CHEM 2122 / Organic Synthesis 2: Wittig Synthesis of Ethyl Cinnamate

What is the unwanted side product of the Wittig reaction that must be removed from the desired product, ethyl cinnamate?

The other product of the Wittig reaction is triphenylphosphine oxide and is considered a contaminating side product that must be removed.

• What temperatures are Wittig condensations usually done at?

• How is this conducted?

• Wittig condensations are usually done at elevated temperatures, i.e. > 100ºC, for an extended period of time to achieve a high yield of the desired alkene.

• The use of microwave heating eliminated the need for external heating and drastically reduced the reaction times - usually to minutes instead of hours.

NOTE: 25 years ago, Wittig reactions are often conducted in a round bottom flask with a condenser, a heating bath, and requires the set up to be stable over time.

In thermal heating, how is heat transferred to the reaction system, and what ultimately drives the reaction?

Heat is transferred from the heating source to the glassware, then to the reaction system, and eventually through convection, heating the entire system. The reaction occurs due to increased molecular collisions with sufficient energy to react.

Why is thermal heating often considered inefficient in chemical reactions?

Because time and energy are wasted transferring heat through the reaction vessel.

• How do microwave reactors generate heat in a reaction system?

• Why do only certain molecules absorb microwave radiation?

• Microwave reactors use EM radiation in the microwave wavelengths to irradiate a system, causing the molecules to rotate, which generates heat.

• Even though the reaction system is exposed to a range of microwave wavelengths, not all molecules will absorb the electromagnetic radiation. Only molecules with dipoles (or ions) will respond to microwaves, e.g. Glass and Teflon are transparent to microwaves because they are nonpolar by symmetry. Therefore, polar reagents and solvents will readily absorb the irradiation whereas non-polar compounds will require the use of a heating element to absorb the microwaves and generate the heat to transfer to the system.

What is a heating element?

A heating element is a component that generates heat when an electric current passes through it.

NOTE: In microwave-assisted reactions, a heating element can be used to indirectly heat nonpolar substances that do not absorb microwaves.

• What is the limitation of thermal heating?

• What is the freedom in microwave heating compared to thermal heating, and why?

• In thermal heating, you can heat up the reaction vessel only to the boiling point in order for the vapours to re-condense into a liquid to carry out the reaction.

• In microwave heating, you can heat up the reaction vessel past the boiling point without the solvent boiling and vaporizing. The reason why it would not vaporize is because the reaction is in a sealed vessel, increasing pressure and raising the boiling point. We cannot use a sealed vessel in thermal heating for the same reason in microwave heating because the use of a seal during thermal heating via convection goes against the efficiency of convection - there is now a physical barrier for heat transfer.

Provide 8 common organic solvents and whether a heating element is required or recommended.

Requires a heating element:

• Chloroform.

• Cyclohexane.

• Dichloromethane.

• Ethyl acetate.

• Toluene.

Heating element recommended:

• Acetone.

• Hexane.

• THF.

Explain how you would prepare the pressure vessel.

Record volume of samples!

• Inspect the Teflon reactor vessel liner and cap for scratches.

• Stand the reactor vessel liner and vessel jacket in a 500mL beaker to deposit chemicals into reactor vessel liner.

  • Add 0.5g phosphine reagent, then 0.15g benzaldehyde, and 1.5mL of THF.

  • Ask Sam to confirm procedure.

• Get a a micro stir bead from your TA, and add it to the reaction vessel liner.

• Add a heating element if necessary. In this synthesis, you will not need.

• Add the solvent to the reaction vessel liner, washing down the sides and ensuring a total volume is around 10mL.

• Place the liner into the vessel jacket.

• Expand the cap Teflon seal with the seal forming tool for about 5 seconds.

• Close the venting screw finger-tight. Do not over tighten.

• Carefully place the cap on the liner.

• Close the cap finger-tight.

• Record which position your reaction vessel is in. With the seal expanded, aim to start the microwave heating within 15 minutes.

Explain how to perform the workup.

• In the fume hood, disassemble the vessel. Remove the liner from the vessel jacket and cap from the liner.

• Rinse the inside of the seal with some water. Remember to keep the cap facing up.

• Transfer the reaction mixture into a round-bottom flask and remove the solvent using the rotovap.

• With the vessel under the fume hood, add 5mL of hexanes to the residue in the flask. You will notice the formation of a precipitate (by-product).

• Set up another round bottom flask with gravity filtration to remove the solid precipitate. Remove the hexane on the rotary evaporator to isolate the product.

How do you clean the Teflon sleeve and cap?

The magnetic stir bead should be cleaned with soap and water and then returned to the TA, The Teflon liner can be first washed with a little bit of soap and water and then rinsed with acetone.

• Where should the ethyl cinnamate and triphenylphosphine oxide be disposed of?

• Where should the hexanes be disposed of?

• Labeled containers for the ethyl cinnamate and triphenylphosphine oxide.

• Non-halogenated waste bottle for the hexanes.