In the Laboratory

edited by

Green Chemistry

Mary M. Kirchhoff
ACS Education Division Washington, DC 20036

Synthesis of Imidazolium Room-Temperature Ionic Liquids Exploring Green Chemistry and Click Chemistry Paradigms in Undergraduate Organic Chemistry Laboratory
Sergei V. Dzyuba,* Katherine D. Kollar, and Salil S. Sabnis Department of Chemistry, Texas Christian University, Fort Worth, TX 76129; *

Ionic liquids or molten salts are compounds that are composed entirely of ions and exist in a liquid state. For example, inorganic salts, such as NaCl or AlCl3 when heated above their melting points can be classified as ionic liquids. Obviously, high melting points of many inorganic salts negate their utility in the molten state. Combinations of anion–cation pairs leading to salts with phase transitions at or below room temperature can be suitable as room-temperature ionic liquids (1). Predominantly, these have been quaternary nitrogen-containing heterocycles (Figure 1). Physical properties of these solvents can be moduA N N R N R A A N R R3 N R R1 R2 A

A = anion [PF6, N(SO2CF3)2, N(CN)2, BF4, etc.] R = alkyl, aralkyl
Figure 1. Structures of some common ionic liquids.



H2O reflux, 1.5 h



KPF6 H2O, 15 min


Scheme I. One-pot synthesis of [C4-mim]PF6 ionic liquid.

lated by modifications of the anion and cation scaffolds (1). One of the main advantages of ionic liquids is their low, almost negligible, vapor pressure compared to volatile and hence hazardous organic solvents. This has prompted the claim that ionic liquids are environmentally benign, “green” solvents. However, it should be noted that the widely popularized benign nature of ionic liquids might understate potential toxicity (2). The possibility to conduct chemical, biochemical, and analytical processes in an ionic, low coordinating, and highly solvating environment over a wide temperature range has contributed to the enormous growth and expansion of the field of ionic liquids for use primarily as alternative solvents in organic reactions (1). Controlling the outcome of a particular process by designing the best available solvent for the desired product holds great promise and potential for both fundamental and applied research (3). Unlike conventional molecular solvents, the structures of ionic liquids can be modulated with ease. Thus, application of “task-specific” ionic liquids can provide additional benefits for a variety of processes (4). Advances in the area of ionic liquids should prompt the introduction of ionic-liquid experiments and concepts into undergraduate organic chemistry laboratories. The nature of the organic laboratory courses often dictates what types of experiments can be carried out within an allocated time period. Previously reported preparations of room-temperature ionic liquids were not suitable for an undergraduate laboratory experiment, either due to the time constraints or the availability of the required equipment and, therefore, are better suited for advanced-level laboratory courses, while still requiring substantial involvement of the instructor (5). Here, we report a facile synthesis of an imidazolium-based ionic liquid (Scheme I), readily adaptable for the basic organic chemistry laboratory. The following abbreviation for ionic liquids can be utilized: 1-butyl-3-methylimidazolium bromide can be described as [C4mim]Br (used in this article), where C4 depicts the butyl group, and mim represents methylimidazole fragment; this particular style is believed to be the most versatile way to abbreviate lengthy names of ionic liquids. The other commonly used abbreviation system would depict 1-butyl-3-methylimidazolium bromide as [bmim]Br; however, this nomenclature has some limitations. For example, 1-hexyl-3-methylimidazolium and 1-heptyl-3-methylimidazolium cations would either be given the same abbreviations, [hmim], or would require the addition of hex and hep. The simple and robust nature of the protocol is an advantage over other available procedures. The experiment can serve as an illustration of one-pot processes, heterocyclic chemistry, and


Journal of Chemical Education Vol. 86 No. 7 July 200 © Division of Chemical Education

the use of dichloromethane during the final stages diminishes such Vol. Ed.. the high viscosity of the ionic liquid leads to significant losses during the phase separation (ionic liquidwater and ionic liquiddrying agent) steps. 99. therefore contact with skin. and anion dependent. and a boiling chip). Chem. R.DivCHED. The anion exchange is established by characteristic bands in the IR spectra of the isolated roomtemperature ionic liquid (11). The synthesis relies on the fact that this ionic liquid is immiscible with water and. Results and Discussion One-pot syntheses of several room-temperature ionic liquids were carried out in water or ethanol according to Scheme I in a four-hour laboratory period using a simple reflux setup (sand bath. and versatile tool for various areas of chemistry. the synthesis of [C4mim]PF6 (Scheme I) is readily accomplished using water as the only reaction solvent. V. 707–710. 2071–2084. state. 361–363. The overall yield for the synthesis of [C4mim]PF6 is about 80%. as well as isolation and purification of the final products. The one-pot procedure is versatile and can be done in a variety of solvents. Acknowledgment The authors thank TCU for financial support of this work..) The reaction can be done under neat conditions (9). such as dichloromethane. Otherwise.. round-bottom flask. P.. I. M. fast reaction times. Literature Cited 1. Subsequent application of the prepared ionic liquids as a reaction medium can be explored. (c) van Rantwijk. This process is done in the “environmentally” preferred solvent. 86 No. eyes. J.3 M reaction in water requires 10–12 h. A boiling chip can also be used and the reaction is still facile (no starting material is observed by 1H NMR after 15–20 min at 160–180 °C). reliable. P. the reaction requires careful monitoring. Sheldon. environmentally benign and safe reactions that utilize renewable feedstocks. and 1-bromobutane are flammable. (i) synthesis of ionic liquids and (ii) application of ionic liquids as solvents for chemical reactions. Green Chem. however.2. Chem. (d) Parvulescu. modular. but also the introduction of various concepts of green chemistry (7) and click chemistry (8). 2. The hazards associated with ionic liquids are not fully explored. R. an organic solvent. The specific nature of the reported synthetic protocol for the synthesis of the ionic liquid allows not only the exploration of various reactions using ionic liquids as solvents (5. The goal of the current article is to make students aware of room-temperature ionic liquids and allow them to get a first-hand experience by synthesizing these materials. A. 2007. This reaction has been demonstrated to be a unique. (a) Welton.In the Laboratory organic reactions in water.5 M reaction in water is completed within 1. engineering. therefore. Chem. T. In case of small-scale reactions. Mechanistically. Carrying out the reaction in a solvent ensures that the resulting ionic liquid does not develop a brown color. starting with readily accessible starting materials. W.. 5. R. dichloromethane. Rev. Int. Holbrey. Chem. Earle. 1077–1236. In particular. dichloromethane is a probable human carcinogen. for example. 40. D. Hazards Caution should be exercised when handling all the chemicals. Dispose all waste according to local. which is still. The syntheses of ionic liquids can be presented as a single. and easy-to-perform paradigm related to preparation of various scaffolds. One of the premier examples of a click chemistry is the copper(I)-catalyzed azide–alkyne cycloaddition yielding 1. Keim. Rogers.. Conclusions The experiment allows students to test and learn several concepts of contemporary chemistry. Lett. Several purification protocols can be utilized to remove colored impurities either at the stage of the bromide or later (10). Swatloski. (It should be noted that equimolar amounts of the starting materials are utilized throughout. (b) Wasserscheid. In view of the facile and robust nature of the reported protocol. Res. C. D. Any improvements to the existing processes as well as the design of the new processes that lead to more efficient. 3772–3789. Angew. J. 3. 39. materials science. the reaction also meets the standards of click chemistry: readily available starting materials. ease of synthesis. when magnetic stirring and precise temperature control are available. the quaternization of 1-methylimidazole with 1-bromobutane serves as a good example of an SN2 reaction.. Org. condenser. >99% pure by 1H NMR. Rev. S. P. F. and biology (8b–e). acetone-d6. 1-Methylimidazole and potassium hexafluorophosphate are corrosives.JCE. such as water (12). if spectroscopic grade ionic liquids are desired. and clothes should be avoided. 107. While the synthesis of [C4mim]PF6 might qualify as green chemistry.5 h. 6. Click chemistry can be described as any facile. and formation of a light brown oil [C4mim]Br is achieved.. 857 © Division of Chemical Education www. R. 2003. 107. reuse and recycle chemicals and solvents constitutes an important and useful area of modern research. (e) Special issue on ionic liquids: Acc. Green chemistry is based on principles that are designed to prevent and reduce the waste and hazard associated with the production of chemicals (7).3-triazoles. 2004. is easily isolated by using a separatory funnel or removing the upper aqueous layer with a pipet. catalytic. Seddon. Chem. a 12. Katdare. Concentration affects efficiency of [C4mim]Br formation. Under these conditions. stand-alone experiment or introduced as a sequence. whereas a 1. 1999. The formation of the imidazolium moiety is confirmed by 1H NMR by the characteristic downfield shift of the heterocyclic protons upon quaternization of the 1-methylimidazole. Hardacre. For example. 7 July 200 Journal of Chemical Education . as prolonged heating leads to the formation of a darker brown oil. 2757–2785. K. 2615–2665. 2007. which are considered harmful and irritants. 2000. The chemical shifts of the imidazolium protons are concentration. has to be used to achieve a facile and convenient extraction step in the preparation of [C4mim]PF6. The undergraduate experiment describing this metal-catalyzed cycloaddition reaction has been reported recently (8f ). useful. 2007. a number of imidazolium-based ionic liquids can be prepared by simply varying the structure of the halide. Gloves should be worn at all times during the experiment. solvent. 19F NMR can also be used to confirm the identity of the anion of the ionic liquid. Rev. and federal regulations. 6).

Supporting JCE Online Material http://www. Tetrahedron 2005. 40.. D. L. C.. Chem... A. K. S. Sharpless. 3. 2001. 61. J. S. J. V.. Soc. K. 2001.. http://www. 943–945. 758–764. K. Jr. Srinivasan. 9. Zheng. (a) Kolb. D. Chem. Chen. Sui.. K. 1072–1077. Baker. 2004–2021. 128. S. 3539–3546. A. 130. (a) Davis. Hansen..-k.-G. Am. A. (a) Earle. 1833–1836. 6.. M.. Introduction to Practical Infrared Spectroscopy. Palimkar.In the Laboratory 4. Mak. 7. Heterocyclic Chem.. Angew. Lahoti.. Green Chem.. Green Chem. Campos.. C. Int. 1951–1954... Biol. Stefaniak. (b) Siddiqui. and IR spectra 858 Journal of Chemical Education Vol. Hawker. Z. T. 9.. Chem.. Some examples of rapid synthetic reactions in ionic liquids. Finn. (a) Dzyuba... Chem. D. J. S. N. Educ. 2006. R. (b) Killops. K. 2. (b) Burrell. W. Gordon. 10. W. T.epa. Jennings. J. 2004. Hu.. Chem. J. M... J. Lindberg. Lai. R. J. 161–166.. A. United States Environmental Protection Agency. H. Nagy. A. Kleine.. B. G. M. Org. Johnson. P. 7 July 200 www.. 2008. H.html Abstract and keywords Full text (PDF) with links to cited URLs and JCE articles Supplement Instructions for the students Notes for the instructor Sample 1H NMR.jce. Chem. A... 33. J... Y. 2392–2393. 1049–1063. Soc. J. (c) Ranu. Baker. Wong. Bartsch. R. (f ) Sharpless. J.. Koberstein. (b) Lee. N. S. J. 2nd ed. J. R. (d) Jang. Bartsch.-C. A. D. Cross. C. 130. (b) © Division of Chemical Education . M..JCE. H.. ACS Chem. 86 No. 11. McCleskey. N. L. Wu. T. 83. 2007. Narkhede. Phys. Chan. Butterwirths: London. 82. M. Eur. P. 3767–3770. K. C.. R. S..divched. S. Daniel. Commun. A. E. V. T.. Am. M. K. (c) Ku. R. Johnson.. 5. Colberg. 2006. J. 5062–5064. Del Sesto. 2005. V.. 449–454. Knight. H. K. T. Finn. 79. D. Z. Lewis. 38. 2007. 2008. Anal. G. G. J. C. M. Alfonsi. J. Bard. Educ. 2006.-G.. Lett. V. M. J. Chem. J. Chem. gov/ (accessed Mar 2009). P. A. B. are (a) Lea. M. J.-G. 2007. 12.. 2002. 2008. S. Welton. 1964. R. 8.. Am. Chem. Jana. G.. V. Dunn. A. S. Ed.. Seddon.. Chem.-T. K. P. Plechkova. C. Y. Diaz. T. D. which can be implemented into an ionic liquid synthesis and application laboratory sequence. 19F NMR.-Y. U.DivCHED. 2006. 6564–6565. Turro.. 775–778. T. Fevig.. Soc. Chem. A. Q.. 10.. 265–268. (e) Fokin V. Chem. 31–38.. Perry. Synthesis 2004. J.