Visualization of Phase-Transfer Catalysis through Charge-Transfer

Laboratory Experiment pubs.acs.org/jchemeduc

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

Visualization of Phase-Transfer Catalysis through Charge-Transfer Complexes Marcos Caroli Rezende,*,† Carolina Aliaga,†,‡ German Barriga,§ and Matías Vidal† †

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Facultad de Química y Biología, Universidad de Santiago de Chile, Avda. Libertador Bernardo O’Higgins 3363, Santiago, Chile 9160000 ‡ Centro para el Desarrollo de la Nanociencia y la Nanotecnología (CEDENNA), Universidad de Santiago de Chile, Avda. Libertador Bernardo O’Higgins 3363, Estación Central, Santiago, Chile 9160000 § Universidad Metropolitana de Ciencias de la Educación, Avda. José Pedro Alessandri 774, Ñ uñoa, Santiago, Chile 7760197 S Supporting Information *

ABSTRACT: Unlike the large number of laboratory experiments on phasetransfer catalysis (PTC) that focus on a catalyzed chemical process, the present laboratory emphasizes the mechanism of phase-transfer catalysis itself. Students can follow visually the actual transfer of the reagent by the catalyst, and its consumption in the organic phase, in a step-by-step process that employs a colored charge-transfer (CT) complex as the transferred reacting species. Consumption of the transferred nucleophile is followed by discoloration of the organic phase. This transfer-consumption cycle can be repeated several times by shaking the two separated phases again, allowing students to finally grasp the whole process as a continuous repetition of these cycles. The experiment also links, through visualization, the important synthetic tool of PTC with abstract concepts based on molecular-orbital and hard−soft acid−base theories, invoked in the formation of a CT complex. KEYWORDS: Second-Year Undergraduate, Organic Chemistry, Inquiry-Based/Discovery Learning, Catalysis, Noncovalent Interactions, Nucleophilic Substitution, Solutions/Solvents, Transport properties

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fats,5 Wittig reactions,6,7 soap preparation,8 fulvene synthesis,9 the Robinson annulation,10 oxidations,11−14 esterifications,15 polyester hydrolysis,16 and the synthesis of carbonyl complexes.17 The emphasis of these lab experiments has always been on the chemical process itself, facilitated by the catalyst. The student performs a reaction in the presence of a phase-transfer catalyst and a product is isolated in good yield. Phenomenologically, the actual catalysis is not directly observed, but only inferred by the student. The effect of the catalyst and its mode of action are not visually evident to the student and are only deduced by an a posteriori rationalization. The aim of the present experiment is to allow a student to visually follow the actual transfer of the nucleophile by the catalyst, and its consumption in the organic phase. In order to achieve this, a colored charge-transfer complex is employed, the formation of which is discussed in the laboratory. The student thus links abstract concepts, normally pertaining to other courses, such as molecular orbitals and the hard−soft acid−base (HSAB) theory, with a synthetic procedure in an organic chemistry lab.

elating and interpreting observations in a chemistry laboratory with abstract concepts is often a challenge for an average student. Not uncommonly, the mechanism of a chemical process, explained with abstract concepts, is supposedly understood when it is carried out and its outcome verified by the student in the laboratory. Teachers are often disappointed when they discover that, for increasingly visually oriented students, verbal, abstract explanations and concepts are surprisingly difficult to grasp without visualization. Accordingly, linking conceptual with visual understanding of chemical processes has been the goal of many publications.1Another frequently encountered obstacle in the learning process is the difficulty to establish links between various chemical concepts, especially if they are transmitted through different courses or regarded as belonging to different areas. The above difficulties and limitations were met when trying to explain the mechanism of phase-transfer catalysis (PTC) to second-year undergraduate organic chemistry students through traditional methods, based on diagrams of equilibria, and reactions that cannot be visually followed by the students. Phase-transfer catalysis has found widespread use in organic synthesis since it was first described nearly half a century ago.2 The large number of papers with applications of PTC to chemical processes testifies to its importance in an undergraduate lab.3−17 PTC has been employed in lab experiments involving nucleophilic substitutions,3,4 tests for unsaturated © XXXX American Chemical Society and Division of Chemical Education, Inc.

Received: January 17, 2018 Revised: June 6, 2018

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DOI: 10.1021/acs.jchemed.7b00988 J. Chem. Educ. XXXX, XXX, XXX−XXX

Journal of Chemical Education

Laboratory Experiment

Application of the method to one of the commonest mechanisms in organic chemistry, a nucleophilic displacement reaction, offers students the opportunity of following the reaction by simply observing the gradual disappearance of the colored reagents in the organic phase. The process is followed qualitatively by visual inspection or more quantitatively with the aid of a UV−vis spectrometer. The lab experiment described herein employs the N-butyl2,4,6-triphenylpyridinium tetrafluoroborate as phase-transfer catalyst for the reaction between 3-bromo-1-propene and the potassium O-ethyldithiocarbonate (“potassium xanthate”) in a two-phase system composed of water and dichloromethane. This nucleophilic displacement is shown in Scheme 1.

Figure 1. Diagram illustrating the process of PTC with the aid of a CT complex that acts as a catalyst, transferring the nucleophile (Nu−) to the organic phase, where it reacts with a halide in a SN2 reaction.

Scheme 1. Nucleophilic Reaction of 3-Bromo-1-propene with Potassium O-Ethyldithiocarbonate

of a model N-methylpyridinium cation was a forbidden process in the case of the HOMO of the hard species but an allowed one in the case of the soft anion (see Figure S2 page S6). This rather abstract theoretical picture was translated into organic concepts, making use of the equilibrium that occurs in the aqueous phase, depicted in Scheme 2. Thus, the nature of the CT complex in Figure 1 became clear to all students. Scheme 2. Equilibrium between the Two Pyridinium− Anion Pairs in the Water−Dichloromethane System

Unlike many tetraalkylammonium salts employed in PTC, the N-alkylpyridinium cation is capable of forming colored charge-transfer (CT) complexes with soft anions in organic solutions. Other N-alkyl-2,4,6-triphenylpyridinium tetrafluoroborates may be employed besides the N-butyl derivative. They are all prepared in a similar way, by reaction of 2,4,6triphenylpyrylium tetrafluoroborate and the corresponding alkyl amine, leading to stable, nonhygroscopic crystalline salts.18 3-Bromo-1-propene is chosen as a convenient alkyl halide because of its fast reaction with this sulfur nucleophile. It may be replaced by other alkyl halides if a visual comparison of the reactivity of different alkyl derivatives is also desired.

After the prelab introduction, the students confirmed visually the formation of the charge-transfer complex in the aqueous phase and its transfer to the organic phase: no change was observed in the colorless organic phase when a mixture of dichloromethane and an aqueous solution of potassium Oethyldithiocarbonate was shaken, and the two phases were allowed to separate again. However, addition of N-butyl-2,4,6triphenylpyridinium tetrafluoroborate to the mixture resulted, after shaking again, in a two-phase system with a yellow dichloromethane layer, due to the formation of a pyridinium/ O-ethyldithiocarbonate charge-transfer complex. The students could notice that no colored complex was formed with the hard BF4− counterion: a dichloromethane solution of the pyridinium tetrafluoroborate was colorless. Its UV−vis spectrum confirmed the presence of the pyridinium cation (λmax at 310 nm) but not of a charge-transfer complex. With the soft dithiocarbonate ion, a yellow species resulted and a small, additional band with a λmax value of 407 nm appeared in its UV−vis spectrum (see Figure S3 page S7)

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EXPERIMENTAL OUTLINE The organic laboratory experiment described here was carried out by second-year undergraduate students in the course of 3− 4 h and consisted of three parts: (1) a prelab introduction; (2) a series of small-scale experiments illustrating the formation of a charge-transfer complex, the mechanism of phase-transfer catalysis, and the different reactivity of two substrates; and (3) the application of PTC in synthesis, in the preparation, isolation, and characterization of the product. Prelab Introduction

In a prelab introduction, the process of phase-transfer catalysis was described with the aid of a diagram (Figure 1). Students were told that the reaction step in the dichloromethane layer was much slower than the other three steps (return → CT formation→ CT complex transfer) and could be observed. CT formation and its transfer from water to the organic layer could also be observed visually

Visualization of the Phase-Transfer Catalysis

After witnessing the formation of the CT complex in the aqueous phase and its transfer to the dichloromethane layer, the students now followed the reaction in the organic phase by adding to it an excess of 3-bromo-1-propene. The gradual disappearance of the yellow color of the organic layer was clearly evident (Figure 2) and was followed both visually (Figure 2) and with the aid of a UV−vis spectrometer (see Figure S4 page S9). After total consumption of the nucleophile in the organic layer, indicated by its complete discoloration, the return step of

Visual Observation of Formation of a Charge-Transfer Complex

The basis for the formation of a charge-transfer complex was explained next, with the aid of an energy diagram that illustrated the difference between a hard species (BF4−) with a large HOMO−LUMO gap and a soft one (C2H5OCS2−) with a smaller HOMO−LUMO gap (see Figure S1 page S5 of the Supporting Information). One-electron transfer to the LUMO B




Figure 2. Discoloration of the yellow solution of the pyridinium/O-ethyldithiocarbonate complex (∼2.3 mM) by the addition of 5 μL (∼0.07 mmol) of 3-bromo-1-propene. Comparison of a blank solution (left tube) with the reacting mixture (right tube) (a) after 30 s (b), 1 min (c), 3 min (d), and 4 min (e). By shaking the decolorized organic solution with 0.5 M aqueous potassium O-ethyldithiocarbonate, the dichloromethane layer recovers its yellow color and a new cycle begins.

Figure 1 closed the first cycle. Another cycle was initiated by shaking the decolorized organic layer with the aqueous solution of potassium O-ethyldithiocarbonate, so that more nucleophile was transferred to the organic layer. After repeating these cycles two or three times, the students could now visually understand the mechanism of phase-transfer catalysis, as a continuous sequence of repeated cycles of nucleophile transfer by the catalyst, and consumption of the transferred nucleophile.

harmful if swallowed, and irritating to the skin. O-Ethyl-S-2propenyldithiocarbonate is a liquid with an unpleasant smell; contact or inhalation should be avoided. It is hydrolyzed to 2propenethiol (allyl mercaptan), a harmful compound if swallowed or inhaled, that causes serious eye irritation.

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PEDAGOGIC GOALS AND ASSESSMENT The present laboratory originated from the idea of visualizing the process of phase-transfer catalysis with the use of a chargetransfer complex, applied to a nucleophilic substitution reaction. The laboratory was carried out for two consecutive semesters, with classes of 8−10 students. The following pedagogic goals, related with each of these subjects, were pursued in this experiment: 1. To have a clear understanding of the mechanism of phase-transfer catalysis. 2. To develop the ability to carry out a nucleophilic substitution reaction employing PTC. 3. To be able to distinguish hard and soft species in terms of their charge densities and of MO theory. 4. To understand the formation of charge-transfer complexes and the capacity to identify them visually and by UV−vis spectroscopy 5. To estimate and compare the reactivities of different alkyl halides in a nucleophilic substitution reaction 6. To develop the ability of relating coupling constants with geometric factors, by the analysis of the 1H NMR spectrum of the product. To assess their achievement in each of these goals, students were asked to answer a set of questions specifically related with their observations. These basic questions were part of the Student Handout (pages S15−S21). In addition, other questions were added to this basic set, asking the students to apply their observations to more general aspects of nucleophilic substitutions and of charge-transfer complexes. In this way, they were asked to relate the in vitro comparison of the two halides as alkylating agents with the in vivo assessment of their relative toxicity, with the aid of the corresponding LD50 values in rats, taken from the literature.20,21 As an application of charge-transfer complexes, they were also asked to relate the structure of the charge-transfer complex formed in this lab experiment, with Kosower’s pyridinium salt as the basis of the Z-scale of solvent polarities.22 Students were evaluated with grades that varied from 1 to 7. Based on their answers to the 13 questions in the Student Handout, the average grades obtained in these semesters were 5.0 and 5.3. Questions related directly with the experiment and with the pedagogic goals were answered satisfactorily. A positive result related with pedagogic goal 2 was their spontaneous suggestion in subsequent classes of the use of PTC to other chemical processes. Students had no difficulty identifying the more reactive halide but had some problem

Comparison of the Reactivity of Different Substrates

The above procedure was flexible enough to be used for a visual comparison of the reactivities of different substrates. Two primary alkyl bromides were used for this comparison, the more reactive 3-bromo-1-propene and 1-bromopropane. By measuring the time required for the total discoloration of the organic phase prepared under the same conditions, the students could compare the two alkyl bromides as substrates of a nucleophilic substitution, relating their reactivities with the nature of the alkyl group. Application of PTC as a Synthetic Tool

Having fully understood the process of phase-transfer catalysis, the students now carried out the same reaction on a preparative, milligram scale, isolating and characterizing the product in an easy and clean process that required little amounts of the reagents. Adopting a variation of a reported procedure,19 the reaction of the O-ethyldithiocarbonate nucleophile with 3-bromo-1-propene was complete after 1 h, with yields that varied among students between 70 and 90% of a rather pure, crude product. The product, O-ethyl-S-2propenyldithiocarbonate, was characterized by its 1H NMR spectrum, which also offered a good opportunity to discuss with the students the relationship between H−H coupling constants and geometric factors (see the Supporting Information for the spectrum and its interpretation, Figures S5, S6, S7, and S8 pages S10, S11, S12, and S13, respectively).

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HAZARDS Dichloromethane [75-09-2] is a possible carcinogenic solvent. Potassium O-ethyldithiocarbonate [140-89-6] is a solid with a sharp, unpleasant smell harmful if swallowed, and irritating to eyes, respiratory system and skin. 2,4,6-Triphenylpyrylium tetrafluoroborate [448-61-3] is a harmful solid if in contact with skin or swallowed. Toxicity of N-butyl-2,4,6-triphenylpyridinium tetrafluoroborate is not known, avoid contact with skin or swallowing the product. 3-Bromo-1-propene [106-95-6] is a lachrymator and a flammable, toxic liquid that should be handled with gloves, avoiding inhalation, or contact with skin or eyes. 1-Bromopropane [106-94-5] is a flammable, harmful liquid, irritating to skin, respiratory system, and eyes. NButylamine [109-73-9] is a flammable, corrosive liquid, harmful by inhalation, in contact with skin or if swallowed. Deuterochloroform [865-49-6] is a possible carcinogen, C




Table 1. Comparison of Students’ Responses to Statements Evaluating Their Experience and Benefits from the Lab Responses by Category, % (N = 18) Statements for Student Response This lab allowed me to understand clearly the mechanism of phase-transfer catalysis. I can now apply PTC in synthesis to other organic reactions. I could understand clearly how and why a charge-transfer complex is formed. Visualization helped me understand abstract concepts more easily. I could distinguish clearly the different reactivities of alkyl halides in a nucleophilic substitution reaction. I could make a link between practical synthetic organic chemistry with theoretical concepts of physical chemistry.

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estimating and comparing quantitatively their reactivities (pedagogic goal 5). Some of them failed to analyze in detail the 1H NMR spectrum of the product (pedagogic goal 6). Such failure could be attributed to the fact that, although with some knowledge of NMR spectroscopy and with the interpretation of simple spectra, they had not taken previously any course on structure determination with the aid of spectroscopic methods. Students had greater difficulties extending their observations to other systems or applications (questions 11−13 of the Student Handout). Nevertheless, they could correctly predict the formation of a charge-transfer complex between a pyridinium cation and an iodide anion, in agreement with Kosower’s polarity indicator.22 Students were also subjected to a questionnaire evaluating their experience and benefits from the lab. Answers were given according to a 5-point Likert scale of agreement.23 Results are summarized in Table 1. Percentages refer to the total of 18 students in two semesters who completed this laboratory experiment as part of their organic chemistry course. Their perception of the experiment and its benefits was rather positive, in agreement with their achievement of the proposed goals, as judged by the evaluations made at the end of the experiment.

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Strongly Disagree

Disagree

Neither Agree nor Disagree

Agree

Strongly Agree

0 0 0 0 0

0 0 0 0 0

0 33 11 0 0

0 56 56 44 11

100 11 33 56 89

0

0

22

45

33

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available on the ACS Publications website at DOI: 10.1021/acs.jchemed.7b00988.

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Instructor’s notes, student handout, and 1H NMR spectrum of the prepared O-ethyl-S-2-propenyldithiocarbonate (PDF, DOC)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Marcos Caroli Rezende: 0000-0003-2040-9009 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS M.C.R. thanks Fondecyt Project 1140212, and G.B. and M.V. thank Project USA 1555-VRIDEI-USACH for research grants. C.A. thanks CEDENNA, Project PB0807.

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REFERENCES

(1) (a) Smith, J. K.; Metz, P. A. Evaluating student understanding of solution chemistry through microscopic representations. J. Chem. Educ. 1996, 73 (3), 233. (b) Russell, J. W.; Kozma, R. B.; Jones, T.; Wykoff, J.; Marx, N.; Davis, J. Use of simultaneous-synchronized macroscopic, microscopic and symbolic representations to enhance the teaching and learning of chemical concepts. J. Chem. Educ. 1997, 74 (3), 330. (c) Sanger, M. J.; Badger, S. M., II Using computer-based visualization strategies to improve students’ understanding of molecular polarity and miscibility. J. Chem. Educ. 2001, 78 (10), 1412. (d) Ellis, J. T. Assessing the development of chemistry students’ conceptual and visual understanding of dimensional analysis via supplemental use of web-based software. J. Chem. Educ. 2013, 90 (5), 554−560. (e) Dangur, V.; Avargil, S.; Peskin, U.; Dori, Y. J. Learning quantum chemistry via a visual-conceptual approach: students’ bidirectional textual and visual understanding. Chem. Educ. Res. Pract. 2014, 15, 297−310. (2) Starks, C. M. Phase-transfer catalysis. I. Heterogeneous reactions involving anion transfer by quaternary ammonium and phosphonium salts. J. Am. Chem. Soc. 1971, 93 (1), 195−199. (3) Reeves, W. P.; White, M. R.; Bier, D. Nucleophilic substitution by phase transfer catalysis. J. Chem. Educ. 1978, 55 (1), 56. (4) Thompson, D. L.; Reeves, P. C. Phase-transfer-catalyzed alkylation of ethyl acetoacetate and diethyl malonate. J. Chem. Educ. 1985, 62 (10), 907−908. (5) Hill, J. W.; Boyd, T. C. A permanganate test for unsaturated fats using phase transfer catalysis. J. Chem. Educ. 1979, 56 (12), 824.

CONCLUSIONS

Phase-transfer processes are easily understood if they can be visually followed.24 The present laboratory experiment departed from the usual applications of phase-transfer catalysis to organic synthesis by emphasizing as its major goal a clear understanding by the student of the PTC process. Each step of the cycle was carried out independently and visually identified by the students, who could finally arrive at the view of PTC as the result of a continuous repetition of the observed cycle. The use of a charge-transfer complex as the catalyst also offered a visualization of abstract concepts related with MO and HSAB theory, not usually covered in a synthetic organic laboratory. Finally, the experiment proved flexible enough to allow a visual comparison of the relative reactivities of alkyl halides in nucleophilic substitutions. By linking abstract concepts with a simple visualization of their application, this laboratory experiment was evaluated very positively by the students. The most rewarding evaluation was perhaps the short but eloquent comment of one of them at the (cool!). end of the lab: D




(6) Gillois, J.; Guillerm, G.; Stephen, E.; Vo-Quang, L. Diphenylbutadienes syntheses by means of the Wittig reaction: Experimental introduction to the use of phase transfer catalysis. J. Chem. Educ. 1980, 57 (2), 161. (7) Breuer, S. W. The Wittig synthesis of alkenes by phase-transfer catalysis: the syntheses of 4,4’-dichlorostilbenes and of E,E-1,4diphenylbutadiene. J. Chem. Educ. 1991, 68 (3), A58−A60. (8) Hill, J. W.; Soldberg, S. J.; Hill, C. S. A catalyst for the synthesis of soap. J. Chem. Educ. 1982, 59 (9), 788. (9) Hill, J. W.; Jenson, J. A.; Yaritz, J. G. Synthesis of fulvenes using phase-transfer catalysis. J. Chem. Educ. 1986, 63 (10), 916. (10) Soriano, D. S.; Lombardi, A. M.; Persichini, P. J.; Nalewajek, D. Example of the Robinson annulation procedure via phase transfer catalysis-a beginning organic synthesis experiment. J. Chem. Educ. 1988, 65 (7), 637. (11) Amsterdamsky, C. Phase transfer catalysis applied to oxidation. J. Chem. Educ. 1996, 73 (1), 92. (12) Hulce, M.; Marks, D. W. Organic-solvent-free phase-transfer oxidation of alcohols using hydrogen peroxide. J. Chem. Educ. 2001, 78 (1), 66−67. (13) Lampman, G. M.; Sharpe, S. D. A phase transfer catalyzed permanganate oxidation: preparation of vanillin from isoeugenol acetate. J. Chem. Educ. 1983, 60 (6), 503−504. (14) Hill, J. W.; Jenson, J. A.; Henke, C. F.; Yaritz, J. G.; Pedersen, R. L. Oxidation of alcohols using calcium hypochlorite and solid/liquid phase-transfer catalysis. J. Chem. Educ. 1984, 61 (12), 1118. (15) Yeadon, A.; Turney, T. A.; Ramsay, G. The preparation of benzoyl esters of phenols and benzoic anhydride by phase-transfer catalysis. J. Chem. Educ. 1985, 62 (6), 518. (16) Priya, R. J.; Sarkar, S.; Shamili, G.; Sugumar, R. W. Microwave assisted depolymerization of post consumer PET waste using phase transfer catalysts. Chem. Educ. 2014, 19, 61−63. (17) Birdwhistell, K. R.; Conroy, K. J.; Schulz, B. E. Greening the inorganic lab: combining microwaves and phase transfer catalysis for the rapid synthesis of group VI carbonyl complexes. Chem. Educ. 2014, 19, 133. (18) Katritzky, A. R.; Kenny, D. H.; Sheikh, H.; Gruntz, U.; Rezende, M. C. Heterocycles in organic synthesis. Part 10. Conversion of amines into esters. J. Chem. Soc., Perkin Trans. 1 1979, 430−432. (19) Degani, I.; Focchi, R. The phase-transfer synthesis of O,Sdialkyl dithiocarbonates from alkyl halides and alkyl methanesulfonates. Synthesis 1978, 1978, 365−368. (20) Handbook of Toxicology, 2nd ed. Derelanko, M. J., Hollinger, M. A., Eds.; CRC Press: New York, 2001; Table 33.1. (21) Sigma-Aldrich. Allyl bromide, Material Safety Data Sheet, version 4.7; Revision Date, May 2, 2013; Print Date January 16, 2014; https://www.nwmissouri.edu/naturalsciences/sds/a/ Allyl%20bromide.pdf (accessed June 2018). (22) Kosower, E. M. The effect of solvent on spectra. I. A new empirical measure of solvent polarity: Z-values. J. Am. Chem. Soc. 1958, 80 (13), 3253−3260. (23) Armstrong, R. The midpoint on a Five-Point Likert-Type Scale. Percept. Motor Skills 1987, 64 (2), 359−362. (24) Alkilany, A. M.; Mansour, S.; Amro, H. M.; Pelaz, B.; Soliman, M. G.; Hinman, J. G.; Dennison, J. M.; Parak, W. J.; Murphy, C. J. Introducing Students to Surface Modification and Phase Transfer of Nanoparticles with a Laboratory Experiment. J. Chem. Educ. 2017, 94 (6), 769−774.

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Visualization of Phase-Transfer Catalysis through Charge-Transfer

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