The syntheses of pyrazino-containing sultines and their application in Diels-Alder reactions with electron-poor olefins and [60]fullerene

Article abstract of DOI:10.1021/jo9918448

The Diels-Alder reactions of heterocyclic o-quinodimethanes, generated in situ from 6,7-disubstituted quinoxalino[2,3-d]-[1,2λ⁴]oxathiine 2-oxides (6a-c), 2,3-disubstituted-8,9-dihydro-6H-8λ ⁴-[1,2]oxathiino[4,5-g]quinoxalin-8-one (7a-c) (sultines), and pyrazinosultine (22), with electron-poor olefins and [60]fullerene are described. The heterocyclic-fused sultines 7a-c and 22 are readily prepared from the corresponding dibromides 9a-c and 24 with the commercially available Rongalite (sodium formaldehyde sulfoxylate). When heated in the presence of electron-poor dienophiles and [60]fullerene, all of the sultines underwent extrusion of SO₂, and the resulting heterocyclic o-quinodimethanes (3a-d, 4a-c, and 25) were intercepted as the 1:1 adducts in good to excellent yields. The temperature-dependent ¹H NMR spectra of fullerene derivatives 31-38 show a dynamic process for the methylene protons. The activation free energies (ΔG_c^?) determined for the boat-to-boat inversion of these pyrazino-containing C₆₀ compounds (31-34 and 38) are found to be in the range of 14.1-14.8 kcal/mol, but they are in the range of 15.2 to >17.1 kcal/mol for adducts 35-37. The activation free energies (ΔG_C^?) are significantly affected by (1) the orientations and (2) the substituents of the quinoxaline rings and (3) the extended benzannulation in the arenes of C₆₀ adducts (see Table 2), which implies that both electronic interactions and steric effects between the aromatic addends and C₆₀ are important. Tautomerization of methylquinoxaline to its enamine is invoked as a rationalization for the lowering of ΔG_C^? in some of the fulleroadducts.

Full text of DOI:10.1021/jo9918448

J . Org. Chem. 2000, 65, 3395-3403
3395
Th e Syn th eses of P yr a zin o-Con ta in in g Su ltin es a n d Th eir
Ap p lica tion in Diels-Ald er Rea ction s w ith Electr on -P oor Olefin s
a n d [60]F u ller en e
J ing-Horng Liu, An-Tai Wu, Ming-Hwei Huang, Chein-Wei Wu, and Wen-Sheng Chung*
Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan 30050, R. O. C.
Received November 30, 1999
The Diels-Alder reactions of heterocyclic o-quinodimethanes, generated in situ from 6,7-
disubstituted quinoxalino[2,3-d]-[1,2λ4]oxathiine 2-oxides (6a -c), 2,3-disubstituted-8,9-dihydro-6H-
8λ4-[1,2]oxathiino[4,5-g]quinoxalin-8-one (7a -c) (sultines), and pyrazinosultine (22), with electron-
poor olefins and [60]fullerene are described. The heterocyclic-fused sultines 7a -c and 22 are readily
prepared from the corresponding dibromides 9a -c and 24 with the commercially available Rongalite
(sodium formaldehyde sulfoxylate). When heated in the presence of electron-poor dienophiles and
[60]fullerene, all of the sultines underwent extrusion of SO2, and the resulting heterocyclic
o-quinodimethanes (3a -d , 4a -c, and 25) were intercepted as the 1:1 adducts in good to excellent
1
yields. The temperature-dependent H NMR spectra of fullerene derivatives 31-38 show a dynamic
q
process for the methylene protons. The activation free energies (∆Gc ) determined for the boat-to-
boat inversion of these pyrazino-containing C60 compounds (31-34 and 38) are found to be in the
range of 14.1-14.8 kcal/mol, but they are in the range of 15.2 to >17.1 kcal/mol for adducts 35-
q
37. The activation free energies (∆Gc ) are significantly affected by (1) the orientations and (2) the
substituents of the quinoxaline rings and (3) the extended benzannulation in the arenes of C60
adducts (see Table 2), which implies that both electronic interactions and steric effects between the
aromatic addends and C60 are important. Tautomerization of methylquinoxaline to its enamine is
q
invoked as a rationalization for the lowering of ∆Gc in some of the fulleroadducts.
Derivatives of [60]fullerene have become the current
focus of research in biological and material science
because of the unique spherical structure of this molecule
and its feasibility for bulk production.1 Among the many
derivatization methods available, cycloaddition reactions
have played an important role, with the Diels-Alder
reaction being particularly useful.1 In the pioneering
stage, many of the cycloadducts to C60 were found to be
thermally unstable because they undergo cycloreversion
to give the component molecules.1 Stable Diels-Alder
adducts of C60 were first explored by Mu¨llen2a-d and
Rubin2e-g in their pioneering work using o-quinodimethane
(1) and its analogues as reactive dienes. These highly
reactive species, generated in situ from a variety of
precursors,2,3 are efficiently trapped by [60]fullerene,
which gains extra stabilization because of the restoration
of the aromatic system.
Although o-quinodimethane 1 has frequently been used
for the derivatization of [60]fullerene, its heterocyclic
analogues 2 have been recognized only recently.4 Various
(3) For reviews of o-quinodimethanes, benzocyclobutenes, and re-
lated chemistry, see: (a) Oppolzer, W. Synthesis 1978, 793; Heterocycles
1980, 14, 1615. (b) Kametani, T. Pure Appl. Chem. 1979, 51, 747. (c)
Funk, R. L.; Vollhardt, K. P. C. Chem. Soc. Rev. 1980, 9, 41. (d) Mart´ın,
N.; Seoane, C.; Hanack, M. Org. Prep. Proced. Int. 1991, 23, 237. (e)
Chou, T.-S. Rev. Heteroat. Chem. 1993, 8, 65. (f) Ando, K.; Kankake,
M.; Suzuki, T.; Takayama, H. Tetrahedron 1995, 51, 129. (g) Collier,
S. J .; Storr, R. C. Prog. Heterocycl.c Chem. 1998, 10, 25. (h) Segura, J .
L.; Mart´ın, N. Chem. Rev. 1999, 99, 3199.
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Tome´, A. C.; Enes, R. F.; Cavaleiro, J . A. S.; Elguero, J . Tetrahedron
Lett. 1997, 38, 2557. (b) Tome´, A. C.; Cavaleiro, J . A. S.; Storr, R. C.
Tetrahedron 1996, 52, 1723; 1996, 52, 1735; 1993, 34, 6639. (c) Boulle,
C.; Cariou, M.; Bainville, M.; Gorgues, A.; Hudhomme, P.; Orduna, J .;
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Shirakawa, Y.; Eguchi, S. Tetrahedron Lett. 1996, 37, 9211; 1995, 36,
6899. (e) Ferna´ndez-Paniagua, U. M.; Illescas, B. M.; Mart´ın, N.;
Seoane, C. J . Chem. Soc., Perkin Trans. 1 1996, 1077 and reference
cited therein. (f) Ohno, M.; Koide, N.; Eguchi, S. Heterocycl. Commun.
1995, 1, 125. (g) Ohno, M.; Kojuma, S.; Eguchi, S. J . Chem. Soc., Chem.
Commun. 1995, 565. (h) Carly, P. R.; Compernolle, F.; Hoornaert, G.
J . Tetrahedron Lett. 1995, 36, 2113. (i) Carly, P. R.; Cappelle, S. L.;
Compernolle, F.; Hoonaert, G. J . Tetrahedron 1996, 52, 11889. (j) Al
Hariri, M.; J ouve, K.; Pautet, F.; Domard, M.; Fenet, B.; Fillion, H. J .
Org. Chem. 1997, 62, 405.
(1) For recent reviews, see: (a) Hirsch, A. Synthesis 1995, 895. (b)
Hirsch, A. The Chemistry of the Fullerenes; Thieme Medical Publish-
ers: New York, 1994. (c) Diederich, F.; Isaacs, L.; Philip, D. Chem.
Soc. Rev. 1994, 243. (d) Averdung, J .; Torres-Garcia, G.; Luftmann,
H.; Schlachter, I.; Mattay, J . Fullerene Sci. Tech. 1996, 4, 633. (e)
Diederich, F.; Kessinger, R. Acc. Chem. Res. 1999, 32, 537. (f) Wudl,
F. Acc. Chem. Res. 1992, 25, 157. (g) Da Ros, T.; Prato, M. Chem.
Commun. 1999, 663. (h) Kra¨utler, B.; Maynollo, J . Tetrahedron 1996,
52, 5033.
(2) (a) Gu¨gel, A.; Belik, P.; Water, M.; Kraus, A.; Harth, E.; Wagner,
M.; Spickermann, J .; Mu¨llen, K. Tetrahedron 1996, 52, 5007. (b) Belik,
P.; Gu¨gel, A.; Kraus, A.; Water, M.; Mu¨llen, K. J . Org. Chem. 1995,
60, 3307. (c) Gu¨gel, A.; Kraus, A.; Spickermann, J .; Belik, P.; Mu¨llen,
K. Angew. Chem., Int. Ed. Engl. 1994, 33, 559. (d) Belik, P.; Gu¨gel,
A.; Spickermann, J .; Mu¨llen, K. Angew. Chem., Int. Ed. Engl. 1993,
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Chem. Soc. 1993, 115, 344. (f) Khan, S. I.; Oliver, A. M.; Paddon-Row,
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M.; Oliver, A. M.; Rothenfluh, D. F.; An, Y.-Z.; Ellis, G. A.; Ranasinghe,
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references therein.
10.1021/jo9918448 CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/11/2000

3396 J . Org. Chem., Vol. 65, No. 11, 2000
Sch em e 1. Syn th eses of 2,3-Disu bstitu ted Qu in oza lin osu ltin es 7a -c
Liu et al.
methods for generating these highly reactive dienes have
been developed. Among them, cheletropic elimination of
SO2 from heteroaromatic-fused 3-sulfolenes and 1,4-
elimination from the corresponding R,R′-dihalides have
drawn the most attention.3,4 Quinoxalines are important
naturally occurring heterocycles and are usually found
to have biological and pharmaceutical activity.5 Although
Chou et al. reported6a the generation of quinoxalino-o-
quinodimethane 3a from SO2 extrusion of the corre-
sponding sulfolene 5, all of their attempts to isolate the
Diels-Alder adducts failed. To our surprise, the 1,4-
elimination from 2,3-bis(bromomethyl)quinoxaline by NaI
in DMF also failed to give the expected Diels-Alder
adducts when strong dienophiles such as N-methyl and
N-phenylmaleimide were applied,6b even though this
method is generally assumed to give the heterosubsti-
tuted o-quinodimethane 3a . Thus, finding an easy and
high-yield method for generating quinoxalino-2,3- and
quinoxalino-6,7-quinodimethanes 3 and 4 is of particular
interest.
cyclicfused sultines 7a -c and 22, sulfolenes 13a -c, and
cyclobutenes 18a -c and their application in Diels-Alder
reactions with electron-poor olefins and C60.9
Resu lts a n d Discu ssion
Previously unknown quinoxalino-fused sultines 7a -c
were readily synthesized from the reactions of Rongalite
(sodium formaldehyde sulfoxylate) with the correspond-
ing 2,3-disubstituted 6,7-dibromomethylquinoxalines 9a-c
(where R ) H, Cl, and phenyl)5 in 55-76% yields (Scheme
1). The 6,7-dibromomethylquinoxaline 9a was obtained
from NBS bromination of 6,7-dimethylquinoxaline 8a ,5b
which, in turn, was obtained from the condensation of
4,5-dimethyl-1,2-phenylenediamine (10) with glyoxal (pro-
cess a) in aqueous sodium hydrogen sulfite at 80 °C. The
preparation of 2,3-dichloro-6,7-bis(bromomethyl)-quinox-
aline 9b followed a method developed by Leeson et al.,5c,d
which also started from 10 but in which 10 was reacted
with oxalic acid to give 1,4-dihydro-6,7-dimethylquinoxa-
line-2,3-dione 11 in 98% yield (process b). Refluxing 11
in POCl3 for 4 h gave the desired 2,3-dichloro-6,7-
Recently, we reported a high-yield method for the
generation and trapping of quinoxalino-2,3-quinodi-
methanes 3a -c from thermolysis of the corresponding
sultines 6a -c.7
(5) (a) Villemin, D.; Martin, B. Synth. Commun. 1995, 25, 2319. (b)
Baudy, R. B.; Greenblatt, L. P.; J irkovsky, I. L.; Conklin, M.; Russo,
R. J .; Bramlett, D. H.; Emrey, T. A.; Simmonds, J . T.; Kowal, D. M.;
Stein, R. P.; Tasse, R. P. J . Med. Chem. 1993, 36, 331. (c) Leeson, P.
D.; Baker, R.; Carling, R. W.; Crutis, N. R.; Moore, K. W.; Williams,
B. J .; Foster, A. C.; Donald, A. E.; Kemp, J . A.; Marshall, G. R. J . Med.
Chem. 1991, 34, 1243. (d) Cai, S. X.; Kher, S. M.; Zhou, Z.-L.; Ilyin, V.;
Espitia, S. A.; Tran, M.; Hawkinson, J . E.; Woodward, R. M.; Weber,
E.; Keana, J . F. W. J . Med. Chem. 1997, 40, 730. (e) Anderson, L. M.;
Butler, A. R. J . Chem. Soc., Perkin Trans. 2 1994, 323.
(6) (a) Chou, T.-S.; Ko, C.-W. Tetrahedron 1994, 50, 10721. (b)
Alexandrou, N. E.; Mertzanos, G. E.; Stephanidou-Stephanatou, J .;
Tsoleridis, C. A.; Zachariou, P. Tetrahedron Lett. 1995, 36, 6777. (c)
Chou, T.-S.; Ko, C.-W. Molecules 1996, 1, 93.
(7) (a) Chung, W.-S.; Liu, J .-H. Chem. Commun. 1997, 205. (b)
Chung, W.-S.; Lin, W.-J .; Liu, W.-D.; Chen, L.-G. J . Chem. Soc., Chem.
Commun. 1995, 2537 and references therein.
(8) Different methods in the synthesis of 31 have been reported,
see: (a) Torres-Garcia, G.; Luftmann, H.; Wolff, C.; Mattay, J . J . Org.
Chem. 1997, 62, 2752. (b) Ferna´ndez-Paniagua, U. M.; Illescas, B. M.;
Mart´ın, N.; Seoane, C.; de la Cruz, P.; de la Hoz, A.; Langa, F. J . Org.
Chem. 1997, 62, 3705. (c) Ohno, M.; Koide, N.; Sato, H.; Eguchi, S.
Tetrahedron 1997, 53, 9075,
(9) Part of this work has already been presented as follows: (a) In
Book of Abstracts; 16th International Congress of Heterocyclic Chem-
istry, Bozeman, MT, 1997; OP-V-13. (b) Presented at the 216th
National Meeting of American Chemical Society, Boston, MA, August
23-27, 1998; Paper 139.
The sultines prove to be excellent precursors for hetero-
cyclic o-quinodimethanes 2 and can react with many good
dienophiles under mild conditions. Interestingly, Mattay
et al.,8a Mart´ın et al.,8b and Eguchi et al.8c have indepen-
dently reported the syntheses of quinoxalino-fused [60]-
fullerene. The latter two groups both used the iodide-
induced 1,4-elimination method to generate reactive 3a
from corresponding 2,3-bis(bromomethyl)quinoxaline and
then trapped it with C60; however, Mattay et al. prepared
the quinoxalino-fused fullerene by condensation of C60-
fused diketone with o-diaminoarenes. We report here the
synthesis of several novel nitrogen-containing hetero-

Pyrazino-Containing Sultines
J . Org. Chem., Vol. 65, No. 11, 2000 3397
Sch em e 2. Sea led -Tu be P yr olysis of Su ltin es 7a -c, Su lfolen es 13a -c, a n d Cyclobu ten es 18a -c in
Tolu en es
Ta ble 1. F or m a tion a n d Tr a p p in g of o-QDM 4a -c w ith Va r iou s Dien op h iles (3 equ iv) in a Sea led Tu be in Tolu en e
precursor to
o-QDM 4a -c
reaction
entry
quencher
conditionsa
products (yield)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
7a
7a
7a
7a
dimethyl fumarate
N-phenylmaleimide
fumaronitrile
MeOH
A
A
A
A
A
D
D
B
B
B
B
B
D
D
C
C
C
C
C
C
C
D
D
14a (75%) + 13a (6%)
16a (87%) + 13a (trace)
17a (75%) + 13a (trace)
13a (57%) + 18a (31%)
18a (63%) + 13a (28%)
no reaction
b
7a
-
13a
18a
7b
7b
7b
7b
7b
13b
18b
7c
7c
7c
7c
7c
7c
7c
13c
18c
N-phenylmaleimide
N-phenylmaleimide
diethyl fumarate
dimethyl maleate
N-phenylmaleimide
MeOH
no reaction
12b (82%) + 13b (6%)
15b (62%) + 13b (15%)
16b (93%) + 13b (trace)
13b (45%) + 18b (42%)
18b (55%) + 13b (35%)
no reaction
b
-
N-phenylmaleimide
N-phenylmaleimide
diethyl fumarate
dimethyl fumarate
dimethyl maleate
N-phenylmaleimide
fumaronitrile
no reaction
12c (92%) + 13c (trace)
14c (83%) + 13c (trace)
15c (60%) + 13c (20%)
16c (98%) + 13c (trace)
17c (60%) + 13c (10%)
13c (45%) + 18c (16%)
13c (74%) + 18c (12%)
no reaction
MeOH
b
-
N-phenylmaleimide
N-phenylmaleimide
no reaction
a
b
Reaction conditions: A, 180 °C for 4 h; B, 200 °C for 4 h; C, 200 °C for 24 h; and D, 210 °C for 24 h. No quencher was added.
dimethylquinoxaline 8b in 93% yield, which, after NBS
bromination, gave the dibromide 9b in 75% yield. Simi-
larly, refluxing 10 with benzil in benzene (process c) led
to the formation of 2,3-diphenyl-6,7-dimethylquinoxaline
8c in 97% yield, which, after NBS bromination, gave the
desired 2,3-diphenyl-6,7-bisbromomethylquinoxaline 9c.
The Diels-Alder reactions of these sultines (7a -c)
with typical dienophiles are presented in Scheme 2 and
Table 1. For example, when heated in toluene (sealed
tube; 4 h for 7a ,b; 24 h for 7c) in the presence of 3 equiv
of diethyl fumarate, dimethyl fumarate, dimethyl male-
ate, fumaronitrile, or N-phenylmaleimide, the sultines
7a -c all underwent extrusion of SO2, and the resulting
quinoxalino-6,7-quinodimethanes 4a -c were intercepted
as the 1:1 adducts (12-17) in 60-98% yields (entries
1-3, 8-10, and 15-19 of Table 1). Small amounts
(e20%) of sulfolenes 13a -c were also formed; however,
they did not react with any of these dienophiles even at
210 °C (entries 6, 13, and 22), in contrast with the high
reactivities of sultines 6a -c7a and 7a -c. The low reactiv-
ity of sulfolenes 13a -c is consistent with that reported
by Chou et al. in the pyrolysis of sulfolene 5.6a

3398 J . Org. Chem., Vol. 65, No. 11, 2000
Liu et al.
Sch em e 3. Syn th esis of P yr a zin osu ltin e a n d its
Tr a p p in g Rea ction s
Although the structure and reactivity of 2,3-disubsti-
tuted quinoxalinosultines 7a -c are very similar to those
of 6,7-disubstituted quinoxalinosultines 6a -c,7a there are
three major differences in their reaction products. In the
absence of a dienophile, sultines 7a -c underwent ther-
mal extrusion of SO2 to form the cyclobuta[6,7-g]qui-
noxalines 18a -c and the rearranged sulfolenes 13a -c
in various ratios depending on the substituents (entries
5, 12, and 21). The same mixtures (13 and 18) were
formed in the pyrolysis of sultines 7a -c in toluene with
added MeOH (entries 4, 11, and 20). This is in contrast
to our previous observation on the thermolysis of sultines
6a -c, in which the corresponding 2,3-dimethylquinoxa-
lines 19a -c were the only products when hydrogen
donors such as MeOH or 1,4-cyclohexadiene were present.
The second important difference between the thermal
reaction of sultines 7a -c and 6a -c is in their trapping
behavior with NPM. The reaction of 6a -c with excess
NPM at 200 °C gave mixtures of cis- and trans-quinox-
alinocyclooctenes 21, but the reaction of 7a -c with excess
NPM gave only the 1:1 Diels-Alder adducts 16a -c.10
The third surprise is that the cyclobuta[6,7-g]quinoxa-
lines 18a -c did not react with any dienophiles (e.g.,
NPM; entries 7, 14, and 23) even at 210 °C for 24 h, but
their analogues, cyclobuta[1,2-b]quinoxalines 20a -c,
reacted smoothly at 180 °C with all of the dienophiles
listed above.7a As a matter of fact, the cyclobutapyrim-
idines have been successfully applied as o-QDM precur-
sors in syntheses of Diels-Alder adducts and fullerene
derivatives.13b,c
The pyrazino-fused sultine 22 can also be prepared
similarly from corresponding bisbromide 24, which was
prepared by bromination of commercial available 2,3-
dimethylpyrazine 23. When sultine 22 was refluxed in
toluene in the presence of 1.2 equiv of dienophiles (e.g.,
N-phenylmaleimide, dimethyl fumarate, etc.), the 1:1
Diels-Alder adducts (27-30) were obtained in good to
excellent yields (Scheme 3). Without any quencher,
sulfolene 266c was obtained in 73% yield. It is important
to note that the reaction temperature decreased from
180-200 °C in quinoxalinosultines 6a -c and 7a -c to
110 °C in pyrazinosultine 22; however, the corresponding
pyrazino sulfolene 26 was reported6c to react with dieno-
philes only at 300 °C!
The quinoxalinosultines 6a -c reported7a previously
and all of the sultines prepared in this work were tested
for their reactivity with [60]fullerene. When C60 (50 mg,
0.069 mmol) was refluxed in o-dichlorobenzene (in tolu-
ene for 22) with a slight excess (1.2 equiv) of the pyrazino-
containing sultines 6, 7, and 22 for a variable period of
time (24 h for 6 and 7, 6 h for 22), the 1:1 cycloadducts
were obtained in moderate to good yields as follows: 31,
66%; 32, 78%; 33, 53%; 34, 51%; 35, 84%; 36, 10%; 37,
29%; and 38, 75% (all based on consumed C60, Scheme
4). The yield for adduct 36 was very poor because of the
difficulty in finding a proper solvent to dissolve both
sultine 7b and C60. The isolation of cycloadducts 31-38
was accomplished by column chromatography on silica
gel using hexane/toluene (4:1) to toluene as the eluent.
Interestingly, the mono-addition product of C60 is pre-
dominantly formed in these pyrazino-containing sultines
without detection of appreciable amounts of bis-addition
products. The reactivity of fullerene double bonds (at the
6,6-ring junction) is probably decreased by a significant
amount after the first addition of a quinoxaline group
on C60, which permits the obtainment of high yields of
mono adducts.2g The structures of the cycloadducts 31-
38 were elucidated by spectral inspections. First, FAB-
MS confirmed the presence of the 1:1 cycloadducts by the
molecular ion peaks (M + 1) at the following m/z values:
(10) In a recent review, Storr3g revised his assignments5a,b of the
eight-membered ring to an ene-reaction-type product. Our results,7a
however, seemed to fit with the cis- and trans-cylooctenes.
(11) (a) Ref 2e. (b) Friebolin, H. Basic One- and Two-Dimensional
NMR Spectroscopy; VCH: Weinheim, Germany, 1993; p 293.
(12) The Tc and ∆Gcq values of naphthaleno-fused [60]fullerene were
reported by Najanyram, Y.; Minowa, T.; Tobita, S.; Shizuka, H.;
Nishimura, J . J . Chem. Soc., Perkin Trans. 2 1995, 2351.
(13) (a) Illescas, B. M.; Mart´ın, N.; Seoane, C.; Ort´ı, E.; Viruela, P.
M.; Viruela, R.; de la Hoz, A. J . Org. Chem. 1997, 62, 7585. (b)
Gonzalez, B.; Herrera, A.; Illescas, B.; Mart´ın, N.; Martinez, R.;
Moreno, F.; Sanchez, L.; Sanchez, A. J . Org. Chem. 1998, 63, 6807. (c)
Herrera, A.; Mart´ınez, R.; Gonza´lez, B.; Illescas, B.; Mart´ın, N.; Seoane,
C. Tetrahedron Lett. 1997, 38, 4873. (d) Illescas, B. M.; Mart´ın, N.;
Seoane, C.; de la Cruz, P.; Langa, F.; Wudl, F. Tetrahedron Lett. 1995,
36, 8307.

Pyrazino-Containing Sultines
J . Org. Chem., Vol. 65, No. 11, 2000 3399
Sch em e 4. Diels-Ald er Rea ction s of Su ltin es
w ith [60]F u ller en e
F igu r e 1. Various temperature measurements of 1H NMR
spectra (600 MHz, 1:3 CDCl3/CS2) of Diels-Alder adducts: (A)
31, for which Tc is 308 K; and (B) 35, for which Tc is 328 K.
methylene protons were measured. On the basis of the
coalescence temperatures of these heteroaromatic-fused
fullerene adducts 31-38, the activation free energies of
q
inversion ∆Gc at the corresponding temperatures were
calculated and are summarized in Table 2. For example,
variable-temperature experiments of 31 revealed that the
ring inversion was in the slow exchange region below 0
°C, giving a well-resolved AB quartet with a chemical
shift difference of 0.25 ppm, and an activation energy
q
∆Gc of 14.5 ( 0.2 kcal/mol was calculated (Figure 1).
Similar activation energies were obtained for adducts 32
and 34 (Table 2). The value for adduct 33 was not
measured because of its poor solubility in most organic
solvents. Interestingly, compound 35 showed a larger
chemical shift difference (0.38 ppm), a higher coalescence
31, 877; 32, 905; 33, 944; 34, 891; 35, 877; 36, 939; 37,
1029; and 38, 827. The base peaks were at m/z 720 in
most cases. In the UV/vis spectra of 31-38, a new sharp
band with λmax near 434 nm appeared, which is very
characteristic of the Diels-Alder monoadducts of [60]-
fullerene at the 6,6-ring junction.1
q
temperature (55 °C), and hence, a larger ∆Gc (15.2 (
0.2 kcal/mol), even though its structure is very similar
q
to those of 31-34. The activation energies ∆Gc were
In 1H NMR spectra measured at 22 °C, the two
methylene protons show two broadened signals (δ 4.8-
4.9 and 5.1-5.2) for adducts 31-34. In contrast, they
show two well resolved AB quartets for adducts 35-37
and a singlet for adduct 38 (see Experimental Section).
The two diastereotopic methylene protons are separated
by 0.27 ( 0.01 ppm for adducts 31-34, but are further
separated by 0.38 ( 0.02 ppm for adducts 35-37.
Variable-temperature NMR measurements (vide infra)
imply that the Diels-Alder adducts 31-38 involve some
flipping motion of the cyclohexene rings and that the
inversion rates of the cyclohexene rings are clearly
different among these adducts. Calculations8,13,14b and
X-ray structural analysis2e,f of many Diels-Alder adducts
of C60 have shown that the most stable conformation of
the cyclohexene ring is the boat form and that the
inversion occurs between the two equivalent boat con-
formations. To estimate the difference in the inversion
rates among these adducts, variable-temperature 1H
NMR measurements11 were carried out, and the coales-
cence temperatures for the two doublet signals of the
astonishingly high for 2,3-dichloroadduct 36 (a low limit
of 17.2 kcal/mol was estimated) and 2,3-diphenyladduct
37 (17.1 kcal/mol). The bulky dichloro and diphenyl
substituents should have lowered the activation energy
barriers in adducts 36 and 37 if steric hindrance were
the only factor affecting the boat-to-boat conformation
transitions. Although steric effects have been proposed12
as the main factor in a study of a series of aromatic
attached fullerene adducts, other factors such as π-π and
n-π electronic interactions are needed to explain the
current results.
Based on their semiempirical PM3 calculations,8b
Mart´ın et al. have found a linear correlation between the
activation energy barriers and the length of the C62-
C63 bond in aromatic-fused fullerenes, i.e., as the bond
length increases the barrier also increases.13a,b They
therefore proposed that the geometrical features, but not
the electronic properties, of the organic addend are
responsible for the activation energy barriers. Scrutiniz-
ing the activation energy barriers in Table 2, one may
suspect that some kind of “electronic interactions” are
involved, because quite different activation energy bar-
riers were obtained for quinoxalino heterocycles of similar
sizes but different orientations with respect to C60. For
example, the activation energy barrier ∆Gcq of fullerene
adduct 31 was found to be smaller (14.5 kcal/mol) than
(14) For strong evidence of through-space orbital interactions in
fulleroids, see: (a) Eiermann, M.; Haddon, R. C.; Knight, B.; Li, Q. C.;
Maggini, M.; Mart´ın, N.; Ohno, T.; Prato, M.; Suzuki, T.; Wudl, F.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1591. (b) Iyoda, M.; Sultana,
F.; Sasaki, S.; Yoshida, M. J . Chem. Soc., Chem. Commun. 1994, 1929.

3400 J . Org. Chem., Vol. 65, No. 11, 2000
Ta ble 2. Activa tion F r ee En er gies (∆Gc‡) of F u ller en e Ad d u cts 31-42 fr om Dyn a m ic 1H NMRa
Liu et al.
a
Various temperature measurements were taken in a Bruker 600 MHz NMR, unless otherwise specified, and the solvents used were
either CDCl3/CS2 ) 3:1 or d4-ortho-dichlorobenzene (for Tc higher than 55 °C). The activation free energies were obtained using equations
2
2
‡
b
from ref 11. kc) 2.22(∆νAB + 6 J AB
)
1/2, ∆Gc ) 4.58 Tc (10.32 + log (Tc/kc)) × 10-3 kcal/mol. Recorded in a 300 MHz NMR. c Data are
reported at the highest temperature that affords well-separated quartets. For example, -12 °C for 31 and 32, -5 °C for 34, 10 °C for 35,
and -60 °C for 38. Recorded in a 500 MHz NMR.
d
that of adduct 35 (15.2 kcal/mol), even though their sizes
are exactly the same except that the pyrazine ring is
closer to C60 framework in the former. We also noted a
general trend in our data that supports the notion of
electronic π-π interactions: the activation energy barrier
is larger with increased benzannulation. For example, a
tomerization, may stabilize the transition state energy
and, thus, decrease the boat-to-boat inversion barriers.15
Interestingly, fulleroadducts with benzoquinone and
naphthoquinone addends (39a -c), have the smallest
q
∆Gc reported thus far for the series of Diels-Alder
adducts of C60 (see Table 2). In adducts 39a -c and 40,
the repulsion between the lone-pair electrons of quinone
and the π-electrons of C60 could conceivably play an
important role in lowering the transition state energy
during the ring-inversion processes.
q
comparison of the ∆Gc values of 38 (14.1 kcal/mol), 31
(14.5 kcal/mol), and 42 (15.8 kcal/mol) shows that 0.4
kcal/mol is added for the first benzannulation and an
additional 1.3 kcal/mol is added for naphthoannulation.
Such a difference has been observed previously by
Nishimura et al.12 and Mart´ın et al.13a for carbocyclic
analogues and was partly assigned to electronic-π inter-
actions between the C60 framework and the overlying
aromatic ring.
It is, however, a surprise to note that pyrazino annu-
lation between C60 and the aromatic ring leads to a
decrease in ∆Gcq of at least 0.5-0.6 kcal/mol (cf. 39c and
40, 41, and 42). In the latter cases, nonbonded repulsion
between the lone-pair electrons of the nitrogens and the
C60 framework is probably involved and, thus, may
decrease the activation energy barriers. Alternatively, the
lowering of the activation energy barriers in the adducts
31-34 compared with those of adducts 35-37 can be
explained by the tautomeric equilibrium between dim-
ethylquinoxaline and its enamine tautomers. That is, the
planarity of the cyclohexene ring, caused by the tau-
Finally, the 13C NMR spectroscopy also provides im-
portant information about the structure of cycloadducts
31-38. The position of attack of these heterocyclic
o-quinodimethanes (3, 4, and 25) on a double bond
between two annelated six-membered rings of the fullerene
is shown by the number of 13C NMR signals. Seventeen
such signals of fullerene indicate a C2v symmetry for the
molecule (resulting from rapid ring inversion of the
cyclohexene unit if measured above the coalescence
temperature Tc).2d However, if the spectrum is taken at
a temperature below Tc, one sees a well-resolved AB
quartet in the 1H NMR for cycloadducts 31-38. The
conformation is frozen, and one expects to observe 32
(15) For tautomerization of quinoxaline, see: (a) Aumiller, W. D.;
Dalton, C. R.; Czarnik, A. W. J . Org. Chem. 1995, 60, 728. (b) Pohmer,
J .; Lakshmikantham, M. V.; Cava, M. P. J . Org. Chem. 1995, 60, 8283.
(c) Scho¨nberg, A.; Mostafa, A. J . Chem. Soc. 1943, 654.

Pyrazino-Containing Sultines
J . Org. Chem., Vol. 65, No. 11, 2000 3401
Hz); 13C NMR (75.4 MHz, CDCl3) δ 145.55 (CH), 145.44 (CH),
142.37 (Cq), 141.85 (Cq), 135.54 (Cq), 130.20 (CH), 128.95 (Cq),
126.18 (CH), 62.79 (CH2), 57.15 (CH2); MS (EI) m/z 220 (M+,
1), 156 (M+ - SO2, 100); HRMS calcd for C10H8N2O2S 220.0306,
found 220.0304.
signals of the fullerene because of its Cs symmetry.
Indeed, we have observed that the peak numbers in 13C
NMR and the symmetry of 31, 32, and 35 are dependent
on measuring temperatures (see Experimental Section).
This explains why some of the reported 13C NMR signal
numbers were less than expected if they were run in a
slow exchanging mode.4c, 8a
2,3-Dich lor o-8,9-d ih yd r o-6H-8λ4-[1,2]oxa th iin o[4,5-g]-
qu in oxa lin -8-on e, Su ltin e 7b: a pale gray solid; mp 182-
1
186 °C; H NMR (300 MHz, CDCl3) δ 7.91 (2H, s), 5.50 (1H,
AB, J ) 14.1 Hz), 5.19 (1H, AB, J ) 14.1 Hz), 4.63 (1H, A′B′,
J ) 15.6 Hz), 3.80 (1H, A′B′, J ) 15.6 Hz); 13C NMR (75.4
MHz, CDCl3) δ 146.40 (Cq), 140.14 (Cq), 139.64 (Cq), 136.93
(Cq), 130.47 (Cq), 129.24 (Cq), 129.16 (CH), 125.05 (CH), 62.52
(CH2), 57.07 (CH2); MS (EI) m/z 288 (M+, 7), 224 (M+ - SO2,
100), 189 (28); HRMS calcd for C10H6Cl2N2O2S 287.9527, found
287.9520. Anal. Calcd for C10H6Cl2N2O2S: C, 41.54; H, 2.09;
N, 9.69. Found: C, 41.35; H, 2.29; N, 9.46.
Su m m a r y a n d Con clu sion s
We report here a convenient, high-yield method for the
syntheses of quinoxalinosultines 7a -c and pyrazinosul-
tine 22 and their application in Diels-Alder reactions
with electron-poor olefins and C60. Although the struc-
tures of 2,3-quinoxalinosultines 7a -c are very similar
to those of 6,7-quinoxalinosultines 6a -c,7a their reaction
products are different in three respects. Among the other
reported syntheses of quinoxalino-fused [60]fullerenes,8
our methods give the best yields. Quinoxalinosultines,
pyrazinosultine, and other heterocyclic analogues7 are
thus useful synthons of heterocyclic o-quinodimeth-
anes 2.
2,3-Dip h en yl-8,9-d ih yd r o-6H-8λ4-[1,2]oxa th iin o[4,5-g]-
qu in oxa lin -8-on e, Su ltin e 7c: a pale yellow solid; mp 219-
1
223 °C; H NMR (300 MHz, CDCl3) δ 8.08-8.07 (2H, d, J )
4.4 Hz), 7.52-7.50 (4H, m), 7.39-7.26 (6H, m), 5.55, 5.21 (2H,
ABq, J ) 13.7 Hz), 4.71, 3.82 (2H, A′B′q, J ) 15.4 Hz); 13C NMR
(75.4 MHz, CDCl3) δ 154.29 (Cq), 154.18 (Cq), 140.85 (Cq),
140.31 (Cq), 138.58 (Cq), 135.64 (Cq), 129.95 (CH), 129.76 (CH),
129.08 (CH), 128.89 (Cq), 128.29 (CH), 126.12 (CH), 63.16
(CH2), 57.75 (CH2); MS (EI) m/z 372 (M+, 6), 309 (27), 308 (M+
- SO2, 100), 307 (56), 102 (24); HRMS calcd for C22H16N2O2S
372.0934, found 372.0941. Anal. Calcd for C22H16N2O2S: C,
70.97; H, 4.30; N, 7.53. Found: C, 70.18; H, 4.54; N, 7.58.
Gen er a l P r oced u r e for th e Tr a p p in g Exp er im en ts of
Qu in oxa lin osu ltin es 7a -c w ith Dien op h iles su ch a s
Dieth yl F u m a r a te, Dim eth yl F u m a r a te, Dim eth yl Ma le-
a te, N-P h en ylm a leim id e, a n d F u m a r on itr ile. A solution
of quinoxalinosultines 7a (50 mg, 0.23 mmol), with or without
their respective dienophiles (3 equiv vs 7), in toluene (4 mL)
was sealed in a 20-mL Pyrex tube by three cycles of the freeze-
pump-thaw method and was heated at 180 °C for 4 h. (The
solutions for 7b were also heated at 200 °C for 4 h, but those
for 7c were heated for 24 h.) After the solution cooled to room
temperature, the solvent was evaporated under vacuum, and
the residue was subjected to silica gel chromatography using
hexane/ethyl acetate (from 1:1 to 1:4) as the eluent. Respective
yields for the trapping experiments with or without dienophiles
are summarized in Scheme 2 and Table 1.
Dynamic NMR spectra were recorded for the hetero-
cyclic-fused [60]fullerenes (31-38), and their boat-to-boat
q
inversion energy barriers (∆Gc ) were determined. Our
results indicate that the π-π and n-π electronic interac-
tions and the “tautomerization-induced planar effects”
are three important factors in determining the activation
free energy barriers. However, how they correlate with
the “bond-length effect of C62-C63” is not yet fully
understood and will be the subject of further theoretical
calculations. Work is in progress in this direction.
Exp er im en ta l Section
Gen er a l. Melting points were determined on a Yanaca MP-
500D melting point apparatus and are uncorrected. H NMR
1
spectra were recorded at either 300 or 600 MHz, 13C and DEPT
NMR spectra were recorded at either 75.4 or 150.9 MHz, and
the chemical shifts are reported in parts per million (δ) relative
to CDCl3 (δ ) 7.25 for a proton and 77 ppm for carbon) or
tetramethylsilane as the internal standard. Coupling constants
are reported in hertz (Hz). The matrix used for FAB mass
spectra was m-nitrobenzyl alcohol. C, H, and N combustion
Dieth yl-(7R,8R)-2,3-d ich lor o-6,7,8,9-tetr a h yd r oben zo-
[g]qu in oxa lin e-7,8-d ica r boxyla te (12b): 82% yield, a pale
yellow solid; mp 151-152 °C; δH 7.75 (2H, s), 4.18 (4H, q, J )
7.2 Hz), 3.38-3.12 (6H, m), 1.27 (6H, t, J ) 7.2 Hz); δC 173.62
(Cq), 144.89 (Cq), 139.53 (Cq), 139.32 (CH), 126.62 (CH), 61.18
(CH2), 41.45 (CH), 31.58 (CH2), 14.12 (CH3); MS (EI) m/z 396
(M+, 13), 322 (39), 249 (71), 238 (100); HRMS (EI) calcd for
analysis was performed on
a Heraeus analyzer, and all
analyzed compounds are within (0.4% of the theoretical value
unless otherwise indicated. Column chromatography was
performed on silica gel 70-230 or 230-400 mesh; thin-layer
chromatography (TLC) was performed on glass plates coated
with silica gel 60 F254. The preparations of 1,4-dihydro-6,7-
dimethylquinoxaline-2,3-dione 11,5d 6,7-bis(bromomethyl)-qui-
noxaline 9a,5b 6,7-dibromomethyl-2,3-dichloro-quinoxaline 9b,5c,d
and 6,7-dibromomethyl-2,3-diphenylquinoxaline 9c5e all fol-
lowed literature procedures.
C
18H18Cl2N2O4 396.0643, found 396.0635.
Dieth yl-(7R,8R)-2,3-d ip h en yl-6,7,8,9-tetr a h yd r oben zo-
[g]qu in oxa lin e-7,8-d ica r boxyla te (12c): 92% yield, a white
solid; mp 141-143 °C; δH 7.91 (2H, s), 7.48-7.45 (4H, m),
7.33-7.28 (6H, m), 4.19 (4H, q, J ) 6.9 Hz), 3.42-3.18 (6H,
m), 1.28 (6H, t, J ) 6.9 Hz); δC 174.03 (Cq), 153.20 (Cq), 140.01
(Cq), 139.09 (Cq), 137.61 (Cq), 129.77 (CH), 128.70 (CH), 128.21
(CH), 127.57 (CH), 61.08 (CH2), 41.91 (CH), 31.88 (CH2), 14.18
(CH3); MS (EI) m/z 480 (M+, 33), 406 (43), 333 (100); HRMS
(EI) calcd for C30H28N2O4 480.2050, found 480.2040. Anal.
Calcd for C30H28N2O4: C, 75.00; H, 5.83; N, 5.83. Found: C,
74.63; H, 5.99; N, 6.10.
Gen er a l P r oced u r es for th e Syn th esis of Qu in oxa li-
n osu ltin es 7a -c. A solution of 9a -c5b,c (e.g., for 9a , 1.40 g,
4.43 mmol) and Rongalite (3.41 g, 22.2 mmol) in DMF (20 mL)
was stirred at room temperature for 2 h. The mixture was
diluted with H2O (40 mL) and extracted three times (20 mL)
with CH2Cl2. The organic layer was dried over MgSO4,
concentrated, and purified by column chromatography (4:1
hexane/ethyl acetate) to give 0.69 g (3.14 mmol, 71%) of 7a as
a pale gray solid. For the synthesis of 7b, a longer reaction
time (4 h) was needed, and the yield was 76%. The reaction
for 7c was carried at 0 °C for 4 h, and the eluent was 5:1
hexane/ethyl acetate, with 26-55% yield.
7,8-Dih yd r o-6H -7λ6-t h ie n o[3,4-g]q u in oxa lin e -7,7-d i-
on e (13a ): a brown solid; mp 257-258 °C; δH 8.90 (2H, s),
8.11 (2H, s), 4.61 (4H, s); δC 145.89 (CH), 142.57 (Cq), 133.66
(Cq), 127.17 (CH), 56.38 (CH2); MS (EI) m/z 220 (M+, 18), 156
(M+ - SO2, 100); HRMS calcd for C10H8N2O2S 220.0306, found
220.0315.
2,3-Dich lor o-7,8-d ih yd r o-6H-7λ6-th ien o[3,4-g]qu in oxa -
lin e-7,7-d ion e (13b): a pale yellow solid; δH 8.00 (2H, s), 4.56
(4H, s); δC 142.05 (Cq), 140.63 (Cq), 135.04 (Cq), 126.01 (CH),
56.37 (CH2); HRMS calcd for C10H6N2O2 S35Cl2 287.9527, found
287.9528.
2,3-Disu b st it u t ed 8,9-d ih yd r o-6H -8λ4-[1,2]oxa t h iin o-
[4,5-g]qu in oxa lin -8-on e, Su ltin e 7a : an off-white solid; mp
1
161-162 °C; H NMR (300 MHz, CDCl3) δ 8.87 (2H, s), 8.00
(2H, s), 5.54 (1H, AB, J ) 13.8 Hz), 5.21 (1H, AB, J ) 13.9
Hz), 4.69 (1H, A′B′, J ) 15.6 Hz), 3.85 (1H, A′B′, J ) 15.5
2,3-Dip h en yl-7,8-d ih yd r o-6H-7λ6-th ien o[3,4-g]qu in oxa -
lin e-7,7-d ion e (13c): a pale yellow solid; mp > 290 °C, dec;

3402 J . Org. Chem., Vol. 65, No. 11, 2000
Liu et al.
δH 8.13 (2H, s), 7.53-7.50 (4H, m), 7.38-7.35 (6H, m), 4.61
(4H, s); δC 154.44 (Cq), 140.78 (Cq), 138.46 (Cq), 133.27 (Cq),
129.78 (CH), 129.22 (CH), 128.34 (CH), 126.71 (CH), 56.50
(CH2); MS (EI) m/z 372 (M+, 62), 308 (M+ - SO2, 100), 307
(73), 154 (33); HRMS calcd for C22H16N2O2S 372.0934, found
372.0921. Anal. Calcd for C22H16N2O2 S: C, 70.97; H, 4.30; N,
7.53. Found: C, 70.92; H, 4.55; N, 7.58.
Dim eth yl-(7R,8R)-6,7,8,9-tetr a h yd r oben zo[g]qu in oxa -
lin e-7,8-d ica r boxyla te (14a ): 75% yield, a pale yellow solid;
mp 142-143 °C; δH 8.77 (2H, s), 7.85 (2H, s), 3.77 (6H, s),
3.44-3.36 (2H, m), 3.33-3.17 (4H, m); δC 174.25 (Cq), 144.63
(CH), 141.69 (Cq), 137.57 (Cq), 127.79 (CH), 52.20 (CH3), 41.54
(CH), 31.53 (CH2); MS (EI) m/z 300 (M+, 23), 240 (51), 181
(100); HRMS (EI) calcd for C16H16N2O4 300.1110, found
300.1115.
Dim eth yl-(7R,8R)-2,3-d ip h en yl-6,7,8,9-tetr a h yd r oben -
zo[g]qu in oxa lin e-7,8-d ica r boxyla te (14c): 83% yield, a
pale yellow solid; mp 199-202 °C; δH 7.91 (2H, s), 7.48-7.45
(4H, m), 7.34-7.24 (6H, m), 3.75 (6H, s), 3.43-3.23 (6H, m);
δC 174.49 (Cq), 153.25 (Cq), 140.03 (Cq), 139.08 (Cq), 137.46 (Cq),
129.78 (CH), 128.74 (CH), 128.23 (CH), 127.60 (CH), 52.31
(CH3), 41.80 (CH), 25.88 (CH2); MS (EI) m/z 452 (M+, 87), 392
(70), 333 (100); HRMS (EI) calcd for C28H24N2O4 452.1737,
found 452.1739. Anal. Calcd for C28H24N2O4: C, 74.34; H, 5.31;
N, 6.20. Found: C, 73.79; H, 5.51; N, 6.37.
Dim et h yl-(7R,8S)-2,3-d ich lor o-6,7,8,9-t et r a h yd r ob en -
zo[g]qu in oxa lin e-7,8-d ica r boxyla te (15b): 62% yield, a
pale yellow solid; mp 178-179 °C; δH 7.76 (2H, s), 3.74 (6H,
s), 3.53-3.30 (6H, m); δC 172.69 (Cq), 144.77 (Cq), 139.15 (Cq),
138.92 (Cq), 127.20 (CH), 52.21 (CH3), 40.17 (CH), 30.03 (CH2);
MS (EI) m/z 368 (M+, 14), 308 (61), 249 (100), 57 (33); HRMS
(EI) calcd for C16H14Cl2N2O4 368.0331, found 368.0338. Anal.
Calcd for C16H14Cl2N2O4: C, 52.05; H, 3.82; N, 7.59. Found:
C, 51.79; H, 3.49; N, 7.57.
Dim eth yl-(7R,8S)-2,3-d ip h en yl-6,7,8,9-tetr a h yd r oben -
zo[g]qu in oxa lin e-7,8-d ica r boxyla te (15c): 60% yield, a
pale yellow solid; mp 143-146 °C; δH 7.95 (2H, s), 7.49-7.46
(4H, m), 7.35-7.26 (6H, m), 3.72 (6H, s), 3.55-3.37 (6H, m);
δC 172.99 (Cq), 153.15 (Cq), 139.83 (Cq), 139.15 (Cq), 137.25 (Cq),
129.76 (CH), 128.66 (CH), 128.19 (CH), 52.13 (CH3), 40.48
(CH), 30.04 (CH2); MS (EI) m/z 452 (M+, 60), 392 (54), 333
(100). Anal. Calcd for C28H24N2O4: C, 74.34; H, 5.31; N, 6.20.
Found: C, 73.97; H, 5.71; N, 6.19.
8-P h en yl-6a ,7,8,9,9a ,10-h exa h yd r o-6H-isoin d olo[5,6-g]-
qu in oxa lin e-7,9-d ion e (16a ): 87% yield, a light yellowish
solid; mp 244-245 °C; δH 8.81 (2H, s), 7.96 (2H, s), 7.30-7.24
(3H, m), 6.89-6.83 (2H, m), 3.58-3.48 (4H, m), 3.28-3.18 (2H,
m); δC 177.71 (Cq), 144.83 (CH), 142.38 (Cq), 137.84 (Cq), 131.35
(Cq), 128.93 (CH), 128.55 (Cq), 127.84 (CH), 126.05 (CH), 39.66
(CH), 29.98 (CH2); MS (EI) m/z 329 (M+, 100), 182 (70), 181
(63); HRMS (EI) calcd for C20H15N3O2 329.1164, found 329.1159.
2,3-Dich lor o-8-p h e n yl-6a ,7,8,9,9a ,10-h e xa h yd r o-6H -
isoin d olo[5,6-g]qu in oxa lin e-7,9-d ion e (16b): 93% yield, a
pale yellow solid; mp 294-297 °C; δH 7.79 (2H, s), 7.30-7.17
(3H, m), 6.90-6.60 (2H, m), 3.50-3.10 (6H, m); δC 177.43 (Cq),
145.35 (Cq), 139.96 (Cq), 139.32 (Cq), 131.28 (Cq), 129.04 (CH),
128.69 (CH), 126.68 (CH), 126.04 (CH), 39.50 (CH), 30.09
(CH2); MS (EI) m/z 397 (M+, 100), 250 (54); HRMS (EI) calcd
for C20H13N3Cl2O2 397.0384, found 397.0378.
Because of a solubility problem, the trapping of 12b with
fumaronitrile was not carried out.
(7R,8R)-2,3-Dip h en yl-6,7,8,9-t et r a h yd r ob en zo[g]q u i-
n oxa lin e-7,8-d ica r bon itr ile (17c): 60% yield, a white solid;
mp 261-263 °C; δH 7.97 (2H, s), 7.49-7.46 (4H, m), 7.36-
7.28 (6H, m), 3.68-3.41 (6H, m); δC 154.14 (Cq), 140.11 (Cq),
138.70 (Cq), 132.66 (Cq), 129.74 (CH), 129.01 (CH), 128.85 (CH),
128.27 (CH), 118.17 (Cq), 30.72 (CH2), 28.55 (CH); MS (EI) m/z
386 (M+, 100), 385 (24); HRMS calcd for C26H18N4 386.1533,
found 386.1534. Anal. Calcd for C26H18N4: C, 80.83; H, 4.66;
N, 14.51. Found: C, 79.99; H, 4.84; N, 14.17.
6,7-Dih yd r ocyclobu ta [g]qu in oxa lin e (18a ): a brown
solid; mp 107-109 °C; δH 8.75 (2H, s), 7.71 (2H, s), 3.43 (4H,
s); δC 149.50 (Cq), 143.95 (Cq), 142.99 (CH), 122.21 (CH), 29.45
(CH2); MS (EI) m/z 156 (M+, 100), 111 (28), 97 (45), 85 (59),
71 (55), 57 (70); HRMS calcd for C10H8N2 156.0687, found
156.0689.
2,3-D ic h lo r o -6,7-d ih y d r o c y c lo b u t a [g ]q u in o x a lin e
(18b): a pale yellow solid; mp 157-160 °C; δH 7.73 (2H, s),
3.40 (4H, s); δC 150.98 (Cq), 142.12 (Cq), 138.42 (Cq), 121.42
(CH), 29.60 (CH2).
2,3-Dip h e n yl-6,7-d ih yd r ocyclob u t a [g]q u in oxa lin e
(18c): a pale yellow solid; mp 113-118 °C; δH 7.76 (2H, s),
7.50-7.47 (4H, m), 7.32-7.30 (6H, m), 3.34 (4H, s); δC 151.37
(Cq), 149.38 (Cq), 142.11 (Cq), 139.31 (Cq), 129.83 (CH), 128.47
(CH), 128.19 (CH), 121.98 (CH), 29.55 (CH2); MS (EI) m/z 308
(M+, 100), 309 (M+ + 1, 21), 307 (M+ - 1, 82), 154 (23), 102
(21); HRMS calcd for C22H16N2 308.1315, found 308.1304.
Syn th esis of P yr a zin osu ltin e 22. A solution of 24 (1 g,
3.79 mmol) and Rongalite (0.86 g, 5.68 mmol) in DMF (10 mL)
was stirred at 0 °C for 6 h. The mixture was diluted with H2O
(10 mL) and extracted three times (5 mL) with CH2Cl2. The
organic layer was dried over MgSO4, concentrated, and purified
by column chromatography (3:2 hexane/ethyl acetate) to give
0.223 g of 22 as a gray solid (34.6%). 22: a gray solid; mp 59-
61 °C; δH 3.95 (1H, AB, J ) 16.4 Hz), 4.38 (1H, AB, J ) 16.5
Hz), 5.15 (1H, A′B′, J ) 15.9 Hz), 5.43 (1H, A′B′, J ) 15.8
Hz); δC 56.23 (CH2), 61.32 (CH2), 141.69 (Cq), 143.47 (CH),
144.44 (CH), 147.33 (Cq); MS (EI) m/z 170 (M+, 15), 106 (M+
- SO2, 100).
Gen er a l P r oced u r e for th e Tr a p p in g Exp er im en ts of
P yr a zin osu ltin e 22 w ith Dien op h iles su ch a s N-P h en yl-
m a leim id e, Dim eth yl F u m a r a te, Dim eth yl Acetylen ed i-
ca r boxyla te, a n d F u m a r on itr ile. A solution of pyrazino-
sultine 22 (50 mg, 0.294 mmol), with or without the respective
dienophiles (0.353 mmol), in toluene (3 mL) was refluxed under
N2 for 12 h. The solvent was evaporated under vacuum, and
the residue was subjected to silica gel chromatography using
hexane/ethyl acetate (from 3:1 to 1:1) as the eluent. Slightly
lower yields were obtained in each case when the reactions
were carried out in a sealed tube at 180 °C for 24 h. Sulfolene
26 was obtained in 73% yield (no quencher). For the trapping
of dienes, the respective yields are: N-phenylmaleimide, 59%
of dimethyl fumarate, 71% of 28, and 12% of 26; dimethyl
acetylenedicarboxylate, 33% of 29 and 20% of 26; and fuma-
ronitrile, 96% of 30.
P yr a zin osu lfolen e 26: a white solid; mp 196-198 °C (lit.6c
188-189 °C); δH 4.60 (4H, s), 8.58 (2H, s); δC 58.01 (CH2),
145.22 (CH), 147.69 (Cq); MS (EI) m/z 170 (M+, 25), 106 (M+
- SO2, 100); HRMS calcd for C6H6O2N2S 170.01500, found
170.01474.
2,3,8-Tr ip h en yl-6a ,7,8,9,9a ,10-h exa h yd r o-6H-isoin d olo-
[5,6-g]qu in oxa lin e-7,9-d ion e (16c): 98% yield, a pale yellow
solid; mp > 270 °C dec; δH 8.00 (2H, s), 7.53-7.50 (4H, m),
7.36-7.27 (9H, m), 6.92-6.89 (2H, m), 3.57-3.22 (6H, m); δC
172.84 (Cq), 153.17 (Cq), 140.50 (Cq), 138.85 (Cq), 137.64 (Cq),
131.39 (Cq), 129.77 (CH), 128.94 (CH), 128.81 (CH), 128.53
(CH), 128.21 (CH), 127.51 (CH), 126.13 (CH), 39.75 (CH), 30.07
(CH2); MS (EI) m/z 481 (M+, 100), 480 (M+ - 1, 15); HRMS
(EI) calcd for C32H23N3O2 481.1792, found 481.1794.
Ad d u ct 27: a white solid; mp 186-189 °C; δH 3.28-3.33
(2H, m), 3.42-3.57 (4H, m), 7.04 (2H, d, J ) 7.5 Hz), 7.32-
7.39 (3H, m), 8.41 (2H, s); δC 31.84 (CH2), 39.36 (CH), 126.06
(CH), 128.7 (CH), 129.02 (CH), 131.35 (CH), 143.20 (CH),
151.13 (Cq), 177.08 (Cq); MS (EI) m/z 279 (M+, 77), 132 [M+
-
(PhNC2O2), 96], 131 [M+ - (PhNC2O2 + H), 100]; HRMS calcd
for C16H13O2N3 279.1001, found 279.10089. Anal. Calcd for
(7R,8R)-6,7,8,9-Tetr a h yd r oben zo[g]qu in oxa lin e-7,8-d i-
ca r bon itr ile (17a ): 75% yield, a pale yellow solid; mp 268-
270 °C; δH 8.84 (2H, s), 7.96 (2H, s), 3.70-3.59 (2H, m), 3.48-
3.37 (4H, m); δC 145.62 (CH), 141.93 (Cq), 132.92 (Cq), 129.33
(CH), 118.06 (Cq), 30.55 (CH2), 28.40 (CH); MS (EI) m/z 234
(M+, 100), 156 (87); HRMS calcd for C14H10N4 234.0905, found
234.0903.
C16H13O2N3: C, 68.81; H, 4.69; N, 15.04. Found: C, 68.87; H,
4.71; N, 15.02.
Cycloa d d ition Rea ction s of C60 w ith P yr a zin osu ltin e
22. A solution of C60 (105 mg, 145 mmol) and pyrazinosultine
22 (30 mg, 176 mmol) in toluene (20 mL) was refluxed for 6 h.
The resulting brown reaction mixture was evaporated to
dryness under reduced pressure. The residue was subjected

Pyrazino-Containing Sultines
J . Org. Chem., Vol. 65, No. 11, 2000 3403
to silica gel chromatographywith toluene as the eluent,
recovering 35 mg of unreacted C60 and 62 mg of adduct 38
(52% yield, 78% based on consumed C60).
13C NMR (0 °C, 150 MHz, 1:3 CDCl3/CS2) δC 20.41* (CH3),
47.10* (CH2), 64.34 (aliph. Cq of C60), 128.32* (CH), 134.89
(CH), 135.21, 139.82, 139.95*, 140.01, 141.26, 141.36, 141.43,
141.45*, 141.66, 141.68, 141.73, 142.18, 142.23, 142.61, 142.78,
144.22, 144.25, 144.40, 144.92, 145.01, 145.06, 145.08, 145.25,
145.33, 145.37, 145.81, 145.93, 146.07, 146.11, 147.26, 151.77*,
154.99, 155.10 (32 fullerene signals and * denotes 6 peaks from
quinoxaline); FAB-MS (MNB) m/z 905 (M + 1, 17), 720 (78),
663 (100); UV (THF) λmax, nm (log ꢀ) 434 (3.15), 326 (4.28),
248 (4.70), 216 (4.66).
Ad d u ct 38: a brown solid; mp > 460 °C; δH (measured at
25 °C) 4.87 (4H, s), 8.73 (2H, s); δC 46.70 (CH2), 64.70 (aliph.
C of C60), 135.14, 140.03, 141.45, 141.73, 141.82, 142.35,
142.86, 143.73, 144.37, 144.68, 145.19, 145.33, 145.41, 146.01,
146.24, 147.40, 153.10, 155.23 [where 20 peaks are expected
(C2v) and 20 carbons observed]; MS (EI) m/z 827 (M+ + 1, 12),
720 (100); HRMS (M + H)+ calcd for C66H7N2 827.0610, found
827.0610.
Gen er a l P r oced u r es for th e Cycloa d d ition Rea ction s
of C60 w ith Qu in oxa lin osu ltin es 6a -c a n d 7a -c. A solu-
tion of C60 (50 mg, 69 mmol) and quinoxalinosultines 6a -d
and 7a -c (83 mmol) in o-dichlorobenzene (20 mL) was refluxed
under nitrogen for variable periods of time (24 h for 6a -c, 7b
and 7c; 4 h for 7a ). The resulting brown reaction mixture was
evaporated to dryness under reduced pressure. The residue
was subjected to silica gel chromatography with hexane/
toluene (2:1 to 1:1) as the eluent, recovering various amount
of unreacted C60 and the adducts 31-37.
31: 51% yield, 66% based on consumed C60; a brown solid;
mp > 495°C; 1H NMR (22 °C, 300 MHz, 1:3 CDCl3/CS2) δH
8.28-8.22 (2H, m), 7.89-7.83 (2H, m), 5.18 (2H, br AB), 4.93
(2H, br AB); 13C NMR (0 °C, 150 MHz, 1:3 CDCl3/CS2) δC
47.09* (CH2), 64.14 (aliph. Cq of C60), 129.15* (CH), 129.64*
(CH), 134.86, 135.19, 139.81, 140.00*, 141.24, 141.38, 141.43,
141.63 (b, 2C), 141.70, 142.16, 142.22, 142.31, 142.59, 142.76,
144.18, 144.21, 144.29, 144.83, 144.99, 145.05, 145.06, 145.23,
145.33 (b, 2C), 145.79, 145.91, 146.06, 146.09, 147.24, 152.85*,
154.77, 154.82 (30 fullerene signals and * denotes peaks from
quinoxaline); 13C NMR (92 °C, 150 MHz, C6D4Cl2) δC 47.67*
(CH2), 64.80 (aliph. Cq of C60), 130.15* (CH), 130.19* (CH),
135.12, 140.05*, 141.43, 141.76, 141.82, 142.32, 142.80, 143.12,
144.37, 144.69, 145.21 (b, 2C), 145.43, 146.01, 146.22, 147.46,
153.42,* 155.42; FAB-MS (M + H)+ m/z 877 (M + 1, 31), 720
(100); UV (THF) λmax, nm (log ꢀ) 434 (3.18), 322 (4.25), 256
(4.61), 244 (4.66).
35: 63% yield, 84% based on consumed C60; a brown solid;
1
mp > 495 °C; H NMR (22 °C, 300 MHz, 1:3 CDCl3/CS2) δH
8.91 (2H, s), 8.37 (2H, s), 5.09 (2H, AB, J ) 14.1 Hz), 4.71
(2H, AB, J ) 14.0 Hz); 13C NMR (22 °C, 150 MHz, 1:3 CDCl3/
CS2) δC 44.90* (CH2), 64.96 (aliph. Cq of C60), 128.03* (CH),
135.11, 135.81, 139.95, 140.17, 140.26,* 141.36, 141.55, 141.69,
141.81, 141.91, 142.37, 142.40, 142.83, 142.93,* 142.97, 144.42,
144.44, 144.63, 144.66* (CH), 145.15, 145.21 (b, 2C), 145.25,
145.40, 145.45, 145.57, 145.98, 146.08, 146.24, 146.27, 147.44,
155.50, 155.63; 13C NMR (95 °C, 150 MHz, C6D4Cl2) δC 45.10*
(CH2), 65.29 (aliph. Cq of C60), 128.04* (CH), 135.37, 140.03,
140.32,* 141.39, 141.81, 141.84, 142.30, 142.79*, 143.34,
144.40, 144.57* (CH), 144.92, 145.19 (b, 2C), 145.45, 145.98,
146.20, 147.44, 155.85; FAB-MS (MNB) m/z 877 (M + 1, 35),
720 (100); UV (THF) λmax, nm (log ꢀ) 434 (3.35), 322 (4.27),
310 (4.25), 254 (4.67), 242 (4.70), 214 (4.83).
Ack n ow led gm en t. We thank the National Science
Council of the Republic of China for its financial support
(Grant NSC 87-2113-M-009-008-L1; NSC 88-2113-M-
009-008-L1).
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C (or
DEPT) NMR spectra for compounds 7a , 12b, 13a , 14a , 16a -
18a , 16c, 18c, 22, and 26-38 and synthetic procedures and
spectral data for 8a -c, 9a -c, 24, 28-30, 33, 34, 36, and 37.
This material is available free of charge via the Internet at
http://pubs.acs.org.
32: 66% yield, 78% based on consumed C60; a brown solid;
1
mp > 495 °C; H NMR (22 °C, 300 MHz, 1:3 CDCl3/CS2) δH
7.98 (2H, s), 5.15 (2H, br AB), 4.88 (2H, br AB); 2.61 (6H, s);
J O9918448