United States
Son Green Chemistry Challenge
2017 Award Recipients
ir M ^
5 ll S
A U.S. EPA Program

2017 Winners
Academic Award:
Professor Eric J. Schelter
University of Pennsylvania	7
Small Business Award:
UniEnergy Technologies, LLC	2
Greener Synthetic Pathways Award:
Merck & Co., Inc.	3
Greener Reaction Conditions Award:
Amgen Inc. and Bachem	4
Designing Greener Chemicals Award:
The Dow Chemical Company and Papierfabrik August Koehler SE	5

2017 Winners
Academic Award
Professor Eric J. Schelter
University of Pennsylvania
Simple and Efficient Recycling of Rare Earth Elements from Consumer Materials Using Tailored Metal Complexes
Innovation and Benefits
Professor Eric Schelter, University of Pennsylvania, is being recognized for developing a simple, fast, and low-cost
technology to help recycle mixtures of rare earth elements. Reducing the costs to recover these materials creates
economic opportunity by turning a waste stream, currently only recycled at a rate of 1%, into a potential revenue
stream. About 17,000 metric tons of rare earth oxides are used in the U.S. annually in materials such as wind turbines,
catalysts, lighting phosphors, electric motors, batteries, cell phones, and many others. Mining, refining, and purification
of rare earths are extraordinarily energy and waste intensive and carry a significant environmental burden.
The rare earths (La-Lu, Sc and Y) are a group of seventeen elements whose intrinsic properties make them
extraordinarily useful and irreplaceable in modern technologies, including renewable energy, electronics,
lighting, and various defense applications. However, rare earths (REs) tend to all have similar chemical
properties and co-occur geologically as mixtures of 5-7 elements in ores, making the primary mining, refining,
and purification of rare earths an extraordinarily energy intensive and waste-generating process that creates
severe environmental burdens. Hard rock mining and refining requires large quantities of water, acid, and
organic solvents, and produces large quantities of hydrofluoric acid, organics, and radionuclide wastes, which
can include uranium, thorium, and their decay products. The U.S. Department of Energy (DOE) has classified
several REs as "critical" materials. For consumer materials, purified REs are typically blended into mixtures for
their application. The challenging separations chemistry of REs is the chief barrier to widespread recycling,
which is currently performed at a rate of only -1%.
Professor Schelter's group has developed a new, targeted approach that simplifies and reduces the costs
of separating mixtures of REs obtained from consumer materials. This method is expected to contribute to
reducing waste, energy use, C02 production, and primary REs mining by adding recycled REs to the domestic
supply chain. The central hypothesis of this work is that tailored organic compounds can provide simple and
effective separations for mixtures of RE metals, based on solubility differences of the RE complexes. Phosphors
(32% of total market) and magnets (38%), comprising mixtures of Nd/Dy and Eu/Y respectively, are the
optimal targets for recycling. Professor Schelter's group has synthesized a new organic compound (a 'ligand'):
tris(2-tert-butylhydroxylaminato)benzylamine (H3TriNOx) for separations. Work is currently under way to
develop these concepts into practical and industrially viable recycling processes. A recent DOE grant award
will support the further development of the technology.
1 2017 Academic Award

Small Business Award
UniEnergy Technologies, LLC
The UniSystem™: An Advanced Vanadium Redox Flow Battery for Grid-Scale Energy Storage
Innovation and Benefits
UniEnergy Technologies, LLC (UET), Mukilteo, Washington, in partnership with Pacific Northwest National Laboratory
(PNNL), is being recognized for an advanced vanadium redox flow battery, originally developed at the PNNL and
commercialized by UET The battery, when used by utility, commercial and industrial customers, allows cities and
businesses more access to stored energy It also lasts longer and works in a broad temperature range with one-fifth
the footprint of previous flow battery technologies. The electrolyte is water-based and does not degrade, and the
batteries are non-flammable and recyclable, thus helping meet the increasing demand of electrical energy storage in
the electrical power market, from generation, transmission, and distribution to the end users of electricity.
The evolving demands of the energy market call for alternative energy storage technologies capable of
both long and short duration operation and as long-lasting assets to deliver a maximum value to customers.
Current battery chemistries based on Li-ion have proved to be competitive for relatively short duration
(2 hours or less) applications such as frequency regulation, given their excellent power capability and battery
cell energy efficiency. However, they may not always be a competitive solution for customers that need long
duration benefits, as Li-ion batteries degrade over time and have limited cycle life. In addition, they cannot use
their full capacity-rated charge and thus are typically operated at 20-80% capacity. Li-ion batteries also have
noted challenges with thermal runaway and flammability.
The vanadium redox flow battery (VFB) has emerged recently as a competitive alternative that is capable
of delivering competitive value to utility, commercial, industrial, and microgrid customers that require long
duration benefits, such as load leveling, peak shaving, islanding, and renewable energy integration, as an
essential part of their overall value propositions for energy storage. However, the traditional VFB's drawbacks
included a large ground footprint to operate and stability limited to a narrow temperature range of 50 to 95 °F.
UniEnergy Technologies'third generation vanadium redox flow battery, the UniSystem™, utilizes a
breakthrough chemistry: a vanadium electrolyte with double the energy density of prior chemistries, and a
much broader operating temperature (-40 to 120 °F) that allows the energy storage system to be deployed
in nearly any ambient temperature or environment on earth.These improvements have resulted in a fully
containerized and deployable megawatt-scale vanadium redox flow battery technology with one-fifth the
ground footprint and greatly reduced chemical usage compared to previous flow battery technologies. The
new vanadium electrolytes, with a chloride-based complex chemistry, have a much improved stability over
traditional sulfate-based chemistries. UET's improvements in system integration and controls have made the
deployment, operation, and maintenance of this chemical battery simpler, cost effective, and safe. Because the
vanadium electrolyte is water-based and does not degrade, the batteries are non-flammable and recyclable.
2017 Small Business Award 2

Greener Synthetic Pathways Award
Merck & Co., Inc.
Letermovir: A Case Study in State-of-the-Art Approaches to Sustainable Commercial Manufacturing Processes
in the Pharmaceutical Industry
Innovation and Benefits
Merck & Co., Inc., Rahway, New Jersey, is being recognized for successfully applying green chemistry design
principles to Letermovir, an antiviral drug candidate that is currently in phase III clinical trials.The improvements
to the way the drug is made, including use of a better chemical catalyst, increases the overall yield by more than
60%, reduces raw material costs by 93%, and reduces water usage by 90%.
Letermovir is an antiviral drug, currently at the end of phase III clinical trials, for the treatment of
cytomegalovirus (CMV) infections. CMV is widely spread in the human population and can cause severe,
life-threatening infections in immunocompromised patients. Letermovir has been granted Fast Track Status
by the FDA and Orphan Product Designation by the European Medicines Agency for the prevention of
CMV viremia in at-risk populations. The chemical process employed to supply most of the phase III clinical
trials was based on a late-stage chiral resolution to obtain the desired steroisomer in the penultimate
intermediate (QP-DTTA). An evaluation of this process revealed several areas for improvement, including
a low overall yield of 10% due in part to a late stage resolution to access the sterogenic center, the use of
nine different solvents, and high palladium loading in a C-H activated Heck reaction.There was also little
opportunity to recycle solvents or reagents.
An early focus for improvement was to increase the efficiency of installing the single asymmetric quinazoline.
Six novel asymmetric reactions were proposed to introduce the stereogenic center with minimal use of
protecting groups, preventing waste on the molecular level. High-throughput reaction discovery tools
facilitated a rapid investigation of these six asymmetric transformations with hundreds of potential
catalysts and reaction conditions. High-throughput technology allowed for thousands of different reaction
conditions to be screened and analyzed in a fraction of the time normally needed and were carried out at the
sub-milligram scale, reducing the amount of solvent typically required for this type of investigation by at least
a factor of 10. Three out of the four successful routes required the use of non-sustainable and costly transition
metal catalysts (e.g. Pd, Ru, Rh) as well as expensive chiral ligands. As such, Merck focused its efforts on a
novel aza-Michael approach with an aspirational goal to develop an economical, stable and fully recyclable
organocatalyst to achieve this transformation in an asymmetric fashion.The new hydrogen bonding catalysts
were easily recovered and re-used.
This new synthesis reduces the process mass intensity (PMI) by 73%, decreases raw material costs by 93%,
and increases the overall yield by more than 60%. Merck estimates that this optimized process will result
in the elimination of more than 15,000 metric tons (MT) of waste over the lifetime of Letermovir. Life-cycle
assessment shows that the new process is expected to decrease the carbon footprint and water usage of the
product by 89% and 90%, respectively.
3 2017 Greener Synthetic Pathways Award

Greener Reaction Conditions Award
Amgen Inc. and Bachem
Green Process for Commercial Manufacture of Etelcalcetide Enabled by Improved Technology for Solid Phase
Peptide Synthesis
Innovation and Benefits
Amgen Inc., Cambridge, Massachusetts, in partnership with Bachem, Switzerland, is being recognized for improving
the process used to manufacture the active ingredient in Parsabiv™, a drug for the treatment of secondary
hyperparathyroidism in adult patients with chronic kidney disease.This improved peptide manufacturing process
reduces chemical solvent use by 71%, manufacturing operating time by 56%, and manufacturing cost by 76%.
These innovations could increase profits and eliminate 1,440 cubic meters of waste or more, including over
750 cubic meters of aqueous waste annually.
Peptides have gained increased interest as therapeutics over the last three decades, largely due to their
advantageous properties including high specificity and affinity, as well as superior safety and tolerance. These
properties make peptide drugs more desirable than small molecule drugs in certain diseases, such as cancer,
enzyme deficiency disorders, protein-dysfunction disorders, genetic and degenerative diseases, and infectious
diseases. Currently, there are over 60 Food and Drug Administration (FDA) approved peptide drugs on the
market and over 600 either in clinical trials or pre-clinical development. Peptide-based pharmaceuticals are
an important class of therapeutic agents with the potential to replace many existing small molecule-based
pharmaceuticals in the near future.
Compared to the manufacturing process of small molecule drugs, the environmental impact of this
technology has not garnered much attention, in part because the high potency of peptide drugs has rendered
supply needs significantly lower than traditional small molecule drugs. Recent investigations have revealed
that, on average, producing 1 kg of peptide requires over 5 metric tons of solvent, significantly higher than
most other types of synthetic small molecules.
Etelcalcetide was manufactured using a standard solid phase peptide synthesis manufacturing platform up to
the phase 3 trial stage, but the expected high demand for the product made full scale commercial production
problematic given the amount of materials needed and the waste generated. Amgen and Bachem redesigned
the manufacturing process to eliminate one of five stages and optimize the remaining four. This improved
process resulted in a 5-fold increase in manufacturing capacity and a 56% decrease in manufacturing time,
mitigating risks to drug supply. In addition, the new process reduced the amount of solvent, completely
eliminated an ion-exchange column process requiring over three liters of water for every gram of drug, and
reduced the number of energy intense lyophilization cycles from 13 per batch to one.
This new commercial manufacturing process was implemented and validated prior to drug approval. These
innovations will result in the annual elimination of more than 1440 cubic meters of waste, including over
750 cubic meters of aqueous waste. Additionally, the broad and general applicability of this improved peptide
manufacturing platform has been demonstrated for other peptide drug candidates.
2017 Greener Reaction Conditions Award 4

Designing Greener Chemicals Award
The Dow Chemical Company and Papierfabrik August Koehler SE
Breakthrough Sustainable Imaging Technology for Thermal Paper
Innovation and Benefits
Dow Chemical Company, Collegeville, Pennsylvania, in partnership with Papierfabrik August Koehler SE, Germany,
is being recognized for developing a thermal printing paper which eliminates the need for chemicals used to create
an image, such as bisphenol A (BPA) or bisphenol S (BPS). Thermal paper is used broadly throughout the world for
cash register receipts, tickets, tags, and labels. This technology reduces costs by creating records that do not fade,
even under severe sunlight, allowing the original document to be preserved for long term storage.The paper is
compatible with thermal printers currently in commercial use around the world.
Thermal paper is widely used for cash register receipts, tickets, tags, and labels. Direct thermal printers form
images by heating the paper, which contains a reactive combination of leuco dye and acidic developer. In the
presence of heat, the dye is protonated by the developer to create a color change from white to black. Current
thermal papers use chemicals such as free bisphenol A (BPA) and bisphenol S (BPS), which are more available
for human exposure than bisphenol polymerized into a resin.
The Dow Chemical Company and Koehler jointly developed a patented thermal paper technology that
completely eliminates the use of chemical developers (BPA or BPS) and other reactive chemistries. This new
thermal printing technology relies solely on the collapse of air voids in the paper coating during printing.
Polymer properties are tailored so that a physical change, rather than a chemical reaction, creates the image.
It is a commercially viable drop-in alternative for conventional thermal papers, avoids retailer and consumer
exposure to imaging chemicals, and does not fade even under severe sunlight. Using this technology,
documents such as medical records would not have to be photocopied for long term storage.
The new voided thermal paper is comprised of three layers, including a top opaque layer, a colored layer and
a base paper.The colored layer contains only polymeric binders and permanent pigments such as carbon
black. The opaque layer contains hollow particles that create air voids in the coating, allowing it to hide
the underlying dark colored layer. When heat is applied to the paper from the thermal print head, it causes
localized collapse of the hollow particles. The opaque coating then becomes transparent only where the
collapse has occurred and the underlying colored layer is visible and creates an image.
The polymer used in the opaque layer, ROPAQUE™ NT-2900 Opaque Polymer, is produced in full scale
commercial reactors.The paper has been tested at four stores owned by a small food chain in Germany and
at a home center in London in 2014. The technology has also received strong interest by larger chain stores. A
large-scale commercial roll-out is planned in 2017.
5 2017 Designing Greener Chemicals Award

Printed on 100% recycled/recyclable paper with a minimum of 50% post-consumer waste
A	Office of Pollution	June 2017
Prevention and
Toxics (7406M)