Heterogeneous Removal of Water-Soluble Ruthenium Olefin Metathesis Catalyst from Aqueous Media Via Host-Guest Interaction

A removable water-soluble N-heterocyclic carbene (NHC) ligand in aqueous media via host-guest interaction has been developed. We demonstrated representative olefin metathesis reactions in water as well as in dichloromethane. Via either host-guest interaction or extraction, the residual ruthenium (Ru) catalyst was as low as 0.14 ppm after the reaction.

This method can help answer key questions in the practical application of transition metal catalyst field, such as polymer science and pharmaceutical industries. We can produce ultra pure product using this technology. The main advantage of this technique is that we can easily remove the homogeneous catalyst which is difficult to do by using Host-Guest Interaction.

The implications of this technique extend toward recyclable homogeneous catalysis, because the catalyst removal method, Host-Guest Interaction is reversible. Though this method can provide insight into the same metastasis catalyst removal. It can also be applied to other metal containing catalyst such as palladium, platinum, copper, nickel and gold catalyst.

Visual demonstration of this method is critical as the synthesis procedure and homogeneous catalyst removal are typical too long because Host-Guest Catalyst remover is new. First dry a 25 milliliter round bottom flask containing a magnetic stir bar, a 20 milliliter vial and a spatula in an oven. Place 118 milligrams of imidazolium salt in a 4 milliliter vial.

Place the prepared imidazolium salt, the dried glassware, a septum, and the spatula in a glovebox chamber and vacuum for 2 hours. After completely removing the air in the glovebox can chamber, purge inert gas into the chamber. Then move the imidazolium salt, glassware, septum and spatula into the glovebox.

In the glovebox, add 54 milligrams of first generation Hoveyda-Grubbs catalyst in the 20 milliliter vial. Dissolve the imidazolium salt in two milliliters of toluene, and transfer it into the 25 milliliter round bottom flask containing the magnetic stir bar. Next, add 0.18 milliliters of a 0.5 molar KH MDS solution to the imidazolium salt solution.

Swirl the flask to mix the reagents. Now dissolve the catalyst in three milliliters of toluene and add the solution to the reaction flask. Seal the flask with the septum.

Then remove the flask from the glovebox. Following this, stir the reaction mixture for three hours at 80 degrees Celsius. After cooling the reaction mixture to room temperature, purify the catalyst by chromatography on neutral alumina.

Using a 15 to one mixture of ethyl acetate and methanol, collect the dark green solution. After combining the fractions containing product, removed the solvent under reduced pressure. When finished, dry the final residue under vacuum to obtain a dark green waxy solid.

Prepare degassed deuterium oxide by bubbling with nitrogen gas for over two hours. Add 4.4 milligrams of the ruthenium catalysts and 41 milligrams of the tetra alkyl ammonium substrate in separate four milliliter vials. Dissolve the tetra alkyl ammonium substrate in 0.5 milliliters of degassed deuterium dioxide.

Then add the solution to the catalyst. Seal the reaction vial and heat the reaction mixture for 24 hours at 45 degrees Celsius. Monitor the reaction conversion by proton NMR.

After the reaction is complete, cool the reaction vial to room temperature. Then add 150 milligrams of beta CD grafted silica to the reaction mixture. Stir the reaction mixture for 10 hours at room temperature.

After 10 hours, filter the reaction mixture through a cotton plug. Then remove the solvent in a freeze dryer. Prepare degassed deuterium oxide by bubbling with nitrogen gas for over two hours.

At 4.4 milligrams of the ruthenium catalysts and 17.1 milligrams of monomer in separate four milliliter vials. Dissolve the monomer in 0.5 milliliters of degassed deuterium oxide. Then add the solution to the catalyst.

Seal the reaction vial and heat the reaction mixture for two hours at 45 degrees Celsius. Monitor the reaction conversion by proton NMR. After the reaction is complete, cool the reaction vial to room temperature.

Then quench the reaction mixture with 0.1 milliliters of ethyl vinyl ether. Next, add 150 milligrams of beta CD grafted silica to the reaction mixture. Stir the reaction mixture for 10 hours at room temperature.

Filter the reaction mixture through a cotton plug. Then remove the solvent in a freeze dryer. Add 4.4 milligrams of the ruthenium catalysts and 48 milligrams of diethyl diallylmalonate in separate form in little vials.

Dissolve the diethyl diallylmalonate in 0.5 milliliters of dichloromethane. Then add the solution to the catalyst. Seal the reaction vial and keep the reaction mixture at room temperature for one hour.

Monitor the reaction conversion by proton NMR. After the reaction is complete, transfer the reaction mixture to a 30 milliliter vial. Dilute the mixture with 15 milliliters of diethyl ether.

Then wash the organic solution five times with 15 milliliters of water. Dry the organic layer with magnesium sulfate. Then filter the solution through a cotton plug to remove the magnesium sulfate.

Following this, add a magnetic stir bar and 60 milligrams of activated carbon to the filtered solution. Stir the mixture for 24 hours at room temperature. Filter the solution through a cotton plug to remove the activated carbon.

Finally, remove the solvent under reduced pressure. The ligand exchange reaction for the ruthenium olefin metathesis catalysis is shown here. The proton NMR spectrum is displayed here.

The ring closing metathesis reaction, an aqueous solution, and subsequent removal of used catalyst via Host-Guest Interaction is shown here. The dark reaction solution turned clear after the Host-Guest removal. The quaternary ammonium substrate was fully converted into the corresponding product with one mole percent of the catalyst and 53 parts per million of residual ruthenium was detected in the final product by inductively coupled plasma mass spectrometry or ICP-MS.

Full conversion of the primary ammonium substrate was achieved with three mole percent of the catalyst, and the residual ruthenium level in the product was 284 parts per million. Ring-opening metathesis polymerisation and aqueous solution is displayed here. And the residual ruthenium content detected by ICP-MS was 269 parts per million.

The ring closing metathesis reaction in dichloromethane and subsequent removal of used catalyst via extraction is shown here. With the exception of highly hindered substrates, the substrates achieved complete conversion in the ring closing metathesis reaction with one mole percent of the catalyst. ICP-MS detected 5.9 parts per million of ruthenium in the product.

Without activated carbon treatment, the residual ruthenium level was 63 parts per million which is not acceptable for pharmaceutical purposes. This technique can be done in 12 hours if it is performed properly. My research group is currently doing research to shorten the time, and to increase the efficiency of catalyst removal.

While attempting this procedure, it is important to remember to add sufficient guest bound solid to capture all available hosts containing catalyst molecules. Following this procedure, other catalysts like a palladium, platinum, copper, nickel and gold centered catalyst can be easily removed from the product by using the new guest containing NHC ligand and Host-Guest Interaction principle. After its development, this technique paved the way for researchers in the field of organometallic catalysis to explore the convenient and efficient removal methods of homogeneous catalysts to produce ultra pure polymers and pharmaceutical products.

After watching this video, you should have a good understanding of how to remove a homogeneous organometallic catalysts from a reaction mixture by Host-Guest Interaction. Don't forget that working with ethyl acetate methanol, ethylene chloride and diethyl ether can be extremely hazardous. Precautions such as conducting the reaction in the fume hood should always be taken while performing this procedure.