Sodium

Laboratory Experiment Cite This: J. Chem. Educ. XXXX, XXX, XXX−XXX

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Semimicro/Microscale Adaptation of the Cobalt Chloride/Sodium Borohydride Reduction of Methyl Oleate James R. McKee,* Murray Zanger, Carmine Chiariello, James A. McKee, Walter Dorfner, Elisabetta Fasella, and Yumee Koo Department of Chemistry & Biochemistry, University of the Sciences, Philadelphia, Pennsylvania 19014, United States

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S Supporting Information *

ABSTRACT: The reduction of alkenes usually involves a hydrogen source and a catalyst. This process is both expensive and not well-suited for a large teaching laboratory. This paper presents an alternative procedure using a mixture of cobalt chloride and sodium borohydride to achieve the reduction of methyl oleate to methyl stearate. This procedure is safe, simple, and inexpensive. NMR spectroscopy is used as an analytical tool to determine the extent of the reduction.

KEYWORDS: Second-Year Undergraduate, Upper-Division Undergraduate, Organic Chemistry, Microscale Lab, Catalysis, Oxidation/Reduction, Laboratory Instruction, NMR Spectroscopy, Green Chemistry, Hands-On Learning/Manipulatives

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INTRODUCTION The reduction of simple alkenes is usually carried out by a direct hydrogenation reaction using hydrogen gas and a metal catalyst such as platinum, palladium, or nickel, or a hydrogen transfer reaction using platinum and a hydrogen donor such as cyclohexene.1 One commercial application of this reaction employs double bond reduction of liquid vegetable oils for the production of margarine, a synthetic butter substitute. The method uses a catalytic hydrogenation system. There are three reasons why catalytic hydrogenation is not a preferred reaction in the undergraduate laboratory. First, the use of pressurized hydrogen gas presents an ignition and explosion hazard. Second, noble metal catalysts are expensive and must be recovered and reused to make the experiment economically sound, and finally, after the reaction is complete, the metal catalyst complexed with hydrogen is very pyrophoric when dry.2 Improper disposal of these materials may result in laboratory fires. In our laboratories we became interested in developing a hydrogenation experiment that avoided these hazards. These reductions can be performed using renewable solvents and sodium borohydride in conjunction with first row transition metal catalysts as an alternative to conventional hydrogenation reductions. The use of first row transition metal catalysts provides not only an economic advantage due to their greater relative abundance with respect to heavier metals, but a reduced carbon dioxide footprint due to manufacturing/refining as well.3 A search of the literature revealed that a viable alternative to catalytic hydrogenation was the use of the hydrogen source sodium borohydride and an inexpensive transition metal such as cobalt.4,5 The described procedure still illustrates the direct reduction of a double bond in the presence of other functional groups but avoids the hazards and expense of the traditional catalytic hydrogenation. © XXXX American Chemical Society and Division of Chemical Education, Inc.

A search of the index of this Journal revealed several papers that described undergraduate experiments for the reduction of alkenes.6−9 Many of these papers used some form of catalytic hydrogenation. Metallic hydrides, such as sodium borohydride, do not typically reduce carbon−carbon double bonds unless the bond is polarized. Sodium borohydride is a mild reducing agent that is safe to handle (with respect to harsher reducing agents such as lithium aluminum hydride) that can be used in aqueous or alcoholic solutions. Sodium borohydride slowly decomposes in water and is thermally stable, although an increase in temperature decreases its stability. Satyanarayana and Perisamy have shown that a variety of double bonds can be reduced effectively using cobalt chloride hexahydrate (CoCl2·6H2O) coupled with sodium borohydride (NaBH4).4 Back et al. have made the same observation with nickel chloride.10 Although the mechanism of the reaction is not fully understood, it may be analogous to a hydrogen transfer process where cobalt tetraborohydride (Co(BH4)2) is formed and serves as a hydrogen donor to the double bond.11,12 The reaction performed in this lab exercise is shown in Scheme 1. Methyl oleate was chosen as the substrate for several reasons: (1) The material was inexpensive and readily available. (2) Both reactant and product were nontoxic. (3) It is the same ester present in unsaturated oils, and it serves as an example for the preparation of commercial materials such as margarine and as a model for this type of reaction. Received: May 16, 2018 Revised: February 18, 2019

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DOI: 10.1021/acs.jchemed.8b00222 J. Chem. Educ. XXXX, XXX, XXX−XXX

Journal of Chemical Education

Laboratory Experiment

Scheme 1. CoCl2/NaBH4 Reduction of Methyl Oleate

Figure 1. Comparison of product of sodium borohydride/cobaltous chloride hexahydrate reduction (lower), and the methyl oleate starting reagent (upper). Proton integrations, in both spectra, are with respect to the methyl group (3.0) of the ester moiety (δ = 3.6 ppm).

scale synthesis. The experiment was tested in one second-year and two upper-division undergraduate organic laboratory classes, for a total of 30 students, working in pairs. The pedagogic goals of this experiment for each student were to gain synthetic and analytical experience from the ability to

(4) The melting points of the starting material and the product are radically different and can illustrate the relationship between structural and physical properties. (5) Second-year undergraduate organic chemistry classes often emphasize only the qualitative nature of NMR spectroscopy. The reduction of methyl oleate to methyl stearate is an excellent opportunity in the laboratory to emphasize NMR spectroscopy as an analytical tool. The extent of the reduction of the alkene moiety in methyl oleate can be quantitatively calculated by the integration of the alkene protons with respect to the protons of the methyl ester. Moreover, these methyl protons act as an excellent internal standard because they not only are left unaffected by the reduction but are sufficiently downfield and isolated from other alkane protons so as to be easily selected for integration. The experiment as described is a modification of a previously published procedure.13 The procedure has been modified to be carried out in a much shorter reaction time and adapted for small

(1) (2) (3) (4) (5)

reduce methyl oleate to methyl stearate understand the importance of temperature control illustrate the use of mixed solvents purify the product using extraction characterize the product using melting point as well as 1H NMR spectroscopy (6) demonstrate NMR spectroscopy as an analytical tool Moreover, an integration of green chemistry principles (renewable solvents, low energy costs, and use of first row transition metal catalysis) into modern academic curricula is an increasing trend and reflects the growing interest of students toward environmental stewardship and responsibility.14 B



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EXPERIMENT The procedure was a very straightforward example of the reduction of a double bond, in this case by a cobalt-catalyzed borohydride reduction. The entire synthetic procedure was accomplished in a typical 3 h laboratory period. NMR spectroscopic and melting point data interpretation was discussed in a subsequent laboratory period. The students began the experiment by preparing a solution of cobalt chloride hexahydrate in ethyl alcohol (for shorter laboratory periods this may be done ahead of time). Once the solution is complete, methyl oleate was added and the solution was cooled in an ice bath to 5 °C. A freshly prepared solution of sodium borohydride in ethyl alcohol was then added at such a rate that the temperature did not exceed 10 °C. Typical addition times were in the range of 20−25 min. The reaction was continued for an additional 15 min, after the end of the borohydride addition, to ensure completion. The dark solution was then poured into 1 M hydrochloric acid and extracted with ether. The ether layer was dried over MgSO4, and then vacuum filtered to remove the drying agent. The ether/ethanol solvent was removed to give methyl stearate as a white solid. The experimental conditions are given in greater detail in the Supporting Information.

goals was accomplished using the written answers to postlab questions. Analysis of the students’ answers indicated that they understood the relationship between the changes in the intensity of the alkene protons and the reduction conditions of the experiment. Comprehension of the beneficial use of renewable solvents, first row transition metal catalysts, and ambient pressure conditions in place of older and more hazardous conditions was observed as well. Students overall performed well in performance of the laboratory experiment, the calculations of alkene reduction, and the subsequent postlab questions.

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CONCLUSIONS Students learned in this experiment that a mixture of cobalt chloride and sodium borohydride in ethanol can reduce alkenes whereas similar reductions usually involve much harsher conditions (e.g., a hydrogen source and a catalyst). Product synthesis was confirmed by NMR spectroscopy and melting point. This procedure is safe, simple, and inexpensive as opposed to conventional reduction procedures that are both expensive and not well-suited for a large teaching laboratory. Moreover, the use of environmentally benign solvents and first row transition metal catalysts in the reaction scheme demonstrated the efficacy of green synthetic chemistry in a laboratory setting.

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HAZARDS Cobalt chloride hexahydrate is a potential carcinogen. It, as well as ethyl alcohol, sodium borohydride, ethyl ether, d6-acetone, and hydrochloric acid, are toxic by ingestion, inhalation, and absorption through the skin. Reaction of NaBH4 with CoCl2 in alcohol is exothermic and deposits a black granular precipitate of cobalt boride (Co2B) while steadily evolving hydrogen gas. Methyl oleate and methyl stearate are considered to be nontoxic. The experiment should be carried out in a hood. Gloves and goggles should be worn.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available on the ACS Publications website at DOI: 10.1021/acs.jchemed.8b00222. Student handout, questions, NMR spectra, and instructor notes (PDF, DOCX)

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AUTHOR INFORMATION

Corresponding Author

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*E-mail: [email protected].

RESULTS AND DISCUSSION A total of 30 students in three sections recovered a white waxy product with an average 52 ± 5% yield. The experiments were completed within a 3 h period. After the samples air-dried, the 1 H NMR spectra and melting points of samples were obtained during a subsequent lab period. The 1H NMR spectra confirmed formation of the desired methyl stearate as indicated by the disappearance of signals of the olefinic and allylic protons at 5.2−5.4 and 2.0 ppm, respectively. Figure 1 illustrates the decrease in signal intensity of the olefinic protons that was used to determine the extent of reduction in the laboratory experiment. Unobstructed NMR resonances in the alkene region and those associated with the methyl protons on the ester moiety (δ = 3.6 ppm) lend themselves to unambiguous integration. The average conversion of alkene to the corresponding alkane based on 1H NMR analysis was 70 ± 6%. The melting point range of the students’ samples was 36−38 °C (lit. value 37−41 °C).15 Melting points could not be recorded within the same period that the experiment was run because the samples were too waxy. The experiment gave the second-year and advanced organic chemistry students experience in techniques of both synthesis and analysis. The students gained synthetic experience using sodium borohydride for reactions other than the reduction of carbonyls and illustrated the use of reagents other than hydrogen to achieve double bond reduction. Assessment of pedagogic

ORCID

James R. McKee: 0000-0002-6943-665X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors would like to thank the students in the organic laboratories for student testing this experiment and providing valuable feedback.

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REFERENCES

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(6) Plummer, B. The Catalytic Hydrogenation of Methyl Oleate by In Situ Hydrogen Generation. J. Chem. Educ. 1989, 66, 518−519. (7) Pavlik, J. W. Catalytic Hydrogenation Using Nickel Boride. J. Chem. Educ. 1972, 49, 528. (8) Wilen, S.; Kremer, C. Hydrocinnamic Acid-Catalytic Hydrogenation. J. Chem. Educ. 1962, 39, 209−210. (9) Kulp, S. Knoevenagel Condensation to α-Phenylcinnamonitriles: Sodium Borohydride Reduction to Propanenitriles. J. Chem. Educ. 1988, 65, 742. (10) Back, T.; Baron, D.; Yang, K. Desulfurization with Nickel and Cobalt Boride: Scope, Selectivity, Stereochemistry, and Deuterium Labeling Studies. J. Org. Chem. 1993, 58, 2407−2413. (11) Heinzman, S.; Ganem, B. Mechanism of Sodium BorohydrideCobaltous Chloride Reductions. J. Am. Chem. Soc. 1982, 104, 6801− 6802. (12) Lundevall, F.; Elumalai, V.; Drageset, A.; Totland, C.; Bjorsvik, H. A Co2B Mediated NaBH4 Reduction Protocol Applicable to a Selection of Functional Groups in Organic Synthesis. Eur. J. Org. Chem. 2018, 2018, 3416−3425. (13) Zanger, M.; McKee, J. Essentials of Organic Chemistry: Small Scale Laboratory Experiments; McGraw-Hill: New York, 1997; pp 73−77. (14) Anastas, P.; Eghbali, N. Green Chemistry: Principles and Practice. Chem. Soc. Rev. 2010, 39, 301−312. (15) Babich, M. W.; Hwang, S. W.; Mounts, R. D. The Thermal Analysis of Energy Storage Materials by Differential Scanning Calorimetry. Thermochim. Acta 1992, 210, 77−82.

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