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Teaching Reaction Efficiency Through the Lens of Green Chemistry: Should Students
Focus on the Yield, or the Process?
Andrew P. Dicks
PII: S2452-2236(18)30032-4
DOI: 10.1016/j.cogsc.2018.03.009
Reference: COGSC 134
Please cite this article as: A.P. Dicks, Teaching Reaction Efficiency Through the Lens of Green
Chemistry: Should Students Focus on the Yield, or the Process?, Current Opinion in Green and
Sustainable Chemistry (2018), doi: 10.1016/j.cogsc.2018.03.009.
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Teaching Reaction Efficiency Through the Lens of Green Chemistry: Should Students Focus
on the Yield, or the Process?
Andrew P. Dicks
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada
M5S 3H6.
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Email: adicks@chem.utoronto.ca
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Teaching Reaction Efficiency Through the Lens of Green Chemistry: Should Students Focus
on the Yield, or the Process?
Andrew P. Dicks
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada
M5S 3H6.
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Email: adicks@chem.utoronto.ca
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Abstract
This Green Chemistry in Education review article focuses on some green metrics of current
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interest to chemistry educators. It highlights a recent shift from the teaching of established reaction
metrics including yield and atom economy (AE) to industrially-relevant global mass metrics such as
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process mass intensity (PMI). Emphasis is placed on students undertaking a “global mass
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inventory” to determine material efficiency in a chemical transformation they perform as part of
their curriculum. Context is provided to each described metric through reference to a common
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undergraduate organic experiment: the aldol condensation of benzaldehyde and acetone to form
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dibenzalacetone. The development of some new life cycle assessment (LCA) pedagogical activities
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is also discussed.
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Keywords
atom economy; reaction mass efficiency; E factor; process mass intensity; global mass inventory.
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Highlights
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• issues when yield used as the sole metric to gauge chemical reaction efficiency
• process mass intensity (PMI) now a “go-to” green chemistry mass metric
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Introduction
Green chemistry metrics are ones that assess the performance of a chemical process in
relation to the Twelve Principles of Green Chemistry [1]. Several recent articles have reviewed
some more commonly-used metrics in this regard with a view to the future [2-5], particularly in the
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educational perspective, a discussion of green metrics has been incorporated as a significant
component of undergraduate courses at different academic levels [6-9]. Of the green metrics, a
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number can be described as mass metrics: those that in some way quantify the operational
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efficiency of a chemical reaction (Figure 1).
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introductory and advanced chemistry courses (although often not through the lens of green
chemistry). Educators often assign a grade to students for achievement of a particular yield to
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reward experimental technique, thus emphasizing the importance of the metric. In doing so,
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students may be misinformed about the actual material efficiency of their reactions. In addition,
many academic journals focused on synthesis do not require reaction efficiencies to be reported in
To illustrate this issue, consider a very common introductory undergraduate organic chemistry
synthesis procedure: the macroscale preparation of dibenzalacetone via the base-catalyzed aldol
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condensation of benzaldehyde and acetone [10] (Figure 2). This reaction typically affords a
68%. From a student perspective, is this a “good”, “average” or “bad” value? Does it indicate to
them that 68% of the input material is converted to the desired product? If students only calculate
this number, is there an overreliance on the yield metric as a measure of reaction efficiency?
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Figure 2. Aldol condensation of benzaldehyde and acetone to form dibenzalacetone.
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Fortunately, the other mass metrics in Figure 1 have gained currency in recent years as a way to
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teach concepts of reaction and process efficiency to undergraduates. This review article summarizes
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progress made in this realm during the last three years, with a particular emphasis on the increasing
importance of process mass intensity (PMI) as an easily-calculated global green chemistry mass
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metric.
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Atom Economy
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The green chemistry metric of atom economy ((AE), Figure 1, [11]) has become very
popular in an instructional setting. AE has high profile as the second of the Twelve Principles of
Green Chemistry [1], is simplistic, and (as it considers reactant and product molecular weights) it
can be calculated for a reaction without undertaking any experimental work. Since Cann and
Dickneider [12] described ways in which to embed AE calculations into organic courses, many
other examples have appeared in the pedagogical literature. Recently, these include through guided-
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inquiry asymmetric aldol reactions [13], by way of epoxidized soybean oil [14], and via coumarin
synthesis in an ionic liquid [15]. However, as a theoretical construct, AE does not take into account
the actual masses of reactants used or the product yield obtained, and consequently can create an
calculated as (234.29 / ((2 * 106.12) + 58.08) = 87%. Based on this alone, the reaction appears to
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have impressive efficiency, with the only “waste” atoms going to two water molecules.
Nonetheless, it is worth noting that the pharmaceutical industry does not consider AE to be a useful
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metric in isolation from other ones.
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Reaction Mass Efficiency
Reaction mass efficiency (RME) was introduced as way to consider the mass balance taking
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place when a chemical reaction proceeds (Figure 1, [16]). As RME is based on actual laboratory
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results, it is a more realistic metric that accounts for an excess reactant present in non-
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stoichiometric proportions, and the isolated yield of the desired product. Recycling of material can
also be taken into consideration if warranted. After early work was published on RME calculations
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in practical and theoretical teaching contexts [17,18], more recent articles have focused on
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classroom activities using interlocking building blocks in general chemistry courses and advanced
green chemistry/industrial chemistry courses [19], and how “Green Star” metrics can be utilized to
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optimize literature syntheses of ethyl acetate and manganese(III) acetylacetonate [20]. From Figure
2, the RME of the student reaction is computed to be (4.0 g / (5.31 g + 1.45 g + 5.0 g) = 34%,
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assuming that no NaOH or other starting compounds are recovered for reuse. This number provides
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a much more reasonable reflection on the mass efficiency of the aldol condensation than the
reaction yield does (68%). A clear drawback of this approach is that only the reaction itself is taken
into consideration, rather than any potential auxiliaries (e.g. reaction/purification solvents and other
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E Factor & Process Mass Intensity
Several green chemistry mass metrics have been embraced by industry that encompass a
reaction as a process that involves more than just reactants and a target product. Two of them are
the E factor [21,22] and process mass intensity (PMI, [23]) and both can be considered as global
mass metrics. As Figure 1 indicates, the E factor metric focuses on preventing waste, with an ideal
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value equalling zero (i.e. no waste is generated during a chemical process). Contemporary
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laboratory [24,25] and in the classroom [19]. It is important to note that water has typically not been
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included in literature E factor calculations, to avoid generating artificially high values. However, it
is the PMI metric that has become increasingly significant in recent years from both industrial and
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teaching perspectives. PMI is very much seen as a “leading” proactive metric rather than a
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“lagging” reactive one with its emphasis on input materials rather than waste (Figure 1). PMI has an
ideal value of unity (i.e. all input materials are converted into the desired product) and is “(the
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metric) used in the pharmaceutical industry to drive more sustainable processes” [23]. Its industrial
importance has latterly been underscored by articles focusing on an analytics framework to predict
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probable PMI outcomes for proposed, potential or unoptimized synthetic routes [26] and high-
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throughput extractions to optimize workups in process development, therefore lowering PMI values
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[27]. A model has also been proposed to set PMI targets for prospective drugs based on projected
The last few years have seen an upsurge in educational initiatives focusing on PMI as a key green
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chemistry metric. In the laboratory, Khuong designed an experiment to facilitate evaluation of three
sodium tungstate/hydrogen peroxide and bleach as oxidants) [29]. Students calculate the PMI value
for each procedure as part of their “greenness” evaluation. Biswas and Mukherjee used the two-step
students [30]. Thirdly, Fennie and Roth devised a synthetic model focusing on green chemistry
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metrics within the framework of amide bond formation from an amine using an acid chloride,
coupling reagent or coupling catalyst. PMI was one of several metrics considered by their students
(along with AE and RMI) [31]. An aza-Baylis-Hillman transformation has also been employed as a
vehicle to promote student analysis of a laboratory process, rather than simply a reaction [32].
Notably, an online tool has been made available by the American Chemical Society that expedites
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the calculation of PMI values by educators and students [33,34]. From a more theoretical viewpoint,
Duarte et al. concluded that PMI and related metrics are insufficient to evaluate the relative green
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nature of microscale and macroscale experiments, as the improvement in safety that microscale
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chemistry engenders is not recognized [35]. Andraos and Hent have published two papers
describing material efficiency green metrics applied to organic syntheses [36,37]. One further
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article emphasizes the importance of balancing chemical equations as a starting point to solve
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problems from Inorganic Syntheses [38].
Returning to the student aldol condensation for a final time, calculation of the PMI for this
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masses of all process components) (Figure 3). This indicates that over 0.5 kg of material is needed
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Figure 3: Calculation of the process mass intensity for dibenzalacetone synthesis via a “global mass
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inventory”.
Bearing in mind that a typical mass of isolated product is around 4.0 g, the PMI can be estimated as
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(501.25 / 4.0) = 125 (i.e. 125 g of material in total is required to generate 1.0 g of dibenzalacetone).
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This calculation places a very different perspective on material efficiency, as one can see that most
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of the mass used is during the purification process (81%), rather than the reaction itself. A further
16% of the process mass is taken up by reaction solvents. The workup of reactions has recently
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been highlighted as a major contributor to process waste and to a general decrease in “greenness”
[20,32,39]. This critical point is lost on students if metric calculations they perform are limited to
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Conclusions
The chemistry teaching literature has recently seen a welcome movement towards the
promotion of global mass metrics (most notably PMI), in an attempt to move away from a “yield is
everything” mentality. In Canada, the annual Canadian Chemistry Contest for high school students
has included a multiple-choice question pertaining to AE, RME and PMI calculations for several
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years [40]. To move beyond simple calculation of yields, it is strongly suggested that all
undergraduates calculate a PMI value by performing a global mass inventory for an experiment
already embedded in their curriculum. Significantly, there is no requirement for a new experiment
to be devised to specifically serve this purpose. On doing this, students will in most cases draw the
conclusion that most mass is “lost” from solvents and workup/purification procedures. This affords
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them an opportunity to “look beyond the reaction” and to make suggestions regarding how less
waste might be generated and how efficiency might be improved. After all, the first of the Twelve
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Principles of Green Chemistry is “it is better to prevent waste rather than treat or clean up waste
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after it has been created” [1].
It is important to conclude this review by emphasizing that reaction mass metrics are but one part of
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a much more complex landscape when it comes to assessing process “greenness”. Progress has been
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made in this regard by development of pedagogical activities that resemble a “life cycle
assessment” (LCA). Mercer et al. developed a multivariate metric green chemistry exercise where
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students select the greenest synthesis from a range of literature protocols. This is achieved by
quantifying the environmental impact of all the materials involved in each synthesis [41]. Since that
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time, interest has been shown in the EcoScale (“a semi-quantitative tool to select an organic
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preparation based on economical and ecological parameters”) [42] as a teaching tool in terms of it
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being a simplified LCA [31,43-44]. A further LCA student activity has recently been published
[45]. It is clear from these review examples that, twenty-five years after the development of the AE
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and E factor metrics [2], the chemistry teaching community still has a huge role to play in educating
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