Reaction of indolin-2-ones with cerium(IV) ammonium nitrate

Article abstract of DOI:10.1016/S0040-4020(02)01284-X

The reaction of indolin-2-ones with CAN is studied. When the reaction is carried out in an alcohol as solvent, 3-alkoxyindolin-2-ones are obtained in very good yields. If a non-nucleophilic solvent is used (THF, acetonitrile) 3-nitroxy derivatives are isolated. If the aromatic ring bears an electron-donating group, reactions are accompanied by aromatic ring nitration.

Full text of DOI:10.1016/S0040-4020(02)01284-X

Tetrahedron 58 (2002) 9541–9545
Reaction of indolin-2-ones with cerium(IV) ammonium nitrate
Carmen Escolano, Llu ´ı s Vallverd u´ and Keith Jones
*
School of Chemical and Pharmaceutical Sciences, Kingston University, Penrhyn Road, Kingston-upon-Thames, Surrey KT1 2EE, UK
Received 9 August 2002; revised 13 September 2002; accepted 3 October 2002
Abstract—The reaction of indolin-2-ones with CAN is studied. When the reaction is carried out in an alcohol as solvent, 3-alkoxyindolin-2-
ones are obtained in very good yields. If a non-nucleophilic solvent is used (THF, acetonitrile) 3-nitroxy derivatives are isolated. If the
aromatic ring bears an electron-donating group, reactions are accompanied by aromatic ring nitration. q 2002 Elsevier Science Ltd. All
rights reserved.
1. Introduction
electronic character, experiments were carried out using the
,3-dimethylindolin-2-one, 6, the methoxyderivative 7 and
1
During the last two decades our group has been interested
in the preparation of indolin-2-one derivatives by intra-
molecular addition of aryl radicals to acrylamides. During
this work, we have found on occasion that the crude
the methoxycarbonylderivative 8. Compounds 6 and 7 are
readily available from the corresponding 2-haloaniline
using a three step sequence previously described by our
1
5
group. Reaction of 2-bromoaniline or 2-bromo-4-methoxy-
3-substituted-indolin-2-ones spontaneously dimerise to
produce 3,3 -leucoisoindigos such as 1. These oxindole
aniline with acryloyl chloride followed by N-alkylation and
radical cyclization [tributyltin hydride (0.02 M) in refluxing
toluene with a sub-stoichiometric amount of AIBN] led to
6 and 7 in good overall yields. Following this general
procedure, compound 8 was prepared from methyl
4-amino-3-iodobenzoate (Scheme 1).
0
dimers have been used as intermediates in the synthesis of
2
3
calycanthine alkaloids such as folicanthine 2. In order to
6
prepare such dimers in a satisfactory manner, we decided to
explore the possible oxidative dimerisation of 3-substituted-
indolin-2-ones with cerium(IV) ammonium nitrate (CAN).
CAN is a versatile reagent for the oxidation of numerous
4
functional groups in organic synthesis. Most of the
transformations mediated by CAN proceed under mild
conditions and give high yields of products. In this paper we
wish to report our systematic investigation of the chemistry
associated with the functionalization of the C-3 position in
indolin-2-ones by CAN (Fig. 1).
Scheme 1.
Oxidation reactions of these compounds were performed at
room temperature dissolving the starting material in
different solvents and adding 2.2 equiv. of CAN (Scheme
Figure 1.
2
isopropanol gave the corresponding oxindole derivatives
). Reacting 6 with CAN in methanol, ethanol or
2
. Discussion
7
1
9
a –c in good yields. The H NMR spectrum of 9a–c
In order to study the effect of substituents with different
13
showed a singlet at ,1.4 ppm and the C NMR spectrum
showed a quaternary carbon at ,79 ppm indicating that
substitution at the 3-positon by an alkoxy group had
occurred. When tert-butanol was used as a solvent only
starting material was recovered. To study the scope of the
Keywords: indolin-2-ones; nitration; oxindole; oxidation.
*
Corresponding author. Tel.: þ44-20-8547-8450; fax: þ44-20-8547-7562;
e-mail: keith.jones@kingston.ac.uk
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01284-X

9542
C. Escolano et al. / Tetrahedron 58 (2002) 9541–9545
Scheme 2.
1
oxidation reaction in other nucleophilic solvents, isopropyl-
amine was used. Reaction of 6 with CAN in isopropylamine
as a solvent gave the 3-hydroxy derivative 9d with no
products arising from the nucleophilic addition of iso-
propylamine being detected. In order to further explore the
reaction, tetrahydrofuran (THF) and acetonitrile were
chosen as non-nucleophilic solvents. When the reaction
was carried out in THF or acetonitrile the nitrooxyoxindole
Characteristic peaks at 1648 and 1353 cm2 in the IR, only
two aromatic protons and a quaternary carbon at d 82.7
indicated that substitution at C-3 by a nitrate group and
nitration in the 6-position had occurred. The nitration of
the electron-rich aromatic ring was not unexpected, since
CAN-mediated nitrations are well documented and several
8
9
mechanisms have been proposed.
9
The IR showed peaks at 1642 and 1616 cm and in the
e was obtained in good yields (74 and 69%, respectively).
2
Finally, the effect of an electron-withdrawing substituent
was explored. When 8 was oxidised by CAN in methanol or
ethanol, compounds 9j (72%) and 9k (88%), respectively,
were obtained. Using isopropanol as a solvent a mixture of
the expected 91 (53%) and 9m (36%) was observed.
As before, the structures of 9j–l were deduced on the basis
of the spectral data. As expected, reaction of 8 with CAN in
THF or acetonitrile afforded the nitrooxy derivative 9m in
80 and 84% yield, respectively. IR peaks (1651 and
1
13
C
NMR a signal at d 83.5 ppm indicated substitution at C-3 by
a nitrate group.
Next, reaction of the oxindole 7, which bears an electron-
donating group in the aromatic ring, was studied. Reactions
in methanol, ethanol and isopropanol were performed with
9
f–h being isolated in good yields. As before, a singlet in
1
21
the H NMR at d,1.5 ppm and a quaternary carbon in the
1621 cm ) and a quaternary carbon at d 82.8 ppm
1
3
C NMR at d,79 ppm indicates that substitution at the
-position by an alkoxy group had occurred. Moreover, only
characteristic for the nitrooxy substitution at C-3 were
observed. No nitration of the aromatic ring was observed
owing to the deactivation of the benzene ring by the
methoxycarbonyl group (Table 1).
3
two peaks in the aromatic region were observed, due to the
nitration of the 6-position. When THF or acetonitrile was
used as a solvent compound 9i was obtained in good yield.
Although further investigations are desirable in order to
fully understand the mechanism of these reactions, we
tentatively proposed the mechanism shown in Scheme 3.
Table 1. Oxidation reactions of compounds 6–8 (Scheme 2)
1
0
Compounds
R
R
1
R
2
Yield (%)
Oxidation of indolin-2-one by CAN could lead to a radical-
cation 10 which in the presence of a nucleophilic alcohol
would give intermediate 11. Further oxidation of 11 by the
second equivalent of CAN would lead to the relatively
stable cation 12 that would lose a proton giving 13 and nitric
acid. The formation of nitric acid during the reaction would
provide an explanation for the aromatic nitration of the
electron-rich benzene ring in 7.
9
9
9
9
9
9
9
9
9
9
9
9
9
a
b
c
d
e
f
g
h
i
H
H
H
H
H
CH
CH
3
H
71
72
66
68
74/69
70
64
2
CH
3
H
H
H
H
NO
NO
NO
NO
H
CH(CH
H
3
)
2
NO
CH
CH
2
OCH
OCH
OCH
OCH
3
3
3
3
3
2
2
2
2
2
CH
3
CH(CH
NO
3
)
2
64
2
57/60
72
88
53
80/84
j
k
l
COOCH
COOCH
COOCH
COOCH
3
3
3
3
CH
CH
3
In conclusion, oxidation reactions with cerium(IV)
ammonium nitrate of indolin-2-ones substituted by different
electronic character groups in the benzene ring, have been
studied. When reactions are carried out in an alcohol as a
2
CH
3
H
H
H
CH(CH
NO
3
)
2
m
2
Scheme 3.

C. Escolano et al. / Tetrahedron 58 (2002) 9541–9545
9543
solvent (methanol, ethanol or isopropanol), 3-alkoxyindo-
lin-2-ones are obtained in very good yield. If a non-
nucleophilic solvent is used (THF or acetonitrile), 3-nitroxy
derivatives are isolated. If the aromatic ring bears an
electron-donating group, substitution at the C-3 position is
accompanied by aromatic ring nitration. No trace of dimeric
oxindole products were isolated in any reaction.
CH ), 3.03 (2q, 2H, J¼7 Hz, OCH CH ), 3.14 (3H, s,
3
2
3
NCH ), 6.77 (1H, dd, J¼8.4, 0.85 Hz, ArH), 7.04 (1H,
3
td, J¼7.6, 0.85 Hz, ArH), 7.26 (2H, m, ArH); d 15.3
C
(CH CH ), 24.1 (CH ), 26.0 (NCH ), 60.9 (CH ), 79.0 (C),
2
3
3
3
2
108.3 (CH), 123.0 (CH), 123.5 (CH), 129.3 (C), 129.5 (CH),
143.2 (C), 176.8 (amide CvO); m/z (EI) 177 (100,
þ
C H NO requires M 205.1116).
þ
M 2C H ), 161 (58), 77 (19) (Found: M , 205.1103.
4
2
1
2
15
2
3
. Experimental
3.2.3. 1,3-Dimethyl-3-isoproxyindolin-2-one, 9c. Oxin-
dole 6 (20 mg, 0.12 mmol) in isopropanol (1 mL) and CAN
(0.15 g, 0.27 mmol) gave a white foam, 9c (18 mg, 66%)
3
.1. General details
after chromatography (SiO , hexane/ethyl acetate 1:1.5).
2
6
21
These were as previously reported.
n
max/cm 2972 (m, C–H), 1725 (s, amide CvO), 1121 (m,
C–O); d 0.89 (3H, d, J¼6 Hz, CH ), 1.02 (3H, d, J¼6 Hz,
H
3
3
.1.1. 1,3-Dimethyl-5-methoxycarbonylindolin-2-one, 8.
A suspension of 5 (800 mg, 2.4 mmol) and a sub-
CH
3
), 1.45 (3H, s, CH
3
), 3.20 (3H, s, NCH
3
), 3.22 (1H,
23.4 (CH ),
), 69.1 (CH), 78.6 (C),
sept., J¼6 Hz, CH), 6.8–7.2 (4H, m, ArH); d
C
3
stoichiometric amount of AIBN (ca. 10 mg) in toluene
24.2 (CH ), 25.0 (CH ), 26.1 (NCH
3
3
3
(
(
160 mL) was heated to reflux. Then, tri-n-butyltin hydride
0.67 mL, 2.50 mmol) was added dropwise and the reaction
108.3 (CH), 122.8 (CH), 123.9 (CH), 129.4 (CH), 130.2
þ
(C),143.0 (C), 178.3 (amide CvO); m/z (EI) 219 (40, M ),
þ
mixture was stirred at this temperature for 1 h. After
evaporation of the solvent the residue was chromatographed
207 (14), 167 (27) (Found: M , 219.1262. C13
requires M 219.1259).
H
17NO
2
(
SiO , hexane/ethyl acetate 1.5:1) to give the title compound
2
8
8
(
6
as a white solid (431 mg, 82%) mp 120–1218C
hexane/ethyl acetate 1:2) (Found: C, 65.69; H, 5.73; N,
.09. C H NO requires C, 65.74; H, 5.98; N, 6.39%).
3.2.4. 1,3-Dimethyl-3-hydroxyindolin-2-one, 9d. Oxin-
dole 6 (20 mg, 0.12 mmol) in isopropylamine (1 mL) and
CAN (0.15 g, 0.27 mmol) gave a white foam, 9d (15 mg,
1
2
13
3
2
1
nmax/cm 1713 (s, ester CvO), 1617 (s, amide CvO); dH
1
68%) after chromatography (SiO
, hexane/ethyl acetate 1:1)
2
d 24.8 (CH ), 26.2 (NCH ), 73.7 (C), 108.5 (CH), 123.2
(CH), 123.4 (CH), 129.6 (CH), 131.4 (C), 143.1 (C), 178.9
.40 (3H, d, J¼7.6 Hz, CH ), 3.15 (3H, s, NCH ), 3.36 (1H,
C
3
3
3
3
q, J¼7.6 Hz, H-3), 3.82 (3H, s, OCH ), 6.77 (1H, d,
3
J¼8.1 Hz, H-7), 7.82 (1H, s, H-4), 7.95 (1H, dd, J¼8.1,
(amide CvO).
0
.76 Hz, H-6); d 15.0 (CH ), 26.2 (NCH ), 40.1 (CH), 51.9
C 3 3
(
OCH ), 107.3 (CH), 124.1 (C), 124.5 (CH), 130.2 (C),
3
3.2.5. 1,3-Dimethyl-3-nitrooxyindolin-2-one, 9e. Oxin-
dole 6 (40 mg, 0.25 mmol) in THF or acetonitrile (2 mL)
and CAN (300 g, 0.54 mmol) gave a white foam, 9e (41 mg,
74%; 38 mg, 69%, respectively) after chromatography
1
CvO); m/z (EI) 219 (100, M ), 188 (90, M 2OCH ), 160
(
30.5 (CH), 148.0 (C), 166.7 (ester CvO), 178.7 (amide
þ
þ
3
70).
2
1
(SiO , hexane/ethyl acetate 1:2). nmax/cm
amide CvO), 1642 and 1616 (s, ONO
1734 (s,
(400 MHz)
.62 (3H, s, CH ), 3.25 (3H, s, NCH ), 6.89 (1H, d,
2
3
.2. General procedure for CAN oxidation
2
); d
H
1
3 3
To a solution of oxindole (1 mmol) dissolved in the solvent
ca. 6 mL) CAN (2.2 mmol) was added slowly in four
J¼7.6 Hz, ArH), 7.10 (1H, t, J¼7.6 Hz, ArH), 7.33 (1H, d,
J¼7.6 Hz, ArH), 7.38 (1H, td, J¼7.6, 0.7 Hz, ArH); d 21.4
(CH ), 26.6 (NCH
), 83.5 (C), 122.5 (CH), 123.3 (2£CH),
126.2 (C), 130.7 (CH),143.4 (C), 173.0 (amide CvO); m/z
(
C
portions during 10 min and the mixture was stirred
overnight. The solvent was evaporated in vacuo and the
residue was dissolved in CH Cl . The organic layer was
3
3
þ
þ
(EI) 223 (20, M þ1), 176 (32), 160 (100) (Found: M þH,
2
2
washed with water, dried and evaporated under reduced
pressure.
223.0726. C10
H N O
11 2 4
requires MþH 223. 0719).
3
.2.6. 3,5-Dimethoxy-1,3-dimethyl-6-nitroindolin-2-one,
7
3
.2.1. 1,3-Dimethyl-3-methoxyindolin-2-one, 9a. Oxin-
9f. Oxindole 7 (91 mg, 0.47 mmol) in methanol (3 mL) and
CAN (630 mg, 1.15 mmol) gave a yellow foam, 9f (89 mg,
dole 6 (50 mg, 0.31 mmol) in methanol (2 mL) and CAN
0.37 g, 0.68 mmol) gave a brown oil, 7a (42 mg, 71%) after
chromatography (SiO , hexane/ethyl acetate 1:1.5). d 1.47
(
70%) after chromatography (SiO
2
, hexane/ethyl acetate
3:1). nmax/cm 2945 (w, C–H), 1728 (s, amide CvO),
1526 (m, NO ), 1352 (w, NO ); d 1.50 (3H, s, CH ), 2.99
(3H, s, COCH ), 3.18 (3H, s, NCH ), 3.92 (3H, s, ArOCH ),
7.09 (1H, s, ArH), 7.27 (1H, s, ArH); d 23.9 (CH ), 26.5
(NCH ), 53.5 (OCH ), 57.3 (ArOCH ), 79.7 (C), 105.4
2
1
2
H
(
(
7
(
3H, s, CH ), 2.92 (3H, s, OCH ), 3.15 (3H, s, NCH ), 6.78
3
2
2
H
3
3
3
1H, d, J¼7.6 Hz, ArH), 7.05 (1H, td, J¼7.6, 1 Hz, ArH),
3
3
3
.25 (2H, m, ArH); dC 23.8 (CH ), 26.1 (NCH ), 53.0
3
C
3
3
OCH ), 79.5 (C), 108.4 (CH), 123.1 (CH), 123.7 (CH),
3
3
3
3
1
1
28.5 (C), 129.3 (CH), 143.4 (C), 176.5 (amide CvO); m/z
þ
(CH), 110.3 (CH), 135.4 (C), 136.8 (C), 140.1 (C), 150.4
þ
91 (77, M ), 175 (58), 160 (100), 132 (53), 77 (10).
(C), 175.2 (amide CvO); m/z (EI) 266 (100, M ), 236 (38),
223 (59), 176 (36), 160 (20), 77 (20) (Found: 266.0894.
C H N O requires M 266.0903).
12 14 2 5
3
6
0
.2.2. 1,3-Dimethyl-3-ethoxyindolin-2-one, 9b. Oxindole
(20 mg, 0.12 mmol) in ethanol (1 mL) and CAN (0.15 g,
.27 mmol) gave a colourless oil, 9b (18.3 mg, 72%) after
3.2.7. 1,3-Dimethyl-3-ethoxy-5-methoxy-6-nitroindolin-
2-one, 9g. Oxindole 7 (45 mg, 0.23 mmol) in ethanol
(1.5 mL) and CAN (289 mg, 0.53 mmol) gave a yellow
chromatography (SiO , hexane/ethyl acetate 1:1.5). nmax/
2
2
1
cm 2977 (m, C–H), 1724 (s, amide CvO), 1124 (m,
C–O); dH 1.06 (3H, t, J¼7 Hz, OCH CH ), 1.48 (3H, s,
foam, 9g (42 mg, 64%) after chromatography (SiO ,
2
2
3

9544
C. Escolano et al. / Tetrahedron 58 (2002) 9541–9545
hexane/ethyl acetate 3:1). nmax/cm2 2965 (w, C–H), 1726
1
and ester CvO); d 1.06 (3H, t, J¼6.9 Hz, CH CH ), 2.98
2 3 3
H
2
3
(
s, amide CvO), 1525 (m, NO ), 1351 (w, NO ); d 1.09
H
and 3.03 (2H, 2q, J¼6.9 Hz, CH CH ), 3.18 (3H, s, N CH ),
2
2
(
3H, t, J¼7.0 Hz, CH CH ), 1.50 (3H, s, CH ), 2.98 and
3.85 (3H, s, COOCH ), 6.82 (1H, d, J¼8.2 Hz, H-7), 7.92
2
3
3
3
3
ArOCH ), 7.08 (1H, s, ArH), 7.25 (1H, s, ArH); d 15.3
.11 (2H, m, CH CH ), 3.16 (3H, s, NCH ), 3.92 (3H, s,
(1H, d, J¼1.6 Hz, H-4), 8.01 (1H, dd, J¼8.2, 1.6 Hz,
2
3
3
H-6); d 15.3 (CH CH ), 24.0 (CH ), 26.3 (NCH ), 52.1
C
3
C
2
3
3
3
(
CH CH ), 24.3 (CH ), 26.5 (NCH ), 57.3 (OCH ), 61.5
3
(COOCH ), 61.0 (CH ), 78.6 (C), 107.9 (CH), 124.8 (CH),
3 2
2
3
3
3
(
1
CH ), 79.1 (C), 105.3 (CH), 110.2 (CH), 136.2 (2£C),
125.0 (C), 129.4 (C), 132.2 (CH), 147.2 (C), 166.6 (amide
CvO), 177.1 (ester CvO); m/z (EI) 263 (12.7, M ), 234
2
þ
(8), 219 (100), 188 (7), 158 (8) (Found: M , 263.1155.
39.7 (C), 150.4 (C), 175.6 (amide CvO); m/z (EI) 280
þ
60 (39), 77 (33) (Found: M , 280.1059. C H N O
þ
þ
þ
(
100, M ), 251 (31, M ), 236 (92, M ), 223 (92), 176 (60),
þ
1
requires M 280.1047).
C H NO requires M 263.1157).
14 17
1
3
16
2
5
4
3.2.12. 1,3-Dimethyl-3-isopropoxy-5-methoxycarbonyl-
3
.2.8. 1,3-Dimethyl-3-isopropoxy-5-methoxy-6-nitro-
indolin-2-one, 9h. Oxindole 7 (91 mg, 0.48 mmol) in
indolin-2-one, 9l. Oxindole 8 (101 mg, 0.46 mmol) in
isopropanol (5 mL) and CAN (549 mg, 1 mmol) gave a
white solid corresponding to a mixture of 9l (68.6 mg,
53%) and 9m (46 mg, 36%) after chromatography (SiO2,
isopropanol (3 mL) and CAN (629 mg, 1.15 mmol) gave a
yellow foam, 9h (90 mg, 64%) after chromatography (SiO ,
2
2
1
hexane/ethyl acetate 3:1). nmax/cm 2975 (w, C–H), 1728
s, amide CvO), 1526 (m, NO ), 1350 (w, NO ); d 0.90
hexane/ethyl acetate 1:1.2). Data for 9l: d 0.90 and 1.01
H
(
(6H, 2d, J¼6.1 Hz, CH(CH ) ), 1.46 (3H, s, CH ), 3.18 (3H,
2
2
H
3 3
3
and 1.06 [6H, 2d, J¼6.1 Hz, CH(CH ) ], 1.47 (3H, s, CH ),
s, N CH ), 3.25 (1H, m, CH(CH ) ), 3.84 (3H, s, OCH ),
3 3 3 3
3
2
3
3.17 (3H, s, NCH ), 3.25 [1H, m, CH(CH ) ], 3.92 (3H, s,
OCH ), 7.10 (1H, s, ArH), 7.26 (1H, s, ArH); d 23.4 (CH ),
6.83 (1H, d, J¼8.2 Hz, H-7), 7.94 (1H, d, J¼1.6 Hz, H-4),
8.01 (1H, dd, J¼8.2, 1.6 Hz, H-6); d 23.4 (CH ), 24.2
(CH ), 24.8 (CH ), 26.4 (NCH ), 52.1 (OCH ), 69.3 (CH),
3 3 3 3
3
3 2
3
C
3
C
3
2
4.2 (CH ), 25.0 (CH ), 26.5 (NCH ), 57.4 (OCH ), 69.9
3
3
3
3
(
(
(
CH), 78.8 (C), 105.3 (CH), 110.5 (CH), 135.9 (C), 137.1
C), 139.7 (C), 150.2 (C), 176.1 (amide CvO); m/z (EI) 294
78.2 (C), 108.0 (CH), 124.8 (C), 125.1 (CH), 130.1 (C),
132.1 (CH), 147.0 (C), 166.6 (amide CvO), 177.7 (ester
CvO).
þ
þ
þ
59.5), 77 (33) (Found: M , 294.1208. C H N O requires
88, M ), 251 (60, M ), 236 (100, M ), 223 (64), 176
þ
(
M 294.1216).
1
4 18 2 5
3.2.13. 1,3-Dimethyl-5-methoxycarbonyl-3-nitrooxy-
indolin-2-one, 9m. Oxindole 8 (103 mg, 0.47 mmol) in
THF or acetonitrile (4 mL) and CAN (551 mg, 1 mmol)
gave a white foam, 9m (105 mg, 80%, 111 mg, 84%,
3
.2.9. 1,3-Dimethyl-5-methoxy-6-nitro-3-nitrooxyindo-
lin-2-one, 9i. Oxindole 7 (86 mg, 0.45 mmol) in THF or
acetonitrile (3 mL) and CAN (631 mg, 1.15 mmol) gave a
yellow foam, 9i (77 mg, 57%; 81 mg, 60%, respectively)
after chromatography (SiO , hexane/ethyl acetate 3:1).
2
nmax/cm 1736 (s, amide CvO), 1648 (s, ONO ), 1528
2
respectively) after chromatography (SiO , hexane/ethyl
2
2
1
acetate 1:1.2). nmax/cm 2947 (m, C–H), 1746 (s, ester
CvO), 1715 (s, amide CvO), 1651 and 1621 (s, O–NO2);
dH 1.65 (3H, s, CH ), 3.29 (3H, s, NCH ), 3.90 (3H, s,
21
3
3
(
NCH ), 3.98 (3H, s, OCH ), 7.16 (1H, s, ArH), 7.38 (1H, s,
s, NO ), 1353 (w, NO ); d 1.67 (3H, s, CH ), 3.28 (3H, s,
OCH ), 6.95 (1H, d, J¼8.2 Hz, H-7), 8.01 (1H, d, J¼1.6 Hz,
2
2
H
3
3
H-4), 8.13 (1H, dd, J¼8.2, 1.6 Hz, H-6); d 21.2 (CH ), 26.9
(NCH ), 52.2 (OCH ), 82.8 (C), 108.6 (CH), 123.9 (CH),
3 3
3
3
C
3
ArH); d 21.4 (CH ), 27.0 (NCH ), 57.4 (OCH ), 82.7 (C),
3
C
3
3
1
1
06.1 (CH), 109.2 (CH), 132.3 (C), 136.2 (C), 140.4 (C),
þ
125.4 (C), 126.3 (C), 133.2 (CH), 147.3 (C), 166.1 (amide
CvO), 177.2 (ester CvO); m/z (EI) 280 (80, M ), 234 (98),
þ
218 (68), 206 (100), 175 (43), 160 (42), 147 (20) (Found:
50.3 (C), 170.2 (amide CvO); m/z (EI) 297 (72, M ), 251
þ
(
89.6), 235 (67), 223 (89), 176 (100), 77 (46) (Found: M ,
97.0605. C H N O requires M 297.0597).
þ
2
M , 280.0693. C H N O requires M 280.0695).
12 12 2 6
1
1
11
3
7
3.2.10. 1,3-Dimethyl-3-methoxy-5-methoxycarbonyl-
indolin-2-one, 9j. Oxindole 8 (99 mg, 0.45 mmol) in
methanol (3 mL) and CAN (559 mg, 1.01 mmol) gave a
white foam, 9j (81 mg, 72%) after chromatography (SiO ,
Acknowledgements
2
2
1
hexane/ethyl acetate 1:1.2). nmax/cm 2930 (m, C–H),
728 (s, amide CvO), 1712 (s, ester CvO); d 1.50 (3H, s,
C. E. thanks the European Union for funding (contract no.
ERBFMICT 983265).
1
CH ), 2.95 (3H, s, OCH ), 3.19 (3H, s, NCH ), 3.85 (3H, s,
H
3
3
3
COOCH ), 6.84 (1H, d, J¼8.3 Hz, H-7), 7.93 (1H, d, J¼
3
1
.6 Hz, H-4), 8.03 (1H, dd, J¼8.3, 1.6 Hz, H-6); d 23.6
C
(
(
(
CH ), 26.3 (NCH ), 52.1 (COOCH ), 53.1 (OCH ), 79.2
3
References
3
3
3
C), 108.0 (CH), 125.0 (CH), 125.1 (C), 128.6 (C), 132.3
CH), 147.4 (C), 166.6 (amide CvO), 176.8 (ester CvO);
þ
28) (Found: M , 249.1001. C H NO requires M
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þ
(
1
3
15
4
2
49.1001).
3
.2.11. 1,3-Dimethyl-3-ethoxy-5-methoxycarbonylindo-
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(
9
2
2
1
acetate 1:1.2). nmax/cm 2979 (w, C–H), 1715 (s, amide

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3
4
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(
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(
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(
3
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6
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(
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(
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(
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1
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