Laboratory Experiment pubs.acs.org/jchemeduc
Cite This: J. Chem. Educ. XXXX, XXX, XXX−XXX
Teaching Atom Economy and E‑Factor Concepts through a Green Laboratory Experiment: Aerobic Oxidative Cleavage of mesoHydrobenzoin to Benzaldehyde Using a Heterogeneous Catalyst Chun Ho Lam,†,‡ Vincent Escande,† Karolina E. Mellor,† Julie B. Zimmerman,†,§ and Paul T. Anastas*,†,∥
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†
Center for Green Chemistry & Green Engineering, Yale and School of Forestry and Environmental Studies, 370 Prospect Street, New Haven, Connecticut 06511, United States ‡ Department of Chemistry, Wesleyan University, 52 Lawn Avenue, Middletown, Connecticut 06457, United States § Department of Chemical and Environmental Engineering, 9 Hillhouse Avenue, New Haven, Connecticut 06511, United States ∥ Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06511, United States S Supporting Information *
ABSTRACT: We herein report an efficient aerobic oxidative cleavage of meso-hydrobenzoin to benzaldehyde using a heterogeneous earth-abundant metal oxide catalyst. The reaction can be carried out at 70 °C in ethanol and uses a balloon filled with O2 as oxidant. Reagents are simple and have long shelf lives, and the whole laboratory exercise can be done in 120 min, which makes it highly implementable to standard undergraduate organic curriculum. meso-Hydrobenzoin cleaves exclusively to benzaldehyde, which gives off a nice almond smell, and generates water as the only byproduct. The exercise also compares the present methodology with two other conventional diol oxidative cleavage protocols to illustrate the use of atom economy and E-factor. This laboratory exercise is suitable for second-year undergraduates because it does not require any prerequisites while demonstrating the concepts of catalysis, ease of separation, atom economy, E-factor, earth-abundant material utilization, and biomass transformation. KEYWORDS: First-Year Undergraduate, Hands-On Learning, Second-Year Undergraduate, Organic Chemistry, Inorganic Chemistry, Green Chemistry, Catalysis, Oxidation
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INTRODUCTION While green chemistry recently marked its 25th anniversary,1−3 an increasing number of institutes are beginning to develop green-chemistry-related programs to accommodate the growing academic interest.4 In addition to ground-breaking publications in various research journals, more pedagogyrelated materials on green chemistry have become available across different platforms such as Internet blogs, books, and proceedings articles in the past decade.5 The 12 Principles of Green Chemistry provide comprehensive guidelines to chemists to design greener products and processes6 and have been made into countless lesson plans to integrate into undergraduate lectures and laboratory exercises.7,8 Whereas many of these works explore safer chemical design, toxicity, and the use of renewable resources, the use of heterogeneous catalysts deserves more attention because it plays an important role in manufacturing platform chemicals.9 The practice of heterogeneous catalysis using an alternative synthetic strategy, such as aerobic catalysis, microwave-assisted synthesis, and electrocatalysis, has drawn much attention to the renewable © XXXX American Chemical Society and Division of Chemical Education, Inc.
feedstock community for their unique abilities to transform chemicals under mild conditions.10−13 About 80% of the industrial chemical synthesis relies on heterogeneous catalysis for bulk chemical production, whereas homogeneous catalysis is more common for fine chemical syntheses, especially in small-volume chemistry such as pharmaceutical manufacturing.14,15 Heterogeneous catalysis is essential to green chemistry and sustainability.16−18 Heterogeneous catalysts can be reactivated conveniently through a simple chemical or heat treatment and, more importantly, can be removed or recovered easily by filtration, saving a countless amount of solvent used for separation. Crumbie reported a heterogeneous chemical transformation, but the reaction would require a stoichiometric quantity of chromium oxide.19 Stahl et al. reported a copperbased catalyst that uses O2 as an oxidant, but its homogeneous nature would require an additional separation step if product Received: January 26, 2018 Revised: January 22, 2019
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DOI: 10.1021/acs.jchemed.8b00058 J. Chem. Educ. XXXX, XXX, XXX−XXX
Journal of Chemical Education
Laboratory Experiment
purification was necessary.20 Other green-chemistry pedagogical examples have focused on comparing different synthetic routes or different scales using known green-chemistry metrics.21 However, some of these may lack the laboratory component to deliver a comprehensive undergraduate laboratory experience.22 Oxidative cleavage of vicinal diols serves as one of the most common reactions to prepare aldehyde or ketones among the fine chemical production industry.23 The reaction is typically carried out using the Criegee or the Malaprade oxidation,24 which employs a stochiometric amount of lead tetraacetate (Pb(OAc)4) and sodium periodate (NaIO4), respectively, to cleave diol into the corresponding carbonyl compounds. Although these reagents are highly robust in cleaving any aliphatic and aromatic vicinal diol, they use a stoichiometric quantity of lead or highly oxidized halogenated reagent, which is often considered to be highly unsuitable in an undergraduate teaching laboratory. Whereas the Malaprade oxidation is a relatively safer option because it is lead-free, it still requires a highly oxidized reagent in a stoichiometric amount, periodic acid or periodate salt, which is undesirable from an environmental perspective. A green protocol to achieve the cleavage of activated diols using an earth-abundant metal oxide, sodium-doped porous sodium manganese oxide (Na-MnOx), was recently reported by Anastas et al.13,25 The protocol is highly selective toward cleaving vicinal diols that are adjacent to an aromatic ring (a.k.a. activated diols) and requires a very low catalyst loading at 1 mol % relative to the substrate. The greatest advantage is that the Na-MnOx catalyst can incorporate O2 as a terminal oxidant and works under mild conditions at 70 °C in ethanol. The Na-MnOx catalyst has a long shelf life and can be prepared easily in large quantity. In addition to demonstrating a simple heterogeneous reaction, the exercise also aims to teach two common green chemistry metrics, atom economy and E-factor,26−28 by comparing the Na-MnOx oxidation route with the Malaprade and Criegee oxidation routes. Fifty undergraduate students in three different sections completed the whole laboratory section, including a prelab introduction, the experiment, the analysis, and small group postexperiment discussions in 120 to 150 min. Participants were surprised that the cleavage of meso-hydrobenzoin could be completed by the elegant use of oxygen gas and a heterogeneous catalyst. The resulting product, benzaldehyde, displayed a distinctive almond smell that boosted the attractiveness of the lab and created a memorable laboratory experience. The goal of this laboratory exercise is to introduce the concept of atom economy and E-factor to students early in their chemistry curriculum while demonstrating the convenience and an interesting aspect of heterogeneous catalysis. meso-Hydrobenzoin was chosen as a testing substrate due to its exclusive production of benzaldehyde, which is the same compound that is used for almond flavoring. Both the starting material and the product are relatively inexpensive, are benign, and have a long shelf life, making them ideal for the teaching laboratory. In addition to the experiment’s simplicity, there is also the opportunity that the almond scent of benzaldehyde may facilitate a discussion on how green chemistry can be applicable in the fragrance industry.29
Information S3) and 20 mg of meso-hydrobenzoin are weighed in a 2-dram vial and stirred in 1 mL of ethanol at room temperature for 1 min using a magnetic star bar. Then, the cap (or rubber adaptor) of the reaction is punctured by the needle connected to an O2 balloon, as shown in Figure 1. The reaction vial is then placed in a 70 °C water bath and is stirred at high speed for 30 min.
Figure 1. (Left) Schematic drawing of the experimental setup for a 1 mL scale. Reaction should be run for 30 min at 70 °C. (Right) Actual experiment setup showing how an O2-filled balloon is connected to the reaction vial using a syringe adaptor.
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ANALYSIS The experiment can be analyzed qualitatively via thin-layer chromatography (TLC) or quantitatively via gas chromatography (GC). Details of the procedures are described in the Supporting Information (S2).
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HAZARDS Personal protective equipment (PPE), such as gloves, lab coat, and safety goggles, must be employed throughout the experiment. The experiment should be set up and conducted in the fume hood. The Na-MnOx catalyst, ethanol (95% or anhydrous), meso-hydrobenzoin, and benzaldehyde are considerably benign. Even though O2 by itself is not considered as flammable, the combined use of O2 with ethanol can be a concern, and thus open flame should be avoided during the experiment. Hexane and ethyl acetate used for TLC analysis are also flammable and should be handled with care. Exposure to UV light should be minimized to avoid skin burn. A gas regulator must be used to ensure the slow flow of oxygen gas. The instructor and students should also review the Material Safety Data Sheets (MSDS) for each of the reagents employed in the laboratory exercise.
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RESULTS AND DISCUSSION
Experimental Results
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On the basis of TLC plate analysis, the spot of mesohydrobenzoin should be faint or absent because of its near-full conversion to benzaldehyde. No benzoic acid was observed, and benzaldehyde was the sole product from the cleavage, as
EXPERIMENTAL PREPARATION Five mg of the Na-MnOx catalyst (Na-MnOx catalyst preparation is described in detail in the Supporting B
DOI: 10.1021/acs.jchemed.8b00058 J. Chem. Educ. XXXX, XXX, XXX−XXX
Journal of Chemical Education
Laboratory Experiment
AE can be calculated as a prelab exercise because it is independent from the experimental yield. The value of E-factor may vary due to the difference in yield. Instructors may predesignate a range of percentage yield to ensure that students’s calculations are comparable. In the Supporting Information, 85% was the default percentage assumption for the example calculation in Table 1, as it reflects the experimental yield obtained in our testing trials.
shown in Scheme 1. TLC analysis gave a clear conversion, showing only the meso-hydrobenzoin and benzaldehyde peaks. Scheme 1. Oxidative Cleavage of meso-Hydrobenzoin Using O2 as Terminal Oxidant To Generate Two Equivalents of Benzaldehyde and One Equivalent of Water
Metrics: Atom Economy (AE)
The AEs of three oxidation protocols shown in Scheme 2 are calculated using eq 1 and are presented in Table 2. The Na(See Figure S2 in the Supporting Information.) Most students could smell the almond flavor from benzaldehyde after the condensed ethanol on the vial wall has been evaporated in air, which generally takes approximately 5−10 s of gently swirling. The remarkably high selectivity makes this experiment very useful as a teaching exercise for undergraduate laboratory. We also observe that quantification can be sensitive by the evaporation of the solvent; it is important to keep the reaction below ethanol boiling temperature and sealed to prevent a dynamic influx of O2 flow from the balloon.
Table 2. Comparison of Atom Economy, Calculated by Equation 1, of Different Methodologies To Cleave mesoHydrobenzoin Oxidatively to Two Equivalents of Benzaldehyde Oxidation Protocol Using the Na-MnOx catalyst Malaprade Criegee
Green Chemistry Metrics
This experiment also provides an opportunity for a student to evaluate the reaction using common green chemistry metrics: atom economy (AE) and environmental factor (E-factor).26−28 One literature example for the Malaprade and the Criegee reactions was selected to enable the E-factor analyses for comparison (Table 1).
a
Reagents Oxidant Solvent Starting materials (mg) Nonrecycled solvent waste (mg) Cat. or reagent (mg) Waste (mg) Benzaldehyde (mg) E-factor (dimensionless)
Malaprade
Criegee
O2 Ethanol 20 79
NaIO4 Dichloromethane 429 4638
Pb(OAc)4 Benzene 26350 15295
5 Water 16.8 5.2a
610 NaIO3 382 13.9
58000 Pb(OAc)2 23490 3.2
AE (%)a
meso-Hydrobenzoin + 0.5 O2
230.3
92.3
meso-Hydrobenzoin + NaIO4 meso-Hydrobenzoin + Pb(OAc)4
428.2 656.1
49.5 32.3
Reactants Involved
M.W. of products for all entries is 212.14 g mol−1
MnOx route shows the highest AE, which means the transformation is the most atom economical, as the reaction is almost byproduct-free.
Table 1. Comparison of E-Factor for All Oxidation Cleavage of meso-Hydrobenzoin NaMnOx
M.W. Reactants (g mol−1)
AE =
M.W. of Desired Products × 100% M.W. of Reactants
(1)
where AE is the atom economy, M.W. of Desired Product is the molecular weight of both benzaldehyde molecules formed in the reaction, and M.W. of Reactants is the molecular weight of the meso-hydrobenzoin and oxidant. The comparison is dramatic and illustrative, as the NaMnOx catalyst uses only O2 to effect the cleavage, whereas the Malaprade and Criegee routes delivered their oxidative equivalents with reagents that have a much higher molecular weight, which contributed significantly to the molecular weight of the reactants but not the desired products. Students should note, however, that AE is a theoretical calculation that is based on two assumptions that all reactions achieve perfect selectivity to desired products and all auxiliary
a
Na-MnOx E-factor was calculated assuming that the conversion of starting material was 85%.
Scheme 2. Comparison of Oxidative Cleavage of meso-Hydrobenzoin to BenzaldehydeA
A
Only the consumable reagents are listed out for clarity purposes. C
DOI: 10.1021/acs.jchemed.8b00058 J. Chem. Educ. XXXX, XXX, XXX−XXX
Journal of Chemical Education
Laboratory Experiment
follows with the convention that solvent accounts for the highest amount of waste generation in the chemical industry.31 Students’ understanding can be assessed quantitatively with the postlab worksheet. In our test runs with 50 students, 42 students scored well in the AE and E-factor calculation exercise after the experiment. This laboratory experiment showed interesting ways to achieve organic transformation compared with conventional reagent mixing and waiting. The use of O2 as an oxidant and the production of benzaldehyde in this laboratory revitalizes the standard organic curriculum with a refreshing, greener prospective method to practice chemical transformation.
components, such as catalyst and solvents, are recyclable. In the case of the Na-MnOx catalyst, both assumptions were valid. However, it is more common that these assumptions do not hold true, and thus it is important to look at the E-factor for a more comprehensive analysis. Metrics: Environmental Factor (E-factor)
E-factor is another important index to evaluate the environmental impact of a reaction. It enables us to estimate the amount of waste that could be generated per kilogram of product produced. The higher the E-factor value, the more waste will be generated. E‐factor =
mass (waste) mass (product )
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CONCLUSIONS We have outlined an educational experiment that illustrates several principles of green chemistry through a simple heterogeneous oxidative cleavage reaction using an earthabundant metal oxide catalyst that can be easily prepared in large quantity. The reaction does not require workup and can be analyzed qualitatively by TLC plate or quantitatively by GC-FID after a simple filtration. It does not require the typical demanding conditions commonly employed for most industrial heterogeneous reactions, yet it demonstrates how a catalyst can be simply removed by filtration and how the reaction can be analyzed without elaborate postprocessing. Two homogeneous analogues of oxidative cleavage were presented for students to practice on the use of AE and Efactor. Both metrics would help students to appreciate the value and limitations of these metrics as a universal index to evaluate the greenness of a reaction but rather should be used together to assess important aspects of the process. Despite a higher E-factor, the use of Na-MnOx is a greener alternative to the conventional homogeneous analogue that uses a toxic lead reagent. Students can attempt to rationalize this irregularity and begin to understand factors beyond what the metrics cover. Green chemistry demands systems thinking to avoid unintended consequences, and this can be good practice for students to see beyond what is presented.
(2)
where mass (waste) and mass (product) represent the amounts of waste and product generated in the same weight unit. Unlike the atom economy, the waste accounts for all nonrecyclable postreaction components including unreacted starting materials, byproducts, and solvents. For example, the oil industrial processes have a lower E-factor because they are highly optimized for their tasks, and the various products generated from the refinery are utilized very efficiently, which minimizes deposals. 30 Higher value products such as pharmaceuticals always have a higher E-factor due to the multistep synthesis procedures. A general description of the trend is given in Table 3. Table 3. General Estimation of E-Factor from Various Industries Industrial Sector
Annual Production (10x − 10y t)
E-Factor
Oil Refining Bulk Chemical Fine Chemical Pharmaceuticals
6−8 4−6 2−4 1−3
ca. 1
