In the Laboratory edited by
The Microscale Laboratory
Arden P. Zipp SUNY-Cortland Cortland, NY 13045
A Microscale Birch Reduction for the Advanced Organic Chemistry Laboratory Mary Ann M. Fuhry,* Christie Colosimo, and Kathleen Gianneschi Department of Chemistry, Slippery Rock University, Slippery Rock, PA 16057; *
[email protected] The design of laboratory experiments for upper-level undergraduates is particularly challenging. As in all laboratory courses, the experiment should illustrate a concept discussed in lecture while it teaches the students a new practical skill. Additionally, for advanced organic chemistry students, an experiment should go beyond the “put something into a flask and take it back out” approach. There may also be time, space, and equipment limitations to consider. The following Birch reduction (1) procedure was developed with all of the above criteria in mind. It gives students the opportunity to work with gaseous reagents, condensing ammonia while maintaining a nitrogen atmosphere. Upon addition of activated lithium, the students are able to witness the appearance and then disappearance of the intense deep blue color of the solvated electron. This visualization, by color, of the generation and consumption of electrons should go a long way toward making the reaction’s single-electron reduction mechanism less abstract. A simple microscale apparatus (Fig. 1), in which a Winston sublimator1 is used as a microcold-finger condenser, can be assembled in even the smallest fume hood; a three-way stopcock, a bubbler, and some flexible tubing eliminate the need for a more elaborate manifold system. The reduction product can be characterized using FTIR and low-field 1H NMR spectroscopy. The reduction of meta-toluic acid to 1-carboxy-3-methyl1,4-cyclohexadiene (1) was studied (Scheme I). Working in groups of two or three, students assembled the oven-dried apparatus, cooled it under N2, and, using THF as a cosolvent, added the reagents (see Experimental Procedures). Generally, one student cut and cleaned the lithium while the other(s) condensed the ammonia.2 It is important to stress to the students that the lithium pieces must be very small—not only do they have to fit through the sidearm of the reaction vial, but they must also dissolve quickly so they don’t disrupt the stirring. As the first few pieces of the lithium were added, students were able to observe the flashes of dark blue color that
dispsable 1-mL plastic syringe, cut off
O
O Li, NH3 (l), THF,t-BuOH
OH
OH H
H H CH3
CH3
1
Mechanism O
O O-
e-
O O-
O-
H
H
H
CH3
H
CH3 H
CH3 O
O
O -
O-
O H3O+
1
e-
H H
H H
H CH3
CH3
H
O
Scheme I
appeared near the lithium, then disappeared as the reaction took place. Eventually, enough lithium was added that there was an excess, and the entire solution remained dark blue for several minutes. At this point, a drop of isoprene was added to consume the excess electrons, and the workup was continued as described below. Students were able to complete the entire procedure through the extraction in a single threehour laboratory period. The stable product was isolated and analyzed the following week.3
Winston sublimator
to N2
flexible tubing 3-way stopcock
needle 5-mL sidearm vial to bubbler
flexible tubing
to NH3
stir bar
Figure 1. Apparatus for Birch reduction.
JChemEd.chem.wisc.edu • Vol. 78 No. 7 July 2001 • Journal of Chemical Education
949
In the Laboratory
Safety and Disposal This experiment must be performed in a properly functioning fume hood in order to minimize exposure to NH3. Check all regulator fittings before use. The amount of Li required for this procedure is very small, but students should be reminded to take only about a 0.5-cm segment from the stock supply of Li wire. They should keep the Li coated in oil until immediately before its addition to the reaction flask (see Experimental Procedure). Any unused Li may be destroyed by carefully adding it to dry butanol under N2. The resulting solution should be neutralized with aqueous acid before packaging and labeling for disposal. Experimental Procedure To an oven-dried apparatus (Fig. 1) under a N2 stream were added meta-toluic acid (0.1036 g, 0.761 mmol) and a small egg-shaped stir bar. To this were added THF (1 mL)4 and tert-butyl alcohol (0.1 mL, 1.046 mmol.) via syringe through the sidearm septum. The apparatus was immersed in a CO2/ acetone bath, and the same was added to the cold finger of the apparatus. The N2 stream was switched to NH3(g), which condensed in the apparatus to NH3(ᐉ) (ca. 4 mL). The gas stream was then switched back to N2 for the duration of the procedure. The stir bar was engaged. The Li wire was prepared by first cutting off any visible oxidized coating while it was still immersed in the storage oil. A small section, about 0.5 cm long, was then transferred to a watch glass, where it was cut into slivers small enough to fit through the sidearm. Each sliver was immersed in hexane to remove the oil before adding it to the reaction mixture. Students were instructed to wait until each piece of lithium reacted completely before adding the next piece. Upon persistence of the dark blue color, a drop of isoprene was added, and the solution was quenched with pH 7 phosphate buffer (ca. 0.5 mL). The CO2/acetone mixture was removed from all parts of the apparatus. The NH3(ᐉ) was evaporated under the N2 stream. The remaining residue was dissolved in H2O (1 mL),
950
acidified with 6 M HCl (ca. 20 mL) and extracted with diethyl ether (3 × 10 mL). The combined organic layers were washed with water, dried over anhydrous Na2SO4, and filtered through a cotton plug. The solvent was removed using a rotary evaporator to give an oily solid (0.099 g, 0.717 mmol), which was analyzed without purification.5 1H NMR (60 MHz, CDCl3): δ 6.0-5.0 (m, 3 H, vinyl H); 4.0–3.5 (m, 1H, C1–H); 3.0–2.5 (m, 2H, C4–H); 1.8 (s, 3H, CH3). FTIR (neat): 3300–2300 cm᎑1 (acid OH); 3050 cm᎑1 (vinyl C–H); 2926 cm᎑1 (aliphatic C–H); 1695 cm᎑1 (C=O). Notes 1. The Winston sublimator and the 5-mL sidearm vial are available from Ace Glass, Inc., Vineland, NJ. The Winston sublimator was designed by Anthony Winston, The Microscale Institute, Department of Chemistry, West Virginia University, Morgantown, WV. 2. Lecture bottles of ammonia were used. Regulators were used on both cylinders to control the flow of the gasses. 3. Infrared spectra were obtained on a Perkin Elmer Series 1600 FTIR as neat solid films. 1H NMR spectra (60 MHz) were obtained in CDCl3 on a Hitachi R-1200 rapid scan instrument. The NMR instrument was not sensitive enough to resolve couplings on this small amount of material, but the chemical shifts were consistent with the predicted 1,4-reduction product (2). 4. Anhydrous THF was purchased from Fisher Scientific (Acros). 5. The product gave satisfactory IR and 1H NMR data without purification. If desired, it may be recrystallized from petroleum ether using a Craig tube apparatus (ca. 25 mg dissolved in 1 mL of hot solvent) to give white needles, mp 83–84 °C (2).
Literature Cited 1. Birch, A. J. Q. Rev. Chem. Soc. 1959, 4, 69. Birch, A. J.; Hinde, A. L.; Radom, L. J. Am. Chem. Soc. 1980, 102, 3370. 2. Van Bekkum, H.; Van Den Bosch, C. B.; Van Minnen-Pathuis, G.; De Mos, J. C.; Van Wijk, A. M. Recl. Trav. Chim. Pays-Bas 1971, 90, 137.
Journal of Chemical Education • Vol. 78 No. 7 July 2001 • JChemEd.chem.wisc.edu
