Catalyst-free straightforward synthesis of 3-cyano-3-arylamino-2-oxindoles through hydrocyanation with benzoyl cyanide

Article abstract of DOI:10.1002/jhet.3809

The effective hydrocyanation of 3-(arylimino)indolin-2-ones with benzoyl cyanide under catalyst-free condition at room temperature to synthesize 3-cyano-3-arylamino-2-oxindoles is described. This protocol benefits from low toxicity, inexpensive, and easy-to-handle cyanating agent, no catalysts, no additives, mild conditions, good substrate tolerance, and simple work-up procedure. This reaction successfully offers an alternative to structurally diverse 3,3-disubstituted oxindoles.

Full text of DOI:10.1002/jhet.3809

Received: 5 September 2019
DOI: 10.1002/jhet.3809
Revised: 13 October 2019
Accepted: 17 October 2019
A R T I C L E
Catalyst‐free straightforward synthesis of 3‐cyano‐3‐
arylamino‐2‐oxindoles through hydrocyanation with
benzoyl cyanide
Xiao Chen | Zheng Li
College of Chemistry and Chemical
Abstract
Engineering, Northwest Normal
The effective hydrocyanation of 3‐(arylimino)indolin‐2‐ones with benzoyl cya-
University, Lanzhou, China
nide under catalyst‐free condition at room temperature to synthesize 3‐cyano‐
Correspondence
Zheng Li, College of Chemistry and
3‐arylamino‐2‐oxindoles is described. This protocol benefits from low toxicity,
Chemical Engineering, Northwest Normal
University, Lanzhou, Gansu, 730070,
China.
inexpensive, and easy‐to‐handle cyanating agent, no catalysts, no additives,
mild conditions, good substrate tolerance, and simple work‐up procedure. This
reaction successfully offers an alternative to structurally diverse 3,3‐
disubstituted oxindoles.
Email: lizheng@nwnu.edu.cn
Funding information
National Natural Science Foundation of
China, Grant/Award Number: 21462038
1 | INTRODUCTION
to explore simpler, greener, safer, and more convenient
method for the synthesis of 3‐cyano‐3‐arylamino‐2‐
The 3,3‐disubstituted oxindole structure motif is a
privileged heterocyclic subunit in a large number of bio-
active natural products and drugs.[1] Much attention has
been devoted to the development of synthetic method
for sufficient amount of these compounds and their ana-
logs for biological evaluation and studies on the
structure‐activity relationship, aiming at the development
of new therapeutic agents or important biological tools.[2]
3‐Cyano‐3‐arylamino‐2‐oxindoles as typical examples
of 3,3‐disubstituted oxindoles may have potential applica-
tion value. For example, the cyano group could serve as a
useful synthetic precursor for further transformation into
desired functionalities, such as amine, carbonyl, amide,
and carboxylic acid.[3] However, the synthetic methods
for them currently are underdeveloped. Only few litera-
tures reported the synthesis via Bronsted or Lewis acids‐
catalyzed Strecker reactions using TMSCN as a cyanating
agent.[4] However, some drawbacks still remain for the
existing methods. For example, the cyanating agent
TMSCN as a hazardous liquid is moisture sensitive, very
toxic, and highly flammable. In addition, corrosive acids
were also utilized as catalysts. These facts make the reac-
tions unsafe and inconvenient. Therefore, there is a need
oxindoles.
Benzoyl cyanide is less toxic cyanating agent, which
can be easily prepared by reaction of commercial avail-
able benzoyl chloride and nontoxic potassium
hexacyanoferrate (II).[5] In recent years, benzoyl cyanide
has been reported to act as cyanating agent for terminal
alkynes,[6] 3‐arylideneindolin‐2‐ones,[7] naphthalenes,[8]
tertiary amines,[9] and aromatic bromides.[10] However,
the reports about benzoyl cyanide as a hydrocyanating
agent were scarce; only the hydrocyanation of aldehydes
was reported.[11]
In this work, we reported a straightforward method for
the synthesis of 3‐cyano‐3‐arylamino‐2‐oxindoles through
direct hydrocyanation of 3‐(arylimino)indolin‐2‐ones
using less toxic and easy‐to‐handle benzoyl cyanide as a
hydrocyanating agent at room temperature under
catalyst‐free and mild condition in high yield.
2 | RESULTS AND DISCUSSION
In the initial research, the reaction of 3‐(phenylimino)
indolin‐2‐one (1a) and benzoyl cyanide was selected as
J Heterocyclic Chem. 2019;1–8.
wileyonlinelibrary.com/journal/jhet
© 2019 Wiley Periodicals, Inc.
1

2
CHEN AND LI
a model reaction to examine the feasibility for the synthe-
sis of 2‐oxo‐3‐(phenylamino)indoline‐3‐carbonitrile (2a)
by hydrocyanation. The reaction first was attempted in
various solvents at room temperature. It was found that
the reaction in tetrahydrofuran (THF), MeCN, and
dimethylformamide (DMF) only gave trace amount of 2a
(Table 1, entries 1‐3). The reaction in MeOH, EtOH and
iPrOH could give 2a in high to low yield (Table 1, entries
4‐6). The highest yield (87%) was afforded by using
MeOH as solvent (Table 1, entry 4). In order to further
improve the yield of 2a, various catalysts were attempted
for the reaction. Bronsted acids, such as p‐toluene sul-
fonic acid (PTSA), HOAc and HCl, and Lewis acids, such
as FeCl3, ZnCl2, AlCl3, and BF3·OEt2, as catalysts were
tested. The product 2a was isolated in good yield, and
some by‐products besides 2a could be observed (Table 1,
entries 7‐13). Inorganic bases, such as NaOH, Cs2CO3
and Na2CO3, and organic bases, such as Et3N, 1,8‐
diazabicyclo[5.4.0]undec‐7‐ene
(DBU)
and
N,N‐
dimethylaminopyridine (DMAP), as catalysts could not
exhibit obvious catalytic effect and gave product 2a in
moderate to good yield (Table 1, entries 14‐19). Iodine
as a catalyst could not improve the yield of 2a (Table 1,
entry 20). In addition, the reaction was also carried out
at elevated temperature. However, no better yield of 2a
was isolated (Table 1, entry 21).
With the optimized conditions in hand, the generality
of the method by reactions of a series of 3‐(arylimino)
indolin‐2‐ones with benzoyl cyanide at room tempera-
ture under catalyst‐free condition to access various 2‐
oxo‐3‐(arylamino)indoline‐3‐carbonitriles in methanol
was examined, and the results are summarized in
Table 2. The reactions could tolerate a wide range of
functional groups and produce the corresponding prod-
ucts in satisfactory yield. 3‐(Arylimino)indolin‐2‐one
bearing electron‐donating groups (Me and MeO) and
electron‐withdrawing groups (NO2, F, Cl, and Br) on
their aromatic rings could give the corresponding prod-
ucts in good to high yield (Table 2, 2b‐2k). Substrates‐
bearing disubstituted aromatic rings also allowed for
the easy synthesis of the corresponding products in mod-
erate to high yield (Table 2, 2l‐2n). The reaction could
also be applied to the substrates bearing substituents
(Me, Cl) on 2‐oxoindoline rings using standard condi-
tions. The corresponding products could be isolated in
good yield (Table 2, 2o‐2t). However, the attempt for
the substrates including aliphatic imino groups, such as
isopropyl‐, tert‐butyl‐, and benzyl‐imino groups, was not
successful, and none of the expected products were
observed under the standard conditions (Table 2,
2u‐2w). The possible reason is that the electron‐donating
effects of aliphatic alkyls render the nucleophilicity of
carbons linked to imino so low that cyano anion is
unable to attack them.
TABLE 1 Optimization of reaction conditions
Entry
Catalyst
Solvent
Yield (%)a
1
‐
THF
Trace
Trace
Trace
87
2
‐
MeCN
DMF
3
‐
4
‐
MeOH
EtOH
5
‐
53
6
‐
iPrOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
20
7
PTSA
HOAc
HCl
FeCl3
ZnCl2
AlCl3
BF3·OEt2
NaOH
Cs2CO3
Na2CO3
Et3N
DBU
DMAP
I2
71
8
76
9
66
10
11
12
13
14
15
16
17
18
19
20
21b
80
70
61
69
72
63
The reactions could also be extended to substituted
benzoyl cyanides bearing electron‐donating or electron‐
withdrawing groups on the aromatic rings as cyanide
sources. For example, the reactions of 1a with 3‐
methylbenzoyl cyanide and 2,3‐dichlorobenzoyl cyanide,
respectively, could give 2a in 74% and 80% yields
(Scheme 1). These results indicated that the existence of
substituents on the aromatic rings of benzoyl cyanides
could slightly decrease the yield of 2a possibly because
of larger steric hindrance.
69
75
40
Trace
75
‐
83
Note. Reaction conditions: 1a (0.5 mmol), benzoyl cyanide (0.6 mmol), and
catalyst (0.1 mmol) in solvent (4 mL) at room temperature for 12 h.
aIsolated yield.
bReaction condition: 50°C.
The other kinds of cyanide sources, such acetone cya-
nohydrin and ethyl cyanoacetate, were also tested for

CHEN AND LI
3
TABLE 2 Scope of 3‐(arylimino)indolin‐2‐ones for the synthesis of 2a‐t
Note. Reaction conditions: 3‐(arylimino)indolin‐2‐one (0.5 mmol), benzoyl cyanide (0.6 mmol), in MeOH (4 mL) at room temperature for 12 h.
the reaction. However, no corresponding products were
observed. In contrast, trimethylsilyl cyanide could act as
a cyanide source to afford product in satisfactory yield,
which has been reported by literature.4c
The studied reaction could also be performed on a
gram scale (Scheme 2). The reaction of 3‐(phenylimino)
indolin‐2‐one (1a) (1.33 g) and benzoyl cyanide (0.94 g)
in MeOH (40 mL) was performed under the optimized
conditions to give 2‐oxo‐3‐(phenylamino)indoline‐3‐
carbonitrile (2a) (1.14 g) in 76% isolated yield. The suc-
cess of this gram scale reaction further showed the
potency of optimized conditions for bulk processes.

4
CHEN AND LI
to give the final product 2a through the double bond
cleavage of imino cation.
3 | CONCLUSION
In conclusion, an efficient method for direct
hydrocyanation of 3‐(arylimino)indolin‐2‐ones using ben-
zoyl cyanide as a cyanating agent at room temperature
under catalyst‐free condition to synthesize 2‐oxo‐3‐
(arylamino)indoline‐3‐carbonitriles has developed. The
application of safe, inexpensive, and easy‐to‐handle cya-
nide source, no catalyst, no additives, mild conditions,
good substrate tolerance, and simple work‐up procedure
renders this protocol a good alternative for the synthesis
of many desired 3,3‐disubstituted 2‐oxindoles. The syn-
thesized products will find applications as good pharma-
ceutical candidates because of their potential biological
activities and as important organic intermediates because
of their structures bearing active cyano, amino, and
oxindole moieties.
SCHEME 1 Synthesis of 2a using substituted benzoyl cyanides
[Color figure can be viewed at wileyonlinelibrary.com]
SCHEME 2 Gram‐scale experiment for the synthesis of 2a
[Color figure can be viewed at wileyonlinelibrary.com]
4 | EXPERIMENTAL
1H NMR and 13C NMR spectra were obtained with
Mercury‐400BB and Mercury‐600BB instrument using
DMSO‐d6 as solvents and Me4Si as the internal standard.
High‐resolution mass spectra (HRMS) (ESI) were
obtained with a Bruker Daltonics APEX II 47e and
Orbitrap Elite mass spectrometer. Melting points were
observed in an electrothermal melting point apparatus
(X‐5, Beijing Tech Instrument Co. Ltd, China).
3‐(Arylimino)indolin‐2‐ones were synthesized according
to literature procedure.[12]
A plausible mechanism is proposed for the synthesis of
2a (Scheme 3). Benzoyl cyanide is first alcoholized by
methanol to give hydrocyanic acid in situ through the
release of methyl benzoate. Methyl benzoate can be
detected and even isolated from reaction system. Then
hydrocyanic acid combines with 1a to form an imino cat-
ion intermediate A and cyano anion. Finally, cyano anion
attacks carbon linked to imino cation of intermediate A
4.1 | General procedure for the
preparation of 2‐oxo‐3‐(arylamino)indoline‐
3‐carbonitriles (2a‐2t)
3‐(Arylimino)indolin‐2‐one (0.5 mmol) and benzoyl cya-
nide (0.6 mmol) in methanol (4 mL) were stirred at room
temperature for 12 hours. The reaction progress was mon-
itored by TLC. After the completion of the reaction, the
mixture was extracted with ethyl acetate (3 × 10 mL),
and the extract was washed with saturated brine
(3 × 10 mL), dried over anhydrous sodium sulfate, and
concentrated under reduced pressure. The residue was iso-
lated by column chromatography using petroleum ether
and ethyl acetate (v/v 3:1) as eluent to give pure product.
The analytical data for products 2a‐2t were given below.
SCHEME 3 The proposed mechanism for 2a [Color figure can be
viewed at wileyonlinelibrary.com]

CHEN AND LI
5
128.94, 125.44, 125.32, 123.57, 117.00, 116.85, 111.54,
58.58, 20.49. HRMS (ESI): Calcd for C16H13N3O
[M + H]+ 264.1131, found 264.1132.
4.2 | 2‐Oxo‐3‐(phenylamino)indoline‐3‐
carbonitrile (2a)
White solid (108 mg, 87%). M.p. 145‐147°C. 1H NMR
(600 MHz, DMSO‐d6)
δ 11.31 (s, 1H), 7.49 (d,
4.6 | 3‐((3‐Methoxyphenyl)amino)‐2‐
oxoindoline‐3‐carbonitrile (2e)
J = 7.6 Hz, 1H), 7.40 (t, J = 7.8 Hz, 1H), 7.15 (s, 1H),
7.11 (d, J = 7.6 Hz, 1H), 7.09 (d, J = 2.2 Hz, 1H), 7.07
(d, J = 7.4 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 6.71 (d,
J = 8.4 Hz, 3H). 13C NMR (150 MHz, DMSO‐d6) δ
170.60, 144.48, 141.80, 132.01, 129.23, 125.45, 125.13,
123.73, 119.79, 116.85, 115.91, 111.66, 58.20. HRMS
(ESI): Calcd for C15H11N3O [M + H]+ 250.0975, found
250.0976.
White solid (84 mg, 60%). M.p. 146‐148°C. 1H NMR
(600 MHz, DMSO‐d6)
δ 11.34 (s, 1H), 7.49 (d,
J = 7.5 Hz, 1H), 7.40 (t, J = 8.4 Hz, 1H), 7.24 (s, 1H),
7.11 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 6.97 (t,
J = 8.1 Hz, 1H), 6.29 (ddd, J = 14.2, 7.8, 2.3 Hz, 2H),
6.21 (t, J = 2.3 Hz, 1H), 3.57 (s, 3H). 13C NMR
(150 MHz, DMSO‐d6) δ 170.62, 160.23, 145.77, 141.76,
132.04, 130.05, 125.41, 125.09, 123.80, 116.77, 111.68,
108.54, 104.95, 101.61, 58.17, 55.05. HRMS (ESI): Calcd
for C16H13N3O2 [M + H]+ 280.1081, found 280.1083.
4.3 | 2‐Oxo‐3‐(o‐tolylamino)indoline‐3‐
carbonitrile (2b)
White solid (115 mg, 88%). M.p. 153‐155°C. 1H NMR
(400 MHz, DMSO‐d6)
δ 11.36 (s, 1H), 7.45 (d,
4.7 | 3‐((3‐Nitrophenyl)amino)‐2‐
oxoindoline‐3‐carbonitrile (2f)
J = 7.5 Hz, 1H), 7.40 (t, J = 7.7 Hz, 1H), 7.11‐7.04 (m,
2H), 7.02 (d, J = 7.9 Hz, 1H), 6.92 (d, J = 7.8 Hz, 1H),
6.73 (t, J = 7.4 Hz, 1H), 6.58 (d, J = 8.0 Hz, 1H), 6.12 (s,
1H), 2.16 (s, 3H). 13C NMR (150 MHz, DMSO‐d6) δ
170.79, 141.88, 141.80, 131.84, 130.90, 127.56, 126.59,
125.46, 125.33, 123.67, 120.92, 117.09, 115.66, 111.63,
58.71, 18.31. HRMS (ESI): Calcd for C16H13N3O
[M + H]+ 264.1131, found 264.1133.
White solid (96 mg, 65%). M.p. 179‐181°C. 1H NMR
(400 MHz, DMSO‐d6) δ 11.50 (s, 1H), 7.88 (s, 1H), 7.68
(t, J = 2.3 Hz, 1H), 7.58 (d, J = 7.1 Hz, 2H), 7.46 (t,
J = 8.5 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.25 (dd,
J = 8.2, 2.5 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.05 (d,
J = 7.8 Hz, 1H). 13C NMR (150 MHz, DMSO‐d6) δ
170.11, 148.75, 145.59, 141.92, 132.49, 130.56, 125.69,
124.16, 123.98, 121.91, 116.10, 114.10, 111.84, 109.33,
57.67. HRMS (ESI): Calcd for C15H10N3O3 [M + H]+
295.0826, found 295.0828.
4.4 | 2‐Oxo‐3‐(m‐tolylamino)indoline‐3‐
carbonitrile (2c)
White solid (109 mg, 83%). M.p. 144‐146°C. 1H NMR
(600 MHz, DMSO‐d6)
δ 11.32 (s, 1H), 7.48 (d,
4.8 | 3‐((4‐Fluorophenyl)amino)‐2‐
oxoindoline‐3‐carbonitrile (2g)
J = 7.6 Hz, 1H), 7.39 (t, J = 7.1 Hz, 1H), 7.10 (t,
J = 7.6 Hz, 1H), 7.07 (s, 1H), 7.00 (d, J = 7.9 Hz, 1H),
6.94 (t, J = 7.8 Hz, 1H), 6.59 (s, 1H), 6.53 (d, J = 7.6 Hz,
1H), 6.48 (d, J = 8.1 Hz, 1H), 2.12 (s, 3H). 13C NMR
(150 MHz, DMSO‐d6) δ 170.67, 144.49, 141.81, 138.31,
131.96, 129.08, 125.43, 125.27, 123.70, 120.69, 116.93,
116.91, 112.92, 111.60, 58.26, 21.68. HRMS (ESI): Calcd
for C16H13N3O [M + H]+ 264.1131, found 264.1130.
Light yellow solid (115 mg, 86%). M.p. 150‐152°C. 1H
NMR (600 MHz, DMSO‐d6) δ 11.30 (s, 1H), 7.50 (d,
J = 6.4 Hz, 1H), 7.39 (td, J = 7.8, 1.3 Hz, 1H), 7.10 (td,
J = 7.6, 1.0 Hz, 1H), 7.02 (s, 1H), 7.00 (d, J = 7.8 Hz,
1H), 6.96 (t, J = 8.9 Hz, 2H), 6.83 (dd, J = 9.1, 4.7 Hz,
2H). 13C NMR (150 MHz, DMSO‐d6) δ 170.64, 157.05 (d,
J = 236.2 Hz), 141.97, 140.93 (d, J = 2.5 Hz), 132.09,
125.64, 125.08, 123.72, 118.44 (d, J = 7.8 Hz), 116.90,
115.81 (d, J = 22.3 Hz), 111.70, 58.70. HRMS (ESI): Calcd
for C15H10FN3O [M + H]+ 268.0881, found 268.0880.
4.5 | 2‐Oxo‐3‐(p‐tolylamino)indoline‐3‐
carbonitrile (2d)
White solid (113 mg, 86%). M.p. 168‐170°C. 1H NMR
(600 MHz, DMSO‐d6)
δ 11.24 (s, 1H), 7.45 (d,
4.9 | 3‐((2‐Chlorophenyl)amino)‐2‐
oxoindoline‐3‐carbonitrile (2h)
J = 8.7 Hz, 1H), 7.38 (s, 1H), 7.09 (s, 1H), 6.97 (d,
J = 7.9 Hz, 1H), 6.88 (d, J = 8.0 Hz, 3H), 6.64 (d,
J = 8.4 Hz, 2H), 2.12 (s, 3H). 13C NMR (150 MHz,
DMSO‐d6) δ 170.68, 141.98, 141.83, 131.86, 129.61,
White solid (96 mg, 68%). M.p. 169‐171°C. 1H NMR
(600 MHz, DMSO‐d6)
δ 11.41 (s, 1H), 7.60 (q,

6
CHEN AND LI
J = 8.0 Hz, 1H), 7.42 (m, J = 7.9 Hz, 1H), 7.36 (q,
J = 8.2 Hz, 1H), 7.13 (m, J = 8.7 Hz, 2H), 7.04 (q,
J = 8.6 Hz, 1H), 6.95–6.89 (m, 1H), 6.84 (p, J = 7.8 Hz,
1H), 6.43–6.35 (m, 1H). 13C NMR (150 MHz, DMSO‐d6)
δ 170.15, 141.85, 140.00, 132.17, 130.14, 128.01, 125.42,
125.01, 123.91, 122.22, 121.60, 116.37, 116.31, 111.79,
58.14. HRMS (ESI): Calcd for C15H10ClN3O [M + H]+
284.0585, found 284.0587.
4.13 | 3‐((3,4‐Dimethoxyphenyl)amino)‐2‐
oxoindoline‐3‐carbonitrile (2l)
White solid (128 mg, 83%). M.p. 138‐140°C. 1H NMR
(600 MHz, DMSO‐d6)
δ 11.22 (s, 1H), 7.47 (d,
J = 7.6 Hz, 1H), 7.38 (t, J = 7.7 Hz, 1H), 7.10 (t,
J = 7.6 Hz, 1H), 6.97 (d, J = 7.9 Hz, 1H), 6.69 (d,
J = 6.5 Hz, 2H), 6.46 (d, J = 2.6 Hz, 1H), 6.28 (dd,
J = 8.6, 2.6 Hz, 1H), 3.60 (s, 3H), 3.56 (s, 3H). 13C NMR
(150 MHz, DMSO‐d6) δ 170.86, 149.38, 143.67, 141.96,
138.33, 131.89, 125.62, 125.38, 123.56, 117.10, 113.26,
111.52, 109.16, 103.89, 59.15, 56.34, 55.48. HRMS (ESI):
Calcd for C17H15N3O3 [M + H]+ 310.1186, found
310.1188.
4.10 | 3‐((3‐Chlorophenyl)amino)‐2‐
oxoindoline‐3‐carbonitrile (2i)
White solid (113 mg, 80%). M.p. 148‐150°C. 1H NMR
(600 MHz, DMSO‐d6)
δ 11.39 (s, 1H), 7.53 (d,
J = 7.5 Hz, 1H), 7.45 (s, 1H), 7.43 (t, J = 7.8 Hz, 1H),
7.15‐7.12 (m, 1H), 7.10 (d, J = 8.1 Hz, 1H), 7.02 (d,
J = 7.8 Hz, 1H), 6.84 (t, J = 2.1 Hz, 1H), 6.75 (dd,
J = 8.0, 1.9 Hz, 1H), 6.72 (dd, J = 8.4, 2.3 Hz, 1H). 13C
NMR (150 MHz, DMSO‐d6) δ 170.30, 145.98, 141.82,
133.71, 132.28, 130.82, 125.57, 124.61, 123.87, 119.31,
116.39, 115.26, 114.20, 111.73, 57.85. HRMS (ESI): Calcd
for C15H10ClN3O [M + H]+ 284.0585, found 284.0587.
4.14 | 3‐((3,5‐Dichlorophenyl)amino)‐2‐
oxoindoline‐3‐carbonitrile (2m)
White solid (103 mg, 65%). M.p. 179‐181°C. 1H NMR
(600 MHz, DMSO‐d6) δ 11.45 (s, 1H), 7.70 (s, 1H), 7.56
(d, J = 7.5 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.17 (t,
J = 8.1 Hz, 1H), 7.02 (d, J = 7.8 Hz, 1H), 6.89 (t,
J = 1.8 Hz, 1H), 6.83 (d, J = 1.8 Hz, 2H). 13C NMR
(150 MHz, DMSO‐d6) δ 170.02, 146.76, 141.86, 134.58,
132.61, 125.77, 124.03, 118.70, 115.91, 113.87, 113.85,
111.78, 57.50. HRMS (ESI): Calcd for C15H9Cl2N3O
[M + H]+ 318.0195, found 318.0193.
4.11 | 3‐((4‐Chlorophenyl)amino)‐2‐
oxoindoline‐3‐carbonitrile (2j)
White solid (87 mg, 61%). M.p. 169‐171°C. 1H NMR
4.15 | 3‐((4‐Chloro‐2‐methylphenyl)
amino)‐2‐oxoindoline‐3‐carbonitrile (2n)
(600 MHz, DMSO‐d6)
δ 11.33 (s, 1H), 7.51 (d,
J = 7.6 Hz, 1H), 7.41 (t, J = 7.7 Hz, 1H), 7.30 (s, 1H),
7.14 (dd, J = 14.1, 8.1 Hz, 3H), 7.00 (d, J = 7.8 Hz, 1H),
6.79 (d, J = 8.6 Hz, 2H). 13C NMR (150 MHz, DMSO‐d6)
δ 170.36, 143.44, 141.83, 132.18, 129.04, 125.55, 124.77,
123.79, 123.54, 117.47, 116.57, 111.73, 58.04. HRMS
(ESI): Calcd for C15H10ClN3O [M + H]+ 284.0585, found
284.0583.
White solid (96 mg, 65%). M.p. 164‐166°C. 1H NMR
(400 MHz, DMSO‐d6)
δ 11.41 (s, 1H), 7.50 (d,
J = 7.3 Hz, 1H), 7.42 (t, J = 7.7 Hz, 1H), 7.15 (d,
J = 2.6 Hz, 1H), 7.11 (t, J = 7.5 Hz, 1H), 7.04 (d,
J = 8.1 Hz, 2H), 6.68 (d, J = 8.5 Hz, 1H), 6.29 (s, 1H),
2.19 (s, 3H). 13C NMR (150 MHz, DMSO‐d6) δ 170.61,
141.82, 140.89, 131.97, 130.34, 130.14, 126.17, 125.37,
125.16, 124.61, 123.75, 117.15, 116.82, 111.70, 58.60,
18.14. HRMS (ESI): Calcd for C16H12ClN3O [M + H]+
298.0742, found 298.0744.
4.12 | 3‐((4‐Bromophenyl)amino)‐2‐
oxoindoline‐3‐carbonitrile (2k)
White solid (103 mg, 63%). M.p. 165‐167°C. 1H NMR
4.16 | 5‐Methyl‐2‐oxo‐3‐(phenylamino)
indoline‐3‐carbonitrile (2o)
(400 MHz, DMSO‐d6)
δ 11.36 (s, 1H), 7.51 (d,
J = 7.5 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.35 (s, 1H),
7.27 (d, J = 8.8 Hz, 2H), 7.13 (t, J = 7.6 Hz, 1H), 7.00
(d, J = 7.8 Hz, 1H), 6.72 (d, J = 8.8 Hz, 2H). 13C NMR
(150 MHz, DMSO‐d6) δ 170.27, 143.80, 141.78, 132.16,
131.86, 125.51, 124.70, 123.78, 117.86, 116.50, 111.71,
111.11, 57.92. HRMS (ESI): Calcd for C15H10BrN3O
[M + H]+ 328.0080, found 328.0082.
White solid (127 mg, 97%). M.p. 160‐162°C. 1H NMR
(600 MHz, DMSO‐d6) δ 11.24 (s, 1H), 7.33 (s, 1H), 7.20
(d, J = 6.8 Hz, 2H), 7.10‐7.05 (m, 2H), 6.91 (d,
J = 7.9 Hz, 1H), 6.74 (d, J = 8.1 Hz, 2H), 6.70 (t,
J = 7.3 Hz, 1H), 2.25 (s, 3H). 13C NMR (150 MHz,
DMSO‐d6) δ 170.69, 144.59, 139.33, 133.03, 132.30,

CHEN AND LI
7
129.25, 125.81, 125.17, 119.68, 116.96, 115.75, 111.48,
58.31, 20.99. HRMS (ESI): Calcd for C16H13N3O
[M + H]+ 264.1131, found 264.1133.
129.74, 129.23, 127.49, 126.96, 125.51, 116.87, 116.42,
113.19, 58.58, 20.53. HRMS (ESI): Calcd for C16H12ClN3O
[M + H]+ 298.0742, found 298.0740.
4.21 | 5‐Chloro‐3‐((3‐chlorophenyl)
amino)‐2‐oxoindoline‐3‐carbonitrile (2t)
4.17 | 5‐Methyl‐2‐oxo‐3‐(p‐tolylamino)
indoline‐3‐carbonitrile (2p)
1
White solid (127 mg, 92%). M.p. 165‐167°C. 1H NMR
(400 MHz, DMSO‐d6) δ 11.21 (s, 1H), 7.32 (s, 1H), 7.21
(d, J = 8.0 Hz, 1H), 6.98 (s, 1H), 6.90 (dd, J = 8.0,
2.2 Hz, 3H), 6.65 (d, J = 8.4 Hz, 2H), 2.26 (s, 3H), 2.13
(s, 3H). 13C NMR (150 MHz, DMSO‐d6) δ 170.75, 142.09,
139.33, 132.88, 132.18, 129.62, 128.67, 125.82, 125.31,
117.06, 116.45, 111.36, 58.59, 20.96, 20.50. HRMS (ESI):
Calcd for C17H15N3O [M + H]+ 278.1288, found 278.1286.
Light red solid (92 mg, 62%). M.p. 169‐171°C. H NMR
(400 MHz, DMSO‐d6)
δ 11.55 (s, 1H), 7.67 (d,
J = 2.1 Hz, 1H), 7.51 (dd, J = 8.4, 2.2 Hz, 1H), 7.48 (s,
1H), 7.15 (t, J = 8.1 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H),
6.88 (t, J = 2.1 Hz, 1H), 6.79 (dd, J = 7.5, 1.6 Hz, 1H),
6.73 (dd, J = 8.3, 2.3 Hz, 1H). 13C NMR (150 MHz,
DMSO‐d6) δ 170.00, 145.72, 140.80, 133.73, 132.30,
130.93, 127.74, 126.23, 125.74, 119.56, 115.78, 115.40,
114.21, 113.32, 57.80. HRMS (ESI): Calcd for
C15H9Cl2N3O [M + H]+ 318.0195, found 318.0193.
4.18 | 3‐((3‐Chlorophenyl)amino)‐5‐
methyl‐2‐oxoindoline‐3‐carbonitrile (2q)
ACKNOWLEDGMENT
White solid (105 mg, 71%). M.p. 162‐164°C. 1H NMR
(400 MHz, DMSO‐d6) δ 11.34 (s, 1H), 7.51 (s, 1H), 7.38
(s, 1H), 7.24 (d, J = 7.3 Hz, 1H), 7.12 (d, J = 3.2 Hz,
1H), 6.94 (d, J = 8.0 Hz, 1H), 6.85 (s, 1H), 6.75 (dd,
J = 13.1, 5.7 Hz, 2H), 2.29 (s, 3H). 13C NMR (150 MHz,
DMSO‐d6) δ 170.30, 146.04, 139.30, 133.71, 133.20,
132.57, 130.82, 125.90, 124.57, 119.16, 116.45, 115.07,
114.02, 111.52, 57.90, 20.95. HRMS (ESI): Calcd for
C16H12ClN3O [M + H]+ 298.0742, found 298.0744.
The authors thank the National Natural Science Founda-
tion of China (21462038) for the financial support of
this work.
ORCID
Zheng Li https://orcid.org/0000-0003-1944-8270
REFERENCES AND NOTES
4.19 | 5‐Chloro‐2‐oxo‐3‐(phenylamino)
indoline‐3‐carbonitrile (2r)
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White solid (138 mg, 98%). M.p. 167‐169°C. 1H NMR
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4.20 | 5‐Chloro‐2‐oxo‐3‐(p‐tolylamino)
indoline‐3‐carbonitrile (2s)
White solid (99 mg, 67%). M.p. 163‐165°C. 1H NMR
(400 MHz, DMSO‐d6)
δ 11.44 (s, 1H), 7.56 (d,
J = 2.2 Hz, 1H), 7.46 (dd, J = 8.4, 2.2 Hz, 1H), 7.01 (d,
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6.66 (d, J = 8.4 Hz, 2H), 2.14 (s, 3H). 13C NMR
(150 MHz, DMSO‐d6) δ 170.35, 141.70, 140.80, 131.90,

8
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How to cite this article: Chen X, Li Z. Catalyst‐
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