H-bond-assisted regioselective (cis-1) intramolecular nucleophilic addition of the hydroxyl group to [60]fullerene

Article abstract of DOI:10.1021/jo802152x

The one-step reaction of 2,6-dihydroxyphenylmethyl ketone and sarcosine with [60]fullerene in refluxing chlorobenzene affords, in a totally regioselective process, the cis-1 bicyclic-fused organofullerene through a new intramolecular nucleophilic addition

Full text of DOI:10.1021/jo802152x

H-Bond-Assisted Regioselective (cis-1) Intramolecular Nucleophilic
Addition of the Hydroxyl Group to [60]Fullerene
Marta Izquierdo,† Sílvia Osuna,‡ Salvatore Filippone,† Angel Mart´ın-Domenech,†
Miquel Sola`,*,‡ and Nazario Mart´ın*,†
Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica, UniVersidad Complutense,
E-28040 Madrid, Spain, and Institut de Qu´ımica Computacional and Departament de Qu´ımica,
UniVersidad de Girona, E-17071 Girona, Catalonia, Spain
nazmar@quim.ucm.es
ReceiVed September 26, 2008
The one-step reaction of 2,6-dihydroxyphenylmethyl ketone and sarcosine with [60]fullerene in refluxing
chlorobenzene affords, in a totally regioselective process, the cis-1 bicyclic-fused organofullerene through
a new intramolecular nucleophilic addition of one hydroxy group to the fullerene double bond. Experimental
findings reveal the presence of a methyl group on C-2 of the pyrrolidine ring as an essential requirement
for the cyclization process, whereas the existence of a H-bond between a second hydroxylic group and
the nitrogen atom of the pyrrolidine ring seems to favor the approaching geometry without determining
the reaction outcome. Theoretical calculations using the two-layered ONIOM approach and density
functional theory support the experimental findings, predicting the strong impact that the presence of the
methyl substituent on the C-2 of the pyrrolidine ring has on the molecular geometry and, hence, on the
intramolecular cyclization process.
Introduction
fullerenes with desired specific chemical and electronic struc-
tures of interest in materials science and biomedical applica-
tions.4
Since the preparation of fullerenes in macroscopic quantities
in 1990,1 a plethora of fullerene derivatives have been synthe-
sized by following the wide variety of effective methods
currently available for the chemical modification of fullerenes.2
In this regard, despite the intensive efforts dedicated to the
functionalization of fullerenes, a wide variety of fundamental
reactions in the arsenal of organic chemistry have never been
investigated in fullerene science.3 Furthermore, still there is a
demand to develop better protocols to prepare tailor-made
Cycloaddition reactions, in particular, Diels-Alder and 1,3-
dipolar cycloaddition, have been, by large, the most studied and
successful reactions for preparing fullerene derivatives. How-
ever, nucleophilic addition of carbon nucleophiles as well as
other species involving nitrogen (cyanide, amines), oxygen
(alkoxides, hydroxides), phosphorus, and others such as silicon
and germanium have also been extensively studied and a wide
variety of derivatives bearing heteroatoms were prepared.2
† Universidad Complutense.
‡ Universidad de Girona.
We have recently developed a methodology directed to the
synthesis of novel fused pyrrolidinofullerenes, from suitably
functionalized pyrrolidino[3,4:1,2][60]fullerenes, as starting
materials for preparing a variety of unprecedented modified
fullerenes.5
(1) Kra¨tschmer, W.; Lamb, L. D.; Fostiropoulos, K.; Huffman, D. R. Nature
(London) 1990, 347, 354–358.
(2) For some recent books, see: (a) Hirsch, A. The Chemistry of Fullerenes;
Wiley-VCH:, Weinheim, Germany, 2005. (b) Fullerenes: From Synthesis to
Optoelectronic Properties; Guldi, D. M., Mart´ın, N., Eds.; Kluwer Academic
Publishers: Dordrecht, The Netherlands, 2002. (c) Taylor, R. Lecture Notes on
Fullerene Chemistry: A Handbook for Chemists; Imperial College Press: London,
1999. (d) Fullerenes; Langa, F., Nierengarten, J.-F., Eds.; RSC Publishing:
Cambridge, U.K., 2007.
(4) (a) Nierengarten, J.-F. Top. Curr. Chem. 2003, 228, 87. (b) Nierengarten,
J.-F. New J. Chem. 2004, 28, 1177–1191. (c) Mart´ın, N. Chem. Commun. 2006,
2093–2104.
(3) Mart´ın, N.; Altable, M.; Filippone, S.; Mart´ın-Domenech, A. Synlett 2007,
20, 3077–3095.
1480 J. Org. Chem. 2009, 74, 1480–1487
10.1021/jo802152x CCC: $40.75 2009 American Chemical Society
Published on Web 01/06/2009

Nucleophilic Addition of the Hydroxyl Group to 60Fullerene
SCHEME 1. Synthesis of Fulleropyrrolidines 3a and 3b
In this work we describe the first observation of an intramo-
lecular nucleophilic addition of the hydroxyl group of a phenol,
covalently linked to the C-2 of the pyrrolidinofullerene, to a
double bond of the C60 sphere assisted by the H-bond formed
between the pyrrolidine nitrogen and a second hydroxyl group.
This intramolecular H-bond determines the favorable geometry
and close proximity of the second OH group to the reactive
fullerene double bond. To the best of our knowledge, this is
the first nucleophilic addition of a neutral hydroxyl group
(phenol) to the fullerene sphere forming a fused oxygen
heterocyclic ring. The reaction proceeds smoothly without the
presence of any catalyst, in contrast to most of the previous
examples reported in the literature on the nucleophilic attack
of alkoxides to fullerenes, which require basic conditions to
generate in situ the alkoxide species,6 or photosensitized electron
transfer.7 Defined alkoxy fullerenes have also been obtained by
nucleophilic substitution reactions of alkoxides with previously
prepared halogenofullerenes.8
SCHEME 2. Synthesis of Fulleropyrrolidine 6
Related polyhydroxylated fullerenes (fullerenols or fullerols)
are a group of elusive fullerene derivatives that exhibit interest-
ing biological properties as radical scavengers.9 These com-
pounds have been typically isolated as a complex mixture of
different isomers, and only recently, they have been obtained
in a controlled way by different chemical protocols.10
In order to gain a better understanding on the mechanism of
the intramolecular nucleophilic addition of the hydroxyl group
of the phenol moiety to the fullerene sphere, we have carried
out theoretical calculations at the density functional theory
(DFT) level using the two-layered ONIOM approach.
The new compounds (3a,b) were easily obtained in moderate
yields by simply heating compounds 2a,b, C60, and sarcosine
(1) in chlorobenzene at reflux temperature, and their chemical
structures were unambiguously confirmed by spectroscopic
techniques.12 Interestingly, the H NMR spectra revealed the
1
presence of the proton for the OH group of 3a,b at 11.12 and
11.59 ppm, respectively (see Figure S20 in Supporting Informa-
tion for more details about the optimized molecular structure
of 3a). These values show that the presence of the methoxy
group in the ortho position in 3b has a strong impact on the
molecular geometry, which results in a closer position of the
OH group to the nitrogen atom of the pyrrolidine ring. Thus, a
(weak) H-bond is formed that is in agreement with the chemical
shift observed for 3b in comparison with 3a (∆δOH ) 0.47).13
Furthermore, no addition reaction occurred between the OH
group and a double bond of the fullerene cage.
These results are in good agreement with those previously
reported by Nierengarten on related 2-arylfulleropyrrolidine
systems in which the substituent in the ortho position is located
atop the fullerene sphere.14 Interestingly, although the formation
of compounds 3a,b can take place affording two diastereomeric
conformers, under our experimental conditions (refluxing chlo-
robenzene) only the atropisomers with the ortho substituent
placed atop the fullerene skeleton were obtained. These
experimental findings have been accounted for by the high
rotational energy barrier (ca. 30 kcal mol-1) exhibited by these
ortho-substituted derivatives, which prevents the free rotation
of the aryl group, affording only one atropisomer in a diaste-
reoselective manner.14
Results and Discussion
The syntheses of the starting functionalized pyrrolidinof-
ullerenes were carried out by following the protocol previously
reported by Prato for these fullerene derivatives.11 Since our
first goal was to show that the pyrrolidine nitrogen could
efficiently participate in the formation of an intramolecular
H-bond with a geometrically close hydroxyl group, we decided
to carry out the synthesis of compounds 3a,b bearing one OH
group (3a) or one OH and one OMe groups (3b) in the ortho
position to favor the proximity to the nitrogen atom (Schemes
1 and 2). Alternatively, the OH group could prefer to react with
the fullerene double bond if the favored geometry would allow
the proximity of both reactant groups.
(5) (a) Mart´ın, N.; Altable, M.; Filippone, S.; Mart´ın-Domenech, A. Chem.
Commun. 2004, 1338–1339. (b) Mart´ın, N.; Altable, M.; Filippone, S.; Mart´ın-
Domenech, A.; Poater, A.; Sola`, M. Chem. Eur. J. 2005, 11, 2716–2729. (c)
Mart´ın, N.; Altable, M.; Filippone, S.; Mart´ın-Domenech, A.; Gu¨ell, M.; Sola`,
M. Angew. Chem., Int. Ed. 2006, 45, 1439–1442. (d) Gu¨ell, M.; Altable, M.;
Filippone, S.; Mart´ın-Domenech, A.; Sola`, M.; Mart´ın, N. J. Phys. Chem. A
2007, 111, 5253–5258.
(6) Fukuzumi, S.; Nakanishi, I.; Maruta, J.; Yorisue, T.; Suenobu, T.; Itoh,
S.; Arakawa, R.; Kadish, K. M. J. Am. Chem. Soc. 1998, 120, 6673–6680.
(7) Lem, G.; Schuster, D. I.; Courtney, S. H.; Lu, Q.; Wilson, S. R. J. Am.
Chem. Soc. 1995, 117, 554–555.
(8) Avent, A. G.; Birkett, P. R.; Darwish, A. D.; Houlton, S.; Taylor, R.;
Thomson, K. S. T.; Wei, X.-W. J. Chem. Soc. Perkin Trans. 2 2001, 782–786.
(9) (a) Chiang, L. Y.; Lu, F.-J.; Lin, J.-T. J. Chem. Soc., Chem. Commun.
1995, 1283–1284. (b) Dugan, L. L.; Gabrielsen, J. K.; Yu, S. P.; Lin, T.-S.;
Choi, D. W. Neurobiol. Dis. 1996, 3, 129–135.
(10) (a) Husebo, L. O.; Sitharaman, B.; Furukawa, K.; Kato, T.; Wilson,
L. J. J. Am. Chem. Soc. 2004, 126, 12055–12064. (b) Tajima, Y.; Hara, T.;
Honma, T.; Matsumoto, S.; Takeuchi, K. Org. Lett. 2006, 8, 3203–3205. (c)
Meier, M. S.; Kiegiel, J. Org. Lett. 2001, 3, 1717–1719. (d) Wang, G.-W.; Li,
F.-B.; Xu, Y. J. Org. Chem. 2007, 72, 4774–4778.
(12) The reaction of 1 with 2b afforded, in addition to the expected compound
3b in 25% yield, a minor compound 4 (8% yield), which was identified as the
parent unsubstituted pyrrolidino[3,4:1,2][60]fullerene. The formation of this
compound in which the aryl group on the pyrrolidine ring has been lost is not
clear yet. However, some related cases have been reported in the literature. See:
(a) Zhou, D.; Tan, H.; Luo, C.; Gan, L.; Huang, C.; Pan, J.; Lu¨, M.; Wu, Y.
Tetrahedron Lett. 1995, 36, 9169–9172. (b) Gan, L.; Zhou, D.; Luo, C.; Tan,
H.; Huang, C.; Lu¨, M.; Pan, J.; Wu, Y. J. Org. Chem. 1996, 61, 1954–1961. (c)
Lu, X.; He, X.; Feng, L.; Shi, Z.; Gu, Z. Tetrahedron 2004, 60, 3713–3716.
(13) Although the presence of two electron-releasing methoxy groups in the
benzene ring could have an impact on the acidic character of the OH group,
their relative meta position prevents the conjugative effect. A weak inductive
effect cannot be, however, ruled out.
(11) (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. (c)
Tagmatarchis, N.; Prato, M. Synlett 2003, 768–779.
(14) Ajamaa, F.; Figueira, T. M.; Bourgogne, C.; Holler, M.; Fowler, P. W.;
Nierengarten, J.-F. Eur. J. Org. Chem. 2005, 3766–3774.
J. Org. Chem. Vol. 74, No. 4, 2009 1481

Izquierdo et al.
SCHEME 4. 1,3-Dipolar Cycloaddition Reaction of
SCHEME 3. 1,3-Dipolar Cycloaddition Reaction of
Sarcosine and 2,6-Dihydroxyphenyl Methyl Ketone
Sarcosine and 2,6-Dihydroxybenzaldehyde
compound 8 in 12% yield (50% based on recovered C60),
together with the desired cyclic compound 9 resulting from the
intramolecular nucleophilic addition of the OH to the fullerene
double bond, which was obtained as the main reaction product
(31% yield, 50% based on recovered C60). It is interesting to
note that because of the chain length between the reactive OH
and CdC groups, the favored cyclization process according to
Baldwin’s rules16 (6-exo-trig) affords a hexagonal heterocyclic
ring (dihydropyran) fused simultaneously to the pyrrolidine and
benzene rings. This results in a single chemical structure in
which the fullerene sphere is covalently connected to a system
formed by three rings that are forming a fourth ring through
the intramolecular H-bond.
To prove that cyclic compound 9 is formed from the open
compound 8 by subsequent intramolecular nucleophilic addition
of the OH group to the fullerene double bond, 8 was heated in
refluxing chlorobenzene for 4 h and quantitative transformation
into cyclic compound 9 was observed by HPLC. Interestingly,
the proton of the OH group forming the hydrogen bond in
compounds 8 and 9 appeared significantly deshielded at 13.92
and 13.23 ppm, respectively, thus confirming the existence of
the H-bond. Furthermore, the second free OH group of
compound 8 was observed at 4.85 ppm, as expected for the
phenol moiety, whereas compound 9 exhibited the proton
connected to the sp3 carbon of the fullerene sphere at 6.29 ppm,
in good agreement with related systems.17
It is worth mentioning that the intramolecular addition of the
OH group to the double bond of the fullerene proceeds in a
totally regioselective and site-selective manner forming exclu-
sively the cis-1 isomer18 in which the oxygen atom is linked to
the carbon adjacent to the pyrrolidine ring.
To determine the influence that the presence of the methyl
group on the C-2 of the pyrrolidine ring has on the cyclization
process, resulting from the nucleophilic attack of the OH group
to the fullerene double bond, affording compound 9, we decided
to carry out the reaction of 2,6-dihydroxybenzaldehyde (10) with
sarcosine (1) and C60 in refluxing chlorobenzene (Scheme 4).19
The formed compound 11 has two hydroxyl groups as in 8 and
9 but is lacking the methyl group on C-2, which has been
replaced by a H atom.
To favor the chemical reactivity of these fullerenes, a double
substitution should be present on C-2 of the pyrrolidime ring,
similarly to the Thorpe-Ingold effect previously observed for
fuller-1,6-enynes.5 In this regard, fulleropyrrolidines bearing a
methyl group on the C-2 of the pyrrolidine ring fulfill the above
requirements, resulting in a different geometry for the reaction
of the OH with the fullerene double bond, and in addition, they
were easily prepared in one simple synthetic step. Thus, we
have obtained compound 6 in 25% yield (50% based on
recovered C60) by reaction of sarcosine (N-methyglycine, 1),
commercially available o-hydroxyphenyl methyl ketone (5), and
C60 in refluxing chlorobenzene. It is worth mentioning that the
reactions of sarcosine with ketones proceeds with yields and
efficiencies lower than those reported for aldehydes.15
Interestingly, in contrast to the previous examples 3a,b, the
1H NMR spectrum of compound 6 reveals the presence of the
proton of the OH group at 13.13 ppm (deshielding effect of
∼2 ppm in comparison with compound 3a), which clearly
suggests the existence of a strong H-bond between the OH and
the N atom of the pyrrolidine ring. This experimental result
indicates that the H-bond is formed with preference to the
nucleophilic addition of the OH to the fullerene double bond,
thus supporting the experimental findings for the location of
the OH group atop the fullerene sphere.14 Once again, although
two possible atropisomers can be obtained for 6, only one was
observed according to NMR data (see Supporting Information)
in a diastereoselective mode. This is confirmed by the relative
energies of the optimized structures for the different conformers
of structure 6 depicted in Figure S21 in Supporting Information.
Taking advantage of the above experimental findings, we
decided to carry out the synthesis of new pyrrolidinofullerenes
endowed with a phenyl group on the C-2 of the pyrrolidine
ring bearing two OH groups at C-2′ and C-6′ positions.
Furthermore, in order to favor the geometrical approach of the
second OH group to the fullerene double bond, it is anticipated
that a methyl group should also be present at C-2 of the
pyrrolidine ring.
The new compound 11 was obtained in 20% yield (28% based
on recovered C60), and the 1H NMR spectrum clearly revealed
a singlet at 11.76 ppm, which indicates the presence of a (weak)
H-bonding between the OH group and the pyrrolidine nitrogen
Thus, we designed compound 8, which fulfils the above
requirements. Its preparation also involves one synthetic step
as is depicted in Scheme 3. Reaction of sarcosine (1) and C60
with commercially available 2,6-dihydroxyphenyl methyl ketone
(7) in chlorobenzene at reflux temperature yielded the expected
(16) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734–736.
(17) Altable, M.; Filippone, S.; Mart´ın-Domenech, A.; Gu¨ell, M.; Sola`, M.;
Mart´ın, N. Org. Lett. 2006, 8, 5959–5962.
(18) For a systematic and simple site labelling system to indicate the relative
positional relationships of addends in fullerene derivatives, see: Hirsch, A.;
Lamparth, I.; Karfunkel, H. R. Angew. Chem., Int. Ed. 1994, 33, 437–438.
(19) We want to thank to one of the referees for this interesting suggestion,
which has allowed a better understanding of this cyclization process.
(15) Maggini, M.; Menna, E. In Fullerenes: From Synthesis to Optoelectronic
Properties; Guldi, D. M., Mart´ın, N., Eds.; Kluwer Academic Publishers:
Dordrecht, 2002; Chapter 1, pp 1-50. See also: (a) Illescas, B.; Rife, J.; Ortun˜o,
R. M.; Mart´ın, N. J. Org. Chem. 2000, 65, 6246–6248. (b) Illescas, B.; Mart´ın,
N.; Poater, J.; Sola`, M.; Aguado, G. P.; Ortun˜o, R. M. J. Org. Chem. 2005, 70,
6929–6932.
1482 J. Org. Chem. Vol. 74, No. 4, 2009

Nucleophilic Addition of the Hydroxyl Group to 60Fullerene
atom, similarly to that found in 3b. Furthermore, in agreement
with this finding, the other OH group appears at 4.75 ppm, as
that found for compound 8. Interestingly, the singlet of the C-H
proton of the pyrrolidine ring appears at 5.81 ppm. The above
assignment was ascertained by adding D2O to the NMR tube
and observing the disappearance of the two signals at 11.76
and 4.75 ppm corresponding to the hydroxyl groups, without
altering the proton at 5.81 ppm.20
This result clearly confirms the presence of the methyl group
on C-2 of the pyrrolidine ring as a necessary requirement for
the cyclization process. However, the presence of the H-bond
between the OH group ortho to the phenyl ring and the N atom
is not so critical since compound 8 having the H-bond is formed
and isolated. Nevertheless, the presence of the H-bond seems
to favor the cyclization process provided that it orientates
favorably the second OH group on the phenyl ring to the
fullerene surface.
Electrochemistry. We have studied the electrochemical
properties of the novel compounds (6, 8, and 9) by cyclic
voltammetry (CV) in o-DCB/MeCN (4:1) as solvent at room
temperature and by using tetrabutylammonium perchlorate as
the supporting electrolyte. The characteristic shapes of the redox
waves and their unequivocal position on the potential scale
virtually fingerprint the individual electrochemical properties
of the different redox systems. For this reason, CV has been
labeled as an electrochemical spectroscopy.21 In our case, the
saturation of one olefinic double bond in fulleropyrrolidines 6
and 8 should lead, in principle, to electrochemical behavior
different from that shown by the related compound 9 in which
two fullerene double bonds are saturated. This should raise the
LUMO energy level, and therefore the reduction waves should
be shifted toward more negative potentials, thus slightly reducing
their accepting ability.22 Therefore, a voltamperometric study
of these compounds should allow us to determine the electronic
effect of the substitution pattern on the electrochemical proper-
ties of the compounds obtained and, simultaneously, to use CV
as a useful characterization technique.
FIGURE 1. Cyclic voltammograms of compounds 8 and 9 measured
in o-DCB/MeCN (4.1) at 100 mV s-1
.
Finally, although it could be expected that compound 9
exhibits a reduction wave significantly shifted to more negative
values due to the saturation of two double bonds on the C60
core, the experimental values reveal that the first reduction wave
is very close to that found for the first reduction wave in
compound 8 with only one saturated double bond. This finding
can be accounted for by the presence of the electronegative
oxygen atom directly connected to the fullerene skeleton, which
decreases the LUMO energy, thus compensating the effect of
the saturation of a second double bond in 9.
This behavior is in agreement with other related examples in
which the presence of strong electronegative atoms on the
fullerene surface has a strong impact on the reduction potential
values observed for these organofullerenes.23
Computational Details. Full geometry optimizations were
carried out with the two-layered ONIOM approach24,25 using
the Gaussian 03 program.26 The density functional theory (DFT)
SVWN method27,28 together with the standard STO-3G basis
set29 was used for the low level calculations and the hybrid
Thus, pyrrolidino[3,4:1,2[60]fullerene (6) presented three
reversible reduction waves (-0.859, -1.259, -1.831 V) at
values more negative than those of the parent C60 (-0.747,
-1.152, -1.627 V) (see Supporting Information). Interestingly,
compounds 8 and 9 showed a similar behavior with the first
two reversible reduction waves (8: -0.871, -1.260 V; 9:
-0.854, -1.246 V) corresponding to the formation of the
radical-anion and dianion species of the C60 moiety.
To illustrate the electrochemical behavior of these organof-
ullerenes, the CVs of 8 and 9 are shown in Figure 1. Compounds
8 and 9 showed, in addition to the first two reversible reduction
waves, the presence of an irreversible additional wave at 1.888
V (8) and 1.885 V (9). The irreversible character of this third
reduction wave suggests the participation of the organic addend.
In fact, compound 8 presents another wave at 1.760 V, whereas
this wave is observed for 9 at 2.095 V.
(23) Suzuki, T.; Maruyama, Y.; Akasaka, T.; Ando, W.; Kobayashi, K.;
Nagase, S. J. Am. Chem. Soc. 1994, 116, 1359–1363.
(24) Svensson, M.; Humbel, S.; Froese, R. D. J.; Matsubara, T.; Sieber, S.;
Morokuma, K. J. Phys. Chem. 1996, 100, 19357–19363.
(25) Dapprich, S.; Koma´romi, I.; Byu, K. S.; Morokuma, K.; Frisch, M. J.
J. Mol. Struct. (Theochem) 1999, 461-462, 1–21.
(26) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery Jr., J. A.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci,
B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.;
Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian,
H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski,
J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg,
J. J.; Zakrzewski, G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.;
Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.;
Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.;
Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill,
P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.;
Gaussian 03, ReVision C.01; Gaussian, Inc.: Pittsburgh, PA, 2003.
(20) Whereas the signals corresponding to the fullerene moiety are easily
observed at 527, 575, 1150-1190 and 1432-1462 cm-1 in the FTIR spectra,
the signals over 3000 cm-1 do not clarify the existence of H-bonding. This
experimental finding has also been observed in related systems where the phenolic
hydroxylic group is forming a H bond with a close nitrogen atom (Lachaud, F.;
Quaranta, A.; Pellegrin, P. D.; Charlot, M.-F.; Un, S.; Leibl, W.; Aukauloo, A.
Angew. Chem., Int. Ed. 2005, 44, 1536-1540). Nevertheless, the presence or
absence of H-bonding is unambiguously determined by 1H NMR spectroscopy.
(21) Heinze, J. Angew. Chem., Int. Ed. 1984, 23, 831–847.
(22) Echegoyen, L.; Echegoyen, L. E. Acc. Chem. Res. 1998, 31, 593–60.
J. Org. Chem. Vol. 74, No. 4, 2009 1483

Izquierdo et al.
SCHEME 5. Different Conformers Considered for the
Model System 1,3-Benzenediola
a The relative energies represented in black have been calculated at the
B3LYP/6-31G(d) level while energies in parentheses have been obtained
using the MP2 method with 6-31G(d) basis set at the B3LYP/6-31G(d)
optimized geometries.
density functional B3LYP method30-32 with the standard
6-31G(d) basis set33,34 was employed for the high level system.
Single point calculations using the ab initio method MP2 at
6-31G(d) for the high level and the DFT method SVWN level
with the STO-3G basis set for the low level (i.e., ONIOM2(MP2/
6-31G(d): SVWN/STO-3G)//ONIOM2(B3LYP/6-31G(d):SVWN/
STO-3G)) were performed. All systems were treated with the
spin-restricted formalism. All transition states (TSs) were
characterized by computing the analytical vibrational frequen-
cies, to have one (and only one) imaginary frequency corre-
sponding to the approach of the two reacting molecules.
Calculations of the intrinsic reaction coordinate (IRC) to ensure
that the TSs located in this work were connecting the expected
reactants and products is extremely computationally demanding.
Instead, a full optimization of each transition state was done
by slightly shifting the geometry of the transition state in either
sense following the direction of the transition vector (the
eigenvector corresponding to the negative eigenvalue). Although
this is not equivalent to performing an IRC, it gives a first idea
of which reactants and products are connected through a given
TS.
FIGURE 2. Optimized structures for 11(A) and 11(B) with the most
relevant distances (Å) and angles (deg). The high level of the ONIOM
approach is constituted by the colored atoms. The relative energy
differences at the (ONIOM2(UB3LYP/6-31G(d):SVWN/STO-3G)) is
represented by black, whereas blue is used for the single point
calculation
ONIOM2(UB3LYP/6-31G(d):SVWN/STO-3G)). All energies are ex-
pressed in kcal mol-1
at
(ONIOM2(MP2/6-31G(d):SVWN/STO-3G)//
.
NMR experimental findings. Because of that hydrogen bond,
the bond distance (O-H) of the involved hydroxyl group has
been increased up to 0.987 Å (in the model system it was 0.970
Å). The oxygen atom of the other hydroxyl group that is not
interacting with the π-system of the fullerene surface has the
same bond distance as in the model system, 0.970 Å.
Theoretical Results and Discussion. Our analysis starts with
the B3LYP/6-31G(d) study of the different conformers of the
1,3-benzenediol, where the hydroxyl groups can adopt different
conformations (see Scheme 5). As it can be seen, the most stable
conformation is b and the energy differences among the
structures are very small, where the less stable conformers a
and c are only +0.7 and +0.3 kcal mol-1, respectively, higher
in energy than b. Thus, changing the conformation from a to b
or c requires less than 1 kcal mol-1. Moreover, the O-H bond
distance in these structures is 0.970 Å, which may be used as
a reference for the study of the fullerene system considered.
Thermodynamic calculations of the different conformers of
the N-methylfulleropyrrolidine have shown that the most stable
structures are 11(A) and 11(B) (see Figure 2). In the case of
the most stable conformer 11(B), the substituent benzenediol
has the most favorable conformation found for the model system
b where one of the hydrogen atoms is forming a hydrogen bond
(1.973 Å) with the nitrogen of the pyrrolidine ring. This
The main difference between structures 11(A) and 11(B) is
that the former has one of the hydrogen atoms of the hydroxyl
groups interacting with the π-system of the fullerene surface.
Those π· · ·H interactions are relatively frequent in areas such
as molecular clusters, molecular recognition, drug design, crystal
packing, and so on. A large component of these π· · ·H
interactions comes from the London dispersion forces.35 This
long-range interaction (2.678 Å) does not have a remarkable
stabilization effect, as product 11(B) is 1.1 kcal mol-1 more
stable than 11(A) at the ONIOM2(B3LYP/6-31G(d):SVWN/
STO-3G) level of theory (this energy also includes the change
on the O-H conformation, but we have seen in the model
system that the energy difference associated with such confor-
mational change is about +0.7 kcal/mol). However, it is well-
known that current DFT methods do not, in general, properly
describe dispersion interactions.36 For instance, the sandwich
configuration of benzene is not bound with the PW91, BLYP,
and B3LYP exchange-correlation functionals.37 Such interaction,
however, is relatively well-described (somewhat overestimated)
with the MP2 method.38 For this reason, we have recomputed
the energy differences at the ONIOM2(MP2/6-31G(d):SVWN/
1
theoretical prediction is in good agreement with the above H
(27) Slater, J. C. Quantum Theory of Molecules and Solids; McGraw-Hill:
New York, 1974; Vol. 4.
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Chem. 1994, 98, 11623–11627.
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2261.
(35) Spirko, V.; Hobza, P. Chem. Phys. Chem. 2006, 7, 640–643.
(36) (a) Van Mourik, T.; Gdanitz, R. J. J. Chem. Phys. 2002, 116, 9620–
9623. (b) Ye, X.; Li, Z.-H.; Wang, W.; Fan, K.; Xu, W.; Hua, Z. Chem. Phys.
Lett. 2004, 397, 56–61. (c) Godfrey-Kittle, A.; Cafiero, M. Int. J. Quantum Chem.
2006, 106, 2035–2043. (d) Cerny, J.; Hobza, P. Phys. Chem. Chem. Phys. 2005,
7, 1624–1626. (e) Bautista-Iba´n˜ez, L.; Ram´ırez-Gualito, K.; Quiroz-Garc´ıa, B.;
Rojas-Aguilar, A.; Cuevas, G. J. Org. Chem. 2008, 73, 849–857.
(34) Hariharan, P. C.; Pople, J. A. Theor. Chim. Acta 1973, 28, 213–222.
(37) Tsuzuki, S.; Luthi, H. P. J. Chem. Phys. 2001, 114, 3949–3957.
1484 J. Org. Chem. Vol. 74, No. 4, 2009

Nucleophilic Addition of the Hydroxyl Group to 60Fullerene
STO-3G)//ONIOM2(B3LYP/6-31G(d):SVWN/STO-3G). Some-
what surprisingly, even at this level of theory 11(B) is still more
stable than 11(A), although now by only 1.0 kcal mol-1. As
expected in this kind of π· · ·H interactions, the O-H bond
distance of the hydroxyl group has been hardly modified (0.971
Å). It is worth mentioning that, quite often, this X-H distance
becomes even shorter after the π· · ·H interaction leading to the
so-called blue-shift H-bonds.39 This π· · ·H interaction present
in conformer 11(A) leads to structural effects as the hydrogen
bond between the other hydroxyl group and the nitrogen atom
of the pyrrolidine ring becomes weaker (the H-N distance is
2.059 and 1.973 Å in conformers 11(A) and 11(B), respectively).
Therefore, the extra-stabilization of structure 11(B) can be
partially produced for the strongest hydrogen bond due to the
lack of the above-mentioned π· · ·H interaction.
Experimentally, it has been observed that the cycloaddition
between compounds 1 and 7 leads to the fulleropyrrolidine
derivatives 8 and 9, where in the latter structure an insertion of
the hydroxyl group of the benzene substituent is produced on
the fullerene surface, leading to the cycled fullerene derivative
9. It has also been found that the reaction is clearly favored
when the carbon atom C-2 of the pyrrolidine ring is endowed
with a methyl group instead of a hydrogen atom. To understand
the origin of the effect of this methyl group on the whole
process, we have studied by means of DFT calculations the
mechanism of this O-H insertion to form the new compound
9 as well as the nonobtained compound 12 (similar to 9 but
bearing a H atom instead of the methyl group on C-2 of the
pyrrolidine ring). The calculated energy profile of the two
reaction mechanisms are represented in Figure 3.
FIGURE 3. Representation of the reaction mechanisms profiles when
the substituent R is a hydrogen (black) and a methyl group (blue). The
energy values obtained with the ONIOM2(UB3LYP/6-31G(d):SVWN/
STO-3G) method are expressed in kcal mol-1. Red represents the free
Gibbs energy barriers.
direction of the reactants indicated that TS9 is connected with
reactant 8 and TS12 with reactant 11(A).
As it is shown in Figures 4 and 5, the introduction of the
methyl substituent on the carbon C-2 of the pyrrolidine ring
leads to important structural changes. Those structures with the
above-mentioned substituent (8, 9, and TS9) present a C-C-C
angle involving the C-2 of the pyrrolidine ring as the central
carbon of 113.8°, 115.5°, and 110.6° in the reactant (8), TS
(TS9), and product (9) respectively, whereas this angle is 127.3°,
121.2°, and 114.6° for theoretical compounds 11, TS12, and
12, respectively. This variation on the angle induced by the
absence/presence of the methyl substituent favors, in all cases,
the interaction between the oxygen atom of the hydroxyl group
and the [6,6] bond of the fullerene structure, because those atoms
that will interact are located closer to the fullerene cage. The
O-C distance of the new bond being formed during the insertion
in reactants 11 and 8 is 2.844 and 2.725 Å, respectively.
Moreover, the introduction of the methyl group favors the
hydrogen bond formation between the other hydroxyl group of
the benzene substituent and the nitrogen atom of the pyrrolidine
ring. The H-N distance is modified from 2.059 Å in 11 to 2.654
Å in 12 for the hydrogen substituent case (there is a partial loss
of this H-bond interaction along the OH insertion in this case),
whereas when the methyl group is added this distance is
approximately equal in either reactant, transition state, or final
product (which is about 1.700 Å). Moreover, the N-H-O angle
is modified upon the substituent change (141.6° and 147.5° in
the case of 11 and 8, respectively).
When the substituent on the carbon atom C-2 of the
pyrrolidine ring is hydrogen, the reaction has a reaction energy
of -9.6 kcal mol-1, whereas in the case of the methyl substituent
the reaction energy becomes slightly more favorable (-10.6
kcal mol-1). The molecular structure of reactant 11 is shown in
Figure 2 (species 11(A)), and those of 8, 9, and 12 are depicted
in Figure 4. We have optimized all possible conformers for
species 9 and 12, and those depicted in Figure 4 correspond to
the most stable conformers. Although both systems present
exothermic reaction energies, thermodynamic results favor the
reaction when the methyl group is present.
From the two products 9 and 12 and by means of linear transit
procedures, we have located the transition state structures TS9
and TS12 represented in Figure 5. We have found that the
reaction is also favored from the kinetic point of view when
the carbon C-2 of the pyrrolidine ring presents the -CH3 group;
the reaction barrier for the 8 f 9 process is relatively large
(+40.6 kcal mol-1) but still more favorable than in the 11 f
12 case (+43.0 kcal mol-1). The Gibbs free energy of the
reaction barriers obtained at 298 K are somewhat smaller at
+39.7 and +37.5 kcal mol-1 in the hydrogen and methyl case,
respectively. The reaction is thermodynamically and kinetically
more favorable for the methyl substituent case. The geometry
optimization of each TS done by slightly shifting the geometry
of the TS following the direction of the transition vector in the
Therefore, theoretical calculations clearly support that the
introduction of the methyl substituent on the carbon atom C-2
of the pyrrolidine ring leads to significant structural changes,
which first reduce the distance between the oxygen and the
carbon atom of the fullerene surface that will react, and second
avoids partial loss of the favorable hydrogen bond interaction
between the other hydroxyl group and the nitrogen atom of the
pyrrolidine ring in the TS. These structural changes have
(38) (a) Sinnokrot, M. O.; Sherrill, C. D. J. Phys. Chem. A 2004, 108, 10200–
10207. (b) Tsuzuki, S.; Honda, K.; Uchimaru, T.; Mikami, M.; Tanabe, K. J. Am.
Chem. Soc. 2002, 124, 104–112. (c) Tsuzuki, S.; Uchimaru, T.; Matsumura, K.;
Mikami, M.; Tanabe, K. Chem. Phys. Lett. 2000, 319, 547–554. (d) Lee, E. C.;
Kim, D.; Jurecka, P.; Tarakeshwar, P.; Hobza, P.; Kim, K. S. J. Phys. Chem. A
2007, 111, 3446–3457.
(39) Hermida-Ramo´n, J. M.; Gran˜a, A. M. J. Comput. Chem. 2006, 28, 540–
546.
J. Org. Chem. Vol. 74, No. 4, 2009 1485

Izquierdo et al.
FIGURE 4. Optimized structure (ONIOM2(UB3LYP/6-31G(d):SVWN/STO-3G)) for 8, 9, and 12 with the most relevant distances (Å) and angles
(deg). The high level of the ONIOM approach is constituted by the colored atoms.
the phenyl substitutent on the C-2 atom of the pyrrolidine ring
facilitates the geometrical approach of the OH group to the
fullerene surface. However, the lack of cyclization from
compound 11 bearing two hydroxyl groups reveals the presence
of the methyl group on the pyrrolidine ring as the essential factor
to form the cyclic compound.
Since the new compounds are readily available in a single
synthetic step from 2,6-dihydroxyphenyl methyl ketones, this
new reaction paves the way for the preparation of a variety of
new heterocycle-fused fullerenes of interest in materials science
as well as for testing their biological properties. Work is
currently in progress to expand the reaction to alcohols and other
heterocycles prepared from sulfur and nitrogen atoms as
nucleophilic reagents.
Experimental Section
General Procedure for the Synthesis of Fulleropyrrolidines
3a, 3b, 6, and 11. To a solution of C60 (0.25 mmol, 180 mg) in
chlorobenzene (70 mL) were added 0.50 mmol of the carbonyl
compound (salicylaldehyde for 3a, 4,6-dimethoxysalicylaldehyde
FIGURE 5. Optimized transition state structures (ONIOM2(UB3LYP/
for 3b, o-hydroxy phenylmethyl ketone for 6, 2,6-dihydroxyben-
6-31G(d): SVWN/STO-3G)) for TS12 and TS9 with the most relevant
zaldehyde for 11) and 0.50 mmol (for 3a, 6, and 11) or 2.00 mmol
distances (Å) and angles (deg). The high level of the ONIOM approach
of sarcosine (for 3b). The mixture was refluxed overnight. After
is constituted by the colored atoms.
cooling, the solvent was removed in vacuo, and the crude product
thermodynamic and kinetic consequences, as the reaction is
much more favored from both points of view, leading to a more
exothermic reaction with a lower activation barrier.
was purified by flash chromatography over silica gel, using initially
CS2 as eluent (to separate the unreacted fullerene) and then toluene/
ethyl acetate 9:1 to obtain the corresponding product: 3a in 13%
yield (44% based on recovered C60), 3b in 33% yield (52% based
on recovered C60), 6 in 25% yield (50% based on recovered C60),
and 11 in 20% yield (28% based on recovered C60).
Summary and Conclusions
1
In summary, we have studied for the first time the intramo-
lecular nucleophilic addition of the hydroxyl group to the
fullerene double bond adjacent to the pyrrolidine ring, in a totally
regioselective process, affording the cis-1 isomer. A crucial
factor to accomplish the pyrano-fused fulleropyrrolidine 9 is
the presence of a methyl group on C-2 of the pyrrolidine ring
as a key requirement to optimize the approaching geometry of
the OH group to the fullerene CdC and to help strengthen the
H-bond interaction between the other hydroxyl substituent of
the aryl group and the nitrogen atom of the pyrrolidine ring in
the TS.
Pyrrolidino[3,4:1,2][60]fullerene (3a). H NMR (CDCl3, 298
K, 300 MHz) δ 3.02 (s, 3H, CH3), 4.31 (d, 1H, J ) 9.7 Hz,
CH2-N), 5.11 (d, 1H, J ) 9.7 Hz, CH2-N), 5.14 (s, 1H, CH-N),
6.90 (dd, 2H, J ) 8.08, 7.6 Hz, H-Ar), 7.24 (d, 1H, J ) 7.6 Hz,
H-Ar), 7.39 (d, 1H, J ) 7.6 Hz, H-Ar), 11.12 (s, 1H, OH); 13C
NMR (CDCl3, 298 K, 75 MHz) δ 41.0, 69.1, 70.0, 77.6, 84.2, 110.7,
117.9, 119.9, 120.0, 128.1, 130.3, 130.7, 130.9, 135.7, 136.0, 137.1,
137.4, 139.7, 140.4, 140.5, 140.6, 141.9, 142.0, 142.1, 142.3, 142.4,
142.48, 142.50, 142.53, 142.56, 142.6, 142.9, 142.99, 143.0, 143.1,
143.4, 143.5, 144.7, 144.8, 145.0, 145.03, 145.5, 145.6, 145.69,
145.7, 145.8, 145.9, 145.99, 146.0, 146.2, 146.3, 146.4, 146.5,
146.6, 146.65, 146.7, 146.8, 146.83, 147.7, 147.8, 151.5, 152.0,
153.3, 153.6, 155.5, 157.2, 162.1; FTIR (KBr, cm-1) 526.28,
574.32, 1184.71, 1432.18; MS (MALDI TOF) m/z 869 [M+].
The existence of an intramolecular H-bond between the N
atom of the pyrrolidine ring and a second OH group located on
1486 J. Org. Chem. Vol. 74, No. 4, 2009

Nucleophilic Addition of the Hydroxyl Group to 60Fullerene
1
1
Pyrrolidino[3,4:1,2][60]fullerene (3b). H NMR (CDCl3/CS2,
Compound 8. H NMR (CDCl3, 298 K, 300 MHz) δ 2.75 (s,
298 K, 500 MHz) δ 2.98 (s, 3H, CH3-N), 3.68 (s, 3H, OCH3),
3.76 (s, 3H, OCH3), 4.30 (d, 1H, J ) 9.6 Hz, CH2-N), 5.07 (d,
1H, J ) 9.6 Hz, CH2-N), 5.70 (s, 1H, CH-N), 5.99 (d, 1H, J )
2.3 Hz, H-Ar), 6.04 (d, 1H, J ) 2.3 Hz, H-Ar), 11.59 (s, 1H,
OH); 13C NMR (CDCl3/CS2, 298 K, 125 MHz) δ 41.0, 55.5, 55.7,
69.2, 69.8, 76.8, 91.4, 94.8, 101.7, 128.7, 134.6, 136.2, 136.7, 137.3,
138.2, 138.4, 139.2, 139.9, 140.0, 140.6, 140.7, 142.0, 142.1,
142.12, 142.4, 142.5, 142.59, 142.6, 142.66, 142.7, 143.0, 143.09,
143.1, 143.4, 144.79, 144.8, 144.9, 145.1, 145.5, 145.57, 145.6,
145.65, 145.7, 145.8, 145.9, 146.0, 146.2, 146.3, 146.4, 146.5,
146.57, 146.6, 146.67, 146.7, 146.74, 146.8, 147.1, 147.7, 147.8,
153.2, 153.4, 155.1, 156.1, 159.6, 159.65, 162.1; MS (ESI) m/z
929 [M+]
3H, CH3), 3.00 (s, 3H, CH3-N), 4.72 (AB system, 2H, CH2N),
4.75 (s, 1H, OH), 6.16 (dd, 1H, J ) 8.0, 1.1 Hz, H-Ar), 6.45 (dd,
1H, J ) 8.0, 1.1 Hz, H-Ar), 6.99 (t, 1H, J ) 8.0 Hz, H-Ar),
13.92 (s, 1H, OH); 13C NMR (CDCl3/CS2, 298 K, 75 MHz) δ 30.4,
35.6, 63.9, 68.0, 80.1, 80.7, 108.0, 111.7, 112.8, 128.7, 130.4, 135.6,
136.5, 137.2, 139.1, 139.7, 140.6, 140.7, 141.9, 142.0, 142.07,
142.1, 142.2, 142.4, 142.47, 142.5, 142.7, 142.77, 142.8, 142.81,
143.0, 143.08, 143.1, 143.4, 143.5, 143.6, 144.8, 145.0, 145.1,
145.4, 145.5, 145.6, 145.7, 145.76, 145.8, 145.9, 146.1, 146.2,
146.3, 146.4, 146.5, 146.56, 146.6, 146.62, 146.7, 146.8, 146.83,
147.8, 147.9, 148.1, 153.7, 154.3, 154.4, 155.8, 156.3, 160.9; FTIR
(KBr, cm-1) 526.50, 574.57, 1151.88, 1452.16; MS (ESI) m/z 898
[M+].
Pyrrolidino[3,4:1,2][60]fullerene (6). 1H NMR (CDCl3, 298 K,
300 MHz) δ 2.45 (s, 3H, CH3), 2.97 (s, 3H, CH3-N), 4.74 (d, 1H,
J ) 10.1 Hz, CH2-N), 4.97 (d, 1H, J ) 10.1 Hz, CH2-N),
6.90-6.85 (m, 2H, H-Ar), 7.20 (bs, 1H, H-Ar), 7.52 (dd, 1H, J
) 8.2, 1.5 Hz, H-Ar), 13.13 (s, 1H, OH); 13C NMR (CDCl3, 298
K, 75 MHz) δ 18.1, 35.4, 65.0, 68.0, 79.1, 80.9, 118.3, 119.8, 125.0,
128.1, 128.5, 130.6, 130.9, 132.96, 136.4, 136.5, 136.7, 136.9,
139.3, 140.2, 140.5, 140.6, 141.6, 141.8, 141.9, 142.0, 142.4, 142.5,
142.57, 142.6, 142.7, 142.8, 143.0, 143.1, 143.5, 144.8, 145.0,
145.07, 145.5, 145.6, 145.69, 145.7, 145.74, 145.8, 146.0, 146.2,
146.27, 146.3, 146.4, 146.5, 146.57, 146.6, 146.68, 146.7, 146.8,
Compound 9. H NMR (CDCl3, 298 K, 300 MHz) δ 2.18 (s,
1
3H, CH3), 3.54 (s, 3H, CH3), 4.76 (d, 1H, J ) 12.7 Hz, CH2N),
5.00 (d, 1H, J ) 12.7 Hz, CH2-N), 6.29 (s, 1H, H-C60), 6.85 (dd,
1H, J ) 7.9, 1.1 Hz, H-Ar), 7.03 (dd, 1H, J ) 7.9, 1.1 Hz, H-Ar),
7.39 (t, 1H, J ) 8.0 Hz, H-Ar), 13.23 (s, 1H, OH); 13C NMR
(CDCl3/CS2, 298 K, 75 MHz) δ 36.5, 57.3, 66.2, 71.3, 75.4, 79.4,
92.4, 111.2, 113.7, 117.7, 130.0, 134.4, 135.5, 135.7, 136.2, 137.6,
140.8, 140.9, 141.6, 142.3, 142.46, 142.5, 142.6, 142.7, 142.8,
143.0, 143.2, 143.4, 143.6, 143.8, 143.9, 144.0, 144.04, 144.2,
144.3, 144.4, 144.5, 144.6, 144.7, 144.9, 145.1, 145.2, 145.3, 145.9,
146.1, 146.3, 146.5, 146.6, 146.9, 147.0, 147.05, 147.3, 147.9,
148.2, 148.7, 149.0, 149.1, 149.2, 150.1, 152.8, 154.0, 157.9; FTIR
(KBr, cm-1) 526.90, 575.17, 1197.22, 1462.20; MS (ESI) m/z 898
[M+].
146.9, 147.8, 153.0, 153.3, 153.9, 156.2, 158.5; FTIR (KBr, cm-1
)
526.58, 575.56, 1155.64, 1462.13; MS (MALDI TOF) 883 [M+].
1
Pyrrolidino[3,4:1,2][60]fullerene (11). H NMR (CDCl3, 298
K, 300 MHz) δ 2.99 (s, 3H, CH3), 4.35 (d, 1H, J ) 9.9 Hz,
CH2-N), 5.02 (s, 1H, OH), 5.09 (d, 1H, J ) 9.9 Hz, CH2-N),
5.81 (s, 1H, CH-N), 6.32 (d, 1H, J ) 8.1 Hz, H-Ar), 6.51 (d, 1H,
J ) 8.1 Hz, H-Ar), 7.07 (t, 1H, J ) 8.1 Hz, H-Ar), 11.77 (s, 1H,
OH); 13C NMR (CDCl3, 298 K, 75 MHz) δ 39.6, 67.9, 68.3, 68.6,
75.3, 105.4, 106.5, 109.5, 127.5, 128.5, 129.4, 133.7, 134.8, 135.4,
135.8, 136.0, 138.6, 138.7, 139.2, 139.3, 140.6, 140.66, 140.7,
140.8, 141.0, 141.1, 141.15, 141.18, 141.2, 141.3, 141.4, 141.6,
141.7, 141.75, 142.0, 142.1, 143.3, 143.4, 143.5, 143.6, 143.7,
144.1, 144.2, 144.25, 144.3, 144.33, 144.4, 144.5, 144.7, 144.8,
144.9, 145.0, 145.08, 145.1, 145.2, 145.25, 145.28, 145.3, 145.4,
145.7, 145.8, 146.3, 146.4, 151.4, 152.0, 153.6, 154.3, 154.4, 157.9;
FTIR (KBr, cm-1) 529.08, 1182.63, 1460. 64.
Synthesis of Pyrrolidino[3,4:1,2][60]fullerenes 8 and 9. To a
solution of 0.50 mmol (360 mg) of C60 in chlorobenzene (80 mL)
were added 0.75 mmol (114 mg) of 2,6-dihydroxyphenyl methyl
ketone (7) and 2.0 mmol (178 mg) of sarcosine. The mixture was
refluxed overnight, and after cooling to room temperature, the
solvent was removed in vacuo. The crude product was purified by
flash chromatography over silica gel, using toluene/ethyl acetate
9:1 to obtain compound 8 in 12% yield and compound 9 in 31%
yield.
Acknowledgment. This work was supported by the MEC of
Spain (project CT2005-02609/BQU, project CTQ2008-03077/
BQU and Consolider-Ingenio 2010C-07-25200), the CAM
(project P-PPQ-000225-0505) and the Catalan Departament
d’Universitats, Recerca i Societat de la Informacio´ (DURSI) of
the Generalitat de Catalunya project 2005SGR-00238. S.F.
thanks the MEC for a Ramo´n y Cajal contract, and S.O. thanks
the MEC for Doctoral Fellowship AP2005-2992. M.I. thanks
the European Science Foundation for Predoctoral contract
(SOHYD 05-SONS-FP-021).
Supporting Information Available: General procedure for
the synthesis of fulleropyrrolidines 3a, 3b, 6, and 11. 1H NMR,
13C NMR, and MS spectra of all compounds. HPLC of
compounds 8 and 9. CV voltammogram of compound 6 and
table of reduction potentials. Xyz optimized Cartesians coor-
dinates and total energies for all minima and transition states
located. Optimized structures and relative energies for the
different conformers of species 3a and 6. This material is
available free of charge via the Internet at http://pubs.acs.org.
Compound 8 was further converted quantitatively to 9 by
refluxing in chlorobenzene for 4 h.
JO802152X
J. Org. Chem. Vol. 74, No. 4, 2009 1487