Green Chemistry Principle #8: Reduce Derivatives

By Trevor Janes, Member-at-Large for the GCI

8. Unnecessary derivatization (e.g. installation/removal of use protecting groups) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste.

In Video #8, Cynthia and Devon look at one common example of derivatization, which is the use of protecting groups in chemical reactions. To help illustrate the concept of a protecting group, they use toy building blocks.

In this blog post, I will use cartoons such as the one shown below (a specific example of the use of protecting groups will be shown at the end of this post).

Principle 8 - unselective reaction

Figure 1 An unselective reaction.

In Figure 1, the starting material contains two reactive sites, represented by U-shaped slots. We only want the slot on the right to react with the reagent, shown as red circles. The starting material is reacted with the reagent in order to make the desired product, but an undesired product also forms, because both U-shaped slots react with the red circle. In other words, Figure 1 shows an unselective reaction because a mixture of products is made.

Formation of the undesired product can be avoided by carrying out a protection reaction before using the red reagent, and then carrying out a final deprotection reaction. This sequence of reactions is shown in Figure 2.

Principle 8 - selectivity through protecting groups

Figure 2 A selective reaction through the use of a protecting group, which temporarily blocks the reactive site on the left side. 

 

Figure 2 shows how a selective reaction is traditionally done – through the use of a temporary block, known as a protecting group. The starting material can be protected by blocking one of the reactive sites, represented by the blue rectangle covering the U-shaped slot on the left. This intermediate only has one reactive site left, so the second reaction with the red reagent can only happen at the empty U-shaped slot on the right. To get the same desired product as in Figure 1, the third and final deprotection step is carried out, which removes the protecting group.

Principle 8 - waste from protecting groups

Figure 3 The waste created by all three reactions in Figure 2.

Even though the product from Figure 2 is the desired product, we had to do three reactions to only make one change, which is inefficient. Also, each step generates waste products (shown underneath each reaction arrow in the above cartoon) , which are depicted in Figure 3.

Protecting groups are a useful tool that chemists use to make the molecules, because we often need to carry out selective reactions on a molecule that has multiple of the same reactive sites. However, as we have talked about here, they are also inefficient and wasteful.

An active area of research is the development of more selective reactions, which eliminate the need to use protecting groups altogether.[1] Selective reactions use slight differences in a molecule’s chemistry to make a reaction happen at only the desired reactive site. This is very similar to the installation of the protecting group in Figure 2.

As more and more highly selective reactions are discovered, our syntheses can be made more efficient by reducing the number of steps required and the amount of waste produced. Looking ahead, protecting groups will be less and less necessary – and that’s a good thing!

 

Appendix – Example from Real Chemistry

A simple, specific example of the use of protecting groups[2] is shown below. Both oxygen-containing sites are reactive, but we only want the one on the left side to react in this case. The first reaction is the installation of the protecting group, (CH3)3SiCl, on the OH oxygen only, protecting the right side. The second reaction shows the reagent, CH3CH2CH2MgBr (for those curious, this is called a Grignard Reagent), which now reacts with just the ketone C=O site on the left, adding the desired new CH3CH2CH2 segment. The last step shows a combination of removing the protecting group to return the OH group, and also removing the [MgBr] segment of the reagent with the help of acid (shown as H3O+), which leaves the desired product with a CH3CH2CH2 chain added only on one side of the molecule.

Principle 8 - real protecting group use in chemistry

This example of a selective reaction uses a protecting group, but this requires 3 steps to only make 1 change. Instead, we can eliminate the need for protecting groups by designing new and more selective reactions that are much more efficient.

References:

[1] I. S. Young and P. S. Baran, Nature Chem. 2009, 1, 193

[2] R. J. Ouellette and J. D. Rawn, in Organic Chemistry, 2014, Elsevier, Boston pp 491-534.

Green Polymer Chemistry: Approaches, Challenges, Opportunity

Green Polymer Chemistry: Approaches, Challenges, Opportunity

By Hyungjun Cho, Member-at-large for the GCI

I was recently inspired by an episode of podcast by NPR’s Planet Money called Oil #4: How Oil Got Into Everything. It told the story of Leo Baekeland’s invention of Bakelite, which is the plastic that made many commodities affordable for the masses.

Plastic is made of polymers, and many of the common items we use are made from one or more of these polymers. Examples of these polymers are polystyrene, polymethylmethacrylate, and polyethylene and some examples of common items that contain these polymers are Styrofoam™, Plexiglas®, and plastic bags, respectively. Polymers are synthesized by forming bonds between many molecules of same structure, called monomers.

Conventionally, these monomers are produced from chemicals derived from oil, which is a non-renewable feedstock. Environmentally conscious scientists have been trying to make polymers in a more eco-friendly way. The biggest challenge lies in how we obtain monomers from renewable sources.

There are two main approaches to this challenge. The first approach is to produce currently used monomers, such as styrene, from a renewable source. A literature review by Hernandez et al.1 called this approach bioreplacement. The biggest progress in this

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Figure 1. Engineered metabolic pathway to produce styrene from glucose. (1)

approach has been made by engineering the metabolic pathways of bacteria cultures. McKenna et al. 3 have been able to feed glucose to engineered E. coli to produce styrene and release it in the culture medium they are incubating in. The E. coli flask cultures were able to produce styrene to reach concentrations of up to 260 mg/L1,3. Figure 1 shows the metabolic pathway from glucose to styrene.

While this method of producing monomers is promising, there are road blocks that are hindering progress. The biggest issue is toxicity of styrene to the E. coli, which limits the maximum concentration of styrene in the bacterial culture (E. coli can only tolerate up to 300 mg/L styrene1,3). Other challenges that exist with using bacteria include long incubation times, obtaining poor yield of desired product relative to amount of glucose added, and scale up. Looking down the road, these kinds of limitations may prevent this method from being economically and practically viable.

The second approach is called bioadvantage. Polymer chemists take chemicals that are already being produced from renewable feedstock, synthesize polymers, and use said polymers to produce polymer products in hopes of replacing already existing polymer materials. There are many molecules that are being studied for this purpose such as cellulose, starch, anethole, methylene-butyrolactone, and myrcene.

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Figure 2. Conventional monomers (styrene, methylmethacrylate, ethylene) and their potentially renewable counterparts. Renewable counterpart monomers tend to be structural analogues of conventional monomers.

During the podcast by Planet Money, research by the Hillmyer group from University of Minnesota was featured. They aim to synthesize eco-friendly polymer using monomers from renewable feedstock (the bioadvantage method). After many failures to produce viable polymer from corn, coconut, orange peels, etc., they were able to develop a polymer synthesized from a menthol derivative obtained from peppermint2.

A critical challenge to bioadvantage polymers is the need for years of study and passing a battery of regulatory tests before they are adopted. The petroleum based polymers that are being used today already have been researched for decades, which allows them to be used easily by industry. By extension, bioadvantage polymers will need to match or exceed their performance in terms of strength, durability, flexibility, and other properties we require from our plastic. Even when industry is willing to allocate resources to adopt eco-friendly polymers, sometimes it’s the consumers that prove to be even less accommodating. We observed this with the biodegradable bag fiasco by Sun Chips.

It should be mentioned that both bioreplacement and bioadvantage polymers are not necessarily biodegradable. Therefore, we should not call them green polymers.

I will conclude with this: I see the impact that plastic has on our daily lives and I see demand for polymers. Being able to make eco-friendly polymers economically will change the world around you, literally. As Planet Money teaches, the world works in a supply-demand swing. When the kinks in the supply side of eco-friendly polymers are fixed, demand for them will present itself. How soon eco-friendly plastics will develop will depend on us. As green chemists, we should see that the biggest impact we might have in the future, will be making eco-friendly polymers.

References

(1)   Hernández, N.; Williams, R. C.; Cochran, E. W. Org. Biomol. Chem., 2014,12, 2834-2849

(2)   Hillmyer, M. A.; Tolman, W. B. Acc. Chem. Res., 201447 (8), pp 2390–2396

(3)   Mckenna, R.; Nielsen, D. R. Metab. Eng. 2011, 13 (5), 544–554.

Green Chemistry: From the Bench Top to Industry, A Chemical Engineer’s Perspective

By Cynthia Cheung, Member-at-Large for the GCI

As a chemist, do you ever think about how to scale up your chemical reactions, or your chemical processes? For most of us, the answer is no. However, this idea of industrial scale is something that is constantly addressed in the Chemical Engineering and Applied Chemistry department. Consequently, the 12 Principles of Green Chemistry become fundamental to scale up a reaction from the bench top in a research lab to mass production in a chemical plant (Figure 1).

Cynthia_blog post figure 1

Figure 1. Example of a chemical plant design [1]

For me, the biggest difference I have found moving from the Chemistry department to the Chemical Engineering department is that the principles of Green Chemistry are not concepts that Chemical Engineers often have to think about or address, because these principles are integrated and engrained into their work as objectives and limitations. A process can be thrown out simply because it uses columns for purification (which cannot be done on a large scale, because you would need truckloads of solvent) or because one of the reagents is toxic.

As a chemist, we do what works and worry about alternatives after we have established what we targeted. So pause and think about it for a second: can you continue what you’re doing and upscale it from milligrams to tonnes? Even theoretically speaking, if you could produce that much product, would that process make sense? For example, would that Stille coupling reaction be safe when you’re using tonnes of tin2, or could you afford to be using or making catalysts when you need tens of kilograms of it? So how to do you go about engineering your process so that it would be suitable for industry? Rather, how do the engineers do it?! Well, broadly speaking (and from asking around) a few of the main considerations that seem to be in common are:

Cost Analysis

How much are all of the reagents and solvents going to cost, and where are there substitutes for cheaper alternatives?

Rate of Reaction

How long is this reaction going to take? Because time is money.

Waste

How much waste is produced, what type of waste and is it recyclable? Also to keep in mind is if the waste is hazardous, then what alternatives can be used from the beginning to avoid any hazardous waste generation? In addition, if there’s pollution, then that also has to be reduced or eliminated altogether.

Work up

This consideration is often tricky, as most organic labs usually use techniques that are not scalable (I’m looking at those purification columns). In addition to that, side products and by-products are also something that often can give engineers a headache. Atom economy is very important for industry, as it lessens the amount of waste produced, and also aids in producing a good product yield.

Energy Consumption

How much energy is required for a reactor and for a chemical plant to run is also part of the cost analysis for a process. It would definitely be preferential to be using less energy (so lower temperature reaction conditions and reactions that generate no heat). Essentially, if all reactions could be at room temperature, that would be perfect.

So with these considerations in mind, could you re-engineer your synthesis?

 

References:

[1] http://en.citizendium.org/wiki/File:FCC.png

[2] Stille, J. Palladium Catalyzed Coupling Of Organotin Reagents With Organic Electrophiles. Pure and Applied Chemistry 1985, 57.

Green Chemistry Applied In Industry: Our 2015 Symposium

By Karl Demmans, 2015 Symposium Coordinator for the GCI

Following the success over the past couple years with our workshops entitled “Future Leaders in Green Chemistry” and “Next Steps in Green Chemistry Research”, we felt that the next logical step after teaching chemists how to apply green chemistry in their own research would be to have a symposium highlighting how these techniques are implemented by the chemical industry in the working world. Therefore we focused on obtaining lecturers from industries across Canada and the United States such as Xerox, VWR, Sigma Aldrich, Dow, 1366 Technologies, Proteaf Technologies, Green Chemistry & Commerce Council, and many more.

Starting off the event was Dr. Andy Dicks’ Crash Course which covered the basics of green chemistry while incorporating industrial case studies from recent years. The industrial lectures followed over two full symposium days, covering a variety of topics with three main goals: 1) how companies are bridging the gap between academia and industry, particularly by adopting promising chemistry from academia, 2) how companies are connecting with each other globally to instill better practices such as industrial transparency through environmental sustainability reports, and 3) chemical synthetic case examples exploring the diverse area that is the industrial green chemistry of today. A few academic lecturers were also invited to share their knowledge of solvent-free chemistry and applying green chemistry to DFT calculations.

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Symposium participants learn about each other’s research during the poster session.

The final lecture, compiled by the GCI and presented by yours truly, was entitled “Preparing for the Future: Advice from Industry”. This lecture presented the responses from our invited speakers to a few questions we asked them, based on the necessary skill sets and experience required to push forward your resume when applying for an industry-based job, as well as their view of working in an industrial lab vs an academic setting. In the end, the best advice was to educate yourself broadly in science and in business, be active with extracurriculars during your studies, and most importantly to develop communication and people skills!

Highlights from the symposium included poster presentations featuring 14 posters (three of which won a monetary prize in a poster competition), dinner with the speakers in small groups, and a social event held at Harvest Kitchen with hors-d’oeuvres and drinks.

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Group picture taken during the social night!

Of course, we’d like to thank our sponsors for their funding to make this event possible: UofT Environmental Resource Network (UTERN), the UofT Chemistry department, GreenCentre Canada, UTGSU, and Ulife. Special thanks goes to Universal Promotions, who were very helpful in the process of making GCI notebooks for our symposium swag.

If you’d like to see more details including a full schedule of our 2015 Symposium, click here. ACCN also published an article featuring our event, please check it out here!

We’re already planning the theme and speakers for our 2016 Symposium, so stay tuned through our social media accounts for more announcements.

Thanks for stopping by and have a great day!