Unusual multistep reaction of C70Cl10 with thiols producing C70[SR]5H

Article abstract of DOI:10.1016/j.tetlet.2016.01.066

We report a reaction of the chlorofullerene C₇₀Cl₁₀ with thiols producing C₇₀[SR]₅H with all organic addends attached around one central pentagon at the pole of the C₇₀ cage. This reaction was shown to proceed via a complicated radical pathway, presumably involving addition, substitution, rearrangement, and/or elimination steps. The obtained C₇₀[SR]₅H products were shown to be very unstable and undergo quantitative decomposition to pristine C₇₀, RSSR, and RSH at elevated temperatures (e.g., 50 °C). Quantum chemical calculations and NMR spectroscopy data showed that cleavage of organic addends from the fullerene cage could be induced by solvation effects in solution.

Full text of DOI:10.1016/j.tetlet.2016.01.066

Accepted Manuscript
Unusual multistep reaction of C70Cl10 with thiols producing C70[SR]5H
Ekaterina A. Khakina, Alexander S. Peregudov, Anastasiya A. Yurkova,
Natalya P. Piven, Alexander F. Shestakov, Pavel A. Troshin
PII:
S0040-4039(16)30065-X
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.01.066
TETL 47230
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
5 January 2016
17 January 2016
19 January 2016
Please cite this article as: Khakina, E.A., Peregudov, A.S., Yurkova, A.A., Piven, N.P., Shestakov, A.F., Troshin,
P.A., Unusual multistep reaction of C70Cl10 with thiols producing C70[SR]5H, Tetrahedron Letters (2016), doi: http://
dx.doi.org/10.1016/j.tetlet.2016.01.066
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Unusual multistep reaction of C70Cl10 with
thiols producing C70[SR]5H
Leave this area blank for abstract info.
Ekaterina A. Khakina, Alexander S. Peregudov, Anastasiya A. Yurkova, Natalya P. Piven, Alexander F.
Shestakov and Pavel A. Troshin*

1
Tetrahedron Letters
Unusual multistep reaction of C70Cl10 with thiols producing C70[SR]5H
Ekaterina A. Khakinaa, Alexander S. Peregudovb, Anastasiya A. Yurkovaa, Natalya P. Pivenc, Alexander F.
Shestakova and Pavel A. Troshin*a
a Institute for Problems of Chemical Physics of Russian Academy of Sciences, Semenov Prospect 1, Chernogolovka, 141432, Russia. E-mail: troshin@icp.ac.ru
b A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavylova St. 28, B-334, Moscow, 119991, Russia
c Institute for Energy Problems of Chemical Physics of RAS (Branch), Semenov Ave., Chernogolovka, 141432, Russia
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
We report a reaction of the chlorofullerene C70Cl10 with thiols producing C70[SR]5H with all
organic addends attached around one central pentagon at the pole of the C70 cage. This reaction
was shown to proceed via a complicated radical pathway, presumably involving addition,
substitution, rearrangement and/or elimination steps. The obtained C70[SR]5H products were
shown to be very unstable and undergo quantitative decomposition to pristine C70, RSSR and
RSH at elevated temperatures (e.g. 50 oC). Quantum chemical calculations and NMR
spectroscopy data showed that cleavage of organic addends from the fullerene cage could be
induced by solvation effects in solution.
Available online
Keywords:
Fullerenes
Thiols
Radical reactions
ESR spectroscopy
DFT calculations
2009 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Chlorinated fullerenes can be easily synthesized with high
selectivity and excellent yields from the parent C60 or C70
compounds.1-4 They represent very promising precursor compounds
which can be converted to many different functional derivatives
using halogen substitution reactions.
We have shown that chlorofullerene C70Cl10 reacts with thiols
in the presence of tertiary amines leading to the cleavage of all
halogen atoms from the equator of the molecule and addition of
five sulfide groups and one proton to different positions of the
carbon cage (Scheme 1).
The chemistry of halogenated fullerenes was pioneered by Taylor
and co-workers who revealed that chlorofullerene C60Cl6 reacts with
C- and O-nucleophiles such as aromatic hydrocarbons in the
presence of Lewis acids, MeLi, H2C=CH-CH2Si(CH3)3 and
alcohols.5-9 More recently we have shown that highly selective
reactions of C60Cl6 could be used for the efficient synthesis of water-
soluble fullerene derivatives bearing amine, carboxylic and
phosphonic acid groups as well as a number of other compounds.10-14
The chemistry of C70Cl10 remains less investigated which
might be related to its lower availability and decreased molecular
symmetry. Taylor and co-workers achieved the synthesis of
C70Me8, C70Ph8, C70Ph9OH, and C70Ph10 from C70Cl10.15-18 We
have reported the preparation of water-soluble carboxylic acid
derivatives of [70]fullerene and its phosphorous-containing
derivatives C70[PO(OEt)2]nHn (n=1, 2).19-20
Scheme 1. Reaction of C70Cl10 with thiols
This reaction demonstrated reasonably high selectivity. Thus,
treatment of C70Cl10 with the methyl ester of 2-
mercaptopropionic acid produced compound 1a (35-40%), traces
of compound 2a and considerable amounts of pristine C70 (40-
60%) as a major side product.
The molecular compositions of 1a and 2a were confirmed by
ESI mass spectrometry (see ESI Fig. S1, S4). The molecular
structure of 1a was deduced from the NMR spectra (Fig. 1 and
ESI S2-S3). Thus, the 1H NMR spectrum (Fig. 1a) exhibited a set
of signals corresponding to three types of symmetrically non-
equivalent organic addends in a 2:2:1 ratio. The signal of the new
proton attached to the carbon cage appeared at 4.88 ppm. It was
Direct addition of various reagents (radicals or ion radicals) to
the carbon cage of pristine [70]fullerene was used to prepare
derivatives bearing hydrogen,21 aryl,22 tert-butoxyperoxide,23-24
amine25 or trifluoromethyl26-27 groups.
Herein, we report an unprecedented reaction of C70Cl10 with
thiols in the presence of organic bases (tertiary amines).

2
Tetrahedron
notable that similar spectra were previously obtained for
stable “pole-on” structure 1 can “survive” under the reaction
conditions and avoid transformation to pristine C70.
C60(SR)5H derivatives of [60]fullerene.13 Therefore, we can
conclude that the reactions of C60Cl6 and C70Cl10 with thiols
proceed in the same way and produce isotypical products. Indeed,
the 13C NMR spectrum obtained for 1a (Fig. 1b) conforms with
the Cs molecular symmetry of this compound.
Compound 1a demonstrated rather intriguing behavior. First of
all, it underwent quantitative decomposition to C70, RSH and
RSSR at slightly elevated temperatures (50-60 oC, Scheme 2).
Moreover, such decomposition also occurred with a solid powder
of 1a at room temperature within a few weeks. Most remarkable
was the fact that cleavage of the organic addends from the
fullerene cage in C70(SR)5H could be induced simply by
solvation. In particular, dissolving
a portion of 1a in a
CS2/acetone-D6 mixture contaminated with traces of moisture
produced NMR spectra characteristic for a highly symmetrical
D5h [70]fullerene molecule and low molecular weight by-
products: RSH and RSSR (ESI Fig. S6-S7). Similar
decomposition also occurred in low concentration solutions of 1a
even in dry solvents which did not allow us to obtain UV-VIS
spectra of this compound.
Scheme 2 Facile decomposition of 1a
The experimentally observed instability of C70(SR)5H is
caused by the low energy cost for elimination of the thiol
molecule which amounts to 11.1 kcal/mole in the case of MeSH.
Water catalyzes this process for two reasons: (i) solvation of the
thiol diminishes the energy costs for the RSH elimination step,
and (ii) realization of the water-assisted H-transfer to the SR
substituent on the fullerene cage (avalanche mechanism) has a
low energy barrier. Transformation of the adduct
C70(SMe)5H(H2O) (ESI Fig. S8) into C70(SMe)4(H2O)(HSMe)
(ESI Fig. S9) requires 8.0 kcal/mol and has an energy barrier of
15.3 kcal/mol. The calculated structures of the transition states
are shown in Figure 2a.
Figure 1.1H (a) and 13C NMR (b) spectra and Schlegel diagrams for two
possible isomeric structures (c) of 1a
It should be emphasized that there are two possible isomers of
C70(SR)5H with Cs symmetry, “side-on” and “pole-on” addend
arrangement (Fig. 1c), which satisfy all the spectroscopic data.
However, DFT calculations carried out for the simplest model
C70(SR)5H molecule (R=Me) showed that the “side-on” isomer
(ESI Fig. S5) was considerably less stable (by ~20 kcal/mol)
compared to the “pole-on” structure.
a
b
Figure 2. Computed molecular structures of the transition states. Small
open circles and larger shadowed ones define H and O atoms, respectively.
Key distances are given in Ǻ.
In view of the fact that compound 1a is formed from C70Cl10 via
a sequence of multiple addition, elimination and rearrangement
steps (called “addend dance”), one can expect realization of
thermodynamic control in this reaction. Similar “addend dance”
reactions known for fullerenes also produce the most
thermodynamically stable products.28-29 Additionally, the low
energy barrier for addend elimination from the cage (see below)
also supports the idea that only the most thermodynamically
However, in the presence of an additional water molecule the
+
formation of the ionic structure H5O2 [C70(SMe)5]- (ESI Fig.
S10) from C70(SMe)5H(H2O)2 (ESI Fig. S11) requires only 5.0
kcal/mol and has small energy barrier of 7.2 kcal/mol (Figure
2b). The energy of this structure is practically the same as the
energy of the neutral isomer C70(SMe)4(MeSH)(H2O)2 (ESI Fig.
S12) and the energy of the transition state corresponding to the H

3
+
atom transfer inside the H5O2 moiety (ESI Fig. S13).
a single electron transfer from the RSH molecule to C70Cl10.
Elimination of the RSH molecule induces the following reactions
This assumption is reasonable since C70Cl10 is known as a strong
electron acceptor, while RSH behaves as a good electron donor.
The radical anion [C70Cl10].- is rather unstable and, therefore,
eliminates Cl- and forms the [C70Cl9]. radical. At the same time,
the thiol radical cation stabilizes via elimination of a proton
forming the RS. radical. Recombination of the [C70Cl9]. and RS.
radicals can produce C70Cl9SR which is a product of the
substitution of one chlorine atom in C70Cl10 with a sulfide group.
The presented sequence of steps demonstrates realization of the
desired reaction pathway (I) leading to the target substitution
products. However, the intermediate [C70Cl9]. radical can be
further reduced with another RSH molecule to the corresponding
of decomposition of
1 with elimination of two disulfide
molecules MeSSMe with energy gains of 11.3 and 17.6 kcal/mol
for the first and second steps, respectively.
Thus, the results of the DFT calculations emphasized the
generally low stability of the C70(SR)5H compounds. Indeed, a
facile solvation-induced degradation was observed not just for
1a, but also for a number of other compounds 1b-d which we
attempted to prepare, isolate and characterize (Scheme 1). ESI
mass spectrometry proved that chromatographically isolated
fractions represented toluene solutions of the target 1b-d
compounds (ESI Fig. S14-S17). However, all attempts to
concentrate these solutions under vacuum and obtain solid
samples suitable for NMR characterization were not successful
due to almost complete degradation of these compounds to C70.
The observed surprisingly low stability of the C70(SR)5H
compounds might prevent their practical application. However,
the examined reaction of C70Cl10 with thiols is fundamentally
interesting. The fact that 10 chlorine atoms are replaced with 6
new substituents in 1a suggests that the investigated reaction
involves redox processes when C70Cl10 or some latter
intermediate undergoes partial or complete reduction with RSH
forming RSSR and HCl (trapped as a salt with the amine). We
emphasize that none of the incoming RS- groups or hydrogen
atom attach to the positions which were previously occupied by
chlorine atoms in C70Cl10 which points to a complicated multistep
reaction mechanism.
.
anion which eliminates Cl- and forms C70Cl8. This represents a
competing reaction pathway (II) leading to the reduction
(chlorine elimination) products. It seems that pathway (II) is
favorable in the case of C70Cl10 which explains the formation of
C70(SR)5H (partial elimination – partial reduction product) and
C70 as the major side product resulting from the complete
reductive elimination of addends from the fullerene cage.
In order to shed light on a general nature of the investigated
reaction, we applied ESR spectroscopy using 5,5-dimethyl-1-
pyrroline N-oxide (DMPO) as a radical trap. The ESR spectrum
of the RSH–DMPO–(iPr)2EtN mixture showed a rather weak
signal for a radical impurity which was also detected in the
solution of DMPO alone (Figure 3). However, the addition of
C70Cl10 to the RSH– (iPr)2EtN mixture resulted in the appearance
of a strong multi-line signal which could be attributed to a radical
species, which was formed as a reaction intermediate trapped
with DMPO. We believe that this signal corresponds to the
adduct of DMPO with the RS. radical since a very similar ESR
spectrum was previously reported.30
RSH-DMPO-(iPr)2EtN
RSH-DMPO-(iPr)2EtN+C70Cl10
2000
1900
1800
1700
1600
1500
1400
1300
Scheme 3. Proposed SET mechanism of the reaction of C70Cl10 with thiols
The regiochemistry of the reaction of C70Cl10 with thiols is very
interesting. We believe that the spin density in the [C70Cl9]. and
intermediate [C70Xn]. (X=Cl or SR) radicals is delocalized
between multiple centers on the C70 cage. It is known that
attachment of nitrogen-centered radicals occurs near the central
pentagon at the pole of the C70 cage.25 Additionally, the reaction
of C70Cl10 with P(OEt)3, proceeding via a radical pathway, also
produced two compounds bearing organic addends attached at the
poles of the C70 cage.20 Considering these experimental facts it is
reasonable to assume that the spin density in the [C70Xn]. radicals
is high enough at the poles of the cage in comparison with the
equator positions which explains the revealed arrangement of the
sulfide groups in 1a. It is also likely that competition between
pathways (I) and (II) produces a [C70(SR)5]. radical which
undergoes further reduction with the formation of stabilized
328
330
332
334
336
338
Magnetic field (mT)
Figure 3. ESR spectra of the RSH–DMPO–(iPr)2EtN system (weak signal
due to an impurity is visible) and the reaction mixture (RSH–DMPO–
(iPr)2EtN +C70Cl10) in toluene.
The obtained experimental and spectroscopic data allowed us to
propose a tentative mechanism of the reaction of C70Cl10 with
thiols (Scheme 3). We assume that the first step of the reaction is

4
Tetrahedron
cyclopentadienyl-type anion [C70(SR)5]-. This anion undergoes
8 Al.-Matar, H.; Hitchckock, P. B.; Avent, A. G.; Taylor, R. Chem. Commun.,
2000, 12, 1071-1072
protonation during workup and chromatography on silica which
results in isolation of the target products C70(SR)5H such as 1a.
The mechanism of the primary reaction between C70Cl10 and
RSH was also analyzed using DFT calculations and the
corresponding discussion is provided in the ESI. Briefly, the
computational results supported our hypothesis concerning the
possibility of the attachment of RS groups to several favorable
locations on the carbon cage besides the one bearing the leaving
chlorine atom. At the same time, the formation of the
cyclopentadienyl moiety surrounded by five RS groups was
9 Al-Matar, H.; Abdul-Sada, A. K.; Avent, A. G.; Taylor, R. Org. Lett., 2001,
3, 1669-1671.
10 Troshina, O. A.; Troshin, P. A.; Peregudov, A. S.; Kozlovskiy, V. I.;
Balzarini, J.; Lyubovskaya, R. N. Org. Biomol. Chem., 2007, 5, 2783-2791
11 Troshina, O. A.; Troshin, P. A.; Peregudov, A. S.; Balabaeva, E. M.;
Kozlovskiy, V. I.; Lyubovskaya, R. N. Tetrahedron, 2006, 62, 10147-10151
12 Kornev, A. B.; Khakina, E. A.; Troyanov, S. I.; Kushch, A. A.; Deryabin,
D. G.; Peregudov, A. S.; Vasilchenko, A.; Martynenko, V. M.; Troshin, P. A.
Chem. Commun., 2012, 48, 5461-5463
13 Khakina, E. A.; Yurkova, A. A.; Peregudov, A. A.; Troyanov, S. I.; Trush,
V.; Vovk, A. I.; Mumyatov, A. V.; Martynenko, V. M.; Balzarini, J.; Troshin,
P. A. Chem. Commun., 2012, 48, 7158-7160
shown to be
a driving force of the process producing
14 Yurkova, A. A.; Khakina, E. A.; Troyanov, S. I.; Chernyak, A.; Shmygleva,
L.; Peregudov, A. A.; Martynenko, V. M.; Dobrovolskiy, Y. A.; Troshin, P.
A. Chem. Commun., 2012, 48, 8916-8918
thermodynamically favorable product 1 (Scheme 1).
We emphasize that the proposed radical substitution
mechanism shown in Scheme 3 conforms with all experimental
results including the ESR observation of the RS. radicals trapped
with DMPO. We strongly believe that the previously reported
reaction of C60Cl6 with thiols13 also proceeds via a radical
mechanism similar to the one outlined in Scheme 3. Indeed, ESR
spectroscopy revealed virtually identical radical species trapped
with DMPO in the system C60Cl6+RSH+R’3N (ESI Fig. S17).
However, the substitution pathway (I) strongly dominates over
the reduction pathway (II) in the case of C60Cl6 thus producing
C60(SR)5H products with an excellent selectivity. This might be a
consequence of the fact that the substituents occupy exactly the
same positions on the C60 cage where the chlorine atoms were
attached in the parent C60Cl6.
15 Avent, A.; Birkett, P. R.; Darwish, A.; Kroto, H. W.; Taylor, R.; Walton, D.
R. M. Tetrahedron, 1996, 52, 5235-5246
16 Al-Matar, H.; Abdul Sada, A. K.; Avent, A. G.; Taylor, R.; Wei, X.-W. J.
Chem. Soc. Perkin Trans. 2, 2002, 7, 1251-1256
17 Birkett, P. R.; Avent, A. G.; Darwish, A. D.; Kroto, H. W.; Taylor, R.;
Walton, D. R. M. Chem. Commun., 1996, 1231-1232
18 Darwish, A. D.; de Guio, P.; Taylor, R. Fuller. Nanot. Carb. Nanostruct.,
2002, 10, 261-272
19 Kornev, A. B.; Peregudov, A. S.; Martynenko, V. M.; Balzarini, J.;
Hoorelbeke, B.; Troshin, P. A. Chem. Commun., 2011, 47, 8298-8300
20 Khakina, E. A.; Yurkova, A. A.; Novikov, A. V.; Piven, N. P.; Chernyak,
A. V.; Peregudov, A. S.; Troshin, P. A. Mendeleev Commun. 2014, 211-213
21 Spielmann, H. P.; Weedon, B. R.; Meier, M. S. J. Org. Chem., 2000, 65,
2755-2758
22 Sawamura, M.; Toganoh, M.; Iikura, H.; Matsuo, Y.; Hirai, A.; Nakamura,
E. J. Mater. Chem., 2002, 12, 2109–2115
3. Conclusion
23 Xiao, Z.; Wang, F.; Huang, S.; Gan, L.; Zhou, J.; Yuan, G.; Lu, M.;. Pan, J.
J. Org. Chem., 2005, 70, 2060-2066
In conclusion, we report a novel reaction of C70Cl10 involving
thiols as reagents which possesses a radical nature as it was
determined from ESR experiments. Unlike a previously known
Friedel-Crafts arylation method producing mainly C70Ar8/10
derivatives, the investigated reaction proceeds through a more
complicated pathway leading to complete detachment of the
chlorine atoms from the equator of the carbon cage and addition
of organic addends around one of the poles.
24 Gan, L. B.; Huang, S. H.; Zhang, X. A.; Zhang, A. X.; Cheng, B. C.;
Cheng, H.; Li, X. L.; Shang, G. J. Am. Chem. Soc. 2002, 124, 13384-1385
25 Troshina, O. A.; Troshin, P. A.; Peregudov, A. S.; Kozlovskiy, V. I.;
Lyubovskaya, R. N. Eur. J. Org. Chem. 2006, 5243-5248
26 Ignat’eva, D. V.; Goryunkov, A. A.; Tamm, N. B.; Ioffe, I. N.;
Avdoshenko, S. M.; Sidorov, L. N.; Dimitrov, A.; Kemnitz, E.; Troyanov, S.
I. Chem. Commun., 2006, 1778-1780
27 Goryunkov, A. A.; Ignat’eva, D. V.; Tamm, N. B.; Moiseeva, N. N.; Ioffe,
I. N.; Avdoshenko, S. M.; Markov, V. Yu.; Sidorov, L. N.; Kemnitz, E.;
Troyanov, S. I. Eur. J. Org. Chem., 2006, 2508-2512
The obtained C70[SR]5H products were shown to be very
unstable and undergo quantitative decomposition to pristine C70,
RSSR and RSH at elevated temperatures (e.g. 50 oC), under
extended storage at room temperature or in solution due to
solvation effects. The surprisingly low stability of C70[SR]5H
compounds was rationalized using DFT calculations.
28 Troshin, P. A.; Lyubovskaya, R. N.; Ioffe, I. N.; Shustova, N. B.; Kemnitz,
E.; Troyanov, S. I. Angew. Chem. Int. Ed. 2005, 44, 235-237; Troshin, P. A.;
Łapin´ski, A.; Bogucki, A.; Połomska, M.; Lyubovskaya, R. N. Carbon 2006,
44, 2770-2777
29 A. A. Gakh, A. A. Tuinman. Tetrahedron Lett. 2001, 42, 7137-7139; A.
Avent, R. Taylor. Chem. Commun. 2002, 2726-2727
30 Clancy, R.; Cederbaum, A. I.; Stoyanovsky, D. A. J. Med. Chem. 2001, 44,
2035-2038
Acknowledgments
Supplementary Material
This work was supported by Russian Science Foundation
(grant 15-13-00102). We thank Dr. V. K. Koltover for DMPO
sample and useful discussions.
Description of the experimental and DFT calculation procedures,
Figures S1-S18.
References and notes
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Walton, D. R. M. J. Chem. Soc. Chem. Commun., 1993, 15, 1230-1232
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Chem. Commun., 2005, 1, 72-75.
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S .T.; Wei, X. W. J. Chem. Soc. Perkin Trans. 2, 2001, 5, 782-786
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