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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

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S2452-2236(18)30032-4

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COGSC 134

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Current Opinion in Green and Sustainable Chemistry

Received Date: 12 February 2018

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Accepted Date: 19 March 2018

10 March 2018

Revised Date: Accepted Date: 19 March 2018 10 March 2018 Please cite this article as: A.P.

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.

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.

Email: adicks@chem.utoronto.ca

Abstract

This Green Chemistry in Education review article focuses on some green metrics of current

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

process mass intensity (PMI). Emphasis is placed on students undertaking a “global mass

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

undergraduate organic experiment: the aldol condensation of benzaldehyde and acetone to form

dibenzalacetone. The development of some new life cycle assessment (LCA) pedagogical activities

is also discussed.

Keywords

atom economy; reaction mass efficiency; E factor; process mass intensity; global mass inventory.

Highlights

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

concept of “global mass inventory” significant for students to grasp

move towards more educational activities focusing on life cycle assessment

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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

context of predictive greener decision-making and industry benchmarking [4,5]. From an

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

number can be described as mass metrics: those that in some way quantify the operational

efficiency of a chemical reaction (Figure 1).

operational efficiency of a chemical reaction (Figure 1). Figure 1. Selected reaction mass metrics of interest

Figure 1. Selected reaction mass metrics of interest to green chemistry educators.

The reaction yield metric is ubiquitously calculated by undergraduates worldwide in both

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

reward experimental technique, thus emphasizing the importance of the metric. In doing so,

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

any other way than percentage yield.

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

dibenzalacetone mass of around 4.0 g after purification by recrystallization, equating to a yield of

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?

on the yield metric as a measure of reaction efficiency? Figure 2. Aldol condensation of benzaldehyde

Figure 2. Aldol condensation of benzaldehyde and acetone to form dibenzalacetone.

Fortunately, the other mass metrics in Figure 1 have gained currency in recent years as a way to

teach concepts of reaction and process efficiency to undergraduates. This review article summarizes

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

metric.

Atom Economy

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

inflated perception of reaction efficiency. The AE of the aldol condensation in Figure 2 is

calculated as (234.29 / ((2 * 106.12) + 58.08) = 87%. Based on this alone, the reaction appears to

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

metric in isolation from other ones.

Reaction Mass Efficiency

Reaction mass efficiency (RME) was introduced as way to consider the mass balance taking

place when a chemical reaction proceeds (Figure 1, [16]). As RME is based on actual laboratory

results, it is a more realistic metric that accounts for an excess reactant present in non-

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

in practical and theoretical teaching contexts [17,18], more recent articles have focused on

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

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%,

assuming that no NaOH or other starting compounds are recovered for reuse. This number provides

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

materials, such as column chromatography adsorbents).

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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

value equalling zero (i.e. no waste is generated during a chemical process). Contemporary

pedagogical applications of E factor calculations have been reported in the undergraduate

laboratory [24,25] and in the classroom [19]. It is important to note that water has typically not been

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

teaching perspectives. PMI is very much seen as a “leading” proactive metric rather than a

“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

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

probable PMI outcomes for proposed, potential or unoptimized synthetic routes [26] and high-

throughput extractions to optimize workups in process development, therefore lowering PMI values

[27]. A model has also been proposed to set PMI targets for prospective drugs based on projected

market demand and molecular complexity [28].

The last few years have seen an upsurge in educational initiatives focusing on PMI as a key green

chemistry metric. In the laboratory, Khuong designed an experiment to facilitate evaluation of three

separate syntheses of benzophenone by benzhydrol oxidation (utilizing potassium permanganate,

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

synthesis of 4-bromoacetanilide from aniline as a way to introduce PMI calculations to their

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

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

nature of microscale and macroscale experiments, as the improvement in safety that microscale

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

article emphasizes the importance of balancing chemical equations as a starting point to solve

problems from Inorganic Syntheses [38].

Returning to the student aldol condensation for a final time, calculation of the PMI for this

transformation is easily accomplished by undertaking a “global mass inventory” (summing the

masses of all process components) (Figure 3). This indicates that over 0.5 kg of material is needed

to undertake the reaction (including all auxiliaries).

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Figure 3: Calculation of the process mass intensity for dibenzalacetone synthesis via a “global mass

inventory”.

Bearing in mind that a typical mass of isolated product is around 4.0 g, the PMI can be estimated as

(501.25 / 4.0) = 125 (i.e. 125 g of material in total is required to generate 1.0 g of dibenzalacetone).

This calculation places a very different perspective on material efficiency, as one can see that most

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

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

reaction yield, AE and even RME.

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

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

Principles of Green Chemistry is “it is better to prevent waste rather than treat or clean up waste

after it has been created” [1].

It is important to conclude this review by emphasizing that reaction mass metrics are but one part of

a much more complex landscape when it comes to assessing process “greenness”. Progress has been

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

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

time, interest has been shown in the EcoScale (“a semi-quantitative tool to select an organic

preparation based on economical and ecological parameters”) [42] as a teaching tool in terms of it

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

and E factor metrics [2], the chemistry teaching community still has a huge role to play in educating

students about green chemistry.

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