LABORATORY EXPERIMENT pubs.acs.org/jchemeduc
Dehydration of Methylcyclohexanol Isomers in the Undergraduate Organic Laboratory and Product Analysis by Gas ChromatographyMass Spectroscopy (GC-MS) Malgorzata M. Clennan* and Edward L. Clennan Department of Chemistry, University of Wyoming, Laramie, Wyoming 82071, United States
bS Supporting Information ABSTRACT: Dehydrations of cis- and trans-2-methylcyclohexanol mixtures were carried out with 60% sulfuric acid at 78-80 °C as a function of time and the products were identified by gas chromatography-mass spectroscopy (GC-MS) analysis. The compounds identified in the reaction mixtures include alkenes, 1-, 3-, and 4-methylcyclohexenes and 1-ethylcyclopentene, as well as the alcohols, 1-, 3-, and 4-methylcyclohexanols, and residual starting material. Independent reactions under identical conditions of the pure cis- and trans-2-methylcyclohexanol isomers, 1-, 3- and 4-methylcyclohexanol were also carried out. These reactions reveal that the cis-isomer reacts predominately to form 1-methylcyclohexene whereas the trans-isomer reacts to give a complicated mixture consisting of the isomeric 1-, 3-, and 4-methylcyclohexanols, 1-, 3-, and 4-methylcyclohexenes, and the ring contraction product, 1-ethylcyclopentene. In the experiment, each student carries out a dehydration of the cis- and trans-2-methylcyclohexanol mixture or of one of the pure isomers and the results from the GC-MS analyses of the whole class are pooled. The analysis reinforces lecture material and provides an appreciation of the complexity of elimination-dehydration reactions that proceed via carbocation intermediates and can undergo intricate rearrangements such as hydride and alkyl shifts. The reaction procedure is straightforward and the GC-MS analysis simple enough so it can easily be used in the first semester of undergraduate organic chemistry laboratory. KEYWORDS: Second-Year Undergraduate, Laboratory Instruction, Organic Chemistry, Inquiry-Based/Discovery Learning, Hands-On Learning/Manipulatives, Alcohols, Carbocations, Gas Chromatography, Mass Spectrometry, Synthesis
D
ehydration of a mixture of cis- and trans-2-methylcyclohexanol, 1 and 2, is a popular first-semester organic undergraduate laboratory experiment designed to illustrate mechanistic features of elimination reactions.1-3 In a typical procedure, the alcohols are heated with 85% phosphoric acid and the products distilled off and identified by gas chromatography.4 The first fraction is rich in higher-boiling 1-methylcyclohexene, 3, and the later fractions contain lower-boiling 3-methylcyclohexene, 4, and methylenecyclohexane. The cis-isomer under these acid-catalyzed conditions is 8.4 times more reactive than the transisomer.3 Unfortunately, this procedure invokes removal of the alkene products by slow distillation from the reaction mixture at temperatures below the boiling point of starting materials and masks the real complexity of the acid-catalyzed dehydration of isomeric 2-methylcyclohexanols. We present herein a redesigned and broadened experiment with an alternative workup procedure followed by analysis by gas chromatography-mass spectroscopy (GC-MS).a The experiment is designed to provide students with an appreciation of the power of GC-MS to sort out the details of complex reactions (Scheme 1) and to simultaneously illustrate the elimination reactions of alcohols as well as reinforce the fundamental chemistry of carbocations (solvolysis, hydride Copyright r 2011 American Chemical Society and Division of Chemical Education, Inc.
and alkyl shifts) presented in lecture. The early introduction of mass spectrometry into the curriculum is consistent with the “gradualism” approach suggested by Heldrich and co-workers5 for the introduction of spectroscopy and by Clennan for GCMS analysis.6
’ OVERVIEW OF THE EXPERIMENT The redesigned experimental procedure is flexible and allows examination of the dehydrations of cis-2-methylcyclohexanol, 1, trans-2-methylcyclohexanol, 2, 1-methylcyclohexanol, 7, 3-methylcyclohexanol, 8, or 4-methylcyclohexanol, 9 and can be utilized to analyze product formation at a fixed time or as a function of time. We believe that the experiment is most instructive when the students are divided into groups and are asked to conduct either a dehydration of a pure isomer, 1, 2, 7-9 at a fixed time or of the cis-trans mixture, 1/2, as a function of time. This allows the class to pool the experimental results and in a discovery-based analysis come to important conclusions about reactivity and mechanisms of product formations. The instructor may need to provide hints about the possibility of a Published: March 22, 2011 646
dx.doi.org/10.1021/ed100368z | J. Chem. Educ. 2011, 88, 646–648
Journal of Chemical Education
LABORATORY EXPERIMENT
dual E1-E2 mechanism to explain the enhanced reactivity of the cisisomer, 1, in comparison to trans-isomer, 2.3,7 The formation of 1-, 3-, and 4-methylcyclohexanols, 7-9, in the reactions of 1 and 2, which was not observed in the distillation-based experiments1-3 and which are most reasonably explained by a hydrides shift in a carbocation intermediate, can be used as an evidence for the operation of an E1 mechanism. Similarly, the formation of a ring contraction product 6a can be explained by the initial alkyl bond shift to form ethylidenecyclopentane, 6b, which isomerizes to 6a.a All products give the recognizable molecular ions under the described GC-MS conditions. The mass spectra of each alcohol are distinctively different from each other and each gives a characteristic [M - 18]þ ion that allow their assignments. The alkenes also differ significantly in fragmentation patterns but the location of the double bond cannot be established unambiguously due to its facile migration in the fragments.8,9
alcohols and 60% H2SO4 were placed in a test tube and heated at 78-80 °C. The reaction mixture was cooled and treated after
Figure 1. Chromatogram of a reaction mixture from dehydration of trans 2-methylcyclohexanol. Peaks at retention times in min are identified as follows: 2.13, 1-methylcyclohexane (impurity from the starting material); 2.21, 3-methylcyclohexene (ascending slope)b and 4-methylcyclohexene (descending slope)b; 2.29, 1-ethylcyclopentene; 2.39, 1-methylcyclohexene; 2.62, ethyl acetate impurity; 3.30, 1-methylcyclohexanol; 3.65, trans-2-methylcyclohexanol; 3.70, 3-methylcyclohexanol; 3.72, 4-methylcyclohexanol. A trace peak barely visible at 2.42 is ethylidenecyclopentane. Polymeric products have retention times of 7.3-7.9 min.
’ EXPERIMENT Dehydrations
A small volume, 1 mL, of a cis- and trans-2-methylcyclohexanol mixture and 0.5 mL of 60% H2SO4 or 1:1 (v:v) of the pure Scheme 1. The Dehydration of Isomeric 2-Methylcyclohexanols with Sulfuric Acid
Table 1. Relative Peak Areas of Reaction Components during Dehydration of 1/2 Mixtures Compounds Reaction Time/min
1
2
3
4/5 6
6.7 nda nd
7
Polymeric Products
2
44.4 45.6
3.3
nd
5
32.1 38.4 12.5 nd nd 17.0
nd
10 15
9.6 33.9 30.7 2.1 nd 18.8 2.0 29.9 24.1 4.9 0.8 18.5
4.9 19.8
30
2.1 23.8 25.4 5.7 0.9 15.0
27.1
40
2.3b 12.5 20.2 7.5 1.2
47.2
9.1
a
Not detected. b Broad, poorly resolved peak consisting of a mixture of 3- and 4-methylcyclohexanols, 8 and 9. These components overlapped extensively with 1 and contribute initially to a minor but increasing extent to the peak area.
Table 2. Relative Peak Areas of Reaction Components during Treatment of Pure 3 and Pure Methylcyclohexanol Isomers Products Starting Material
a
Unreacted Starting Material
3
4/5
6
1
Aa: ndb
63.1
2.6
2
A: 48.2
2.8
3.5
7
B: 27.5 A: 2.5
11.9 90.1
8d,e
A: 78.2 B: 49.9
Polymeric Products
7
8/9
nd
1.9
nd
0.7
18.4
15.5
10.9
7.2 nd
1.2 nd
13.0 --
6.3 nd
32.9 7.4
0.9
5.2
nd
3.5
--
1.8
3.7
16.4
nd
10.0
--
15.0
9d,e
A: 46.6
5.3
18.7
nd
3f
A: 69.1
--
1.9
nd
7.8 nd
24.5c
--
1.0
1.6
27.4
a
A is the 10 min reaction and B is the 20 min reaction. b Not detected. c 2-Methylcyclohexanone present (ca. 8%). d 10.4% and 20.6% of 2 found in the reactions listed in 4A and 5A, respectively. e The isomeric starting materials were not resolved on the chromatogram. f Violent reaction occurred when acid was added to 4 and 5 and tars were formed instantly. 647
dx.doi.org/10.1021/ed100368z |J. Chem. Educ. 2011, 88, 646–648
Journal of Chemical Education time t (Tables 1 and 2) with 2 mL of 10% NaOH, diluted with 20 mL water, and extracted with 10 mL of ethyl acetate. The organic layer was washed with 10 mL of 10% NaHCO3, dried with Na2SO4, and analyzed by GC-MS.
LABORATORY EXPERIMENT
obtained. Enthusiasm is maintained in the laboratory as each piece of the puzzle is discovered and put into place.
’ ASSOCIATED CONTENT
bS
GC-MS Conditions
An Agilent 6890 GC/5973 MSD with an automatic liquid sampler and HP-5, 30 m 0.25 mm column was used. Temperatures were inlet, 250 °C; detector, 280 °C; and oven, initial 75 °C was held for 2 min and ramped 30°/min to 120 °C, held for 3 min, and ramped 30°/min to 250 °C.
’ HAZARDS Sulfuric acid is corrosive and students should wear gloves when transferring it. Sodium hydroxide (10% NaOH) and sodium bicarbonate (10% NaHCO3) are both corrosive. All organic compounds are flammable and precaution should be undertaken to avoid open flames and sparks when handling them. ’ RESULTS AND DISCUSSION A typical example of a total ion chromatogram for dehydration of trans-2-methylcyclohexanol, 2, with 60% H2SO4 is shown in Figure 1. All of the peak assignments were established by comparison to authentic samples of the alkenes and alcohols with the exception of 6a, which was independently synthesized by acid-catalyzed rearrangement of ethylidenecyclopentane 6b. The results from a typical “time-resolved” dehydration of a mixture of cis- and trans-2-methylcyclohexanol, 1/2, are shown in Table 1 and of several pure cyclohexanols in Table 2. The relative peak areas have not been corrected; nevertheless, several conclusions can be drawn by cautiously comparing only peaks areas for similar compounds (e.g., alcohols to alcohols and alkenes to alkenes) that are likely to have similar response factors. The data in Table 1 confirm the observations in the literature2,3 that trans2-methylcyclohexanol, 2, is less reactive than its cis-isomer, 1, and that 1-methylcyclohexene, 3, is the first formed alkene. It also provides evidence for the formation of substantial quantities of 1-methylcyclohexanol, 7, that is not observed in the reaction products previously removed from the reaction mixtures by distillation.2,3 Finally, the data demonstrate that formation of polymeric and oligomeric products increase as a function of reaction time. These materials were not analyzed but are likely formed by capture of carbocations by alcohols or by acidcatalyzed polymerizations of the alkene products.7 Both of these processes are expected to become more important as the alkene products begin to accumulate in the reaction mixtures at longer reaction times. Methylenecyclohexane that had previously been reported as a product of the dehydration2,3 was not observed and instead 1-ethylcyclopentene, 6a, was identified in the reaction mixture.c
Supporting Information
Directions and experimental procedure used by students; instructor notes; spectra of the compounds. This material is available via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION Corresponding Author
*E-mail:
[email protected].
’ ACKNOWLEDGMENT The authors thank the National Science Foundation for the funds necessary for the purchase of the GC-MS (DUE-0125911), Robert C. Corcoran (University of Wyoming) and Paul Scudder (New College of Florida) for helpful discussions. ’ ADDITIONAL NOTE a See Supporting Information for experiment organization and MS analyses. b
Identified by mass spectrum of original samples and confirm by NIST98 Library.
c
The dehydrations with 85% H3PO4 under the same conditions as with 60% H2SO4 and for 40 min heating yielded 1-methylcyclohexene, 1-methylcyclohexanol, and about 80% of 2-methylcyclohexanol was recovered.
’ REFERENCES (1) Taber, R. L.; Champion, W. C. J. Chem. Educ. 1967, 44, 620. (2) Todd, D. J. Chem. Educ. 1994, 71, 440. (3) Cawley, J. J.; Lindner, P. E. J. Chem. Educ. 1997, 74, 102–104. (4) Ault, A. Techniques and Experiments for Organic Chemistry, 6 th ed.; University Science Books: Sausalito, CA, 1998; Exp. 18, pp 381-384. (5) (a) Alexander, C. W.; Asleson, G. L.; Bern, C. F.; Doig, M. T.; Heldrich, F. J.; Studer-Martinez, S. J. Chem. Educ. 1999, 76, 1297–1298. (b) Alexander, C. W.; Asleson, G. L.; Doig, M. T.; Heldrich, F. J. J. Chem. Educ. 1999, 76, 1294–1296. (6) Clennan, M. M.; Clennan, E. L. J. Chem. Educ. 2005, 82, 1676–1678. (7) Vollhardt, P.; Schore, N. Organic Chemistry. Structure and Function, 6th ed.; W.H.Freeman and Co.: New York, 2011. (8) McLafferty, F. W. Interpretation of Mass Spectra, 3rd ed.; University Science Books: Mill Valley, CA, 1980; pp 191-193. (9) Silverstein, R. M.; Webster, F. X.; Kiemle, D. J. Spectrometric Identification of Organic Compounds, 7th ed.; John Wiley & Sons, Inc.; New York, 2005; p 22.
’ CONCLUSIONS In this experiment, students discover that GC-MS can be effectively used to unravel the complexities of reactions that involve carbocations. In addition, writing the structures of the products and drawing electron-pushing mechanisms for their formations reinforces lecture material. Completion of this discovery-based experiment provides students with a sense of satisfaction and accomplishment and perhaps most importantly an appreciation of how data and conclusions found in their textbook are 648
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