ACS Summer School on Green Chemistry and Sustainable Energy 2017

ACS Summer School on Green Chemistry and Sustainable Energy 2017

By Samantha Smith, Yuchan Dong, and Shira Joudan

Yuchan Dong, who previously studied in China, had begun to miss life with roommates while in Canada. She reminisced about how you could talk about your lives late into the night, and spend meals chatting with friends in the cafeteria. “Luckily, at the ACS summer school, [she] got the chance to experience such life again and got to know a lot people who share same interests.” The summer school brought us back to the more carefree times of our undergraduate lives. Living in dormitories, sharing a floor with fifty-two other highly educated students, sharing every meal with our newly-formed friends, and even tackling homework assignments were just like the “good old days”. The level of diversity strengthened the value of peer-networking and real friendships were made throughout the week.

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The week wasn’t just filled with relaxing chats in the Colorado sun; that was merely how we spent our free time. The days were jam-packed with riveting lectures during the day, assignments in the evening, and getting to know the local Golden beers at night (which was obviously a duty of ours as tourists). We also had the chance to take in the local scenery with hikes and whitewater rafting.

The ACS summer school on green chemistry is a competitive program offered to graduate students, post-doctoral fellows, and industry members every year in Golden, Colorado. Hosted by the Colorado School of Mines, the program consists of five days of lectures from green chemistry and sustainable energy experts, two poster sessions, a whitewater rafting trip, and lots of opportunity for networking. This program teaches global sustainability challenges with a focus on sustainable energy. The ACS Summer School is free of charge for successful attendees, including travel, accommodation on campus, and meals.

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Samantha, Yuchan, and Shira at the ACS Summer School

Jim Hutchison, a professor at the University of Oregon, spoke about how his department has completely reformatted their undergraduate chemistry curriculum to contain green and sustainable chemistry, something that particularly sparked Shira’s interest as lead of GCI’s Education Subcommittee. Bill Tolman, Chair of the University of Minnesota Chemistry Department, shared how students successfully cultivated the safety culture within his department. This had inspired Samantha to create new initiatives within our chemistry department. Queens University’s Professor Philip Jessop taught us about Life-Cycle Analysis (LCA) and assigned us multiple processes for which we calculated the gate-to-gate LCA. Mary Kirchhoff and David Constable from ACS gave talks on green chemistry and ACS resources, many of which would be useful to other departments. The format of the summer school allowed plenty of time to chat with the guest lecturers during coffee breaks, lunches, and poster sessions.

Many real-world issues were discussed. The worldwide energy usage and sources of energy were a main topic of discussion, as was the use of alternative sources. We were blown away by how multi-disciplinary green chemistry is, and we were enlightened on how we need experts in all fields to successfully create sustainable chemistry. We learned that to be able to effectively tackle environmental issues we need great synthetic chemists, whether they specialize in organic, materials or catalysis, as well as analytical chemists, engineers, environmental chemists, and toxicologists. We also need effective entrepreneurs and lobbyists.

Nearing the end of the summer school, a large group of us hiked up Tabletop mountain to get the most amazing view of the valley. A warm feeling of appreciation towards the summer school for bringing us out of the isolation of individual research in the busy city life was shared. We would like to thank ACS for giving us the chance to attend this amazing week. This experience has truly been beneficial to us, and we plan to use the knowledge gained during the week in our own studies as well as pass this knowledge on to our coworkers at the University of Toronto.

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Tabletop mountain in Golden, CO

We highly encourage anyone interested in green chemistry and sustainability to attend this beneficial program. Application deadlines are early in the year and submitted online. The application consists of the applicant’s CV, unofficial transcript, letter of nomination from faculty advisor or another faculty member, and a one-page essay describing your interest in green chemistry and sustainability as well as how it will benefit the applicant.

Green Chemistry Principle #9: Catalysis

By Alex Waked, Member-At-Large for the GCI

9. Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.

In Video #9, Lilin and Jamy discuss the advantages of catalytic reagents over stoichiometric reagents.


In stoichiometric reactions, the reaction can often be very slow, may require significant energy input in the form of heat, or may produce unwanted byproducts that could be harmful to the environment or cost lots of money to dispose of. Most chemical processes employing catalysts are able to bypass these drawbacks.

A catalyst is a reagent that participates in a chemical reaction, yet remains unchanged after the reaction is complete. The way they typically work is by lowering the energy barrier of a given reaction by interacting with specific locations on the reactants, as demonstrated in Figure 1 below. The reactants are represented by the red and blue objects, and the catalyst by the green one. Without catalyst, the reactants cannot react with each another to form the desired product. However, once the catalyst interacts with them, the reactants become compatible and can subsequently react together. The desired product is released and the catalyst is regenerated to continue interacting with the remaining reactants to produce more product.

Principle 9 Figure 1 - catalysis

Figure 1. Graphic of a catalyst’s function in a catalytic reaction. The catalyst is green, and the reactants are red and blue.

In other words, a catalyst can be thought of as a key that can unlock specific keyholes, where a keyhole represents a particular chemical reaction. One common example of a catalytic reaction that is taught in introductory organic chemistry is the hydrogenation of ketones (Scheme 1, also discussed in the video). The stoichiometric reaction involves the addition of sodium borohydride, followed by addition of water. In this reaction, borane (BH3) and sodium hydroxide are (formally) generated as waste. By simply employing palladium on carbon as catalyst, the ketone can react directly with H2 to generate the same desired product without producing any waste.

Principle 9 Scheme 1 - catalysis example

Scheme 1. Stoichiometric vs. catalytic reduction of a ketone.

While catalytic reagents appear to play an impactful role in the development of greener processes, there are always a couple points on the flip side of the coin to consider. For instance, a reaction employing a catalyst may not necessarily be “green”, since the “greenness” of the catalyst itself should be considered as well (ie. Is the catalyst itself toxic? Is it environmentally benign?). In addition, the lifetime of a catalyst matters; a catalyst can in theory perform a reaction an infinite number of times, but in practice it loses its effectiveness after a certain period of time.

Nevertheless, when these points are considered and addressed, the impact of catalytic reagents on green processes cannot be ignored. The production of fine chemicals and the pharmaceutical industries are just a couple areas where this impact is seen.[1] By focusing innovative research around the principle of catalysis, together with the other principles of Green Chemistry, we are moving in the right direction by paving the way to new sustainable processes.

Reference:
[1] Delidovich, I.; Palkovits, R. Green Chem. 2016, 18, 590-593.

A New Green Chemistry Metric: The Green Aspiration Level™

A New Green Chemistry Metric: The Green Aspiration Level™

By Samantha A. M. Smith, Member-at-Large for the GCI

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Figure 1. Process materials – green mass metric relationships

Green Chemistry Principle number two, Atom Economy, focuses on metrics used to compare the efficiency of a reaction.1 However, Atom Economy doesn’t take into account solvents, reagents such as catalysts, drying agents, energy, or recyclability of any of the materials. Is it reasonable for an industry such as pharma to use such a metric? What about E-factor, which is a measure of process waste and, if “complete” (cEF = complete E-factor), also recyclability of solvents and catalysts? It’s known that the pharmaceutical industry generally has the highest E-factor values compared to petrochemicals, bulk, and fine chemicals, indicating more waste generated per mass of desired product.2 But if you wanted to compare your technology to already implemented pharmaceutical processes, where would you find such information?

Roschangar, Sheldon, and Senanayake created a new metric for such a purpose: the Green Aspiration Level™.3,4 This new metric allows one to compare an ideal process with the average commercial process in terms of environmental impact for the production of a pharmaceutical. Say you have an alternative product to Viagra™ and want to know if its production is more or less impactful. You could apply any of the existing metrics (including yield, atom economy, E-factor, and more, summarized in Table 1 of reference 3), or you could use the Green Aspiration Level™ (GAL). To do so, you determine the waste (Complete Environmental Impact Factor (cEF) or Process Mass Intensity (PMI)) and assess the complexity of the process, and use those to calculate the GAL, and in turn the Relative Process Greenness (RPG). From there, you can consult Table 1 (below) to determine the greenness rating of such a process.4

Waste and Complexity

Waste refers to a simple metric such as cEF or PMI (with reactor cleaning and solvent recycling excluded). Complexity of the process refers to the number of steps with no concession transformations, that is those that do not directly contribute to the building of the target molecules’ skeleton.5 The waste and complexity metrics require that the process starting materials are less than $100 USD/mol for proper comparison.

Green Aspiration Level™

Roschangar and coworkers have collected data on many commercial processes to develop an appropriate metric, and they currently use 26 kg of waste per kg of product as a standard based on their findings. This value is known as the average GAL, or tGAL.3,4

GAL        = (tGAL) x Complexity

= 26 x Complexity

Relative Process Greenness

RPG       = GAL/cEF

This metric is used as the comparison point for processes. The comparison can be done at different stages of development, either early or late development, and then again for those processes that are commercialized. In Table 1, there are minimum RPG values that will associate the process with an appropriate greenness percentile.

RPI         = RPG(current) – RPG(early)

RPG can also be used to determine the improvement of a process. From early development, to late development, to commercialization, the difference in consecutive RPG values will give your Relative (Green) Process Improvement (RPI). In this case, the higher the number the better.

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Table 1. Rating Matrix for Relative Process Greenness (RPG) in Pharmaceutical Drug Manufacturing [3]

It turns out the current commercial process for Viagra™ is actually quite efficient and is currently in the 90th percentile, exceeding the commercial average by 143% (RPG). The full process of determining and using this new metric, the Green Aspiration Level™, is described by Roschangar and coworkers in two very in-depth articles.3,4

References

1 Anastas, P. T., Warner, J. C. “Principles of green chemistry.” Green chemistry: Theory and practice (1998): 29-56.

2 Sheldon, R. A., Catalysis and Pollution Prevention, Chem. Ind. (London), 1997, 12–15.

3 Roschangar, F., Sheldon, R. A., Senanayake, C. H., Green Chem. 2015, 17, 752. DOI: 10.1039/C4GC01563K

4 Roschangar, F., Colberg, J., Dunn, P. J., Gallou, F., Hayler, J. D., Koenig, S. G., Kopach, M. E., Leahy, D. K., Mergelsberg, I., Tucker, J. L., Sheldon, R. A., Senanayake, C. H., Green Chem. 2017, 19, 281. DOI: 10.1039/c6gc02901a 

5 Crow, J. M., “Stepping toward ideality”, Chemistry World, accessed July 13th, 2017. URL: https://www.chemistryworld.com/feature/stepping-toward-ideality/5190.article

Figures from Roschangar et al. 2015 reproduced with the permission of the Royal Society of Chemistry.

Green Chemistry at CSC2017 – The 100th Canadian Chemistry Conference and Exhibition

By Kevin Szkop and Alex Waked

This year, the GCI partnered with the Chemical Institute of Canada (CIC), the organizing body of the CSC2017, to be closely involved in various aspects of Canada’s largest chemistry meeting.

In collaboration with GreenCentre Canada and CIC, the GCI organized a Professional Development Workshop as part of the CSC2017 program. This event consisted of four components:

The green chemistry crash course, led by Dr. Laura Reyes. Laura is a founding member of the GCI, and is now working in marketing & communications with GreenCentre Canada.

A case study, led by Dr. Tim Clark, Technology Leader at GreenCentre Canada. The case study gave attendees a unique opportunity to learn about some projects that GreenCentre has been developing and in collaboration with peers, learn how to find applications for new intellectual property (IP) and how to make contacts within relevant companies.

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Dr. Tim Clark leading the GreenCentre Canada Industry Case Study

Career panel discussion, sponsored by Gilead, featuring members of academia and industry.

A coffee mixer for an opportunity for informal networking.

 

Supplementary to the Professional Development Workshop, the GCI organized a technical session, co-hosted by the Inorganic, Environmental, and Industrial sections of the conference. This new symposium, entitled “Recent Advances in Sustainable Chemistry”, brought together students, professors, industry, and government speakers to showcase a diverse and engaging collection of new trends in green and sustainable chemistry practices across all sectors of chemistry. Highlighted talks included Dr. Martyn Poliakoff from the University of Nottingham, also a CSC2017 Plenary Lecturer, Dr. David Bergbreiter from Texas A&M University, and Dr. William Tolman from the University of Minnesota.

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Dr. Martyn Poliakoff teaching the audience about NbOPO4 acid catalysts found in Brazilian mines

Dr. Bergbreiter’s lecture was an engaging one. His enthusiastic approach to the use of renewable and bio-derived polymers as green solvents was captivating to both industrial and academic chemists.

Dr. Martyn Poliakoff, a plenary speaker at the conference, gave a phenomenal talk during the first day of the symposium. His charismatic style complimented perfectly the cutting-edge research ongoing in his group at the University of Nottingham. Particularly interesting was the use of flow processes in tandem with photochemistry to yield large quantities of natural products useful in the drug industries.

Dr. Tolman’s talk was of interest to essentially anyone working in an academic environment, especially for student run groups, like the GCI, with both academic interests as well as safety awareness initiatives. In the first part of the talk, synthetic and mechanistic studies of renewable polymers were discussed. The second part shifted focus to student-led efforts to enhance the safety culture in academic labs, which stood out from most of the other talks in our symposium.

One highlight was a group of graduate students at the University of Minnesota organizing a tour of Dow Chemicals to observe the work and safety codes in an industrial setting, which they used as a lesson to bring back to their own research labs. This caught the eye of most of the GCI members, which inspired us to organize a similar day trip in the future.

In further efforts to make our symposium accessible to undergraduate and graduate students, the GCI partnered with GreenCentre Canada to award five Travel Scholarships to deserving students from across Canada to provide financial aid to participate in the conference.

We thank all of our speakers, both national and international, for their participation in the program. It was a great success!

 

Issues of Sustainability in Laboratories Outside the Field of Chemistry: Pipette Tips

Issues of Sustainability in Laboratories Outside the Field of Chemistry: Pipette Tips

By David Djenic, Member-at-Large for the GCI

As a biochemistry student in the Green Chemistry Initiative, I’m interested in looking at how to implement the principles of green chemistry in molecular biology and biochemistry labs. While molecular biology labs focus more on studying biological systems and molecules rather than synthesizing new molecules, like in synthetic chemistry, there are still problems when it comes to performing environmentally sustainable research.

Pipette tips and pipette tip racks are major contributors to non-chemical waste in biomedical labs because of the volume of tips thrown out and the lack of recycling programs to deal with tips and racks. Pipette tip racks are commonly used because they reduce the risk of contaminating pipette tips. Pipette tip racks are made of #5 plastic (polypropylene), the same material as yogurt cups, medicine bottles and David_blog 1microwavable containers, making them lightweight and very safe to use [1].
However, #5 plastics are rarely accepted by curbside recycling programs and are placed in landfills and incinerators instead [2]. The plastic from the empty polypropylene racks take hundreds, if not thousands, of years to degrade [3].

Biomedical companies have worked in the past 10 years to reduce the amount of waste from pipette tip racks. For example, Anachem, a pipette and pipette tip manufacturing company in the UK, has collaborated with a plastic recycling company to collect racks from qualifying laboratories, ground them down, melt them, and remould into new products [3]. A similar program is run at the Environment, Health and Safety (EHS) division of the National Cancer Institute at Frederick (NCI-Frederick), where, from 2003 to 2006, approximately 8,400 pounds of pipette tip boxes were recycled, saving approximately $7,400 in medical waste contract money [4].

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Pipette tip box waste to be recycled through the EHS program [4].

There aren’t many statistics on the waste produced by the pipette tips themselves. But whenever I’m in a biochemistry lab course, the orange bins where used tips are thrown are filled to the brim with pipette tips, microcentrifuge tubes, Falcon tubes, etc. It is more difficult to reduce and recycle tips rather than tip racks because they are heavily contaminated after use. GreenLabs at the University of Chicago offers some interesting suggestions on reducing pipette waste, such as using pipette tip refills, buying pipette tips made from sustainable material, and generally reducing pipette tip use when possible. However, more research on pipette tip waste is needed to quantifiably analyze the impact of tips and come up with solutions to reduce potential waste.

I think undergraduate biomedical teaching and research labs do apply basic green chemistry principles, even if they are not explicitly brought up. Many of the reactions are done in very small, precise quantities and waste is generally disposed of in the proper place. However, there does not seem to be much exposure, if at all when it comes to green chemistry issues; biochemistry and biomedical students aren’t aware of the environmental impact they generate in labs. Introducing green chemistry education in biomedical laboratories at U of T, especially when it comes to the issue of pipette tips and racks, would help U of T reduce its environmental impact even more.

 

References

[1] http://www.davidsuzuki.org/publications/downloads/2010/plasticsbynumber.pdf

[2] http://earth911.com/home/recycling-mysteries-5-plastics/

[3] http://www.labnews.co.uk/features/consumables-dont-cost-the-earth-01-07-2005/

[4] G. A. Ragan, J. Chem. Health Saf. 2007, 14, (6) 17-20.  http://www.sciencedirect.com/science/article/pii/S1871553206001344

Triclosan: A Controversial Chemical in Your Soap

Triclosan: A Controversial Chemical in Your Soap

By Connie Tang, Member-at-Large for the GCI

Triclosan: it’s in your soap, body wash, and your toothpaste. It can be even found in yoga mats.

Triclosan is an antibacterial agent added to household products. While soap is rarely the centre of a news story, triclosan has garnered significant controversy after the United States Food and Drug Administration (FDA) banned these potentially hazardous chemicals (along with 18 others) from hand soaps.1 Meanwhile, Canada has labelled the chemical as toxic for the environment, and maintained that it does not meet the standard for human health toxicity.2

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What is triclosan and where is it beneficially used?

Antibacterial soaps (also known as antimicrobial or antiseptic soaps) contain additional chemicals with the intent of reducing bacterial infection. Triclosan is one of these chemicals and is often used in personal care products, cosmetics, and can even be found in toys, kitchenware, and furniture. In the past two decades, its use has expanded commercially and by the year 2000, triclosan was found in 75% of liquid soaps and almost 30% of bar soaps.3

Antibacterial agents, like triclosan, were originally used in surgical scrubs and hand washes to protect health workers in medical settings from bacteria that can cause infections in hospitals. In surgical units, triclosan is effective against bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to most antibiotics.

Additionally, triclosan can be found in toothpastes, because it has been linked to improved protection against cavities.

In 2008, the Environmental Working Group (EWG) found high levels of triclosan in San Francisco Bay, which prompted studies of this chemical in blood and urine samples of teenage girls to explore its impact on endocrine hormonal processes. Since 2008, the EWG has been submitting reports to the FDA to ban triclosan in personal care products.8

Is triclosan dangerous?

Short answer: Triclosan is most likely harmful to the environment, and possibly harmful to humans.

Environment Canada has categorized triclosan as potentially toxic to aquatic organisms since it bioaccumulates (becomes more concentrated). Even at low concentrations in aquatic plants and animals, it can cause growth reduction and decreased reproduction, impacting survival. Triclosan’s structure is similar to thyroid hormones, so scientists have suggested triclosan’s mechanism of toxicity might involve binding to hormone receptors, impacting hormone functions.4

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Animal studies with triclosan have shown that mice exposed to antibacterial ingredients were more likely to develop liver cancer.8 Another study exposed triclosan to pregnant rats9 and found their hormone (progesterone, estradiol, testosterone) levels dropped, potentially affecting fetal development. Triclosan can interfere with normal thyroid hormone functions,10 raising concerns about reproductive impacts. However, no definitive study has proven how harmful triclosan is to humans.11

Triclosan is also persistent, meaning that it does not degrade easily.12 Once it is washed down the drain, most wastewater treatment plants cannot effectively filter out triclosan, and it enters our Great Lakes and waterways.

Lab studies with triclosan suggest it can randomly generate mutations in bacteria.13 This will likely lead to increasing antibiotic resistance in bacteria, creating “superbugs” and decreasing the effectiveness of antibiotics.

Why was triclosan (one of 19 active ingredients) banned in soaps by the FDA?

The FDA banned triclosan and other ingredients from soaps, because there is no compelling evidence the ingredients are safe.1 In 2013, the FDA asked manufacturers to submit evidence that antibacterial ingredients are safe for long-term use and more effective than regular soap at reducing the spread of germs. Neither was proven. Resulting research suggested triclosan and similar agents might be harmful.

“Consumers may think antibacterial washes are more effective at preventing the spread of germs, but we have no scientific evidence that they are any better than plain soap and water,” said Dr. Janet Woodcock, director of the FDA’s Centre for Drug Evaluation and Research in a press release.1

While triclosan is useful in medical settings to protect against bacteria like MRSA, it is not necessary in consumer soaps. So, this ban applies to consumer products, not to antibacterial soaps used in hospitals and food service settings. Products not under the purview of the FDA (like toys, furniture, apparel) are not subject to the ban.

What is Canada’s response?

Health Canada has restricted the amounts of triclosan in mouthwash and personal care products, but has not banned the chemical.2 While concentration limits of triclosan are low (0.03% in mouthwashes, 0.3% in cosmetics),5 even these small amounts will bioaccumulate in our aquatic ecosystems.

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The Canadian government has announced that triclosan is not hazardous to human health, but has declared it toxic under the Environmental Protection Act because of its negative effect on aquatic organisms. Environment Canada has flagged triclosan for future assessment.6

Health Canada has said, “The health and safety of Canadians is of utmost importance… The government will continue to monitor new scientific evidence related to triclosan and will take further action if warranted.”

Canada does plan to introduce measures to limit the release of triclosan from consumer products into waterways.6 But this may prove more challenging as this requires manufacturers to develop plans and upgrade for waste-treatment equipment – a costly endeavor.

Many environmentalists and scientists are pushing for Canada to implement a ban of these chemicals in consumer products. In the meantime, should we, as Canadian consumers, refrain from buying antibacterial soaps?

“It really should not be left to the consumers to try to avoid these products, especially given that there is very little benefit to using them,” says Fe de Leon, Canadian Environmental Law Association researcher.7

References

  1. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm205999.htm
  2. https://www.canada.ca/en/health-canada/services/chemicals-product-safety/triclosan.html
  3. http://blog.nacwa.org/washing-away-triclosan-with-legislation-and-regulation/
  4. http://www.environmentalhealthnews.org/ehs/news/triclosan-and-dolphins
  5. http://www.hc-sc.gc.ca/cps-spc/cosmet-person/labelling-etiquetage/ingredients-eng.php#a4.14
  6. http://www.chemicalsubstanceschimiques.gc.ca/fact-fait/glance-bref/triclosan-eng.php
  7. http://www.cbc.ca/news/technology/ban-antibacterials-triclosan-and-triclocarban-report-says-1.2703095
  8. http://www.ewg.org/release/fda-finally-bans-toxic-triclosan-antibacterial-hand-soaps

Triclosan laboratory studies

  1. Feng, Y.et al. PLoS ONE 11(5).
  2. Yueh, M. F. et al. Proc Natl Acad Sci U S A 2014, 111(48), 17200.
  3. Gee, R. H. et al. Appl. Toxicol. 2008, 28, 78.
  4. Calafat, A. M. et al. Health Perspect. 2008, 116(3), 303.
  5. Ricart, M. et al. Toxicol. 2010, 100(4), 346.
  6. Pycke, B. F. G. et al. Appl. Environ. Mircobiol. 2010, 76(10), 3116.

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.