In the Laboratory edited by
Cost-Effective Teacher
Harold H. Harris University of Missouri—St. Louis St. Louis, MO 63121
Effective, Safe, and Inexpensive Microscale Ultrasonic Setup for Teaching and Research Laboratories
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Ángel M. Montaña* and Pedro M. Grima Departamento de Química Orgánica, Universidad de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain; *
[email protected] The term ultrasound refers to acoustic waves having a frequency from 16 kHz to about 10 MHz (beyond the limit of human hearing). Depending on its power input, ultrasound can be classified as follows (1–7): diagnostic ultrasound (frequency 2–10 MHz, power on the order of mW cm᎑2 or below), used in detecting flaws in materials, fetal scanning in medicine, and sonar measurements; and destructive ultrasound (frequency 16–100 kHz, power from 1 to 103 W cm᎑2), which brings about irreversible physical or chemical changes. This latter type of ultrasound has been used as a source of energy in chemical reactions (8–16 ). In some processes, sonication with ultrasound produces a substantial increase in both reaction rate and product yield. Energy is released in sonication via a cavitation process, which involves the formation and collapse of microbubbles with liberation of sufficient heat to reach temperatures up to 5000 K and pressures up to 1000 atm within the microbubble in microseconds (1–7). It is worth noting the use of ultrasound in heterogeneous reactions involving metals, where sonication produces four main effects (17–19): Activation of the surface of metal particles (removal of metallic oxides); Removal of reaction products from the surface of solid particles, facilitating access by new molecules of reactants; Vigorous dispersion of metallic or solid particles in the reaction medium; and Generation of the activation energy necessary for the reaction to take place.
There are three common sources of ultrasound on the laboratory scale (1–7 ): ultrasonic bath cleaners, cup-horn sonicators, and ultrasonic horns (which use an internal sonication probe) (see Fig. 1). The ultrasonic cleaners are simple sonicators; the sample or reaction mixture is not in direct contact with the ultrasound source but rather needs a fluid
medium to transfer the vibrational perturbation. The main drawbacks of this system are the low energy generated (0.1 to 1 W cm᎑2) and the low reproducibility. The cup-horn sonicators are more satisfactory than the ultrasonic cleaners for activating reactions but they are not designed to allow direct contact of the ultrasound source with the reaction mixture. Thus, a certain degree of energy is absorbed by the bath and the glass walls of the reactor. The most powerful and efficient sonication systems are the ultrasonic horns that allow insertion of an ultrasonic probe into the reaction vessel, in direct contact with reactants and solvent. This minimizes energy losses resulting from deadening, and the power supplied can be much higher (>100 W cm᎑2). New Design of a Microscale Sonication Reactor Vessel We present here a homemade, safe, effective, and inexpensive reactor vessel for ultrasonic horns, with applications in microscale experiments in teaching and research laboratories. We have designed a reactor vessel for an ultrasonic probe1,2 that allows reactions to be run at the microscale level, at a wide range of temperatures (from room temperature to ᎑78 °C) and under inert atmosphere (N2 or Ar). The reactor vessel was made by an experienced glassblower from Pyrex borosilicate glass and was designed to be resistant to vibrations, included stress fractures. It is a one-piece vessel shaped to match the sonication probe, attached to the probe’s upper part by means of a threaded stopper system,3 with a central hole to introduce the probe. An O-ring Teflon gasket seals the reactor and guarantees a gas-tight closure (Fig. 2). The reactor is clamped on this upper part, and no decrease of sonication efficiency has been observed from deadening. In our design, the vessel has two side ports4,5 that allow the insertion of temperature probes6,7 or inert-gas lines, or
Threaded cap Internal O-ring gasket Thread
Gas inlet / outlet
Side port
Septum
Ultrasonic bath cleaner
Cup-horn sonicator
Ultrasonic horn
Figure 1. Sources of ultrasound on the laboratory scale.
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Figure 2. Reactor design: closing system and side ports.
Journal of Chemical Education • Vol. 77 No. 6 June 2000 • JChemEd.chem.wisc.edu
In the Laboratory
the removal of samples from the reaction mixture, through a septum,5 by a syringe (Fig. 2). The body of the reactor is cylindrical, with a conical bottom (Fig. 3). This conical design allows use of the reactor with the small reaction volumes (from 2–3 mL up to 50 mL) optimal for microscale reactions. The tip of the sonication probe extends to the bottom of the vessel, producing vigorous agitation. This is very important for heterogeneous reactions in which the solid particles accumulate in the bottom of the reactor by sedimentation. Agitation disperses the solid phase in the reaction medium, increasing the reaction rate. Regardless of the reaction volume, direct contact between the tip of the sonication probe and the reaction mixture is assured. The minimum reaction volume is determined by the insertion depth of the probe in the reaction vessel. (In no case should the probe tip touch the glass walls of the vessel.) Other advantages of this system from the operational point of view are: 1. It allows work with small reaction volumes of 2 to 3 mL (microscale). Microscale has economic advantages in allowing the exploration of a variety of reactions with minimal consumption of reactants or solvents.
Vessel dimensions
3. Our homemade reactor for ultrasonic horns is much less expensive than the standard commercial reactors (ca. $100–$150 vs >$600–$700), which are also not adequate for microscale work. 4. The sonication setup is quite safe because the reaction vessel is a robust piece (4-mm wall thickness) and because the quantities of reactants and volume of solvent are small. Moreover, due to the relatively small size of the reactor, it fits inside a small protecting cabinet or shield.
We think that this reactor for ultrasonic horns could be very useful for research and teaching laboratories owing to its operational advantages, safety, and low cost. Application of the Reactor An example of application of the sonication vessel is the cycloaddition of furan (or derivatives) with the oxyallyl cation (1) intermediate generated in situ from 2,2′-dihaloketones and copper (Fig. 4), under sonication, to synthesize diastereo-
O
H3C
CH3 Br
+ Cu + 2 NaI
+
Br 1
O
2
Reductive formation of the oxyallyl cation
Lower conical part h: 8.5 cm M.d.: 1.4 cm m.d.: 0.3 cm Horn tip h: 2.0 cm d.: 0.3 cm
Lower conical part h: 7.3 cm M.d.: 2.8 cm m.d.: 1.3 cm
isomeric 8-oxabicyclo-[3.2.1]oct-6-en-3-ones 3 and 4 in high yield (in a 3:4 ratio of 96:4), in only 20 min. To realize the importance of these sonochemical conditions, consider that the same reaction carried out at 60 °C without sonication affords both diastereoisomers (in a 3:4 ratio of 80:20) in 40– 48% yield in 4 hours (20). We present here an experimental procedure, with optimized reaction conditions, that has been carried out more than 50 times in a microscale level and has yielded highly repeatable results from different students working during many laboratory sessions. It is a simple procedure, from the operational point of view, with an easy workup. Moreover, it is a very instructive experiment because students learn to use several laboratory techniques. The reaction does not involved toxic materials, so no special safety measures need be taken except for the usual ones: wearing safety goggles and gloves and working in a laboratory hood far from ignition sources. Care should be taken with 2,2′-dibromo-3-pentanone because it is slightly lacrimatory; it should be handled in the laboratory hood. There are minimal wastes to be disposed of. The wastes can be classified as (i) organic (acetonitrile and nonflammable methylene chloride), which should be stored in a container for residual halogenated solvents to be sent for proper disposal; (ii) inorganic (NaBr and CuI2 aqueous solutions to be stored O H3C
+
CH3 O
+ CuI2 + 2 NaBr
4
3
Cu
Cylindrical part h: 11.0 cm d.: 1.4 cm
Cylindrical part h: 13.0 cm i.d.: 2.0 cm o.d.: 2.8 cm
CH3 O
Upper conical part h: 1.5 cm
Upper conical part h: 2.0 cm
O H3C
Probe head h: 8.0 cm d.: 3.7 cm
Vessel head h: 5.7 cm i.d.: 4.9 cm o.d.: 5.7 cm
Figure 3. Diagram of the homemade ultrasonic horn reactor vessel and sonication probe, showing dimensions: i.d. = inner diameter, o.d. = outer diameter, M.d. = major diameter, m.d. = minor diameter, h = height, d = diameter.
2. The small diameter and moderate thickness (4 mm) of the glass wall of the reactor facilitates heat transmission to an external cooling bath, making possible reactions at temperature as low as ᎑78 °C (A commercial Dewar vessel, 20 cm long with internal diameter of 4.5 cm, can be used for the dry-ice bath).
O
Probe dimensions
96:4
O− H3C
+
Cycloaddition
CH3
Figure 4. [4+3] Cycloaddition mediated by ultrasound: an example of microscale sonochemical reaction.
I
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In the Laboratory
and adequately disposed according to the institution’s policy and local and state laws); (iii) ammonia solution containing Cu(NH3)4+, to be properly disposed by neutralization with HCl and excess metallic copper, which can be recovered by filtration and recycled.
Experimental Procedure Preliminary Work The reactor vessel and all glassware necessary for the reaction process are oven-dried at 120 °C for two hours. Also, the threaded glass-probe connector, septa, and plasticware to be used are dried in a stove at 80 °C for 3 h. However, all these materials could be dried overnight to start the experiment the next day. Before use they should be allowed to reach room temperature in a desiccator (with P2O5) to avoid condensation of moisture during cooling. Reaction Setup In the reactor vessel, closed with septa and purged with argon (argon is more convenient than nitrogen because it is denser than air), 102 mg (1.60 mmol) of activated (21) copper bronze (Aldrich #29,258-3) and 240 mg (1.60 mmol) of anhydrous sodium iodide are placed via a weighing boat. The sonication probe is introduced into the vessel and fitted to it with the threaded glass-probe connector. The system is purged again with argon, and the inert atmosphere is maintained by using a balloon filled with argon connected to the gas side-port. At room temperature, 3 mL of dry acetonitrile (distilled from calcium hydride) and 0.15 mL (144 mg, 2.12 mmol) of dry furan (distilled from anhydrous KOH) are added by syringe through the septum fitted to the other side port. To homogenize the mixture, the system is sonicated for 30 s. The reactor vessel is introduced into an ice-water bath and 130 mg (0.53 mmol) of 2,4-dibromo-3-pentanone 1 (prepared according to ref 20), dissolved in 3 mL of dry acetonitrile, is added dropwise by syringe.8 Reaction The mixture is sonicated at 40% of maximum power, establishing sonication cycles of 15 min spaced by 5-min pauses, at 0 °C, under argon atmosphere. Monitoring the Reaction Reaction progress is monitored by GC, using the following analytical conditions: Column: capillary column Hewlett-Packard cross-linked MePh-silicone, 25 m long, i.d. 0.2 mm, thickness of the stationary phase 2.5 mm. Carrier gas: helium. Detector: FID (flame ionization detector). Apparatus setup: temperature of detector and injector, 250 °C; H2 pressure, 4.2 psi; air pressure, 2.1 psi; column head pressure, 24 psi; split ratio, 150/1. Temperature program: initial temperature, 100 °C; initial time, 1 min; heating rate, 10 °C/min; final temperature, 165 °C; final time, 1 min.
Under these chromatographic conditions the observed retention times for organic reagents and products are furan 2, 1.20 min; meso-1, 4.90 min; rac-1, 5.56 min; 3, 6.92 min; and 4, 6.54 min. 756
Under the reaction conditions a 95% conversion of dibromoketone 1 is observed after 10 min, 97% after 15 min, and 100% after 20 min of sonication. Quenching The reaction is quenched to destroy excess reactive intermediates by adding 2 mL of distilled water. Workup The system is opened to the atmosphere (products 3 and 4 are not moisture or air sensitive), the sonication probe is removed, and the crude mixture is filtered through a sinteredglass filter (4 Å) to recover the unreacted metallic copper. The reaction vessel and copper powder are respectively washed with 5 mL and 25 mL of methylene chloride and then with 10 mL of water. The filtered liquid is transferred to a separatory funnel and the organic (lower) phase is decanted and washed with successive 5-mL portions of 3% (w/w) aqueous ammonia until no blue color (Cu(NH3)4+) is observed in the aqueous phases. Finally, the organic phase is dried over anhydrous magnesium sulfate, filtered through filter paper, and concentrated to dryness in a rotary evaporator. In this way 65 mg (80% yield with respect to 1) of the diastereomeric cycloadducts is obtained in a 96:4 ratio of 3 to 4. Because the byproducts generated in this reaction are volatile reduction products of dibromoketone 1 and are removed from the reaction mixture during distillation of solvent, the cycloadducts are obtained in pure form (as determined by GC). W
Supplemental Material
Photographs of the ultrasonic horn reaction vessel and probe are available in this issue of JCE Online. Notes 1. Sonication probe: Microtip 1/8-in. diameter, from Branson Mod. EDP No. 101-148-062. Alternative suppliers: Ace, ColeParmer, Aldrich, Bioblock Scientific. 2. Ultrasound energy source: Branson Ultrasonics Co., Model 250 Sonifier. 3. Threaded cap (glass-probe connector): standard size ISO45 (similar to Ace’s cap joint, with hole, #7616-27). 4. Vessel’s gas port. Stopcock: conical stopper made of Teflon, 2-mm pass diameter (orifice), tube (i.d., 5 mm; o.d., 8 mm), tubing connector (width/length = 8/9 mm). 5. Side port: nonthreaded, ungrounded glass port; i.d., 10 mm; o.d., 13 mm. Designed to fit Aldrich rubber septa ref. #Z10,073-0. 6. Temperature probe: Teflon-coated flexible thermocouple Fluke, Mod. 80PK-1, type K (Chromel-Alumel). 7. Digital thermometer: Fluke Mod. 51K/J. Alternative suppliers: Ace, Cole-Parmer, Aldrich, Bioblock Scientific. 8. An excess of reagents is used with respect to the stoichiometric amount of dibromoketone 1, to accelerate reaction kinetics and achieve complete conversion of 1 in less than half an hour.
Literature Cited 1. Pestman, J. M.; Engberts, J. B. F. N.; de Jong, F. Recl. Trav. Chim. Pays-Bas 1994, 113(12), 533. 2. Suslick, K. S. Science 1990, 247, 1439.
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In the Laboratory 3. Lorimer, J. P.; Mason, T. J. Chem. Soc. Rev. 1987, 16, 239. 4. Mason, T. J.; Lorimer, P. J. Endeavour 1989, 13(3), 123. 5. Mason, T. J.; Lorimer, P. J. Sonochemistry: Theory, Applications and Uses of Ultrasound in Chemistry, 1st ed.; Wiley: New York, 1988, pp 1–245. 6. Mason, T. J. Chemistry with Ultrasound, 1st ed.; Elsevier: London, 1990; pp 1–186. 7. Mason, T. J. Sonochemistry: The Uses of Ultrasound in Chemistry, 1st ed.; Royal Society of Chemistry: London, 1990; pp 1–151. 8. Lash, T. D. J. Chem. Educ. 1985, 62, 720. 9. Lash, T. D.; Berry, D. J. Chem. Educ. 1985, 62, 85. 10. Joshi, N. N.; Hoffmann, H. M. R. Tetrahedron. Lett. 1986, 27, 687. 11. Souza-Barboza, J. C.; Pétrier, C.; Luche, J.-L. J. Org. Chem. 1988, 53, 1212.
12. Worthy, W. Chem. Eng. News 1991, 69(Oct 7), 18. 13. Einhorn, C.; Einhorn J.; Luche, J.-L. Synthesis 1989, 11, 787; review article. 14. Addulla, R. F. Aldrichimica Acta 1988, 21(2), 31. 15. Lindley, J.; Mason, T. J. Chem. Soc. Rev. 1987, 16, 275. 16. Boudjouk, P. J. Chem Educ. 1986, 63, 427. 17. Suslick, K. S.; Doktycz, S. J. J. Am. Chem. Soc. 1989, 111, 2342. 18. Suslick, K. S.; Casadonte, D. J. J. Am. Chem. Soc. 1987, 109, 3459. 19. Doktycz, S. J.; Suslick, K. S. Science 1990, 247, 1067. 20. Ashcroft, M. R.; Hoffmann, H. M. R. Org. Synth. 1978, 58, 17. 21. Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R. Vogel’s Textbook of Practical Organic Chemistry, 5th ed.; Longman Scientific and Technical: Harlow, Essex, England, 1989, p 426.
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