In the Laboratory
A Flexible Solvolysis Experiment for the Undergraduate Organic Laboratory John J. Esteb, John R. Magers, LuAnne McNulty,* Paul Morgan, Kathryn Tindell, and Anne M. Wilson Department of Chemistry, Butler University, Indianapolis, IN 46208; *
[email protected] Substitution reactions are valuable teaching tools in the undergraduate classroom. They teach students the fundamentals of organic reactivity and provide the foundation for understanding many organic reaction mechanisms. SN1 reactions are particularly useful for imparting students with a solid understanding of carbocations, including their stability, resonance, and ability to rearrange. Despite the utility of these reactions for explaining the basis of reactivity, there are few examples in the educational literature. Background Experiments that demonstrate the use of an SN1 reaction for the synthesis of ethers exist (1, 2). Procedures for the acidcatalyzed ether formation of ethyl t-butyl ether (1) and Methyl Diantilis, a fragrance (2), are available from this Journal. Although these experiments provide options for implementing a SN1 reaction, there are drawbacks to both procedures. The ethyl t-butyl ether synthesis requires the use of sulfuric acid and the isolation of the ether involves both a distillation and a liquid–liquid extraction. The fragrance is available from vanillin in two steps. However, the first step is a sodium borohydride reduction reaction of an aldehyde, which is often addressed much later than substitution reactions in the course curriculum. In addition, the analysis of the fragrance involves both 1H NMR and IR spectroscopy, which is usually performed in the second semester of the laboratory. There are a number of experiments that look at the formation of carbocations to determine the stability of the carbocation or the rate of formation of the carbocation (3–7). A semi-empirical and DFT computational experiment has been reported that looks at the dissociation of alkyl halides to show the order of stability of alkyl substituted carbocations (3). The analysis of the dissociation of alkyl halides is valuable in terms of reinforcing the stability of cations, but there is no hands-on synthesis involved in this laboratory. Many of the published solvolysis experiments are designed to measure the rate of carbocation formation (4–7). These are good experiments for a physical chemistry laboratory, but they do not allow students to experience the isolation of the solvolysis products, which is an important part of the learning process. Rationale There is a lack of experiments available for the SN1 reaction that meet the following criteria: short reaction times, easy product isolation, easy product purification, high yields, relatively benign reagents (no strong acids or strong lachrymators), and no competing reactions. Owing to the utility of SN1 reactions in providing a strong foundation for understanding organic reactivity, a new laboratory was developed that would allow the students to apply the optimal conditions for a solvolysis
reaction. The reaction of bromodiphenylmethane is quick (7), and it was anticipated that bromotriphenylmethane would undergo reaction more readily and quickly, due to the additional stability associated with a tertiary carbocation that is highly resonance stabilized (8). In addition, bromodiphenylmethane is a lachrymator whereas bromotriphenylmethane is not. Bromo triphenylmethane was chosen as a substrate because it dissociates quickly to generate a stable carbocation intermediate and allows the reaction to occur in a reasonable time. In addition, triphenylmethanol and many triphenylmethyl ethers are solids, which would allow the students to isolate a product, determine the melting point for product confirmation, and highlight the solvolysis of a tertiary substrate. The triphenylmethyl cation is well known for its stability. It is commercially available from Sigma–Aldrich as the tetrafluoroborate salt. One method for the generation of the highly colored cation is the treatment of triphenylmethanol with a strong acid, such as fluoroboric acid or sulfuric acid (9). Also, substituted triphenylmethyl cations are dyes that are used for wool and silk (10), which provides relevance for this experience to everyday life. Experiment Bromotriphenylmethane (1.6 mmol) 1 is added to acetone then a large excess of water or the appropriate alcohol is added. The reaction to generate triphenylmethanol 2 and the remaining triphenylmethyl ethers is almost instantaneous. Ph Ph
Br Ph
1
Ph
ROH
Ph
R= H: Me: Et: 1-Pr: 1-Bu:
OR Ph
2 3 4 5 6
The reaction to generate triphenylmethanol 2 and the remaining triphenylmethyl ethers is almost instantaneous. The process of monitoring the reaction by GC–MS shows that even after 1 minute, no bromotriphenylmethane remains in the reaction mixture. Product isolation is straightforward for triphenylmethanol 2, triphenylmethyl methyl ether 3, and triphenylmethyl ethyl ether 4 (9); the addition of the reaction solution to ice causes the product to crystallize and precipitate from solution so that it may be collected by suction filtration. The crude product is recrystallized from 2-propanol. In the cases of the 1-propyl ether 5 and 1-butyl ether 6, the product must be extracted from the aqueous solution with dichloromethane and concentrated to give a solid product.
© Division of Chemical Education • www.JCE.DivCHED.org • Vol. 86 No. 7 July 2009 • Journal of Chemical Education
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In the Laboratory
Hazards Bromotriphenylmethane and t-butanol are corrosive. Methanol, ethanol, 2-propanol, t-butanol, and acetone are flammable. Triphenylmethanol, acetone, 1-propanol, 1-butanol, and t-butanol are irritants. Dichloromethane is an irritant and reasonably anticipated to be carcinogenic (11). The ethers may be irritating to the skin and eyes. Results and Discussion Although the primary procedure uses water for the solvolysis reaction, other sterically unhindered substrates, such as methanol and ethanol, generate ethers 3 and 4 that can be crystallized over ice, although percent yields are higher if the ether is extracted from the solution using dichloromethane. GC–MS analysis shows that 1-propanol and 1-butanol are effective nucleophiles for this reaction as well, but the products 5 and 6 must be isolated by liquid–liquid extraction. As expected, increasing the steric bulk of the nucleophile to 2-propanol and t-butanol severely hinders the substitution process. The triphenylmethyl 2-propyl ether can be isolated by extraction but only as a minor product with triphenylmethanol 2 forming as the major product in the reaction. No triphenylmethyl t-butyl ether is formed during the reaction time. An excess of nucleophile was added to ensure complete reaction of the starting material (Table 1). The use of multiple nucleophiles in this laboratory highlights the impact of nucleophile bulk even on a SN1 reaction. Although the nucleophile does not affect the rate of carbocation formation, product formation can be inhibited by the use of a bulky nucleophile such as t-butanol. The added benefit of looking at steric bulk of the nucleophile allows students to examine the SN1 reaction from another perspective. Also, the change in isolation procedure dependent on the alcohol nucleophile opens the possibility of presenting the experiment as more of a discovery process, where the student must determine the optimal conditions for product isolation.
Table 1. Representative Yields from the Solvolysis Reaction with Different Nucleophiles Product
Nucleophile
Yield (%)a
Conclusions A new SN1 reaction is reported. This experiment has an easily implemented procedure, uncomplicated product isolation, and straightforward product purification. In addition, this procedure may be performed with a single nucleophile to highlight the process of hydrolysis or with multiple alcohol nucleophiles to explore the effect of steric bulk on product formation from the solvolysis reaction. The use of multiple nucleophiles allows the students to determine what type of isolation procedure is optimal for their product, whether it is crystallization from ice water or liquid–liquid extraction. In addition, this experiment can be easily expanded to include more advanced analysis than is currently used. GC–MS analysis would show the difference in masses effect the ether products. 1H NMR determination of the products would give different signals to indicate the presence of either the alcohol or the ether.
2
Water
94b
3
Methanol
66
Acknowledgment
4
Ethanol
75
5
1-Propanol
89c
6
1-Butanol
86c
The authors would like to thank Butler University 2007 fall organic chemistry classes for helping assist with the preparation and testing of this laboratory.
—
2-Propanol
minord
—
t-Butanol
0
aThe
yields are from the lab development by the authors. bThe average student yield was 50%. cProducts were extracted from solution with dichloromethane. dMajor
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The products can be characterized by IR and 1H NMR spectroscopy. The IR spectra of bromotriphenylmethane and triphenylmethanol are available from SDBS (12). Owing to the reactivity of the bromide, even at room temperature, the IR spectra are nearly identical, with an OH stretch around 3470 cm–1. Additional peaks corresponding to the sp2 C−H bonds and the double bonds in the aromatic rings are found at 3061, 1698, 1491, 1463, and 1448 cm–1. Proton NMR spectroscopy is useful for the analysis of all the products, but especially for identifying the alkyl chains in the ethers. In the case of the ethers, the 1H NMR offers identification of the aromatic ring and provides confirmation of the C−O bond, which is sometimes difficult to distinguish in the IR spectrum. In addition, the splitting of the alkyl chains is easy to distinguish, giving clear evidence of product formation. The pre- and postlaboratory questions for this experiment are designed to probe the students’ understanding of the laboratory experiment. This is the first time our students are introduced to recrystallization, so it is an experiment that has a secondary purpose of teaching a necessary skill to the students. The prelaboratory questions are intended to elicit student thought about the procedure and the techniques before they enter the laboratory while the postlaboratory questions should encourage the students to draw conclusions about the experiment and the effect of changing variables on the outcome of the reaction.
product is 2.
Literature Cited 1. Donahue, C. J.; D’Amico, T.; Exline, J. A. J. Chem. Educ. 2002, 79, 724–726. 2. Miles, W. H.; Connell, K. B. J. Chem. Educ. 2006, 83, 285–286. 3. Waas, J. J. Chem. Educ. 2006, 83, 1017–1021. 4. Duncan, J. A.; Pasto, D. J. J. Chem. Educ. 1975, 52, 666–668.
Journal of Chemical Education • Vol. 86 No. 7 July 2009 • www.JCE.DivCHED.org • © Division of Chemical Education
In the Laboratory 5. Cyr, T.; Prudhomme, J.; Zador, M. J. Chem. Educ. 1973, 50, 572–574. 6. (a) Markgraf, J. H.; Anton, M. J. Chem. Educ. 1977, 54, 773–774. (b) Perkins, R. J. Chem. Educ. 1979, 56, 208. 7. Horman, I.; Strauss, M. J. J. Chem. Educ. 1969, 46, 114–116. 8. (a) Smith, H. A.; Smith, R. J. J. Am. Chem. Soc. 1948, 70, 2400–2401. (b) Brauman, J. I.; Archie, W. C., Jr. J. Am. Chem. Soc. 1970, 92, 5981–5986. 9. Lehman, J. W. Multiscale Operational Organic Chemistry: A Problem-Solving Approach to the Laboratory Course; Prentice-Hall: Upper Saddle River, NJ, 2002; pp 232–242, 477. 10. Streitweiser, A.; Heathcock, C. H.; Kosower, E. M. Introduction to Organic Chemistry, 4th ed.; Prentice-Hall: Upper Saddle River, NJ, 1992; p 1231. 11. Young, Jay A. J. Chem. Educ. 2004, 81, 1415.
12. Spectral Database for Organic Compounds, SDBS. http:// riodb01.ibase.aist.go.jp/sdbs/cgi-bin/direct_frame_top.cgi (accessed Mar 2009).
Supporting JCE Online Material
http://www.jce.divched.org/Journal/Issues/2009/Jul/abs853.html Abstract and keywords Full text (PDF) Links to cited URL and JCE articles Supplement
Student handout including pre- and postlaboratory questions
Instructor notes including the answers to the pre- and postlaboratory questions and the NMR and IR spectra
© Division of Chemical Education • www.JCE.DivCHED.org • Vol. 86 No. 7 July 2009 • Journal of Chemical Education
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