Pre-lab

Prepare a Table of Physical Constants, and a table of hazard/disposal information for the following compounds:

• Week 1 - methyl vinyl ketone, isoprene, 4-acetyl-1-methylcyclohexene [CAS 6090-09-1] , AlCl₃ (aluminum trichloride), dichloromethane, diethyl ether, 10% aqueous Na₂SO₄
   
• Week 2 - 4-acetyl-1-methylcyclohexene, "instant ylide" reagent (methyltriphenylphosphonium bromide + sodium amide), limonene, THF (tetrahydrofuran), hexane, 10% aqueous K₂CO₃

As is often the case in chemical research, hazard and disposal information may not be available for all of your compounds. If you cannot find the necessary information, you should still make a "best guess" entry in your notebook for each compound.

AlCl₃ is a strong Lewis acid. It reacts vigorously with a variety of Lewis bases, including water (HCl is released when AlCl₃ comes into contact with water). Therefore, it must be protected from water, wet solvents, and wet glassware. AlCl₃ must be treated chemically before it can be disposed of. Please refer to a MSDS for additional info.

The "instant ylide" reagent contains a strong base, NaNH₂. This compound reacts vigorously with water and with other weak acids, releasing NH₃. Therefore, "instant ylide" must be protected from water, wet solvents, and wet glassware. "Instant ylide" must also be treated chemically before it can be disposed of. Please refer to a MSDS for additional info (hint: if you can't find anything information on "instant ylide", try looking up its components).

Diels-Alder Reaction & Workup

Conduct all operations in a fume hood.

Make a solution of MVK (0.15 mL) and isoprene (0.15 mL) in dichloromethane (3-4 mL) [NOTE 1]. Cool the solution and add a spatula tip of AlCl₃ [NOTE 2]. Warm the mixture to 25 ^oC and monitor the mixture by TLC [NOTE 3]. When the reaction is complete, dilute the mixture with ether. Wash the mixture with 10% aqueous Na₂SO₄, dry, and concentrate by distillation. The residue will be used without further purification in the next reaction.

Wittig Reaction & Workup

Conduct all operations in a fume hood.

Place a stir bar in a small round bottom flask. Dry the apparatus with a heat gun (FIRE/BURN hazard [NOTE 4]) and allow it to cool. Place methyltriphenylphosphonium bromide-sodium amide ("instant ylide", approx. 250 mg [NOTE 5]) in the cool flask. Add dry THF (1 mL) to the reagent and stir the mixture at 25^oC for 15 minutes [NOTE 6].

Pass 4-acetyl-1-methylcyclohexene through a microcolumn (silica gel, dry THF [NOTE 7]) directly into the yellow ylide solution. Attach a reflux condenser fitted with a drying tube to the flask and reflux the solution for 45 minutes. Use TLC to confirm the presence of limonene in the reaction mixture [NOTE 3].

Work up the reaction by diluting the mixture with hexane (30 mL), washing with 10% aqueous K₂CO₃ (5 mL), and drying. Concentrate the organic layer to 2-3 mL by carefully and gently boiling the mixture on a hot plate. Finally, pass the residue through a fresh microcolumn (silica gel, hexane). Collect two or three ~2 mL fractions and use TLC to test them for limonene. Analyze the fraction that appears to contain the most limonene by GC-MS [NOTE 8].

Molecular Modeling

Isoprene. Use SPARTAN (Chemistry computer lab) to build a model of isoprene in the conformation shown below [NOTES 9 & 10].

Click on the minimize button (or select Minimize from the Build menu). Click on Calculations... from the Setup menu. Set up a "Calculate: Equilibrium Geometry at Ground state with Semi-Empirical AM1" calculation and click on Submit.

When your calculation is complete, click on Surfaces from the Setup menu. Click on Add... in the Surfaces window. Select Surface: HOMO and Resolution: medium and click on OK (this should place a "pending" HOMO surface in the Surfaces window). Click on Submit from the Setup menu. (this should change the "pending" surface into a "completed" surface).

Click on Properties in the Display menu. Record the HOMO and LUMO energies (listed in eV). Click on the yellow box in the Surfaces window to display the HOMO surface. Record which end of the diene displays a larger HOMO surface [NOTE 11]. This is the site that creates the best HOMO-LUMO overlap .

MVK. Build a model of methyl vinyl ketone in the conformation shown below [NOTE 12].

Follow the same procedure described above for isoprene to 1) minimize MVK, 2) calculate MVK's AM1 equilibrium geometry, and 3) calculate MVK's LUMO surface (repeat the isoprene procedure, but select LUMO in place of HOMO).

Click on Properties in the Display menu. Record the HOMO and LUMO energies (listed in eV). Click on the yellow box in the Surfaces window to display the LUMO surface. Record which end of the dienophile displays a larger LUMO surface (or a darker blue on the |LUMO| map [NOTE 11]). This is the site that creates the best HOMO-LUMO overlap.

MVK-AlCl₃. Build a model of the methyl vinyl ketone-aluminum chloride adduct in the conformation shown below [NOTE 13].

Follow the same procedure described above for MVK to 1) minimize the adduct's energy, 2) calculate the adduct's AM1 equilibrium geometry, and 3) calculate the adduct's LUMO surface.

Click on Properties in the Display menu. Record the HOMO and LUMO energies (listed in eV). Click on the yellow box in the Surfaces window to display the LUMO surface. Record which end of the dienophile displays a larger LUMO surface (or a darker blue on the |LUMO| map [NOTE 11]). This is the site that creates the best HOMO-LUMO overlap.

Important points. Compare the LUMO energies of MVK and MVK-AlCl₃. Which dienophile should be more reactive?

Compare the LUMO surfaces (or LUMO maps) of MVK and MVK-AlCl₃. Which LUMO is more unsymmetric? Which dienophile should react more regioselectively? Based on your assessment of the isoprene HOMO and the dienophile LUMOs, which regioisomer should form most rapidly?

We assumed that diene = nucleophile and dienophile = electrophile. Do your frontier MO energies support this assumption?