1 The Diels-Alder Cycloaddition Reaction Matthew M. Davis ...

The Diels-Alder Cycloaddition Reaction
Matthew M. Davis
Department of Chemistry, University of Pittsburgh
July 2006
From lecture and/or your textbook you have learned the basics of the Diels-Alder reaction. The
purpose of this assignment is to provide a more complete understanding of the reactivity of the
components involved in a Diels-Alder reaction. Using the CAChe software package you will
calculate the energy of the HOMO and LUMO of various dienes and dienophiles. From this
information you will examine the trends in the relative energy of HOMO’s and LUMO’s in
terms of the substitution of the dienes and dienophiles and how substitution affects the relative
reactivity of a pair of Diels-Alder partners.
1. a. Draw (freehand) the π orbitals for 1,3-butadiene (diene) and ethylene (dienophile).
b. Based on the occupancy of the orbitals designate, which orbital is the HOMO (Highest
Occupied Molecular Orbital) and which is the LUMO (Lowest Unoccupied Molecular
Orbital) for each molecule.
1,3-butadiene
ethylene
Energy
2. In CAChe calculate the HOMO and LUMO for both the 1,3-butadiene (s-cis form) and
ethylene using PM3 geometry and the PM3 wavefunction. Make sure you beautify the
structure before running calculations. (See Supplemental CAChe Instructions at the back of
this document).
HOMO
LUMO
1,3-butadiene
ethylene
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3. Freehand sketch, or cut and paste from the calculated results, the HOMO and LUMO for 1,3-
butadiene and for ethylene based on the CAChe results. Compare the shape of the HOMO
and the LUMO calculated in CAChe to the HOMO and LUMO you drew in response to
question 1. Comment on the comparison.
4. Calculate the HOMO and LUMO for the following dienophiles
OMe
O
methoxyethene
acrolein
HOMO
LUMO
5. a. Compare the HOMO’s and LUMO’s for ethylene, methoxyethylene, and acrolein.
Relative to ethylene what do electron donating or electron withdrawing groups do to the
energy of the HOMO and LUMO?
b. Is the HOMO or LUMO energy affected more by a withdrawing group?
c. s the HOMO or LUMO energy affected more by a donating group?
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6. Calculate the HOMO’s and LUMO’s for the following dienes (be sure the 1,3-butadiene
portion is in the s-cis conformation)
OMe
HOMO
LUMO
HOMO
LIMO
OMe
(E)-1-methoxybuta-1,3-diene
O
(E)-penta-2,4-dienal
2-methoxybuta-1,3-diene
O
2-methylenebut-3-enal
7 Compare the HOMO’s and LUMO’s for 1,3-butadiene, (E)-1-methoxybuta-1,3-diene, 2-
methoxybuta-1,3-diene, (E)-penta-2,4-dienal, and2-methylenebut-3-enal. Relative to 1,3-
butadiene what do electron donating or electron withdrawing groups do to the energy of the
HOMO and LUMO? How does changing the position of the methoxy or aldehyde
functionality influence the size of the change in energy for the HOMO and LUMO?
8. The energy difference between the HOMO’s and LUMO’s of the dienes and the dienophiles
determines their reactivity in a Diels-Alder reaction and whether the reaction is classified as a
normal or inverse demand Diels-Alder reaction. During a normal demand Diels-Alder
reaction the HOMO of the diene donates electrons into the empty LUMO of the dienophile.
Conversely in an inverse demand Diels-Alder reaction the HOMO of the dienophile donates
electrons into the LUMO of the diene. The HOMO and LUMO pair with the smallest
difference in energy determines the type of Diels-Alder reaction that will occur. Calculate the
difference between the HOMO’s and LUMO’s of the following dienes and dienophiles and
determine whether a Diels-Alder reaction between the two would be normal or inverse
demand. (The sign of the difference does not matter, only the magnitude)
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Dienophile
Diene
OMe
O
OMe
HOMO diene minus
LUMO dienophile
methoxyethene
LUMO diene minus
HOMO dienophile
Type of Diels-Alder
HOMO diene minus
LUMO dienophile
ethylene
LUMO diene minus
HOMO dienophile
Type of Diels-Alder
O
HOMO diene minus
LUMO dienophile
acrolein
LUMO diene minus
HOMO dienophile
Type of Diels-Alder
9. The numbers calculated above may be thought of as a relative energy barrier for the
corresponding reactions. As is the case for most reactions a smaller energy barrier indicates a
more favorable (faster) reaction.
a. From the calculations above, which reaction is the most energetically favorable normal
demand?
b. Which reaction is the most favorable inverse demand?
c. For these two types of Diels-Alder reactions what combination of substitution
(donating/withdrawing) on the diene and dienophile gave the most favorable result?
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10. While the HOMO and LUMO of a diene and a dienophile may be examined to determine the
propensity towards a Diels-Alder reaction, they also indicate how the two molecules will
react regiochemically. This becomes especially important when reacting unsymmetrical pairs
of dienes and dienophiles. In a Diels-Alder reaction the HOMO and LUMO react in such a
way that the orbitals overlap as fully as possible. Consequently the largest lobes at the ends
of the diene and dienophile in the appropriate HOMO and LUMO will be oriented together.
a. Sketch, or cut and paste from CAChe, the appropriate HOMO and LUMO for the Diels-
Alder reaction below and indicate, which is the larger end.
b. Using the appropriate HOMO and LUMO orientation draw the product of a Diels Alder
reaction between methoxyethene and 2-methlenebut-3-enal. (You will probably have to
rotate the molecule to see which orbital is larger)
OMe
+
O
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Supplemental Instructions for CAChe for The Diels-Alder Cycloaddition Reaction
Matthew M. Davis
Department of Chemistry, University of Pittsburgh
July 2006
Select Tool
Select Molecule Tool
Select Similar Tool
Select Group Tool
Atom/Bond Tool
Rotate Tool
Translate Tool
Scale Tool
Pull Down Menus
The CAChe Workspace may be found by going to Start/All Programs/CAChe and selecting
Workspace.
1. Drawing
Select the Atom/Bond tool from the sidebar
Make sure the pull down menu says the desired atom (carbon in most cases)
Click in the workspace to add an atom
Click on previously placed atom and drag to place a second atom of the same type bonded to
the first.
To draw a double bond click and drag from an existing atom to another existing atom.
To draw a different type of atom go to the top and the pull down menu and change it from
carbon to the desired atom
Note 1: You do not have to add all the hydrogens. Using the select tool click in the
workspace to deselect the molecule. Then going to Beautify/Comprehensive will add
hydrogens, set bond lengths, and bond angles automatically. This is necessary before you
calculate the HOMO and LUMO.
Note 2: After beautification of the dienes it may be necessary to set the dihedral angles to get
the appropriate s-cis orientation for the Diels-Alder reaction. To set the dihedral angle click
on the terminal carbon of the diene then hold shift and click the three other carbons in
sequence. Click Adjust/ Dihedral Angle… In the Set Dihedral Angle window set the angle to
0 degrees and click ok.
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2. Modifying
Click on the select tool
Click on the desired atom (becomes highlighted)
Use pull down menus to change type, hybridization, or charge on that atom.
To delete click atom as before then push the delete key.
To modify bonds select the bond same as selecting atoms (becomes highlighted) then use the
pull down menu to change bond type from single to desired type.
3. Manipulating the molecule
To the move the molecule click the Translate Tool and drag to move the molecule around the
workspace.
To rotate the molecules click the Rotate Tool. Clicking and dragging will rotate the molecule.
Dragging outside the circle rotates it in the plane of the screen and dragging inside the circle
rotates out of the plane of the screen.
4. Calculating and Viewing HOMO’s and LUMO’s
Click File/Save As and save using the appropriate chemical name
Click Experiment/New
Select the following from the pull down menus: Property of = Chemical sample; Property =
HOMO & LUMO; Using = PM3 geometry with PM3 wavefunction.
Click Start and let the experiment run until it says “Tabulation complete”.
Close the Experiment Status window and the Experiment Window to get back to the
Workspace.
To view HOMO and LUMO select Analyze/Show Surfaces … In the show surfaces window
select a surface (first one is HOMO second is LUMO). The orbitals should be displayed and
a numerical value for the HOMO or LUMO in eV should be visible. Record this value and
repeat (deselecting the first choice for clarity in viewing).
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