Diels-Alder Cycloadducts of Fullerene with Pyrimidine o-Quinodimethanes

Article abstract of DOI:10.1021/jo980189l

Novel organofullerenes bearing a pyrimidine nucleus covalently attached to the C60 cage have been prepared by <4+2> cycloaddition reactions of C60 and pyrimidine o-quinodimethanes generated "in situ" from the readily available cyclobutapyrimidines which are prepared in a one-pot procedure from cyclobutanone and alkyl or aryl nitriles. The reaction mechanism involves formation of a nitrilium cation with participation of two molecules of the respective nitrile. A side-product (16) formed from two cyclobutanone molecules is obtained together with the target cyclobutapyrimidines 4a-d. Compounds 4a-d are appropriate precursors for the generation of substituted pyrimidine o-quinodimethanes 5a-d which are efficiently trapped by the C60 molecule in a cycloaddition reaction which according to theoretical calculations is controlled by the HOMO of the diene. 1H NMR spectra indicate the presence of a dynamic process attributed to the boat-to-boat interconversion of the cyclohexene ring. The activation free energy has been measured by dynamic NMR experiments showing values ΔG(act.) ca. 16-17 kcal/mol for both methylene groups, depending upon the substituents on the pyrimidine unit. Theoretical calculations at the semiempirical PM3 level confirm the presence of a boat conformation for the cyclohexene ring which undergoes a rapid flipping motion resulting in an average C_s symmetry as it is observed in the 1H NMR spectra. The cyclic voltammetry measurements show the presence of reduction waves cathodically shifted, related to C60, due to the saturation of a double bond of the C60 cage. A weak electronic interaction is observed between the pyrimidine moiety and the C60 core.

Full text of DOI:10.1021/jo980189l

J . Org. Chem. 1998, 63, 6807-6813
6807
Diels-Ald er Cycloa d d u cts of [60]F u ller en e w ith P yr im id in e
o-Qu in od im eth a n es
Beatriz Gonza´lez, Antonio Herrera,* Beatriz Illescas, Nazario Mart´ın,* Roberto Mart´ınez,
Florencio Moreno, Luis Sa´nchez, and Angel Sa´nchez
Departamento de Quı´mica Orga´nica, Facultad de Quı´mica, Universidad Complutense,
E-28040 Madrid, Spain
Received February 3, 1998
Novel organofullerenes bearing a pyrimidine nucleus covalently attached to the C60 cage have been
prepared by [4 + 2] cycloaddition reactions of C60 and pyrimidine o-quinodimethanes generated
“in situ” from the readily available cyclobutapyrimidines which are prepared in a one-pot procedure
from cyclobutanone and alkyl or aryl nitriles. The reaction mechanism involves formation of a
nitrilium cation with participation of two molecules of the respective nitrile. A side-product (16)
formed from two cyclobutanone molecules is obtained together with the target cyclobutapyrimidines
4a -d . Compounds 4a -d are appropriate precursors for the generation of substituted pyrimidine
o-quinodimethanes 5a -d which are efficiently trapped by the C60 molecule in a cycloaddition reaction
which according to theoretical calculations is controlled by the HOMO of the diene. 1H NMR spectra
indicate the presence of a dynamic process attributed to the boat-to-boat interconversion of the
cyclohexene ring. The activation free energy has been measured by dynamic NMR experiments
showing values ∆Gq ≈ 16-17 kcal/mol for both methylene groups, depending upon the substituents
on the pyrimidine unit. Theoretical calculations at the semiempirical PM3 level confirm the presence
of a boat conformation for the cyclohexene ring which undergoes a rapid flipping motion resulting
in an average Cs symmetry as it is observed in the 1H NMR spectra. The cyclic voltammetry
measurements show the presence of reduction waves cathodically shifted, related to C60, due to
the saturation of a double bond of the C60 cage. A weak electronic interaction is observed between
the pyrimidine moiety and the C60 core.
In tr od u ction
membered ring heterocycle-containing organofullerenes
(1) are known so far.6 Furthermore, we have recently
reported the [4 + 2] cycloaddition reactions of six-
membered heterocyclic o-quinodimethanes, generated in
situ from 2,3-bis(bromomethyl)pyrazine derivatives to
[60]fullerene yielding cycloadducts 2.8
The synthesis of novel chemically modified fullerenes
is mainly directed to the search of other features to add
to the already known unique properties of fullerenes.
Among the different chemical procedures available for
such modifications of C60, cycloaddition reactions have
proved to be one of the most important methods for the
preparation of novel organofullerenes, and a wide variety
of cycloadducts have been reported.1 Addition of o-
quinodimethanes2 to C60 affords to a set of particularly
stable cycloadducts as a consequence of the aromatization
process which takes place during product formation.
Much less is known, however, on the reaction of hetero-
cyclic analogues of o-quinodimethane3 despite the interest
they have in the preparation of organofullerenes with
potential biological4 or materials science5 applications.
Recently, the first cycloadducts formed from C60 and
heteroaromatic o-quinodimethanes have been described
by Eguchi6 et al. and us.7 Only a limited number of five-
In this work we describe the synthesis of novel pyri-
midine-containing organofullerenes 17a -d prepared by
Diels-Alder cycloaddition of C60 and pyrimidine o-
quinodimethanes 5 which are in turn generated in situ
from readily available cyclobutapyrimidine derivatives
4a -d . As it is well-known, the pyrimidine ring occurs
(4) Sijbesma, R. P.; Srdanov, G.; Wudl, F.; Castoro, J . C.; Wilkins,
Ch.; Friedman, S. H.; DeCamp, D. L.; Kenyon, G. L. J . Am. Chem.
Soc. 1993, 115, 6510. Friedman, S. H.; DeCamp, D. L.; Sijbesma, R.
P.; Srdanov, G.; Wudl, F.; Kenyon, G. L. J . Am. Chem. Soc. 1993, 115,
6506. Tokuyama, H.; Yamago, S.; Nakamura, E. J . Am. Chem. Soc.
1993, 115, 7918. Toniolo, C.; Bianco, A.; Maggini, M.; Scorrano, G.;
Prato, M.; Marastoni, M.; Tomatis, R.; Spisani, S.; Palu`, G.; Blair, E.
D. J . Med. Chem. 1994, 37, 4558. da Ros, T.; Prato, M.; Novello, F.;
Maggini, M.; Banfi, E. J . Org. Chem. 1996, 61, 9070. Zan, Y.-Z.; Chen,
C.-H.; Anderson, J . L.; Sigman, D. S.; Foote, C. S.; Rubin, Y.
Tetrahedron 1996, 52, 5179. For a recent review, see: J ensen, A. W.;
Wilson, S. R.; Schuster, D. L. Bioorg. Med. Chem. 1996, 4, 767.
(5) Prato, M. J . Mater. Chem. 1997, 7, 1097.
(6) For a recent review on the synthesis of heterocycle-containing
[60]fullerenes, see: Eguchi, S.; Ohno, M.; Kojima, S.; Koide, N.;
Yashiro, A.; Shirakawa, Y.; Ishida, H. Fullerene Sci. Technol. 1996, 4,
303.
(7) Ferna´ndez-Paniagua, U. M.; Illescas, B. M.; Mart´ın, N.; Seoane,
C. J . Chem. Soc., Perkin Trans. 1 1996, 1077.
(1) Khan, S. I.; Oliver, A. M.; Paddon-Row: M. N.; Rubin, Y. J . Am.
Chem. Soc. 1993, 115, 4919. Belik, P.; Gu¨gel, A.; Spickermann, J .;
Mu¨llen, K. Angew. Chem., Int. Ed. Engl. 1993, 32, 78. Diederich, F.;
J onas, H.; Gramlich, V.; Hermann, A.; Ringsdorf, H.; Thilgen, C. Helv.
Chim. Acta 1993, 76, 2445. Prato, M.; Suzuki, T.; Foroudian, H.; Li,
Q.; Khemani, K.; Wudl, F.; Leonetti, J .; Little, R. D.; White, T.;
Rickborn, B.; Yamago, S.; Nakamura, E. J . Am. Chem. Soc. 1993, 115,
1594. Wilson, S. R.; Kaprinidis, N.; Wu, Y.; Schuster, D. J . Am. Chem.
Soc. 1993, 115, 8495. For a review see: Hirsch, A. Synthesis 1995,
895.
(2) For a review on o-quinodimethanes, see: Mart´ın, N.; Seoane,
C.; Hanack, M. Org. Prep. Proced. Int. 1991, 23, 237.
(3) Ando, K.; Takayama, H. Heterocycles 1994, 37, 1417. Chou, T.-
S. Rev. Heteroat. Chem. 1993, 8, 65. Chou, T.-S.; Chang, R.-C. J . Org.
Chem. 1993, 58, 493. Chaloner, M. L.; Crew, A. P. A.; O’Neill, P. M.;
Storr, R. C.; Yelland, M. Tetrahedron 1992, 48, 8101.
(8) (a) Ferna´ndez-Paniagua, U. M.; Illescas, B. M.; Mart´ın, N.;
Seoane, C.; de la Cruz, P.; de la Hoz, A.; Langa, F. J . Org. Chem. 1997,
62, 3705. An alternative synthetic procedure was simultaneously
reported from 2-hydroxycyclohexanone-fused [60]fullerene. See: (b)
Torres-Garc´ıa G.; Luftmann, H.; Wolff, Ch.; Mattay, J . J . Org. Chem.
1997, 62, 2752. (c) Ohno, M.; Koide, N.; Sato, H.; Eguchi, S. Tetrahe-
dron 1997, 53, 9075.
S0022-3263(98)00189-3 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/12/1998

6808 J . Org. Chem., Vol. 63, No. 20, 1998
Gonza´lez et al.
Ch a r t 1
Sch em e 2
pyrimidinoquinodimethanes (5) to [60]fullerene. The
reactive intermediate 5 is generated “in situ” by ther-
mally allowed conrotatory [σ2 + π2] electrocyclic ring
opening of cyclobutapyrimidines 4 in o-dichlorobenzene
(ODCB) at 180 °C. The starting cyclobutapyrimidines 4
are readily prepared in an expeditious one-step procedure
by reaction of aliphatic or aromatic nitriles 8 with
cyclobutanone 6 and triflic anhydride (Tf2O) according
to the method previously reported for other related
aliphatic or alicyclic ketones leading to differently sub-
stituted pyrimidines.11
Sch em e 1
widely in compounds with biological and pharmaceutical
activity and, therefore, pyrimidine-containing organo-
fullerenes are of particular interest in the search of novel
properties.
The mechanism proposed for the formation of the novel
cyclobutapyrimidines is analogous to that previously
reported for the reaction of nitriles with highly enolizable
ketones in the presence of trifluoromethanesulfonic
anhydride (Tf2O).11 This mechanism starts with an
electrophilic attack of triflic anhydride to cyclobutanone
6 leading to the formation of a (triflyloxy)carbenium ion
7 followed by nucleophilic attack of the nitrile to form a
resonance-stabilized nitrilum cation (9). This cation is
subsequently attacked by a second molecule of nitrile to
yield the cationic intermediate 10 which undergoes
elimination of triflic acid to afford 11. A further intramo-
lecular cyclization and loss of a proton yields the target
cyclobutapyrimidines 4 (Scheme 2).
The lower yields obtained for 5,6-dihydrocyclobuta[d]-
pyrimidines (4) in comparison to other aliphatic or
alicyclic ketones11 can be explained by considering the
difficulty of elimination of triflic acid which leads, in this
case, to a highly strained cyclobutenyl intermediate (11).
This result is in agreement with the higher difficulties
found in the formation of the cyclobutene ring in com-
parison to other related larger systems.12
Pyrimidine o-quinodimethane (5) has been generated
very recently by two different procedures (Scheme 1): (a)
from pyrimidine-fused-3-sulfolenes 3 by thermal extru-
sion of sulfur dioxide in a multistep synthetic procedure
in which the starting sulfolenes 3 were prepared in a
synthesis involving four steps.9 (b) A straightforward
route from substituted cyclobutapyrimidines 4 which are
in turn prepared in a one-step procedure from com-
mercially available nitriles and cyclobutanone, according
to the procedure that we have recently reported.10 By
following this approach, we have prepared a series of
novel organofullerenes 17a -d bearing alkyl- or aryl-
substituted pyrimidines from the readily available sub-
stituted cyclobutapyrimidines 4.
Dynamic behavior of the cycloadducts 17 has been
investigated by using variable-temperature 1H NMR
measurements. The redox properties of the different
organofullerenes have been measured by cyclic voltam-
metry (CV) in solution in order to determine the influence
that the substituted pyrimidine ring has on the reduction
potentials of the [60]fullerene moiety. Finally, theoretical
calculations at the semiempirical PM3 level were also
performed in order to predict the geometry of the
obtained cycloadducts and to gain some understanding
of the experimental findings.
Compounds 4 are thus obtained in moderate yields due
to the competitive formation of N-[1-(2′-oxocyclobutyl)]-
cyclobutylamide (16) as side-products which are isolated
in 20-30% yields. The formation of such unexpected
products could be explained from dimer 12 resulting from
an aldol condensation of cyclobutanone. Reaction of 12
with Tf2O followed by easy nucleophilic substitution by
Resu lts a n d Discu ssion
The target pyrimidine-containing cycloadducts 17a -d
were prepared by [4 + 2] cycloaddition of the respective
(9) (a) Tome´, A. C.; Cavaleiro, J . A. S.; Storr, R. C. Tetrahedron 1996,
52, 1735. (b) Tome´, A. C.; Cavaleiro, J . A. S.; Storr, R. C., Tetrahedron
1996, 52, 1723.
(10) Herrera, A.; Mart´ınez, R.; Gonza´lez, B.; Illescas, B.; Mart´ın,
N.; Seoane, C. Tetrahedron Lett. 1997, 38, 4873.
(11) Garc´ıa Mart´ınez, A.; Herrera Ferna´ndez, A.; Moreno J ime´nez,
F.; Garc´ıa Fraile, A.; Subramanian, L. R.; Hanack, M. J . Org. Chem.
1992, 57, 1627.
(12) Schlosser, M. Houben-Weyl “Methoden der Organishen Chemie”;
Georg Thieme: Stuttgart, 1972; Vol V/1b, p 201.

Diels-Alder Cycloadducts of [60]Fullerene
J . Org. Chem., Vol. 63, No. 20, 1998 6809
Sch em e 3
Sch em e 4
absorption band at around 430 and 700 nm.14 The 13C
NMR spectra clearly indicate that the molecule has an
average Cs symmetry resulting from the fast flipping
motion of the cyclohexene ring linking the pyrimidine
ring to the C60 cage. The methylene groups appear at
around δ 40 and 47 ppm, and the quaternary sp3-
hybridized carbon atoms of attachment to the organic
addend appear at δ 67.7 and 68.1 ppm for 17a , δ 64.8
and 65.3 ppm for 17b, and δ 64.7 and 65.2 ppm for 17d ,
thus confirming the 6,6-ring junction on the C60 cage. The
lower solubility of cycloadduct 17c prevented the record-
ing of its 13C NMR spectrum.
a molecule of nitrile leads to the stabilized nitrilium
cation 14 which undergoes basic hydrolysis (15) and a
1
further isomerization to yield amides 16 (Scheme 3). H
NMR spectra of 16a -c show the same characteristic
pattern for the aliphatic framework corresponding to the
two directly attached rings. 13C NMR spectra, H,C-COSY
experiments and selective 1D INEPT spectrum are in full
agreement with the structure of 16a -c. Since the molec-
ular ion is not observed in the mass spectra recorded with
ionization by electronic impact (70 eV), we have regis-
tered the spectra obtained with chemical ionization using
methane as reagent gas. This method of shoft ionization
yields the molecular ion and a small extent of cleavage.
The mass spectra of the three compounds are in total
agreement with the proposed structures.
5,6-Dihydrocyclobuta[d]pyrimidines (4) are versatile
precursors for the generation of the highly reactive
pyrimidinoquinodimethanes (5) which are efficiently
trapped by C60 or by other dienophiles such as N-phen-
ylmaleinimide (NPM) or p-benzoquinone derivatives.10
This result offers an elegant and straightforward pro-
cedure for the “in situ” generation of pyrimidinoquin-
odimethanes from readily available cyclobutapyrimi-
dines 4 in comparison to the alternative multistep pro-
cedure from substituted sulfolenes 3. By following the
sulfolene approach, the synthesis of pyrimidine and py-
rimidone derivatives of [60]fullerene has been very re-
cently reported from the respective heterocyclic o-quinodi-
methanes.13
1
The H NMR spectra of cycloadducts 17a -d show the
methylene protons as two broad singlets at δ 4.7-5.0 at
room temperature. The singlets become sharp at higher
temperatures which indicate a dynamic process due to
the boat-to-boat interconversion of the cyclohexene ring.
This behavior has already been reported for other related
organofullerenes.8,14b,15,16 The activation free energy for
the boat-to-boat inversion has been determined for the
new cycloadducts 17a -d by dynamic NMR experiments,
and the experimental data are collected in Table 1.
We have shown that the coalescence temperature and
∆Gq values depend on the pentagonal or hexagonal
nature of the heterocyclic system covalently attached to
the C60 core.8 In fact, a good linear correlation between
the activation energies ∆Gq, measured experimentally for
a series of C60-o-quinodimethane adducts, and the bond
lengths calculated for the fused double bond between the
cyclohexene and the aromatic ring was found.16 The
coalescence temperature and ∆Gq values show a remark-
able dependence on the alkyl or aryl substitution on the
pyrimidine ring in cycloadducts 17a -d (Table 1).
The 1H NMR spectrum of 17a at 293 K in CDCl3
solution displays two broad signals centered at δ 4.72 for
CH2(a) and δ 4.66 ppm for CH2(b) respectively, which
become sharp with increasing temperature. At 214 K two
According to theoretical calculations, carried out at a
semiempirical level (PM3 and AM1) (Hyperchem 3.0), the
cycloaddition to form the novel organofullerenes 17a -d
is controlled by the HOMO of the pyrimidine o-quin-
odimethanes. The HOMO(diene)-LUMO(C60) energy
differences are clearly in the range of energetically
favored cycloadditions (5.4-5.6 eV).
The structure of organofullerenes 17a -d was estab-
lished on the basis of their spectroscopic data. The UV-
vis spectra of compounds 17a -d show a typical weak
AB systems are observed [δB ) 4.86, δA ) 4.54, J AB
)
14.15 Hz for CH2(a); δB ) 4.66, δA ) 4.63, J AB ) 14.65
(14) (a) Isaacs, L.; Wehrsig, A.; Diederich, F. Helv. Chim. Acta 1993,
76, 1231. (b) Rubin, Y.; Khan, S.; Freedberg, D. I.; Yeretzian, C. J .
Am. Chem. Soc. 1993, 115, 344.
(15) (a) Zhang, X.; Foote, C. S. J . Org. Chem. 1994, 59, 5235. (b)
Tago, T.; Minowa, T.; Okada, Y.; Nishimura, J . Tetrahedron Lett. 1993,
34, 8461. (c) Nakamura, Y.; Minowa, T.; Shizuka, H.; Nishima, J . J .
Chem. Soc., Perkin Trans. 2 1995, 2351.
(13) Tome´, A. C.; Enes, R. F.; Cavaleiro, J . A. S.; Elguero, J .
Tetrahedron Lett. 1997, 38, 2557.
(16) Illescas, B. M.; Mart´ın, N.; Seoane, C.; Ort´ı, E.; Viruela, P. M.;
Viruela, R.; de la Hoz, A. J . Org. Chem. 1997, 62, 7585.

6810 J . Org. Chem., Vol. 63, No. 20, 1998
Ta ble 1. Activa tion F r ee En er gies Deter m in ed for Cycloa d d u cts 17a -d
Gonza´lez et al.
Ta ble 2. Red ox P oten tia ls of Novel Or ga n ofu ller en esa
nofullerenes (∼17 kcal/mol) and could be due to the high
torsional and angular constraints of these structures
because of the rigidity of the C60 cage,14b,15a which now is
reinforced by the presence of the aryl groups on the
pyrimidine ring.
compound
E1
E2
E3
E4
red
red
red
red
C60
17a
17b
17c
17d
-0.60
-0.66
-0.65
-0.66
-0.64
-1.00
-1.05
-1.03
-1.04
-1.03
-1.52
-1.64
-1.61
-1.65
-1.64
-2.04
-
-
-
-
To rationalize the above experimental findings, we
have optimized the molecular structure of the parent
organofullerenes 17a and 17b bearing methyl and phenyl
groups as substituents on the pyrimidine moiety at the
semiempirical PM3 level.18 Figure 2 displays the opti-
mized structure of 17b together with the bond lengths
and bond angles obtained for the organic addend.
The PM3 method predicts a geometry with the cyclo-
hexene ring adopting a boat conformation as the mini-
mum energy structure. The cycloadducts present, how-
a
V
vs SCE; GCE as working electrode; 0.1 mmol/dm3
NBu4+ClO4-; toluene:MeCN (5:1); 200 mV/s.
Hz for CH2(b)]. These quartets coalesce at temperature
of 270 and 263 K, respectively. A similar behavior is
1
observed in the H NMR spectra of compounds 17b-d
(see Table 1).
The closer proximity of the heterocyclic nitrogen to the
methylene hydrogens (a) could be responsible for the
observed slight shift of the CH2(a) signals to lower field
1
ever, a Cs symmetry in the H NMR spectra as a result
of the rapid flipping motion of the cyclohexene moiety.
The C1-C2 bond, to which the organic addend is fused
in a 6/6 junction, has a bond length of 1.586 Å which is
quite similar to that calculated for other organofullerenes
in which the pyrimidine ring is substituted by an un-
substituted benzene ring (1.586 Å)16 or a pyrazine ring
(1.583 Å).8a These bond lengths are very close to those
observed by X-ray analysis for other related 1,2-dihy-
drofullerenes.14b,19
1
in the H NMR spectra.
It is interesting to note that cycloadduct 17a , bearing
methyl substituents on the pyrimidine ring, presents a
lower activation free energy for both methylene groups
(a and b) than those determined for cycloadducts bearing
aryl groups (17b-d ) on the pyrimidine moiety (Table 1).
The experimental values obtained are in the range of
those previously measured for other carbocyclic (14.6-
16.6 kcal/mol)14b,15 analogues or six-membered heterocy-
clic (15.4-15.8 kcal/mol)8a analogues, being much higher
than those determined for pentagonal heterocycles (11-
12 kcal/mol).8a The experimental values now reported
are the highest observed so far for these type of orga-
(17) Sandstro¨m, J . Dynamic NMR Spectroscopy; Academic Press:
London, 1982; p 96.
(18) Stewart, J . J . P. J . Comput. Chem. 1989, 10, 209; 1989, 10,
221. The calculations were carried out using the Hyperchem 3.0
program.

Diels-Alder Cycloadducts of [60]Fullerene
J . Org. Chem., Vol. 63, No. 20, 1998 6811
groups linked to the pyrimidine ring has a very slight
influence on the first reduction potential values since the
presence of the most electronegative chlorine atoms
anodically shift the E1 value (Table 2). Although the
red
presence of a pyrimidine unit shifts the first reduction
potential of the C60 unit to more positive values in
comparison to a benzene ring,21 the effect of the nitrogen
atoms in the pyrimidine ring is smaller than in the
pyrazine ring8a due, probably, to the longer bond con-
nectivity of the second nitrogen atom to the C60 core.
Thus, the pyrimidine nucleus does not significatively
alter the redox properties of the parent [60]fullerene.
Su m m a r y a n d Con clu sion s
The synthesis of novel pyrimidine-containing organo-
fullerenes 17a -d has been carried out by Diels-Alder
reaction of C60 and pyrimidine o-quinodimethanes which
are, in turn, generated in situ from novel cyclobutapy-
rimidines 4a -d . These compounds (4a -d ) are easily
prepared in a one-pot procedure through a mechanism
involving the formation of a nitrilium cation. Cyclo-
butapyrimidines open up an elegant and convenient route
for the generation of the highly reactive pyrimidine
o-quinodimethanes. Theoretical calculations confirm
that cycloaddition to form 17a -d are controlled by the
HOMO of the pyrimidine o-quinodimethanes, being
energetically favored reactions.
The energy barriers for the boat-to-boat inversion of
the cyclohexene ring have been determined by dynamic
NMR experiments, and the ∆Gq values show a significant
dependence of the alkyl or aryl substitution on the
pyrimidine unit. The molecular geometry of cycloadducts
17a and 17b have been optimized at the semiempirical
PM3 level and predict a structure in which the cyclohex-
ene ring adopts a boat conformation, thus confirming the
Cs symmetry observed in the 1H NMR spectra. The redox
properties of the novel organofullerenes determined by
cyclic voltammetry indicate a certain interaction between
the organic addend and the C60 moiety.
This methodology for the preparation of cyclobutapy-
rimidines paves the way to the generation of elusive
pyrimidine o-quinodimethanes with other substituents
and functional groups on the pyrimidine nucleus from
the appropriately substituted nitriles. These modified
fullerenes bearing a pyrimidine nucleus offer a prospect
for biological probes based on the possibilities that the
pyrimidine ring presents for further functionalization and
the unique properties of [60]fullerene.
F igu r e 1. Temperature-dependent 1H NMR spectra of com-
pound 17b.
The remaining bond lengths and bond angles are
similar to those found for the benzene- or pyrazine-
containing analogues and are in good agreement with the
reported X-ray data.14b,19 The bond length between C4-
C9 (1.408 Å) (see Figure 2) is slightly larger than that
found when the pyrimidine unit is substituted by a
benzene ring (1.400 Å).16 Taking into account the linear
correlation found between the activation energies, ∆Gq,
measured experimentally for this type of organo-
fullerenes, and the lengths calculated for the respective
C4-C9 bond,16 a value of ∼16 kcal/mol should be
expected. These values confirm that for these organo-
fullerenes reasonably good predictions for activation
barriers can be obtained from readily performed theoreti-
cal calculations.
The redox properties of the novel cycloadducts 17a -d
were studied by cyclic voltammetry (CV) measurements
at room temperature in toluene/acetonitrile (5/1) as
solvent. The reduction potential peaks are shown in
Table 2 together with those of the parent [60]fullerene
measured under the same experimental conditions for
comparison purposes.
Compounds 17a -d show the presence of three reduc-
tion waves at potential values shifted to more negative
values, related to the parent C60, as expected for most
dihydrofullerenes20 due to the saturation of a double bond
in the C60 cage which raises the LUMO energy of these
organofullerenes (17a -d ). Substitution on the phenyl
Exp er im en ta l Section
Syn t h esis of 5,6-Dih yd r ocyclob u t a [d ]p yr im id in es.
Gen er a l P r oced u r e. To a well stirred solution of triflic
anhydride (2.70 g, 9.6 mmol) and the corresponding nitrile
(16.8 mmol) in anhydrous CH2Cl2 was added slowly a solution
of cyclobutanone (0.56 g, 8 mmol) in 10 mL of CH2Cl2. The
brown mixture was stirred under reflux for the appropriate
time. Saturated NaHCO3 solution (50 mL) was carefully
added, and the organic layer was washed with brine (2 × 50
mL) and dried over MgSO4. The solvent was removed under
(20) (a) Chlistunoff, J .; Cliffel, D.; Bard, A. J . Handbook of Organic
Conductive Molecules and Polymers; Nalwa, H. S., Ed., J ohn Wiley &
Sons Ltd.: New York, 1997; Ch. 7, Vol. 1. (b) Suzuki, T.; Maruyama,
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6812 J . Org. Chem., Vol. 63, No. 20, 1998
Gonza´lez et al.
F igu r e 2. Detail of the PM3-optimized molecular structure of 17b. (a) Cyclohexene aleatory numbering used in the text. (b)
Geometry of the organic addend for 17b. (c) Minimum energy conformation of 17b. Bond lengths are in angstroms and bond
angles in degrees.
vacuum, and the crude product was column chromatographed
over silica gel 60 (Merck) using hexane/ethyl acetate as the
eluent, allowing the isolation of pure 5,6-dihydrocyclobuta[d]-
pyrimidines 4a -d and N-[1-(2′-oxocyclobutyl)]cyclobutyla-
mides 16a -c as byproducts.
2,4-Dim eth yl-5,6-d ih yd r ocyclobu ta [d ]p yr im id in e (4a ):
20% yield; bp 25 °C/2 mbar (bulb to bulb); 1H NMR (300 MHz,
CDCl3) δ 2.33 (s, 3H), 2.66 (s, 3H), 3.13 (dist. t, 2H), 3.36 (t, J
) 4.6 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 20.1, 26.5, 26.6,
35.0, 133.7, 157.9, 167.4, 173.0; MS m/z 174 (M+, 49), 93 (29),
66 (44), 52 (100), 42 (94).
(82), 123 (8), 119 (100), 95 (16), 81 (9). Anal. Calcd for C16H19-
NO2: C, 74.68; H, 7.44; N, 5.44. Found: C, 74.13; H, 7.19; N,
5.41.
2,4-Bis(4-ch lor op h en yl)-5,6-d ih yd r ocyclobu ta [d ]p yr i-
m id in e (4d ): 25% yield; mp 157-158 (MeOH); 1H NMR (300
MHz, CDCl3) δ 3.50, 3.62 (4H, dist. AA’BB’), 7.50, 7.63 (4H,
AA′BB′), 8.10, 8.50 (4H, AA′XX′); 13C NMR (75 MHz, CDCl3)
δ 29.0, 36.2, 128.6, 129.0, 129.2, 132.0, 134.0, 136.5, 136.9,
137.2, 153.5, 163.4, 174.5; IR (KBr) 1600, 1580, 1500, 1100,
800 cm-1; MS m/z 326 (M+, 100), 291 (82), 154 (38), 52 (92).
Syn th esis of Or ga n ofu ller en es 17a -d . Gen er a l P r o-
ced u r e. A solution of the corresponding dihydrocyclobutapy-
rimidine 4a -d and [60]fullerene in 10-20 mL of o-dichlo-
robenzene was heated under reflux for a variable period of
time. The solvent was removed under reduced pressure, and
the residue was purified by column chromatography on silica
gel. Further purification of the solid was accomplished by
washing and centrifuging three times with methanol.
1′,2′,3′,4′-Tet r a h yd r o-6′,8′-d im et h ylq u in a zolin o[2′,3′:
1,2][60]fu ller en e (17a ). According to the general procedure,
a solution of 2,4-dimethyl-5,6-dihydrocyclobuta[d]pyrimidine
(4a ) (30 mg, 0.22 mmol) and [60]fullerene (161 mg, 0.22 mmol)
in 10 mL of o-dichlorobenzene was refluxed for 24 h. The
product was purified by using toluene as the eluent, yielding
27 mg (14%, 96% based on consumed C60) of 17a : 1H NMR
(CDCl3/CS2) δ 2.79 (s, 3H), 2.87 (s, 3H), 4.66 (s, 2H), 4.73 (bs,
2H); 13C NMR (CDCl3) δ 26.9, 29.9, 39.6, 46.4, 67.7, 68.1, 110.6,
114.2, 125.5, 136.0, 140.1, 141.4, 141.8, 142.4, 142.9, 144.34,
144.5, 144.8, 145.2, 145.4, 146.0, 146.3, 155.0, 155.3, 163.0,
165.5, 166.4; FTIR (KBr): 2919, 1570, 1426, 1412, 1181, 766,
697, 577, 525 cm-1; MS m/z: 854 (M+, 33), 720 (C60, 100). UV-
vis (CHCl3), λmax (nm): 254, 294, 334, 434, 700.
N-[1-(2′-Oxocyclobu tyl)cyclobu tyl]acetam ide (16a): 20%
1
yield; mp: 107-108 °C (hexane); H NMR (300 MHz, CDCl3)
δ 2.10 (m, 11H), 2.90 (m, 2H), 4.15 (m, 1H), 5.56 (s, 1H); 13C
NMR (75 MHz, CDCl3) δ 13.2, 15.2, 27.8, 30.3, 31.0, 44.5, 56.5,
65.4, 169.3, 210.0; IR (KBr) 3250, 3050, 2990, 2950, 1775, 1630
cm-1; MS (CI, CH4) m/z (%): 182 (M + H, 30), 123 (81), 95
(100), 87 (71). Anal. Calcd for C10H15NO2: C, 66.27; H, 8.34;
N, 7.73. Found: C, 66.08; H, 7.77; N, 8.15
2,4-Dip h en yl-5,6-d ih yd r ocyclobu ta [d ]p yr im id in e (4b):
27% yield; mp: 118-119 °C (hexane); 1H NMR (300 MHz,
CDCl3) δ 3.53-3.61 (4H, AA’BB’), 7.51 (m, 5H), 8.25 (m, 3H),
8.54 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 28.2, 36.3, 127.9,
128.2, 128.6, 129.0, 130.4, 131.1, 132.2, 135.9, 138.8, 155.0,
164.4, 174.4; IR (KBr) 3050, 1600, 1580, 1560, 1500, 760, 700
cm-1; MS m/z 258 (M+, 62), 155 (13), 104 (19), 77 (19), 52 (100).
N-[1-(2′-Oxocyclobu tyl)cyclobu tyl]ben zam ide (16b): 23%
yield; mp: 129-130 °C (hexane); IR (KBr) 3310, 1775, 1640,
730, 700 cm-1; 1H NMR (300 MHz, CDCl3) δ 2.05 (m, 8H), 2.95
(m, 2H), 4.25 (m, 1H), 6.40 (bs, 1H), 7.60 (m, 5H); 13C NMR
(75 MHz, CDCl3) δ 13.6, 15.5, 30.7, 31.5, 44.9, 57.0, 65.8, 127.0,
128.7, 131.6, 134.9, 166.9, 210.2; MS (CI, CH4) m/z (%): 244
(M + H, 22), 122 (65), 105 (100), 95 (23), 81 (16). Anal. Calcd
for C15H17NO2: C, 74.05; H, 7.04; N, 5.76. Found: C, 73.83;
H, 6.74; N, 5.75
2,4-Bis(4-m eth ylp h en yl)-5,6-d ih yd r ocyclobu ta [d ]p yr i-
m id in e (4c): 30% yield; mp: 162-163 °C (hexane); 1H NMR
(300 MHz, CDCl3) δ 2.40 (s, 6H), 3.40, 3.50 (4H, AA′BB′), 7.30
(m, 4H), 8.10, 8.45 (4H, AA′XX′); 13C NMR (75 MHz, CDCl3) δ
21.6, 21.7, 29.1, 36.2, 127.9, 128.1, 129.3, 129.7, 131.5, 133.2,
136.2, 140.4, 141.4, 154.7, 164.4, 174.0; IR (KBr) 1610, 1580,
1520, 795 cm-1; MS m/z 286 (M+, 66), 154 (23), 118 (33), 91
(16), 52 (100).
1′,2′,3′,4′-Tet r a h yd r o-6′,8′-d ip h en ylq u in a zolin o[2′,3′:
1,2][60]fu ller en e (17b). According to the general procedure,
a solution of 2,4-diphenyl-5,6-dihydrocyclobuta[d]pyrimidine
(4b) (40 mg, 0.16 mmol) and C60 (112 mg, 0.16 mmol) in
o-dichlorobenzene (20 mL) was refluxed during 69 h. The
product was purified by using CHCl3 as the eluent, yielding
70 mg (46%, 74% based on consumed C60) of 17b: 1H NMR
(300 MHz, CDCl3/CS2) δ 4.90 (bs, 2H), 4.98 (bs, 2H), 7.56-
7.58 (m, 6H), 7.89-7.91 (m, 2H), 8.73-8.76 (m, 2H); 13C NMR
(CDCl3/CS2) δ 40.7, 47.3, 64.8, 65.3, 128.6, 128.7, 128.8, 129.6,
129.8, 130.9, 137.4, 137.7, 140.3, 140.5, 141.8, 141.9, 142.0,
142.1, 142.2, 142.3, 142.7, 142.7, 143.2, 144.7, 144.8, 145.6,
145.6, 145.8, 145.8, 146.3, 146.4, 146.6, 147.7, 147.8, 155.8,
163.3, 163.7, 167.7; FTIR (KBr): 2919, 1550, 1425, 1392, 1180,
766, 748, 696, 525 cm-1; MS m/z: 978 (M+, 13), 720 (C60, 27);
UV-vis (CHCl3), λmax (nm): 256, 294, 318, 434, 702.
N -[1-(2′-Oxocyclob u t yl)cyclob u t yl]-4-m e t h ylb e n za -
1
m id e (16c): 26% yield; mp: 121-122 °C (hexane); H NMR
(300 MHz, CDCl3) δ 1.95 (m, 2H), 2.30 (m, 6H), 2.40 (s, 3H),
2.95 (m, 2H), 4.25 (m, 1H), 6.40 (br s, 1H), 7.40 (m, 4H); 13C
NMR (75 MHz, CDCl3) δ 13.5, 15.5, 21.5, 30.8, 31.4, 44.8, 57.0,
67.8, 127.0, 129.3, 132.1, 142.0, 166.8, 210.3; IR (KBr) 3300,
1785, 1640 cm-1; MS (CI, CH4) m/z (%): 258 (M + H, 36), 136
1′,2′,3′,4′-Tetr ah ydr o-6′,8′-bis(p-m eth ylph en yl)qu in azoli-
n o[2′,3′:1,2][60]fu ller en e (17c). According to the general

Diels-Alder Cycloadducts of [60]Fullerene
J . Org. Chem., Vol. 63, No. 20, 1998 6813
procedure, a solution of 2,4-bis(4-methylphenyl)-5,6-dihydro-
cyclobuta[d]pyrimidine (4c) (40 mg, 0.14 mmol) and C60 (101
mg, 0.14 mmol) in 20 mL of o-dichlorobenzene was refluxed
for 27 h. The product was purified by using cyclohexane/CHCl3
1/1 as the eluent, yielding 41 mg (29%, 54% based on consumed
130.0, 130.9, 134.6, 135.5, 136.0, 136.4, 136.5, 140.3, 142.1,
142.8, 144.8, 146.3, 146.4, 146.6, 146.7, 147.8, 155.6; FTIR
(KBr): 2922, 1576, 1550, 1392, 1259, 1092, 814, 767, 527 cm-1
;
MS m/z: 1049 (M+, 47), 720 (C60, 100); UV-vis (CHCl3), λmax
(nm): 254, 294, 433, 700.
C
60) of 17c: 1H NMR (CDCl3/CS2) δ 2,50 (s, 6H); 4,75-5,07
(bm, 4H); 7,32-7,38 (m, 4H); 7,79 (d, 2H, J ) 8.1 Hz); 8,60 (d,
2H, J ) 8.1 Hz); FTIR (KBr): 2920, 1551, 1507, 1393, 1260,
Ack n ow led gm en t. We are gratefully acknowledged
to the DGICYT (Spain, Grant PB-95-0911 and PB95-
0428-CO2) for financial support. We thank “Centro de
Espectroscop´ıa de la UCM” for determining NMR and
mass spectra.
1021, 811, 795, 573, 526 cm-1; MS m/z: 1006 (M+, 8), 720 (C60
17); UV-vis (CHCl3), λmax (nm): 256, 292, 434, 702.
,
1′,2′,3′,4′-Tetr ah ydr o-6′,8′-bis(p-ch lor oph en yl)qu in azoli-
n o[2′,3′:1,2][60]fu ller en e (17d ). According to the general
procedure, a solution of 2,4-bis(p-chlorophenyl)-5,6-dihydro-
cyclobuta[d]pyrimidine (4d ) (50 mg, 0.15 mmol) and [60]-
fullerene (110 mg, 0.15 mmol) in o-dichlorobenzene (30 mL)
was refluxed for 47 h. The product was purified by using
cyclohexane/CHCl3 1/1 as the eluent, yielding 43 mg (27%, 76%
based on consumed C60) of 17d : 1H NMR (CDCl3/CS2) δ 4.85
(bs, 2H), 4.97 (bs, 2H), 7.52-7.58 (m, 4H), 7.84 (d, 2H, J ) 8.4
Hz), 8.68 (d, 2H, J ) 8.4 Hz); 13C NMR (CDCl3/CS2) δ 40.6,
47.2, 64.7, 65.2, 113.8, 122.2, 123.2, 125.9, 128.9, 129.1, 129.8,
Su p p or tin g In for m a tion Ava ila ble: H,C COSY and
mass spectra of compounds 16a -c and 1D INEPT of compound
16c (7 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
J O980189L