Green Chemistry Metrics Research Articles

New One-Pot Methods for Preparation of Cyclohexanecarbonitrile—Green Chemistry Metrics Evaluation for One-Pot and Similar Multi-Step Syntheses

Three new multi-step one-pot processes for high-yielding cyclohexanecarbonitrile synthesis starting from cyclohexanone were developed for industrial application. In contrast to the current synthetic process, all of the processes described were designed to proceed completely in methanol as a uniform solvent and the key oxidation step can be realized either as stoichiometric or catalytic. Atom efficiency of processes is relatively advanced with high regioselectivity, reaction by-products are either from environmental pool—carbon dioxide and nitrogen—or they can be reused—sodium chloride. Solvent—methanol—and other auxiliaries—cyclohexane, copper catalyst—can be reused after recycling as well. EcoScale for all three designed processes was evaluated and compared with current synthesis described in the past. Green chemistry metrics, including newly introduced evaluative tool—Sustainability Index of the Synthesis (SIS), were applied to evaluate design of described one-pot syntheses.

Using metrics and sustainability considerations to evaluate the use of bio-based and non-renewable Brønsted acidic ionic liquids to catalyse Fischer esterification reactions

Ionic liquids have found uses in many applications, one of which is the joint solvation and catalysis of chemical transformations. Suitable Brønsted acidic ionic liquids can be formed by combining lactams with sulphonic acids. This work weighs up the relative benefits and disadvantages of applying these Brønsted acidic ionic liquid catalysts in esterifications through a series of comparisons using green chemistry metrics. A new bio-based ionic liquid was synthesised from N-methyl pyrrolidinone and p-cymenesulphonic acid, and tested as a catalyst in three Fischer esterifications under different conditions. An evaluation of the performance of this Brønsted acidic ionic liquid was made through the comparison to other ionic liquid catalysts as well as conventional homogeneous Brønsted acids. Extending the argument to feedstock security as well as mass utilisation, ultimately in most instances traditional mineral acids appear to be the most sensible option for Brønsted acid esterification catalysts. Ester yields obtained from Brønsted acidic ionic liquid catalysed procedures were modest. This calls into question the diversity of research exploring esterification catalysis and the role of ionic liquids in esterifications.

Holistic Metrics for Assessment of the Greenness of Chemical Reactions in the Context of Chemical Education

Two new semiquantitative green chemistry metrics, the green circle and the green matrix, have been developed for quick assessment of the greenness of a chemical reaction or process, even without performing the experiment from a protocol if enough detail is provided in it. The evaluation is based on the 12 principles of green chemistry. The performance of these metrics was evaluated for several syntheses made in our laboratory, under different sets of conditions. They were compared with a more complex set of metrics, assembled previously in our work, the green star, which was used to validate these new tools. These new metrics are useful for curricula designers and teachers in the evaluation and selection of green chemistry experiments. They are also appropriate for students to use in the context of chemical education for evaluating their experiments. These new metrics seem adequate to stimulate the incorporation of green chemistry in the teaching environment.

The use of environmental metrics to evaluate green chemistry improvements to the synthesis of (S,S)-reboxetine succinate

The Pfizer Green Chemistry metrics program is described and exemplified with a case history involving the synthesis of (S,S)-reboxetine succinate. The initial route used a classical resolution approach and generated high levels of waste. This route was replaced by an enantiospecific synthesis which used Sharpless epoxidation chemistry, an enzymatic process to selectively protect a primary alcohol and a new efficient method of chiral morpholine construction as key steps. These improvements reduced the levels of waste produced by the synthesis by more than 90%. Detailed metrics starting from a common starting material (trans-cinnamyl alcohol) for all routes of synthesis are presented.

A comparison of green chemistry metrics for two methods of bromination and nitration of bis-pyrazolo[3,4-b;4′,3′-e]pyridines

Abstract Green chemistry metrics (E-factor, atom economy, reaction mass efficiency) and the EcoScale have been compared for conventional heating and microwave assisted bromination and nitration of bis-pyrazolo[3,4-b;4′,3′-e]pyridines. The major advantages in microwave-assisted reactions in relation to traditional evaluation of the process have encompassed higher yields, shorter reaction time and higher selectivity. The microwave-assisted reactions have shown better green chemistry parameters and EcoScale ranks than those in conventionally heated reactions. Mass reaction efficiency values have been critical for considering ‘green’ the reactions conducted under traditional conditions. Additional advantages of using microwaves, not considered in calculated parameters, include easier purification of the reaction mixture and isolation of the product.

Green Chemistry and Green Engineering: A Framework for Sustainable Technology Development

Green chemistry and engineering seek to maximize efficiency and minimize health and environmental hazards throughout the chemical production process. This review demonstrates how green chemistry principles and metrics can influence the entire life cycle of a chemical from design through disposal. After reviewing essential metrics and recent advances in the field within this context, we consider the case of nanotechnology. As an emerging field, nanotechnology provides an instructive framework to consider the influence and application of green chemistry. Interdisciplinary innovation guides both fields, and both seek to transform the nature of technology. The applications and implications of emerging green technology are discussed, and future opportunities for interdisciplinary collaborations are highlighted.

Analytical Method Volume Intensity (AMVI): A green chemistry metric for HPLC methodology in the pharmaceutical industry

Analytical Method Volume Intensity (AMVI), a simple metric developed to measure the total solvent consumption of an HPLC method, can help chemists make informed decisions on how to lower an analytical method's environmental impact.

“Green Star”: a holistic Green Chemistry metric for evaluation of teaching laboratory experiments

This paper presents a new semi-quantitative metric, Green Star (GS), for evaluation of the global greenness of chemical reactions used in teaching laboratories. Its purpose is to help choose the more acceptable reactions for implementing Green Chemistry (GC) and to identify suitable modifications of protocols to improve the greenness of the chemistry practiced by students. GS considers globally, in principle, all the Twelve Principles of GC. The metric consists in the evaluation of the greenness of the reaction for each principle by pre-defined criteria, followed by graphical representation of the results in an Excel radar chart – the fuller the chart, the higher degree of greenness. To illustrate the construction and the scope of the metric, a case study is presented – the iron(II) oxalate dihydrate synthesis performed under several sets of conditions to pursue the implementation of greenness.

ChemInform Abstract: The Development of an Ecofriendly Procedure for Alkaline Metal (II) Sulfate Promoted Synthesis of N,N′‐Dimethyl Substituted (Unsubstituted)‐4‐aryl‐3,4‐dihydropyrimidones (Thiones) and Corresponding Bis‐Analogues in Aqueous Medium: Evaluation by Green Chemistry Metrics.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The development of an ecofriendly procedure for alkaline metal (II) sulfate promoted synthesis of N,N′‐dimethyl substituted (unsubstituted)‐4‐aryl‐3,4‐dihydropyrimidones (thiones) and corresponding bis‐analogues in aqueous medium: Evaluation by green chemistry metrics

Abstract magnified imageDifferent alkaline metal (II) sulfates were used as catalysts for the N,N′‐dimethyl substituted as well as unsubstituted 4‐aryl‐3,4‐dihydropyrimidones (thiones) and their corresponding bis‐analogues in aqueous medium. Among the various salts, MgSO4·7H2O (Epsom salt) proved to be the best catalyst giving the desired products in good to excellent yields. This catalyst enables the construction of a series of compound libraries particularly for N,N′‐dimethyl substituted DHPM's whose synthesis is very rare in the literature. The reaction on a wide variety substrates was evaluated by the application of green chemistry metrics and a very good correlation was obtained. J. Heterocyclic Chem., 2010.

Uma métrica gráfica para avaliação holística da verdura de reacções laboratoriais - "Estrela Verde"

A new semi-quantitative metrics, Green Star (GS), for evaluation of the global greenishness of chemical reactions used in teaching laboratories has been developed. Its aim is to help choosing the more acceptable reactions for implementing Green Chemistry (GC) and to identify suitable modifications of reaction protocols to improve the greenishness of chemistry. GS considers globally all the Twelve Principles of GC. To illustrate its construction, the tetraamminecopper(II) sulfate monohydrate laboratory synthesis, performed under several sets of conditions to pursue greenishness, is presented. A comparative study with other GC metrics showed the advantages of GS and that it accomplishes its purpose.

Greener Pharmaceuticals

Future Medicinal ChemistryVol. 1, No. 3 CommentaryGreener pharmaceuticalsJames H Clark, Simon W Breeden & Louise SummertonJames H Clark† Author for correspondenceGreen Chemistry Centre of Excellence, Department of Chemistry, University of York, UK. Search for more papers by this authorEmail the corresponding author at jhc1@york.ac.uk, Simon W BreedenGreen Chemistry Centre of Excellence, Department of Chemistry, University of York, UK. Search for more papers by this authorEmail the corresponding author at jhc1@york.ac.uk & Louise SummertonGreen Chemistry Centre of Excellence, Department of Chemistry, University of York, UK. Search for more papers by this authorEmail the corresponding author at jhc1@york.ac.ukPublished Online:29 Jun 2009https://doi.org/10.4155/fmc.09.46AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articlePapers of special note have been highlighted as: ▪ of interestBibliography1 Sheldon RA. The E factor 15 years on. Green Chem.9,1273–1283 (2007).▪ A large number of other metrics are available; an attempt to unify green metrics has been made by Andraos [12].Crossref, CAS, Google Scholar2 NHS SDU. NHS England carbon emissions: carbon footprinting emissions projections to 2020 – January. NHS Sustainable Development Unit, Cambridge, UK (2009).Google Scholar3 Dunn PJ, Galvin S, Hettenbach K. The development of an environmentally benign synthesis of sildenafil citrate (Viagra) and its assessment by green chemistry metrics. Green Chem.6,43–48 (2004).Crossref, CAS, Google Scholar4 Kuzemko MA, Van Arnum SD, Niemczyk HJ. A green chemistry comparative analysis of the syntheses of (E)-4-cyclobutyl-2-[2-(3-nitrophenyl)ethenyl] thiazole, Ro 24–5904. Org. Process Res. Dev.11(3),470–476 (2007).▪ First paper to refer to the sildenafil synthesis as the industry ‘gold standard’.Crossref, CAS, Google Scholar5 Constable DJC, Dunn PJ, Hayler JD et al. Key green chemistry research areas – a perspective from pharmaceutical manufacturers. Green Chem.9,411–420 (2007).Crossref, CAS, Google Scholar6 Comerford JW, Clark JH, Macquarrie DJ, Breeden SW. Clean, reusable and low cost heterogeneous catalyst for amide synthesis. Chem. Commun. (Camb.) DOI: 10.1039/B901581G (Epub ahead of print).Google Scholar7 Polshettiwar V, Varma RS. Nanoparticle-supported and magnetically recoverable ruthenium hydroxide catalyst: efficient hydration of nitriles to amides in aqueous medium. Chemistry15,1582–1586 (2009).Crossref, Medline, CAS, Google Scholar8 Polshettiwar V, Baruwati B, Varma RS. Magnetic nanoparticle-supported glutathione: a conceptually sustainable organocatalyst. Chem. Commun. (Camb.)1837–1839 (2009).Crossref, Medline, Google Scholar9 Anastas P, Warner J. Green Chemistry: Theory and Practice. Oxford University Press, NY, USA (1998).Google Scholar10 Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Del. Rev.46,3–26 (2001).Crossref, Medline, CAS, Google Scholar11 NHS SDU. (2009) NHS carbon reduction Strategy for England: key actions. NHS Sustainable Development Unit, Cambridge, UK (2009).Google Scholar12 Andraos J. Unification of reaction metrics for green chemistry II: evaluation of named organic reactions and application to reaction discovery. Org. Process Res. Dev.9,404–431 (2005).▪ A large number of metrics are available, with Andraos providing an attempt to unify green metrics.Crossref, CAS, Google Scholar101 Janusinfo: environment and pharmaceuticals. www.janusinfo.se/imcms/GetDoc?meta_id=7241Google ScholarFiguresReferencesRelatedDetailsCited ByThe role of solvent selection at exploratory and production stages in the pharmaceutical industryDaniel R Nicponski & P Veeraraghavan Ramachandran1 September 2011 | Future Medicinal Chemistry, Vol. 3, No. 12 Vol. 1, No. 3 Follow us on social media for the latest updates Metrics Downloaded 114 times History Published online 29 June 2009 Published in print June 2009 Information© Future Science LtdFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

The development of an environmentally benign sulfideoxidation procedure and its assessment by green chemistry metrics

Different Iron (III) species were used as catalysts in sulfoxidation reactions giving excellent yields and high chemoselectivity. Among the iron (III) species, the best one was a solid β-cyclodextrin-FeBr3 complex. Sulfoxidation takes place with high chemoselectivity in the presence of other groups such as isothiocyanate. Good results were obtained when these reactions were analyzed using green chemistry metrics.

Global Green Chemistry Metrics Analysis Algorithm and Spreadsheets: Evaluation of the Material Efficiency Performances of Synthesis Plans for Oseltamivir Phosphate (Tamiflu) as a Test Case

This work discloses an easy-to-use algorithm to evaluate the global material efficiency performance of any kind of synthesis plan regardless of complexity to a given target molecule according to green metrics criteria. The algorithm is robust and has been adapted to Excel spreadsheets for rapid calculation and graphing of the numerical results. In order to demonstrate the facile utility of this exceptional tool for process and synthetic chemists in the evaluation and ranking of synthetic performance, various synthesis plans for oseltamivir phosphate, a neuraminidase inhibitor used to treat the H5N1 influenza virus, have been investigated. In particular, six industrial syntheses and nine plans from academic groups have been thoroughly and rigorously evaluated according to kernel and global reaction mass efficiencies and E-factors, atom economy, and overall yield performances. In addition, all reported plans were evaluated according to new synthesis elegance parameters including fraction of sacrificial reag...

A Methodology for Evaluation and Selection of Nanoparticle Manufacturing Processes Based on Sustainability Metrics

A set of sustainability metrics, covering the economic, environmental and sociological dimensions of sustainability for evaluation of nanomanufacturing processes is developed. The metrics are divided into two categories namely industrial engineering metrics (process and safety metrics) and green chemistry metrics (environmental impact). The waste reduction algorithm (WAR) is used to determine the environmental impact of the processes and NAIADE (Novel Approach to Imprecise Assessment and Decision Environments) software is used for evaluation and decision analysis. The methodology is applied to three processes used for silica nanoparticle synthesis based on sol-gel and flame methods.

Toward Green Nano

SummaryCommercial and research interest in nanotechnology has exploded in recent years, with nearly US$9 billion in investment from public and private sources in 2005. While the list of potential applications for nanotechnologies continues to grow, there is increasing pressure from governments and researchers alike to understand the implications of this new class of materials. The emerging field of green nano applies green chemistry and engineering principles to the synthesis of nanomaterials. Here we outline several strategies for the development of green nano and review past policy and research activities in understanding nanotechnology's environmental implications. By means of the green chemistry metric of E‐factor, an analysis is undertaken of the traditional syntheses of several specific nanomaterials, including carbon nanotubes, fullerenes, and metal nanoparticles. It was found that the E‐factors of these production processes vary over several orders of magnitude, making it difficult to comment generally about the resource use efficiencies of nanomaterials production. For gold nanoparticles specifically, E‐factors for six different production methods are found to range from 102 to 105, demonstrating that greener synthesis routes are possible and that environmental benefits can begin to be quantified. Expanding the analysis to include life‐cycle stages upstream and downstream of production and to incorporate environmental health effects is encouraged, though significant data gaps exist.

Green chemistry metrics: a comparative evaluation of dimethyl carbonate, methyl iodide, dimethyl sulfate and methanol as methylating agents

The methylating efficiency of dimethyl carbonate (DMC), dimethyl sulfate (DMS), methyl iodide (MeI), and methanol (MeOH) was assessed based on atom economy and mass index. These parameters were calculated for three model reactions: the O-methylation of phenol, the mono-C-methylation of phenylacetonitrile, and the mono-N-methylation of aniline. The analysis was carried out over a total of 33 different procedures selected from the literature. Methanol and, in particular, DMC yielded very favourable mass indexes (in the range 3–6) indicating a significant decrease of the overall flow of materials (reagents, catalysts, solvents, etc.), thereby providing safer greener catalytic reactions with no waste.

Fabrication of laterally ‘sliced’ metal plated carbon nanotubes under aqueous continuous flow conditions

Metal plating carbon nanotubes and controlling the dimensionality of nanotubes has thus far been severely hampered due to their clumping and poor wettability. Spinning disc processing (SDP) is an instantaneously scalable, continuous flow and high throughput flash nano-fabrication technology which embraces green chemistry metrics. Herein we highlight the efficient use of SDP in fabricating metal plated carbon nanotubes and slicing them laterally in aqueous media at room temperature under continuous flow conditions. The reported continuous flow approach addresses key issues of scalability, effluent treatment and hazardous work environment at the seed stage rather than spending enormous time/effort in making the technology scalable and non-toxic after development.

Continuous flow nano-technology: manipulating the size, shape, agglomeration, defects and phases of silver nano-particles

Spinning disc processing (SDP) is an instantaneously scalable, continuous flow and high throughput flash nano-fabrication technology which embraces green chemistry metrics. It has been used to prepare silver nano-particles with remarkable control in size (5-200 nm), shape (spheroidal, acicular or agglomerate rosettes), surface characteristics, and phase (cubic versus hexagonal), along with imparting defects for particles >10 nm diameters. The control is associated with changing the nature of the stabilising surfactant (respectively, starch, polyethylene glycol and poly(4-vinylpyridine)), the concentration of the reactants, and flow rates.

Green chemistry and the health implications of nanoparticles

Until recently the spectacular developments in nanotechnology have been with little regard to their potential effect on human health and the environment. There are no specific regulations on nanoparticles except existing regulations covering the same material in bulk form. Difficulties abound in devising such regulations, beyond self-imposed regulations by responsible companies, because of the likelihood of different properties exhibited by any one type of nanoparticle, which are tuneable by changing their size, shape and surface characteristics. Green chemistry metrics need to be incorporated into nanotechnologies at the source. This review scopes this issue in the context of potential health effects of nanoparticles, along with medical applications of nanoparticles including imaging, drug delivery, disinfection, and tissue repair. Nanoparticles can enter the human body through the lungs, the intestinal tract, and to a lesser extent the skin, and are likely to be a health issue, although the extent of effects on health are inconclusive. Nanoparticles can be modified to cross the brain blood barrier for medical applications, but this suggests other synthetic nanoparticles may unintentionally cross this barrier.