Facile and exclusive formation of aziridinofullerenes by acid-catalyzed denitrogenation of triazolinofullerenes

Article abstract of DOI:10.1021/ol302928d

Variously substituted [6,6]closed aziridinofullerenes were exclusively obtained from acid-catalyzed denitrogenation of triazolinofullerenes without formation of relevant [5,6]open azafulleroids, which are the major products on noncatalyzed denitrogenation

Full text of DOI:10.1021/ol302928d

ORGANIC
LETTERS
2012
Vol. 14, No. 23
6040–6043
Facile and Exclusive Formation of
Aziridinofullerenes by Acid-catalyzed
Denitrogenation of Triazolinofullerenes
Naohiko Ikuma,* Tsubasa Mikie, Yuta Doi, Koji Nakagawa, Ken Kokubo, and
Takumi Oshima*
Division of Applied Chemistry, Graduate School of Engineering, Osaka University,
2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
ikuma@chem.eng.osaka-u.ac.jp, oshima@chem.eng.osaka-u.ac.jp
Received October 24, 2012
ABSTRACT
Variously substituted [6,6]closed aziridinofullerenes were exclusively obtained from acid-catalyzed denitrogenation of triazolinofullerenes
without formation of relevant [5,6]open azafulleroids, which are the major products on noncatalyzed denitrogenation. The mechanistic con-
sideration by DFT calculations suggested a reaction sequence involving initial pre-equilibrium protonation of the triazoline N1 atom, generation of
aminofullerenyl cation by nitrogen-extrusion, and final aziridination.
Aziridinofullerenes, bearing a strained aziridine ring, are
useful synthetic intermediates for highly efficient and
regioselective addition of spherical fullerene cages, such
as acid-induced 1,4-bisaddition of aromatic compounds,1,2
[2 þ 2] cycloaddition with alkynes,2 and isomerization to
azafulleroids.1b,3 The aziridinofullerenes have been hither-
to widely prepared by 1,3-dipolar cycloaddition of azides
toC60, followed by thermal orphotochemicaldenitrogena-
tion of the triazolinofullerene adducts.4 Although some new
synthetic methods of certain aziridinofullerenes by nucleo-
philic addition of chloramines,1 iminophenyliodinanes,2
sulfilimines3 and N,N-dihalosulfonamides5 were recently
reported, the classical denitrogenation of labile triazolino-
fullerenes is still a useful procedure for the introduction of
various substituents and functional groups R at the triazo-
line N1 position such as amino acids,6 saccharides7 and
lipid substituents.8 However, the thermal denitrogenation
has some difficulty in controlling the reaction conditions
and also preventing the formation of major concomitant
[5,6]open azafulleroids.4,9,10 In this context, it is eagerly
desired to find an efficient aziridination reaction and hence
(1) (a) Minakata, S.; Tsuruoka, R.; Nagamachi, T.; Komatsu, M.
Chem. Commun. 2008, 323–325. (b) Tsuruoka, R.; Nagamachi, T.;
Murakami, Y.; Komatsu, M.; Minakata, S. J. Org. Chem. 2009, 74,
1691–1697.
(2) Nambo, M.; Segawa, Y.; Itami, K. J. Am. Chem. Soc. 2011, 133,
2402–2405.
(3) (a) Nakahodo, T.; Okada, M.; Morita, H.; Yoshimura, T.;
Ishitsuka, M. O.; Tsuchiya, T.; Maeda, Y.; Fujihara, H.; Akasaka, T.;
Gao, X.; Nagase, S. Angew. Chem., Int. Ed. 2008, 47, 1298–1300. (b)
Okada, M.; Nakahodo, T.; Ishitsuka, M. O.; Nikawa, H.; Tsuchiya, T.;
Akasaka, T.; Fujie, T.; Yoshimura, T.; Slanina, Z.; Nagase, S. Chem.
Asian J. 2010, 6, 416–423.
(4) (a) Prato, M.; Li, Q. C.; Wudl, F.; Lucchini, V. J. Am. Chem. Soc.
1993, 115, 1148–1150. (b) Grosser, T.; Prato, M.; Lucchini, V.; Hirsch,
A.; Wudl, F. Angew. Chem., Int. Ed. 1995, 34, 1343–1345. (c) Averdung,
J.; Mattay, J. Tetrahedron 1996, 52, 5407–5420. (d) Shen, C. K. F.; Yu,
H.-H.; Juo, C.-G.; Chien, K.-M.; Her, G.-R.; Luh, T.-Y. Chem.;Eur.
J. 1997, 3, 744–748. (e) Wu, R.; Lu, X.; Zhang, Y.; Zhang, J.; Xiong, W.;
Zhu, S. Tetrahedron 2008, 64, 10694–10698.
(5) Nagamachi, T.; Takeda, Y.; Nakayama, K.; Minakata, S.
Chem.;Eur. J. 2012, 18, 12035–12045.
(6) Strom, T. A.; Barron, A. R. Chem. Commun. 2010, 46, 4764–4766.
(7) Kato, H.; Yashiro, A.; Mizuno, A.; Nishida, Y.; Kobayashi, K.;
Shinohara, H. Bioorg. Med. Chem. Lett. 2001, 11, 2935–2939.
(8) (a) Murakami, H.; Watanabe, Y.; Nakashima, N. J. Am. Chem.
Soc. 1996, 118, 4484–4485. (b) Nakanishi, T.; Morita, M.; Murakami,
H.; Sagara, T.; Nakashima, N. Chem.;Eur. J. 2002, 8, 1641–1648. (c)
Murakami, H.; Nakanishi, T.; Morita, M.; Taniguchi, N.; Nakashima,
N. Chem. Asian J. 2006, 1, 860–867.
r
10.1021/ol302928d
Published on Web 11/27/2012
2012 American Chemical Society

we have applied possible acid-catalyzed denitrogenation of
usual triazoline compounds.11 Here, we present the success-
ful and exclusive formation of [6,6]closed aziridinofullerenes
from simple Brønsted/Lewis acid-catalyzed denitrogenation
of triazolinofullerenes.
ammounts (0.1ꢀ0.5 equiv) of superacid CF3SO3H (TfOH)
and Lewis acid BF3 (Table 1).12 For phenyl-substituted 1f,
an equivalent amount of TfOH was needed tocomplete the
denitrogenation (entry 13), probably because of the far
more reduced basicity of the phenyl-sustituted N1-atom than
that of alkyl-substituted one. Noticeably, the [6,6]closed
aziridinofullerenes 2aꢀf were exclusively obtained with no
appreciable amount of [5,6]open azafulleroids as exemplified
for the denitrogenation of 1a under BF3 (Figure 1). The C2v
symmetric structures of 2aꢀf were fully characterized by
1H/13CꢀNMR spectroscopy (Supporting Information).
The preparation of various triazolinofullerenes 1aꢀf is
described in Table 1. For the sake of safety, the employed
alkyl azides were prepared from alkyl halides with sodium
azide in acetonitrile, and then immediately used in situ for the
subsequent 1,3-dipolar cycloaddition by adding C60 solution
in o-dichlorobenzene (o-DCB) at elevated temperature
(∼50 °C). To reduce the multiaddition, the reaction was
ceased at the 60ꢀ70% consumption of C60 (12ꢀ36 h) except
for the syntheses of 1e and 1f, which were prepared at room
temperature for the prolonged reaction time (96 h) to sup-
press the unfavorable thermal denitrogenation into the cor-
responding azafulleroids. The yields of 1aꢀf were compa-
rable with those of the previous syntheses of triazolinofuller-
enes.4 All triazolinofullerenes were fully identified with
1H/13CꢀNMR and HRMS spectrometry.
Table 1. Synthesis of Aziridinofullerenes 2aꢀf via Acid-induced
Denitrogenation of Triazolinofullerenes 1aꢀf
Figure 1. HPLC trace of denitrogenation of 1a into 2a by BF3 in
toluene (cf. Table 1, entry 5).
It was also found that the denitrogenation rates of
triazolinofullerens 1aꢀf by several Brønsted/Lewis acids
depend on their acidities (Table 1). The weaker CH3SO3H
needed longer reaction time (0.5h) than CF3SO3H (entries
1 and 2), and much weaker CF3COOH was ineffective
(entry 3). BF3 was found to more efficiently cause the
denitrogenation than B(C6F5)3 (entries 4 and 6), but no
reaction occurred with AlCl3 and TiCl4 (entries 7 and 8).
These results suggest the protonation (or coordination of
Lewis acids) at the basic triazoline N1 atom would be a key
step of the denitrogenation (vide infra). In fact, the reaction
was accelerated with increasing solvent polarity as seen in a
entry
reactant
acidd
time (h)
conv (%)
1
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
TfOH
<0.1
0.5
24
100
100
0
2
CH3SO3H
CF3COOH
BF3
3
4
0.5
3
100
81
e
5
BF3
6
B(C6H5)3
AlCl3
5
100
0
7
24
8
TiCl4
24
0
(10) Exceptionally, the reaction of hydrazoic acid with C60 gave
aziridinofullerene, as recently reported by Akhmetov et al. In the light
of our results and discussion in this paper, one can suppose that the
excess amount of sulfuric acid used for in situ preparation of hydrazoic
acid causes the formation of aziridinofullerene. See: Akhmetov, A. R.;
Tuktarov, A. R.; Dzhemilev, U. M.; Yarullin, I. R.; Gabidullina, L. A.
Russ. Chem. Bull. 2011, 60, 1885–1887.
9
TfOH
0.1
0.1
0.1
0.1
0.1
100
100
100
100
100
10
11
12
13
TfOH
TfOH
TfOH (0.5 equiv)
TfOH (1.0 equiv)
(11) (a) Mishchenko, A.; Prosyanik, A.; Belov, P.; Romanchenko,
V.; Belova, Y.; Markov, V. Khim Geterotsikl. Soedinenii 1984, 338–342.
Chem. Heterocycl. Compd. 1984, 20, 270–274. (b) Wladkowski, B. D.;
Smith, R. H.; Michejda, C. J. J. Am. Chem. Soc. 1991, 113, 7893–7897.
(c) Smith, R. H.; Wladkowski, B. D.; Taylor, J. E.; Thompson, E. J.;
Pruski, B.; Klose, J. R.; Andrews, A. W.; Michejda, C. J. J. Org. Chem.
1993, 58, 2097–2103. (d) Rozhkov, V.; Voznesenskii, V.; Kostyanovsky,
R. Russ. Chem. Bull. 1998, 47, 115–118. (e) Prosyanik, A.; Rozhkov, V.;
Moskalenko, A.; Mishchenko, A.; Forni, A.; Moretti, I.; Torre, G.;
Brukner, S.; Malpezzi, L.; Kostyanovsky, R. Russ. Chem. Bull. 1998, 47,
119–126. (f) Benati, L.; Calestani, G.; Nanni, D.; Spagnolo, P. J. Org.
Chem. 1998, 63, 4679–4684. (g) Troyer, T. L.; Muchalski, H.; Hong,
K. B.; Johnston, J. N. Org. Lett. 2011, 13, 1790–1792.
a Isolated yield. b At rt. c >95% isolated yield. d Unless otherwise
noted, 0.1 equiv of acid was used. e Toluene solvent.
Acid-catalyzed denitrogenation of variously alkyl-sub-
stituted 1aꢀe readily occurred on addition of catalytic
(9) Although addition of nitrenes by denitrogenation of azides gave
aziridinofullerenes with relatively high yields, their substituents were
limited to carbonyl/sulfonyl compounds. See: (a) Banks, M.; Cadogan,
J.; Gosney, I.; Hodgson, P.; Langridgesmith, P.; Millar, J.; Taylor, A.
Tetrahedron Lett. 1994, 35, 9067–9070. (b) Smith, A. B.; Tokuyama, H.
Tetrahedron 1996, 52, 5257–5262. (c) Ulmer, L.; Mattay, J. Eur. J. Org.
Chem. 2003, 2933–2940.
(12) An excess amount of acid in toluene led to further reaction,
probably electrophilic arylation of aziridinofullerene as previously
reported in refs 1b and 2.
Org. Lett., Vol. 14, No. 23, 2012
6041

plot of log k vs solvent polarity parameter ET (Figure 2),13,14
probably because of the stabilization of such polar
acidꢀbase complexes.
Scheme 1. Suggested (a) Thermal and (b) TfOH-catalytic
Pathways with Calculated Energies (B3LYP/6-31G(d)
with Solvent Parameter), which are Relative to the Heat
of Formation of 1a (for Thermal) and the Summation of
Those of 1a and TfOH (for Acid-catalyzed)
Figure 2. Plot of log k vs solvent polarity parameter ET for the
reaction of 1a with BF3
13
Why does the present acid-catalyzed condition exclu-
sively provide the [6,6]closed aziridinofullerene in contrast
to the thermal denitrogenation? Thermal condition has
been well-known to prefer the formation of [5,6]open
azafulleroid via the possible three pathways: (1) concerted,
(2) ionic stepwise and (3) radical stepwise.4d,e,15 A DFT
calculation (B3LYP/6-31G(d))16 with solvent parameters
(IEFPCM, o-dichlorobenzene) suggested a concerted-like
transition state 1a-TS (Scheme 1, path a, and Figure 3b)
as previously reported for its carbon analog, pyrazoli-
nofullerene.17 The barrier energy (34.3 kcal/mol) for the
denitrogenation of 1a is lower than those of previously
reported two types of ionic transition states (N1ꢀN2 or
N3ꢀC1 cleavage) by AM1 calculations (46.8 and 45.2
kcal/mol, respectively).15 Moreover, the calculation of
inherent reaction coordinate (IRC) showed the sp2-like
N1 atom considerably approached the C2 atom (purple
cross in Figure 3a), implying enhanced aza-bridging over
the 5,6-conjunct bond. The optimization of the forward-
edge structure of the IRC calculation showed transient
[5,6]closed aziridinofullerene 3a capable of undergoing
labile valence isomerization to [5,6]open azafulleroid
4a (Scheme 1 and Figure 3c). This computational result
(13) The 0.1 equiv of BF3 was used (1.29 ꢁ 10ꢀ3 M). The k value in
toluene is 0.310 Mꢀ1 sꢀ1 and the relative k values in other solvents are
1.97 (b), 2.42 (c), 3.03 (d), and 6.84 (e), respectively.
Figure 3. (a) Energies and atomic distances of IRC calculation
(B3LYP/6-31G(d) with solvent parameters) for the thernal
denitrogenation of 1a. The energies are relative to the initial
state 1a. (b) Geometry of the concerted transition state 1a-TS.
(c) Geometry of [5,6]open 4a (and N2) derived from the optimi-
zation of the IRC forward-edge structure (s = 2.50).
(14) Reichardt, C. Chem. Rev. 1994, 94, 2319–2358.
(15) Cases, M.; Duran, M.; Mestres, J.; Martın, N.; Sola, M. J. Org.
ꢀ
Chem. 2001, 66, 433–442.
(16) All DFT calculations were carried out with Gaussian 09 soft-
ware. Its full citation is shown in Supporting Information.
(17) Wallenborn, E.; Haldimann, R.; Klarner, F.; Diederich, F.
Chem.;Eur. J. 1998, 4, 2258–2265.
6042
Org. Lett., Vol. 14, No. 23, 2012

By contrast, TfOH can protonate an N1 atom to give
triazolinium intermediate 1a Hþ with a long N1ꢀN2
3
distance (1.7 A) (Scheme 1, path b, and Figure 4b).18
transition state calculation of denitrogenation of
A
1a Hþ showed far more lower barrier energy (3.3 kcal,
3
Figure 4c) than that of the thermal reaction (34.3 kcal).
In contrast to the case of thermal condition, the dis-
tance between the sp3-like ammonium N1 and C2
(or C3) is little changed by the IRC calculation, due
to the absence of potential N1 lone pair electrons
(Figure 4a). Furthermore, the optimization of the
IRC forward-edge structure resulted in aminofullerenyl
cation 5a, with N1 being located almost perpendicular to
the C1ꢀC2ꢀC3 plane (Scheme 1 and Figure 4d). The
higher LUMO coefficient and/or positive natural bond-
ing charge on C1 (relative to C2 and C3) by a DFT
calculation would be responsible for the formation of
[6,6]closed aziridinofullerene. The total barrier energy
of the rate-determing protonation (10.6 kcal/mol) and
the fast denitrogantation (3.3) is still less than the half
of the thermal denitrogenation (34.3), so that the acid-
catalyzed reaction seems to proceed very soomthly at
room temperature and exclusively provide [6,6]closed
aziridinofullerenes.
In conclusion, synthetically useful aziridinofullerenes
were exclusively obtained from simple acid-catalyzed deni-
trogenation of triazolinofullerenes, and the DFT calcula-
tions suggested a possible mechanism involving the initial
protonation at the N1 atom, followed by denitrogenation
into the aminofullerenyl cation, and the final aziridination.
This effective synthetic method would open a way to more
versatile and regioselective functionalization of fuller-
enes directed to photovoltaic materials5,19 and biological
applications.7
Figure 4. (a) Energies and atomic distances of IRC calculation
(B3LYP/6-31G(d) with solvent parameters) for the acid-cata-
tytic denitrogenation. The energies are relative to the initial state
1a Hþ. (b) Geometry of N1-acidified 1a Hþ. (c) Transition
Acknowledgment. This work was partly supported by
Grant-in-Aid for Young Scientist (B) (No. 24750039)
from Japan Society for the Promotion of Science
(JSPS), and by Health Labour Sciences Research Grants
from the Ministry of Health, Labour and Welfare of Japan
(MHLW)
3
3
state geometry (1a Hþ-TS) of denitrogenation of 1a Hþ. (d)
3
3
Geometry of aminofullerenyl cation 5a (and N2) derived from
the optimization of the IRC forward-edge structure (s = 2.64).
(e) LUMO orbital distribution and natural bonding orbital
charge (in parentheses) of the ionic intermediate 5a.
Supporting Information Available. General procedure
for the reaction and identification of compounds by
1H, 13C NMR spectra, and FAB/MALDI-MS of 1aꢀf
and 2aꢀf, and calculational results (energy, imagi-
nary frequency and coordinates). This material is
available free of charge via the Internet at http://
pubs.acs.org.
obviously conforms with the selective formation of azaful-
leroids on usual thermal conditions.
(18) Although the triazoline N3 atom would be more easily proto-
nated, such N3-protonated species does not lead to the denitrogenation
(see, ref 11b).
(19) (a) Yang, C.; Cho, S.; Heeger, A. J.; Wudl, F. Angew. Chem., Int.
Ed. 2009, 48, 1592–1595. (b) Park, S. H.; Yang, C.; Cowan, S.; Lee, J. K.;
Wudl, F.; Lee, K.; Heeger, A. J. J. Mater. Chem. 2009, 19, 5624–5628.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 23, 2012
6043