Hydroxide-initiated conversion of aromatic nitriles to imidazolines: Fullerenes vs TCNE

Article abstract of DOI:10.1021/ol401834j

Transformation of aromatic nitriles to imidazolines has been achieved under basic conditions with the electron-deficient C₆₀ and C₇₀ fullerenes, but not with the electron-deficient olefin of tetracyanoethylene (TCNE). In situ UV-vis-

Full text of DOI:10.1021/ol401834j

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Hydroxide-Initiated Conversion of
Aromatic Nitriles to Imidazolines:
Fullerenes vs TCNE
Hui-Lei Hou, Zong-Jun Li, Shu-Hui Li, Si Chen, and Xiang Gao*
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied
Chemistry, University of the Chinese Academy of Sciences, Chinese Academy of
Sciences, 5625 Renmin Street, Changchun, Jilin 130022, China
xgao@ciac.ac.cn
Received July 1, 2013
ABSTRACT
Transformation of aromatic nitriles to imidazolines has been achieved under basic conditions with the electron-deficient C60 and C70 fullerenes,
but not with the electron-deficient olefin of tetracyanoethylene (TCNE). In situ UVꢀvisꢀNIR indicates that the ability of RC60ꢀ to undergo single-
electron transfer (SET) to C60 is crucial for the reaction.
Organonitriles are a class of molecules widely used for
conversion to various functionalities including amides,
aldehydes, amines, carboxylic acids, ketones, hydrazones,
lactams, imidates, and amidines.1 Weak nucleophilic inter-
Scheme 1. Structural Illustrations of Anionic Amidines,
Fullerene Oxazolines, and Imidazolines
mediates of anionic amidines with the negative charge
located on the imine nitrogen atom (Scheme 1) are known
to form via the base-mediated dimerization of aromatic
nitriles,2 which may in principle further react withelectron-
deficient olefins to form imidazolines. However, no such
reaction has been reported so far.
Previous work has shown that OHꢀ can undergo nu-
Fullerenes, represented by C60 and C70, are very electron-
cleophilic addition to C60 to form a strong nucleophile
deficient molecules as evidenced by their ability to undergo
[C60O]2ꢀ, which further reacts with benzonitrile to form
fullerene oxazolines (Scheme 1) at rt.6 However, it is
intriguing that no fullerene product resulting from reac-
tions involving OHꢀ with PhCN was isolated, since the
base-mediated hydrolysis is one of the most conventional
reactions for nitriles. Interestingly, by elevating the reac-
tion temperature to 90 °C, new fullerene heterocycles of
imidazolines (Scheme 1) are indeed formed via a multi-
component reaction of OHꢀ with nitriles and fullerenes.
Such compounds have been reported recently by reactions
of C60 with amidines.7
six reversible one-electron reductions.3 In the meantime, they
are reactive in addition reactions and behave as electron-
deficient olefins.4 It is therefore of interest to explore the
transformation reactions of organonitriles with fullerenes,
which can serve as models to explore novel reactions.5
(1) (a) Kukushkin, V. Y.; Pombeiro, A. J. L. Chem. Rev. 2002, 102,
1771. (b) Murahashi, S.-I.; Takaya, H. Acc. Chem. Res. 2000, 33, 225.
(2) (a) Oliver, S. W.; Smith, T. D. J. Chem. Soc., Perkin Trans. 2 1987,
11, 1579. (b) Kikukawa, Y.; Fukuda, T.; Fuyuhiro, A.; Ishikawa, N.;
Kobayashi, N. Chem. Commun. 2011, 47, 8518.
(3) Echegoyen, L.; Echegoyen, L. E. Acc. Chem. Res. 1998, 31, 593.
(4) Hirsch, A.; Brettreich, M. Fullerenes: Chemistry and Reactions;
Wiley-VCH: Weinheim, Germany, 2005.
(5) (a) Martın, N. Chem. Commun. 2006, 2093. (b) Maroto, E. E.;
Filippone, S.; Martın-Domenech, A.; Suarez, M.; Martın, N. J. Am.
Chem. Soc. 2012, 134, 12936.
(6) (a) Chang, W.-W.; Li, Z.-J.; Yang, W.-W.; Gao, X. Org. Lett.
2012, 14, 2386. (b) Li, Z.-J.; Li, F.-F.; Li, S.-H.; Chang, W.-W.; Yang,
W.-W.; Gao, X. Org. Lett. 2012, 14, 3482.
r
10.1021/ol401834j
XXXX American Chemical Society

Table 1. Screening of the Reaction Conditions and the Substrate
Scopea
OHꢀ temp
yieldb
(%)
entry
ArCN
PhCN
fullerenes (equiv) (°C) product
1
C60
C60
C60
C60
C60
C60
C60
C60
C60
C60
C70
3
9
3
6
9
9
12
9
6
9
9
rt
rt
1
1
39
25
26
32
43
41c
32
40
37
36
41
2
3
4
5
6
7
8
9
PhCN
PhCN
PhCN
PhCN
PhCN
PhCN
PhCN
3-ClPhCN
3-CH3PhCN
PhCN
90
90
90
90
90
120
90
90
90
2a
2a
2a
2a
2a
2a
2b
2c
3
10
11
Figure 1. ORTEP diagrams of (a) 2a and (b) 3 with 50% thermal
ellipsoids. H-atoms and solvent molecules were omitted for
a Reaction conditions: TBAOH (tetra-n-butylammonium hydro-
xide, 1.0 M in MeOH) was added into ArCN (30 mL), and the mixture
was stirred for 20 min at the preset temperature under argon. C60 or C70
(50 mg) was added, and the reaction was stirred for 30 min before
quenching with I2 (1 equiv to TBAOH). b Isolated yield. c The reaction
˚
clarity. Selected bond lengths (A): (a) N1ꢀC61 1.399(9),
C61ꢀN2 1.257(8), C68ꢀO1 1.221(8); (b) N1ꢀC71 1.414(4),
C71ꢀN2 1.272(5), C78ꢀO1 1.211(4).
was allowed to proceed for 90 min after adding C60
.
The same heterocycle is bonded to the C70 cage at the
C1ꢀC2 bond of compound 3 as shown in Figure 1b.9 Due
to the lower symmetry of C70 and the heterocycle, two 1,2-
regioisomers can be formed in principle with the hetero-
cycle orientated toward different directions.10 However,
only one regioisomer is obtained in the reaction, with the
imine N bonded to the apical C2 carbon, while the amino
N bonded to the C1 carbon. The exhibited regioselectivity
for the heterocycle provides an important clue for the
reaction mechanism as shown below.
The structures of 2a and 3 are further supported by
spectroscopic characterizations, where the protonated mo-
lecular ions of 2a and 3 are shown in the HRMS (Figures
S3 and S18), and resonances due to the aromatic protons
are exhibited in the 1H NMR spectra (Figures S4 and S19).
The 13C NMR spectrum of 2a shows two weak resonances
at 93.29 and 82.63 ppm (Figure S5), corresponding to the
sp3 fullerene carbons bonded to the imine6,11 and amino12
N-atoms respectively, and is consistent with the recently
reported data for C60 imidazolines.7 As for 3, only one
weak resonance corresponding to the sp3 C70 carbon
bonded to the amino nitrogen is shown at 78.22 ppm
(Figure S20), while the one bonded to the imine nitrogen
is missing probably due to the weak nature of this reso-
nance as observed in 2a and also C70 oxazolines.13 Also,
resonances for the carbonyl and the imine C-atoms of 2a
and 3 appear in the range 160ꢀ170 ppm. A total of 29 and
34 signals appear for the sp2 carbons of the fullerene
cage for 2a and 3, in agreement with the Cs symmetry of
The reaction conditions and substrate scope were
screened, and the results are listed in Table 1. Only full-
erene oxazoline (1) was obtained at rt (entries 1 and 2). As
the temperature was increased to 90 °C, 10-benzoyl-20-
phenyl-20-imidazolino[50,40:1,2][60]fullerene (2a) was ob-
tained (entries 3ꢀ7). The increase in temperature to 120 °C
did not improve the yield (entry 8). A molar ratio of 9:1 for
OHꢀ to C60 is most appropriate for the reaction (entry 5); a
smaller or larger amount of OHꢀ would result in a lower
yield for the product (entries 4 and 7), where less C60 would
react if less OHꢀ was used, while more toluene-insoluble
materials would be formed if too much OHꢀ was used.
Also, a prolonged reaction time would not improve the
yield of imidazolines either (entry 6). Aromatic nitriles
3-ClPhCN and 3-CH3PhCN can also result in the imidazo-
line products 2b and 2c with a similar yield as PhCN.
Higher fullerene C70 also works as an effective substrate to
achieve this transformation and results in compound 3.
The structures of 2a and 3 are identified by the single-
crystal X-ray diffraction (Figure 1). As for 2a, an imidazo-
line heterocycle, which consists of benzamide and benzo-
nitrile units, is unambiguously shown with two N-atoms
bonding to C60 at the [6,6] bond (Figure 1a). The sum of
the bond angles of C62ꢀC61ꢀN2, C62ꢀC61ꢀN1, and
N1ꢀC61ꢀN2 is 360°, indicating that C61 is an sp2 carbon.
˚
The bond lengths of N1ꢀC61 (1.399 A) and C61ꢀN2
˚
˚
(1.257 A) are in good agreement with the CꢀN (1.47 A)
8
and CdN (1.28 A) bond lengths, indicating explicitly that
˚
an imidazoline heterocycle is formed on the C60 cage. The
˚
bond length of C68ꢀO1 (1.221 A) is consistent with the
(10) (a) Meier, M. S.; Poplawska, M.; Compton, A. L.; Shaw, J. P.;
Selegue, J. P.; Guarr, T. F. J. Am. Chem. Soc. 1994, 116, 7044. (b)
Thilgen, C.; Diederich, F. Top. Curr. Chem. 1999, 199, 135.
8
typical CdO bond length (1.20 A), demonstrating that 2a
˚
is 10-benzoyl-20-phenyl-20-imidazolino[50,40:1,2][60]fullerene.
(11) (a) Zheng, M.; Li, F.-F.; Ni, L.; Yang, W.-W.; Gao, X. J. J. Org.
Chem. 2008, 73, 3159. (b) Li, F.-B.; Liu, T.-X.; Wang, G.-W. J. Org.
Chem. 2008, 73, 6417. (c) Takeda, Y.; Enokijima, S.; Nagamachi, T.;
Nakayama, K.; Minakata, S. Asian J. Org. Chem. 2013, 2, 91.
(12) (a) Butts, C. P.; Jazdzyk, M. D. S. Org. Biomol. Chem. 2005, 3,
(7) He, C.-L.; Liu, R.; Li, D.-D.; Zhu, S.-E.; Wang, G.-W. Org. Lett.
2013, 15, 1532.
(8) Gokel, G. W. Dean’s Handbook of Organic Chemistry, 2nd ed.;
McGraw-Hill: New York, 2004; p 3.13.
(9) For the numbering of C70, refer to: Godly, E. W.; Taylor, R. Pure
ꢀ
1209. (b) Isobe, H.; Tanaka, T.; Nakanishi, W.; Lemiegre, L.; Nakamura,
E. J. Org. Chem. 2005, 70, 4826.
(13) Ni, L.; Yang, W.-W.; Li, Z.-J.; Wu, D.; Gao, X. J. Org. Chem.
Appl. Chem. 1997, 69, 1411.
2012, 77, 7299.
B
Org. Lett., Vol. XX, No. XX, XXXX

Scheme 2. Proposed Mechanism for the Transformation of
Nitriles to Fullerene Imidazolinesa
a The negative charge, which is likely delocalized over a large area of
fullerenes due to π-conjugation, is drawn in a hexagon of the fullerene
cage for clarity.
Figure 2. In situ visꢀNIR spectra of (a) 625 μmol of TBAOH
(1.0 M in MeOH, 625 μL) in PhCN (30 mL) after heating
at 90 °C for 20 min; (bꢀf) after adding C60 (50 mg) into solution
(a) for 3, 13, 23, 30, and 40 min respectively. All measurements
were performed with a 1-mm cuvette under Ar.
stronger absorptions than the pristine C60•ꢀ in the region
below 1050 nm, implying the existence of other anionic
species (likely RC60ꢀ) in the mixture.
A plausible reaction mechanism for the conversion of
nitriles to fullerene imidazolines is shown in Scheme 2. The
reaction is initiated by the attack of OHꢀ at the C-atom of
the nitrile with the formation of intermediate Aꢀ (amide
anion), which further reacts with another nitrile molecule
and results in intermediate Bꢀ (amidine anion) with the
negative charge on the imine N. Subsequently, the Bꢀ would
attack the electron-deficient fullerenes and afford BC2nꢀ (n =
30 or 35), which would undergo an SET to a C2n molecule,
resulting in BC2n• and C2n•ꢀ. Intermediate BC2n• would then
undergo a ring-closure reaction with the formation of a new
C2nꢀN (amino) bond, accompanied with the loss of a
proton, resulting in 2•ꢀ or 3•ꢀ. The fullerene imidazolines
are finally obtained by oxidation with I2 to remove the
negative charge from the fullerene cage. The formation of
the intermediate Bꢀ is unambiguously demonstrated by the
isolation of compound 4 (N-benzoylbenzamidine) via pro-
tonation of the reaction mixture of PhCN and OHꢀ with
water (see Experimental Section in the SI for details).
Previous work has shown that a heterocyclic rearrange-
ment is involved during the formation of the fullerene
oxazolines, which is driven by the formation of the
more stable ring-opened dianionic intermediate.6b,13 How-
ever, such a rearrangement is unlikely to occur during the
formation of fullerene imidazolines, since only monoanio-
nic intermediates are involved in the formation of fullerene
imidazolines. Consequently, the formation of only one C70
imidazoline product (Figure 1b), in which the imine N is
bonded to the C2, while the amino N is bonded to the C1,
explicitly demonstrates that the negative charge is located
on the imine N-atom of intermediate Bꢀ, since the C2
carbon is preferred as the first reaction site of C70 for
reactions involving anionic species due to the favored
formation of the 2ꢀRC70ꢀ intermediate.13,14c
the compounds as shown by the X-ray single-crystal
structures. The UVꢀvis spectrum of 2a (Figure S2) is
similar to that of C60 oxazolines,11a,c while the spectrum of
3 (Figure S17) shows the typical absorptions for the C70
C1ꢀC2 adducts.13,14
The reaction of TBAOH with PhCN and C60 was fol-
lowed with the in situ visꢀNIR spectroscopy (Figure 2).
No absorption appears from 400 to 1100 nm during the re-
action of TBAOH with PhCN (Figure 2a), while the strong
characteristic absorption of C60 appears at 1079 nm15
•ꢀ
(Figure 2bꢀf) after C60 is added, indicating that a signifi-
cant amount of C60•ꢀ is generated during the formation of
imidazolines. The results therefore imply that the C60
imidazolines are likely formed via a monoanion mecha-
nism (RC60ꢀ) rather than a dianion mechanism (RC602ꢀ),
which was involved in the formation ofꢀC60 oxazolines,6,16
•ꢀ
since C60 can be generated by RC60 via SET,17 while
2ꢀ
C602ꢀ (∼ 950 nm) would be produced if there were RC60
according to the relationships of reduction potentials of
C60nꢀ/(nþ1)ꢀ with those of RC60nꢀ/(nþ1)ꢀ (n = 0 or 1).3,18
The absence of the dianionic intermediates during the
reaction is further confirmed by the absence of absorption
bands arising from the dianion of 2a, which was produced
via controlled-potentialbulk electrolysis (see Experimental
Section in the Supporting Information (SI) for details) and
exhibits absorptions at 651, 724, and 975 nm (Figure S25).
Notably, when the in situ spectrum of Figure 2f is overlaid
with the spectrum of C60•ꢀ by normalizing the absorption
at 1079 nm (Figure S26), the reaction mixture exhibits
(14) (a) Wang, Z.; Meier, M. S. J. Org. Chem. 2003, 68, 3043. (b)
Wang, Z.; Meier, M. S. J. Org. Chem. 2004, 69, 2178. (c) Ni, L.; Chang,
W.-W.; Hou, H.-L.; Li, Z.-J.; Gao, X. Org. Biomol. Chem. 2011, 9, 6646.
(15) (a) Lawson, D. R.; Feldheim, D. L.; Foss, C. A.; Dorhout, P. K.;
Elliott, C. M.; Martin, C. R.; Parkinson, B. J. Electrochem. Soc. 1992,
139, L68–L71. (b) Khaled, M. M.; Carlin, R. T.; Trulove, P. C.; Eaton,
G. R.; Eaton, S. S. J. Am. Chem. Soc. 1994, 116, 3465.
NBO calculations with Gaussian09 at the B3LYP/6-
311G(d)//B3LYP/6-31G level for the charge distributions
of Aꢀ and Bꢀ were performed. The calculations predict that
the imine N-atom bears a charge of ꢀ0.882 and ꢀ0.701 for the
intermediates of Aꢀ and Bꢀ respectively (Figure S30), imply-
ing that Bꢀ is a weaker nucleophile as compared with Aꢀ,
which may account for the incapability of Bꢀ to further react
with another nitrile molecule to form the trimeric intermediate.
(16) Hou, H.-L.; Gao, X. J. Org. Chem. 2012, 77, 2553.
(17) (a) Komatsu, K.; Wang, G.-W.; Murata, Y.; Tanaka, T.;
Fujiwara, K. J. Org. Chem. 1998, 63, 9358. (b) Fukuzumi, S.; Nakanishi,
I.; Maruta, J.; Yorisue, T.; Suenobu, T.; Itoh, S.; Arakawa, R.; Kadish,
K. M. J. Am. Chem. Soc. 1998, 120, 6673.
(18) (a) Yang, W.-W.; Li, Z.-J.; Li, F.-F.; Gao, X. J. Org. Chem. 2011,
76, 1384. (b) Yang, W.-W.; Li, Z.-J.; Gao, X. J. Org. Chem. 2011, 76, 6067.
Org. Lett., Vol. XX, No. XX, XXXX
C

Since a novel transformation of aromatic nitriles to
imidazolines was demonstrated under the basic conditions
with the use of electron-deficient fullerenes, it was of
interest to investigate whether such a transformation can
be achieved with other typical electron-deficient alkenes.
TCNE is an ideal substrate to study, since it is even more
electron-deficient than C60 and C70 as evidenced by the more
positive potential for the first reduction (E1/2 vs SCE: 0.30 V
for TCNE, ꢀ0.43 V for C60, ꢀ0.42 V for C70, Figure S29),
and is capable of undergoing a nucleophilic addition reaction
with nucleophiles including cyanide and Grignard reagents.19
Reactions of TCNE with OHꢀ and PhCN were carried
out with a TCNE:OHꢀ molar ratio of 1:9, 1:6, 1:3, and
20:1, while other conditions remained similar to those when
fullerenes were used (see Experimental Section in the SI for
details). The reaction crude products were separated with a
flash silica column. Surprisingly, no TCNE imidazoline
product was obtained. Since the BTCNEꢀ is expected to
form, as TCNE is more electron-deficient than fullerenes
and capable of addition reactions with nucleophiles, it
implies that the intermediates of anionic fullerene species
(BC2nꢀ) may possess a unique character that is absent for
the conventional anionic alkene species.
Figure 3. In situ UVꢀvis spectra of the reaction mixture of
TBAOH (1.0 M in MeOH) and TCNE with a molar ratio of (a)
9:1 (2.2 mM for TCNE) and (b) 1:20 (9.2 mM for TCNE) in
PhCN after heating at 90 °C for 30 min. See Experimental
Section in the SI for details. All measurements were performed
with a 1-mm cuvette under Ar.
negativeꢀcharge located at the individual fullerene C-atom
of BC2n is significantly reduced, while the C-atom in
BTCNEꢀ may bear a greater negative charge due to a
poorer delocalization, rendering BTCNEꢀ a better nucleo-
ꢀ
ꢀ
As shown in Scheme 2, an SET from BC2n to C2n to
phile compared with BC2n
.
form the BC2n• and C2n•ꢀ is required in order to form the
second C2nꢀN bond via a nucleophilic attack of amino N to
the fullerene cage. Such an electron transfer is supported by
the appearance of characteristic absorptions for C60•ꢀ in the
in situ visꢀNIR spectrum of the reaction mixture and has
been proposed for the mechanochemical synthesis of C120
and the reaction of C60 with alkoxide ions.17 However, it
seems that no electron transfer occurs from BTCNEꢀ to
TCNE as indicated by the in situ UVꢀvis spectra of the
reaction mixture of TCNE with OHꢀ and PhCN (Figure 3).
The in situ UVꢀvis spectra of the reaction mixture
display absorption bands at 400 and 419 nm, which have
been assigned to originate from the 1,1,2,3,3-pentacyano-
propenyl anion (PCNPꢀ)20 likely formed via an oligomer-
ization initiated by nucleophilic attack of RTCNEꢀ to
neutral TCNE.19c Additional absorption bands are shown
between 510 and 564 nm for the reaction mixture with
a 1:20 molar ratio of OHꢀ to TCNE, which likely arise
from the anionic species from further oligomerization due
to a higher TCNE concentration. The most important
information is that no absorptions due to TCNE•ꢀ within
350ꢀ500 nm21 (Figure S27) are shown in the spectra,
indicating that the resulting BTCNEꢀ likely favors the
nucleophilic attack to another TCNE and undergoes an
oligomerization reaction,19c rather than undergoing an
SET to neutral TCNE. Such a reactivity difference can
be understood by the variation of electron delocaliza-
tion between BC2n•ꢀ and BTCNE•ꢀ. Due to the effective
π-delocalization of fullerene cages, the amount of the
ꢀ
The weaker nucleophilicity of BC2n compared with
BTCNEꢀ is further supported by DFT calculations with
Gaussian09 at the B3LYP/6-311G(d)//B3LYP/6-31G
level, which predict that the largest NBO negative charge
isꢀ0.163 for BC60ꢀ, ꢀ0.141 for BC70ꢀ, and a much greater
value of ꢀ0.525 for BTCNEꢀ, located at the C-atom
adjacent to the one bonded to the amidine addend for
BC2nꢀ and BTCNEꢀ (Figure S30).
In summary, a novel transformation of aromatic nitriles
to imidazolines has been achieved under basic conditions
with the use of electron-deficient C60 and C70 fullerenes.
The reaction mechanism is proposed on the basis of in situ
visꢀNIR spectral measurement and also the structures of the
obtained C60 and C70 imidazolines. However, no such trans-
formation is achieved when TCNE, an electron-deficient
alkene, is used even though it is more electron-deficient than
fullerenes and capable of nucleophilic additions. Such a
ꢀ
difference is attributed to the distinction between RC2n
and RTCNEꢀ in their ability of transferring electrons to
the neutral counterparts, which is closely related to the
intrinsic nature of the electron delocalization of the two types
of molecules. This is a good example of employing fullerenes
as models for exploring novel reactions.
Acknowledgment. The work was supported by the NSFC
(21172212 and 20972150 for X.G., 21202157 for Z.J.L.)
and the Solar Energy Initiative of the Chinese Academy of
Sciences (KGCX2-YW-399þ9).
Supporting Information Available. Experimental and
calculation details, crystallographic data (CIF), HPLC
traces, and spectra of the new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
(19) (a) Webster, O. W.; Mahler, W.; Benson, R. E. J. Am. Chem. Soc.
1962, 84, 3678. (b) Dhar, D. A. Chem. Rev. 1967, 67, 611. (c) Gardner,
H. C.; Kochi, J. K. J. Am. Chem. Soc. 1976, 98, 558.
(20) Chen, C.; Kurose, H.; Iino, M. Energy Fuels 1999, 13, 180.
(21) Del Sesto, R. E.; Miller, J. S.; Lafuente, P.; Novoa, J. J. Chem.;
Eur. J. 2002, 8, 4894.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX