alder ReactionDiels Alder Reaction

Endo Product

FURAN

Malonic Anhydride

Endo Transition State

Energy

Energy

1.89 kcal/mol

0.51 kcal/mol

B3LYP/6-31G

-609.11

-609.10

-609.08

-609.07

-609.09

Reaction progress

Methodological particularities: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: 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: 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: 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.

AcknowledgmentsAcknowledgments

Andrew P. Dicks

Scott Browning, Jamie DonaldsonAndrew Woolley

Frank Buries, Michael Yoo

$$ Chemistry Department, University of Toronto$$ Instructional Technology Courseware Development Fund