Trends in Green Chemistry Research between 2012 and 2022: Current Trends and Research Agenda

Chapter 8 - Introductory chapter: Understanding green chemistry principles for extraction of green solvents

Everyone is becoming more environmentally conscious and therefore, chemical processes are being developed with their environmental burden in mind. This also means that more traditional chemical methods are being replaced with new innovations and this includes new solvents. Solvents are everywhere, but how necessary are they? They are used in most areas including synthetic chemistry, analytical chemistry, pharmaceutical production and processing, the food and flavour industry and the materials and coatings sectors. However, the principles of green chemistry guide us to use less of them, or to use safer, more environmentally friendly solvents if they are essential. Therefore, we should always ask ourselves, do we really need a solvent? Green chemistry, as a relatively new sub-discipline, is a rapidly growing field of research. Alternative solvents - including supercritical fluids and room temperature ionic liquids - form a significant portion of research in green chemistry. This is in part due to the hazards of many conventional solvents (e.g. toxicity and flammability) and the significant contribution that solvents make to the waste generated in many chemical processes. Solvents are important in analytical chemistry, product purification, extraction and separation technologies, and also in the modification of materials. Therefore, in order to make chemistry more sustainable in these fields, a knowledge of alternative, greener solvents is important. This book, which is part of a green chemistry series, uses examples that tie in with the 12 principles of green chemistry e.g. atom efficient reactions in benign solvents and processing of renewable chemicals/materials in green solvents. Readers get an overview of the many different kinds of solvents, written in such a way to make the book appropriate to newcomers to the field and prepare them for the 'green choices' available. The book also removes some of the mystique associated with 'alternative solvent' choices and includes information on solvents in different fields of chemistry such as analytical and materials chemistry in addition to catalysis and synthesis. The latest research developments, not covered elsewhere, are included such as switchable solvents and biosolvents. Also, some important areas that are often overlooked are described such as naturally sourced solvents (including ethanol and ethyl lactate) and liquid polymers (including poly(ethyleneglycol) and poly(dimethylsiloxane)). As well as these additional alternative solvents being included, the book takes a more general approach to solvents, not just focusing on the use of solvents in synthetic chemistry. Applications of solvents in areas such as analysis are overviewed in addition to the more widely recognised uses of alternative solvents in organic synthesis. Unfortunately, as the book shows, there is no universal green solvent and readers must ascertain their best options based on prior chemistry, cost, environmental benefits and other factors. It is important to try and minimize the number of solvent changes in a chemical process and therefore, the importance of solvents in product purification, extraction and separation technologies are highlighted. The book is aimed at newcomers to the field whether research students beginning investigations towards their thesis or industrial researchers curious to find out if an alternative solvent would be suitable in their work.

Everyone is becoming more environmentally conscious and therefore, chemical processes are being developed with their environmental burden in mind. This also means that more traditional chemical methods are being replaced with new innovations and this includes new solvents. Solvents are everywhere, but how necessary are they? They are used in most areas including synthetic chemistry, analytical chemistry, pharmaceutical production and processing, the food and flavour industry and the materials and coatings sectors. However, the principles of green chemistry guide us to use less of them, or to use safer, more environmentally friendly solvents if they are essential. Therefore, we should always ask ourselves, do we really need a solvent? Green chemistry, as a relatively new sub-discipline, is a rapidly growing field of research. Alternative solvents - including supercritical fluids and room temperature ionic liquids - form a significant portion of research in green chemistry. This is in part due to the hazards of many conventional solvents (e.g. toxicity and flammability) and the significant contribution that solvents make to the waste generated in many chemical processes. Solvents are important in analytical chemistry, product purification, extraction and separation technologies, and also in the modification of materials. Therefore, in order to make chemistry more sustainable in these fields, a knowledge of alternative, greener solvents is important. This book, which is part of a green chemistry series, uses examples that tie in with the 12 principles of green chemistry e.g. atom efficient reactions in benign solvents and processing of renewable chemicals/materials in green solvents. Readers get an overview of the many different kinds of solvents, written in such a way to make the book appropriate to newcomers to the field and prepare them for the 'green choices' available. The book also removes some of the mystique associated with 'alternative solvent' choices and includes information on solvents in different fields of chemistry such as analytical and materials chemistry in addition to catalysis and synthesis. The latest research developments, not covered elsewhere, are included such as switchable solvents and biosolvents. Also, some important areas that are often overlooked are described such as naturally sourced solvents (including ethanol and ethyl lactate) and liquid polymers (including poly(ethyleneglycol) and poly(dimethylsiloxane)). As well as these additional alternative solvents being included, the book takes a more general approach to solvents, not just focusing on the use of solvents in synthetic chemistry. Applications of solvents in areas such as analysis are overviewed in addition to the more widely recognised uses of alternative solvents in organic synthesis. Unfortunately, as the book shows, there is no universal green solvent and readers must ascertain their best options based on prior chemistry, cost, environmental benefits and other factors. It is important to try and minimize the number of solvent changes in a chemical process and therefore, the importance of solvents in product purification, extraction and separation technologies are highlighted. The book is aimed at newcomers to the field whether research students beginning investigations towards their thesis or industrial researchers curious to find out if an alternative solvent would be suitable in their work.

Green chemistry which is the latest and one of the most researched topics now days has been in demand since 1990’s. Majority of research in green chemistry aims to reduce the energy consumption required for the production of desired product whether it may be any drug, dyes and other chemical compounds. It aims to reduce or even eliminates the production of any harmful bi-products and maximizing the desired product without compromising with the environment. The three key developments in green chemistry include use of super critical carbon di oxide as green solvent, aqueous hydrogen peroxide as an oxidizing agent and use of hydrogen in asymmetric synthesis. It also focuses on replacing traditional methods of heating with that of modern methods of heating like microwave radiations so that carbon footprint should be reduces as low as possible. This review emphasize on principle, methodology and recent applications of green chemistry. © 2011 IGJPS. All rights reserved.

Is there a role for green and sustainable chemistry in chemical disarmament and nonproliferation?

An educational workshop is proposed for undergraduate students in chemistry to consciousness-raising about their environmental responsibilities as future chemists. Since 1990s, green or sustainable chemistry has been implemented mainly in research [1]. However, the green chemistry principles are particularly relevant in industry and education, since they are focused on reduction/removal of reagents and dangerous residues, decreasing the energy consumption in chemistry processes and methods. In fact, UNESCO stablished the Decade of Education in Sustainable Development during the period 2005-2014. Since pedagogy on green chemistry can be the most effective way to awareness-raising to future scientific, teaching and professional community; this matter should be taken into consideration in the curricula of undergraduate students. Green chemistry teaching can be a challenge due to the complexity of sustainability factors involved, as well as socio-economic considerations [2]. In this sense, different metrics that evaluate the greenness of a chemical process can be used to conduct different activities and develop values and attitudes among students. Specifically, it is proposed the use of analytical eco-scale, developed by Galuszka et al [3]. In order to apply the eco-scale, the didactic methodology of workshop was used to seek the active participation of students. The planning followed included an introduction to green chemistry, the establishment of agreed objectives with the students, group activities for case studies, presentation of activities results, evaluation and conclusions. In particular, students evaluated some analytical methods from the point of view of green chemistry, applying the eco-scale. This tool awards penalty points according to type and volume of reagents, required instrumentation, used energy and generated residues. The reached value on the eco-scale is calculated as 100 minus the sum of the individual penalty points. Then analytical methods can be classified as excellent (> 75 points), acceptable (75-50) and inadequate (<50). This type of workshops makes the students understand and be aware of green chemistry when they perform laboratory practices, in relation for example with the amount of reagents used or the generation of residues. Additionally, undergraduate students work with recently published articles that especially motivate them. This application helps students to be critical with the laboratory practice, assessing the importance of their work in order to avoid environmental pollution or overspend of reagents or energy. The proposed activities were highly appreciated by the students, because they can learn themselves how to use metrics to assess the greenness of chemical processes. At the same time, it increases their motivation to study subjects related with chemistry and environment.

The principles of green chemistry (GC) can be comprehensively implemented in green synthesis of pharmaceuticals by choosing no solvents or green solvents (preferably water), alternative reaction media, and consideration of one-pot synthesis, multicomponent reactions (MCRs), continuous processing, and process intensification approaches for atom economy and final waste reduction. The GC's execution in green synthesis can be performed using a holistic design of the active pharmaceutical ingredient's (API) life cycle, minimizing hazards and pollution, and capitalizing the resource efficiency in the synthesis technique. Thus, the presented review accounts for the comprehensive exploration of GC's principles and metrics, an appropriate implication of those ideas in each step of the reaction schemes, from raw material to an intermediate to the final product's synthesis, and the final execution of the synthesis into scalable industry-based production. For real-life examples, we have discussed the synthesis of a series of established generic pharmaceuticals, starting with the raw materials, and the intermediates of the corresponding pharmaceuticals. Researchers and industries have thoughtfully instigated a green synthesis process to control the atom economy and waste reduction to protect the environment. We have extensively discussed significant reactions relevant for green synthesis, one-pot cascade synthesis, MCRs, continuous processing, and process intensification, which may contribute to the future of green and sustainable synthesis of APIs.

Green (sustainable) chemistry provides a framework for chemists, pharmacists, medicinal chemists and chemical engineers to design processes, protocols and synthetic methodologies to make their contribution to the broad spectrum of global sustainability. Green synthetic conditions, especially catalysis, are the pillar of green chemistry. Green chemistry principles help synthetic chemists overcome the problems of conventional synthesis, such as slow reaction rates, unhealthy solvents and catalysts and the long duration of reaction completion time, and envision solutions by developing environmentally benign catalysts, green solvents, use of microwave and ultrasonic radiations, solvent-free, grinding and chemo-mechanical approaches. 1,2,4-thiadiazole is a privileged structural motif that belongs to the class of nitrogen–sulfur-containing heterocycles with diverse medicinal and pharmaceutical applications. This comprehensive review systemizes types of green solvents, green catalysts, ideal green organic synthesis characteristics and the green synthetic approaches, such as microwave irradiation, ultrasound, ionic liquids, solvent-free, metal-free conditions, green solvents and heterogeneous catalysis to construct different 1,2,4-thiadiazoles scaffolds.

Recent years have seen a disheartening string of revelations in which everyday items once considered safe—food packaging, toys, clothes, furniture, electronic components, and many more products—are found to contain carcinogens, endocrine disruptors, and other harmful chemicals.1 Growing demand for healthier alternatives, already seen in food production and housing construction,2 is also happening at the building-block level of manufacturing, where so-called green chemistry represents a revolutionary change in preventing pollution and health problems starting at the chemical design stage. Many industry and government entities are beginning to espouse the principles of green chemistry on their websites and in public statements. Now comes the task of crafting policy to put those principles into action. The U.S. Environmental Protection Agency (EPA) defines green chemistry as “the design of chemical products and processes that reduce or eliminate the use or generation of hazardous substances. Green chemistry applies across the life cycle of a chemical product, including its design, manufacture, and use.”3 Green chemistry also aims to mitigate the type of uncertainty Alan Gold-berg, a professor of toxicology at the Johns Hopkins Bloomberg School of Public Health, recently described to The New York Times: “I can get [toxicity] information on only 20 percent of chemicals we interact with on a daily basis.”4 Of that 20%, he now says, he may be able to find information on overt toxicity for about half, but for details on specific effects such as developmental neurotoxicity, the figure shrinks toward zero. So what does green chemistry look like? Consider the example of pregabalin, the active ingredient in the neuropathic pain drug Lyrica®. Pfizer developed an alternative green-chemistry process that converted several steps of pregabalin synthesis from use of organic solvents to water. That reduced both health hazards and production heating requirements. With the new synthesis, waste from the process dropped from 86 kg of waste per kg product to 17 kg, and energy use dropped by 82%.5 Proponents say that’s how the field can offer a win–win–win solution: good performance, lower cost, and less environmental impact—what Richard Engler, program manager of the EPA Green Chemistry Program, calls the “triple bottom line.” For many, a standard is a logical next step. “At some point you have to go beyond a definition and principles,” says Engler. “I think that’s something the standard will enable.”

A special green chemistry course was offered at Grand Valley State University, GVSU, in 2006. Among other assignments, students designed an electronic survey probing the knowledge and the interest in learning about green chemistry. Over 1600 students responded. The responses to the questions “where did you hear about green chemistry” clearly showed the lack of green chemistry inclusion into the curricular program GVSU at that time. Under the driving force of the students’ interest and the imperative need to feel the gap between the traditional content of industrial processes teaching and the principles of green chemistry, we were compelled to change. The result is a new course, Green Chemistry and Industrial Processes, based on green industrial applications. It is a bridge between the principles of green chemistry and industrial processes currently in use, between traditional topics and real-life cases, provided by the global and the local economy. Partnership with local area businesses constitutes an ideal ground for challenging the students’ ability to analyze and understand the existing problems and to develop their critical thinking, while finding creative solutions. This communication summarizes one of the invited papers to the spring 2010 online ConfChem Conference on Educating the Next Generation: Green and Sustainable Chemistry, held from May 7 to June 30, 2010. ConfChem conferences are hosted by the ACS DivCHED Committee on Computers in Chemical Education (CCCE).

Abstract: Advancement in green synthetic methodologies has brought a revolution in heterocyclic synthesis. Green synthesis has bypassed the classical procedures involving toxic/hazardous solvents or catalysts and improved the current environmental safety standards by many folds. Green chemistry research has continuously made significant contributions to the development of heterocyclic scaffolds both at laboratory and commercial scales. Researchers are continuously developing and exploring the principles of green chemistry for the development of novel therapeutic agents. Quinoxaline lies in the category of versatile heterocyclic motifs, which possesses a wide diversity in its derivatives as well as a broad profile of its therapeutic potential. In the past decades, many new green synthetic protocols have been developed and employed successfully for the synthesis of quinoxaline derivatives. These include the use of reusable nanocatalysts, polymers, various green solvents, tonsils, catalysts, water as a catalyst, microwave irradiation, ultrasonic waves, non-toxic metal catalysts, surfactants, etc. The present review focuses on various green synthetic procedures reported for quinoxalines along with the specializations and applications of the reactions.

This study analyzes green chemistry research trends in chemistry education. This study used a quantitative bibliometric approach. The number of publications analyzed is 104 publication documents from 2019 – 2024. This research collects, processes, and filters information in Scopus journals and articles. Metadata results show that the distribution of publication frequency peaked in 2019, with 26 documents identified. The green chemistry research area is dominated by chemistry research (31.3%). The country with the most documents and the most productive in publishing green chemistry is the United States, with 30 papers identified. At the same time, Indonesia is ranked fifth as the most productive country in publishing green chemistry, with 10 documents identified. Canada ranked second with 17 papers, and Germany ranked third with 15 documents. The institutions that contributed the most came from Germany: the University of Bremen, with 11 papers 10.58%, and the University of Toronto with 8 documents (7.69%). The authors with the most citations are Chen Tse-Lun et al., with 245 citations. Meanwhile, when viewed from the number of documents published by the author, Eilks I. has 11 papers with a contribution of 4.91%. There are 5 clusters with the most popping keywords: green chemistry, human, and chemical reaction. Research and publications on this topic have been sparse in the past five years. Surveys and analyses of green chemistry literature are essential because tracking research trends in green chemistry in chemistry education is vital to directing the future.

We are grateful to Environmental Health Perspectives for implicitly embracing green chemistry as a field with profound connections to the environmental health sciences. We also commend the efforts of Wilson and Schwarzman (2009) to create greater transparency and accountability around chemicals of concern. We take issue, however, with their approach to key scientific concepts and terminology—specifically their effort to change the definition of “green chemistry.” Precision in terminology is paramount for science to function; all parties to a scientific discussion must share the same set of definitions for knowledge to advance effectively. In their review, Wilson and Schwarzman (2009) ignored the original and current definition of green chemistry, which for almost two decades has been recognized as a scientific discipline within the field of chemistry. Defined in the early 1990s by the U.S. Environmental Protection Agency (2009) as “the design of chemical products and processes that reduce or eliminate the use or generation of hazardous substances,” green chemistry is now guided by a set of 12 principles (Anastas and Warner 1998) that are used in both research and teaching in chemis try laboratories around the world. Based on these principles, dozens of universities around the world teach green chemistry as a science. Seven graduate programs offer degrees in green chemistry. Two established peer-reviewed scientific journals focus specifically on research in green chemistry. The impact factor of the journal Green Chemistry (published by the Royal Society of Chemistry) has increased from 2.5 to almost 5 over the past 5 years. More than 1,500 articles on green chemistry have been published in the scientific literature over the past 15 years. Rather than embracing green chemistry’s widely used scientific definition, Wilson and Schwarzman (2009) instead conflate science and policy: The laws governing the chemical enterprise help define the incentives and disincentives that guide economic behavior in the market …. We use the term green chemistry in this context: as an analytical framework that encompasses both the science of safer chemistry and the laws and policies that will motivate its development and adoption by society. This conflation brings with it two risks. First, it undermines clarity in scientific communication, something that is especially important as the fields of environmental health and green chemistry attempt to establish cross-disciplinary collaboration. Such collaborations are likely to prove vital for both fields. Second, it saddles the intellectual and scientific enterprise of green chemistry with policy and, potentially, political baggage, as considerations of chemical policies unfold in the political arena. We are most certainly not arguing that the science of green chemistry should not inform chemical policies. Science and policy will be more effective, however, if political actors do not muddy accepted scientific terminology in service of a political/policy agenda, no matter how noble.

This feature article summarises our recent contributions (2019-2023) in designing and developing a handful of promising organic transformations for accessing several diversely functionalised biologically relevant organic scaffolds, following the green chemistry principles, particularly focusing on the application of low-energy visible light, electrochemistry, ball-milling, ultrasound, and catalyst- and additive-free synthetic strategies.

The need to develop environmentally friendly analytical approaches has driven the pharmaceutical industry to seek greener alternatives. Ultra-Performance Liquid Chromatography (UPLC) is known for its efficiency but traditionally relies on toxic solvents. Integrating Green Analytical Chemistry (GAC) principles aims to address environmental concerns while maintaining analytical performance. This work aims to advance and authenticate a green, efficient UPLC method for the concurrent quantification of Metformin (MET) and Empagliflozin (EPI) in tablet formulations, adhering to green chemistry principles and ensuring high analytical accuracy. The method was optimized using a UPLC-PDA system with a phenyl column and a mobile phase of ethanol and perchloric acid. Analytical Quality by Design (AQbD) was employed to optimize critical method parameters. Environmental impact was assessed using metrics such as GAPI, AMGS, and AGREE. Degradation studies under various stress conditions were performed to test method robustness. The method achieved high recovery rates for MET and EPI, with minimal interference from excipients. The environmental evaluation showed a high Analytical Eco-Score (AES) of 97, indicating low environmental impact. The AGREE score of 0.89 confirmed excellent alignment with green chemistry principles. Degradation studies confirmed the method's stability and reliability under stress conditions. The developed UPLC method demonstrates a significant advancement in analytical sustainability, offering an eco-friendly, efficient, and precise approach to drug analysis. The method's high alignment with green chemistry principles and its effectiveness in quantifying MET and EPI highlight its potential as a model for sustainable analytical practices in pharmaceutical analysis.