The formation of quinolin-2(1H)-ones via electrocyclic reaction of o-isocyanatostyrenes generated in situ from o-isocyanostyrenes

Article abstract of DOI:10.1246/cl.2000.798

A convenient one-pot preparation of 4-substituted or 3,4-disubstituted quinolin-2(1H)-ones from 2-isocyanostyrene derivatives, which involves mCPBA oxidation to the corresponding isocyanate intermediates followed by electrocyclization, is described.

Full text of DOI:10.1246/cl.2000.798

798
Chemistry Letters 2000
The Formation of Quinolin-2(1H)-ones via Electrocyclic Reaction of o-Isocyanatostyrenes
Generated in situ from o-Isocyanostyrenes
Kazuhiro Kobayashi,* Taichi Kitamura, Keiichi Yoneda, Osamu Morikawa, and Hisatoshi Konishi
Department of Materials Science, Faculty of Engineering, Tottori University, Koyama-minami, Tottori 680-8552
(Received April 6, 2000; CL-000321)
A convenient one-pot preparation of 4-substituted or 3,4-
disubstituted quinolin-2(1H)-ones from 2-isocyanostyrene
derivatives, which involves mCPBA oxidation to the correspon-
ding isocyanate intermediates followed by electrocyclization, is
described.
Quinolin-2(1H)-one derivatives have been of use in organ-
ic synthesis.1 Moreover, some compounds having this skeleton
have interesting biological profile,2 exhibiting, for example,
angiotensin II receptor2b and oxytocin2c antagonist activities.
Therefore, a number of new methods for the synthesis of this
class of molecules have recently appeared.3 In this paper, we
wish to describe the results of our investigation, which offer a
facile route to 4-substituted or 3,4-disubstituted quinolin-2(1H)-
ones 3 based on mCPBA oxidation of 2-isocyanostyrene deriv-
atives 1. As outlined in Scheme 1, this one-pot procedure
involves initial formation of the corresponding isocyanate
intermediates 2, followed by in situ electrocyclic reaction.4
Reports on the synthesis of quinolin-2(1H)-one derivatives by
electrocyclization of 2-isocyanatostyrenes, generated in situ by
Curtius rearrangements of the respective acyl azides, have been
recorded.5a–c The kinetic and computational studies of this elec-
trocyclic reaction in hexadueteriobenzene, have recently been
reported by Dolbier, Jr. et al.5d The methods, however, involve
tedious reaction conditions and/or incomplete generality.
The starting isocyanides 1 were prepared as follows.
Treatment of the respective o-aminostyrenes, which were com-
mercially available or readily prepared using the procedure of
Smith and Livinghouse6 or Bell et al.,7 with formic acid in
refluxing toluene gave the corresponding formamide, which
were then dehydrated with phosphorous oxychloride in the
presence of triethylamine in THF to give 1 in high overall
yields.8 While these isocyanides appeared to be somewhat
unstable, most of them could be purified by column chromatog-
raphy on silica gel and storable for prolonged periods at refrig-
erator temperature.
The isocyanides 1 were treated with an equimolar amount
of mCPBA in dichloromethane at room temperature overnight.
After usual workup, the residual products were recrystallized to
give quinolin-2(1H)-ones 3. The results are summarized in
Table 1. The 4-substituted quinolin-2(1H)-one derivatives 3a–e
and 3h were obtained in fair-to-good yields (Entries 1–5 and 8).
α,β-Disubstituted 2-isocyanostyrenes 1f and 1g were also treat-
ed with mCPBA under the same conditions to obtain 3,4-disub-
stituted derivatives 3f and 3g, respectively. The reactions pro-
ceeded more slowly than those of the reactions forming 4-sub-
stituted derivatives and gave rather diminished yields of the
expected products (Entries 6 and 7). The presence of the iso-
cyanato intermediates in the reaction mixtures from 1f or 1g
was confirmed on the basis of their IR spectra, which exhibited
intense absorption bands (ν ca. 2250–2260 cm–1) assignable to
the isocyanato group. It should be noted that a similar treat-
ment of 2-isocyanostilbene (1, R = R" = H, R' = Ph) with
mCPBA unfortunately resulted in the formation of a mixture
including the corresponding isocyanato derivative, as judged
from its IR spectrum (ν ca. 2254 cm–1). Heating of this mix-
ture resulted in the formation of an intractable mixture of prod-
ucts, from which no trace amount of the expected 3-
phenylquinolin-2(1H)-one was obtained. These results can
probably be understood in terms of the strained hindrance of the
transition state of isocyanate intermediates together with the
results of kinetic studies by Dolbier, Jr. et al,5 which indicated
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
799
J. Chem., Sect. B, 23B, 720 (1984); S. Chorbadzhiev, Synth.
Commun., 20, 3495 (1990); A. Furstner, D. N. Jumbam, and N.
Shi, Z. Naturforsch, B: Chem. Sci., 50, 326 (1995); P. Ferrer, C.
Avendano, and M. Soellhuber, Liebigs Ann. Chem., 1995, 1895;
C. W. Holzapfel and C. Dwyer, Heterocycles, 48, 215 (1998).
For related electrocyclic reactions affording quinoline deriva-
tives, L. G. Qiang and N. H. Baine, J. Org. Chem., 53, 4218
(1988); T. Saito, H. Ohmori, E. Furuno, and S. Motoki, J. Chem.
Soc., Chem. Commun., 1992, 22; P. Molina, M. Alajarin, A.
Vidal, and P. Sanchez-Andrada, J. Org. Chem., 57, 929 (1992);
T. Saito, H. Ohmori, T. Ohkubo, and S. Motoki, J. Chem. Soc.,
Chem. Commun., 1993, 1802.
a) J. S. Swenton, Tetrahedron Lett., 1967, 2855. b) F. Eloy and
A. Deryckere, J. Heterocycl. Chem., 7, 1191 (1970). c) R. L.
Williams and M. G. Elfayoumy, J. Heterocycl. Chem., 9, 1021
(1972). d) L. Luoi, M. D. Bartberger, and W. R. Dolbier, Jr., J.
Am. Chem. Soc., 119, 12366 (1997).
that β-substituted o-isocyanatostyrenes requires high activation
energies for cyclization.
A number of reagents,9 such as ozone,9a halogens in the
presence of dimethyl sulfoxide,9b nitrogen oxide,9c or pyridine
oxide,9d have been reported to oxidize isocyanides to the corre-
sponding isocyanates. These reagents, however, are undoubt-
fully unsuitable for the present transformation. To the best of
our knowledge, this is the first report which indicates that
mCPBA can oxidize isocyano group to isocyanato group.
A typical procedure is illustrated by the preparation of 4-
methylquinolin-2(1H)-one (3a). To a stirred solution of 1a
(0.28 g, 2.0 mmol) in dichloromethane (10 mL) at 0 °C was
added mCPBA (80%, purchased from Kanto Chemical Co.,
Inc.; 0.43 g, 2.0 mmol) in several portions. The reaction mix-
ture was then allowed to warm to room temperature and stirred
overnight at that temperature. The resulting mixture was trans-
ferred to a separating funnel using dichloromethane (20 mL),
washed with saturated aqueous sodium carbonate, and dried
over anhydrous sodium sulfate. After evaporation of the sol-
vent, the crude solid material was purified by recrystallization
from diethyl ether–hexane to afford the pure quinolinone 3a
(0.11 g, 70%) as a white solid; mp 217–220 °C; identified by a
direct comparison with commercially available compound (pur-
chased from Tokyo Kasei Kogyo Co., Ltd.) (mp 221–223 °C).10
In comparison to the previously described syntheses of
quinolin-2(1H)-one derivatives,6 the advantages of the synthe-
sis described here are that the reaction procedure is simple and
the products are readily obtained by recrystallization in high
purity. Applications of the present process to the synthesis of
related heterocycle–fused pyridone derivatives are now in
progress in our laboratory.
4
5
6
7
R. Smith and K. Livinghouse, Tetrahedron, 41, 3559 (1985).
S. C. Bell, T. S. Sulkowski, G. Gochman, and S. J. Childress, J.
Org. Chem., 27, 562 (1962).
1
8
1a: Rf 0.78 (1:2 EtOAc–hexane); IR (neat) 2122 cm–1; H NMR
(270 MHz, CDCl3) δ 2.10 (3H, s), 5.07 (1H, s), 5.29 (1H, s), and
7.2–7.35 (4H, m); MS m/z (%) 143 (M+, 20) and 117 (100). 1b:
Rf 0.72 (1:2 EtOAc–hexane); IR (neat) 2122 cm–1; 1H NMR
(270 MHz, CDCl3) δ 5.40 (1H, s), 5.87 (1H, s), and 7.25–7.4
(9H, m); MS m/z (%) 205 (M+, 87) and 204 (100). 1c: Rf 0.77
1
(1:2 Et2O–hexane); IR (neat) 2120 cm–1; H NMR (270 MHz,
CDCl3) δ 2.02 (3H, s), 5.55 (1H, d, J = 1.1 Hz), 5.69 (1H, d, J =
1.1 Hz), and 7.1–7.35 (8H, m); MS m/z (%) 219 (M+, 22), 218
(29), and 204 (100). 1d: Rf 0.65 (1:2 EtOAc–hexane); IR (neat)
1
2123 and 1607 cm–1; H NMR (270 MHz, CDCl3) δ 3.80 (3H,
s), 5.27 (1H, d, J = 1.0 Hz), 5.77 (1H, d, J = 1.0 Hz), 6.84 (2H, d,
J = 8.9 Hz), 7.18 (2H, d, J = 8.9 Hz), and 7.3–7.45 (4H, m); MS
m/z (%) 235 (M+, 100). 1e: mp 79–81 °C (Et2O–hexane–CH2Cl2);
IR (KBr disk) 2124 and 1601 cm–1; 1H NMR (270 MHz, CDCl3)
δ 3.85 (3H, s), 3.88 (3H, s), 5.31 (1H, s), 5.79 (1H, s), 6.71 (1H,
dd, J = 8.2 and 2.0 Hz), 6.79 (1H, d, J = 8.6 Hz), 6.87 (1H, d, J =
2.0 Hz), and 7.3–7.45 (4H, m); MS m/z (%) 265 (M+, 100). 1f:
Rf 0.85 (1:2 EtOAc–hexane); IR (neat) 2121 cm–1; 1H NMR
(270 MHz, CDCl3) δ 1.80 (3H, dd, J = 6.9 and 1.1 Hz), 2.03
(3H, t, J = 1.3 Hz), 5.63 (1H, qd, J = 6.9 and 1.3 Hz), and
7.15–7.35 (4H, m); MS m/z (%) 157 (M+, 100). 1g: Rf 0.80 (1:2
Assistance in MS experiments by Mrs. Miyuki Tanmatsu
of this Department is gratefully acknowledged.
EtOAc–hexane); IR (neat) 2121 cm–1 1H NMR (270 MHz,
;
References and Notes
1
a) S. Kwon and K. Isagawa, Yuki Gosei Kagaku Kyokai Shi, 31,
313 (1973). b) R. F. Cookson and R. E. Rodway, J. Chem. Soc.,
Perkin Trans. 1, 1975, 1854. For recent examples see c) K. Hino,
K. Furukawa, Y. Nagai, and H. Uno, Chem. Pharm. Bull., 28,
2618 (1980). d) F. Haviv and R. W. Denet, US Patent 4407803
(1983); Chem. Abstr., 100, 6508b (1983). e) K. Hino, K.
Kawashima, M. Oka, Y. Nagai, H. Uno, and J. Matsumoto,
Chem. Pharm. Bull., 37, 110 (1989). f) S. Nakahara, Y. Tanaka,
and K. Kubo, Heterocycles, 36, 1139 (1993). g) K. Sakurai, S.
Niwa , S. Oono, and H. Uchita, Jpn. Patent 29979 (1998); Chem.
Abstr., 128, 192665y (1998).
a) K. Eistetter, E. Kraas, G. Ludwig, M. Miklovich, E. Rapp, and
H. Wolf, Eur. Patent, 24638 (1981); Chem. Abstr., 95, 80757b
(1981). b) H. Akashi, M. Akiyama, T. Shiga, T. Matsui, Y.
Hayashi, T. Kimura, and H. Kobayashi, Jpn. Patent 45819
(1986); Chem. Abstr., 106, 129393s (1987). c) N. Beier, E.
Labitzke, W. W. K. R. Mederski, and B. Schneider,
Heterocycles, 39, 117 (1994). d) H. Ogawa, H. Miyamoto, K.
Kondo, H. Yamashita, K. Nakaya, M. Tanaka, and K. Kitano,
PCT Int. Patent 01113 (1994); Chem. Abstr., 120, 290828m
(1994). e) T. Hasegawa, E. Sato, Y. Akiyama, T. Mori, M.
Yamauchi, T. Imanishi, T. Imai, and D. Kubota, PCT Int. Patent
07703 (1998); Chem. Abstr., 128, 204906w (1998).
CDCl3) δ 1.92 (3H, d, J = 7.1 Hz), 6.02 (1H, q, J = 7.1 Hz), and
7.15–7.45 (9H, m); MS m/z (%) 219 (M+, 43) and 218 (100). 1h:
1
mp 86–88 °C (hexane); IR (KBr disk) 2124 m–1; H NMR (270
MHz, CDCl3) δ 5.40 (1H, d, J = 1.0 Hz), 5.88 (1H, d, J = 1.0
Hz), and 7.2–7.35 (8H, m); MS m/z (%) 241 (10), 239 (M+, 31)
and 204 (100).
a) H. Feuer, H. Rubinstein, and A. T. Nielsen, J. Org. Chem., 23,
1107 (1958). b) H. W. Johnson, Jr. and P. H. Daughhetee, Jr., J.
Org. Chem., 29, 246 (1964). c) T. Saegusa, S. Kobayashi, and Y.
Ito, Bull. Chem. Soc. Jpn., 43, 275 (1970). d) H. W. Johnson, Jr.,
and H. Krutch, J. Org. Chem., 32, 1939 (1967).
9
2
10 Physical and spectral properties for new quinolinones 3 follows.
3c: mp 201–203 °C (Et2O); IR (KBr disk) 3439 and 1651 cm–1;
1H NMR (270MHz, CDCl3) δ 2.14 (3H, s), 6.62 (1H, s),
7.05–7.55 (8H, m), and 12.2 (1H, br); MS m/z (%) 235 (M+,
100). 3e: mp 243–246 °C (Et2O–CHCl3); IR (KBr disk) 3426
and 1651 cm–1; 1H NMR (270 MHz, CDCl3) δ 3.91 (3H, s), 3.97
(3H, s), 6.70 (1H, s), 6.95–7.1 (3H, m), 7.17 (1H, t, J = 7.9 Hz),
7.45–7.6 (2H, m), 7.70 (1H, d, J = 7.9 Hz), and 11.6 (1H, br);
MS m/z (%) 281 (M+, 0.8), 237 (12), and 208 (100). 3f: mp
265–268 °C (CHCl3–Et2O); IR (KBr disk) 3442 and 1649 cm–1;
1H NMR (270 MHz, CDCl3) δ 2.32 (3H, s), 2.49 (3H, s),
7.15–7.7 (3H, m), 7.70 (1H, d, J = 7.9 Hz), and 11.2 (1H, br);
MS m/z (%) 173 (M+, 100). 3g: mp 227–230 °C (hexane–Et2O);
IR (KBr disk) 3449 and 1654 cm–1; 1H NMR (270 MHz, CDCl3)
δ 2.07 (3H, s), 7.05–7.7 (2H, m), 7.2–7.3 (2H, m), 7.35–7.6 (5H,
m), and 11.6 (1H, br); MS m/z (%) 235 (M+, 57) and 234 (100).
3
G. Merault, P. Bourgeois, and N. Duffaut, Bull. Soc. Chim. Fr.,
1974, 1949; N. A. Cortese, C. B. Ziegler, Jr., B. J. Henjez, and
R. F. Heck, J. Org. Chem., 43, 2952 (1978); S. Kano, T. Ozaki,
and S. Hibino, Heterocycles, 12, 489 (1979); M. Matarajan, T.
Manimaran, and V. T. Ramakrishnan, Indian J. Chem., Sect. B,
23B, 529 (1984); M. Matarajan and V. T. Ramakrishnan, Indian