Introduction of azetidinimine skeleton on C60

Article abstract of DOI:10.1002/hc.20703

The azacyclobutane structure is introduced into C₆₀ fullerene using a photochemical reaction with formamidines. Three azetidinofullerenes (2c-2e) were synthesized; their molecular structures were characterized using ¹H, ¹³

Full text of DOI:10.1002/hc.20703

Heteroatom Chemistry
Volume 22, Number 3/4, 2011
Introduction of Azetidinimine Skeleton on C
60
Nobuaki Ueda, Hidefumi Nikawa, Yuta Takano, Midori O. Ishitsuka,
Takahiro Tsuchiya, and Takeshi Akasaka
Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki
305-8577, Japan
Received 29 September 2010; revised 23 November 2010
Among many fullerene derivatization methods,
ABSTRACT: The azacyclobutane structure is intro-
the introduction of an azacyclobutane structure
duced into C60 fullerene using a photochemical re-
is interesting because it is possible to form a
action with formamidines. Three azetidinofullerenes
β-lactam structure and its bioactive derivatives [6,7].
(2c–2e) were synthesized; their molecular structures
A few reports have described introduction of a
were characterized using 1 H, 13C, and 2D NMR,
four-membered ring on fullerene cages. To the
matrix-assisted laser desorption ionization (MALDI)
best of our knowledge, only benzyne adducts have
mass spectrometry, visible spectroscopy, and electro-
been reported as C60 derivatives possessing a four-
chemistry. Single crystal X-ray crystallographic anal-
membered ring [8,9].
ysis of 2e reveals a unique strained four-membered
Here we report the synthesis of novel fullerene
ring including nitrogen atom attached on the fullerene
derivatives having an azetidinimine framework with
ꢀ
C
cage.
2011 Wiley Periodicals, Inc. Heteroatom Chem
their full characterizations, including structural elu-
cidation using single-crystal X-ray crystallographic
analysis of a compound (2e).
22:426–431, 2011; View this article online at wileyonlineli-
brary.com. DOI 10.1002/hc.20703
INTRODUCTION
RESULTS AND DISCUSSION
C60 is a promising material because it has a unique
molecular structure comprising a ball-like shape,
a largely delocalized π-conjugation system, and a
high molecular symmetry [1,2]. Recently, biochem-
ical and medicinal applications were proposed for
the use of fullerenes [3]. A key for the biological
use is introducing nitrogen atoms on the fullerene
cage to mimic bioactive molecules. For this purpose,
numerous nitrogen-introduced fullerene derivatives
have been reported to date [1,4,5].
Formamidines (1a–1e) were synthesized by refer-
ring to reported procedures (Scheme 1) [10,11]. We
performed photoreaction of C60 using N,Nꢁ-bis(2,6-
dialkylphenyl)formamidines (1c–1e) to afford cor-
responding C60 adducts (Scheme 2). The C60 adducts
were isolated by two-step HPLC separation. How-
ever, the reactions did not proceed when 1a or 1b
was used because of their poor solubility in the sol-
vent system that was used: toluene.
Structural Determination
Dedicated to Professor Kin-ya Akiba on the occasion of his 75th
birthday.
Correspondence to: Takeshi Akasaka; e-mail: akasaka@tara
.tsukuba.ac.jp.
Contract grant sponsor: Ministry of Education, Culture, Sports,
Science, and Technology of Japan.
Structures of 2c–2e were identified using spectro-
scopic methods. Matrix-assisted laser desorption-
ionization–time-of-flight (MALDI-TOF) mass spec-
troscopic measurements confirmed the formation of
2c–2e. The spectra of 2c–2e respectively display par-
ent peaks at m/z 970.3, 1026.9, and 1082.5.
Contract grant numbers: 20108001, 20245006, and 21550032.
2011 Wiley Periodicals, Inc.
c
ꢀ
426

Introduction of Azetidinimine Skeleton on C60 427
SCHEME 1
R1
R1
N
N
R2
R2
R1
R2
R1
R2
hν
(>400 nm)
Toluene
+
N
N
H
1c–e
2c–e
SCHEME 2
FIGURE 1 1H NMR spectrum of 2e in 1:4 (v/v) = CD2Cl2/CS2.
The 1H NMR spectra of 2c–2e show characteris-
tic peaks attributed to the corresponding addends
(Fig. 1 and the Supporting Information). For in-
stance, the 1H NMR spectrum of 2e displays proton
signals of the two isopropyl group attaching benzene
rings at 1.40–1.89 ppm along with a multiplet sig-
nal from the protons in the aromatic rings at about
7.13–7.79 ppm, and two septet signals at 3.79 and
4.56 ppm from methine protons.
a [6,6]-closed structure, which has two sp3 car-
bons in the fullerene cage, and Cs symmetry of 2e.
The remaining signals are assigned to the aromatic
and aliphatic carbon atoms. The 2D NMR (HMQC,
HMBC) measurements of 2e confirm correlations
between the proton and the carbon signals of the
addend.
It is noteworthy that the azacyclobutane frame-
work was introduced to C60 through the reaction
with formamidines. It was also found that the
photoreactions did not proceed in the absence of
oxygen. These results suggest that oxygen molecule
plays an important role in the reactions to determine
addition patterns to C60. Isobe et al. [12] reported
The 13C NMR spectrum of 2e shows two sig-
nals with relative intensities of 1 and 28 signals
with the intensities of 2 from the sp2 carbons of
the fullerene cage (Fig. 2). The observed charac-
teristic signals at δ = 79.6 and 89.3 ppm indicate
Heteroatom Chemistry DOI 10.1002/hc

428 Ueda et al.
SCHEME 3 Proposed reaction mechanism.
FIGURE 2 13C NMR spectrum of 2e in 1:4 (v/v) = CD2Cl2/CS2.
multiple additions of a secondary amine with C60
under photochemical aerobic conditions to produce
tetra(amine)-fullerene epoxide.
Electronic Properties
The visible absorption spectra of 2c–2e and pris-
tine C60 in toluene are shown in Fig. 5. 2c–2e show
characteristic absorption bands around 410 nm as
In this regard, the reaction mechanism can be
proposed as shown in Scheme 3. Initially, a single
electron transfer occurred from the formation of a
stable C60 anion radical and an amidinium cation
radical through an electron transfer from a formami-
dine. Once generated, the C60 anion radical reduces
molecular oxygen to generate superoxide anion rad-
ical. C60 and an amidinium cation react together to
form a protonated 3. The superoxide anion then de-
protonates radical 3; the resulting HO−2 must be a
sufficiently powerful oxidant to convert 4 into azeti-
dinimine 2.
The 2e molecular structure was determined
clearly by single-crystal X-ray structure analysis
(Fig. 3). Unambiguously, 6,6-closed structure of
the azetidino[60]fullerene was demonstrated. The
characteristic strained azacyclobutane structure is
shown clearly from the crystal structure with bond
˚
˚
lengths of C1–C2 [1.551(2) A], C2–C3 [1.606(2) A],
˚
˚
N2–C3 [1.480(2) A], C1–N1 [1.261(2) A], and C1–N2
FIGURE 3 ORTEP drawing of 2e with 50% probability
ellipsoids.
˚
[1.372(2) A] (Fig. 4).
Heteroatom Chemistry DOI 10.1002/hc

Introduction of Azetidinimine Skeleton on C60 429
TABLE 1 Redox Potentials (V)a
Compound
oxE1
redE1
redE2
redE3
C60
2e
+1.21b
–1.12
–1.11
–1.50
–1.50
–1.95
–2.02
+0.97b
aValues were obtained by differential pulse voltammetry/pulse am-
plitude = 50 mV; scan rate 20 mV s−1. Versus Fc/Fc+ in 1,2-
dichlorobenzene with 0.1 M (nBu)4NPF6 at Pt working and coun-
FIGURE 4 Schematic drawing of the azetidinimine frame-
work in 2c–2e.
terelectrodes; scan rate = 20 mV s−1
.
bIrreversible.
alize C60 because it can be converted to a β-lactam
framework, which is expected to be useful for bio-
logical applications [8].
broadening shoulder peaks, which are identical for
[6,6]-closed fullerene derivatives [13,14].
The redox property of 2e was investigated using
cyclic voltammetry and differential pulse voltamme-
try measurements. Table 1 shows the redox poten-
tials of the cycloadduct (2e) and C60 as a comparison.
In addition, 2e exhibits three one-electron reversible
reduction steps and one-electron irreversible oxida-
tion step, as well as pristine C60. The reduction poten-
tials of 2e were almost unchanged from those of C60,
indicating that the introduction of the azacyclobu-
tane ring has no important influence on the electron-
accepting property. On the other hand, the first ox-
idation potential is shifted cathodically by 0.24 V,
which may be rationalized by the attachment of ni-
trogen atom on the fullerene cage as described in the
previous report for aziridino[60]fullerenes [15].
In conclusion, novel C60 derivatives were synthe-
sized with a new methodology using formamidines.
They were characterized using spectroscopic meth-
ods, revealing a unique four-membered ring contain-
ing a nitrogen atom. The introduction of the aza-
cyclobutane structure did not change the electronic
properties of the fullerene cage drastically, which in-
dicates that this is a promising approach to function-
EXPERIMENTAL
General
All chemicals and solvents were obtained from Wako
(Wako Pure Chemical Industries, Ltd., Osaka, Japan)
and Aldrich (Sigma-Aldrich, St. Louis, MO), and
were used without further purification unless oth-
erwise stated. Toluene was distilled over benzophe-
none sodium ketyl under an argon atmosphere prior
to use in a reaction.
Matrix-assisted laser desorption ionization–
time-of-flight mass spectra were measured (BI-
FLEX III; Bruker Analytik, GmbH, Germany) with
1,1,4,4-tetraphenyl-1,3-butadiene as a matrix. The
visible absorption spectra were measured using
a spectrometer (UV3150; Shimadzu Corp., Kyoto,
Japan) in toluene. The 1H, 13C NMR, and 2D
NMR (HMQC and HMBC) spectra were recorded
on a spectrometer (AVANCE 300; Bruker BioSpin
K.K., Karlsruhe, Germany), in CS2 and CD2Cl2
(4/1 = v/v). Cyclic voltammograms and differential
pulse voltammograms were measured on a poten-
tiostat/galvanostat (BAS CW-50; BAS Inc., Tokyo,
Japan), in o-dichlorobenzene with 0.1M (nBu)4NPF6
at a Pt working electrode. All potentials are ref-
erenced to the ferrocene/ferrocenium ion couple
(Fc/Fc+) as a standard.
General Procedure for Synthesis of
N,Nꢁ-Bis(2-Alkylphenyl)Formamidines (1a–1b)
and N,Nꢁ-Bis(2,6-Alkylphenyl)Formamidines
(1c–1e)
N,Nꢁ-bis(2-alykylphenyl)formamidines (1a–1b) and
N,Nꢁ-bis(2,6-alkylphenyl)formamidines
(1c–1e)
were prepared using the method described by
Grubbs and coworkers [10].
Acetic acid (86 mL, 1.5 mmol, 0.050 equiv) was
added to a round-bottomed flask charged with the
corresponding aniline (60 mmol, 2.0 equiv) and
FIGURE 5 Vis-absorption spectra of 2c–2e and C60 in
toluene.
Heteroatom Chemistry DOI 10.1002/hc

430 Ueda et al.
triethyl orthoformate (5.0 mL, 30 mmol, 1.0 equiv).
The flask was fitted with a distillation head and
was heated with stirring overnight. Upon cooling
to room temperature, the solution solidified. The
crude product was triturated with cold hexanes,
collected by vacuum filtration, and dried in vacuo,
providing the pure product as a white crystalline
solid. The following formamidines were prepared
using this procedure.
Photoreaction of [60]Fullerene with
N,Nꢁ-Bis(alkylphenyl)formamidine
Irradiation of toluene solution (20 mL) of
[60]fullerene (20.0 mg, 28.0 nmol) and an excess
molar amount of N,Nꢁ-bis(alkylphenyl)formamidine
(0.84 mmol, 30 equiv) in a glass tube at room tem-
perature for 48 h using a high-pressure mercury-arc
lamp (cutoff < 400 nm) caused the formation of the
adduct, which was purified using preparative HPLC
with a Buckyprep column and a Buckyprep M col-
umn (nacalai tesque, Kyoto, Japan).
N,Nꢁ-Bisphenylformamidine (1a)
Spectrum data of 2c:Yield 62%, 1H NMR
(300 MHz, CS2/CD2Cl2, 293 K): δ = 2.42 (s, 6H),
3.01 (s, 6H), 6.23–6.87 (m, 2H), 7.06–7.22 (m, 2H),
7.35 (m, 1H); 13C NMR (75 MHz, CS2/CD2Cl2, 293 K):
δ = 20.0, 21.0, 79.5, 89.2, 124.4, 128.3, 129.2, 129.3,
130.1, 134.2, 138.5, 139.3, 140.2, 140.6, 140.6, 141.9,
142.0, 142.3, 142.5, 142.7, 142.9, 143.0, 143.0, 143.1,
144.3, 144.7, 145.0, 145.2, 145.3, 145.3, 145.7, 146.1,
146.1, 146.2, 146.2, 146.3, 146.7, 147.0, 147.2, 149.1.
MALDI-TOF mass: calcd: [M] 970.15, found: [M−]
970.27. Vis (toluene) λmax: 321, 459, 691 nm.
1
Yield 51%. H NMR (300 MHz, CDCl3, 293 K): δ
= 7.01–7.31 (m, 5H), 8.21 (s, 1H), 10.1 (brs, 1H);
13C NMR (75 MHz, CDCl3, 293 K): δ = 119.0, 123.3,
129.4, 145.2, 149.7.
N,Nꢁ-Bis(2-methylphenyl)formamidine (1b)
1
Yield 76%. H NMR (300 MHz, CDCl3, 293 K): δg
= 2.29 (s, 6H), 6.97–7.18 (m, 8H), 8.03 (brs, 1H); 13
C
Spectrum data of 2d: Yield 24%, 1H NMR
(300 MHz, CS2/CD2Cl2, 293 K): δ = 1.08–1.20
(m, H), 2.20–2.70 (m, H), 6.50–7.50 (m, 6H). 13C
NMR (75 MHz, CS2/CD2Cl2, 293 K): δ = 14.4,
15.1, 15.8, 25.3, 26.0, 26.1, 79.3, 89.0, 124.6, 126.3,
126.7, 127.2, 130.3, 135.1, 140.1, 140.4, 140.7, 141.9,
142.0, 142.3, 142.6, 142.7, 142.9, 143.0, 143.1, 143.2,
144.3, 144.7, 145.1, 145.1, 145.2, 145.3, 145.4, 145.5,
145.9, 146.1, 146.2, 146.2, 146.3, 146.4, 146.8, 146.9,
147.2, 147.3, 149.3, 154.0; MALDI-TOF mass: calcd:
1026.21, found: [M−] 1026.87. Vis (toluene) λmax: 325,
457, 693 nm.
NMR (75 MHz, CDCl3, 293 K): δ = 17.9, 117.6, 123.4,
126.9, 130.7.
N,Nꢁ-Bis(2,6-dimethylphenyl)formamidine (1c)
Yield 28%. 1H NMR (300 MHz, CDCl3, 293 K):
δ = 2.24 (s, H), 2.27 (s, H), 6.91–7.36 (m, 6H); 13C
NMR (75 MHz, CDCl3, 293 K): δ = 17.9, 18.7, 123.1,
126.3, 128.2, 128.3, 128.6, 128.8, 133.7 136.2, 145.1,
146.6.
Spectrum data of 2e: Yield 51%, 1H NMR
(300 MHz, CS2/CD2Cl2, 293 K): δ = 1.43 (m, 12H),
1.61 (d, J = 4.2 Hz, 6H), 1.88 (d, J = 4.2 Hz,
6H), 3.79 (sep, J = 4.2 Hz, 1H), 4.56 (sep, J = 4.2
Hz, 1H), .13 (s, 3H), 7.67–7.79 (m, 3H). 13C NMR
(75 MHz, CS2/CD2Cl2, 293 K): δ = 22.3, 26.4, 26.4,
29.6, 31.0, 79.6, 89.3, 123.5, 125.6, 125.8, 131.4,
138.7, 139.8, 140.7, 141.0, 141.1, 142.4, 142.6, 142.8,
143.2, 143.3, 143.5, 143.5, 143.7, 143.7, 144.9, 145.4,
145.6, 145.7, 145.7, 145.9, 145.9, 146.1, 146.6, 146.7,
146.7, 146.8, 146.8, 147.0, 147.3, 147.8, 147.8, 150.2,
150.4. MALDI-TOF mass: calcd: 1082.27, found:
[M−] 1082.49. Vis (toluene) λmax: 319, 461, 692 nm.
Crystal data of a black block of 2e : MW: 1083.14,
0.14 mm × 0.11 mm × 0.09 mm, monoclinic, P21/n
N,Nꢁ-Bis(2,6-diethylphenyl)formamidine (1d)
Yield 29%. 1H NMR (300 MHz, CDCl3, 293 K):
δ =1.15 (t, J = 7.5 Hz, 3H), 1.21 (t, J = 7.5 Hz, 6H),
1.26 (t, J = 7.5 Hz, 3H), 2.60 (q, J = 7.5 Hz, 4H), 2.66
(q, J = 7.5 Hz, 4H), 7.035–7.313 (m, 6H); 13C NMR
(75 MHz, CDCl3, 293 K): δ = 14.2, 14.8, 15.0, 24.1,
24.9, 24.9, 123.4, 126.2, 126.4, 126.9, 127.1, 134.4,
134.9, 140.6, 144.0, 147.2.
N,Nꢁ-Bis(2,6-diisopropylphenyl)formamidine
(1e)
Yield 51%. 1H NMR (300 MHz, CDCl3, 293 K):
δ = 1.11 (d,J = 6.6 Hz, 15H), 1.18 (d,J = 6.6 Hz,
3H), 3.178–3.440 (sep, J = 6.6 Hz, 4H), 7.09–7.27
(m, 6H), 8.99 (brs, 1H); 13C NMR (75 MHz, CDCl3,
293 K): δ = 23.5, 28.0, 123.1, 125.4 (br), 134 (br),
143.5 (br), 154.0 (br).
˚
˚
(No. 14), a = 10.3025(6) A, b = 24.6572(12) A,
◦
˚
c = 19.2788(11) A, β = 101.654(4) , V = 4796.5(5)
A , Z = 4, Dcalcd = 1.500, μ (Mo Kα) = 0.087 mm−1,
3
˚
Rigaku R-AXIS RAPID θ = 6.13–47.99, T = 100
K, Number of observations (all reflections): 13502,
Heteroatom Chemistry DOI 10.1002/hc

Introduction of Azetidinimine Skeleton on C60 431
number of variables: 792, reflection/parameter ratio:
17.04, R [7972Fo > 2σ(Fo)] = 0.0519, R(for all 13,502
data) = 10.0833, ωR2 (all reflections) = 0.1255. Good-
ness of fit indicator 0.909, restrained goodness of fit
indicator 0.909 for all data. CCDC 794153 contains
the supplementary crystallographic data for this pa-
per. 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 CB2 1EZ, UK; Fax: +44
1223 336033; or deposit@ccdc.cam.ac.uk.
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SUPPORTING INFORMATION
The supporting information related to this arti-
cle is available from the corresponding author
(e-mail: akasaka@tara.tsukuba.ac.jp) on request.
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ACKNOWLEDGEMENTS
This work was supported by a Grant-in-Aid for Sci-
entific Research on Innovation Areas (No. 20108001,
“pi-Space”) and a Grant-in-Aid for Scientific Re-
search (A) (No. 20245006) and (C) (No. 21550032)
from the Ministry of Education, Culture, Sports, Sci-
ence, and Technology of Japan.
Heteroatom Chemistry DOI 10.1002/hc