Synthesis of fullerotetrahydroquinolines by cycloaddition reaction of C60 with aza-ortho-xylylenes

Article abstract of DOI:10.1055/s-1999-2587

This paper reports on the successful synthesis of fullerotetrahydroquinolines by using in sire generated aza-ortho-xylylenes using a Diels-Alder reaction.

Full text of DOI:10.1055/s-1999-2587

LETTER
207
Synthesis of Fullerotetrahydroquinolines by Cycloaddition Reaction of C60
with Aza-ortho-xylylenes
Masatomi Ohno,* Haruhiko Sato, Shoji Eguchi
Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Chikusa, Nagoya 464-8603, Japan
Fax +81-52-789-4671, E-mail: ohno@apchem.nagoya-u.ac.jp
Received 2 November 1998
mentary two-step conversion was rather effective
Abstract: This paper reports on the successful synthesis of fullero-
(Scheme 2);9 acylation of 1 with ethyl chloroformate in
tetrahydroquinolines by using in situ generated aza-ortho-xylylenes
the presence of pyridine and, without purification of car-
using a Diels-Alder reaction.
bamate 2, following cyclization with DBU in refluxing
Key words: [60]fullerene, hetero Diels-Alder reaction, aza-ortho-
toluene gave 3 in 88% overall yield.10 According to the es-
xylene, tetrahydroquinoline, pyramidal nitrogen
tablished procedure, 3 was converted to N-substituted 3,1-
benzoxazin-2-ones 4a-e with NaH and appropriate ha-
lides.6
Various types of [2+3] and [2+4] cycloadditions have
been exploited for the purpose of the exohedral function-
alization of fullerenes.1 Introduction of heterocycles on
the C60 surface has been performed satisfactorily by such
methodologies for developing new materials based on
combination of the interesting properties of these two ring
systems.2 The 1,3-dipolar cycloaddition has been applied
as a reliable method for constructing five-membered ful-
leroheterocycles.1,2 On the other hand, six-membered ful-
leroheterocycles have been so far achieved by hetero
Diels-Alder reaction; for example, 2-aza-1,3-diene was
applied for synthesis of d-lactam-fused C60.3 In relevance
to the reasonable use of o-quinodimethane to prepare a cy-
Scheme 2
cloirreversible cycloadduct in fullerene chemistry,4 its
oxa and thia heterologs were demonstrated to give fulle-
rochroman and -thiochroman derivatives (Scheme 1:
The desired cycloaddition, typically with N-ethoxycarbo-
nylated aza-ortho-xylylene 5a, was conducted by heating
X=O, S).5 In this series, we now wish to report a success-
ful aza version (Scheme 1: X=NR) by using in situ gener-
a solution of C60 and 4a (1.5 equiv.) in 1,2,4-trichloroben-
ated aza-ortho-xylylenes with electron-withdrawing and
zene at reflux temperature under a nitrogen atmosphere.
The color change of the solution from purple to dark
electron-donating substituents and even no substituent on
an imino group. The last case exemplified the first inter-
molecular Diels-Alder reaction of this heterodiene.
brown showed the formation of new products together
with TLC analysis (Rf=0.6, silica gel/toluene). After re-
fluxing for 4.5 h, the cycloadduct was isolated by flash
chromatography on a silica gel column (hexane/tolu-
ene=1/1) to give 1,2,3.4-tetrahydroquinoline-fused C60 6a
in 46% yield (69% yield based on consumed C60) (Scheme
3). The structural determination was based on spectral in-
spections. The usual evidence required for a 1:1 cycload-
duct at (6,6) junction was obtained by FAB-MS peaks at
m/z 897 (M+) and 720 (base), IR absorptions at 1709 and
526 cm-1, and a UV maximum at 434 nm. While the pres-
ence of a tetrahydroquinoline ring and an ester group was
indicated as expected by both 1H- and 13C-NMR signals,11
the 13C-NMR spectrum showed 53 lines at d 134.61-
156.51 due to fullerene cage sp2-carbons together with
two lines at d 70.36 and 80.22 due to junction sp3-carbons,
contradicting a Cs-symmetric structure which may intu-
itively be expected by considering the common sp2-con-
Scheme 1
Thermal decarboxylation of a 3,1-benzoxazin-2-one ring
was documented recently to effect the generation of aza-
ortho-xylylenes6 and then employed for the present reac-
tion with C60. The parent 1,4-dihydro-2H-3,1-benzoxazin-
2-one 3 is available easily from the reaction of o-ami-
nobenzyl alcohol 1 with phosgene.7 Because of high tox-
icity of the latter reagent, we simply considered that it
could be replaced with carbonyldiimidazole (Im2CO).8
However, attempted cyclocondensation of 1 with this
popular alternative gave no expected product. A comple-
1
figuration of amide nitrogen. Consistently, the H-NMR
spectrum showed a couple of unequivalent ring methylene
Synlett 1999, No. 2, 207–209 ISSN 0936-5214 © Thieme Stuttgart · New York

208
M. Ohno et al.
LETTER
signals at d 4.31 and 4.82 (each 1 H, d, J=13.5 Hz). Fur- 149.46 and 136.23-155.81, respectively, indicating Cs-
thermore, the methylene protons of an ethoxycarbonyl symmetricity of the cycloadducts.17 In the 1H-NMR spec-
group appeared in a complex coupling pattern (d 4.33 and tra, signals due to methylene protons appeared as a singlet
4.47, each 1 H, dq, J=10.5 and 7 Hz) due to diastereotopic at d 4.55 (2 H) for 6f and as a collapsed doublet at d 4.30
non-equivalency. The lack of Cs-symmetry and the diaste- and 4.80 for 6c. These results reflect that the free inver-
reotopic nature can be ascribed to sp3-configuration and sion at the nitrogen center occurs within the 13C NMR
no free inversion of a nitrogen atom involved in the tet- time scale in both 6c and 6f. Coalescence is complete in
rahydroquinoline ring. When this is the case, both methyl- 6f and not in 6c within the 1H-NMR time scale. Since all
ene protons become no longer equivalent irrespective of of the optimized geometries of 6a,c,f calculated by PM3
free ring-flipping. In the constrained boat form favored were estimated to have a boat form, the nitrogen is sp3-like
for an azacylohexene ring to link with a fullerene back and inversion is influenced by bulkiness of N-substituents
bone,12 the nitrogen center may take advantage of pyrami- with freedom in the order of 6f>6c>6a.
dalization in a way to avoid steric congestion between a
In conclusion, Diels-Alder reaction of C60 with the aza an-
C60 surface and an N-substituent which should emerge on
alog of o-quinodimethane generated by thermal decompo-
going to sp2-hybridization. In fact, these methylene sig-
sition of 3,1-benz-oxazin-2-one as a precursor took place
nals did not coalesce in variable temperature experiments
smoothly to lead to the formation of fullerotetrahydro-
up to 150°C. The present system provides a unique exam-
quinolines. While intermolecular cycloaddition of aza-
ortho-xylylene has not yet been recorded, this was effec-
ple for the pyramidal nitrogen of amide group.13
In the same manner, the reaction with N-tosylated benzox- tive in the particular case with C60. The nitrogen atom of
azinone 4b afforded the corresponding cycloadduct 6b in the C60-fused N-ethoxycarbonyltetrahydroquinoline was
38 % yield (70% yield based on consumed C60), and the found to be sp3-hybridized, providing a unique example
structure was elucidated in analogy with 6a.14 While the for the pyramidal nitrogen of amide group.
aza-ortho-xylylene is known to undergo [4+2]cycloaddi-
tion more favorably with an electron-withdrawing substit-
Acknowledgment
uent on an imino group, an electron-donating one was
found to sustain the cycloaddition reactivity with C60.6
This work was financially supported by a Grant-in-Aid for Scienti-
fic Research on Priority Area (A) (No. 10146101) from the Ministry
of Education, Science, Sports and Culture, Japan.
Thus, N-methylated benzoxazinone 4c was treated as
above except using 5 equiv. of the precursor to give 6c in
45% yield (78% yield based on consumed C60). Notably,
C60 shows in some cases extraordinary Diels-Alder reac-
tivity which was not seen in a usual dienophile.15 The par-
ent 3 is known to cycloadd only intramolecularly.16
However, when C60 is a reaction partner, intermolecular
[4+2]cycloaddition was accomplished under the same
conditions employed for 4c to give 6f in 37% yield (46%
yield based on consumed C60). In contrast to the success-
ful cycloadditions as observed above, those with N-acetyl-
ated 4d and N-benzoylated 4e did not give the correspond-
ing cycloadducts; instead, 6f was obtained in less effec-
tive yields as a result of deacylation before or after the
cycloaddition step.
References and Notes
(1) (a) Hirsch, A. Synthesis 1995, 895. (b) Sliwa, W. Fullerene
Sci. Tech. 1995, 3, 243. (c) Averdung, J.; Torres-Garcia, G.;
Luftmann, H.; Schlachter, I.; Mattay, J. Fullerene Sci. Tech.
1996, 4, 633.
(2) Eguchi, S.; Ohno, M.; Kojima, S.; Koide, N.; Yashiro, A.;
Shirakawa, Y.; Ishida, H. Fullerene Sci. Tech. 1996, 4, 303.
(3) Ohno, M.; Kojima, S.; Shirakawa, Y.; Eguchi, S. Tetrahedron
Lett. 1996, 37, 9211.
(4) (a) Belik, P; G gel, A.; Spickermann, J.; Müllen, K. Angew.
Chem. Int Ed. Engl. 1993, 32, 78. (b) Belik,P.; Gügel, A.;
Kraus, A.; Walter, M.; Müllen, K. J. Org. Chem. 1995, 60,
3307. (c) Taki, M.; Sugita, S.; Nakamura, Y.; Kasashima, E.;
Yashima, E.; Okamoto, Y.; Nishimura, J. J. Am. Chem. Soc.
1997, 119, 926.
(5) (a) Ohno, M.; Azuma, T.; Eguchi, S. Chem. Lett. 1993, 1833.
(b) Ohno, M.; Kojima, S.; Shirakawa, Y.; Eguchi, S. Tetrahe-
dron Lett. 1995, 36, 6899.
(6) Consonni, R.; Croce, P. D.; Ferraccioli, R.; La Rosa, C. J.
Chem. Soc., Perkin Trans. 1 1996, 1809.
(7) Testa, E.; Fontanella, L. Il Farmaco 1966, 549.
(8) Wright, Jr. W. B. J. Heterocyclic Chem. 1965, 2, 41.
(9) Hutchins, J. C. E.; Fife, T. H. J. Am. Chem. Soc. 1973, 95,
3786.
(10) Acylation of 1 was carried out by treating with ClCO2Et (1
equiv.) and pyridine (1 equiv.) in CH3CN at r. t. for 12 h and
at reflux temperature for 2 h. After extraction of the product,
cyclization of crude 2 with DBU (20 mol %) in refluxing to-
luene for 1.5 h gave pure 3 after recrystallization from
CH2Cl2/C6H14
Scheme 3
In the cycloadducts of 6c and 6f, FAB-MS, IR, and UV
data were comparable with those of 6a, the 13C-NMR
spectra were in part different; 30 lines due to fullerene sp2-
carbons were observed for both 6c and 6f at d 136.46-
(11) NMR data for 6a: 1H-NMR (500 MHz, CDCl3): d = 1.38 (t, J
= 7.0 Hz, 3 H), 4.31 (d, J = 13.5 Hz, 1 H), 4.33 (dq, J = 10.5
and 7.0 Hz, 1 H), 4.47 (dq, J = 10.5 and 7.0 Hz, 1 H), 4.82 (d,
Synlett 1999, No. 2, 207–209 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Synthesis of Fullerotetrahydroquinolines by Cycloaddition Reaction of C60 with Aza-ortho-xylylenes
141.88, 141.98, 142.25, 142.50, 142.56, 142.59, 142.63,
209
J = 13.5 Hz, 1 H), 7.54-7.76 (m, 4 H). 13C-NMR (125 MHz,
CDCl3): d = 14.79, 43.94, 63.04, 70.36, 80.22, 128.07, 128.28,
128.54, 128.60, 129.27, 134.61, 135.30 (2C), 135.61, 136.20,
137.12, 138.93, 139.72, 140.12, 140.42, 140.43, 141.54,
141.67, 141.76, 141.96, 142.01, 142.18, 142.35, 142.43,
142.54, 142.59, 142.75, 142.82, 142.89, 142.93, 143.07,
143.57, 144.55, 144.63, 144.71, 144.79, 144.95, 145.10,
145.34, 145.42, 145.46, 145.63, 145.64, 145.68 (2C), 145.74,
145.90 (2C), 146.11, 146.31, 146.36, 145.84, 146.53, 146.56,
146.72, 146.79 (2C), 147.93, 148.45, 150.85, 151.79, 154.28,
155.26, 156.51 (cf. Two lines between d 134.61 and 156.51
are due to sp2-carbons of a tetrahydroquinoline ring and a car-
bonyl group).
142.75, 142.86, 142.91, 142.98 (2C), 143.06, 143.36, 143.89,
144.12, 144.49, 144.74, 144.79, 144.88, 145.09, 145.26,
145.60 (2C), 145.62, 145.63, 145.68, 145.83, 145.90 (2C),
145.92, 146.31, 146.44, 146.45, 146.47, 146.51, 146.62,
146.79, 146.82, 146.93, 147.15, 147.87, 148.51, 152.61,
154.87, 156.97.
(15) (a) Ohno, M.; Shirakawa, S.; Eguchi, S. Synthesis in press.
(b) Ohno, M.; Kojima, S.; Shirakawa, S.; Eguchi, S. Hetero-
cycles 1997, 46, 49.
(16) Fishwick, C. W. G.; Storr, R. C., Manley, P. W. J. Chem. Soc.,
Chem. Commun. 1984, 1304.
(17) 13C-NMR (125 MHz, CDCl3): For 6c, d = 37.36, 43.78, 70.11,
83.59, 116.55, 122.41, 127.49, 128.70, 131.55, 136.46,
136.66, 137.63, 138.55, 138.75, 138.95, 140.54, 141.60,
141.74, 141.88, 142.24, 142.31, 142.61, 142.70, 143.14,
144.72, 144.94, 145.08, 145.35, 145.65, 145.76, 146.21,
146.35, 146.40, 146.50, 146.83, 147.62, 148.17, 148.53,
148.89, 149.46. For 6f, d = 43.17, 67.91, 78.24, 117.65,
122.66, 128.22, 128.80, 129.97, 136.23, 136.70, 139.98,
140.32, 141.70, 141.99, 142.16, 142.30, 142.35, 142.58,
142.71, 142.78, 143.10, 143.18, 144.43, 144.73, 144.94,
145.07, 145.43, 145.46, 145.50, 145.78, 146.03, 146.30,
146.31, 146.50, 146.58, 146.65, 147.78, 148.26, 155.81. (cf.
As ref. 9, one line around d 143 is due to the sp2-carbon of a
tetrahydro-quinoline ring in both compounds).
(12) Rubin, Y.; Khan, S.; Freeberg, D. I.; Yeretzian, C. J. Am.
Chem. Soc. 1993, 115, 344.
(13) Ohwada, T.; Achiwa, T.; Okamoto, I.; Shudo, K. Tetrahedron
Lett. 1998, 39, 865.
(14) Spectral data for 6b: FAB MS: m/z = 979 (M+), 720 (base). IR
(KBr): n = 1340, 1159, 526 cm-1. UV-Vis (hexane): l = 432
nm. 1H-NMR (500 MHz, CDCl3): d = 2.42 (s, 3 H), 4.12 (d, J
= 13.5 Hz, 1 H), 4.83 (d, J = 13.5 Hz, 1 H), 7.31 (d, J = 8.5 Hz,
2 H), 7.60-7.99 (m, 4 H), 8. 01 (d, J = 8.5 Hz, 2 H). 13C-NMR
(125 MHz, CDCl3): d = 21.97, 44.00, 69.43, 81.89, 128.25,
128.75, 129.04, 129.13, 129.43, 130.04, 130.60, 131.36,
135.14, 136.34, 136.58, 137.66, 138.14, 138.65, 138.73,
139.64, 139.83, 140.14, 140.77, 141.20, 141.50, 141.76,
Synlett 1999, No. 2, 207–209 ISSN 0936-5214 © Thieme Stuttgart · New York