Combining Molecular Modeling with - American Chemical Society

Chapter 7

Downloaded by KANSAS STATE UNIV on September 29, 2016 | http://pubs.acs.org Publication Date (Web): September 15, 2016 | doi: 10.1021/bk-2016-1221.ch007

Combining Molecular Modeling with 13C and DEPT NMR Spectroscopy To Examine the Dehydration of 1-Methylcyclohexanol Julia P. Baker* Division of Business, Mathematics and Sciences, Columbia College, 1301 Columbia College Drive, Columbia, South Carolina 29203, United States *E-mail: [email protected]

In the organic chemistry laboratory, first semester students often undertake a dehydration experiment using one of the methycylohexanol isomers. In an experiment at Columbia College, students explore the dehydration of 1-methylcyclohexanol, using molecular modeling to predict the major product and 13C and DEPT NMR spectroscopy for product analysis. The students are also tasked with adapting a procedure for the experiment from a published method employing an isomeric reagent. Combining the molecular modeling with the 13C and DEPT NMR spectroscopy has enabled students to more readily understand the reaction mechanism and product outcomes.

Introduction Integrating both 1H and 13C NMR into the general chemistry (1–6) and first semester organic chemistry (7–13) courses in order to expose students earlier to spectroscopy is a growing trend. These techniques have been used in introductory courses to help students investigate structural isomerism (5–8, 12), electronegativity (2), conformational analysis (8, 11), kinetics (13), aromaticity and proton exchange (11) as well as to identify products (1, 2, 9). The use of molecular modeling in the organic lab has also become a common experience . (14–17).

© 2016 American Chemical Society Soulsby et al.; NMR Spectroscopy in the Undergraduate Curriculum: First Year and Organic Chemistry Courses Volume 2 ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


The dehydration of methylcyclohexanol isomers is a traditional undergraduate organic experiment most often employing either 2-methylcyclohexanol or 4-methylcyclohexanol. The reaction using 4-methylcyclohexanol as shown in Scheme 1 produces only one product and the experiment’s major purpose is to expose students to a simple dehydration reaction (17). In contrast, the dehydration of the isomeric 2-methylcyclohexanols gives a more complex product mixture as shown in Scheme 2 and the experimental focus is generally for the students to determine the mechanisms by which the different products are formed (18–23). The products of the reaction can be analyzed by GC (18–20), 1H NMR (21, 23) or GC-MS (22). Additionally, examination of the product profile by molecular modeling followed by GC analysis has been reported with this experiment (24).

Scheme 1. Dehydration of 4-methylcyclohexanol.

Scheme 2. Dehydration of 2-methylcyclohexanols. In an effort to introduce Columbia College students to NMR spectroscopy in their first semester of organic chemistry, provide them with more molecular modeling experience, and give them practice with adapting and rescaling an experimental procedure, we developed a lab that explores the dehydration of 1-methylcyclohexanol. Using 1-methylcyclohexanol offers the advantage that it can produce more than one dehydration product (Scheme 3) which students can compare using molecular modeling but doesn’t give the complex mixture seen with 2-methylcyclohexanol which may overwhelm the novice student.

Scheme 3. Dehydration of 1-methylcyclohexanol. 100 Soulsby et al.; NMR Spectroscopy in the Undergraduate Curriculum: First Year and Organic Chemistry Courses Volume 2 ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


Columbia College students are introduced to modeling software early in their first semester of organic chemistry in an exercise investigating molecular conformers. This experiment, however, allows them to employ this tool in a predictive fashion as they use calculated heats of formation to hypothesize which product will be the major one. In reality the reaction gives almost exclusively one product which can be identified by 13C and/or DEPT (distortionless enhancement by polarization transfer) NMR spectroscopy. Introducing NMR spectroscopy through proton decoupled 13C and DEPT NMR in the first semester of organic chemistry seems to be a more logical approach than starting with coupled 1H NMR. The 13C and DEPT spectra are easier to interpret than the more complex 1H spectra which require students to consider peak integrations and spin-spin coupling. The 13C and DEPT spectra also fit well with concepts covered in the first semester of organic chemistry such as molecular structure and symmetry and distinguishing between primary, secondary and tertiary carbons (12). The students are also asked to develop their own procedure for the experiment based on a published procedure for the reaction of 4-methylcyclohexanol. This exercise challenges them to do a little thinking but doesn’t overwhelm them in their first attempt to adapt a reaction procedure. It also helps them develop skills that will be needed in future experiments and undergraduate research. This experiment is often done before we begin our study of alkenes so the students are unfamiliar with Zaitsev’s rule or the relative stability of alkenes and so it is, in essence, a discovery-based experiment.

Experimental Methods 1-Methylcyclohexanol and tetramethylsilane were purchased from Sigma-Aldrich and used without further purification. NMR spectra were obtained using an Anasazi Eft-90 NMR spectrometer. Prior to the lab exercise, the students are given a lab handout which contains an overview of the experiment, a generic dehydration mechanism (E1), and an introduction to 13C and DEPT NMR spectroscopy. As a pre-lab exercise, the students are asked to draw out the reaction mechanism using 1-methylcyclohexanol based on the generic example and to predict the possible products. They are also asked to write out a procedure for the dehydration process based on the dehydration of 4-methylcyclohexanol in their lab text (17) rescaled from 12 mmoles of the methylcyclohexanol to a 20 mmole scale. When the students come to lab, the mechanism, the possible products and the procedure are all discussed before the students proceed with the actual experiment. The students are also given a brief introduction to 13C and DEPT NMR spectroscopy. Part of the introductory materials are the 13C and DEPT spectra of 1-butanol and 2-butanol through which the students work in groups while waiting for the completion of their reactions or waiting to take the spectra of their compounds. After the introductory information, the students’ first tasks are to calculate the energies of the expected products using the Spartan Student (Wavefunction, Inc.) molecular modeling program and then to use this information to predict the major product. The students then proceed to the actual experiment using the 101

Soulsby et al.; NMR Spectroscopy in the Undergraduate Curriculum: First Year and Organic Chemistry Courses Volume 2 ACS Symposium Series; American Chemical Society: Washington, DC, 2016.

procedures they developed. Below is an example procedure using microscale glassware adapted for this experiment.


Dehydration of 1-Methylcyclohexanol 1-Methylcyclohexanol (2.5 mL; 0.020 mol) is placed in a tared 10-mL round bottom flask equipped with a magnetic stir bar or spin vane. To this flask is added 0.67 mL of 85% phosphoric acid and 10 drops of concentrated sulfuric acid. A Hickman distillation head and a water-cooled condenser are then attached to the 10-mL flask and a drying tube filled with calcium chloride is also added. After starting the circulation of the cooling water, the reaction is heated in a sand bath set between 160-180 °C so that the distillation requires approximately 30-45 minutes. During the distillation, a bent tip Pasteur pipet or a 1-mL syringe with a bent needle is used to remove the distillate from the side port of the Hickman head well as it collects. The distillate is placed in a clean, dry 5-mL conical vial and the distillation continued until no more liquid collects. When the distillation is complete, the remaining distillate is removed and the inside of the Hickman distillation head is washed with 1.5-2.0 mL of saturated sodium chloride solution. The wash is then transferred to the 5-mL vial containing the distillate. After the layers have separated, the bottom aqueous layer is removed and the organic layer is dried over granular anhydrous sodium sulfate for 1015 minutes. The dried distillate is then carefully transferred to a tared storage vial using a Pasteur pipet being careful not to transfer any sodium sulfate. The storage vial is then weighed and the percent yield of the reaction calculated. The 13C and DEPT NMR spectra of the product are obtained as a neat sample with tetramethylsilane added (25).

Results and Discussion Heats of formation for 1-methylcyclohexene and methylenecyclohexane determined using the semi-empirical (PM3) calculation in Spartan Student are shown in Scheme 4. Similar values calculated using CAChe have been reported (26). The actual experimental procedure is fairly straight forward and can be completed within an hour leaving time for the students to take 13C NMR spectra assisted by the instructor using a 90 MHz Anasazi instrument. As a time saving practice, only one DEPT experiment is done for each lab section and copies are then made for each student in the section. The reaction carried out as described above yields almost exclusively 1-methylcyclohexene. Analysis of the reaction distillate using 1H NMR shows it does contain 1-2% of methylenecyclohexane but this small amount is not visible on the 13C NMR spectrum. Other authors have reported no methylenecyclohexane in the dehydration of 1-methylcyclohexanol carried out under slightly different conditions and analyzed by GC-MS (22).

102 Soulsby et al.; NMR Spectroscopy in the Undergraduate Curriculum: First Year and Organic Chemistry Courses Volume 2 ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


Scheme 4. Calculated heat of formation values.

When we first began doing this experiment, only 13C NMR was used for product identification. The two isomers are easily distinguishable since the 1-methylcyclohexene gives a carbon spectrum with 7 resonances (Figure 1) and methylenecylohexane produces a spectrum with 5 resonances. Spectra of the possible products are not provided to students in their lab handouts because we do not want them to approach product identification as a matching game but instead want them to analyze the two possible products and realize they will produce rather different spectra. Our students, however, had difficulty with this analysis. They either attempted to carry out an in-depth interpretation of the spectrum trying to assign each individual signal, which at this point was more detail than required, or were baffled at how to approach the problem even after examining several examples in the prelab discussion. Inclusion of the DEPT experiment (Figure 2) seemed to greatly enhance student understanding of the product analysis since they could easily determine the number of CH3’s, CH2’s, CH’s and quaternary carbons in the product from these spectra. An ATP (attached proton test) NMR experiment could also be used since it provides similar information.

Figure 1.

13C

NMR spectrum of distillate (1-methylcyclohexene).

103 Soulsby et al.; NMR Spectroscopy in the Undergraduate Curriculum: First Year and Organic Chemistry Courses Volume 2 ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


Figure 2. DEPT spectra of distillate (1-methylcyclohexene).

This lab has proven to be a good experiment for students to attempt their first procedure adaption since they can model it on an experiment using an isomeric compound and the reaction will still work even if the amounts of H2SO4 and H3PO4 are not exactly correct. In addition to having to rescale the amounts of reagents, this process also forces students to think about whether they need to change glassware and alter the volume of solutions used in the work-up. This activity helps prepare the students for rescaling reactions in their second semester organic lab course and for modifying and adapting procedures in undergraduate research.

Conclusion The dehydration of 1-methylcyclohexanol provides an excellent opportunity to introduce NMR spectroscopy to students in their first semester of organic chemistry. This dehydration reaction produces almost exclusively one product which can easily be distinguished from other possible isomers by 13C and DEPT NMR. These spectra are much easier to interpret than those from 1H NMR and our experience suggests that the combination of 13C with DEPT NMR makes product analysis more comprehensible to novice organic students. This experiment also allows students to experience molecular modeling used in a predictive manner and serves as a way to introduce students to the relative stability of 104 Soulsby et al.; NMR Spectroscopy in the Undergraduate Curriculum: First Year and Organic Chemistry Courses Volume 2 ACS Symposium Series; American Chemical Society: Washington, DC, 2016.

alkenes. Finally, this lab provides the opportunity for students to see how reaction procedures can be adapted from published methodology helping prepare them for an undergraduate research project.

References


1.

Paramentier, L. E.; Lisensky, G. C.; Spencer, B. A Guided Inquiry Approach to NMR Spectroscopy. J. Chem. Educ. 1998, 470–471. 2. Davis, D. S.; Moore, D. E. Incorporation of FT-NMR throughout the Chemistry Curriculum. J. Chem. Educ. 1999, 76, 1617–1618. 3. Steehler, J. K. Should Advanced Instruments Be Used in Introductory Courses? J. Chem. Educ. 1998, 75, 274–275. 4. Beard, D. J.; Henry, W. P.; Dunaway, R. G. Implementation of FT-NMR Across the Chemistry Curriculum. In Excellence in Education with CCLI: Notes from Recent Awardees; Proceedings of the Fall 2009 ConfChem Conference, October 16−22, 2009, Dungey, K, Voss, E. J., Eds.; http://www.ccce.divched.org/Fall2009ConfChem (accessed August 2015). 5. Pavel, J. T.; Hyde, E. C.; Bruch, M. D. Structure Determination of Unknown Organic Liquids Using NMR and IR Spectroscopy: A General Chemistry Laboratory. J. Chem. Educ. 2012, 89, 1450–1453. 6. Pulliam, C. R.; Pfeiffer, W. F.; Thomas, A. C. Introducing NMR to a General Chemistry Audience: A Structural-Based Instrumental Laboratory Relating Lewis Structures, Molecular Models, and 13C NMR Data. J. Chem. Educ. 2015, 92, 1378–1380. 7. Reeves, P. C.; Chaney, C. P. A Strategy for Incorporating 13C NMR into the Organic Chemistry Lecture and Laboratory Courses. J. Chem. Educ. 1998, 75, 1006–1007. 8. Ball, D. B.; Miller, R. Impact of Incorporation of High Field FT-NMR Spectroscopy into the Undergraduate Chemistry Curriculum. J. Chem. Educ. 2002, 79, 665–666. 9. Kjonaas, R. A.; Tucker, R. J. F. A Discovery-Based Experiment Involving Rearrangement in the Conversion of Alcohols to Alkyl Halides. J. Chem. Educ. 2008, 85, 100–101. 10. Livengood, K.; Lewallen, D. W.; Leatherman, J.; Maxwell, J. L. The Use and Evaluation of Scaffolding, Student Centered-Learning, Behaviorism, and Constructivism To Teach Nuclear Magnetic Resonance and IR Spectroscopy in a Two-Semester Organic Chemistry Course. J. Chem. Educ. 2012, 89, 1001–1006. 11. Bonvallet, P. A.; Amburgurgey, J. C. Data versus Dogma: Introducing NMR Early in Organic Chemistry To Reinforce Key Concepts. In NMR Spectroscopy in the Undergraduate Curriculum; Soulsby, D., Anna, L. J., Wallner, A. S., Eds.; ACS Symposium Series 1128; American Chemical Society: Washington, DC, 2013, pp 45−55. 12. Chamberlain, P. H. Identification of an Alcohol with 13C NMR Spectroscopy. J. Chem. Educ. 2013, 90, 1365–1367. 105



13. Mobley, T. A. NMR Kinetics of the SN2 Reaction between BuBr and I−: An Introductory Organic Chemistry Laboratory Exercise. J. Chem. Educ. 2015, 92, 534–537. 14. Horowitz, G. The State of Organic Teaching Laboratories. J. Chem. Educ. 2007, 84, 346–353. 15. Clauss, A. D.; Nelson, S. F. Integrating Computational Molecular Modeling into the Undergraduate Organic Chemistry Curriculum. J. Chem. Educ. 2009, 86, 955–958. 16. Williamson, K. L.; Masters, K. M. Macroscale and Microscale Organic Experiments, 6th ed.; Brooks/Cole, Cengage Learning: Belmont, CA, 2011; pp 178−183, 292-310. 17. Pavia, D. L.; Lampman, G. M.; Kriz, G. S.; Engel, R. G. Organic Laboratory Techniques: A Microscale Approach to Organic Laboratory Techniques, 5th ed.; Brooks/Cole, Cengage Learning: Belmont, CA, 2013; pp 209−214. 18. Lehman, J. W. Multiscale Operational Organic Chemistry: A Problem Solving Approach to the Laboratory Course, 1st ed.; Prentice Hall: Upper Saddle River, NJ, 2002; pp 162−171. 19. Taber, R. L.; Champion, W. C. Dehydration of 2-Methylcyclohexanol. J. Chem. Educ. 1967, 44, 620. 20. Todd, D. The Dehydration of 2-Methylcyclohexanol Revisited: The Evelyn Effect. J. Chem. Educ. 1994, 71, 440. 21. Crawley, J. J.; Linder, P. E. The Acid Catalyzed Dehydration of an Isomeric 2-Methylcyclohexanol Mixture. J. Chem. Educ. 1997, 74, 102–104. 22. Clennen, M. M.; Clennan, E. L. Dehydration of Methylcyclohexanol Isomers in the Undergraduate Organic Laboratory and Product Analysis by Gas Chromatography-Mass Spectroscopy (GC-MS). J. Chem. Educ. 2011, 88, 646–648. 23. Friesen, J. B.; Schretzman, R. Dehydration of 2-Methyl-1-cyclohexanol: New Findings from a Popular Undergraduate Laboratory Experiment. J. Chem. Educ. 2011, 88, 1141–1147. 24. Jones, M. B. Molecular Modeling in the Undergraduate Chemistry Curriculum. J. Chem. Educ. 2001, 78, 867–868. 25. These concentrated samples give spectra with a good signal to noise ratio using 16 scans on our Anasazi instrument. 26. Moores, B. W. Dehydration of 2-Methylcyclohexanol; http:// www.thecatalyst.org/experiments/Moores/Moores.html (accessed August 2015). Additionally, the DfH°gas for 1-methylcyclohexene has been reported as -81.25 kJ/mol: Labbauf, A.; Rossini, F. D. Heats of combustion, formation, and hydrogenation of 14 selected cyclomonoolefin hydrocabons. J. Phys. Chem. 1961, 65, 476–480. Values for DfH°liquid for 1-methylcyclohexene of -81.17 kJ/mol and -87.4 kJ/mol have been calculated from heat of combustion data: NIST Chemistry WebBook. http://webbook.nist.gov/cgi/cbook.cgi?ID=C591491&Mask=FFF (accessed December 2015) as well as a DfH°liquid for methylenecyclohexane of -56.9 kJ/mol: NIST Chemistry WebBook. http://webbook.nist.gov/cgi/ cbook.cgi?ID=C1192376&Units=SI&Mask=20#Ion-Energetics (accessed Dec 2015). 106


Combining Molecular Modeling with - American Chemical Society

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