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Expt 41

The Reaction of Maleic Anhydride and Cycloheptatriene


Synthesis of anti-Tricyclo[3.2.2.0
2,4
]non-6-en-endo,endo-8,9-dicaboxylic Anhydride
A Valence Isomer Trapping Procedure
Adapted by R. Minard and Carolyn S. Yatsko (Penn State Univ.) from D.W. Kurtz and R.P. Johnson, J. Chem. Ed. 66, 873-874 (1989). Revised 10/5/00
Introduction:
This experiment illustrates valence isomerization and trapping of a reactive intermediate. Valence isomerism is usually defined as a
thermal equilibrium between two isomeric species of different bond lengths and angles achieved without passing through an electronic
excited state or intermediate loss of any atom. Species displaying such a thermal equilibrium are termed fluctional molecules
1
. Well-
known cases of fluctional behavior include cycloheptatriene-norcaradiene (eq 1), cycloctatetraene-bicyclo[4.2.0]octa-2,4,7-triene (eq 2),
and fluctionally degenerate molecules such as semibullvalene
2
and bullvalene
3
(eqs 3 and 4 below).
norcaradiene cycloheptatriene
(4)
(3)
(2)
(1)
Although the photoconversion of benzene to benzvalene and Dewar benzene is sometimes termed valence isomerization, being
nonthermal, it is not a case of fluctional behavior.
benzvalene
Dewar benzene
hn
Nor are keto-enol tautomerizations considered valence isomerizations, since their equilibria are generally mediated through
intermolecular proton shifts. However, many common sigmatropic shifts such as the Claisen, Cope, and vinylcyclopropane
rearrangements are essentially valence isomerizations with large enthalpy differences between the isomers.
The rearrangements and cycloadditions of cycloheptatrienes have been scrutinized for over a century and continue to be investigated
4
.
The cycloheptatriene system seems almost profligate in the variety of its reactions; the ene reaction
5a
, 2 + 2
5b
, 2 + 4
5c
, and even 4 +
6 cycloadditions
5d
are documented. The earliest investigations of cycloheptatriene reactions by Buchner revealed difficulties in
separating and identifying the reaction products of cycloheptatriene with diazoacetic esters. In 1939, the Diels-Alder reaction between
cycloheptatriene and maleic anhydride was first studied, but the major adduct defied structure elucidation until 1953, when Alder and
Jacobs demonstrated that it contained a cyclopropane ring
6
. By that time Doering
7
and Corey
8
had formulated the hypothesis that
cycloheptatriene is in rapid equilibrium with bicyclo-[4.1.0]hepta-2,4-diene (norcaradiene, eq 1) and used this hypothesis to explain the
presence of a three-membered ring in many of the cycloaddition products of cycloheptatriene. The most thoroughly investigated system
displaying this equilibrium is the parent hydrocarbon, cycloheptatriene. Cycloheptatriene preponderates in the equilibrium, with
norcaradiene estimated to be less than 0.1% of the mixture at ambient temperature
9
. None of the numerous direct
spectroscopic attempts to detect norcaradiene in the equilibrium mixture have succeeded; thus, although
norcaradiene has been photolytically produced and directly observed in low-temperature argon matrix
10
,
its experimental heat of formation and exact percentage in equilibrium with cycloheptatriene remain
conjectural.
The cycloheptatriene form is estimated to be 4 - 6 kcal/mol more stable than the norcaradiene form. In view of the small amount of
norcaradiene tautomer present in unsubstituted cycloheptatriene, it is somewhat surprising that most dienophiles give Diels-Alder
adducts only with the norcaradiene tautomer. Indeed, the only reactants presently known to give any "normal" 2 + 4 adduct with the
open form of cycloheptatriene are nitroso benzene
13
and maleic anhydride
14
.
O
O
O
O
O
O
H
H
O
O
O
H
H
O
O
O
H
H
1
2
3
4 5
maleic anhydride
A thorough reinvestigation of the Diels-Alder reaction between cycloheptatriene and maleic anhydride established that three 2 + 4
adducts are formed (see figure above)
14
. The major product, 3, composing slightly more than 90% of the product mixture, is the
adduct from endo addition of maleic anhydride to norcaradiene in which the cyclopropane ring is syn to the double bond. Next most
plentiful is 4, the exo adduct of norcaradiene with its cyclopropane ring again syn to the alkene; 4 is about 9% of the total product.
The adduct 5 from maleic anhydride and open cycloheptatriene is 0.5-1% of the product mixture; this minor product might be called the
"expected" or "normal" Diels-Alder adduct.
Prelaboratory Exercises:
Xylenes contain conjugated double bonds; why doesn't maleic anhydride undergo a Diels-Alder reaction with the
solvent?
Draw electron movement arrows to show how bond rearrangement and formation takes place to form 3.
O
O
O
H
H
O
O
O
H
H
3
Cautions:
Aniline is a suspected carcinogen. Handle with care and do all manipulations in a hood. Ether is extremely
flammable. Work in a hood and be alert for open flames or spark sources.
Synthesis:
To a dry, tared reaction tube, add 0.276 g cycloheptatriene, 0.274 g finely powdered maleic anhydride,
and 2 mL mixed xylenes. Insert a boiling stick and reflux the mixture for 30 minutes. Then, a 10-drop
sample of the reaction mixture is withdrawn and placed in a reaction tube for conversion to derivatives and
TLC analysis.
Isolation and Purification:
The remainder is left in the open reaction tube in your locker to allow evaporation of the mixed xylenes.
Alternatively, the xylenes can be removed by an instant microscale distillation until only about 0.5 to 0.7
mL of liquid remains. Then 0.6 mL ethyl acetate and 2 mL hexane are added and the solution chilled in an
ice bath yielding large, cream colored needles of 3 containing a small amount of the exo-adduct, 4, and an
Exp't 41
even smaller amount of 5. Remove the solvent by pipet filtration and allow the crystals to dry until the
next lab period. Then take a melting point (lit m.p. for pure 3 is101C
14
) and determine the yield.
TLC Analysis:
TLC analysis is performed on the N-phenylimide derivatives, 6, 7, and 8, formed by reacting the reaction
product mixture of3, 4, and 5 with aniline, Ph-NH
2
.
N
O
O
H
H
N
O
O
H
H
N
O
O
H
H
6
7 8
Ph
Ph
Ph
If the aniline is badly discolored, it should be purified by distillation. In a hood, carry out an instant
microscale distillation of aniline (b.p. = 184C). You only need about 0.5 mL of the impure aniline from
the side shelf to do the distillation. Use a boiling stone. Discard the first two or three cloudy pipet fractions
from the instant microscale distillation as these contain mainly water. The material to be used should be
clear, not cloudy. (You may need several small collections to get a total of 0.5 mL.) Also discard the
undistilled aniline into the Nonhalogenated Organics Waste container. Unused, but distilled aniline can be
returned to the side shelf bottle.
One drop of purified aniline is added to the 10 drop sample from the synthesis above and the mixture is
heated for three minutes, then cooled to room temperature. Dilution with 4 mL of diethyl ether (use the
wet ether found in a supply bottle in each hood) yields a solution for TLC spotting on silica gel plates.
TLC development in ethyl acetate yields a high R
f
spot for 6, a low R
f
spot for 8 (very faint), and an
intermediate R
f
spot for 7.
Cleaning Up:
Dispose of the filtrate, the unused TLC solution, and the aniline distillation residue in the Nonhalogenated
Organics Waste container.
Analysis:
Analyze your product by the method assigned in your Experiment Assignment sheet. (See the Lab
Guide for specific details on the method of analysis.) In most cases, the TLC analysis described above
is all that is required.
Final Report:
Include properly annotated TLC plates, including R
f
's, taped to your report. Turn in product. Give yield and melting point.
Answer the following questions at the end of your report:
1. Given that cycloheptatriene is the major valence isomer (99.9%) at equilibrium, explain how the Diels-Alder reaction with
maleic anhydride can give such a high yield of the norcaradiene valence isomer adduct, 3? Use LeChatelier's principle in
your answer.
2. Propose a mechanism for the reaction between aniline and the maleic anhydride/cycloheptatriene Diels-Alder product.
3. Draw all possible products of the cycloheptatriene tautomer of

C
7
H
8
reacted with maleic anhydride
Literature Cited:
1. For reviews see (a) Schrder, G.; Oth, J.F.M.; Merenyi, R. Angew. Chem Int'l Ed. Engl. 1965, 4, 762; (b) Maier, G. Angew. Chem Int'l Ed. Engl. 1967, 6, 402.
2. Cheng, A.K.; Anet, F.A.L.; Mioduski, J.; Meinwald, J. J. Am. Chem. Soc. 1974, 96, 2887.
3. Doering, W.v.E.; Roth, W.R. Tetrahedron 1963, 19, 715.
4. (a) Buchner, E.; Curtius, T. Ber. 1885, 18, 2377; (b) Baren, W.; Buchner, E. Ber. 1901, 34, 982; (c) Leitich, J.; Sprintschnik, G. Ber. 1986, 119, 1640.
5. (a) Cinnamon, J.M.; Weiss, K. J. Org. Chem. 1961, 26, 2644; (b) Kato, M.; Okamoto, Y.; Chickamoto, Y.; Miwa, T. Bull. Chem. Soc. Japan 1978, 51, 1163; (c)
Kanematsu, K.; Morita, S.; Fukushima, S.; Osawa, E. J. Am. Chem. Soc. 1981, 103, 5211; (d) Bower, D.H.; Howden, M.E.H. J. Chem. Soc. Perkin Trans. I
1980, 672.
6. (a) Kohler, E.P.; Tischler, M.; Potter, H.; Thompson, H. J. Am. Chem. Soc. 1939, 61, 1057; (b) Alder, K.; Jacobs, B. Ber. 1953, 86, 1528.
7. Doering, W.v.E.; Knox, L.H. J. Am. Chem. Soc. 1950, 72, 2305.
8. Corey, E.J.; Burke, H.J.; Remers, W.A. J. Am. Chem. Soc. 1955, 77, 4941.
9. Huisgen, R. Angew. Chem. Int'l Ed. Engl. 1970, 9, 755.
10. Rubin, M.B. J. Am. Chem. Soc. 1981, 103, 7791.
11. Ciganek, E. J. Am. Chem. Soc. 1971, 93, 2207.
12. Hoffman, R. Tet. Letts. 1970, 2907.
13. Krese, G.; Schulz, G. Tetrahedron 1961, 12, 7.
14. Ishitobi, H.; Tanida, H.; Tori, K.; Tsuji, T. Bull. Chem. Soc. Japan 1971, 44, 2293.
15. Pickering, M. J. Chem. Educ. 1988, 65, 143.
Synthetic Experiment PreLab Grading Sheet
Name(s):
TA:
Date:
PreLab For Exp't #:41
Title: The Reaction of Maleic Anhydride with Cycloheptatriene
Possible Missed
Points Points
Date, Name, Desk #, Experiment # & Title(abbreviated after 1
st
pg), Section &
TA Name
4
Summary 10
Goals 10
Reactions, structures, conditions, diagrams 14
Completeness of Chemical Data Table(s) 10
PreLab Exercise 16
Chromatographic Behavior Comparison 12
Spectral Features Comparison 12
Work-up- isolation and purification 12
TOTAL FOR PRELAB 100
Date Handed in:
General Comments: Total Points:
Synthetic Experiment Final Report Grading Sheet
Name:
TA:
Date:
Final Report For Exp't #: 41
Title: The Reaction of Maleic Anhydride with Cycloheptatriene
Possible Missed
Points Points
Name, Date, Experiment Title (abbreviated after 1st page) and every page
numbered
4
OBSERVATION and DATA - Overall organization, readability, completeness 8
Data: Weighing data, molecular weights, moles, d, v, R
f
's, analysis conditions
for TLC, TLC plates.
12
Yield: Show % yield calculations, wt & limiting reagent clearly stated.
Purity: melting point, color of crystals.
12
RESULTS AND DISCUSSION - Overall organization, readability, completeness 8
Results; Achievement of goals 16
Product Analysis Data: Quality and Interpretation Structure(s) drawn on
each Spectrum or Chromatogram
TLC analysis and discussion of spots
24
POSTLAB QUESTIONS & TLCs
16
TOTAL POINTS 100
Date Handed in:
General Comments: Total Points: