The Synthesis of 4,6,8=Trimethylazulene An Organic Laboratory Experiment Michael E. Garst,' Jill Hochlowski, J a m e s G. Douglass, Ill,' and Scott Sasse University of California, San Diego, La Jolla, CA 92093 Azulene was detected bv the alchemists over four-hundred 1 % ) puri~ymany o i ~ h c , mid fifty ywrs ,igt) > I > thcq ~~tt~mptc:cl essential uils. The swrce or swthe;is , ~ i . I . ~ i . o - t r i ~ n e ~ I ~ v l dwe , u Ihave ~ ~ ~ emcodified . the ~ a f n e rpyrylium salt procedure reported in Organ~c Synthesis (2) 2,4,6-Trimethylpyrylium fluoroborate was prepared as described by Balaban and Boulton (3).This reaction required from 1to 1.5 hr for completion. The crude product was not recrystallized but used directly in the next step. Treatment of this salt with sodio-cyclopentadiene yielded the azulene directly. Our key experimental modification is the generation of this sodium salt with sodium metboxide in anhydrous dimethylformamide in a stoppered flask. An inert atmosphere is not required. Purification of this product is effected by sequential extraction, chromatography on alumina, sublimation, andlor recrystallation. Student yields of azulene range from 0.5-1.5 g (12-36%) after purification. The preparation requires a full 3-hr lab period; the ourification. another laboratorv ~ e r i o d . The experiment is introducedto the students by a short summary of the history of azulene ( I ) . The concept of aromaticity is then presented by comparing naphthalene and azulene. Azulene adheres to the Hiickel rule with ten n elec-
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510
Journal of Chemical Education
hnOMe
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trons, possesses a stabilization energy of 48.7 kcallmol, and exhibits a diamagnetic ring current as shown by NMR spectroscopy. The bond lengths of azulene vary between 1.27 A and 1.48 A, but eight of these bonds are between 1.37 A and 1.42 A. Azulene undergoes electrophilic aromatic substitution with mild acid catalysis. Zwitterionic resonance structures oermit the orediction that the 1 and 3 ~ositionsof azulene ;ndergo ele&ophilic aromatic substitution more rapidly than benzene. These structures also rationalize the ranee " of bond lengths and the dipole moment of azulene.
' We are grateful to a Regents' Instructional Improvement grant
(UCSD) for summer support for J.R.D.
The y ,,, for napthalene occurs at 32,000 cm-' (312 mw) and azulene at 17,300 cm-' (580 mw). The azulene value determined by this method is 0.65flcompared to 0.836flcalculated using LCAO-MO by Heilbronner (ref. (8)). Although the relationship of molecular orbital theory and UV spectroscopy and the HOMO-LUMO energy difference are discussed in all of the elementary organic texts, none of these include azulene or naohthalene. Heilbronner's discussion usina both naothalene and azulene MO schemes as modified cyclodeca&taenes' is easily understood by the students (see ref. (la)).
T h e source of t h e blue color is discussed i n t e r m s of t h e simple molecular orbital theory. T h e s t u d e n t s realize t h a t azulene m u s t have a narrow H O M O - L U M O gap. Heilhronner's (la) explanation is easily understood. Both naphthalene a n d azulene are treated as perturbed cyclodecapentaenes. T h e orbital diagrams a r e presented to t h e s t u d e n t s a n d t h e LCAO-MO calculated values of 1.20 for naphthalene a n d 0.840 for azulene. Using t h e Sadtler value for naphthalene t h e y calculate a n expected UV adsorption for azulene before measuring t h e s p e c t r ~ m . ~ , 3 Finally, t h e formation of t h e pyrylium s a l t a n d of azulene permits a review of t h e stahility a n d reactivity of carhonium ions. T h e effect of solvent a n d counterion o n t h e pyrylium salt life time a r e discussed. Olefin acylation a n d El reactions a r e summarized during a n examination of t h e mechanism of t h e salt formation. Although carhonyl additions have n o t been covered in our lecture courses when t h i s experiment is completed, t h e s t u d e n t s readily follow t h e mechanism proposed for azulene formation using simple olefin addition con cepts. T h i s exneriment highlights conceuts which a r e n o t usually covered i n t h e laboratory. T h e formation of a colored, organic substance excites t h e s t u d e n t a n d could be used to introduce t h e chemistry of vision.
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Procedure-Azulene Trimethylpyryliurn fluoroborote: In a 250-ml Erlenmeyer flask provided with a thermometer, 50 ml(530 mmol) of acetic anhydride and 4.0 ml(41 mmol) t-hutyl alcohol are added. Fluorohoric acid (7 ml, 39 mmol) is added carefully to the mixture in 0.1-0.3 mi portions a t a rate so as the final temperature reaches =10O0C. Keep the reaction mixture well agitated. If the temperature rises above 100DC (too much HBFd added), eool the mixture with an ice bath to ahaut 80°C and continue the addition. The mixture should turn from colorless to straw yellow to dark brown. After all of the fluorohoric acid has been added, allow the reaction to cool to -80°C. When the temperature reaches 80°C, use an ice bath to eool the mixture to - 5 T . A salt should begin to precipitate. Complete the precipitation by the addition of 100 ml of anhydrous ether. Collect the white or pale yellow product by suction filtration. Wash the product with 30 ml of anhydrous ether to leave from 3.94.1 g (41-5090) of pyrylium salt melting at 218-220°C with decomposition. Do not recrystallize this salt. 4,6,8-Trimethylozulenet Outfit a 25-ml round-bottomed flask with the distillation column, distillation head, condenser, and adaptor far fractional distillation. Use a 25-ml graduated cylinder for a receiver. Place this cylinder in an ice bath. Place =15 ml dieyelopentadiene in distillation flask and distill being careful to keep the head temperature helow -80°C to crack the cyclopentadiene dimer. The receiver should be kept cold to prevent redirnerization. More than 10 ml should he collected. The cyelopentadiene must he used shortly after distillation. In a dry 125-mlErlenmeyer flask fitted with a rubber stopper place 8.0 g of sodium methaaide. Add about 50 ml of dry dimethylformamide. Keep the Erlenmeyer stoppered. Cool the stoppered flask in an ice bath. Quickly add 10 ml of cyelopentadiene and re-stopper the flask. Swirl the flask keeping it coal. The suspension will be strawcolored to dark brown. The dark hrown color is due to the eyelopentadienyl anion reaction with oxygen. After 1-2 min, add the solid pyrylium salt (about 4 g) and again rapidly restopper the flask. A deep
azure color should develop. Failure to observe a blue color at this time has always indicated that no azulene will he isolated. Thus far this has resulted from incorrect order of addition (sodium methylate and pyylium salt) or from cyclopentadieneredirnerization. Allow the flask to stand at room temperature for 30 min to I hr, swirling it occasionally Then dilute the suspension with 60 ml of water and wash the aqueous layer with 20 ml of petroleum ether three times. The layers are very dark and difficult to see during the first extractions. The students might he able to see the layer separation by holding a flashlight behind the separatory f u n n d 4 If necessary, remove most of the liquid, separating the last 10-20 ml. This process can then be repeated 3-4 times. The pooled top layers should he washed with saturated sodium chloride solution. This maroon petroleum ether solution is dried aver magnesium sulfate and filtered. The solvent is removed by simple evaporation on a steam bath to leave 1-2 g dark oily residue in the 25 rnl distillation pot. Pack a chromatography column by placing a glass wool plug above the stopcock. Add a layer of sand =1 cm thick on top of this glass wool. Fill the column with petroleum ether and start a slow drip rate. Slowly add 15 g of alumina to the tap of the column allowing it to smoothly settle in a column. After all of the alumina has been added, increase the flow rate to permit all of the petroleum ether to drain from the column above the alumina. Turn off the stopcock when the solvent is about 1in. above the top of the alumina. Add enough sand to the tap of the alumina to make about 1cm layer of sand. Dilute the distillation residue with 0.5 ml petroleum ether and carefully pipette this material onto the top of the column. Open the stopcock allowing the solvent to drain untilit barely covers thesand. Add 5 mlof petroleum ether to the column and drain the column until the solvent barely covers the sand. A dark hand should be on top of the column at this time. Fill the column with oetroleum ether. Omn the stoocoek al-
to leave 0.5-2.0 g of oily solid.
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Alternatively, the crude azulene may be sublimed prior to recrystallation using a sublimation apparatus constructed from a 50-ml, side-armed Erlenmeyer and a 12 X 100 mm test tube. The crude azulene (0.5 g) is placed in the Erlenmeyer. The tube, secured in the Erlenmeyer with a large rubber stopper, serves as a cold finger when loaded with drv ice and acetone. A house or asoirator vacuum is sufa portion of their azulene, even IF not necessary. In several instances students have removed the remaining material (yellowish hands) from the column withether or methanol. Speetroscapic examination (NMR, IR, MS) of this mixture suggests it to he pyrylium salt derived compounds. Note Added in Proof W e now have s t u d e n t s prepare l-trifluoromethylacetyl4,6,8-trimethylazulene a n d 4,6,8-trimethylazulene carboxylic acid by trifluoromethyl acetylation a n d base treatment. T h e detailed procedures will b e available o n request. Literature Cited I
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Failure to complete the extraction of the crude azulene after 1-2 hr in DMF-base has led to only trace amounts of azulene.
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