Pyrimidine ortho-quinodimethanes. Part 2: Synthesis of new [60]fullerene adducts based on substituted pyrimidine derivatives and their 1H NMR dynamic study

Article abstract of DOI:10.1016/j.tet.2009.05.026

The Diels-Alder reaction of various pyrimidine ortho-quinodimethanes generated in situ with C₆₀ gives access to a variety of new fullerodihydroquinazoline derivatives. This variety is increased since substituents on the pyrimidine ring can be e

Full text of DOI:10.1016/j.tet.2009.05.026

Tetrahedron 65 (2009) 5817–5823
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Pyrimidine ortho-quinodimethanes. Part 2: Synthesis of new [60]fullerene
1
adducts based on substituted pyrimidine derivatives and their H NMR
dynamic study
a
a
,
a
a
,
,
x
Antonio Herrera , Roberto Martınez-Alvarez , Nazario Martın , Mourad Chioua y, Rachid Chioua a
,
*
´
´
b
b
c
´
´
Dolores Molero , Angel Sanchez-Vazquez , John Almy
a
´
´
´
Departamento de Quımica Organica, Facultad de Ciencias Quımicas, Universidad Complutense, E-28040 Madrid, Spain
b CAI de RMN, Facultad de Ciencias Qu´ımicas, Universidad Complutense, E-28040 Madrid, Spain
c Department of Chemistry, California State University, Stanislaus, Turlock, CA 95382, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The Diels–Alder reaction of various pyrimidine ortho-quinodimethanes generated in situ with C60 gives
access to a variety of new fullerodihydroquinazoline derivatives. This variety is increased since sub-
stituents on the pyrimidine ring can be easily modified before or after its reaction with C60. Variable
temperature 1H NMR spectra provided thermodynamic parameters related to the boat-to-boat in-
terconversion of the cyclohexene ring fused to the fullerene moiety. The mass spectra of the prepared
cycloadducts show that the retro-Diels–Alder process takes place easily with elimination of the corre-
sponding diene molecule.
Received 26 February 2009
Received in revised form 28 April 2009
Accepted 5 May 2009
Available online 18 May 2009
Keywords:
Pyrimidines
Fullerenes
Ó 2009 Elsevier Ltd. All rights reserved.
ortho-Quinodimethanes
Diels–Alder reaction
Dynamic 1H NMR
1. Introduction
supramolecular ensembles through hydrogen bonds7 or other mo-
tifs.8 Heterocyclic fullerene derivatives, mainly prepared by 1,3-di-
Fullerene derivatives have been extensively studied due to the
outstanding properties they exhibit.1 Thus, for instance, pyrrolidino-
fullerenes2 as well as fullerene-stoppered molecular shuttles3 have
non-linear optical properties. Since fullerenes are known to show
remarkable electron accepting properties, they have been co-
valently and supramolecularly connected to a wide variety of elec-
tron donating species to form donor–acceptor dyads with
interesting photoinduced electron transfer processes, thus mim-
icking the photosynthetic process.4 Furthermore, photovoltaic de-
polar cycloaddition reactions involving fullerenes as dienophiles,
have been extensively studied as one of the most versatile pro-
cedures to prepare fullerene derivatives.9
An alternative synthetic approach to homo- and heterocyclic
fused fullerenes has involved the use of Diels–Alder reactions of
suitably functionalized ortho-quinodimethanes (o-QDMs) as dienes
and C60 or C70 as dienophiles.10 In particular, heterocyclic ortho-
quinodimethanes, generated in situ from appropriate precursors,
are highly reactive dienes used frequently in this cycloaddition
process. Thus, the thermolysis of adequate bis(bromomethyl)pyr-
vices have been prepared from semiconducting
p-conjugated
11
oligomers and some fullerene derivatives, mainly from the well-
known PCBM.5 On the other hand, ambipolar organic field effect
transistor has been fabricated, for instance, from thioxanthene–
fullerene dyad systems.6 Substituted fullerene derivatives with
appropriate functional groups can be also used to form
azine derivatives or pyrazine-fused sultines12 in the presence of
C60 affords the corresponding pyrazine-fused fullerenes. In addition,
pyrimidine-fused fullerenes have been prepared by Diels–Alder
reaction from substituted pyrimidine ortho-quinodimethanes (o-
QDMs) generated by thermal extrusion of sulfur dioxide of the
corresponding pyrimidine-fused 3-sulfolenes.13 Higher-fullerene
derivatives were also prepared by DA reaction of C70 and C76 with
o-QDMs generated in situ.14
We report herein a synthetic procedure for the preparation of
new dihydroquinazoline-fused fullerene (Scheme 1) based on the
easy generation of 2,4-functionalized pyrimidine ortho-quinodi-
methanes by heating the corresponding 2,4-disubstituted
* Corresponding author. Tel.: þ34 913944325; fax: þ34 913944103.
´
E-mail address: rma@quim.ucm.es (R. Martınez-Alvarez).
y
´
´
Present address: Instituto de Quımica Organica General, CSIC, E-28006 Madrid,
Spain.
x
Permanent address: De´partement de Chimie, Faculte´ des Sciences, Universite´
ˆ
´
Abdelmalek Essaadi, Tetouan, Morocco.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.05.026

5818
A. Herrera et al. / Tetrahedron 65 (2009) 5817–5823
cyclobutapyrimidines, which are, in turn, prepared from cyclo-
butanone and different nitriles. This versatile proposed approach
provides a diverse set of products and allows to prepare fullerene
derivatives with functional groups, which can be easily
transformed.
a relatively low energy LUMO, which facilitates the cycloaddition
(in the scheme the LUMO energy values of other widely used
dienophiles are included for comparison). In contrast, the ortho-
quinodimethane derived from 4 bearing the electron withdrawing
–SO2Me groups exhibits an unfavourable HOMO energy value for
the DA cycloaddition, thus accounting for the lower yield obtained
in the reaction of 4 with C60
.
As we have previously reported,16 the methylsulfonyl groups
attached to the pyrimidine ring can be easily transformed into other
functional groups whose electronic character allows an easier
Diels–Alder process. Thus, using as starting material the amino-
methylsulfonyl derivative 5, the corresponding cycloadduct 6 is
obtained in moderate yield (Scheme 4) as a result of a narrower
HOMO–LUMO energy difference. Unfortunately, the low solubility
of 6 limits its use for further synthetic applications. In order to study
the cycloadducts whose solubilities permit to record their NMR
spectra in liquid phase, we prepared the dimethoxycyclobutapyr-
imidine 7 from 4 by nucleophilic substitution of the methylsulfonyl
groups with sodium methoxide.16 Compound 7 reacts with C60 to
form the corresponding cycloadduct 8 (Scheme 4). The acid hy-
drolysis of the dimethoxy cycloadduct 8 with 6 M HCl led to the
formation of the uracil fullerene derivative 9 in a straightforward
manner. Although the uracil derivative resulted to be poorly soluble
in common organic solvents, the 1H NMR spectrum can be recorded
using a mixture of DMF-d7 and carbon disulfide. Amino protons at
positions 5 and 7 appear as deshielded broad singlets at 11.7 and
11.9 ppm, respectively (see Supplementary data). It is worth men-
tioning that the new compound 9 endowed with a uracil moiety is
an appealing building block for the construction of a variety of su-
pramolecular ensembles involving fullerene derivatives.
5
N
4´
3
R1
2
4
9
6
3´
2´
8
N
1
7
10
1´
R2
Scheme 1. Numbering used in the text.
2. Results and discussion
Following our general method for the synthesis of pyrimi-
dines,15 the reaction of cyclobutanone with methylthiocyanate and
triflic anhydride (Scheme 2) affords 2,4-bis(methylsulfanyl)-5,6-
dihydrocyclobuta[d]pyrimidine 1.15,16 The thermolysis of 1 with C60
in ortho-dichlorobenzene (ODCB) at 180 ꢀC produces cycloadduct 2
in moderate yield via the corresponding ortho-quinodimethane
intermediate. We have previously reported the use of this pro-
cedure to obtain 2,4-dimethyl- and 2,4-diphenylsubstituted pyr-
imidine cycloadducts.17 However, cycloadduct 2 bears functional
groups capable of further chemical transformations to afford a new
assortment of fullerene derivatives. Thus, the reaction of 2 with m-
CPBA under mild conditions leads to the formation of cycloadduct 3
in very good yield (Scheme 2). It should be noted that the extremely
low solubility of compound 3 makes it impossible to record its NMR
spectra in liquid phase. An alternative synthetic approach to
cycloadduct 3 consists of the modification of the pyrimidine de-
rivative 1 before its reaction with C60. Thus, 2,4-bis(methylsulfa-
nyl)cyclobutapyrimidine 1 can undergo a mild oxidation to 4 in
almost quantitative yield, which then reacts with C60 to form the
cycloadduct 3 in a significant lower yield. The fact that the oxida-
tion can take place before or after the Diels–Alder cyclization
confers considerable versatility to this procedure. The Diels–Alder
reaction is controlled by the energy differences between HOMO
(diene) and LUMO (dienophile). These energies are closely related
to the electronic nature of the substituents attached either to the
2.1. Dynamic 1H NMR spectroscopy
The structure of the new cycloadducts was established on the
basis of their spectroscopic data. The 13C NMR spectra indicated that
the cycloadduct molecule has an average Cs symmetry attributed to
the fast flipping motion of the cyclohexene ring linking the pyrim-
idine ring to the C60 core. The methylene carbons (C3 and C10) ap-
pear between 39 and 47 ppm while the quaternary sp3 carbon
atoms of attachment to the cyclohexene ring (C1 and C2) resonate
around 65 ppm. These chemical shift values confirm the 6,6-ring
junction on the C60 cage. The 1H NMR spectra show the methylene
diene or dienophile. Scheme
3
indicates that C60 possesses
MeS
N
O
2 MeSCN
Tf2O
N
SMe
1
MeS
N
N
SMe
C60
ODCB
180 °C
1
N
N
SMe
SMe
2 (43%)
r. t.
m-CPBA
N
SO2Me
MeO2S
N
MeS
N
C60
m-CPBA
N
N
ODCB
(19%)
N
r.t.
SO2Me
SO2Me
4 (93%)
SMe
3 (90%)
1
Scheme 2. The two-step synthesis of cycloadduct 2 and alternative approaches to cycloadduct 3.

A. Herrera et al. / Tetrahedron 65 (2009) 5817–5823
5819
EtOOC
-0.907
LUMO
O
COOEt
-1.146
LUMO
O
E (eV)
-1.267
LUMO
N
Ph
O
O
-2.947
LUMO
MeS
N
-8.237
HOMO
MeO
N
N
-8.661
HOMO
N
SMe
OMe
MeO2S
N
-9.095
N
HOMO
NH2
MeO2S
N
-9.735
HOMO
N
SO2Me
Scheme 3. Energy levels for the HOMO (diene) and LUMO (dienophile).
protons at C3 and C10 as two broad singlets at room temperature. At
higher temperatures, these singlets sharpen indicating a dynamic
process. This is attributed to a boat-to-boat cyclohexene ring in-
terconversion, which was studied by variable temperature NMR (VT
dB¼4.54, J¼14.16 Hz for (CH2)a and dA¼4.52, dB¼4.49, J¼14.65 Hz for
(CH2)b. The coalescence of (CH2)a is observed at 258 K while the
(CH2)b protons coalesce at 261 K (see Supplementary data). Com-
pound 8 exhibits a similar spectroscopic behaviour (Scheme 6),
showing two broad singlets at 298 K centred at 6.05 (CH2)a and 5.99
(CH2)b ppm. Cooling to 228 K produces two overlapped AB systems
fromwhich were calculated chemicalshifts and coupling constants of
dA¼6.15, dB¼5.90, J¼13.92 Hz for (CH2)a and dA¼6.14, dB¼5.78,
J¼14.65 Hz for (CH2)b. Coalescences were at 254 K for (CH2)a and
263 K for (CH2)b (see Supplementary data). The calculated thermo-
dynamic parameters for compounds 2 and 8 are collected in Table 1.
It is noteworthy that cycloadducts 2 and 8 have lower activation
free energies for both methylene groups (a and b) than those de-
termined for similar cycloadducts bearing methyl or aryl sub-
stituents on the pyrimidine ring.18 However, the experimental values
are in the range of those previously determined for six-membered
heterocycles analogues11 while values for pentagonal heterocycles
are much higher.12 These findings demonstrate a clear relationship
NMR). The coalescence temperature, and thus the D
Gz value for this
interconversion, depend on the nature of the heterocyclic ring
(pyrazine or thiophene).11 For the pyrimidine cycloadducts, these
thermodynamic parameters are a function of the alkyl or aryl sub-
stitution on the pyrimidine ring.18 Pyridine and benzene cyclo-
adducts with a hydroxyl group attached to the cyclohexene ring
adopt conformers with the OH group in pseudoaxial and pseudo-
equatorial position, respectively.19
The 1H NMR spectrum of 2 at 298 K in a mixture of CS2 and CDCl3
shows two broad singlets at 4.65 (CH2)a and 4.59 ppm (CH2)b,
respectively (Scheme 5). These assignments were based on the
smaller distance from (CH2)a (in red) to the nearest nitrogen atom in
the pyrimidine ring. At 228 K two overlapped AB systems can be
observed and have the following calculated parameters: dA¼4.71,
MeO2S
N
MeO2S
N
N
SO2Me
C60
NH3
r.t.
N
N
ODCB
N
NH2
SO2Me
NH2
5 (90%)
4
6 (41%)
NaOMe MeOH
H
N
MeO
N
N
OMe
O
C60
HCl 6M
Δ
N
ODCB
N
NH
OMe
OMe
O
7 (81%)
8 (47%)
9 (38%)
Scheme 4. Synthesis of aminomethylsulfonyl fullerene derivative 6, dimethoxy cycloadduct 8, and uracil derivative 9.

5820
A. Herrera et al. / Tetrahedron 65 (2009) 5817–5823
CH2 (b)
CH2 (a)
298 K
4.750
ppm (f1)
4.700
4.650
4.600
4.550
Ha
Ha
N
SMe
N
SMe
Hb
228 K
Hb
2
4.80
ppm (f1)
4.70
4.60
4.50
Scheme 5. Temperature-dependent 1H NMR spectra of compound 2.
between activation free energy and the electronic character of the
substituents attached at positions 2 and 4 of the pyrimidine moiety.
Although these groups are not spatially close to the cyclohexene
bridge, their electronic character plays an important role in the
flipping motion of the cyclohexene ring. In contrast, VT NMR ex-
periments on adducts having various aromatic rings other than
pyrimidine showed that steric effects mainly influence the inversion
rate of the cyclohexene ring.21 MM2 calculations reveal that the
cyclohexene ring in these polyaromatic cycloadducts adopts a half-
boat as its most stable conformation.21
For cycloadduct 8, the PM3 method predicts a boat as the lowest
energy conformation for the cyclohexene (Fig. 1). At room
(CH2)a
(CH2)b
298 K
6.100
ppm (f1)
6.050
6.000
5.950
5.900
Ha
Ha
N
OMe
N
OMe
Hb
Hb
8
228 K
6.20
ppm (f1)
6.10
6.00
5.90
5.80
5.70
Scheme 6. Temperature-dependent 1H NMR spectra of compound 8.

A. Herrera et al. / Tetrahedron 65 (2009) 5817–5823
5821
Table 1
2.2. Mass spectra of cycloadducts
Activation of free energies determined for cycloadducts 2 and 8
a
b
Gz (kJ molꢂ1
)
JAB (Hz)
D
Gz (kJ molꢂ1
)
d (ppm)
Mass spectrometry of fullerene cycloadducts is a powerful tool
to investigate the gas-phase reactions of this class of compounds.22
The electrochemical properties of fullerene derivatives permit the
analysis of these molecules by electrospray ionization (ESI) mass
spectrometry.23 The well-known retro-Diels–Alder reaction (RDA)
24can be originated in a mass spectrometer25 and is one of the most
investigated spectrometric process in the fullerene chemistry.26
Thus, ESI-MS demonstrates that isoxazolino fullerene derivatives
undergo retro-cycloaddition reaction with elimination of the cor-
responding 1,3-dipole molecule.27 The FAB mass spectra of methyl-
and arylsubstituted fulleropyrimidine cycloadducts show that the
RDA reaction takes place easily forming as base peak the corre-
sponding m/z 720 ion.28 The ESI and APCI mass spectra (in positive
as well negative mode of detection) of the reported 2, 6, 8, and 9
exhibit a similar behaviour, where the MS2 spectra reveal that the
RDA process is the main fragmentation pattern. However, com-
pound 3 extrudes consecutively two sulfur dioxide molecules
(2ꢁ64 u) forming a dimethylated pyrimidine cycloadduct,27 which
finally undergoes the expected RDA elimination (Scheme 7). It is
important to note that this is the first observation where an RDA
reaction takes place not directly from the isolated molecular ion but
from a prior double elimination of a small molecule.
Compound
Tc (K)
D
2
258 (a)
261 (b)
61.7
61.9
14.16
14.17
59.2
62.3
a1¼4.71
a2¼4.49
b1¼4.54
b2¼4.52
8
254 (a)
263 (b)
60.6
68.0
13.92
14.65
60.7
68.2
a1¼6.15
a2¼5.90
b1¼6.14
b2¼5.78
a
Activation free energies at the coalescence temperatures calculated according to
D
Gz¼aT[9.972þlog(TþDn)]; a¼1.914ꢁ10ꢂ2 kJ molꢂ1 (Ref. 20).
b
Activation free energies at the coalescence temperatures calculated according to
D
Gz¼aT[9.972þlog(Tþ(dn2þ6J2AB
)
1/2)]; a¼1.914ꢁ10-2 kJ molꢂ1 (Ref. 20).
temperature the cycloadducts have a Cs symmetry in the NMR
spectra as a result of the rapid motion of the cyclohexene unit at
room temperature. This boat conformation was also found in the
case of alkyl- and arylsubstituted pyrimidine cycloadducts.18
3. Conclusion
In summary, we have carried out the synthesis of novel
[60]fullerene cycloadducts bearing a pyrimidine ring endowed
with substituents, which have been further transformed into dif-
ferent chemical functionalities. The dynamic behaviour of the new
cycloadducts has been studied by VT 1H NMR and the thermody-
namic parameters determined for the flipping cyclohexene reveal
the influence of the substituents on the coalescence process. Fi-
nally, the mass spectra of the cycloadducts confirm the retro-Diels–
Alder process in a straightforward method or by following a double
elimination process involving a small molecule. Work is in progress
Figure 1. Minimum energy conformation of the PM3 optimized structure of cyclo-
adduct 8.
N
R1
MS2
N
RDA
R2
R1=R2=SMe, 2,[M+H]+=919
R1=R2=OMe, 8, M+H]+=887
m/z 721 [C60H]+
m/z 720 [C60
]
R1=SO2Me, R2=NH2, 6, [M-H]-=918
R1=R2=CO, 9, [M-H]-=857
N
SO2Me
N
SO2Me
MS2
N
N
-64 u
SO2Me
Me
3, [M-H]-=981
m/z 917
-64 u
MS3
N
Me
MS4
N
RDA
Me
m/z 853
m/z 720 [C60
]
Scheme 7. ESI mass spectra of new cycloadducts 2, 3, 6, 8, and 9.

5822
A. Herrera et al. / Tetrahedron 65 (2009) 5817–5823
in order to determine the usefulness of some of the novel fullerene
cycloadducts such as the uracil containing derivative as building
blocks for the construction of further supramolecular architectures.
13C NMR (57 MHz, DMSO-d6, 25 ꢀC):
d
¼26.5 (CH2), 34.0 (CH2), 38.8
ꢃ
(SO2Me), 121.0, 156.6, 157.4, 170.1; MS (EI, 70 eV) m/z (%B) 199 (Mþ
,
27), 184 (MꢂCH3, 65), 120 (MꢂSO2Me, 56), 42 (100). Anal. Calcd for
C7H9N3O2S: C, 42.20; H, 4.55; N, 21.09; S, 16.09. Found: C, 41.90; H,
4.33; N, 20.89; S, 15.87.
4. Experimental
4.1. General
4.2.3. 2,4-Dimethoxy-5,6-dihydrocyclobuta[d]pyrimidine (7)
Compound 7 was prepared from 4 according to previously
reported methods15 in 81% yield, mp 46–47 ꢀC (MeOH); IR (KBr)
Triflic anhydride was prepared from TfOH29 and distilled twice
over P2O5 before use. 1H NMR and 13C NMR for cyclo-
butapyrimidines were recorded in CDCl3 and DMSO-d6 at 300
(Bruker Avance 300) and 500 MHz (Bruker AM-500) and 57 and
125 MHz and referenced to 7.26 and 77.00 ppm for chloroform, 2.50
and 39.5 ppm for DMSO, respectively. NMR spectra of cycloadducts
were recorded in mixtures of CDCl3/CS2 and DMF-d7/CS2. In this last
case, spectra were referenced to 8.01 and 166.5 ppm for DMF. 1H
NMR of compound 6 was recorded in 1,1,2,2-tetrachloroethane-d2
at 80 ꢀC and referenced to 5.94 ppm. Homonuclear J couplings were
confirmed by single-frequency experiments. Multiplicity assign-
ments of 13C NMR signals were made from DEPT spectra. Solid state
NMR experiments were performed with a Bruker DSX 500 Wide
Bore spectrometer (magnetic field strength 11.7467 T, resonate
frequency of 13C 125.75 MHz). Samples were packed in 4 mm zir-
n
¼1211, 1085 cmꢂ1
;
1H NMR (300 MHz, CDCl3, 25 ꢀC):
d¼3.03 (t,
J¼4 Hz, 2H, CH2), 3.24 (t, J¼4 Hz, 2H, CH2), 3.93 (s, 6H, OMe); 13C
NMR (57 MHz, CDCl3, 25 ꢀC):
54.7 (OMe), 113.9, 163.5, 166.0, 175.2 (arom); MS (ESI) m/z 189
[MþNa]þ, 166 [MþH]þ. Anal. Calcd for C8H10N2O2: C, 57.82; H, 6.07;
N, 16.86. Found: C, 57.57; H, 5.88; N, 16.58.
d
¼25.5 (CH2), 34.6 (CH2), 53.8 (OMe),
4.3. Synthesis of Diels–Alder cycloadducts: general procedure
A solution of the appropriate cyclobutapyrimidine (1 mmol) and
C60 (1 mmol) in o-dichlorobenzene (20 mL) was heated under
reflux (180 ꢀC) for 48 h. The progress of the reaction was monitored
by TLC. Some part of the solvent was removed under reduced
pressure and the residue was fractionated by column chromato-
graphy using first as eluent carbon disulfide to eliminate the rest of
solvent and the C60 not transformed. A mixture of eluents (hexane/
ethyl acetate 8/2) permits to obtain the corresponding
cycloadducts.
conia rotors and spun at 9 KHz under magic angle using p1¼5
ms
and p15 (contact time)¼5 ms. The chemical shifts were referenced
to external carbonyl group of glycine at 176.1 ppm. VT NMR was
carried out at 500 MHz using a methanol standard for the cali-
bration of temperature. ESI and APCI mass spectra were recorded
on a Bruker Esquire LC while HRMS were recorded using an FTMS
Bruker APEX Q IV at 4.7 T under ESI conditions.
4.3.1. 10,20,30,40-Tetrahydro-60,80-bis(methylsulfanyl)quinazolino-
[20,30:1,2][60]fullerene (2)
4.1.1. 2,4-Bis(methylsulfanyl)-5,6-dihydrocyclobuta[d]-
pyrimidine (1)
Following the general procedure, the reaction of 1 with C60 af-
fords the compound in 40% yield. IR (KBr)
858 cmꢂ1 1H NMR (300 MHz, CDCl3/CS2, 25 ꢀC):
SMe), 2.77 (s, 3H, SMe), 4.58 (br s, 2H, CH2), 4.65 (br s, 2H, CH2); 13
n
¼2921, 1535, 1338,
Compound 1 was prepared from cyclobutanone, methythio-
cyanate, and triflic anhydride following reported synthetic meth-
;
d
¼2.75 (s, 3H,
C
ods15b,16 in 42% yield, mp 102–103 ꢀC (MeOH); IR (KBr)
n
¼1546,
¼2.51 (s, 3H,
SMe), 2.53 (s, 3H, SMe), 3.10 (t, J¼3.9 Hz, 2H, CH2), 3.30 (t, J¼3.9 Hz,
NMR (57 MHz, CDCl3/CS2, 25 ꢀC):
d
¼12.7 (SMe), 14.8 (SMe), 39.7
1427, 1334 cmꢂ1
;
1H NMR (300 MHz, CDCl3, 25 ꢀC):
d
(CH2), 45.9 (CH2), 64.3 (Csp3of C60), 64.7 (Csp3 of C60), 122.9, 140.8,
142.2, 142.3, 142.5, 142.6, 142.7, 145.5, 145.6, 145.9, 146.1, 146.2,
146.3, 146.7, 146.8, 147.0, 148.2, 155.7, 155.9, 163.9, 167.4, 171.9; 13C
13
2H, CH2); C NMR (57 MHz, CDCl3, 25 ꢀC):
d
¼11.5 (SMe), 14.2
(SMe), 27.1 (CH2), 35.0 (CH2), 129.5, 136.5, 161.6, 170.2 (arom); MS
NMR (CP-MAS):
d
¼13.5(SMe), 19.4 (SMe), 32.9 (CH2), 40.9 (CH2),
ꢃ
(EI, 70 eV) m/z 198(Mþ , 198), 183 (MꢂCH3, 72), 137 (183ꢂSCH2, 19),
65.1 (Csp3of C60), 123.8, 135.8, 140.1, 141.7, 142.5, 145.5, 155.9, 163.7,
166.2, 172.0; MS (ESI) m/z 919 [MþH]þ; HRMS calculated for
[MþH]þ C68H11N2S2: 919.03638, found: 919.04003.
78 (21). Anal. Calcd for C8H10N2S2: C, 48.45; H, 5.08; N, 14.13; S,
32.34. Found: C, 48.31; H, 4.89; N, 13.98; S, 32.14.
4.2. General procedures for the functionalization of
cyclobutapyrimidines
4.3.2. 10,20,30,40-Tetrahydro-60,80-bis(methylsulfonyl)quinazolino-
[20,30:1,2][60]fullerene (3)
Following the general procedure, the reaction of 4 with C60 af-
fords the compound in 19% yield. Compound 3 can also be prepared
(90% yield) by reaction of cycloadduct 2 with m-CPBA in dichloro-
methane following the same procedure used to obtain 4. The low
solubility avoids to record the NMR spectra in liquid phase. 13C NMR
4.2.1. 2,4-Bis(methylsulfonyl)-5,6-dihydrocyclobuta[d]-
pyrimidine (4)
Compound 4 was prepared by oxidation from 1 according to
previously reported method15 in 88% yield, mp 185–186 ꢀC (EtOH);
IR (KBr)
25 ꢀC):
n
¼1620, 1427, 1176, 1072 cmꢂ1
;
1H NMR (300 MHz, CDCl3,
(CP-MAS):
d
¼32.9 (SO2Me), 41.2 (SO2Me), 42.5 (CH2), 46.9 (CH2),
d
¼3.21 (s, 3H, OMe), 3.27 (s, 3H, OMe), 3.56 (t, J¼5 Hz, 2H,
63.8 (Csp3of C60), 131.0, 136.7, 142.5, 145.5, 155.3, 161.6, 175.2; MS
(APCI) m/z 982, [Mꢃꢂ]; HRMS calculated for C68H10N2O4S2:
982.00824, found: 982.01055.
13
CH2), 3.72 (t, J¼5 Hz, 2H, CH2); C NMR (57 MHz, CDCl3, 25 ꢀC):
d¼29.1 (CH2), 38.3 (SO2Me), 39.4 (CH2), 39.6 (SO2Me), 139.3, 156.2,
160.2, 181.3 (arom.); MS (ESI) m/z 263 [MþH]þ. Anal. Calcd for
C8H10N2O4S2: C, 36.63; H, 3.84; N, 10.68; S, 24.45. Found: C, 36.50;
H, 3.90; N, 10.53; S, 24.11.
4.3.3. 10,20,30,40-Tetrahydro-60-methylsulfonyl-80-
aminoquinazolino[20,30:1,2][60]fullerene (6)
Following the general procedure, the reaction of 5 with C60 af-
4.2.2. 4-Amino-2-(methylsulfonyl)-5,6-dihydrocyclo-
buta[d]pyrimidine (5)
fords the compound in 41% yield. IR (KBr)
1051, 785 cmꢂ1 1H NMR (300 MHz, 1,1,2,2-tetrachloroethane-d2,
80 ꢀC)
¼2.92 (br s, 2H, CH2), 3.09 (br s, 2H, CH2), 3.53 (s, 3H,
n
¼3139, 1635, 1429, 1205,
;
Compound 5 was prepared from 4 according to previously
d
reported methods15 in 89% yield, mp 183–184 ꢀC (EtOH); IR (KBr)
SO2Me), 8.19 (br s, 2H, NH2); 13C NMR (CP-MAS):
d¼29.5 (SO2Me),
n
¼3495, 3300, 3120, 1404, 1190, 1010 cmꢂ1
;
1H NMR (300 MHz,
40.3 (CH2), 71.4 (Csp3of C60), 82.9 (Csp3of C60), 136.5, 141.3, 143.4,
148.8, 164.4; MS (ESI) m/z 918 [MꢂH]ꢂ; HRMS calculated for [MH]ꢂ
C67H8N3O2S: 918.03369, found: 918.03998.
DMSO-d6, 25 ꢀC):
d
¼2.95 (t, J¼3.9 Hz, 2H, CH2), 3.09 (s, 3H, SO2Me),
3.19 (t, J¼3.9 Hz, 2H, CH2), 3.23 (s, 3H, SO2Me), 3.87 (br s, 2H, NH2);

A. Herrera et al. / Tetrahedron 65 (2009) 5817–5823
5823
4.3.4. 10,20,30,40-Tetrahydro-60,80-dimethoxyquinazolino-
[20,30:1,2][60]fullerene (8)
3525; (b) Mateo-Alonso, A.; Guldi, D. M.; Paolucci, F.; Prato, M. Angew. Chem.,
Int. Ed. 2007, 46, 8120–8126.
4. As representative examples, see: (a) Guldi, D. M.; Prato, M. J. Am. Chem. Soc.
Following the general procedure, the reaction of 7 with C60 af-
´
´
1997, 119, 974–980; (b) Martın, N.; Sanchez, L.; Herranz, M. A.; Illescas, B.; Guldi,
D. M. Acc. Chem. Res. 2007, 40, 1015–1024; (c) Pe´rez, E. M.; Sa´nchez, L.; Fer-
na´ndez, G.; Martı´n, N. J. Am. Chem. Soc. 2006, 128, 7172–7173.
fords the compound in 44% yield. IR (KBr)
1074, 727 cmꢂ1 1H NMR (300 MHz, CDCl3/CS2, 25 ꢀC):
3H, OMe), 4.14 (s, 3H, OMe), 4.55 (br s, 2H, CH2), 4.61 (br s, 2H, CH2);
13C NMR (57 MHz, CDCl3/CS2, 25 ꢀC):
n
¼2921, 1579, 1453, 1375,
;
d
¼4.13 (s,
5. (a) Ma, W.; Yang, C.; Gong, X.; Lee, K.; Heeger, A. J. Adv. Funct. Mater. 2005, 15,
1617–1622; (b) Li, G.; Shrotriya, S.; Huang, J.; Yao, Y.; Moriarty, T.; Emery, K.;
Yang, Y. Nat. Mater. 2005, 4, 864–868; (c) Riedel, I.; von Hauff, E.; Parisi, J.;
Martı´n, N.; Giacalone, F.; Dyakonov, V. Adv. Funct. Mater. 2005, 15, 1979–1987;
(d) Kim, J. K.; Lee, K.; Coates, N. E.; Moses, D.; Nguyen, T.-Q.; Dante, M.; Heeger,
A. J. Nature 2007, 317, 222–225; (e) For a recent review, see: Thompson, B. C.;
Fre´chet, J. M. J. Angew. Chem., Int. Ed. 2008, 47, 58–77.
6. Amriou, S.; Mehta, A.; Bryce, M. R. J. Mater. Chem. 2005, 15, 1232–1234.
7. For a review, see: Sa´nchez, L.; Martı´n, N.; Guldi, D. M. Angew. Chem., Int. Ed.
2005, 44, 5374–5382.
d
¼46.1 (OMe), 46.2 (OMe),
54.1 (CH2), 54.7 (CH2), 64.8 (Csp3of C60), 65.0 (Csp3 of C60), 109.6,
133.3, 140.0, 141.4, 141.9, 142.0, 142.4, 142.9, 144.4, 144.5, 144.9,
145.1, 146.3, 147.5, 155.7, 164.4, 167,6, 168.1; MS (ESI) m/z 887
[MþH]þ; HRMS calculated for [MþH]þ C68H11N2O2: 887.08203;
found: 887.08522.
8. For reviews, see: (a) Pe´rez, E. M.; Martı´n, N. Chem. Soc. Rev. 2008, 37, 1512–1519;
(b) Guldi, D. M.; Martı´n, M. J. Mater. Chem. 2002, 12, 1978–1992.
9. (a) Maggini, M.; Scorrano, G.; Prato, M. J. Am. Chem. Soc. 1993, 115, 9798–9799;
(b) Prato, M.; Maggini, M. Acc. Chem. Res. 1998, 31, 519–526.
4.3.5. 10,20,30,40-Tetrahydroquinazolino[20,30:1,2][60]fullerene-
60,80(5H-7H)-dione (9)
Cycloadduct 8 (88 mg, 0.1 mmol) is suspended in aqueous 6 M
HCl and heated for 6 h. The solvent was removed at reduced
pressure and the residue washed with water and methanol. The
´
10. Segura, J. L.; Martın, N. Chem. Rev. 1999, 99, 3199–3246.
11. Ferna´ndez-Paniagua, U. M.; Illescas, B.; Martı´n, N.; Seoane, C.; de la Cruz, P.; de
la Hoz, A.; Langa, F. J. Org. Chem. 1997, 62, 3705–3710.
12. Liu, J.-H.; Wu, A.-T.; Huang, M.-H.; Wu, C.-W.; Cheng, W.-S. J. Org. Chem. 2000,
65, 3395–3403.
uracil 9 was obtained in 38% yield. IR (KBr)
1460,1375,1120, 769 cmꢂ1; 1H NMR (300 MHz, DMF-d7/CS2, 25 ꢀC):
¼4.70 (br s, 2H, CH2), 4.95 (br s, 2H, CH2), 11.68 (br s, 1H, NH), 11.89
n
¼3423, 3200, 1681,
´
13. (a) Tome, A. C.; Ener, R. F.; Cavaleiro, J. A. S.; Elguero, J. Tetrahedron Lett. 1997, 38,
2557–2560; (b) Tome´, A. C.; Enes, R. F.; Tome´, J. P. C.; Rocha, J.; Neves, M. G. P.
M. S.; Cavaleiro, J. A. S.; Elguero, J. Tetrahedron 1998, 54, 11141–11150; (c) Enes,
R. F.; Tome´, A. C.; Cavaleiro, J. A. S. Tetrahedron 2005, 61, 1423–1431.
14. Hermann, A.; Diederich, F.; Thilgen, C.; ter Meer, H.-U.; Mu¨ller, W. H. Helv. Chim.
Acta 1994, 77, 1689–1706.
15. (a) Garcı´a Martı´nez, A.; Herrera Ferna´ndez, A.; Moreno Jime´nez, F.; Garcı´a
Fraile, A.; Subramanian, L. R.; Hanack, M. J. Org. Chem. 1992, 57, 1627–1630; (b)
Garcı´a Martı´nez, A.; Herrera, A.; Moreno, F.; Luengo, M. J.; Subramanian, L. R.
Synlett 1994, 559–560.
d
13
(br s, 1H, NH); C NMR (57 MHz, DMF/CS2, 25 ꢀC):
d¼40.9 (CH2),
41.4 (CH2), 65.7 (Csp3of C60), 66.8 (Csp3 of C60), 107.7, 135.8, 136.3,
140.3, 140.4, 141.4, 141.9, 142.3, 142.5, 142.7, 142.8, 143.4, 144.9,
145.0, 145.6, 145.7, 145.8, 145.9, 146.1, 146.5, 146.7, 146.8, 147.9,
148.0, 151.9, 152.8, 156.5; MS (ESI) m/z 857 [MꢂH]ꢂ; HRMS calcu-
lated for [MꢂH]ꢂ C66H5N2O2: 857.03510; found: 857.02997.
´
´
´
16. Herrera, A.; Martınez-Alvarez, R.; Martın, N.; Chioua, M.; Chioua, R.; Sanchez-
Vazquez, A.; Molero, D.; Almy, J. Tetrahedron 2009, 65, 1697–1703.
´
´
´
17. Herrera, A.; Martınez, R.; Gonzalez, B.; Illescas, B.; Martın, N.; Seoane, C. Tet-
rahedron Lett. 1997, 27, 4873–4876.
Acknowledgements
18. Gonza´lez, B.; Herrera, A.; Illescas, B.; Martı´n, N.; Martı´nez, R.; Moreno, F.;
Sa´nchez, L.; Sa´nchez, A. J. Org. Chem. 1998, 63, 6807–6813.
19. Nakamura, Y.; O-Kawa, K.; Minami, S.; Ogawa, T.; Tobita, S.; Nishimura, J. J. Org.
Chem. 2002, 67, 1247–1252.
20. Sandstro¨m, J. Dynamic NMR Spectroscopy; Academic: London, 1982; p 96.
21. Nakamura, Y.; Minowa, T.; Tobita, S.; Shizuka, H.; Nishimura, J. J. Chem. Soc.,
Perkin Trans. 2 1995, 2351–2357.
We thank the DGESIC (Spain, Grant CTQ2007-61973) for finan-
cial support and the CAIs of the UCM (Madrid, Spain) for de-
termining spectra and CHN analyses.
Supplementary data
22. Darwish, A. D.; Avent, A. G.; Birkett, P. R.; Kroto, H. W.; Taylor, R.; Waltom, D. R.
M. J. Chem. Soc., Perkin Trans. 2 2001, 1038–1044 and references therein.
23. (a) Rondeau, D.; Kreher, D.; Cariou, M.; Hudhomme, P.; Gorgues, A.; Richomme,
P. Rapid Commun. Mass Spectrom. 2001, 15, 1708–1712; (b) Rondeau, D.; Mar-
tineau, C.; Blanchard, P.; Roncali, J. J. Mass Spectrom. 2002, 10, 1081–1085; (c)
Kozlovski, V.; Brusov, I.; Sulimenkov, A.; Pikhtelev, A.; Dodonov, A. Rapid
Commun. Mass Spectrom. 2004, 18, 780–786; (d) Marchesan, S.; Da Ros, T.;
Prato, M. J. Org. Chem. 2005, 70, 4706–4713.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.05.026.
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