the microscale lcrborator y Microscale Synthesis of Azulene Gotifried Brieger
Oakland University Rochester, MI 48309-4401 Azulene represents an interesting synthetic challenge. As a nonhenzenoid isomer of naphthalene, the conventional synthetic pathways for six-membered rings are not applicable to it. Recently a convenient synthesis for this substance was presented ( I ) .
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Azulene
This report represents a microscale adaptation of this work. The synthesis has several valuable didactic features including examples of a [2+41 cycloreversion, a wndensation, addition-elimination, a [6+41 cycloaddition, and a cheletropic elimination, and the synthesis of an aromatic and an anti-aromatic compound. In addition the techniques of working under an inert atmosphere, column chromatography, and UV spectroscopy are introduced. Finally there is the satisfaction of an "indicator" of success as the brilliant blue product elutes from the column. Experimental Sectlon Synthesis of 6-Dimethylaminofulvene(1)
Fit a 3.0-mL conical vial with a Claisen head and several boiling stones, and attach a saewcap with a septum or a standard rubber septum to the straight arm. Equip the other arm with a water condenser. Flush the apparatus with nitrogen, using a needle through the septum, and stopper the condenser. Fill a balloon with nitrogen, twist the end closed, remove the stopper from the condenser, and attach the balloon in its place. Aballoon that stays inflated indicates a sealed system. Through the septum, inject 805 pL (10 mmoles) of freshly distilled cyclopentadiene' and 1.71 mL (10 m o l e s ) dimethylformamide diethyl acetal. Heat the solution with a sandhath maintained at 100-110 'C for 1h. The solution should turn orange-red and refluxPresented at the 11th Biennial Conferenceon Chemical Education, Atlanta, GA, August 5 4 , 1990. 'Cyclopentadiene is best prepared in bulk for the entire class by thermal cracking of dicyclopentadiene. For this purpose, a 100-mL round-bottom flask is fitted with a Vigreux condenser, distillation head, thermometer, condenser, takeofl adapter, and an ice-cooled collection flask. Slow distillation of dicyciopentadiene yields cyclopentadiene, b.p. 41-42.C. The cyclopentadiene should be used shortly after preparation since it will redimerize at room temperature. A262
Journal of Chemical Education
ARDENP. ZIPP SUNY-Coniand c0~land~Ny1~5
ing should he very slow near the end of this time. Remove the condenser and Claisen head and apply a vacuum to the end of the vial while keeping it in the sand bath in order to remove residual volatile reaeents. On cooline the Droduct tends to crystallize partiallfor completely. 6issoive it in au~roximatelv30 mL of ~etroleumether and recrvstallize. he melting point of theApureproduct is 6&67 '6.Typical student yields are 25-35% Synthesis of 3,4-Dibromotetrahydrothiophene1 , 1 -dioxide (2)
Fit a 5.0-mL conical vial with a water condenser and a calcium chloride drying tube. Place 1.0 g (8.4 mmoles) butadiene sulfone and 2.0 mL chloroform in the vial with several boiling stones. Heat the solution to reflux, then add 433 pL Brz in 500 pL chloroform through the top of the condenser over a period of 5-10 min and continue to reflux for 1h. At this point the solution may still he colored, and the dihromide may begin to precipitate. Cool the mixture, then filter the crystals with a Hirsch funnel, and wash the crystals with a small amount of cold chloroform. The dibromide may be recrystallized from chloroform if necessary. The melting point is 142-143 T!.A typical yield is approximately 80%. Synthesis of Jhiophene 1,l-dioxide (3)
Place 20 mL of freshly distilled tetrahydrofuran and 444 me (1.6 mmoles) of 3.4dibromotetrahvdrothio~hene1.1di&de (2) in a ~ O O -Erlenmeyer m~ fl&k equidped with a magnetic stirring bar. Flush the flask with nitrogen, stopper tightly, and cool in an ice bath. Quickly add approximately 0.8 g freshly powdered NaOH, flush again with nitrogen, stopper, and allow to stir a t 0 "C for lh. The suspended NaOH may turn purple during this reaction. Just prior to the next step, prepare a funnel for vacuum filtration. Suspend approximately 1g of Filter-aid (Celite) in dry tetrahydrofuran and filter it in such a way as to ohtain an even layer of Celite on the filter paper. Carefully vacuum-fdter the reaction supension through the Filteraid. The clear filtrate that results must be kept cold until used in the next step. Synthesis of Azulene (4)
Equip a 100-rnL round-bottom flask with a water wndenser and a few hoiling stones. Add 160 mg (1.3 mmoles) of 6-dimethylaminofulvene(1)and the freshly filtered wld solution of thiophene 1,l-dioxide (3).Flush the setup with nitrogen and attach a nitrogen-filled balloon to the top of the condenser. Reflux the solution for 3 h, noting any color changes. At the end of this time, remove the solvent at rwm temperature using a rotary evaporator. Alternatively apply an aspirator vacuum while keeping the flask slightly warm. Be careful to avoid bumping. Extract the residue with several small portions of pentane, until the extracts are no longer blue. Combine these extracts and carefully evaporate to dryness. Dissolve in 200 pL of pentane. Prepare a chromatographic column using approximately 3 g alumina in a 4-mL Pasteur pipet. Wet-pack the column using 60-80 'C petroleum ether. Apply the azulene extract and develop the column with pentane.
the microscale laboratory Discussion The reactions shown in Figure 1are carried out in this experiment. The thermal decomposition of dicyclopentadiene introduces the theme of electrocvclic reactions, i n t h i s case a [2+41 cycloreversion. The reaction is + (CH&H20)2CHN(CH3)2 CHN(CH3)2 2CH3CHzOH particularly easy to carry out because of the low enerm requirements. The condensation reaction of the diethylacetal with cyclopentadiene illustrates the ease with which a proton may be removed from cyclopentadiene as the reagent is also a base and functions catalytically The presence of the anti-ammatic thiophene 1,l-dioxide 3 can be demonstrated in solution by UV spectrometry (2). I t reacts via a remarkable thermally allowed [6+41 cycloaddition. ~ r e s u m a b l v to eive initialfi the unisoiated iitermediate pictured. This is followed by cheletropic elimination of SO2 and elimination of dimethylamine driven by the 4 formation of t h e stable aromatic system of azulene. Figure 1. The series of reactions carried out in this experiment. The beautiful wlor is due to a low-lying excited singlet state Collect the blue band in a weighed vial, evaporate the (LUMO), compared to the isomeric naphthalene a s pentane, and weigh the product. The azulene may be reillustrated in Figure 2(3). crystallized from 95% ethanol; the melting point is 9&99 Literature Clted 'C. The yield varies with a maximum of 48% obtained so far. If a UV-vis spectrometer is available, the visible spectrum will show the following absorbtions ( in petroleum = 541 nm;log em, = 2.34; 558 ether or cyclohexane): (2.43); 580 (2,541; 603 (2.46); 632 (2.48); 661 (2.12); 697 Improvements in the Ultra-Micro (2.07).
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Boiling-Point Technique Gerald Rausch and John Tonnis University of Wiswnsin-Lacrosse Lacrosse, WI 54601
Naphthalene
Azulene
Figure 2. Molecular orbital diagram for naphthalene and azulene. A264
Journal of Chemical Education
Of all the microscale techniques, the ultra-micro boiling point is usually the most difficult for students to master. Students frequently pull 10-20 capillaries before fabricating a bell of appropriate size and straightness to enter a melting point capillary tube. In addition, the bells may be so short that they have a tendency to climb out of the liquid when heat is applied. The use of commercial micmpipets solves both problems and isvery economical. A 10-pL pipet can be cut easily into three segments that can be flame sealed to provide three bulbs (Drumond "microcaps" VWR Scientific, Catalog #53440-103). These sealed micropipet segments provide both ideal diameter and length for liquid samples of about 5uL.
