Solvent-free Diels-Alder reactions of in situ generated cyclopentadiene

Article abstract of DOI:10.1039/b813485e

A solvent-free Diels-Alder reaction was carried out by heating a mixture of dicyclopentadiene and a dienophile. Cyclopentadiene, formed in situ, reacted with the dienophile in a thermodynamically controlled reaction. Besides being solvent-free, the descri

Full text of DOI:10.1039/b813485e

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/greenchem | Green Chemistry
Solvent-free Diels–Alder reactions of in situ generated cyclopentadiene†
David Huertas, Melinda Florscher and Veljko Dragojlovic*
Received 4th August 2008, Accepted 10th October 2008
First published as an Advance Article on the web 7th November 2008
DOI: 10.1039/b813485e
A solvent-free Diels–Alder reaction was carried out by heating a mixture of dicyclopentadiene
and a dienophile. Cyclopentadiene, formed in situ, reacted with the dienophile in a
thermodynamically controlled reaction. Besides being solvent-free, the described procedure allows
for almost complete utilization of dicyclopentadiene and avoids handling of noxious and
hazardous cyclopentadiene. The reaction worked well with dienophiles such as maleic anhydride
and unsaturated esters. However, unsaturated acids were not suitable dienophiles, yielding
Diels–Alder adducts in a low yield.
considerably higher temperature for cracking. Thus, when
Introduction
cyclopentadiene is obtained by cracking of dicyclopentadiene,
The Diels–Alder reaction is one of the most important methods
one can expect, at best, an overall 65–70% reaction yield with
for formation of six-membered rings.1 Cyclopentadiene is one of
respect to dicyclopentadiene. Therefore, a procedure that allows
the dienes frequently used in Diels–Alder reactions. It is unstable
use of dicyclopentadiene directly would have important practical
under ordinary conditions and, at room temperature, dimerizes
advantages. Finally, such a procedure may allow isolation of
into dicyclopentadiene. Usually it is obtained by cracking
stereoisomers that are not commonly produced in a Diels–Alder
of dicyclopentadiene and is used immediately in a reaction.
reaction of cyclopentadiene. Recently, Diels–Alder reactions
Cyclopentadiene has a rather strong and disagreeable odor and
under solvent-free conditions in the presence of a catalyst9
cracking has to be done in a fumehood. Furthermore, while retro
or under microwave irradiation10 have been reported. A retro
Diels–Alder reactions are well known and have been extensively
used in organic synthesis,2 with numerous examples of an in situ
Diels–Alder reaction of oxanorbornenes under solvent-free con-
ditions and microwave irradiation afforded the corresponding
generated diene being trapped by a more reactive dienophile,3
products in high yields.11 A patent that describes preparation
other than a report of a solvent-free reaction of dicyclopen-
of 5-norbornene-2-carboxylic acid by heating dicyclopentadine
tadiene with ethylene under high temperarature and pressure
with acrylic acid at ambient pressure in the presence of a free
in an autoclave4 and a similar process described in a patent,5
radical inhibitor12 will be discussed in detail in the Results and
dicyclopentadiene as an in situ source of cyclopentadiene has
received relatively little attention. That is surprising given both
Discussion section.
We have developed a solvent-free procedure in which cy-
clopentadiene generated in situ is used in a Diels–Alder reaction
(Scheme 1). Advantages of this procedure are that cyclopen-
its importance and safety implications. Pure cyclopentadiene
has to be stored at a low temperature (-20 ◦C). Under ordinary
conditions it undergoes a spontaneous and highly exothermic
tadiene reacts as it is generated and thus there are neither
dimerization into dicyclopentadiene6 and has been implicated in
safety problems associated with use of cyclopentadiene nor
a fatal accident.7 Moreover, only about 2/3 of dicyclopentadiene
problems with formation of oligomers. As a result, most of
can be cracked.8 The rest of it forms oligomers, which require
the starting dicyclopentadiene is utilized. Furthermore, as◦the
reaction is done at a relatively high temperature (162–206 C),
thermodynamically preferred reaction products are obtained.
Wilkes Honors College of Florida Atlantic University, 5353 Parkside
Ordinarily, Diels–Alder reactions involving cyclopentadiene
proceed under kinetic conditions to give predominantly or
exclusively the endo isomer.13 By adjusting the reaction times,
one can obtain either the exo or endo isomer as the major
Drive, Jupiter, FL 33458, USA. E-mail: vdragojl@fau.edu;
Fax: 561-799-8602; Tel: 561-799-8012
† Electronic supplementary information (ESI) available: Additional
1
experimental details and H NMR spectra of the isolated compounds.
See DOI: 10.1039/b813485e
Scheme 1
This journal is
The Royal Society of Chemistry 2009
Green Chem., 2009, 11, 91–95 | 91
©

View Article Online
Table 1 Solvent-free Diels–Alder reactions of in situ generated cyclopentadiene
Entry
Dienophile
Reaction time/min
Products
Yield (exo/endo)
Procedure
1
2
3
4
3
3
6
15–22
8–10
25
4/5
5
7/8
9
37%a : 35%a,c
32%a (1:6)b
78%a (57:35)b
83%a
A
A
A
A
15
10
5
12
88%a
A
11
13
14
12
6
7
8
5
5
5
4/5
<10%d
~20%d
0
B
B
B
4/5
15
16
18
9
5
~5%d
B
17
a Isolated yield. b GC ratio. c Product was 95:5 endo/exo mixture according to GC analysis. d Estimated yield based on the amount of recovered
material and GC analysis.
reaction product. Finally, by avoiding use of a reaction solvent
this is a “greener” procedure compared to traditional Diels–
Alder reactions.
dicyclopentadiene with 2.30 equivalents (1.15 equivalents with
respect to in situ generated cyclopentadiene) of maleic anhydride
gave 5-norbornene-2,3-dicarboxylic anhydride cleanly and in
good yield (Table 1, entry 1). Very little of the cyclopentadiene
oligomers were formed (<5% according to GC-MS analysis).
It was important to keep the reaction times within the optimal
range. The reaction should be run until the reaction mixture
turns dark yellow and the reflux stops. Shorter reaction times
resulted in an incomplete reaction, while longer reaction times
gave charred products and lower yields. The reaction was
successfully scaled up to 0.6 mol scale (67.6 g maleic anhydride
and 49.8 mL dicyclopentadiene in a 300 mL round bottom
flask). As there was some foaming in the course of the reaction,
it may be tempting to use larger flasks. Furthermore, a larger
reaction flask would allow for a more efficient heat transfer.
Interestingly, use of larger reaction vessels resulted in charred
products and lower yields. Use of smaller reaction vessels (10 mL
round bottom flask for 75 mmol, 200 mL for 0.3 mol and 300 mL
Results and discussion
Reactions of dicyclopentadiene with dienophiles were relatively
fast (5–25 min). In addition, none, or very little, of the
byproducts such as tri- and tetracyclopentadienes, which are
formed in the course of an ordinary cracking, were observed
and one did not have to isolate or handle noxious and unstable
cyclopentadiene.
Usually, in a Diels–Alder reaction the diene is used in
an excess. However, in this case, use of the diene precursor,
dicyclopentadiene, in an excess resulted in lower yields and
lower purity of the products. In particular, a larger amount of
cyclopentadiene oligomers were formed. Therefore, we opted
for use of a small excess of the dienophile. Thus, reaction of
92 | Green Chem., 2009, 11, 91–95
This journal is
The Royal Society of Chemistry 2009
©

View Article Online
Table 2 Solvent-free reaction of cyclopentadiene with maleic anhy-
for 0.6 mol reaction) gave better results. Overall, our experience
was that it was best to use the smallest possible flask, which
should be ~1/3 filled.
dride on a mixture that corresponds to 50% conversion
Entry
Added adducta
Time
Isolated Yield (exo/endo)
Both dicyclopentadiene and cyclopentadiene react with
maleic anhydride in the presence of a free radical catalyst
to give polymers.14 However, while a solvent-free reaction of
cyclopentadiene with ethylene under high pressure and high
temperature gave norbornene in an acceptable yield,4 to our
knowledge reaction of neat dicyclopentadiene with maleic
anhydride has not been investigated. In contrast to a Diels–Alder
reaction conducted at ambient temperature,15 the reaction was
thermodynamically controlled and a mixture of exo and endo
isomers in approximately equilibrium amounts was obtained.
The reaction time was only 15–22 minutes which compares favor-
ably with the standard procedure for obtaining a thermodynamic
mixture of exo and endo isomers by equilibrating the endo isomer
1
2
3
exo
4¢30¢¢
5¢30¢¢
5¢
44% : 42%
36% : 35%
41% : 39%
endo
exo/endo (1:1)
a Reaction conditions: 37.5 mmol of Diels–Alder adduct and 37.5 mmol
of maleic anhydride were heated for 2 minutes followed by addition of
16.25 mmol of dicyclopentadiene. Heating was continued for the time
indicated.
32.5 mmol of dicyclopentadiene), an approximately thermo-
dynamic ratio of exo and endo isomers was obtained in only
5 minutes (Table 2). Interestingly, the reaction outcome was
about the same regardless of whether the added 5-norbornene-
2,3-dicarboxylic anhydride was the exo-isomer, the endo-isomer,
or a 1:1 mixture of the exo and endo isomers. Yields were
slightly better compared to a reaction of maleic anhydride and
cyclopentadiene (Table 1, entry 1). Under the same conditions,
equilibration of a pure endo isomer took 15 minutes.
◦
at 190 C for 1.5 hours.16 A small excess of maleic anhydride
ensured complete utilization of cyclopentadiene and simplified
the work up. The isolated yield of a mixture of exo- and endo-
5-norbornene-2,3-dicarboxylic anhydride was ~72% (average of
five runs, Table 1, entry 1). Remaining endo-isomer can be re-
equilibrated according to a literature procedure16 to give an
overall yield of ~60% of the exo-compound. It has been reported
that the thermodynamic mixture contains 57% and 43% of exo
and endo isomers by Craig,16 or 54% and 46% of exo and endo
isomers by Pincock et al.17 Our results were similar, and the
equilibrium mixtures contained a small excess of the exo isomer.
These results are in contrast to recent calculations, according to
which the endo isomer is more stable by 1.9 kJ/mol.18
Esters (Table 1, entries 3–5) worked very well and yields were
very good. The reaction products were those expected for a
Diels–Alder reaction run under a thermodynamic conditions. As
the Diels–Alder reaction usually gives a kinetic (endo) product,
this is a way to obtain a thermodynamic product. Dimethyl
maleate gave exo and endo isomers in a 57:35 ratio (Table 1,
entry 3). There was some isomerization of dimethyl maleate into
dimethyl fumarate and a small amount (~5%, GC analysis, not
isolated) of dimethyl trans-5-norbornene-2,3-dicarboxylate was
observed (GC analysis, Scheme 2). Both dimethyl fumarate and
dimethyl acetylenedicarboxylate gave the corresponding Diels–
Alder adducts cleanly and in high yields (Table 1, entries 4 and 5).
Carboxylic acids were not suitable substrates for this reaction
(Table 1, entries 6–8). Complex mixtures that consisted mainly
of insoluble, presumably polymeric, material were obtained
accompanied by small amounts of Diels–Alder adducts. Re-
action of dicyclopentadiene with maleic acid gave very little
(<10% according to GC-MS analysis) of a ~1:1 mixture of exo
and endo isomers of 5-norbornene-2,3-dicarboxylic anhydride
(Table 1, entry 6). It is known that upon heating, maleic acid
isomerizes into fumaric acid, which in turn isomerizes into
maleic anhydride.19 Fumaric acid gave a somewhat better yield
of the anhydrides (Table 1, entry 7) and it may be possible to
optimize the reaction conditions to improve the yield. However,
since maleic anhydride itself works quite well there was no
apparent reason to attempt such an exercise. According to the
previously mentioned patent, a solvent-free reaction between
dicyclopentadiene and acrylic acid works well in the presence
of a free radical inhibitor such as hydroquinone.12 While it
The endo isomer was obtained as the major reaction product
when the conversion was kept low by keeping the reaction time
short. Attempts to increase the amount of endo isomer by slow
addition of dicyclopentadiene, either manually or by use of
syringe drive, failed. Reproducibility was very poor, with both
yields and exo/endo ratios varying considerably between the
individual trials. The amount of the starting maleic anhydride
did not appear to play a role. Thus, the reaction times, yields of
the reaction products and exo/endo ratio were about the same
when maleic anhydride was used in 2–6 equivalent amounts (1–3
equivalents with respect to in situ generated cyclopentadiene).
The best yield (32% of a 6:1 mixture of endo and exo isomers)
of the endo product was obtained when dicyclopentadiene
was added to an excess (4.50 equivalents) of boiling maleic
anhydride (206 ◦C) and the reaction time was kept short (Table 1,
entry 2). Craig reported that a reaction of maleic anhydride and
cyclopentadiene at 190 ◦C for 10 minutes gave an 82:18 ratio of
endo and exo isomers.16
When the reaction was done at 206 ◦C on a mixture that
corresponded to 50% conversion (37.5 mmol of 5-norbornene-
2,3-dicarboxylic anhydride, 37.5 mmol of maleic anhydride and
Scheme 2
This journal is
The Royal Society of Chemistry 2009
Green Chem., 2009, 11, 91–95 | 93
©

View Article Online
was stated that 5-norbornene-2-carboxylic acid was isolated in
89% yield, there was no mention of the exo/endo ratio and
very few experimental details were provided. In our hands,
the reaction was rather slow and heating of dicyclopentadiene
prior to addition of a dienophile resulted in formation of a
large amount of tri- and tetracyclopentadienes. As expected,
addition of a free radical inhibitor prevented polymerization
of acrylic acid, but had no effect on oligomerization of in situ
generated cyclopentadiene. Thus, the best result we obtained
was ~40% yield of 5-norbornene-2-carboxylic acid. We found
that a slow reverse addition (dicyclopentadiene to a boiling
acrylic acid in the presence of hydroquinone) gave better results
and 5-norbornene-2-carboxylic acid was obtained in ~60% yield
(~1:1 endo/exo mixture isolated as the corresponding methyl
esters). As addition of a free radical inhibitor only prevents
polymerization, such modification does not address thermal
instability of acids, which is the main problem when using maleic
and fumaric acids.
fumaric acid, acetylene dicarboxylic acid, dimethyl maleate,
dimethyl fumarate, dimethyl acetylene dicarboxylate and 1,4-
benzoquinone were purchased from Acros Organic and used
without further purification. Acetone, hexanes and ethyl acetate
were purchased from Fisher Scientific Company and used
without further purification. Deuterated solvents and silica gel
were purchased from Aldrich Chemical Company and used
without further purification. Separations were done either by
column chromatography or by preparative radial thin layer
chromatography (Harrison Chromatotron). All of the isolated
products were known compounds and gave satisfactory 1H
NMR and GC-MS data.
Procedure A
Dienophile (75 mmol) was placed in a 10 mL round bottom
flask equipped with a condenser. It was heated with stirring until
it began to boil. Dicyclopentadiene (5.35 mL, 32.5 mmol) was
added in a single portion and the reaction was continued until the
reflux stopped and the reaction mixture turned yellow. Exo and
endo isomers were separated by radial thin layer chromatography
(Harrison Chromatotron) eluting with ethyl acetate:hexanes
(1:4 by volume) in the case of dimethyl cis-5-norbornene-2,3-
dicarboxylate or ethyl acetate:acetone:hexanes (1:2:6 by volume)
in the case of 5-norbornene-2,3-dicarboxylic anhydride. Other
products were purified by column chromatography eluting with
ethyl acetate:hexanes (1:3 by volume).
Reaction of dicyclopentadiene with an excess of molten 1,4-
benzoquineone was extremely vigorous. Within ~5 minutes most
of the reaction mixture was a charred solid. Extraction yielded
the Diels–Alder adduct and dehydrogenated product 18 in a low
yield accompanied by a considerable amount of hydroquinone
(Table 1, entry 9).
Conclusion
We have developed an environmentally friendly methodology for
Diels–Alder reactions of cyclopentadiene by using dicyclopen-
tadiene directly in the reaction, without previous cracking,
and by conducting the reactions under solvent-free conditions.
Reaction products were obtained in multi-gram quantities.
Limitations of the described procedure include use of thermally
unstable dienophiles, such as benzoquinone and unsaturated
acids. The Meinwald and Hudak article, as well as previously
published patents, provide complementary procedures, which
may be useful for reactions involving low boiling and poly-
merizable dienophiles.4,5,12 Somewhat less reactive dienophiles,
such as esters and maleic anhydride, worked very well and
gave a thermodynamic mixture of exo and endo isomers. This
is a “point reaction” – there is a relatively narrow range of
optimal conditions and deviation from them reduces the yield.20
Although there are some limitations to the choice of suitable
dienophiles, advantages of the process are that it generates
no waste, maximizes incorporation of starting materials into
products, is done under ambient pressure, is solvent-free, utilizes
no other reagents nor catalysts, avoids safety hazards associated
with handling of cyclopentadiene and thus conforms to most
of the twelve green chemistry principles.21 Finally, and perhaps
most importantly, it allows for a fast and convenient preparation
of thermodynamic products of Diels–Alder reactions.
Procedure B
Diene (75 mmol) and dicyclopentadiene (5.35 mL, 32.5 mmol)
were placed in a 10 mL round bottom flask equipped with
a condenser. The mixture was heated to reflux for the time
indicated (Table 1, entries 6–9). Products were extracted from
the solid residue with ethyl acetate and analyzed by GC-MS.
Acknowledgements
We thank Salvatore Lepore, Department of Chemistry, Florida
Atlantic University, for helpful discussions and Nicole Wind-
mon from Department of Chemistry, Florida Atlantic Univer-
sity, for recording H NMR spectra. Partial financial support
from the Wilkes Honors College of Florida Atlantic University
is gratefully acknowledged.
1
Notes and references
1 K. Takao, R. Munakata and K. Tadano, Chem. Rev., 2005, 105,
4779–4807; E. J. Corey, Angew. Chem., Int. Ed., 2002, 41, 1650–1667;
K. C. Nicolaou, S. A. Snyder, T. Montagnon and G. Vassilikogian-
nakis, Angew. Chem., Int. Ed., 2002, 41, 1668–1698; U. Pindur, G.
Lutz and C. Otto, Chem. Rev., 1993, 93, 741–761.
2 B. Rickborn, Organic Reactions (New York), 1998, 52, 1–393; A.
Ichihara, Synthesis, 1987, 207–222; J. L. Ripoll, A. Rouessac and F.
Rouessac, Tetrahedron, 1978, 34, 19–40.
3 J. H. M. Lange, A. J. H. Klunder and B. Zwanenburg, Tetrahedron
Lett., 1988, 29, 2365–2368; D. Mackay, D. Papadopoulos and N.
J. Taylor, J. Chem. Soc. Chem. Commun., 1992, 325–327; R. N.
Warrener, M. A. Houghton, A. C. Schultz, F. R. Keene, L. S. Kelso,
R. Dash and D. N. Butler, Chem. Commun., 1996, 1151–1152.
4 J. Meinwald and N. J. Hudak, Organic Syntheses Coll., 1963, 4,
738, http://www.orgsyn.org/orgsyn/pdfs/CV4P0738.pdf, accessed
on April 13, 2008.
Experimental
1H NMR spectra were recorded on a Bruker Avance 400 spec-
trometer. GC-MS analyses were performed by means of Agilent
6890 N Gas Chromatograph equipped with HP-5MS 30 m ¥
0.25 mm column (Cat. No. 19091S-433) and Agilent 5973
N MSD. Dicyclopentadiene, maleic anhydride, maleic acid,
94 | Green Chem., 2009, 11, 91–95
This journal is
The Royal Society of Chemistry 2009
©

View Article Online
5 U. Takashi and K. Shoichi, Jpn. Kokai Tokkyo Koho (1974), JP,
49–048650 A (in Japanese), Chem. Abstr., 1974, 81, 135555.
6 D. J. am Ende, D. C. Whritenour and J. W. Coe, Org. Process Res.
Dev., 2007, 11, 1141–1146.
7 A. Starkie and S. Rowe, Chem. Br., 1996, 32(2), 34–8.
8 R. B. Moffett, Organic Syntheses Coll., 1963, 4, 238, http://www.
orgsyn.org/orgsyn/pdfs/CV4P0238.pdf, accessed on April 13,
2008.
9 F. Fringuelli, R. Girotti, F. Pizzo and L. Vaccaro, Org. Lett., 2006,
8, 2487–2489; S. Imachi and M. Onaka, Tetrahedron Lett., 2004, 45,
4943–4946; J. Long, J. Hu, X. Shen, B. Ji and K. Ding, J. Am. Chem.
Soc., 2002, 124, 10–11; D. Bradley, Chemistry in Britain, 2002, 38,
42–45; M. Avalos, R. Babiano, J. L. Bravo, P. Cintas, J. L. Jimenez,
J. C. Palacios and B. C. Ranu, Tetrahedron Lett., 1998, 39, 2013–
2016.
translation is available on the Japanese Patent Office web site:
http://www.jpo.go.jp/.
13 D. Sua´rez and J. A. Sordo, Chem. Commun., 1998, 385–386; R.
Gleiter and M. C. Bo¨hm, Pure Appl. Chem., 1983, 55, 237–244; M.
Kakushima, Can. J. Chem., 1979, 57, 2564–2568.
14 N. G. Gaylord and A. B. Deshpande, Journal of Macromolecular
Science, Part A, 1977, 11, 1795–1807; N. G. Gaylord, A. B.
Deshpande and M. Martan, J. Polym. Sci. Polym. Letters Ed., 1976,
14, 679–682.
15 W. J. Sheppard, J. Chem. Educ., 1963, 40, 40–41.
16 D. Craig, J. Am. Chem. Soc., 1951, 73, 4889–4892.
17 R. E. Pincock, K. R. Wilson and T. E. Kiovsky, J. Am. Chem. Soc.,
1967, 89, 6890–6897.
ˇ
ˇ
18 L. Rul´ısˇek, P. Sebek, Z. Havlas, R. Hrabal, P. Capek and A. Svatosˇ,
J. Org. Chem., 2005, 70, 6295–6302.
10 A. Loupy, F. Maurel and A. Sabatie-Gogova, Tetrahedron, 2004, 60,
19 W. D. Robinson and R. A. Mount, Kirk-Othmer Encycl. Chem.
Technol., 1981, 14, 778–779.
1683–1691.
11 M. Bortolussi, R. Bloch and A. Loupy, J. Chem. Res. (S), 1998,
34–35.
12 Y. Murakami, M. Asagai, and I. Yamane, Jpn. Kokai Tokkyo
Koho (2000), JP, 2000–319222 A (in Japanese). A mechanical
20 S. Turner, Design of Chemical Synthesis, Elsevier, Amsterdam, 1976,
21–22.
21 P. T. Anastas and J. C. Warner, Green Chemistry: Theory and Practice,
Oxford University Press, Oxford, 1998.
This journal is
The Royal Society of Chemistry 2009
Green Chem., 2009, 11, 91–95 | 95
©