Isobutylene Dimerization: A Discovery-Based Exploration of

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

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Isobutylene Dimerization: A Discovery-Based Exploration of Mechanism and Regioselectivity by NMR Spectroscopy and Molecular Modeling Mariah L. Schuster,† Karl P. Peterson,† and Stacey A. Stoffregen*,‡ †

Department of Chemistry and Biotechnology, University of WisconsinRiver Falls, 410 S. Third Street, River Falls, Wisconsin 54022, United States ‡ Department of Chemistry, Bethel University, 3900 Bethel Drive, St. Paul, Minnesota 55112, United States S Supporting Information *

ABSTRACT: This two-period undergraduate laboratory experiment involves the synthesis of a mixture of isomeric unknowns, isolation of the mixture by means of distillation, and characterization of the two products primarily by NMR spectroscopy (1D and 2D) supported with IR spectroscopy and GC−MS techniques. Subsequent calculation and examination of the relative energies of the products and of the lowest unoccupied molecular orbital of the products’ common cationic intermediate provide a means of understanding the unique regioselectivity of the reaction. The combination of spectroscopic, spectrometric, and molecular modeling data obtained by students allows them not only to identify the products and propose a reasonable stepwise mechanism for the reaction, but also to rationalize why the non-Zaitsev product predominates. KEYWORDS: Second-Year Undergraduate, Laboratory Instruction, Organic Chemistry, Inquiry-Based/Discovery Learning, Alkenes, Conformational Analysis, Constitutional Isomers, Mechanisms of Reactions, Molecular Modeling, NMR Spectroscopy

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INTRODUCTION The dimerization of isobutylene (Scheme 1) produced by the dehydration of 2-methylpropan-2-ol was extensively studied in the 1930s.1−3

mixture predominantly by NMR and molecular modeling data. Computational molecular modeling is increasingly being incorporated into the organic chemistry laboratory curriculum as a means of supporting wet-chemical observations.8−13 Discovery-based and guided-inquiry laboratory experiments are also becoming prevalent in the organic chemistry laboratory curriculum, and informal evidence suggests students are more engaged when these approaches are used.14−16 Many discoverybased and guided-inquiry laboratory experiments involving the identification of unknowns, product analysis, and mechanistic studies have appeared in the recent literature.17−31 The experiment reported herein combines the discoverybased laboratory approach and the use of molecular modeling to assist students in characterizing a reaction with unusual regioselectivity. In the reported experiment students are given a procedure for conducting a reaction and isolating a product mixture for which the composition and structures are not provided. Students then use a combination of GC−MS, IR spectroscopy, 1H NMR spectroscopy, and 13C NMR spectroscopy (decoupled and DEPT) to determine that the product contains a mixture of isomers, to solve the structures of the two dimerization products that were selectively collected by distillation, and to propose a reasonable stepwise mechanism

Scheme 1. Dimerization of Isobutylene

This reaction has been commonly used as an example of alkene dimerization and has been the basis of an expository laboratory experiment that allows students to verify the expected results.4−6 One limitation of this experiment as a preparative experiment is that two isomeric trimethylpentenes are produced and analyzed as a mixture. Additionally, the reaction produces the less substituted alkene as the major component of the product mixture. A previous report in which this experiment was adapted to a “puzzle”-based approach focused on the use of GC−MS and IR spectroscopy alone to analyze both the dimerization and trimerization products collected.7 In this report, the dimerization reaction has been repackaged as a discovery-based, culminating experience for a secondsemester organic chemistry laboratory course in which the students’ discovery involves analysis of an unknown product © XXXX American Chemical Society and Division of Chemical Education, Inc.

Received: July 20, 2017 Revised: March 23, 2018

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DOI: 10.1021/acs.jchemed.7b00453 J. Chem. Educ. XXXX, XXX, XXX−XXX

Journal of Chemical Education

Laboratory Experiment

is provided in the Supporting Information. The student handout also includes a list of the principles of green chemistry that apply to the experiment, in order to raise student awareness of efforts that may be made when conducting reactions to lessen their impact on the environment.32

for the transformation. Additionally, students use molecular modeling to optimize the structure of the common cationic intermediate from which the two products form and calculate the energies of the two products. Students are ultimately charged with using the LUMO of the optimized cationic intermediate to rationalize the observation that the less substituted alkene is the major product of the reaction. The experiment gives students the opportunity to apply a range of instrumental and computational modeling techniques toward understanding a chemical reaction in which the less substituted/less stable alkene is favored. This experiment was introduced in the University of WisconsinRiver Falls second-semester organic chemistry laboratory curriculum in the Spring of 2010 and has been conducted every semester (Spring, Summer, and Fall) since then to class sections of up to 22 students. Approximately 700 students, in groups of two, have completed this experiment. The experiment was carried out after students had been formally introduced to all of the techniques required in the experiment, allowing them to focus their attention on the use of spectroscopic, spectrometric, and molecular modeling data to elucidate the product structures and reaction mechanism. Students were allotted two 3 h laboratory periods to complete the experiment which includes the following pedagogic goals. (1) Student acquisition of spectra and interpretation of results from the GC−MS, IR spectroscopy, and NMR spectroscopy ( 1 H, 13 C, and DEPT) experiments conducted on their isolated mixture of isomers. (2) Student use of molecular modeling software to obtain optimized intermediate and product structures. (3) Student use of data analysis and critical thinking skills to identify the components of the mixture. (4) Student evaluation of the intermediate’s LUMO and conformational analysis to understand the reaction mechanism and product distribution. Upon completion of the laboratory experiment, students write a laboratory report in which they discuss their spectroscopic and spectrometric data, propose a reaction mechanism, and answer a specific question regarding the reaction and product distribution. Achievement of the pedagogic goals was assessed through the laboratory reports. The average score on 194 student laboratory reports from several spring semesters (2010, 2011, 2012, 2013, 2014, and 2016) was 81 ± 5.6%.

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HAZARDS Sulfuric acid is a strong oxidizer, is corrosive, and can cause eye, skin, and respiratory burns. 2-Methylpropan-2-ol is a highly flammable liquid that can cause eye and respiratory irritation. Anhydrous sodium sulfate is a mild skin and eye irritant. Chloroform-d is an acute oral, inhalation, and reproductive toxin, a skin and eye irritant, and a carcinogen. 2,4,4Trimethylpent-1-ene is a highly flammable liquid. 2,4,4Trimethylpent-2-ene is a highly flammable liquid; is a skin, eye, and respiratory irritant; and may be fatal if swallowed. Use gloves and proper eye protection when handling all of the chemicals and avoid inhaling vapors. The reaction and workup should be conducted in a fume hood.

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RESULTS AND DISCUSSION Upon isolation and characterization of the product mixture, students are generally able to identify the structures of the two products through interpretation of the data with minimal supplemental instruction. GC−MS

The chromatogram clearly indicates the presence of two compounds in a ratio of ∼3.5 to 1 (Supporting Information, Figure S1). The mass spectrum of the major product gives a molecular ion of 112 amu and a major fragment of mass 57 amu from allylic cleavage of the C3−C4 bond (Figure S2). The mass spectrum of the minor product gives a molecular ion of 112 amu and major fragments at 97 from the allylic fragmentation of the C4−C5 bond, and 57 and 55 amu from the vinylic fragmentation of the C3−C4 bond (Figure S3). From this information students determine that the reaction generates two products in a ratio of ∼3.5:1. Students recognize that the two products are isomers with a molecular weight of 112 amu. Students generate a formula of C8H16 (one degree of hydrogen deficiency), although some students also briefly consider C7H12O (two degrees of hydrogen deficiency). Students are not experienced enough with mass spectral data interpretation to use the fragmentation data alone to solve the structures, but they are able to identify reasonable fragmentation events once the product structures are known.

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EXPERIMENTAL PROCEDURE 2-Methylpropan-2-ol (15.0 mL, 157 mmol) and sulfuric acid (9 M, 32 mL) are refluxed for 30 min. Upon cooling, the twophase reaction mixture undergoes a workup with water, followed by treatment with a dilute sodium bicarbonate solution to isolate the organic layer. The organic layer is dried over anhydrous sodium sulfate and purified by simple distillation. The fraction that distills from 98 to 106 °C is isolated, and each pair of students analyzes their collected product by GC−MS, FTIR spectroscopy, and NMR (1H, decoupled 13C, and DEPT) spectroscopy in chloroform-d. Typical student percent yields are 38.2 ± 4.7%, corresponding to 3.4 g (30 mmol) of product. Optimized geometries, performed at the B3LYP/6-31G(d) level, of the two alkene products and the cationic intermediate are obtained using molecular modeling software. The student handout, which includes a detailed procedure for all aspects of the experiment,

Infrared Spectroscopy

The infrared spectrum of the product mixture provides strong indications of alkene functionality (Figure S4). There is a vinyl CH stretch at 3076 cm−1, an aliphatic CH stretch from 2867 to 2955 cm−1, and a CC stretch at 1641 cm−1. There is a prominent geminal disubstitution signal at 892 cm−1 from the major product and a small trisubstitution signal at ∼825 cm−1 from the minor product. Students identify that the spectrum clearly indicates the presence of a CC, although many students do not initially account for the geminal disubstitution signal at 892 cm−1. The trisubstitution signal at ∼825 cm−1 is nearly always overlooked by students until the structure of the minor product is solved. The lack of evidence in the IR spectrum for CO, CO, or OH stretching generally causes students to reject C7H12O as a possible molecular formula at this stage in their interpretation. B




Figure 1. Representative student 1H NMR spectrum of product mixture.

Figure 2. (A) Structure of the common cationic intermediate leading to the formation of the two products. (B) Structure of the cationic intermediate optimized at B3LYP/6-31G(d). (C) Lowest unoccupied molecular orbital (LUMO) looking down the C*-carbocation C bond. (D) Side view of the LUMO. (E) LUMO looking down the CX-carbocation bond. 1

H NMR Spectroscopy

Additionally, students are not expected to uniquely identify the vinylic protons in the major product (Figure 1G,H) or the allylic methyls in the minor product (Figure 1c,d). Time permitting, the experiment may be expanded to include conclusive assignment of proton signals c, d, G, and H by use of a NOESY experiment (Figures S9−S10) and by comparison of the observed chemical shifts with calculated and scaled chemical shifts of those protons (B3LYP/6-31G(d)) (Table S4).33

All of the signals for both products are completely resolved in the 1H NMR spectrum (Figure 1). The signals are clean singlets or singlets with very small coupling. The major product displays a t-butyl signal at 0.92 ppm, an allylic methyl signal at 1.77 ppm, an allylic methylene signal at 1.93 ppm, and two vinylic signals at 4.62 and 4.82 ppm. The minor product shows a t-butyl signal at 1.09 ppm, two allylic methyl signals at 1.66 and 1.71 ppm, and a vinylic signal at 5.17 ppm. Students are initially presented with the challenge of determining which signals are for each of the two compounds. A confounding factor is that the ratio of the products is often ∼3.5:1, which causes a 3H signal in the minor product to integrate nicely with a 1H signal in the major product. The overall integration becomes nonsensical at this point, which encourages students to reevaluate their integration work. Students are told that all of the signals should be considered as singlets, despite the fact that very small coupling constants are observed. Students are not experienced with geminal or allylic coupling and are not expected to interpret the coupling data to solve the structures.

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C NMR Spectroscopy

All of the signals for both products are completely resolved (Figure S7). There are eight aliphatic signals at 18.78, 25.25, 27.98, 30.06, 31.16, 31.34, 32.07, and 51.68 ppm. There are also four vinylic signals at 113.70, 130.20, 135.04, and 144.06 ppm. Students confirm the presence of four vinylic carbons and eight types of aliphatic carbons. With DEPT 45, 90, and 135 data (Figure S8) students are able to conclusively assign 3 of the 12 signals: (1) the vinylic CH of the minor product, (2) the allylic CH2 of the major product, and (3) the vinylic CH2 of the major product. C




Molecular Modeling

incomplete purpose section, and/or insufficiently detailed procedure and observation sections in their laboratory report.

Students are able to confirm that the trisubstituted alkene is 2.33 kcal/mol lower in energy than the geminally disubstituted alkene (Table S2). This leaves them to reconcile why the more stable product is not the major product as would be expected for this type of reaction. Students often initially propose that the observed product distribution is a result of probability [i.e., the major product arising from removal of one of six methyl hydrogen atoms (labeled * in Figure 2) and the minor product arising from removal of one of two methylene hydrogen atoms (labeled x in Figure 2)]. Examination of the LUMO of the optimized cationic intermediate structure allows students to see that one of the two methyl groups (labeled * in Figure 2) adjacent to the cationic carbon has a hydrogen atom that is coplanar with the empty p orbital on the cationic carbon. Rotation of 68° would be required for one of the methylene hydrogen atoms (labeled x in Figure 2) to adopt the necessary coplanar orientation for elimination to occur, and rotation of 59° would be required for the other methylene hydrogen atom to adopt the needed orientation (Figure 2). Ultimately, students use this structural observation to rationalize the greater abundance of the geminally disubstituted alkene. A coordinate scan at the B3LYP/6-31G(d) level indicates a 4.3 kcal/mol barrier to the aforementioned rotation. Although students are not instructed to conduct a coordinate scan to identify the energy barrier associated with the rotation, the instructor may share data from the scan with his or her students to demonstrate additional support for the observed regioselectivity.

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Student Assessment

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SUMMARY The preparation of isobutylene dimers has been successfully adapted as a discovery-based experiment for the organic laboratory which incorporates computational molecular modeling. Students have found studying this alkene dimerization reaction to be rewarding and intellectually challenging as evidenced by the results of an informal survey distributed at the completion of the semester in which students rate the laboratory experiments they have conducted during the semester. The experiments conducted, ranging from expository to discovery-based, received ratings that ranged from 3.1 to 4.3 on a 5-point scale from a typical semester, with an average of 3.9. The experiment reported herein received the top rating of 4.3. Students are able to apply many of the laboratory techniques that they have learned throughout the organic chemistry laboratory curriculum toward understanding a reaction whose outcome deviates from that expected on the basis of the thermodynamics of the products.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available on the ACS Publications website at DOI: 10.1021/acs.jchemed.7b00453. Student handout (PDF, DOCX) Notes for instructors and detailed spectroscopic information (PDF, DOCX)

Upon completion of the experiment, students organize and interpret their data on a provided report form (Supporting Information). The report form encourages students to compile their data in a tabular format and serves as a means for assessing their ability to interpret the spectrometric and spectroscopic data. On the mass spectral data table, students are asked to identify each molecular ion’s structure and the associated fragments. The median student score from a typical semester on this portion of the laboratory report was 88%. Students are generally quite successful in identifying the functional groups evident in the IR spectrum of the mixture and providing their interpretation on an IR spectral data table for which the median score was 100%. The 1H NMR data table requests that students provide the two product structures, including the assignment of each hydrogen atom to its signal. The majority of students showed minor or no errors on the table resulting in a median score of 94%. A student’s ability to successfully assign the vinylic and allylic signals in the 13C NMR spectrum to C atoms in the product structures is assessed by completion of the 13C NMR data table. The median student score from a typical semester on this portion of the laboratory report was 100%. In addition to completing data tables, the students are asked to proposed a reasonable stepwise mechanism accounting for the formation of the two observed isomers. With the exception of minor mistakes, such as the occasional misplaced charge or the omission of a conjugate base byproduct, students typically demonstrate a strong understanding of the mechanistic principles related to the dimerization, accounted for by a median score of 94%. Although the average score of 81 ± 5.6% on the full laboratory report, including the report form, is lower than the assessment scores reported above, the difference can largely be accounted for by the inclusion of either an

AUTHOR INFORMATION

Corresponding Author

*E-mail: s-stoff[email protected]. ORCID

Stacey A. Stoffregen: 0000-0002-3959-0875 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Funding for this project has been provided by the University of WisconsinRiver Falls Chemistry and Biotechnology Department, the University of WisconsinRiver Falls College of Arts and Sciences and Provost’s Office, and by the National Science Foundation CCLI program (DUE-0736504) and MRI program (DUE-1039925).

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Isobutylene Dimerization: A Discovery-Based Exploration of

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