A Novel Computer Lab Experiment Studies of DielsAlder

A Novel Computer Lab Experiment Studies of Diels-Alder Reactions Stanislaw Skonieczny and Mima Staikova Department of Chemistry, University of Toronto, Ontario, Canada, M 5 S 3 H 6 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 348 F (Organic Reaction Mechanisms) : - Lectures - “Wet” labs - Computer labs The Diels-Alder Reaction: + a diene a dienophile transition state a cyclohexene derivative

Dienes: Dienophiles:

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 = 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

Molecular Orbital Analysis of Diels-Alder reaction HOMO LUMO butadiene ethene HOMO-1 HOMO LUMO+1

Molecular Orbital Analysis – cont. Therefore the reaction is said to be a "symmetry allowed"

Molecular Orbital Analysis – cont. energy difference larger, less overlap - lower stabilization 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. HOMO: -0. 32348 LUMO: 0. 1212 -0. 38622 -0. 34261 -0. 29698 0. 10006 0. 19862 0. 14441

LUMO HOMO dienes dienophiles

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 E = 0. 10006 – (-0. 29698) = 0. 39704 Hartree = 246. 76 kcal/mol

LUMO HOMO dienes dienophiles

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

The Undergraduate Computer Lab - UCL Chemistry Department § CHM 138 Introductory Organic Chemistry | § CHM 151 Chemistry: The Molecular Science § CHM 247 Introductory Organic Chemistry || § CHM 348 H Organic Reaction Mechanisms § CHM 379 Biomolecular Chemistry § CHM 415 Atmospheric Chemistry § CHM 441 F Applications of Spectroscopy to Organic Structure Determination § CHM 443 S Physical Organic Chemistry § CHM 447 F Bio-Organic Chemistry

Linux Computer Cluster 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 § Web. Mo Pro interactive computer interface Hope College, Holland, MI, US http: //www. webmo. net/index. html

CHM 348 Diels – Alder Reactions Computational Experiment using Gaussian 03 suit of programs and Web. Mo interface Before you begin: 1. Read these instructions beforehand then start working. 2. 3. 4. 5. 6. 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) 4. Conversion factor to kcal/mol: 5. 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 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 B 3 LYP/6 -31 G -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 theoretical knowledge of the students gained in the courses to real problems, from the real environment.

Benefits to the educational process: § relates 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 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