Oxidation of 3-alkyl-substituted 2-pyrazolino[60]fullerenes: A new formyl-containing building block for fullerene chemistry

Article abstract of DOI:10.1021/ol801308g

(Figure Presented) A new building block for fullerene chemistry, endowed with a formyl group on C-3 of the 2-pyrazoline ring, has been prepared in a simple two-step synthesis by oxidation of readily available 3-alkyl-substituted 2-pyrazolino[60]fullerenes; the new building block paves the way for the preparation of new light-harvesting fullerenes.

Full text of DOI:10.1021/ol801308g

ORGANIC
LETTERS
2008
Vol. 10, No. 17
3705-3708
Oxidation of 3-Alkyl-Substituted
2-Pyrazolino[60]fullerenes: A New
Formyl-Containing Building Block for
Fullerene Chemistry
Juan Luis Delgado,† Franc¸ois Cardinali,‡ Eva Espíldora,† M. Rosario Torres,§
Fernando Langa,*,‡ and Nazario Martín*,†,|
Departamento de Química Orga´nica and Laboratorio de Difraccio´n de Rayos X,
Facultad de Ciencias Químicas, UniVersidad Complutense de Madrid,
28040, Madrid, Spain, Instituto de Nanociencia, Nanotecnología y Materiales
Moleculares (INAMOL), UniVersidad de Castilla-La Mancha, 45071 Toledo, Spain,
and IMDEA-Nanociencia, Facultad de Ciencias, Mo´dulo C-IX, 3a planta, Ciudad
UniVersitaria de Cantoblanco, 28049 Madrid, Spain
nazmar@quim.ucm.es; fernando.lpuente@uclm.es
Received June 10, 2008
ABSTRACT
A new building block for fullerene chemistry, endowed with a formyl group on C-3 of the 2-pyrazoline ring, has been prepared in a simple
two-step synthesis by oxidation of readily available 3-alkyl-substituted 2-pyrazolino[60]fullerenes; the new building block paves the way for
the preparation of new light-harvesting fullerenes.
Recent studies on the retro-cycloaddition process of a variety
of fullerene cycloadducts, namely, pyrrolidino[3′,4′:1,2][60]-
fullerenes1 and isoxazolino[4′,5′:1,2][60]fullerenes,2 have
shown the usefulness of these reactions as a new protection-
deprotection protocol that has been successfully used in the
isolation of endohedral metallofullerenes.1 In contrast to the
former studies, the retro-cycloaddition reaction of related
2-pyrazolino[4′,5′:1,2][60]fullerenes afforded, in addition to
the expected pristine fullerene, a side product whose nature
was not determined.3
Studies have stimulated an interest in this new fullerene
derivative, and in this Letter we report on its unambiguous
structural determination as well as the improvement carried
† Departamento de Química Orga´nica, Universidad Complutense de
Madrid.
‡ Universidad de Castilla-La Mancha.
§ Laboratorio de Difraccio´n de Rayos X, Universidad Complutense de
Madrid.
| Ciudad Universitaria de Cantoblanco.
10.1021/ol801308g CCC: $40.75
Published on Web 08/08/2008
2008 American Chemical Society

Figure 1. C-Alkyl-N-aryl-2-pyrazolino[60]fullerenes investigated
(1a-d).
Figure 2.
1H NMR spectrum of compounds 2 and 3.
out on its synthetic preparation. Moreover, in order to
investigate the interest of the new compound as a building
block in fullerene chemistry, it has been used as starting
material for the preparation of a new fullerene derivative
strongly absorbing in the visible region. Thus, we have
carried out new reactions on a variety of 2-pirazolinofullerene
derivatives (1a-d) bearing different substituents on the pyra-
zoline carbon atom.
For a better understanding of this singular allylic-type
oxidation process involving Cu(II) and to evaluate its possible
scope, we synthesized two new C-Alkyl-N-(4-nitrophenyl)-
2-pyrazolino[60]fullerene derivatives 1c,d (Table 1). These
Reactions of 1a and 1b under standard retro-cycloaddition
conditions3 were monitored by HPLC, and [60]fullerene and
the unknown fullerene-based compounds were isolated by
column chromatography (toluene). A thorough study of this
new compound was performed by using different spectro-
scopic techniques (FT-IR, 1H and 13C NMR, UV-vis, MS).
The results of these analyses clearly indicate that both
derivatives (1a,b) yield the same side compound endowed
with a formyl group on C-3 of the 2-pyrazoline ring, and
whose structure corresponds to compound 2. The study of
both reactions by HPLC showed the formation of a small
shoulder in addition to aldehyde 2 (Figure S1, Supporting
Information), its UV-vis spectrum showing the typical
Table 1. Experimental Conditions used for the Retro-cycloaddition
Reaction of 2-Pyrazolino[60]fullerenes 1c,da and Formation of
Pristine C60 (%) Determined by HPLC
entry
experiment
1c
1d
1
2
3
4
5
6
7
8
o-DCB, 24 h
o-DCB, 48 h
MA, 24 h
59
60
53
78
83
92
84
96
10
19
20
24
77
82
36
70
MA, 48 h
CuTf2, 24 h
CuTf2, 48 h
MA, CuTf2, 24 h
MA, CuTf2, 48 h
a All reactions were performed in o-DCB at reflux; MA ) 30 equiv of
maleic anhydride; CuTf2 ) 1 equiv of copper triflate.
1
features of another fullerene-based compound with a H
NMR spectrum very similar to that observed for 2(Figure 2).
MS analysis revealed that oxidation of a double bond
of the fullerene cage takes place, forming an epoxy group
on the fullerene sphere, affording the new compound 3. Thus
the peak at 911.8 amu for compound 2, as well as the peak
at 928.8 amu (M + 16) for compound 3 are observed in the
MS.
It is important to note that oxidations of alkyl chains in
fullerene cycloadducts are not studied, despite their synthetic
availability and interest for further chemical transformations
molecules bearing a tert-butyl group (1c) and a benzyl unit
(1d) were synthesized by 1,3-dipolar cycloaddition of the
corresponding nitrile-imines, which were in turn generated
from the corresponding hydrazones.4
The highest efficiency for the retro-cycloaddition process
to afford pristine C60 (96%) was obtained for derivative 1c,
where formation of compound 2 or 3 was not detected.
Derivative 1d showed a similar trend, and only the retro-
cycloaddition process was observed. It is important to note,
however, that the retro-cycloaddition rate observed for both
derivatives is higher than that observed for other C-alkyl-
N-(4-nitrophenyl)-2-pyrazolino[60]fullerenes.3
(1) (a) Martín, N.; Altable, M.; Filippone, S.; Martín-Dome´nech, A.;
Echegoyen, L.; Cardona, C. M. Angew. Chem., Int. Ed. 2006, 45, 110. (b)
Lukoyanova, O.; Cardona, C. M.; Echegoyen, L.; Altable, M.; Filippone,
´
S.; Martín Dome´nech, A.; Martín, N. Angew. Chem., Int. Ed. 2006, 45,
These experimental findings support the existence of an
additional allylic-type oxidation process, which occurs
7430.
(2) (a) Martín, N.; Altable, M.; Filippone, S.; Martín-Dome´nech, A.;
Martínez-Alvarez, R.; Suarez, M.; Plonska-Brzezinska, M. E.; Lukoyanova,
O.; Echegoyen, L. J. Org. Chem. 2007, 72, 3840. (b) Da Ros, T.; Prato,
M.; Novello, F.; Maggini, M.; De Amici, M.; De Micheli, C. Chem.
Commun. 1997, 59. (c) Da Ros, T.; Prato, M.; Lucchini, V. J. Org. Chem.
2000, 65, 4289.
(3) Delgado, J. L.; Oswald, F.; Cardinali, F.; Langa, F.; Martín, N. J.
Org. Chem. 2008, 73 (8), 3184.
(4) Espíldora, E.; Delgado, J. L.; de la Cruz, P.; de la Hoz, A.; Lo´pez-
Arza, V.; Langa, F. Tetrahedron 2002, 58, 5821.
3706
Org. Lett., Vol. 10, No. 17, 2008

simultaneously with the retro-cycloaddition reaction. For 1a
and 1b both processes take place, and the result (by HPLC)
is the formation of compound 2 and C60 in an almost 1:1
ratio (see Supporting Information). The behavior observed
for 1d resembles that observed for C-aryl-N-(4-nitrophenyl)-
2-pyrazolino[60]fullerenes, where only the retro-cycloaddi-
tion process was detected. Derivative 1c, which lacks the
allylic hydrogen, gives the highest efficiency for the retro-
cycloaddition process (96%).
weak interactions that contribute to stabilize the supramo-
lecular network. Hydrogen bonds (C-H···O-N) between
nitro and formyl groups (d ) 2.377 Å) and π-π stacking
between p-NO2-phenyl units (d ) 3.095 Å) led to the
formation of fullerene dimers in the crystal (Figure 3).
In order to shed some light on the allylic-type oxidation
process, we carried out a number of experiments under
different conditions. Thus, using the same protocol described
above, derivative 1a was stirred with a catalytic amount (6
% w/w) of copper triflate in refluxing o-DCB for 24 h. HPLC
analysis showed that compound 1a did not undergo any
oxidative process under these conditions, and only the
thermal retro-cycloaddition was observed.
It is worth mentioning that no other catalyst except for
copper(II) triflate such as CuCl2, Cu(OAc)2, KTf, or LaTf3
with different anions or metalic cations afforded aldehyde 2
(HPLC) (see Supporting Information).
Interestingly, reaction of compound 1a under standard
conditions in argon atmosphere and using dry o-DCB (dried
over calcium hydride) as solvent led to the formation of only
aldehyde 2, and no evidence of compound 3 was observed.
This result allowed us to conclude that atmospheric oxygen
could play a role in the oxidation of the double bond on the
fullerene cage to form 3.
We performed new experiments with 1a and 1b under
argon atmosphere in order to fully characterize the isolated
aldehyde 2. Both reactions were monitored by HPLC, and
evolution of the process revealed the competition between
the oxidation and retro-cycloaddition reactions. Once the
reaction was completed (by HPLC), we isolated compound
2 and carried out its full structural characterization. Analysis
by X-ray diffraction of a single crystal obtained by slow
diffusion of hexane vapor into a solution of 1a in chloroben-
zene5 evidenced the chemical structure of compound 2, where
the formyl group is responsible for the existence of different
Figure 3.
X-ray crystal structure of 2:5 (A) π-π stacking
interactions and (B) hydrogen bond interactions.
A plausible explanation for the formation of aldehyde 2
is that the oxidation of 1a and 1b takes place through
coordination of copper either to the N sp2 or the CdN in
the 2-pyrazole ring and to a neighbor CdC of the C60
sphere.6 Although the mechanism of this oxidation is not
yet clear, copper(II) triflate is the reagent that produces the
oxidation by assisting the allylic-type oxidation through the
formation of Cu/O complexes, which upon formation un-
dergo a rapid decomposition to yield compound 2.7 To the
best of our knowledge, this unexpected reaction represents
the first example of an allylic-type oxidation accomplished
in the presence of copper(II) triflate, without using classical
oxidants.8
(5) Crystal data: C68H5N3O3·1.5(C6H5Cl), Mr ) 1080.07, red thin plate
(0.6 × 0.6 × 0.04 mm3), triclinic, space group P-1, a ) 9.9093(8) Å, b
) 10.0293(8) Å, c ) 24.979(2) Å, R ) 80.616(2)°, ꢀ ) 85.699(1)°, γ )
62.232(1)°, V ) 2167.2(3) Å3, Z ) 2, Fcalcd ) 1.655 g cm-3, F(000) )
1089, µ ) 0.191 mm-1, 2θmax ) 50.0°, T ) 296(2) K, 7567 unique
reflections [R(int) ) 0.1106], R1 ) 0.0510, wR2 ) 0.1454 (all data),
GOF(F2) ) 0.957, N0/NV ) 7567/769, highest residual electron density
1.289 e Å-3. X-ray diffraction data were measured on a Bruker Smart CCD
diffractometer, with graphite-monochromated Mo-KR radiation (λ )
0.71073 Å) operating at 50 kV and 35 mA. The intensity data were collected
over a hemisphere of the reciprocal space by combination of three exposure
sets. Each exposure of 20 s covered 0.3 in ω. Reflection range for the data
collection were 1.65° < θ < 25.0°. The first 100 frames were recollected
at the end of the data collection to monitor crystal decay, and no appreciable
decay was observed. Structure solution and refinement: The structure was
solved by direct methods. The refinement was done by full matrix least-
squares procedures on F2 (SHELXTL version 5.1). The non-hydrogen atoms
were refined anisotropically. All hydrogen atoms were calculated at their
geometrical positions and refined as riding on their respective carbon atoms
except H2 bonded to C2 atom (from formyl group) which was located from
Fourier synthesis difference and the coordinates were refined. CCDC 687339
contains the supplementary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.
html (or from the Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB21EZ, UK; fax (+44)1223-336-033; or deposit@
ccdc.cam.ac.uk).
To improve the allylic-type oxidation, we carried out the
reaction of 1a with SeO2 as a classical reagent used in related
allylic oxidations. Compound 1a was heated at reflux in the
presence of an excess of selenium dioxide under argon
atmosphere, and the reaction was monitored by HPLC. In
this case, the reaction was completed in 24 h, and almost no
retro-cycloaddition was detected, thus forming compound 2
in 60% yield.
(6) To shed light on the influence of the fullerene unit, we performed
the same experiments on a similar 2-pyrazolino-based molecule, 3-methyl-
1-phenylpyrazole without the fullerene moiety. TLC analysis of reaction
of this compound with copper(II) triflate in o-DCB at reflux for 2 days
revealed that this derivative does not undergo any oxidation process.
(7) (a) For a review, see: Gamez, P.; Aubel, P. G.; Driessen, W. L.;
Reedijk, J. Chem. Soc. ReV. 2001, 30, 376. (b) Maiti, D.; Lucas, R.; Sarjeant,
A. A. N.; Karlin, K. D. J. Am. Chem. Soc. 2007, 129, 6998. (c) Mahapatra,
S.; Halfen, J. A.; Tolman, W. B. J. Am. Chem. Soc. 1996, 118, 11575.
(8) (a) Hudlicky, M. Oxidations in Organic Chemistry; ACS Monograph
186; American Chemical Society: Washington, DC, 1990. (b) Alvarez, L.
X; Lorraine, C. M.; Sorokin, B. Appl. Catal., A 2007, 325, 303. (c) Hoang,
V. D. M.; Reddy, P. A. N; Kim, T.-J. Organometallics 2008, 27, 1026.
Org. Lett., Vol. 10, No. 17, 2008
3707

Scheme 1
Compound 2 bearing a formyl group on the pyrazoline
ring is suitably functionalized to carry out a wide variety of
further chemical transformations affording new and appealing
derivatives. As an immediate application of 2, we have
carried out its Knoevenagel condensation with malononitrile
(4) to form the dicyanovinylene derivative (5) in moderate
yield (31%) (Scheme 2). The structure of 5 was determined
Figure 4. UV-vis spectra of 1a, 2, and 5 recorded in methylene
chloride (1 × 10-5 M).
results in orange-colored solutions of 5 in organic solvents.
This finding is very important to prepare new colored
fullerenes with stronger absorption properties in the visible
region, which are a key issue in the search for new light-
harvesting materials for the construction of organic solar
cells.
In summary, in contrast to previous studies on fullerene
derivatives, copper(II) triflate is able to oxidate moderately
alkyl-substituted 2-pyrazolino[60]fullerenes to form a formyl
group through an allylic-type oxidation process whose
mechanism is not completely understood. The yield of
formyl-containing fullerene is significantly improved by
using SeO2 as oxidant reagent. The new compound 2 can
be considered an appealing building block that open the way
to the preparation of colored fullerenes of interest in PV
applications.
by spectroscopic measurements (UV-vis, FTIR, 1H and 13
C
NMR, MS). Thus, the presence of the conjugated cyano
groups was confirmed by the intense band at 2222 cm-1 in
the FT-IR spectrum. The 1H NMR spectrum of 5 shows, in
addition to the aromatic protons as two doublets centered at
8.44 and 8.50 ppm, the diagnostic presence of the vinyl
proton at 8.07 ppm. Interestingly, the organic addend on the
fullerene sphere results in a push-pull moiety due to the
electron-accepting ability of the dicyanovinyl unit.
The UV-vis spectrum of compound 5 reveals the strong
influence of the dicyanovinylene group on the electronic
properties. Thus, in contrast to compounds 1a and 2 that
show similar absorption properties with λmax at around 370
nm, compound 5 presents a strong shift to the visible region
with a λmax at 492 nm, with the onset reaching 600 nm
(Figure 4). This dramatic change in the electronic properties
Acknowledgment. This work was supported by the MEC
of Spain (Juan de la Cierva Program and projects CTQ2005-
02609/BQU and Consolider-Ingenio 2010C-07-25200), the
CAM (project P-PPQ-000225-0505) and the ESF (project
05-SONS-FP-021). MEC: CTQ2007-63363/PPQ, Consolider
CSD2007-00007 and JCCM Project PCI 08038.
Scheme 2
Supporting Information Available: Synthetic procedures
and characterization details for the new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL801308G
3708
Org. Lett., Vol. 10, No. 17, 2008