D. J. Porto anu J. A. Duncon University of Notre Dome Notre Dame, Indiana 46556 E. F. Silversmith Morgon State College Baltimore, Marylond 21239
I I
I
Stereospecific Thermal Cycloadditions and Catalyzed lsomerizations An organic laboratory project
We have reo oared a seauence of experiments for our undergraduat; organic chemistry laborkory concerned with the preparation of cis- and trans-1.4-diphenvl-2-butene- . 1,4-dionis, their cycloaddition reactions with cyclopentadiene, and with related isomerization reactions of both the dienophiles and cycloadducts. We feel that this particular sequence, which has met with much success experimentally, clearly and collectively demonstrates certain aspects of the concepts of thermodynamics, kinetics, stereochemistry, and photochemistry. The sequence begins with the preparation of trans-1,4diphenyl-2-butene-l,4-dione (I) by a typical Friedel-Crafts ). The nroceacvlation of benzene with fumarvl chloride (, I-, d u e uses only the typical apparatus available in most undermaduate laboratories. Fumawl chloride is moderatelv lacKrymatory; however, when it 'is measured into a stoppered addition funnel in a fume hood, the reaction can be carried out on an open bench without contamination of the laboratory atmosphere. Although large quantities of aluminum chloride are used, the slow hydrolysis of the aluminum chloride-product complex is safely accomplished over crushed ice. is The yellow trans-1,4-diphenyl-2-butene-l,4-dione converted to the colorless cis-isomer (11)in high yield by irradiating the trans-isomer in ethanol with an unfiltered GE 275-W sun lamp ( 2 - 4 ) .Upon treatment with a trace pf acid catalyst in ethanol solution, the cis-1,4-diphenyl-2butene-1,4-dione is rapidly isomerized to the more thermodynamically stable (I)(3, 5).
(1)
The 6 2
+ .4]
1111
cycloaddition reactions of hoth cis- and. trans-1,4-diphenyl-2-butene-l,4-diones with cyclopentadiene to give endo,endo:2,3-dibenzoylhicyclo[2.2.l]hept5-ene (III) and racemic exo,endo-2,3-dibenzoylbicyclo[2.2.l]hept-5-ene (IV), respectively, have been previously reported by Adams (6). The far greater reactivity of the reaction of the trans-dienophile is evident by the different reaction conditions employed in each case. In the final part of our experimental sequence, the students are asked to perform a n analytical separation of the two cycloadducts (111) and (IV) by thin layer chromatography (tlc) and then to equilibrate each separately in ethanolic sodium ethoxide. By following the catalytically induced isomerizations the student is given the opportunity to discover experimentally which of the three possible geometric isomers of 1,2-dibenzoylbicyclo[2.2.l]hept-5-ene is most stable. Periodic thin layer chromatographic analyses clearly reveal that the endo, endo-isomer (III)is quite clearly isomerized to exo,endo-2.3-dihenzoylbicyclo[2.2.l]hept-5-ene (IV) within 30 minutes; no third adduct, the exo,exo-2,3-dibenzoyl-bicyclo[2.2.1]hept-5-ene, was detected. After treatment of hoth adducts with ethanolic sodium ethoxide the products are readily isolated and
identified by their melting points and mixture-melting points with original adducts (111) and (IV).
4;
%%F&2h
COPh
COPh
+
kpcoph WPh
H CN)
(111)
With careful coordination of the individual parts of this experiment, its completion can he accomplished in approximately five average (3-4 hr) laboratory periods. We recommend the following schedule for this laboratory experience: The first and second periods are utilized for the initiation and completion of Part A (See Experimental). During the third period, Parts B and C are initiated and followed as soon as possible by Part D. I n the fourth period the product from Part B is secured from the workup procedure and used immediately for Part E. The product from Part D is then worked up and Part F. performed as well. During the fifth and final period, the product obtained in Part E is purified and Part G is done. We believe that this particular experiment lends itself well to the preparation of a special written laboratory report which we suggest might consist of the following sections I. Abstract. A very brief summary statement of the total experiment, its results, and major canelusions (one or two paragraphs maximum). 11. Results and Discusion. Important data and results should he provided and the discussion of these should include the following: A) A rationale for the photochemical transformation of the more thermodynamically stable tms-1.4-diphenyld-hutene-1,4-dione (I)toits lessstable cis-isomer U. B) An explanation for the color difference of the two 1,4-diphenyl-2-butene-1.4-diones(I, yellow; It, colorless). C) Structures and systematic names for the three possible geometric isomen of the cycloadduct and clear identifieation of the two isomers actually ohtained in the reactions of1 and I1with eyclopentadiene. D) Identification of the most thermodynamically stable isomeric cycloadduet and a clear explanation as to how this assignment can be made from evidence gained in the exneriment. r~~~~ E) A rationale for the marked difrkrence in the renrrivrty of a n h rvclopenrnthe t w o 1.4-d~phenyl-2-hut~ne.l,4~diones ~~~~~
F, .\lrchnnirm~for rhe phorocheml~.altranaformsrion of 1 to I I andror the ac~d-catalyzedisurnrrlzarion of I1 to I. G I A rnrchanisrir propoval fur thr hase-catalyzed iaornariza-
tion of the cycloaddition product(s).
H)An explanation for the use of a large excess of cyclopentadime in the cycloaddition reactions. III. Conclusions. Major conclusions reached should be provided and related to the theoretical concepts involved. IV. Ezpwimental. The experimental procedure followed should he written in the student's own words and patterned after the "Experimental Section" of a major research journal. V. References. Pertinent literature references which supplement the repgrt should be cited. Volume 51. Number
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Experimental Part A. Trans-l,4-Diphenyl-2-butene-1,4-dione ( I ) Equip a 500-ml three-necked flask with a thermometer, an addition funnel (with a side-arm if available) and a condenser fitted with a "T-tube" by means of a one-hole stopper a t its top. Place the assembled apparatus on a steam bath and support it by a single clamp about the center neck to allow for ease of swirling during the course of the reaction. Charge a 250-ml suction filter flask with 150 ml of 10% aaueous sodium hvdronide and conned one side of the "T-tube" with rubher tubing to a short section of glass tubing which is inserted through a one-hole rubber stopper. Complete the trap assembly by adjusting the lower end of the glass tube so that it is below the surface of the base solution, and connect the suction outlet of the flask to a water aspirator. Place 180 ml of dry henzene in the flask and add 35 g of aluminum chloride thmugh a powder funnel with swirling. Carefully measure 15.3 g of fumaryl chloride and place in the addition funnel (equipped with a stopper). (It is recommended that both the aluminum chloride and fumaryl chloride he weighed out in a hood.) Heat the benzene-aluminum chloride suspension t o W"C with the steam bath and adjust the water aspirator such that a steady stream of air is drawn across the top of the condenser and through the aqueous sodium hydroxide in the trap. Initiate the reaction with the dmpwise addition of the fumaryl chloride. Adjust the addition rate t o maintain a moderate rate of gas evolution and a reaction temperature in the 60-80'C range and vigorously swirl the mixture frequently to prevent caking of the red aluminum chloride-product complex which forms. (It may he necessary to monitor the heating with the steam bath to keep the temperature in this range and caution must be exercised to avoid excessive foaming.) Upon completion of the addition of fumaryl chloride (15-25 min), continue t o heat the mixture until all hydrogen chloride evolution has ceased (approximately 5-10 min). Using a n ice hath, cool the reaction mixture to room temperature and then, in a hood, cautiously, pour small portions (10-15 ml) of the mixture over 400 g (-500 ml) of cracked ice in a 800ml beaker to which has been added 7.5 ml of concentrated hydrochloric acid. After each portion of the reaction mixture is added, stir thoroughly with a glass rod t o break up any large chunks of the insoluble red aluminum chloride-product complex. Hydrolyze any residue in t h e reaction flask by cautious addition of small quantities of ice and add this mixture t o the bulk of the hydrolyzed mixture. Heat the hydrolyzed mixture on a steam bath under a hood until all of the yellow product dissolves in the upper benzene Layer. Decant the product layer into a 400-ml beaker, add 40 ml of fresh henzene t o the hydrolysis residue, heat and stir if necessary t o dissolve any remaining product, and decant this benzene layer into the heaker containing the original benzene solution. Warm the solution with a steam hath and slowly add 2 3 g of anhydrous magnesium sulfate with thorough stirring. (If the solution does not become perfectly clear, add an additional 2 g of magnesium sulfate and stir again.) Filter the hot solution by gravity thmugh a heated funnel with fluted filter paper into a n appropriate size Erlenmeyer flask. Stopper the flask and store until the next laboratory period. Dissolve any precipitated product by heating on a steam hath and pour the solution into an appropriate distillation flask, transferring any residual solid product with excess warm henzene. Concentrate the benzene solution to a volume of 3 M ml by distillation. (An ail bath is recommended for heating; if a heating mantle is employed care must he exercised to avoid overheating, which may result in some decomposition and the formation of a dark red impurity.) Pour the distillation residue into a 125-ml Erlenmeyer flask and rinse the distillation flask with 25 ml of hot 95% ethanol and add the solution t o the Erlenmeyer flask. Chill the contents in an ice hath, collect the yellow product and reerystallize once fmm 95%ethanol. Mp 110°C.
Part B. Ph.otochemicai lsomerization of Trans-7,4Diphenyl-Pbentene-1,4-dione ( I ) to the Cis-isomer ( I i ) Dissolve 3.0 g of trans-1,4-diphenyl-2-butene-1,4-dione in 120 ml of 95% ethanol in a 250-ml Erlenmeyer flask by heating on s steam bath. While still hot, stopper the flask l o w l y with a cork and irradiate the contents with a n unfiltered GE 275-W sun lamp a t a distance of 4-6 in. for about 6-8 hr. (Up to four flasks can he successfully irradiated simultaneously with one lamp if the lamp and flasks are surrounded with sheets of aluminum foil.) Cool the flask in an ice hath and induce crystallization by 278
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scratching with a stirring rod if necessary. Collect the white solid and recrystallize fmm 95% ethanol. Mp 136'C.
Part C. Cyclopentadiene by Thermal Cycloreversion of Dicyclopentadiene Charge a 125-ml distillation flask with 30 ml of dicyelopentadiene and attach it to a fractional distillation apparatus containing stainless steel packing. Immerse the receiving flask (50-ml) in an ice bath and heat the distillation flask carefully with a mieroburner until the contents begin to reflun. Continue the heating such that the cyclopentadiene distils over a t 4042'C until approximately 15 ml of it has been collected. Stopper the receiving flask and store it in a beaker of ice or a refrigerator.
+
Part D. [,2 .4] Cycloaddition of Trans-1,4-Diphenyl-2butene-1.4-dione with Cyclopentadiene In a 50-ml Erlenmeyer Flask, dissolve 2.0 g of trans-1,Cdiphenyl-2-butene-1,4-dione in 10 ml of henzene by heating on a steam bath. Add 2.5 ml (-2 g) of cyclopentadiene and after the initial exothermic reaction has subsided, heat the flask on a steam bath for 2 hr. Stopper the flask and store until the following laboratory period. Remove most of the benzene by heating the flask on a steam bath in a hood. (A disposable pipet connected to a water aspirator and suspended by a clamp so that the tip of the capillary is positioned just above the surface of the solution provides a convenient means of removing volatile solvents when a hood is not available and for more rapid solvent evaporation in either case.) Add 5 ml of 95% ethanol and cool the flask and its contents until crystals form (scratch the inside of the flask if necessary). Collect the crystals by suction and recrystallize from methanol. Mp 79'C.
+
Part E. [,2 ,4] Cycloaddition of Cis-I,#-Diphenyl-2butene-1.4-dione with Cyclopentadiene. Dissolve 1.0 g of ci+l,4-diphenyl-2-butene-1,4-dione in 30 ml of absolute ethanol in a 50-ml round bottom flask. Add 2.5 ml (-2 g) of cyclopentadiene, attach a condenser, and heat the mixture a t reflux for 3.5 hr or until the end of the laboratory period. Cool the flask, stopper, and store until the next laboratory period. If crystals have formed on standing, cool the flask momentarily in a n ice bath, then collect the crystals and recrystallize from ethanol. In the event that no crystals have formed, evaporate approximately half of the solvent on a steam bath, and proceed as above. Mp 161'C.
Part F. Acid-Catalyzed lsomerization of Cis-1,CDiphenyl2-butene- 1,4-dione Dissolve 0.2 g of eis-1,4-diphenyl-2-hutene-1,4-dione in 10 ml of 95% ethanol in a 50-ml Erlenmeyer flask by heating on s steam bath. Add one drop of concentrated hydrochlaric acid and boil the mixture for 5 min. Add 10 ml of water to the hot reaction mixture and cool. Collect and air dry the product; then determine and record the melting point.
Part G. Base-Catalyzed lsomerization of the [,2 Cycloaddition Adducts
+ .4]
Prepare dilute solutions of the two cycloadducts (Parts D and E) in chloroform (-50 mg adduct/ml CHCls), and a 1:l mixture of the two adducts in ehlomform. Place very small drops of each of the three solutions near the bottom of a single Silica Gel thin layer chromatographic (tlc) plate (we employed 2.5- X 7.5-em Baker-flex Silica Gel 1B sheets) using drawn-out melting point capillaries. Develop the chmmatogram in a suitable fashion using 3:l benzene-chloroform as the solvent system. Visualize the spots by placing the air-dried plate into a screwcap bottle containing several crystals of iodine. In each of two 125-ml Erlenmeyer flasks containing 30 ml of absolute ethanol, cautiously add two pea-size pieces of sodium metal, one s t a time. When the sodium has dissolved, add 0.5 g of the cycloadduet secured in Part D to one flask and 0.5 g of the adduct obtained in Part E to the other. Stopper each flask loosely with a cork and heat both on a stesm bath. With emphasis on perceiving the formation of (a) different isomer(s) in each ease, analyze each reaction mixture by tlc, using the same developing system and visualization method suggested above. Analyze a t 10-15 min intervals for a t least 30 min, or until equilibration is apparently established (no further change, if any, detected). Critically judge the outcome of the equilibrations by making suffi-
cient comparisons of the equilibrated solutions with the solutions of the cycloadduets previously prepared, together on the same tlc plate. To each reaction mixture add 30 ml of water and heat on a steam bath (to effect homogeneity it may he necessary to add a small amount of ethanol). Slowly cool the clear solutions to room temperature and then further in an ice bath. Collect the crystalline pmduets and recrystallize from methanol. Record their melting points and determine mixture-melting points of each product with the initial adducts.
Literature Cited Canant, J . B., and Lut., R. E.. J Am= C k m . Sm., 15, 1303 (192.3); Lutz. R. E.. "OrganiiSyntha+u." Coll. Vol. 111,248(1955). (2) Silversmith. E. F.. andDunmn, F. C., J. CHEM. EDUC., 50.568 11973). ds.hdu,M.,Bol. JS.lBs(Lm). (4) ~ d k H.. . ~ u t e m a * .R.,and v. ~ a l b a n ,M.. ~ d u chim. . Arro, 23, 512 (1946): Cauru. G., Mazzucato. U.. and Fdfsni, A.. Bull. Soe. Chim. B d m 71. 838 11962); Zimmerman, H., D m , H.,L e d , R.. and B n m , S., J . Amer Chrm. S o r . 84, 1149 119621; Zimmnmao. H.. end Hull. J.. J. Amen C k m . S o r . 92. 6515 11970). (5) h e z , R. E., and ~ a i l q P. , S., J ~m~~ c h m . sac., 61, 2229 (19451;Lutz, R. E., and GOI~spie,J. S., Jr., J. Amar. C k m . Soe.. 72, Sd4 (19501: Campanelli, M., Mazrucata. U.,end Foffani, A.,Ann. Chim. (Rome). 54.195 (ISM). ( 6 ) Adarns, R.. and Gold. M. H.. J A m e r . C b m Sac., 62. %(lIUOl. (1)
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