Lewis Acid Catalysis of a Diels-Alder Cycloaddition An Undergraduate Organic Experiment Alan P. Marchand. V. Vidyasagar, . - . Mark 6. Buckner, and Philmore 0. Holman North Texas State University, Denton, TX 76203 In response to the current emphasis on applying nuclear magnetic resonance (NMR) spectroscopy to structural problems in undergraduate organic chemistry laboratory courses, we have recentlv developed an experiment that relies on proton NMR spectrosco& both fo; product identification1 characterization and for quantitative analysis of a product mixture. The experiment is based upon thk ~ i e l s - ~ i d ecyr cloaddition of methylcyclopentadiene to p-benzoquinone, two readily available and inexpensive reagents. Thermal cracking of methylcyclopentadiene dimer affords a mixture of 1-methyl- and 2-methylcyclopentadienes ( I ) . Diels-Alder addition of this diene mixture to p-benzoquinone affords exclusively the endo (2) cycloadducts l a and l b (product ratio -45.55) (3). Adducts l a and l b both undergo facile intramolecular photocyclization to the corresponding cage diketones (2a and 2b, respectively) (3,4).
of methylcyclopentadienes to a-chloroacrylonitrile in henzene at 0-5 "C followed by hydrolysis of the resulting mixture of adducts affords 1-methyl-5-norbornen-2-one as the predominant product ( 8 ) .
Product ratio:
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Za 2b Yates and Eaton first observed that the rates of several Diels-Alder reactions of dienes with carbonyl-containing dienophiles increased dramatically when these reactions were performed in the presence of aluminum chloride (5).In addition, other investigators have shown that added Lewis acid catalysts also greatly enhance both the regioselectivity and stereoselectivity of reactions of this type (6).Typically, the endolexo ratio of the mixture of Diels-Alder adducts formed via the reaction of cyclic dienes with substituted ethylenes is increased markedly relative to that of the product mixture resulting from the corresponding uncatalyzed Diels-Alder reaction (7). Of particular relevance to the present experiment is the fact that dramatically increased positional regioselectivity (as well as reaction rate enhancement) is encountered when Lewis acid catalysts are added to reactions of, for example, methylcyclopentadienes with unsymmetrically substituted ethylenes as dienophiles. Thus, for example, C ~ ( B F ~ ) ~ - c a t a l yDiels-Alder zed cycloaddition
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Journal of Chemical Education
CH,
0
In order to demonstrate the effect of added Lewis acid catalysts on the regioselectivity of Diels-Alder reactions, undergraduate organic laboratory students did the following: (1) A mixture of monomeric methylcyclopentadienes was ohtained via thermal cracking (9) of the commercially available dimer. (2) The monomer thereby ohtained was reacted with an equimolar amount of p-benzoquinone. (3) The two possible endo products ( l a and l b ) were separated and purified via fractional recrystallization, and each was characterized via analysis of its proton NMR spectrum. (4) The composition of the product mixture initially obtained from the uncatalyzed reaction of methylcyclopentadiene withp-benzoquinone was analyzed quantitatively by proton NMRspectroscopy. (5) The equimolar reaction of methylcyclopentadiene with p-benzoquinone was performed in the presence of anhydrous aluminum chloride, and the NMR spectrum of the product was obtained. ( 6 ) The composition 01 rhr resulting prodm1 mixture wiisnnalgmd qunnt/tarivelv by p w t m XhlH sperrroscupy. 17, The re>ult>otnainr(l from steps (4) and (6) were compared, and conclusions were drawn regarding the effect of added Lewis acid catalyst upon the regioselectivity of the Diels-Alder addition of methylcyclopentadienes to p-henzoquinone. The Experlmeni
Warning: Care should be exercised in handling aluminum chloride. Contact with moist air or water liberates HCI gas. Avoid contact with skin, eyes, and clothing. In case of contact, immediately flush skin or eyes with water for 15 minutes. If eyes are affected, seek medical attention immediately. Care should also be taken to avoid skin contact with the reaction products ( l a or lb).
UncatalyzedDiels-Alder Reaction In a typical experiment, a solution of p-henzoquinone (10.8 g, 100 mmol) in methanol (100 mL) is placed in a 250-mL round-bottom flask, and the reaction mixture is cooled via external application of a dry ice-isopropanol bath. A cold solution of freshly cracked (9) methylcyclopentadiene (8.W g, 100 mmol) in methanol (25 mL) is then added to the reaction vessel, and the resulting cold mixture is stirred for 2 h. The cooling bath is then removed, and the reaction is allowed to warm slowly to room temperature. The reaction mixture is then concentrated, and the residue is air dried. A mixture of Did-Alder cycloadduets l a and Lh is thereby obtained as a pale yellow microcrystalline solid (17 g, 90%. mp 65-73 "C). The proton NMR spectrum of this mixture is then obtained and carefully integrated. The individual components of this mixture can be isolated via careful fractional recrystallization from methanol. The less soluble material, "isomer A", is thereby obtained as a pale yellawmicrocrystalline solid (mp 116-117 'C). The combined mother liquors are then concentrated, and the residue is fractionally recrystallized by using 1:l methanol-hexane. "Isomer B" is thereby obtained as a pale yellow microcrystalline solid (mp 101.0-101.5 "C). Proton NMR spectra of the individual pure Diels-Alder adducts are then obtained and carefully integrated. Aluminum Chloride Catalvzed Diels-Alder Reaction Best results are obtained bv usine.. reaeent-made anhvdrous alu. " minum rhloride.'l'hr mtnlyst should he taken from a lrrshly opened buttlr and med immrdintely, therebv minimizing its rrposure to atmospheric moisture. In a typical experiment, a mixture of anhydrous aluminum chloride (2.62 g, 19.6 mmol) and dry methylene chloride (20 mL) is placed in a 250-mL round-bottom flask. To this mixture is added a solution of p-benzoquinone (10.8 g, 100 mmol) in dry methylene chloride (80 mL), and the reaction flask is fitted with a calcium chloride drying tube and adropping funnel. The reaction mixture is then cooled to -10 OC via application of an external iee-salt bath. The dropping funnel is then charged with a cold solution of freshly cracked (9) methylcyclopentadiene (8.0 g, 100 mmol) in dry methylene chloride (25 mL), and this solution is added dropwise with stirring during -3 min to the cooled reaction mixture. The reaction mixture is then stirred with external cooling for 1h after addition of methylcyclopentadiene has been completed. The cold bath is then removed, and the reaction mixture is allowed to warm slowly to room temperature. The mixture is then filtered to remove the catalyst, and the filtrate is washed sequentially with 20% aqueous sodium bicarbonate solution (50 mL), brine (50 mL) and water (50 mL). The organic layer is then dried by adding anhydrous magnesium sulfate to the filtrate and swirling the resulting mixture. Since hydration of magnesium sulfate is a very rapid reaction, the drying agent can be removed by filtration after 3-5 min. The filtrate thereby obtained is concentrated in vacuo (rotary evaporator), leaving a mixture of Diels-Alder adduets l a and l b as a oale vellow microcrystalline solid (16.8 g, 89.570, mp 68-78 'C). T h e broton NMR spectrum of this mixture is then obtained and carefully integrated.
isomers A a n d B t h a t were isolated via fractional recrystallization of t h e product of t h e uncatalvzed Diels-Alder reaction can b e assigned readily b y noting t h a t resonances corresponding to vinyl protons i n isomer A integrate t o four protons, whereas in t h e isomer B only t h r e e vinyl proton resonances a r e present. Hence, isomer A corresponds to structure l a , a n d , therefore, isomer B m u s t correspond to
Ib. Quantitative analysis b y NMR spectroscopy of t h e mixt u r e of Diels-Alder adducts t h a t results via cycloaddition of methylcyclopentadienes t o maleic anhydride has been re-
PPM
PPM
NMR Spectral Analysis P r o t o n NMR chemical shifts a n d spectral assignments for la a n d l b a r e summarized i n t h e table. The structures of Proton NMR Asslgnmenis for l a and l b
61.40 (br s. 2 H. H-9a and H-9s) 1.55 ( 5 , 3 H, I C H d 2.73-3.07 (m. 1 H. H-4) 3.20-3.58 (m. 2 H. H-4a and H-8a) 5.98 (AB. JAB = 6 Hz, H-2 and H-3) 6.53 (s. 2 H. H-6 and H-7)
61.51 (AB. JAB= 9 Hz, H-9aand H-9s) 1.60 (6. J = 1-2 Hz. 2 6 H d 3.07-3.60(br s.4H. H-1.H-4, H-4% K8a) 5.62 (br s. 1 H, H-3) 6.57 (s.2H. H-6 and H-7)
PPM
PPM
Partial 60-MHz proton NMR spectra of (a) la, (b) lb, (c)a mixture of la and i b formed via the uncatalyzed Diels-Alder cycloaddition of methylcyclopentadienes topbenzoquinone, (d)a mixtureof l a and lb formed via thealuminum chloride catalyzed Diels-Alder cycloaddition of methylcyclopentadienes to p benzoquinone.
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ported by Kamezawa and Ueda (10).In this instance, quantitative analysis of the product mixture could be made via careful integration of the vinyl proton region. However, this region of the proton NMRspectrum of mixtures of l a and l b is not well resolved. Accordingly, the region between -62.73.6 was chosen instead for quantitative analysis of these mixtures. The figure depicts the NMR spectral region of interest for la, lb, and for mixtures of la and l b obtained via uncatalyzed and catalyzed Diels-Alder addition of methylcyclopentadienes to p-benzoquinone. Absorptions in this region fall into two distinct patterns: a multiplet a t 62.7-3.0 that corresponds to proton H-4 in l a and a broad multiplet a t 63.1-3.6 that corresponds to H-4a and H-8a in l a plus H-1, H-4, H-4a, and H-8a in l b (cf. spectral assignments in the table). The areas under the signals can be obtained via spectral integration. Thus, the ratio of these signal areas affords the following information: tnrcu .undo multiple1 at6'2.7-3.0) !area under n~ultiplrrn t 63.1 3 ti,
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Acknowledgment -
Financial support of this study by the Robert A. Welch Foundation (Grant B-963) and the North Texas State University Faculty Research Committee is gratefully acknowledged. I. Csicsery, S. M . J . o r g Chem. 1960,21,518. 2. la1 Alder, K.;Stcin,G.Angeiu. Chem. 1937,50,510:(blforareviewafthemeehsnismof the DielcAlder resetion, see: Sauer. J. Angem. Chzm. Intarnat. Ed. E n g l 1967.6, Ifi. Suri. C.: Esrlywine. A. D.: Powell, D. R.:van der Helm, D. J. Or#. Chsm. 1984.49.670, Na8h.E. G. J. Chem.Edur. Yates, P.; Eaton, P. E.J. Am. Cham. Sac. 1960,82,4436. Fur areview ofcatalysisaf Did-Alder reaefion%.see: J.L'oeiulit@Chim. 1984. (10).42. Houk. K. N.; Strozier. R.W. J. Am. Chem. Soc. 1973,95,C94. Goerin8.H. J. O m Chem. (a) Muifetr R. B. O r g Synth. Collecl. Vol. 1963.4, 238: (bl Megnusron, G.J. Org. Chem 1985.50.1998. Kamezawa. N.: Ueda. T.Org. Mag. Re$. ~~
X
3. Marchand, A.
+ 4Y
4.
u,here X = mol fraction of la and \' = mu1 fraction uf I h in rht: mixture. Since this isa two-cumponenr m i x r ~ ~ r e ,+XY = I; simultaneous sohtion d thrw t w o rquatims affords corresponding values f g w X and Y. Quantitative analysis d mixrures o i la and Ib obtained via ilncatal\,zed and alumi-
644
num chloride catalyzed Diels-Alder cycloadditions of methylcyclopentadiene to p-benzoquinone by this NMR method affords the following results: uncatalyzed Diels-Alder reaction. 1a:lb = 4555: AICL catalvzed Diels-Alder reaction. 1a:l'b = 7525. We theref&e canconclude that the additiod of anhvdrous aluminum chloride to the reaction mixture has a profound effect upon the positional regioselectivity of this Diels-Alder reaction.
5. 6.
7. 8. 9. lo.
P.:
S.
1974.51,619.
Lssrlo,P.;Lueehetti,
L.:Chang,C.-S.
I375,40,2565.
1971.3.557.
