Synthesis of substituted nitrooxindoles via intramolecular oxidative nucleophilic substitution of hydrogen in m-nitroacylanilides

Article abstract of DOI:10.1055/s-2002-34850

A simple method of the synthesis of substituted nitrooxindoles via intramolecular oxidative nucleophilic substitution of hydrogen is described.

Full text of DOI:10.1055/s-2002-34850

PAPER
2203
Synthesis of Substituted Nitrooxindoles via Intramolecular Oxidative Nucleo-
philic Substitution of Hydrogen in m-Nitroacylanilides
S
ynthesis of Substitute
i
d
N
itro
e
oxindole
s
czys aw M kosza,* Maciej Paszewski
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44, 01-224 Warszawa 42, POB 58, Poland
Fax +48(22)6326681; E-mail: icho-s@icho.edu.pl
Received 30 April 2002; revised 10 July 2002
be replaced by a substituent, for instance, a methyl group.
Abstract: A simple method of the synthesis of substituted nitroox-
indoles via intramolecular oxidative nucleophilic substitution of hy-
drogen is described.
Thus, N-methyl m-nitroacylanilides were used in our stud-
ies. Amongst a few base-solvent systems typically used
for generation of carbanions, t-BuOK/DMSO at room
temperature was found to give the best results. It should
be mentioned that formation of oxindoles via the intramo-
lecular ONSH reaction of m-nitroacylanilides is accompa-
nied with a deep blue or red coloration of the reaction
mixture because highly colored o- and p-nitrobenzylic
carbanions are produced. The process and results are pre-
sented in Scheme 1 and Table 1.
Key words: nucleophilic aromatic substitution, oxindoles, nitro-
acylanilides
The indole ring system is present in many natural prod-
ucts, pharmaceuticals, agrochemicals, etc. Thus, there is a
continuous quest for efficient methods of synthesis of in-
dole derivatives.1 Of great interest are also methods of
synthesis of oxindoles.2 Amongst numerous methods ap-
plicable for construction of the indole ring, we are partic-
ularly interested in those based on nucleophilic
substitution of hydrogen in nitroarenes.3 These methods
use two principal approaches. One of them consists in the
introduction of substituents ortho to the nitro group via vi-
carious nucleophilic substitution (VNS) or oxidative nu-
cleophilic substitution of hydrogen (ONSH). After further
transformations of the products, including reduction of the
nitro group, the indole ring is formed.4,5 Alternative ap-
proach use m-nitroaniline as the basic starting material, its
further transformations including the key process of nu-
cleophilic substitution of hydrogen with proper carban-
ions, leads to nitroindoles in which the nitrogen atom of
the amino groups is found in the indole ring.6 Perhaps the
most attractive variant of the latter approach is the recent-
ly reported synthesis of nitroindoles via direct condensa-
tion of m-nitroaniline with enolates of ketones.7
Nitrooxindoles were prepared via intramolecular VNS re-
action of m-nitroanilides of -halocarboxylic acids.8
Intramolecular substitutions of hydrogen in the nitroaryl
ring, which proceeds in the vicinity of the amide moiety,
can take place in two positions: ortho and para in relation
to the nitro group giving two isomeric 4- and 6-nitrooxin-
doles 2 and 3, respectively. In all cases of the m-nitroacyl-
anilides studied there was strong preference for the reac-
tion to occur in the more sterically hindered position ortho
to the nitro group to give 4-nitrooxindoles 2 as the main
products. Tendency for such orientation was already ob-
9
served in inter- and intramolecular VNS reactions and
also in the synthesis of nitroindoles via the reaction of ke-
tones with m-nitroaniline.7 The intramolecular reaction of
carbanions generated from 6-chloro-3-nitroacylanilides
can proceed via ONSH at position 2 to produce 7-chloro-
4-nitrooxindoles or by conventional nucleophilic substitu-
tion of the halogen (SNAr) to give 6-nitrooxindoles. Al-
though in the reaction of anilides 1e–h two nitrooxindoles
are formed: expected 7-chloro-4-nitrooxindoles and prod-
ucts which do not contain the halogen, the latter were
identical to the main products obtained from anilides
1a–d, thus were obviously produced not via intramolecu-
lar SNAr of the halogen but via dehalogenation proceeding
during the reaction. A similar dehalogenation process was
observed in the synthesis of indoles via direct condensa-
tion of enolates with 2-chloro-5-nitroaniline.7
In this paper, we report that nitrooxindoles can be readily
obtained from simpler starting materials, m-nitroanilides
of carboxylic acids via intramolecular ONSH reaction.
The reaction consists in the treatment of m-nitroanilides of
alkanoic acids with a strong base, which abstracts a proton
from the acyl moiety. The generated carbanions add in-
tramolecularly to the nitroaromatic ring ortho/para to the
nitro group giving anionic H adducts that are subsequent-
ly oxidized to form the oxindole ring. Since acidity of NH
hydrogen of the m-nitroanilides is similar or even higher
than that of -methyl or -methylenic protons of the acyl
moieties, for the reaction to proceed the NH proton should
This observation provides additional support to the gener-
al rule that nucleophilic addition of carbanions to nitroar-
omatic rings proceeds usually faster in positions occupied
with hydrogen than in those, similarly activated, occupied
with halogens.10
H
It appears that the anionic
adducts produced via in-
tramolecular addition of the carbanion of nitroacylanil-
ides are oxidized by air oxygen always present in the
system. When the reaction of 1b was carried out in metic-
ulously deoxygenated system, the oxindole was not
Synthesis 2002, No. 15, Print: 29 10 2002.
Art Id.1437-210X,E;2002,0,15,2203,2206,ftx,en;Z06902SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

2204
M. M kosza, M. Paszewski
Scheme 1
formed; on the other hand bubbling of oxygen in the reac- 1H NMR (200 MHz, CDCl3): = 1.11 (t, 3 H, J = 7.4 Hz), 2.16 (br,
2 H), 3.34 (s, 3 H), 7.55–7.68 (m, 2 H), 8.08–8.12 (m, 1 H), 8.17–
tion mixture does not change the results.
8.24 (m, 1 H).
13C NMR (CDCl3): = 9.41, 27.70, 37.37, 122.21, 130.41, 133.32,
Table 1 Substituted Nitrooxindoles 2 (and 3) Prepared
145.24, 148.89, 173.40.
MS (EI): m/z (%) = 208 (M+, 14), 152 (100), 106 (14), 57 (32).
Entry
X
R1
H
No
1a
1b
1c
1d
1e
1f
Products, Yield (%)
1a
2
H
2a, 35
2b, 64
2c, 56
2d, 45
2e, 29
2f, 33
2g, 38
2h, 32
–
3a, traces
Anal. Calcd for C10H12N2O3: C, 57.69; H, 5.81; N, 13.45. Found: C,
57.33; H, 6.05; N, 13.27.
H
Me
Et
–
3b, traces
N-Methyl-3 -nitrobutyranilide (1c)
Yield: 87%; mp 51°C (hexane–toluene).
3
H
–
3c, 9
4
H
Ph
H
–
3d, 12
1H NMR (400 MHz, CDCl3): = 0.88 (br, 3 H), 1.45 (m, 2 H), 2.1
(br, 2 H), 3.34 (s, 3 H), 7.56–7.66 (m, 2 H), 8.09 (m, 1 H), 8.20 (m,
1 H).
13C NMR (CDCl3): = 13.75, 18.66, 36.15, 37.37, 122.33, 130.47,
133.44, 145.28, 148.88, 172.61.
MS (EI): m/z (%) = 222 (M+, 13), 152 (100), 106 (16), 71 (42), 43
(61).
5a
6
Cl
Cl
Cl
Cl
–
–
–
–
–
Me
Et
2b, 17
2c, 23
2d, 27
7
1g
1h
8
Ph
a Three equivalents of t-BuOK were used.
Anal. Calcd for C11H14N2O3: C, 59.45; H, 6.35; N, 12.6. Found: C,
59.42; H, 6.54; N, 12.65.
N-Methyl-(3 -nitro)phenylacetanilide (1d)
Yield: 75%; mp 70–72 °C (hexane–toluene).
Commercial DMSO and DMF were distilled over CaH2 and stored
over molecular sieves. Column chromatography was performed us-
ing Merck Kieselgel 60. 1H NMR and 13C NMR were recorded on
Varian Gemini (200 MHz) and Varian Mercurry (400 MHz) spec-
trometers. Chemical shifts ( ) are given in ppm downfield from
TMS. Coupling constants are given in Hz. MS were measured on
AMD 604 spectrometer.
1H NMR (400 MHz, acetone-d6): = 3.32 (br, 3 H), 3.58 (br, 2 H),
7.1 (br, 1 H), 7.16–7.26 (m, 2 H), 7.7–7.78 (m, 3 H), 8.12 (br, 1 H),
8.21 (br, 1 H).
13C NMR (CDCl3): = 37.61, 41.67, 96.6, 127.25, 128.99, 131.39,
136.39, 146.21, 149.62.
Starting materials: 3 -nitroacetanilide,11 2 -chloro-5 -nitroacetanil-
ide,11 N-methyl-3 -nitroacetanilide (1a),12 N-methyl-3-nitro-
aniline12 and N-Methyl-2 -chloro-5 -nitroacetanilide (1e)12 were
prepared according to reported procedures. Compounds 1b–d were
prepared via acylation of N-methyl-3-nitroaniline with appropriate
acyl chlorides, whereas 1f–h were prepared via methylation of ap-
propriate 2 -chloro-5 -nitroacylanilides.
It was observed that in 1H and 13C NMR spectra of compounds 1a–
h some signals were broadened or doubled. This is caused by re-
stricted internal rotation of N–C(O) bond and is often observed in
the NMR spectra of amides.13
MS (EI): m/z (%) = 270 (M+, 22), 152 (50), 118 (36), 91 (100).
Anal. Calcd for C15H14N2O3: C, 66.66; H, 5.22; N, 10.36. Found: C,
66.6; H, 5.17; N, 10.25.
(2 -Chloro-5 -nitro)acetanilide
Yield: 86%; mp 160 °C (EtOH).
1H NMR (200 MHz, CDCl3): = 2.28 (s, 3 H), 7.51 (d, 1 H, J = 8.8
Hz), 7.65 (br s, 1 H), 7.86–7.92 (m, 1 H), 9.3 (br s, 1 H).
13C NMR (CDCl3): = 24.86, 96.1, 116.27, 118.97, 128.37, 129.49,
135.47, 147.17, 168.33.
MS (EI): m/z (%) = 214 (M+, 18), 179 (25), 172 (100), 126 (20), 90
N-Methyl-3 -nitropropionanilide (1b); Typical Procedure
To a solution of N-methyl-3-nitroaniline (4.26 g, 28 mmol) in anhyd
toluene (60 mL) were added a solution of propionyl chloride (2.98
g, 32 mmol) in toluene (5 mL) and Et3N (3.4 g, 33.6 mmol). The
mixture was stirred for 3 h at r.t. and treated with H2O (150 mL) and
EtOAc (100 mL). The organic layer was separated washed and
dried. The solvents were evaporated and the residue recrystallized
from hexane–toluene to give 1b; yield: 4.95 g (85)%; mp 64 °C.
(17), 43 (79).
Anal. Calcd for C8H7ClN2O3: C, 44.77; H, 3.29; Cl, 16.52; N, 13.05.
Found: C, 44.76; H, 3.36; Cl, 16.69; N, 13.06.
(2 -Chloro-5 -nitro)propionanilide
Yield: 71%; mp 124–125 °C (hexane–toluene).
Synthesis 2002, No. 15, 2203–2206 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Substituted Nitrooxindoles
2205
1H NMR (200 MHz, CDCl3): = 1.3 (t, 3 H, J = 7.5 Hz), 2.54 (q, 2
H, J = 7.5 Hz), 7.54 (d, 1 H, J = 8.8 Hz), 7.77 (s, 1 H), 7.9 (dd, 1 H,
J = 8.8, 2.7 Hz), 9.35 (d, 1 H, J = 2.7 Hz).
13C NMR (CDCl3): = 9.25, 30.91, 116.16, 118.77, 128.36, 129.43,
135.5, 147.19, 172.06.
MS (EI): m/z (%) = 228 (M+,4), 213 (9), 193 (92), 186 (66), 140
(33), 104 (14), 77 (20), 43 (100).
Anal. Calcd for C10H11ClN2O3: C, 49.5; H, 4.57; Cl, 14.61; N,
11.54. Found: C, 49.61; H, 4.71; Cl, 14.72; N, 11.48.
N-Methyl-(2 -chloro-5 -nitro)butyranilide (1g)
Yield: 90%; mp 46–47 °C (heptane).
1H NMR (200 MHz, CDCl3): = 0.85 (t, 3 H, J = 7.3 Hz), 1.56–
1.72 (m, 2 H), 1.90–2.00 (m, 2 H), 3.23 (s, 3 H), 7.74 (d, 1 H, J = 8.6
Hz), 8.18–8.24 (m, 2 H).
MS (EI): m/z (%) = 228 (M+, 25), 193 (23), 172 (59), 126 (17), 90
(22), 57 (100).
Anal. Calcd for C9H9ClN2O3: C, 47.28; H, 3.97; Cl, 15.51; N, 12,25.
Found: C, 47.36; H, 4.11; Cl, 15.52; N, 12.18.
(2 -Chloro-5 -nitro)butyranilide
Yield: 67%; mp 129–130 °C (hexane–toluene).
13C NMR (CDCl3): = 13.69, 18.34, 35.66, 35.85, 124.17, 125.19,
131.5, 140.60, 142.36, 147.18, 172.25.
1H NMR (200 MHz, CDCl3): = 1.05 (t, 3 H, J = 7.3 Hz), 1.7–1.9
(m, 2 H), 2.48 (t, 2 H, J = 7.3 Hz), 7.54 (d, 1 H, J = 8.8 Hz), 7.75
(br, 1 H), 7.92 (dd, 1 H, J = 8.8, 2.6 Hz), 9.35 (d, 1 H, J = 2.6 Hz).
13C NMR (CDCl3): = 13.62, 18.72, 39.68, 116.21, 118.79, 128.39,
129.43, 135.49, 147.11, 171.35.
MS (EI): m/z (%) = 221 (M+, 69), 188 (32), 186 (100), 140 (12), 71
(81), 43 (99), 41 (19).
Anal. Calcd for C11H13ClN2O3: C, 51.47; H, 5.1; Cl, 13.81; N,
10.91. Found: C, 51.23; H, 5.26; Cl, 13.98; N, 10.77.
N-Methyl-(2 -Chloro-5 -nitro)phenylacetanilide (1h)
Yield: 88%; mp 164 °C (hexane–EtOAc).
MS (EI): m/z (%) = 242 (M+, 13), 172 (73), 71 (60), 43 (100).
Anal. Calcd for C10H11ClN2O3: C, 49.58; H, 4.58; Cl, 14.45; N,
11.57. Found: C, 49.36; H, 4.72; Cl, 14.37; N, 11.48.
1H NMR (400 MHz, CDCl3): = 3.24 (s, 3 H), 3.33 (d, 1 H, J = 15
Hz), 3.51 (d, 1 H, J = 15 Hz), 6.92–6.96 (m, 2 H), 7.18–7.23 (m, 3
H), 7.68 (d, 1 H, J = 8.8 Hz), 7.89 (d, 1 H, J = 2.7 Hz), 8.18 (dd, 1
H, J = 8.8, 2.7 Hz).
13C NMR (CDCl3): = 36.10, 41.72, 124.22, 125.80, 127.04,
128.51, 128.71, 131.32, 134.05, 140.64, 141.83, 146.86, 170.36.
(2 -Chloro-5 -nitro)phenylacetanilide
Yield: 65%; mp 188–190°C (EtOH–H2O).
1H NMR (400 MHz, acetone-d6): = 3.93 (s, 2 H), 7.27–7.34 (m, 1
H), 7.35–7.42 (m, 2 H), 7.42–7.5 (m, 2 H), 7.73 (d, 1 H, J = 8.7 Hz),
7.98 (dd, 1 H, J = 2.8, 8.7 Hz), 8.91 (br, 1 H), 9.21 (d, 1 H, J = 2.8
Hz).
MS (EI): m/z (%) = 304 (M+, 4), 269 (54), 213 (12), 186 (19), 118
(45), 91 (100).
13C NMR (acetone-d6): = 44.39, 96.61, 117.63, 120.0, 127.93,
129.49, 130.3, 131.02, 135.83, 137.02, 170.64
Anal. Calcd for C15H13ClN2O3: C, 59.12; H, 4.3; Cl, 11.63; N, 9.19.
Found: C, 58.92; H, 4.23; Cl, 11.55; N, 8.98.
MS (EI): m/z (%) = 290 (M+, 10), 255 (14), 118 (89), 91 (100), 65
(10).
1,3-Dimethyl-4-nitrooxindole (2b); Typical Procedure
To a stirred solution of t-BuOK (170 mg, 1.5 mmol) in anhyd
DMSO (10 mL) was added dropwise a solution of 1b (208 mg, 1
mmol) in DMSO (5 mL) during 20 min at r.t. The dark blue mixture
was stirred for 40 min, treated with dil. HCl (100 mL) and extracted
with EtOAc. The combined organic extracts were washed, dried,
the solvent evaporated and the residue purified by column chroma-
tography on silica gel using hexane–EtOAc as eluent to give 2b;
yield: 64%; mp 148–150 °C (hexane–EtOAc).
1H NMR (400 MHz, CDCl3): = 1.52 (d, 3 H, J = 7.5 Hz), 3.27 (s,
1 H), 4.03 (q, 1 H, J = 7.5 Hz), 7.12 (d, 1 H, J = 7.8 Hz), 7.47 (m, 1
H), 7.82 (m, 1 H).
Anal. Calcd for C14H11ClN2O3: C, 57.84; H, 3.81; Cl, 12.2; N, 9.64.
Found: C, 57.69; H, 3.73; Cl, 12.32; N, 9.43.
Methylation of 2 -Chloro-5 -nitroacylanilides; N-Methyl-(2 -
chloro-5 -nitro)propionanilide (1f); Typical Procedure
To a solution of (2 -chloro-5 -nitro)propionanilide (3.63 g, 15
mmol) in anhyd DMF (50 mL) under argon at r.t. was added t-
BuOK (2.02 g, 18 mmol). After 5 min, to the dark red solution was
added MeI (2.8 mL, 45 mmol) and the mixture was stirred for 1 h.
The mixture was treated with dil. HCl (150 mL) and extracted with
EtOAc. The extracts were washed, dried (MgSO4) and the solvent
evaporated. The residue was recrystallized from hexane–toluene to
give 1f; yield: 85%; mp 54 °C.
13C NMR (CDCl3): = 14.9, 26.64, 41.83, 113.07, 117.38, 126.67,
129.07, 144.94, 146.32, 177.74,
1H NMR (400 MHz, CDCl3): = 1.09 (t, 3 H, J = 7.4 Hz), 1.94–
2.05 (m, 2 H), 3.24 (s, 3 H), 7.73 (d, 1 H, J = 8.7 Hz), 8.19–8.24 (m,
2 H).
13C NMR (CDCl3): = 9.22, 27.40, 35.74, 124.20, 125.19, 131.52,
140.65, 142.33, 147.27, 173.10.
MS (EI): m/z (%) = 206 (M+, 100), 189 (17), 160 (35), 117 (38).
Anal. Calcd for C10H10N2O3: C, 58.25; H, 4.89; N, 13.59. Found: C,
58.03; H, 5.09; N, 13.37.
1-Methyl-4-nitrooxindole (2a)
Yield: 35%; mp 149–151 °C (hexane–EtOAc).
1H NMR (400 MHz, CDCl3): = 3.28 (s, 3 H), 4.00 (s, 2 H), 7.12
MS (EI): m/z (%) = 242 (M+, 2), 213 (25), 207 (79), 186 (85), 57
(100).
(d, 1 H, J = 7.7 Hz), 7.49 (m, 1 H), 7.87 (dd, 1 H, J = 9.6, 0.8 Hz).
13C NMR (CDCl3): = 26.61, 37.02, 113.10, 117.03, 121.25,
129.16, 144.31, 147.24, 173.85.
Anal. Calcd for C10H11ClN2O3: C, 49.5; H, 4.57; Cl, 14.61; N,
11.54. Found: C, 49.61; H, 4.71; Cl, 14.73; N, 11.48.
N-Methyl-(2 -chloro-5′-nitro)acetanilide (1e)
Yield: 70%; mp 105–107 °C (EtOH).
1H NMR (400 MHz, CDCl3): = 1.84 and 2.32 (2 s, 3 H each), 3.24
and 3.38 (2 s, 3 H each), 7.74 (m, 1 H), 8.21–8.24 (m, 2 H).
13C NMR (CDCl3): = 21.65, 21.92, 35.69, 38.36, 96.10, 123.49,
124.22, 125.07, 131.02, 131.50, 140.47, 142.71, 147.31, 169.51.
MS (EI): m/z (%) = 192 (M+,100), 175 (35), 147 (38), 117 (31), 91
(28).
Anal. Calcd for C9H8N2O3: C, 56.25; H, 4.2; N, 14.58. Found: C,
56.02; H, 4.26; N, 14.41.
3-Ethyl-1-methyl-4-nitrooxindole (2c)
Yield: 56%; mp 114–115 °C (hexane–EtOAc).
Synthesis 2002, No. 15, 2203–2206 ISSN 0039-7881 © Thieme Stuttgart · New York

2206
M. M kosza, M. Paszewski
1H NMR (200 MHz, CDCl3): = 0.67 (t, 3 H, J = 7.5 Hz), 2.05–
2.25 (m, 2 H), 3.27 (s, 3 H), 4.11 (m, 1 H), 7.10 (d, 1 H, J = 7.7 Hz),
7.47 (m, 1 H), 7.82 (dd, 1 H, J = 0.9, 8.5 Hz).
13C NMR (CDCl3): = 9.23, 22.45, 26.49, 47.55, 112.75, 117.37,
124.81, 129.08, 145.11, 146.99, 177.03.
MS (EI): m/z (%) = 240 (M+, 100), 223 (72), 208 (21), 195 (44), 166
(12), 131 (22).
Anal. Calcd for C10H9ClN2O3: C, 49.91; H, 3.77; Cl, 14.73; N,
11.64. Found: C, 49.82; H, 3.83; Cl, 14.57; N, 11.8.
7-Chloro-3-ethyl-1-methyl-4-nitrooxindole (2g)
Yield: 38%; mp 115 °C (hexane–EtOAc).
1H NMR (400 MHz, CDCl3): = 0.7 (t, 3 H, J = 7.6 Hz), 2.0–2.1
(m, 1 H), 2.1–2.2 (m, 1 H), 3.63 (s, 3 H), 4.8 (m, 1 H), 7.39 (dd, 1
H, J = 9.1, 0.7 Hz), 7.72 (d, 1 H, J = 9.1 Hz).
MS (EI): m/z (%) = 220 (M+, 32), 192 (100), 161 (14), 146 (17), 133
(12).
3-Ethyl-1-methyl-6-nitrooxindole (3c)
Yield: 9%; mp 117 °C (hexane–EtOAc).
1H NMR (200 MHz, CDCl3): = 0.9 (t, 3 H, J = 7.5 Hz), 2.05–2.11
(m, 2 H), 3.29 (s, 3 H), 3.52 (m, 1 H), 7.39 (m, 1 H), 7.65 (d, 1 H,
J = 2.1 Hz), 7.98 (dd, 1 H, J = 2.1, 8.1 Hz).
13C NMR (CDCl3): = 9.99, 23.5, 26.44, 46.64, 102.73, 117.95,
123.98, 136.2, 145.73, 148.28, 177.03
13C NMR (CDCl3): = 9.28, 22.96, 29.55, 47.19, 118.09, 120.79,
127.63, 131.29, 142.56, 143.62, 177.18.
MS (EI): m/z (%) = 254 (M+, 33), 228 (32), 226 (100), 220 (13), 196
(17), 180 (15).
Anal. Calcd for C11H12ClN2O3: C, 51.88: H, 4.35; Cl, 13.92; N,
11.00. Found: C, 51.72; H, 4.46; Cl, 13.71; N, 11.04.
MS (EI): m/z (%) = 220 (M+, 29), 192 (100), 161 (12), 146 (19).
Anal. Calcd for C11H12N2O3: C, 59.99; H, 5.49; N, 12.72. Found: C,
59.84; H, 5.41; N, 12.55.
7-Chloro-1-methyl-4-nitro-3-phenyloxindole (2h)
Yield: 32%; mp 165–166 °C (hexane–EtOAc).
1-Methyl-4-nitro-3-phenyloxindole (2d)
Yield: 45%; mp 168 °C (hexane–EtOAc).
1H NMR (200 MHz, CDCl3): = 3.29 (s, 3 H), 5.14 (s, 1 H), 7.08
(m, 2 H), 7.2 (d, 1 H, J = 7.8 Hz), 7.22–7.30 (m, 3 H), 7.56 (m, 1
H), 7.85 (m, 1 H).
1H NMR (400 MHz, acetone-d6): = 3.61 (s, 3 H), 5.22 (s, 1 H),
7.11–7.15 (m, 2 H), 7.24–7.31 (m, 3 H), 7.66 (dd, 1 H, J = 9.0, 0.7
Hz), 7.79 (d, 1 H, J = 9.0 Hz).
13C NMR (acetone-d6): = 52.84, 96.61, 118.90, 121.38, 128.41,
128.44, 128.69, 129.52, 132.87, 136.08, 144.05, 144.5, 175.52.
13C NMR (CDCl3): = 26.97, 53.12, 96.60, 114.65, 117.75, 125.46,
128.22, 128.63, 129.41, 130.93, 136.55, 145.63, 148.46, 175.17.
MS (EI): m/z (%) = 268 (M+, 100), 251 (24), 234 (65), 165 (25).
MS (EI): m/z (%) = 302 (M+, 100), 285 (28), 268 (65).
HRMS: m/z calcd for C15H11ClN2O3: 302.04582; found: 302.04849.
Anal. Calcd for C15H12N2O3: C, 67.16; H, 4.51; N, 10.44. Found: C,
67.01; H, 4.37; N, 10.27.
Acknowledgement
This work was supported by State Committee for Scientific Rese-
arch Grant No. PBZ 6.01.
1-Methyl-6-nitro-3-phenyloxindole (3d)
Yield: 12%; mp 169–71 °C (hexane–EtOAc).
1H NMR (400 MHz, CDCl3): = 3.34 (s, 3 H), 4.69 (s, 1 H), 7.13–
7.2 (m, 2 H), 7.26–7.38 (m, 4 H), 7.74 (d, 1 H, J = 2.1 Hz), 7.99 (dd,
1 H, J = 2.1, 8.1 Hz).
13C NMR (CDCl3): = 26.81, 51.88, 103.08, 118.31, 125.37,
128.13, 128.31, 129.16, 134.92, 135.85, 145.60, 148.58, 175.25.
References
(1) (a) Sundberg, R. J. Indoles; Academic Press: San Diego,
1996. (b) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1
2000, 1045.
(2) Lee, S.; Hartwig, J. F. J. Org. Chem. 2001, 66, 3402.
(3) (a) M kosza, M.; Wojciechowski, K. Heterocycles 2001, 54,
445. (b) M kosza, M. Pure Appl. Chem. 1997, 69, 559.
(4) (a) Wojciechowski, K.; M kosza, M. Bull. Chim. Soc. Belg.
1986, 95, 671. (b) Wojciechowski, K.; M kosza, M.
Synthesis 1986, 651.
MS (EI): m/z (%) = 268 (M+, 100), 251 (20), 239 (12), 222 (30), 193
(26).
Anal. Calcd for C15H12N2O3: C, 67.16; H, 4.51; N, 10.44. Found: C,
66.69; H, 4.25; N, 10.00.
(5) M kosza, M.; Danikiewicz, W.; Wojciechowski, K. Liebigs
Ann. Chem. 1988, 203.
7-Chloro-1-methyl-4-nitrooxindole (2e)
Yield: 29%; mp 165 °C (hexane–EtOAc).
(6) Wojciechowski, K.; M kosza, M. Tetrahedron Lett. 1984,
25, 4793.
(7) Moskalev, N.; M kosza, M. Tetrahedron Lett. 1999, 40,
5395.
(8) M kosza, M.; Hoser, H. Heterocycles 1994, 37, 1701.
(9) M kosza, M.; Glinka, T.; Kinowski, J. Tetrahedron 1984,
40, 1863.
1H NMR (200 MHz, CDCl3): = 3.64 (s, 3 H), 4.03 (s, 2 H), 7.41
(d, 1 H, J = 9.0 Hz), 7.79 (d, 1 H, J = 9.0 Hz).
13C NMR (CDCl3): = 29.62, 37.00, 96.10, 117.77, 121.11, 123.86,
131.37, 142.86, 173.83.
MS (EI): m/z (%) = 226 (M+, 100), 209 (30), 181 (29), 179 (12), 151
(14), 117 (35).
(10) (a) M kosza, M. Russ. Chem. Bull. 1996, 45, 491.
(b) Terrier, F. Nucleophilic Aromatic Displacement; VCH:
New York, 1991. (c) Chupakhin, O. N.; Charushin, V. N.;
van der Plas, H. C. Nucleophilic Aromatic Substitution of
Hydrogen; Academic Press: San Diego, 1999.
(11) Rosevear, J.; Wilshire, J. F. K. Aust. J. Chem. 1985, 38, 723.
(12) Svoboda, P.; Pytela, O.; Vecera, M. Collect. Czech. Chem.
Commun. 1987, 52, 2217.
Anal. Calcd for C9H7ClN2O3: C, 47.7; H, 3.11; Cl, 15.64; N, 12.36.
Found: C, 47.81; H, 3.24; Cl, 15.30; N, 12.29.
7-Chloro-1,3-dimethyl-4-nitrooxindole (2f)
Yield: 33%; mp 124–125 °C (hexane–EtOAc).
1H NMR (400 MHz, CDCl3): = 1.50 (d, 3 H, J = 7.5 Hz), 3.67 (s,
3 H), 4.07 (q, 1 H, J = 7.5 Hz), 7.38 (dd, 1 H, J = 9.1, 0.6 Hz), 7.73
(d, 1 H, J = 9.1 Hz).
(13) Curray, D. P.; Yu, H.; Liu, H. Tetrahedron 1994, 50, 7343.
13C NMR (CDCl3): = 15.28, 29.73, 41.53, 118.13, 121.04, 129.38,
131.27, 141.98, 143.52, 177.88.
Synthesis 2002, No. 15, 2203–2206 ISSN 0039-7881 © Thieme Stuttgart · New York