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Green Chemistry

Inside this journal, see cutting-edge research for a greener sustainable future

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Green Chemistry  is a Transformative Journal, and Plan S compliant

Impact factor: 9.8*

Time to first decision (all decisions): 13.0 days**

Time to first decision (peer reviewed only): 35.0 days***

Chair: Javier Pérez-Ramírez

Indexed in Web of Science

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Journal scope

Green Chemistry provides a unique forum for the publication of innovative research on the development of alternative green and sustainable technologies. 

The scope of Green Chemistry is based on, but not limited to, the definition proposed by Anastas and Warner ( Green Chemistry: Theory and Practic e, P T Anastas and J C Warner, Oxford University Press, Oxford, 1998).  Green chemistry is the utilisation of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design, manufacture and application of chemical products.

Green Chemistry is at the frontiers of this  continuously-evolving  interdisciplinary science and publishes research that attempts to reduce the environmental impact of the chemical enterprise by developing a technology base that is inherently non-toxic to living things and the environment. Submissions on all aspects of research relating to the endeavour are welcome.

The journal publishes original and significant cutting-edge research that is likely to be of wide general appeal. To be published, work must present a significant advance in green chemistry.  Papers must contain a comparison with existing methods and demonstrate advantages over those methods before publication can be considered. For more information please see this Editorial .

Coverage includes the following, but is not limited to:

• Design (e.g. biomimicry, design for degradation/recycling/reduced toxicity…)
• Reagents & Feedstocks (e.g. renewables, CO 2 , solvents, auxiliary agents, waste utilization…)
• Synthesis (e.g. organic, inorganic, synthetic biology…)
• Catalysis (e.g. homogeneous, heterogeneous, enzyme, whole cell…)
• Process (e.g. process design, intensification, separations, recycling, efficiency…)
• Energy (e.g. renewable energy, fuels, photovoltaics, fuel cells, energy storage, energy carriers…)
• Applications (e.g. electronics, dyes, consumer products, coatings, pharmaceuticals, preservatives, building materials, chemicals for industry/agriculture/mining…)
• Impact (e.g. safety, metrics, LCA, sustainability, (eco)toxicology…)

Green chemistry is, by definition, a continuously-evolving frontier. Therefore, the inclusion of a particular material or technology does not, of itself, guarantee that a paper is suitable for the journal. To be suitable, the novel advance should have the potential for reduced environmental impact relative to the state of the art.  Green Chemistry  does not normally deal with research associated with 'end-of-pipe' or remediation issues.

Occasionally the Editors may decide to publish something outside the defined scope of the journal if the work would be of interest to the green chemistry community and/or have the potential to shape the field.

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Green Chemistry: What is the green advance?

One of the main requirements for papers to be published in Green Chemistry is to clearly demonstrate a green advance over the incumbent technology or approach. Past Editorial Board Chair, Philip Jessop (Queen's University, Canada), has put together two short videos to explain what this concept really means and how to incorporate it into your own work.  

This video explains that the green advance requirement at Green Chemistry is a benchmarking requirement. Benchmarking experiments run throughout science and that they need not be labour-intensive. Your paper must contain a comparison of your new method to the current best method available and describe the advantages and disadvantages. 

There are a range of benchmarking metrics that can be used to satisfy the green advance requirement at Green Chemistry. Ecotoxicity, Bioaccumulation, Carcinogenicity and Smog formation are some of the metrics that can be used to demonstrate the green advance. For more information, please watch the video below:  

See who's on the team

Meet our Chair and all other board members for the Green Chemistry journal.

Javier Pérez-Ramírez , ETH Zurich, Switzerland

Associate editors

Aiwen Lei , College of Chemistry and Molecular Sciences, The Institute for Advanced Studies, Wuhan University, P. R. China

Elsje Alessandra Quadrelli , CNRS and ESCPE Lyon, France

Magdalena Titirici , Imperial College London, UK

Keiichi Tomishige , Tohoku University, Japan

Luigi Vaccaro , University of Perugia, Italy

Editorial board members

André Bardow , ETH Zürich, Switzerland

Francois Jérôme , University of Poitiers, France

Jean-Paul Lange , University of Twente and Shell Projects & Technology, The Netherlands

Serenella Sala , European Commission - Joint Research Centre, Italy

Laurel Schafer , The University of British Columbia, Canada

Helen Sneddon , University of York, UK

Charlotte Williams , University of Oxford, UK

Tao Zhang , Dalian Institute of Chemical Physics, Chinese Academy of Sciences, China

Paul Anastas , Yale University, USA

Isabel Arends , TU Delft, Netherlands

Gregg Beckham , NREL, USA

Asim Bhaumik , Indian Association for the Cultivation of Science, India

Fabrizio Cavani , University of Bologna, Italy

James Clark , University of York, UK

Avelino Corma , UPV-CSIC, Spain

Robert H Crabtree , Yale University, USA

Paul Dauenhauer , University of Minnesota, USA

James Dumesic , University of Wisconsin-Madison, USA

Martin Eastgate , Bristol Myers Squibb, USA

Karen Goldberg ,   University of Washington, USA

Buxing Han , Institute of Chemistry, Chinese Academy of Sciences, China

Steve Howdle , Nottingham University, UK

Andrew J. Hunt,  Khon Kaen University, Thailand

Graham Hutchings , Cardiff University, UK

Philip Jessop , Queen's University, Canada

C Oliver Kappe , University of Graz, Austria

Shu Kobayashi , University of Tokyo,Japan

Burkhard Koenig , University of Regensburg, Germany

Michael Kopach , Lilly, USA

Walter Leitner , RWTH Aachen University, Germany

Chao-Jun Li , McGill University, Canada

Bruce Lipshutz , University of California, USA

Doug MacFarlane , Monash University, Australia

Tomoo Mizugaki , Osaka University, Japan

Regina Palkovits , RWTH Aachen, Germany

Alvise Perosa , Universita Ca Foscari, Italy

Martina Peters , Bayer AG, Germany

Martyn Poliakoff , University of Nottingham, UK

Colin Raston , Flinders University, Australia

Roberto Rinaldi , Imperial College London, UK

Robin D Rogers , McGill University, Canada

Susannah Scott , University of California, USA

Roger Sheldon , Delft University of Technology, The Netherlands

Christian Stevens , Ghent University, Belgium

Natalia Tarasova , Mendeleev University of Chemical Technology, Russia

Rajender Varma , US Environmental Protection Agency, USA

Tom Welton , Imperial College, UK

Kevin C. W. Wu , National Taiwan University, Taiwan

G D Yadav , Institute of Chemical Technology Mumbai, India

Hisao Yoshida , Kyoto University, Japan

Suojiang Zhang ,  Institute of Process Engineering, Chinese Academy of Sciences, China

Julie Beth Zimmerman , Yale School of Engineering and Applied Sciences, USA

Vânia Zuin Zeidler , Institute of Sustainable Chemistry Faculty/School of Sustainability, Leuphana University, Germany

Michael A. Rowan , Executive Editor

Vikki Pritchard , Deputy Editor

Bee Hockin , Development Editor

Andrea Carolina Ojeda-Porras , Development Editor

Gisela Scott , Editorial Production Manager

Robin Brabham , Senior Publishing Editor

Jeanne Andres , Publisher

Catherine Au , Publishing Editor

Isobel Darlington , Publishing Editor

Konoya Das , Publishing Editor

Alexandre Dumon , Publishing Editor

Amy Lucas , Publishing Editor

Kieran Nicholson , Publishing Editor

Rini Prakash , Publishing Editor

Charlotte Pugsley , Publishing Editor

Hugh Ryan , Publishing Editor

Daphne Houston , Editorial Assistant

Robert Griffiths , Publishing Assistant

Article types

Green Chemistry publishes:

Communications

Full papers, critical reviews, tutorial reviews, perspectives.

These must report preliminary research findings that are highly original, of immediate interest and are likely to have a high impact on the green chemistry community. Communications are given priority treatment, are fast-tracked through the publication process and appear prominently at the front of the journal in a dedicated Communications section.

The key aim of Communications is to present innovative chemical concepts with important implications. Authors should provide at the time of submission a short paragraph explaining why their work justifies urgent publication as a Communication. Ideally, a Full paper in Green Chemistry should follow each Communication.

These must represent a significant development in the particular field and are judged according to originality, quality of scientific content and contribution to existing knowledge. Although there is no page limit for Full papers, appropriateness of length to content of new science will taken into consideration.

These must be a critical evaluation of the existing state of knowledge on a particular facet of green chemistry; however, original work may be included. Simple literature surveys will not be accepted for publication. Potential review writers should contact the editor before embarking on their work.

Tutorial reviews are a type of review that provide an essential introduction to a particular area of green chemistry. The article should have particular appeal to younger researchers and established researchers seeking new fields to explore. Tutorial reviews should not contain unpublished data.

These may be articles providing a personal view of part of one discipline associated with Green Chemistry or a philosophical look at a topic of relevance.

Comments and Replies are a medium for the discussion and exchange of scientific opinions between authors and readers concerning material published in Green Chemistry .

For publication, a Comment should present an alternative analysis of and/or new insight into the previously published material. Any Reply should further the discussion presented in the original article and the Comment. Comments and Replies that contain any form of personal attack are not suitable for publication. 

Comments that are acceptable for publication will be forwarded to the authors of the work being discussed, and these authors will be given the opportunity to submit a Reply. The Comment and Reply will both be subject to rigorous peer review in consultation with the journal’s Editorial Board where appropriate. The Comment and Reply will be published together.

Journal specific guidelines

All submissions should include evidence of the green advance that the work presents. This should also be highlighted in a cover letter.

All papers must be written so as to be widely accessible (conceptually) to a broad audience of chemists and technologists as well as, for example, final year undergraduates.

If toxic or otherwise potentially harmful solvents, reagents or materials are used, authors need to ensure that alternatives have been checked or their use can be justified by other technical reasons. For further information on the use of solvents please refer to: CHEM21 selection guide of classical- and less classical-solvents’ by Denis Prat et. al., Green Chem ., 2016, 18 , 288-296. DOI: 10.1039/C5GC01008DJ .

It is the responsibility of authors to provide fully convincing evidence for the homogeneity, purity and identity of all compounds they claim as new. This evidence is required to establish that the properties and constants reported are those of the compound with the new structure claimed. Referees will assess, as a whole, the evidence presented in support of the claims made by the authors. The requirements for characterisation criteria are detailed below.

Organic compounds

Authors are required to provide unequivocal support for the purity and assigned structure of all compounds using a combination of the following characterisation techniques.

Analytical Elemental analysis (within ±0.4% of the calculated value) is required to confirm 95% sample purity and corroborate isomeric purity. Authors are also encouraged to provide copies of 1 H, 13 C NMR spectra and/or GC/HPLC traces. If satisfactory elemental analysis cannot be obtained, copies of these spectra and/or traces must be provided.

For libraries of compounds, HPLC traces should be submitted as proof of purity. The determination of enantiomeric excess of nonracemic, chiral substances should be supported with either SFC/GC/HPLC traces with retention times for both enantiomers and separation conditions (that is, chiral support, solvent and flow rate) or, for Mosher Ester/Chiral Shift Reagent analysis, copies of the spectra.

Physical Important physical properties, for example, boiling or melting point, specific rotation, refractive index, etc, including conditions and a comparison to the literature for known compounds should be provided. For crystalline compounds, the method used for recrystallisation should also be documented (that is, solvent etc).

Spectroscopic Mass spectra and a complete numerical listing of 1 H, 13 C NMR peaks in support of the assigned structure, including relevant 2D NMR and related experiments (that is, NOE, etc.) is required. Authors are encouraged to provide copies of these spectra. Infrared spectra that support functional group modifications, including other diagnostic assignments should be included.

High-resolution mass spectra are acceptable as proof of the molecular weight provided the purity of the sample has been accurately determined as outlined above. The synthesis of all new compounds must be described in detail.

Synthetic procedures must include the specific reagents, products and solvents and must give the amounts (g, mmol, for products; % for all of them), as well as clearly stating how the percentage yields are calculated. They must include the 1 H, 13 C and MS data of this specific compound.

For multistep synthesis papers, spectra of key compounds and of the final product should be included.

For a series of related compounds, at least one representative procedure that outlines a specific example that is described in the text or in a table, and which is representative for the other cases, must be provided.    

For all soluble polymers an estimation of molecular weight must be provided by a suitable method (for example, size exclusion chromatography, including details of columns, eluents and calibration standards, intrinsic viscosity, MALDI TOF, etc.) in addition to full NMR characterisation ( 1 H, 13 C) - as for organic compound characterisation (see above).

The synthesis of all new compounds must be described in detail. Synthetic procedures must include the specific reagents, products and solvents and must give the amounts (g, mmol, for products; % for all of them), as well as clearly stating how the percentage yields are calculated. They must also include all the characterisation data for the prepared compound or material.

For a series of related compounds, at least one representative procedure which outlines a specific example that is described in the text or in a table, and which is representative for the other cases, must be provided.

Inorganic and organometallic compounds

A new chemical substance (molecule or extended solid) should have a homogeneous composition and structure. New chemical syntheses must unequivocally establish the purity and identity of these materials.Where the compound is molecular, minimum standards have been established.

For manuscripts that report new compounds or materials, data must be provided to unequivocally establish the homogeneity, purity and identification of these substances. In general, this should include elemental analyses that agree to within ±0.4% of the calculated values.

In cases where elemental analyses cannot be obtained (for example, for thermally unstable compounds), justification for the omission of this data should be provided. Note that an X-ray crystal structure is not sufficient for the characterisation of a new material, since the crystal used in this analysis does not necessarily represent the bulk sample.

In rare cases, it may be possible to substitute elemental analyses with high-resolution mass spectrometric molecular weights. This is appropriate, for example, with trivial derivatives of thoroughly characterised substances or routine synthetic intermediates.

In all cases, relevant spectroscopic data (NMR, IR, UV-vis, etc.) should be provided in tabulated form or as reproduced spectra. Again, these may be relegated to the electornic supplementary information (ESI) to conserve journal space. However, it should be noted that in general mass spectrometric and spectroscopic data do not constitute proof of purity, and in the absence of elemental analyses additional evidence of purity should be provided (melting points, PXRD data, etc.).

Experimental data for new substances should also include synthetic yields, reported in terms of grams or moles, and as a percentage.Where the compound is an extended solid it is important to unequivocally establish the chemical structure and bulk composition. Single crystal diffraction does not determine the bulk structure. Referees will normally look to see evidence of bulk homogeneity.

A fully indexed powder diffraction pattern that agrees with single crystal data may be used as evidence of a bulk homogeneous structure and chemical analysis may be used to establish purity and homogeneous composition. The synthesis of all new compounds must be described in detail. Synthetic procedures must include the specific reagents, products and solvents and must give the amounts (g, mmol, for products; % for all of them), as well as clearly stating how the percentage yields are calculated. They must also include all the characterisation data for the prepared compound or material.

For a series of related compounds, at least one representative procedure that outlines a specific example that is described in the text or in a table, and which is representative for the other cases, must be provided.

Nano-sized materials (such as quantum dots, nanoparticles, nanotubes, nanowires)

For nano-sized materials it is essential that the authors not only provide detailed characterisation on individual objects (see above) but also a comprehensive characterisation of the bulk composition. Characterisation of the bulk of the sample could require determination of the chemical composition and size distribution over large portions of the sample.The synthesis of all new compounds must be described in detail.

Synthetic procedures must include the specific reagents, products and solvents and must give the amounts (g, mmol, for products; % for all of them), as well as clearly stating how the percentage yields are calculated. They must also include all the characterisation data for the prepared compound or material. For a series of related compounds, at least one representative procedure that outlines a specific example described in the text or in a table, and that is representative for the other cases, must be provided.

Biomolecules (for example, enzymes, proteins, DNA/RNA, oligosaccharides, oligonucleotides)

Authors should provide rigorous evidence for the identity and purity of the biomolecules described. The techniques that may be employed to substantiate identity include the following.

• Mass spectrometry
• Sequencing data (for proteins and oligonucleotides)
• High field 1 H, 13 C NMR
• X-Ray crystallography.

Purity must be established by one or more of the following.

• Gel electrophoresis
• Capillary electrophoresis
• High field 1 H, 13 C NMR.

Sequence verification also needs to be carried out for nucleic acid cases involving molecular biology. For organic synthesis involving DNA, RNA oligonucleotides, their derivatives or mimics, purity must be established using HPLC and mass spectrometry as a minimum.

For new derivatives comprising modified monomers, the usual organic chemistry analytical requirements for the novel monomer must be provided (see Organic compounds section above). however, it is not necessary to provide this level of characterisation for the oligonucleotide into which the novel monomer is incorporated.

Open access publishing options

Green Chemistry  is a hybrid (transformative) journal and gives authors the choice of publishing their research either via the traditional subscription-based model or instead by choosing our gold open access option.  Find out more about our Transformative Journals. which are Plan S compliant .

Gold open access

For authors who want to publish their article gold open access , Green Chemistry  charges an article processing charge (APC) of £2,750 (+ any applicable tax). Our APC is all-inclusive and makes your article freely available online immediately, permanently, and includes your choice of Creative Commons licence (CC BY or CC BY-NC) at no extra cost. It is not a submission charge, so you only pay if your article is accepted for publication.

Learn more about publishing open access .

Read & Publish

If your institution has a Read & Publish agreement in place with the Royal Society of Chemistry, APCs for gold open access publishing in Green Chemistry  may already be covered.

Use our journal finder to check if your institution has an open access agreement with us.

Please use your official institutional email address to submit your manuscript and check you are assigned as the corresponding author; this helps us to identify if you are eligible for Read & Publish or other APC discounts.

Traditional subscription model

Authors can also publish in Green Chemistry  via the traditional subscription model without needing to pay an APC. Articles published via this route are available to institutions and individuals who subscribe to the journal. Our standard licence allows you to make the accepted manuscript of your article freely available after a 12-month embargo period. This is known as the green route to open access.

Learn more about green open access .

Readership information

The journal appeals to a broad international readership spanning many communities, including all academic and industrial scientists interested in the development of alternative sustainable technologies.

Subscription information

Green Chemistry  is part of the RSC Gold subscription package. Online only 2024 : ISSN 1463-9270, £2,784 / $4,907

*2022 Journal Citation Reports (Clarivate Analytics, 2023)

**The median time from submission to first decision including manuscripts rejected without peer review from the previous calendar year

***The median time from submission to first decision for peer-reviewed manuscripts from the previous calendar year

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Green Chemistry  

About Green Chemistry

The home of cutting-edge research on the development of alternative sustainable technologies. Editorial Board Chair: Javier Pérez-Ramírez Impact factor: 9.8 Time to first decision (peer reviewed only): 35 days

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• v.24(12); 2021 Dec 17

Green and sustainable chemistry – The case for a systems-based, interdisciplinary approach

David j.c. constable.

1 American Chemical Society Green Chemistry Institute, 1155 16th St. N.W., Washington, DC 20036, USA

Although the concepts underpinning green chemistry have evolved over the past 30 years, the practice of green chemistry must move beyond the environmental and human health-related roots of green chemistry towards a more systems-based, life cycle-informed, and interdisciplinary practice of chemistry. To make a transition from green to sustainable chemistry, one must learn to think at a systems level; otherwise green chemistry-inspired solutions are unlikely to be sustainable. This perspective provides a brief description of why the current situation needs to change and is followed by how life cycle thinking helps chemists avoid significant systems-level impacts. The transition from batch to continuous flow processing and novel approaches to isolation and purification provide a case for interdisciplinary collaboration. Finally, an example of end-of-useful-life considerations makes the case that systems and life cycle thinking from an interdisciplinary perspective needs to inform the design of new chemical entities and their associated processes.

Graphical abstract

• • Green and sustainable chemistry must include a systems and life cycle perspective
• • Green and sustainable chemistry requires extensive interdisciplinary collaboration
• • Catalysis, purification and isolation, and batch to flow processing are discussed

Chemistry; Organic chemistry; Green chemistry; Green engineering

Introduction

For much of the past 30 years, green chemistry has been largely identified with two central ideas: the reduction or elimination of toxic substances and pollution prevention ( U.S. E.P.A, 2021 ). Much of what has been written and spoken about green chemistry is rooted in environmentalism, environmental policies, and governmental regulations promulgated since the 1980's. For the period between 1995 and about 2010, proponents of green chemistry struggled with being seen as a legitimate part of chemistry within the traditional chemistry community for many reasons, but three stand out. The first is that green chemistry was seen as being environmentally-related, applied, and not innovative. The second is that because of the association with the environment, it was seen as more of an environmental movement and not science ( Breyman and Woodhouse, 2005 ). The third is that many in industry felt that they had been doing the pollution prevention aspects incorporated in green chemistry for many years, but especially through the 1970's and 1980's ( Murphy, 2018 , 2020 ).

When considering chemistry research from a green chemistry perspective, another challenge to chemistry researchers in traditional chemistry disciplines is the necessity of drawing from multiple scientific and engineering disciplines to not only understand the underlying chemical and physical phenomena, but to better understand why the current approaches to chemistry need to change ( Constable, 2017 ; Whitesides, 2015 ; Matlin, et al., 2016 ). Similar to non-traditional chemistry fields like biochemistry and nanochemistry, to be successful in green chemistry-related research, one must draw from many different disciplines.

I would also say that this need for an interdisciplinary approach is amplified as one moves from a singular focus on green chemistry to one that incorporates a consideration of two related ideas, sustainability and sustainable development. For the purposes of this article and the current argument, sustainability will be confined to thinking about environmental sustainability; i.e., actions and behaviors one must take to ensure that the chemistry being practiced is not creating current or generational environmental impacts. It should be understood that the use of the term sustainability typically envisions a “triple bottom line” approach that includes a concurrent consideration of environmental, societal and economic impacts ( Elkington, 2018 ), but such considerations are generally not embraced by the chemistry community which fails to see the point or necessity of connecting molecular-scale chemical phenomena to macro-scale impacts. The most frequent definition of sustainable development is from “Our Common Future,” also known as the Brundtland Report ( World Commission on Environment and Development, 1987 ), and is “Sustainable Development is development that meets the needs of the present without compromising the needs of future generations to meet their own needs.” The practice of chemistry is inherently rooted in the present and by design, on a time scale of less than a second to perhaps hours. In addition, for many academic research chemists and the institutions that fund them, “real” chemistry is decoupled from any notion of application or development; it is science to advance the science of chemistry, not to fulfill the needs of human society.

Therefore, to make a transition from green chemistry to sustainable chemistry, one must learn to think at a systems level, otherwise green chemistry-inspired solutions are unlikely to be sustainable. Although systems thinking is routinely taught in a variety of scientific and engineering disciplines, it has only recently been introduced to chemistry educators as something that needs to be included in chemistry education ( Mahaffy, et al., 2018 , 2019 ). There are a variety of definitions for systems thinking in science, engineering, social, and organizational contexts, and an agreed, or authoritative, or standard definition of a system or systems thinking for the chemistry context has yet to be established ( York and Orgill, 2020 ). In essence, it is best to understand a system as being a logical construct or model of real-world phenomena that contains a collection of components or parts. These components are coherently organized and interconnected in patterns or in a structured and usually hierarchical manner to produce a characteristic set of behaviors, often classified as the system's “function” or “purpose,” or to answer a question related to systems outputs and outcomes. The study of changes in the state of a system over time and space are included in what is known as systems dynamics. Although it is beyond the scope of this article to discuss the details of systems thinking, one should appreciate that systems are everywhere, of different scales, and usually a part of a system of systems. This connectedness of system components with and between other systems is generally not explicitly seen as being a part of chemistry and that is one reason why systems thinking is critical to understanding how to practice green and sustainable chemistry.

Systems thinking also helps one to manage the complexity that is inherent to sustainability and the implementation of green and sustainable chemistry ( Constable, et al., 2019 ). Figure 1 shows a systems-level view of chemical evaluation. An important point to be made about thinking in systems within the chemistry context is that this should be accompanied by life cycle thinking, i.e., a consideration of environmental safety and health hazards and risks associated with the constituents of a material or product. Chemical trees may be used to visualize the gate-to-gate manufacturing processes and an inventory made of the associated inputs, outputs, and emissions for each step leading to the constituent parts of a material or product, from raw material extraction to a factory gate. Once the product is made, life cycle thinking considers a similar input/output inventory for the distribution, use and end-of-life phases of the product. In recent years, the end-of-life phase is increasingly incorporating a consideration of recycling/reuse and impacts related to waste management to advance the circular economy ( Kirchherr et al., 2017 ). In a full life cycle inventory/assessment, there is a detailed, quantitative accounting for all the impacts and these impacts are combined into discrete categories (e.g., greenhouse gas equivalents, etc.) where they may be assessed for their cumulative impacts for the material or product life cycle. As is hopefully evident, life cycle thinking requires one to think of the material, process, or product in terms of a system of systems where the output of the life cycle is limited to the cumulative environmental impacts associated with the material or product. As important as life cycle thinking is, it should be understood that systems thinking is a broader, more comprehensive and holistic approach to considering material, process, or product benefits and impacts.

Systems-level view of chemical evaluation

Life cycle and systems thinking should be practiced as complementary and synergistic lines of thinking. Merely formalizing a benchtop chemical reaction, or industrial chemical process, as a system, without consideration of a molecule's system and life cycle impacts defeats the purpose of systems thinking for green chemistry. Systems thinking also requires an interdisciplinary approach if one is to understand sustainability drivers and to correctly define the system, draw meaningful boundaries, recognize causal and feedback loops, and see the inter-system interactions that are common to considerations of sustainability. Chemistry impacts, and is impacted by, human/social systems, economic systems, and environmental systems. Figure 2 contains some, but by no means all, of the professions and skills that might contribute to systems thinking in chemistry and the system-of-systems supporting chemistry. Sustainable chemistry, to be successful, requires one to develop disciplinary skills outside of chemistry, and partner routinely with other scientists, engineers, businesses, and many other non-science-based professions. If a chemist does not do this, they will never arrive at a sustainable solution to chemical problems.

Contributors to systems thinking for green and sustainable chemistry

The remainder of this article highlights a few key considerations and the interdisciplinary needs associated with selected aspects of making molecules from a mostly bioactive molecule perspective e.g., pharmaceuticals or crop protection agents. Green chemistry in the minds of many has been popularized as a limited number of easily accomplished practices a chemist needs to do to make a molecule green, greener, or more sustainable. If that was truly the case, there would be less of a reason to still be discussing the rationale for practicing and implementing green, greener, and now, more sustainable chemistry. What follows are several illustrations to show chemists need to employ systems thinking. The first is a high-level overview of some sustainability pitfalls of modern catalysis and what is needed to make it more sustainable. The second illustration is the underlying need to move as many batch chemical operations currently done in batch to a flow regime as warranted. The third illustration concerns the isolation, work-up and purification of biologically active molecules and the general need to reduce the impacts associated with this common operation. Finally, the case is made for chemists to develop a greater understanding of the life cycle impacts associated with the choices chemists make at the bench, pilot and process level, and work collaboratively with other scientists and engineers to make chemistry greener and more sustainable while addressing the world's grand challenges of sustainability ( National Research Council, 2006 ).

Catalysis - metal and organometallic catalysts are generally not sustainable

It is probably best to use a short example to illustrate how systems thinking that includes an interdisciplinary mindset might be applied. One that immediately comes to mind is catalysis, which most will recognize as one of the 12 Anastas and Warner principles: “Catalytic reagents (as selective as possible) are superior to stoichiometric reagents ( Anastas and Warner, 1998 ).” Catalysis is enormously important to the petrochemical and chemical processing industries, with many products relying on one or more catalytic steps in their synthesis routes. The use of catalysis is almost always considered to be green. From the earliest journal articles pertaining to green chemistry and in green chemistry-related programming at ACS National Meetings and Green Chemistry and Engineering conferences, catalysis has represented a significant part of the scientific discourse around green chemistry. Much of this discourse has been related to discoveries in catalysis where, for example, metal salts, zeolites, or complex organometallic compounds are used.

With respect to metals like Zn, Sn, Co, Ni, etc., or the transition metals centered around platinum on the periodic table that are used in organometallic catalysts, environmental and occupational toxicologists help the chemist understand environmental and human health hazards and risks. Interestingly, the greenness of the organometallic catalyst synthesis itself, where large or complex ligands are made using hazardous reagents, and difficult, inefficient, multi-step syntheses are common, is not featured in most catalysis discussions. Or, the catalytic reaction requires the use of reagents like triphenylphosphine, organoboranes, or similarly activating reagents that are not only mass inefficient, but hazardous. Moreover, many of these catalysts are only active as homogeneous catalysts; their binding to an inert substrate renders them less active or inactive. And while some in academic research think about catalyst recovery, homogeneous catalyst recovery and reuse remains technically difficult and largely an afterthought.

From a sustainability, systems, and life cycle perspective, the type and chemical nature of the catalyst matters. Where and how the metals, the reagents, chemicals, and solvents are sourced, the reaction conditions required for the catalysis to proceed, the disposition of these components in use and in final disposal, should all be carefully considered. At this point, a sustainability minded green and sustainable chemist should in the first instance be thinking about delivering catalytic function in some other way than organometallic catalysts, perhaps considering how the chemical transformation could be carried out enzymatically or with organocatalysts. Instead of creating an organometallic enzyme mimic, evolve an enzyme. Secondarily, if you have to use a precious metal catalyst, develop protocols that reduce the quantity of metal required to the ppm level as has been done with, e.g., performing reactions in micellar aqueous solutions using nanoparticulate, earth-abundant iron (Fe) particles containing low concentrations of the precious metals ( Lipshutz, 2017 ; Lipshutz et al., 2018 ; Romney, et al., 2018 ).

Transitioning from batch to flow

Outside of the laboratory and in a manufacturing environment, there are two main types of chemical processing technologies that are used in the chemical and allied industries. These are batch chemical operations carried out in multi-purpose chemical plants to produce low tonnages of chemicals, and chemical processing in flow, such as are found in large, high-volume petrochemical operations. The operation of chemistry in flow within the large petrochemical operations is dominated by chemical engineering expertise whereas batch chemical operations are dominated by process chemists and in many respects, are scaled-up laboratory operations. High-volume, petrochemical flow operations are also characterized by comparatively chemically simpler reactions taking place and with higher efficiency in terms of low mass and energy intensity, but it would be wrong to conclude that the control of these reaction spaces is unsophisticated. In fact, there is a high degree of automation and sophistication in the design of the reaction system and its control technology to ensure heat and mass transfer and reaction kinetics are optimized to achieve required high process mass and energy efficiencies for low-margin commodity chemicals. Higher process mass and energy efficiency is a key measure of greenness although it is only one part of it.

As there is a push towards converting more batch chemical operations to flow ( Ding, 2018 ) to take advantage of the unrealized potential in chemical reaction technologies such as photochemistry ( Noel, 2017 ; Halperin, et al., 2015 ), electrochemistry ( Noël et al., 2019 ; Tanbouza et al., 2020 ) and others ( Glasnov and Kappe, 2011 ; Dallinger and Kappe, 2017 ), there will be a need for greater interdisciplinary collaboration, especially between chemists and chemical engineers, to achieve the required level of quality or purity, cost, sophistication in design, and reaction control for molecules that are inherently more complex. Because the volumetric demand for chemicals is relatively smaller in batch operations compared to petrochemical or commodity chemical flow operations, the process trains will be much smaller, modular, highly automated, and in many respects, more technologically complex. It should be understood that flow is not a batch chemical panacea for making processes greener or more sustainable, especially if a chemist uses highly hazardous reactants and reagents as suggested by some ( Gutmann et al., 2015 ), or there is a reduction in overall process efficiency. One challenge in the transition from batch to flow is the frequent need for larger volumes of solvent to ensure the appropriate flow regime. This is a decidedly unwelcome trade-off in making a process greener or more sustainable especially if in-process and out-of-process recycle and reuse options ( Chea et al., 2020 ) are limited.

Isolation and purification

Isolation and purification, especially in batch chemical operations for small molecules (MW < 750), accounts for a significant portion of the total process mass intensity ( Jimenez-Gonzalez et al., 2011 ). Process mass intensity is a very good proxy for energy and the associated life cycle environmental impacts associated with batch processes because at least 80% of the mass is organic solvents and water. Isolation and purification in most cases entails solvent and water removal via distillation in multiple steps of the synthesis process and distillation is the main driver of energy intensity in batch process operations. Given this fact, there are currently few strategies that one can employ to overcome the mass intensity associated with isolation and purification. The first obvious one is to do as few isolations and purifications as possible. The second would be to employ one-pot, multi-step syntheses, but this is very difficult to do in practice at scale for a variety of competing reasons beyond the scope of this article.

To optimize a multi-step process requires a close collaboration between process chemists and engineers to select solvents, use as few solvent classes as possible across multiple steps, avoid azeotropes and emulsions, optimize reflux or near-reflux conditions for extended reactions at high temperatures, and finally, optimize distillation in the process and solvent recovery. As with the preceding examples, there needs to be a close collaboration between process chemists and chemical engineers who are generally better trained in distillation, azeotrope formation, and process optimization.

As bioactive molecules common to the pharmaceutical industry, e.g., oligonucleotides, polypeptides, antibodies, drug-antibody conjugates, etc., become much larger and more prevalent, isolation and purification across compound synthesis and manufacture becomes an even bigger driver of process mass intensity ( Isidro-Llobet et al., 2019 ; Andrews et al., 2021 ). Solvent use is greater and the separation technology changes to solid phase linking and large-scale chromatographic processing in the place of distillation. Opportunities to green this kind of process are more limited ( Bryan et al., 2018 ; Jiménez-González et al., 2000 ) and will require the development of novel synthetic approaches and more efficient chromatographic processing, but once again, close collaboration between chemists and chemical engineers will be highly beneficial.

Towards avoiding life cycle impacts

Most chemists I encounter have little idea about how the basic chemicals and framework molecules they use are made at an industrial scale and they do not they possess an intuitive sense of the life cycle environmental impacts associated with chemicals or the molecules they synthesize. In my opinion, every chemist should employ life cycle thinking as noted in the introduction, but the ability to perform a modular cradle-to-gate life cycle inventory/assessment ( Jiménez-González et al., 2000 , 2001 ; Jiménez-González and Overcash, 2000 ) is a skill a chemist is well advised to develop, or they should partner with someone (usually a chemical engineer) who can perform one. I say modular cradle-to-gate methodologies purposefully since these approaches are the only ones that visualize how chemicals are built through the chemical processing steps that lead to the desired molecule, chemical, or product. Every element in the periodic table, and every chemical, has a history with origins that are spread across the world. Although I think chemists understand the elements that appear on a periodic table don't originate at a local chemical supplier, they don't typically know which minerals or ores are mined and the chemical purification processes that are used to obtain the pure elements or salts they use in their experiments. Modular cradle-to-gate life cycle inventory/assessment methodologies enable one to see inputs and outputs each step of the journey from raw material extraction through each processing step.

Different functional groups on molecules provide a desired property or function in a chemical process or product, but their presence may also have adverse effects on living organisms, the facilities we work in, and the environment. Chemists need to be trained to recognize functional groups and structural motifs that lead to hazardous properties (environmental, safety, and human health) and make a conscious effort to avoid them. This is an important point that should be repeated in a different way. Chemists currently accept the inherent hazard of many molecules as just the way chemistry is done; i.e., the chemistry system is inherently hazardous and there is no other way to do chemistry but through the use of highly hazardous substances. Chemists should recognize and pursue ways to change the chemistry system to one that has minimal adverse impacts and promotes a more sustainable planet.

To understand and avoid negative life cycle impacts associated with chemical process inputs and outputs, a chemist must rely on other disciplines like toxicology, where chemical interactions with, and effects on, living organisms are studied ( DeVito, 1996 ; Anastas, 2016 ; Maertens et al., 2014 ). Regardless of the science or engineering discipline or sub-discipline, the common theme is that the chemistry, chemical mechanisms, and chemical technology govern a system's processes and outcomes. Understanding environmental chemistry, the molecular drivers of eco- or human toxicology, environmental fate (where chemicals distribute; i.e., air, water, and land), etc., are all dependent on a good understanding of fundamental chemistry, chemical properties, and chemical phenomena. What other science and engineering disciplines like toxicology, molecular genetics, safety engineering, chemical engineering, public health experts, etc. should provide to the research and development chemist is continuing insight and molecular design guidance that would enable the chemist to avoid problematic molecular structural motifs, functional groups, and other chemical and physico-chemical properties that lead to environmental, safety, and health impacts. A chemist needs to know how to understand, interpret, and apply these environmental, safety, and health data and most importantly, to avoid the use of materials that are hazardous. This is an important point worth repeating in a different way; the status quo of the chemistry system means that chemists routinely, knowingly, and purposefully use hazardous materials (environmental safety and health) to make new molecules and this simply is not sustainable.

End of useful life

Humanity is using an ever-increasing quantity of materials and energy to drive its pursuit of affluence. To put this into perspective, in 1900, global material use was estimated to be 7.1 Gt per year, which increased to 70 Gt by 2010 ( Krausmann et al., 2017 ). Sadly, most materials moving through a modern economy become waste in a short period of time. Obviously, this is not all chemical waste, but a significant proportion of it is related to energy, and chemical production does require a significant amount of energy. Among OECD countries, it is estimated that 1.75 million metric tons of solid waste are produced every day, whereas on a global scale, solid waste is projected to grow from 3.5 million metric tons/day in 2010 to 6 million metric tons/day in 2025 ( Hoornweg et al., 2013 ). This is a somewhat sobering realization and there are at least two main ideas worth pondering. The first is that managing this waste and moving from a linear to a circular economy where waste is reused is only now becoming a topic of serious consideration and will require multiple disciplines to overcome the profound challenges involved. Green chemistry has always been associated with the reduction or elimination of waste through pollution prevention by source reduction, but the scope of that has typically been limited to manufacturing, not the rest of the product life cycle. Moreover, manufacturing waste is something that is disposed of and it becomes someone else's problem, not something that is repurposed or reused, so there's a psychological barrier to overcome.

An additional burden for waste reuse in the pharmaceutical realm is the institutional imperative surrounding the purity of the drug substance. This is completely understandable in that no one wants an impurity appearing in the final formulation containing the active pharmaceutical ingredient that has not been previously observed, characterized, and has passed through all clinical testing proving it does not have any adverse impacts on the patient. Purity is clearly a design constraint for the system that produces a pharmaceutical product. An unintended consequence of this, however, is that solvent recycling can be perceived as a potential source for the introduction of impurities in the final drug substance, and solvent recycling is generally not considered to be a design constraint for the pharmaceutical product system. Solvent recycling does of course occur in the pharmaceutical industry ( Tiwari, 2019 ), but the industry also incinerates a large amount of solvent and water to avoid potential issues like pharmaceuticals in the environment or human health impacts. Analogous concerns are associated with food production and personal care products like cosmetics.

The second big idea is that apart from food, most products are made to be durable since product durability is greatly valued by society. Simply put, there is a desire for the products on the market to retain their original as-manufactured appearance and functionality for as long as possible. Another way to say this is that the system that produces a product is constrained by the perceived value of durability. The implications of this for chemists is that the chemistry subsystem that is part of the pharmaceutical product system sets molecular design constraints to synthesize new molecules that are difficult to degrade chemically, through physical processes, or through biological processes that are a part of human and environmental systems. Designing chemicals, and the products we make from chemicals, to deliver a desired function at a robust performance level for only as long as we need them, and then have a low-energy, low-mass process to return them to raw materials, should be a design constraint for every product system, and it is a problem that chemistry alone will not solve. The chemistry subsystem of the product systems needs to be informed by biology to know, e.g., common microbiological degradation mechanisms; by environmental science to understand the fate and effects of chemicals and predict environmental risk; by engineering to assist with treatment and closing the loop; by business to help make the business case; by waste management practices to seek opportunities for design for circularity, etc.

In the case of pharmaceuticals that are small molecules (MW < 750), because most are designed to survive the digestive system, to make it to the desired organ and produce the intended effect, have reasonable shelf lives, i.e., be resistant to photochemical degradation and/or humidity, etc., they are very durable and retain their bioactivity, which has led to increased concerns about the presence of pharmaceuticals in the environment ( Kümmerer, 2010 ; aus der Beek et al., 2016 ). Ideally, pharmaceuticals would produce the desired physiological effect only for as long as they are in our body and then they and their metabolites would degrade into benign products. For many of these molecules, the design for stability system constraint during the use phase of their life cycle means that the molecule does not readily degrade in the environment during its end-of-useful-life phase of their life cycle, although in most cases it will be inherently biodegradable over time. By contrast, large pharmaceutical molecules like oligonucleotides, peptides, monoclonal antibodies, and other macromolecular molecules have very selective physiological effects and they are readily biodegradable during the end-of-useful-life phase of their life cycle although they have a much larger process mass intensity in the manufacturing phase of their life cycle than a small molecule. As can be seen, a change in the pharmaceutical product system to these large molecules involves a few environmental trade-offs, but the larger process mass intensity associated with these larger molecules is likely to be reduced over time through changes in synthesis technology, adoption of semi-synthetic approaches and better water management practices.

Conclusions

For chemistry to thrive in the future, it needs to be increasingly focused on meeting the needs of the world as envisioned through the U.N. Sustainable Development Goals ( United Nations, 2015 ). Chemistry and chemical engineering are absolutely essential to society's ability to achieve these goals given the considerable amount of work to be accomplished. As essential as these two science and engineering disciplines are, it is also essential for chemists to think in terms of the systems that are impacted by the chemicals and materials they make, and they must draw on a wide range of disciplines to ensure that the most sustainable chemistry and chemical engineering are accomplished; they cannot act in isolation or only for the advance of the discipline. To reiterate, in order to make a transition from green to sustainable chemistry, chemists must learn to think at a systems level; otherwise green chemistry-inspired solutions are unlikely to be sustainable. Moreover, there is no doubt that the world will need to innovate in chemistry and related disciplines at an unprecedented rate to avoid major reductions in quality of life. As a recently published patent analysis revealed, the rate of green and sustainable chemistry-related U.S. patents has held steady at about 1.2% per year for the past 30 years ( Constable, 2020 ) and this suggests change in the status quo is essential. The flip side of the waste dilemma noted previously is the ever-increasing and unprecedented rate of material extraction to meet societal demands that are directly correlated with increasing affluence in many nations throughout the world. Without a change in the material and energy intensity of our collective affluence, the future looks anything but sustainable. Chemists and chemical engineers working in collaboration and partnership with their science and engineering peers have an enormous role to play in making the world more sustainable.

Declaration of interests

The author declares no competing interests.

Inclusion and diversity

While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list.

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Industrial applications of green chemistry: Status, Challenges and Prospects

• Review Paper
• Published: 23 January 2020
• Volume 2 , article number  263 , ( 2020 )

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• Rajni Ratti 1  

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Green Chemistry is expanding its wings from academic laboratories to industrial units. Sustainable practices include replacement of volatile organic solvents which constitute the bulk of a reaction material, developing recyclable catalysts, developing energy efficient synthesis and encouraging the use of renewable starting material. By following the principles of green chemistry, turn-over of many companies have increased immensely leading to both environmental as well as economic benefits. This review explores various examples wherein green chemistry has enhanced the sustainability factor of industrial processes immensely and suggests the measures which should be taken to promote as well as popularize the green practices in synthesis.

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1 Introduction

The 20th century has seen a phenomenal growth of global economy and a continuous improvement of standard of living in the industrialized countries. The increasingly competitive economic outlook and the shrinking graph of natural resources on the planet pose an urgent need to reduce the energy expenditure as well the production of waste. Sustainability is one of the main drivers for innovations in order to allow the technical industries to work for the well-being of consumers in a safe and healthy environment. The most attractive concept towards achieving sustainability is “Green Chemistry”—a term coined at United States Environmental Protection Agency by Anastas and Warner [ 1 ], and is defined as the utilization of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design, manufacture and application of chemical products [ 2 , 3 , 4 ]. The term ‘hazardous’ is used in its broadest context which includes physical (e.g. explosive, flammable), toxicological (e.g. carcinogenic, mutagenic) and global (e.g. ozone depletion, climate change) factors. The tools of green chemistry are alternative feedstock, solvents and reagents, and catalytic versus stoichiometric processes. Developing green methodologies is a challenge that may be viewed through the framework of the “Twelve Principles of Green Chemistry” (Designed by P.T. Anastas and Warner).

2 The twelve guiding principles of green chemistry

Since its inception in early 1990s, green chemistry has grown into a significant, internationally engaged focus area within chemistry [ 5 , 6 , 7 , 8 ]. Green chemistry is basically a proactive approach aimed at designing a synthesis/process in a sustainable way right from the beginning. Preventing waste formation rather than devising methods to cleaning it up, developing atom efficient technologies based on renewable feedstock using minimum energy requirements and inherently safer chemicals, discouraging the use of volatile organic solvents and replacing them by greener alternatives are the main aims of green chemistry. To develop sustainable processes stoichiometric reagents should be replaced by catalytic reagents, end products should be bio-degradable and analytical methodologies should allow real time in-process monitoring. It is not always possible to incorporate all the principles in a particular process, however efforts should be made to follow as many principles as possible.

3 Industrial applications of green chemistry

Green Chemistry is not a lab-curiosity; instead it aims at big objective of creating a sustainable tomorrow. Increasing number of green methodologies developed by academic and industrial researchers enables companies to commercialize these ideas. Industry, from small businesses to large corporations, has already made strategic moves towards sustainability by adopting the principles of green chemistry. The development of less hazardous processes and commercial products, the shift from inefficient chemical routes towards bio-based synthesis, and the replacement of oil-based feed stocks by renewable starting materials are only a few examples of the major decisions taken that will ultimately have vast consequences for the world chemical markets.

As per the analysis of Environmental Protection Agency, the US drug industry has decreased the use of VOCs by 50% between 2004 and 2013 by adopting principles of green chemistry. In the same time span, the amount of chemical waste released to air, land and water decreased by 7% as per Toxics Release Inventory (TRI) of EPA.

Recently four industrial drug units located in Hyderabad region of India has been closed on account of creating pollution [ 9 ]. China, too, has strict environmental concerns and has taken regulatory action on 40% of the industrial units located in thirty provinces [ 10 ]. These changes in policy suggest that it has become imperative to follow green practices.

Plastics, in spite of several uses, have a bad reputation owing to their origin from polymers derived from non-renewable petrochemicals and their non-bio-degradable nature. However, the same can be made from renewable feedstock as shown by a study carried out by Utrecht University [ 11 ]. Studies by Utrecht University also show that the market of bio-plastics will grow by approximately 37% per year till 2013 and at a rate of 6% between 2013 and 2020. Many marketing hubs have joined the initiative to replace plastics with bio-plastics. Wal-Mart has been using bio-plastics in packaging wherever possible [ 12 ]. On similar lines Nokia, a mobile making company, used 50% bio-plastics in Nokia 3111 Evolve phone cover as well as in Nokia C7 phone [ 13 ].

Procter & Gamble replaced most of the PVC based materials with greener alternatives [ 14 ]. Along with other companies P&G have taken the initiative to develop new solvents so as to replace volatile organic carbons in glossy paints.

Greener synthesis of Ibuprofen launched by BASF involves half the number of steps as compared to traditional method. Atom efficiency of new process is almost double than the old synthesis. In pursuit for the development of sustainable methodologies, BASF developed BASIL™ (Bi-phasic Acid scavenging utilizing ionic liquids) process involving the production of generic photo initiator precursor alkoxyphenylphosphine [ 15 ]. Using this technology the yield increased from 50 to 98%.

The Warner Babcock institute for Green Chemistry has developed a green hair-dye “Hairprint” which is a non-toxic, vegetable based product providing an alternative to the toxic, skin irritating and carcinogenic dyes [ 16 ].

USA based Merck & Co., Inc. has successfully applied the principles of green chemistry to the synthesis of antiviral drug (cytomegalovirus infection) Letermovir which is currently in phase III of clinical trials. Cytomegalovirus (CMV) is a common virus whose infections are generally asymptomatic in healthy individuals but can cause severe damage in patients with immuno-depressed systems. The importance of this drug can be judged from the fact that it has been granted Fast-Track status by FDA and Orphan product designation by European Medicine agency for the prevention of CMV viremia in high risk population.

An evaluation of its traditional synthesis scheme revealed several areas for improvements like a very low overall yield of 10% due to a late stage resolution to access a stereogenic center, the use of nine different solvents, high palladium loading in Heck coupling. Moreover, no recycling of solvents and reagents had been there in the scheme.

Greener synthesis, as published by Merck, involves a novel cinchonidine based PTC-catalyzed Aza-Michael reaction for configuring the single stereocenter as shown in Scheme 1 [ 17 ]. Also, there is an increase in overall yield by 60%, reduction in raw material cost by 93% and reduction in water usage by 90%. It has been estimated that, once operational, this optimized process will lead to reduction of more than 15,000 MT of waste over the life time of Letermovir. Life-Cycle Assessment reveals that the green process is expected to decrease the carbon foot-print by 89%. It is quite evident from the green synthesis of Letermovir that the Green Chemistry is not only environmentally friendly but also economically lucrative. This scheme has won the EPA’s Presidential green chemistry award under the category “Greener synthetic pathways” in 2017 [ 18 ].

Green synthesis of Letermovir

Of the various technologies used in green chemistry, biocatalysis holds an important place [ 19 ]. Most of the reactions occurring in physiological systems are catalyzed by enzymes which are nature’s catalysts. Enzymes are not only biodegradable but are renewable as well due to the ease of production by fermentation of sugar etc. In order to achieve the aims of sustainability, more and more companies are working in the area of designing and using enzymes as biocatalysts. An impressive case highlighting the impact of biocatalysis on pharmaceutical manufacturing is the greener synthesis of Pregabalin, an active ingredient of neuropathic pain reliever Lyrica ® . In 2008, Pfizer improved the classical route for the synthesis of Pregabalin by adopting biocatalysis as a key step which led to 90% reduction in solvent usage, 50% reduction in the requirement of raw materials besides energy savings [ 20 ]. Solvent and energy saving in the process is equivalent to reducing 3 million tons of CO 2 emissions which is actually equivalent to taking 1 million Indian cars off the road for a year. Schemes  2 and 3 compare the classical and greener route for the synthesis of pregabalin.

Conventional synthesis of Pregabalin

Enzyme catalyzed synthesis of Pregabalin

Not only in drug synthesis, biocatalysts also find important applications in the synthesis of plastics. Now a days, research is mainly targeted towards the synthesis of biodegradable plastics from renewable resources.

California based start-up “Newlight Technologies”, founded in 2003, took a funding of $9.2 million for developing a carbon negative technology that combines air with methane emissions to produce Aircarbon™ a thermoplastic. Aircarbon™ is approximately 40% oxygen from air and 60% carbon and hydrogen from methane emissions. The technology itself was not new but the use of a proprietary biocatalyst by Newlight Technologies made it actually commercially viable by increasing the yield nine times and decreasing the cost by a factor of three thereby making Aircarbon cheaper than oil based plastics. With the commercial scale-up in 2013, Aircarbon™ was adopted by a number of leading brands like Dell, Hewlett-Packard, IKEA, Sprint, The Body Shop and Vinmar for manufacturing their respective products. In recognition of the company’s commercial achievements, Newlight was named “Most innovative company of the year” in 2013 and Aircarbon™ was named “Tech innovation of the year” by The American Business Awards [ 21 ]. For the green attributes of the process involving capturing and using greenhouse gases, Newlight technologies has been awarded the prestigious EPA’s Presidential Green Chemistry Challenge award in 2016 [ 22 ].

Most chemical processes involve solvents in the reaction and separation step to dissolve solids, reduce viscosity, modulate temperature, and recover products by means of extraction or recrystallization as reaction media or for cleaning purposes. Solvents not only dissolve the reactants but they also affect the rates, chemo-, regio- and stereoselectivities of reaction. However, majority of the organic solvents used in industry, despite their inherent advantages, are associated with several ill-effects on human health and environment. Moreover, these solvents are derived from non-renewable resources like petroleum. These parameters are in contradiction to the very basics of Green Chemistry. Due to these reasons, the only alternative available is to substitute these environmentally harmful solvents with some benign solvents. Hungerbuhler et al. [ 23 ] discussed the following four directions towards the development of green solvents

Substitution of hazardous solvents with one that show better EHS (Environment, Health, Safety) properties such as increased biodegradability or reduced ozone depletion potential [ 24 ].

Use of “bio-solvents” i.e. solvents produced from renewable resources such as ethanol produced by fermentation of sugar-containing feeds, starchy feed materials or lignocellulosic materials [ 25 ].

Substitution of organic solvents with supercritical CO 2 in polymer processing avoids the use of chlorofluorocarbons, and reduces the ozone depletion [ 26 ].

With ionic liquids that show low or negligible vapour pressure, and thus fewer emissions to air [ 27 ].

Fabric dyeing consumes a lot of water. About 7 gallons of water is used up to dye a T-shirt and lot of energy is wasted in drying the dyed material. A Dutch start-up recently launched water-free dyeing using supercritical carbon dioxide as a solvent under pressure and at elevated temperature. As no water is used so energy required in drying is also saved [ 28 ].

Elevance Renewable Sciences, Inc., used a nobel prize winning metathesis technology developed by Grubb’s to produce two green solvents

In collaboration with the surfactant manufacturer Stepan, Elevance produced a surfactant called STEPOSOL MET-10U as a replacement for N-methyl pyrrolidone and dichloromethane in adhesive removers and paint strippers. This surfactant can also be used in household and industrial cleaners in place of glycol ethers. STEPOSOL MET-10U is a unique unsaturated di-substituted amide derived from a bio-based feedstock [ 29 ]. With a Kauri-Butanol value greater than 1000, STEPOSOL MET-10U provides superior cleaning performance and is environmentally friendly due to a low vapor pressure, high boiling point, and Biorenewable Carbon Index (BCI) of 75%.

Another heavy-duty green degreasing solvent developed by Elevance Renewable Sciences is Elevance Clean™ 1200 which is a VOC free bio-based solvent [ 30 ]. In 2015, Elevance Clean™ 1200 was awarded bio-based product innovation of the year at WBM bio business awards for its out-standing cleaning performance. Being produced from natural oils this non-flammable solvent meets the various restrictive environmental regulations. Therefore, Elevance Clean™ 1200 is

VOC exempt (Directive 2004/42/CE of the European Parliament and the Council)

REACH registered

Readily biodegradable (by OCED method)

Free of components listed in the EU dangerous substances directive (Regulation No. 1272/2008).

The various advantages of Elevance Clean™ 1200 are enlisted below

Strong solvency characteristics greater than even of d-limonene, dibasic esters, vegetable esters and isoparaffins on the Kauri butanol (Kb) scale.

Excellent performance across a broad range of cleaning applications which includes metal cleaning, industrial and institutional degreasing, transportation and food processing.

Being non-flammable, it is easy to handle. It works very well in the neutral pH range (6–9) thereby eliminating the need of caustic cleaning products.

In 2014, Solberg Company won the first Insight Innovation award at the 3 rd annual THINC for its environmentally-friendly fire-fighting foam concentrate RE-HEALING. Conventional firefighting foams use fluorinated surfactants which are hazardous for the environment. The RE-HEALING firefighting foam concentrate use a blend of non-fluorinated surfactants, sugars, solvent and corrosion inhibitor leading to far less environmental impacts. Control, extinguishing time, and re-ignition resistance are necessary for the safety of fire-fighters and RE-HEALING fulfills all these conditions. The company also won the 2014 EPA Presidential Green Chemistry award for this innovation. [ 31 ].

Using catalytic reagents over stoichiometric reagents is one of the principles of green chemistry. Developing recyclable and recoverable catalyst adds to the green profile of a technology. Exhausts from the automobile engines pose a major threat to the environment. Inside the engine, temperature being very high, oxygen and nitrogen react to form nitric oxide (NO). Conversion of NO to NO 2 is highly desirable for the removal of oxides of nitrogen. However, this reaction is, in general, quite slow. A team of scientists from U.S, China and South Korea developed the catalyst using Mn-Mullite (Sm, Gd) Mn 2 O 5 –manganese–mullite materials containing either Samarium or Gadolinium to convert the toxic diesel engine exhaust product nitric oxide to a more benign nitrous oxide [ 32 ]. Over a range of temperatures, the new catalyst performed better than platinum (around 64% better at 300 °C and 45% better at 120 °C).

RCHEM Pvt. Ltd. Hyderabad, in collaboration with Chaudhuri et al. [ 33 ] developed a green synthesis of anti-ulcer drug Ranitidine. The conventional synthesis generates dimethylsulfide which is a hazardous to human health. Prof. Chaudhuri, from IIT Guwahati, and Prof. Kantam from IICT Hyderabad developed vanadium-titanium and titanium phosphorous based solid supported catalysts. In the presence of these heterogeneous catalysts H 2 O 2 acts as an oxidant to convert the dimethylsulfide to colourless odourless liquid dimethyl sulfoxide (DMSO). The DMSO generated is further used in the manufacturing process of drug thereby reducing the cost of production by 20%.

There are numerous applications where green chemistry has marched beyond the research laboratories and finding commercial applications. However, a lot more efforts are required, particularly in the area of life-cycle analysis so as to evaluate the environmental impact of the various “green” drugs after these traverses the human physiological system. Terry Collins, from the University of Pittsburg, developed a series of tetra-amido macrocyclic ligand based catalysts modelled on peroxidase enzymes [ 34 ]. Collins proposed that addition of these at a late stage in the sewage treatment process could help break down a wide variety of chemical residues from the drugs before they can affect the environment.

4 Challenges

Just being green is not enough for a process to be a commercial success. Regulatory, economic, political and technical challenges often impede the industrial implementation of a green process.

Current regulations are focused on reducing risk through reductions in exposure while green chemistry promotes the reduction of inherent risk by reduction of hazard. In U.S, the regulations require that every time a manufacturer changes the production process, it has to undergo a re-certification process with the FDA. This process is both costly and time- consuming, and hence serves to dissuade firms that would otherwise invest in developing atom efficient chemistries that reduce waste. Changes to more benign processes are inhibited by cost-intensive, control-oriented regulation. Lack of awareness among the different stake-holder groups poses a barrier to the implementation of green processes. Developing a successful green process is not only about green chemistry, it involves the knowledge of green engineering, biotechnology, economics and above all toxicology. The chemists generally lack the training in these disciplines which further hampers the implementation of green chemistry on an industrial scale. Even if all factors are the in the favour of a green process, it can be rejected on a commercial-scale if it fails to be economically attractive. Green industrial processes should be comparable to the traditional processes in terms of costs of the products.

There are a number of examples of technically robust, environmentally-friendly processes that have been started at first but were withdrawn at a later stage due to commercial implications. It does not always pay to be green in the chemicals sector. Thomas Swan and Company in Consett, UK, implemented the work of Martyn Poliakoff (Nottingham University), to start world’s first continuous-flow reactor using supercritical carbon dioxide as a solvent [ 35 ]. Sc-CO 2 system lead to selective hydrogenation of isophorone to 3,3,5-trimethylcyclohexanone without any by-product formation. This lead to elimination of an expensive and energy-intensive separation required by the conventional technique. But due to the lack of government subsidies, the plant could not provide chemicals more cheaply than those made by the traditional non-green methods. Therefore, after commercially running from 2002 to 2009, this plant was taken out of production.

Similar things happen with the process involving isomerization of 3,4-epoxybut-1-ene to 2,5-dihydrofuran in a phosphonium iodide ionic liquid developed by Eastman Chemical Company.

Capital investment also prevents the commercialization of a green technology. IFP (France) used ionic liquids, as solvent as well as co-catalyst, on a large scale for the nickel catalyzed dimerization of alkenes, named as Difasol process [ 36 ]. This is a biphasic process wherein the product forms a separate layer above the ionic liquid layer and thus can be easily separated. Compared to the conventional Dimersol process, this method has many advantages like better catalytic activity, ease of separation of product, better dimer selectivity and higher reactor space time yields. However, the cost of capital equipment posed a hurdle towards its commercial implementation.

The commercialization of green processes also requires many changes in all part of the long and global supply chain. Eden Organic foods developed a BPA-free coating for food packaging which was found to be compatible with some foods like beans but not for highly acidic tomato sauce. Switching to different coating type for different food type implies a smaller market size and change in manufacturing machines and consequently a higher cost. The implementation of such initiatives requires that everyone in the value chain agrees and is willing to accept the changes.

As most of the industries have been driven by monetary profits therefore voluntary adoption of the sustainable practices seems less feasible. A strong, attractive and balanced regulation is required so as to enforce the greener practices. The most promising and significant regulation is the REACH (Registration, Evaluation, Authorization and Restriction of Chemical substances) regulation framed and launched by European Union in 2007 [ 37 ]. On one hand REACH makes it mandatory for the chemical companies to disclose more information on the environmental and health risks of their products; on the other hand it grants potential exemptions on registration for five years for a process which favours new sustainable innovation. This move of European Union has motivated other countries to devise similar regulations so as to create a sustainable chemical industry.

5 Prospects

Green chemistry holds the key to a sustainable society. It has the inherent potential to bridge the gap between society and science. Innovations, backed by sound policies and regulations, will accelerate the large-scale implementation of green processes. Next generation of chemists should be taught the basics of green chemistry at a very early stage so that they can think green and develop safer methodologies. Interdisciplinary and multidisciplinary research can help in solving the various technical hurdles for commercializing this philosophy. Subsidizing the greener initiatives and tax exemptions to the companies adopting green processes will have a positive impact. Industries should realize the fact that getting a new greener process registered and making capital investment is a one-time investment which can have positive impacts on various aspects of society and environment. Collective and sincere efforts by researchers, engineers, corporates and policy- makers can actually make the chemistry Green.

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Ratti, R. Industrial applications of green chemistry: Status, Challenges and Prospects. SN Appl. Sci. 2 , 263 (2020). https://doi.org/10.1007/s42452-020-2019-6

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• Omar M. Yaghi

MOF-derived nanoporous carbons with diverse tunable nanoarchitectures

Direct carbonization of zeolitic imidazolate framework-type metal-organic frameworks, as described in this protocol, results in nanoporous carbons that can be used for diverse electrochemical applications.

• Ruijing Xin
• Yusuke Yamauchi

Radical generation and fate control for photocatalytic biomass conversion

This Review summarizes advanced photocatalytic systems for value-added chemical production from renewable biomass, with specific attention on the efficient strategies for controlling the generation of key radical intermediates and their subsequent conversion towards desired chemicals.

• Zhipeng Huang
• Nengchao Luo

Integrating sustainability into scientific research

Laboratories have a large environmental impact, with high levels of resource consumption and waste generation. In this article, the author discusses some of the actionable strategies that can bring real and impactful improvements, encompassing education, community engagement and the adoption of best practices by researchers. Building a global culture of sustainability in science will be crucial to reducing the carbon footprint of laboratories.

• Namrata Jain

Lignin as a multifunctional photocatalyst for solar-powered biocatalytic oxyfunctionalization of C–H bonds

The pulp and paper industry produces approximately 50 million metric tons of lignin per year as a waste product. Here, lignin is shown to act as a photocatalyst for the solar-driven synthesis of hydrogen peroxide from H 2 O and O 2 under visible light. Coupling this photocatalytic process with unspecific peroxygenases enables the enantioselective oxyfunctionalization of C–H bonds.

• Jinhyun Kim
• Trang Vu Thien Nguyen
• Chan Beum Park

Critical enzyme reactions in aromatic catabolism for microbial lignin conversion

For microbial industrial lignin conversion, a key challenge is to overcome rate-limiting steps in the upper pathways of aromatic catabolism. This Review discusses the critical enzymatic reactions of aromatic O -demethylation, decarboxylation and hydroxylation for lignin valorization via biological funnelling.

• Erika Erickson
• Alissa Bleem
• Gregg T. Beckham

Graphene oxide and starch gel as a hybrid binder for environmentally friendly high-performance supercapacitors

Environmentally friendly binders for energy materials may improve sustainability, but can suffer from poor performance. Here a gel derived from graphene oxide and starch is used as a hybrid binder for supercapacitors, providing good rate performance and stability over 17,000 cycles.

• Mario Rapisarda
• Frank Marken
• Michele Meo

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