A facile method for the synthesis of 3-(aminomethylene)oxindoles from isatylidene malononitriles and α-azido ketones

Article abstract of DOI:10.1055/s-0032-1316583

A simple one-pot synthesis of 3-(aminomethylene)oxindoles was achieved by the reaction of α-azido ketones and isatylidene malononitriles via Michael addition followed by the conversion of azides to amines. All the synthesized 3-(aminomethylene)oxindoles exhibited good diastereoselectivity. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1316583

1950▌
LETTER
lAetteFr acile Method for the Synthesis of 3-(Aminomethylene)oxindoles from
Isatylidene Malononitriles and α-Azido Ketones
3-(Aminomethylene)oxindoles
Jayabal Kamalraja, Thelagathoti Hari Babu, Doraiswamy Muralidharan, Paramasivan Thirumalai Perumal*
Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamil Nadu, India
Fax +91(44)24911589; E-mail: ptperumal@gmail.com
Received: 23.04.2012; Accepted after revision: 05.06.2012
electron-withdrawing azido moiety would provide 2-ami-
Abstract: A simple one-pot synthesis of 3-(aminomethylene)oxin-
no-4H-pyrans on reaction with arylidene malononitriles
doles was achieved by the reaction of α-azido ketones and isatyli-
via Michael addition followed by O-ring closure.3 In-
dene malononitriles via Michael addition followed by the
spired by these observations, we envisioned that treatment
of α-azido ketones with isatylidene malononitriles in the
presence of base would form azide moiety bearing fused
spiro[4H-pyranoxindole] heterocycles via Michael addi-
tion followed by O-ring closure4 or would lead to oxo-
spiro[indoline-3,3′-pyrrole] heterocycles via Michael
addition followed by N-ring closure (Scheme 1).2 Quite
surprisingly, when we carried out the reaction of α-azido
ketone 2 with isatylidene malononitrile 1 in the presence
of piperidine, we observed an unexpected domino process
leading to functionalized 3-(aminomethylene)oxindole
derivative 5, instead of the anticipated spiroxindole deriv-
atives 3 and 4.
conversion of azides to amines. All the synthesized 3-(aminometh-
ylene)oxindoles exhibited good diastereoselectivity.
Key words: isatylidene malononitriles, azido ketones, oxindoles,
3-(aminomethylene)oxindoles, one-pot synthesis
α-Azido ketones constitute an important class of synthet-
ically useful azides that exhibit double reactivity in C–C
bond formation. The electrophilic carbonyl function of α-
azido ketone acts as an electrophile for the attack of carb-
anions leading to the formation of synthetically important
2-azido alcohols. On the other hand, the active methylene
group of α-azido ketones facilitates the controlled genera-
tion of carbanions followed by trapping with various car-
bon electrophiles that results in the formation of aldol-
type products.1
3-(Aminomethylene)oxindoles are well known to serve as
useful building blocks in total syntheses of natural prod-
ucts,5 and additionally these oxindoles have been identi-
fied as protein kinease inhibitors.6 Although several
methods have been developed recently for the synthesis of
3-(aminomethylene)oxindole derivatives including palla-
dium-catalyzed cyclization of α,β-acetylenic amides,7 re-
action of 2-alkynylaryl isocyanates with amides8 and
stereoselective synthesis of 3-(aminomethylene)oxin-
doles via Ugi-carbopalladative cyclization–Buchwald
reaction pathways,9 the synthesis of 3-aminomethylene
Marco and co-workers demonstrated that the reaction of
α-azido ketones with highly stabilized Michael acceptors
such as arylidene malononitriles leads to the formation of
polyfunctionalized pyrroles via sequential 1,4-conjugate
addition followed by deprotonation which induced the
formation of an anion by a loss of nitrogen and intramo-
lecular nucleophilic attack to the cyano function.2 And
also it was anticipated that α-azido ketones having a good
NH2
N
O
NH2
CN
O
or
N3
CN
O
NC
O
O
CN
N
H
N
H
piperidine
3
4
O
+
EtOH, r.t.
N3
N
O
H
2
1
NH2
O
N
H
5
Scheme 1 Reaction of α-azido ketone with isatylidene malononitrile
SYNLETT 2012, 23, 1950–1954
Advanced online publication: 23.07.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1316583; Art ID: ST-2012-B0350-L
© Georg Thieme Verlag Stuttgart · New York

LETTER
3-(Aminomethylene)oxindoles
1951
NC
N
O
O
CN
O
NH2
piperidine (1.0 equiv)
EtOH, r.t., 2.7 h
+
N3
O
N
1c
2a
5c
Scheme 2 Synthesis of 3-(aminomethylene)oxindole 5c
product 5c was isolated as a single diastereomer by col-
umn chromatography and the structure was established by
spectroscopic analysis. In the IR spectrum of 5c, the peaks
at 3407 and 3285 cm–1 were diagnostic of the primary
amine group. In the 1H NMR spectrum, the NH2 protons
were observed at δ = 8.64 and 8.99 ppm as two singlets.
In the 13C NMR spectrum, carbon attached to amino group
resonated at δ = 155.5 ppm. The mass spectrum of 5c dis-
played the molecular ion [M+ + H] peak at m/z = 303. Fur-
ther the stereochemistry of 5c was confirmed as Z-
selectivity based on its single crystal X-ray diffraction
analysis (Figure 1).11
Table 1 Effect of the Different Solvents and Bases on the Time and
Yield of Reactiona
Entry
Solvent
Base
Time (h) Yield (%)
1
2
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
H2O
K2CO3
24
24
24
16
–
NaOMe
–
3
NaOEt
–
4
DABCO
piperidine
pyrrolidine
Et3N
12
67
40
8
5
2.7
6
5
24
24
8
Since α-azido ketones and isatylidene malononitriles are
readily available, the domino approach to 3-aminometh-
ylene oxindoles is highly attractive. Therefore we extend-
ed the substrate scope to various isatylidene
malononitriles and α-azido ketones using the optimized
conditions (Scheme 3, Table 2).12 It is noteworthy that all
3-(aminomethylene)oxindoles showed excellent diastereo-
selectivity as established by 1H NMR spectroscopy.
7
8
piperidine
piperidine
piperidine
piperidine
piperidine
–
9
MeOH
MeCN
toluene
DMF
30
trace
–
10
11
12
24
24
24
–
a All the reactions were conducted at r.t.
oxindoles from readily available starting materials such as
isatylidene malononitriles and azido ketones has not been
yet documented. Based upon the above considerations and
in continuation of our efforts on developing new strategies
towards spiroxindoles using isatylidene malononitriles as
electrophiles,10 herein we wish to report a simple one-pot
method for the synthesis of 3-(aminomethylene)oxindole
derivatives.
Initially we examined the reaction of α-azido ketone 2a
(1.25 mmol) with isatylidene malononitrile 1c (1.0 mmol)
in ethanol in the presence of catalytic amount (30 mol%)
of piperidine at room temperature for five hours after
which time we obtained the product in 35% yield. En-
hancement in the yield of the product to 67% was
achieved by using equimolar amount of piperidine
(Scheme 2). Further the reaction was conducted in the
presence of various bases (Table 1, entries 1–7). Out of all
bases screened, pyrrolidine and piperidine were found to
be suitable for this transformation (Table 1, entries 5 and
6). To find out the effect of solvent on the yield of the re-
action, different solvents were examined (Table 1, entries
8–12). Maximum yield of the product was achieved when
ethanol was used as the solvent (Table 1, entry 5). The
Figure 1 ORTEP diagram of compound 5c with DMSO solvate
Synlett 2012, 23, 1950–1954
© Georg Thieme Verlag Stuttgart · New York

1952
J. Kamalraja et al.
LETTER
R3
NC
N
O
O
R4
R2
CN
O
R3
R4
R2
piperidine (1.0 equiv)
EtOH, r.t., 2–5 h
NH2
O
+
N3
R1
N
R1
1
2
5
Scheme 3 Synthesis of 3-(Aminomethylene)oxindoles 5a–n
O
+
Ph
N
N3
H
2
– H2O
N
H
N3
NC
N
N
CN
CN
O
Ph
CN
Ph
Ph
+
O
N3
N3
N
N
6
7
1
8
H
H
H
O
N
N
O
N
O
O
O
O
H2O
Ph
N
N
H
N
N3
Ph
Ph
Ph
CN
CN
N
NH
NH2
N
Ph
CN
CN
–
H2O
– N2O
O
O
O
O
O
N
N
N
H
N
H
N
H
H
H
9
10
11
12
5
Scheme 4 Plausible mechanism for the formation of 5
To account for the formation of products, a plausible adduct 9 results in the formation of vinyl azide 10. Intra-
mechanism is depicted in Scheme 4. Initially piperidine molecular cyclization of vinyl azide 10 may take place to
reacts with α-azido ketone 2 to form enamine 7, which un- form a oxatriazine 11,13 which transforms to intermediate
dergoes Michael addition with isatylidene malononitrile 1 12 by the addition of water. Finally the intermediate 12 re-
to form adduct 9. Elimination of malononitrile from the arranges to form product 5.
Table 2 Synthesis of 3-(Aminomethylene)oxindoles 5a–n from Isatylidene Malononitriles and α-Azido Ketones
Entry
Isatylidene malononitrile 1
Azido ketone 2
Product 5
Time (h)
Yield (%)a
R1
R2
R3
R4
1
2
3
4
5
6
7
8
9
10
H
H
H
H
H
H
H
H
H
H
H
5a
5b
5c
5d
5e
5f
2.0
2.5
2.7
2.4
3.0
3.5
4.5
4.2
5.0
4.5
65
60
67
70
65
59
61
62
56
52
allyl
H
H
propargyl
CH2COOEt
benzyl
Me
H
H
H
H
H
H
H
H
H
Me
Cl
H
H
5g
5h
5i
H
H
propargyl
allyl
C4H4
C4H4
H
5j
Synlett 2012, 23, 1950–1954
© Georg Thieme Verlag Stuttgart · New York

LETTER
3-(Aminomethylene)oxindoles
1953
Table 2 Synthesis of 3-(Aminomethylene)oxindoles 5a–n from Isatylidene Malononitriles and α-Azido Ketones (continued)
Entry
Isatylidene malononitrile 1
Azido ketone 2
Product 5
Time (h)
Yield (%)a
R1
R2
R3
R4
11
12
13
14
H
H
H
H
H
H
H
H
H
Cl
Cl
Cl
Cl
5k
5l
3.9
3.2
3.8
3.1
50
55
51
64
CH2COOEt
allyl
5m
5n
propargyl
a Isolated yield after column chromatography.
(10) (a) Shanthi, G.; Subbulakshmi, G.; Perumal, P. T.
Tetrahedron 2007, 63, 2057. (b) Shanthi, G.; Perumal, P. T.
Tetrahedron Lett. 2008, 49, 7139. (c) Lakshmi, N. V.;
Thirumurugan, P.; Perumal, P. T. Tetrahedron Lett. 2010,
51, 1064. (d) Babu, T. H.; Joseph, A. A.; Muralidharan, D.;
Perumal, P. T. Tetrahedron Lett. 2010, 51, 994.
Acknowledgment
The authors J.K. and T.H. thank the Council of Scientific and Indu-
strial Research (CSIR), New Delhi, India for the research fellow-
ships.
(e) Nandakumar, A.; Thirumurugan, P.; Perumal, P. T.;
Vembu, P.; Ponnuswamy, M. N.; Ramesh, P. Bioorg. Med.
Chem. Lett. 2010, 20, 4252. (f) Kiruthika, S. E.; Lakshmi, N.
V.; Banu, B. R.; Perumal, P. T. Tetrahedron Lett. 2011, 52,
6508. (g) Lakshmi, N. V.; Josephine, G. A. S.; Perumal, P.
T. Tetrahedron Lett. 2012, 53, 1282.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
References and Notes
(1) (a) Langer, P.; Freifeld, I.; Shojaei, H. Chem. Commun.
2003, 3044. (b) Freifeld, I.; Shojaei, H.; Langer, P. J. Org.
Chem. 2006, 71, 4965. (c) Freifeld, I.; Shojaei, H.; Dede, R.;
Langer, P. J. Org. Chem. 2006, 71, 6165.
(2) Marco, J. L.; Grau, A. M.; Martin, N.; Seoane, C.
Tetrahedron Lett. 1995, 36, 5393.
(11) Crystallographic data for compound 5c in this paper have
been deposited with the Cambridge Crystallographic Data
Centre as supplemental publication number CCDC 840032.
Copies of the data can be obtained, free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [fax: +44(1223)336033 or email:
(3) Kuthan, J. Adv. Heterocycl. Chem. 1983, 34, 146.
(4) (a) Dabiri, M.; Bahramnnejad, M.; Baghbanzadeh, M.
Tetrahedron 2009, 65, 9443. (b) Lee, Y. R.; Hari, G. S.
Synthesis 2010, 453. (c) Wang, L. M.; Jiao, N.; Qiu, J.; Yu,
J. J.; Liu, J. Q.; Guo, F. L.; Liu, Y. Tetrahedron 2010, 66,
339. (d) Yuling, L.; Hui, C.; Chunling, S.; Daqing, S.;
Shunjun, J. J. Comb. Chem. 2010, 12, 231. (e) Zhu, S.-L.; Ji,
S.-J.; Zhang, Y. Tetrahedron 2007, 63, 9365. (f) Sridhar, R.;
Srinivas, B.; Madhav, B.; Reddy, V. P.; Nageswar, Y. V. D.;
Rao, K. R. Can. J. Chem. 2009, 87, 1704. (g) Litvinov, Y.
M.; Mortikov, V. Y.; Shestopalov, A. M. J. Comb. Chem.
2008, 10, 741. (h) Rad-Moghadam, K.; Youseftabar-Miri, L.
Tetrahedron 2011, 67, 5693.
(5) Trost, B. M.; Brennan, M. K. Synthesis 2009, 3003.
(6) (a) Treu, M.; Guertler, U.; Karner, T.; Kraemer, O.; Quant,
J. J.; Zahn, S. K. WO2008152013 A1, 2008; Chem. Abstr.
2009, 150, 55987y. (b) Treu, M.; Mantoulidis, A.; Tontsch-
Grunt, U. WO2007122219 A1, 2007; Chem. Abstr. 2007,
147, 502230v. (c) Heckel, A.; Roth, G. R.; Joerg, K.; Hoerer,
S.; Uphues, I. U.S. Patent US20050203104 A1, 2005; Chem.
Abstr. 2005, 143, 306172f. (d) Burgdorf, L. T.; Bruge, D.;
Greiner, H.; Kordowicz, M.; Sirrenberg, C.; Zenke, F.
(Merck) WO2006131186 A1, 2006; Chem. Abstr. 2006,
146, 62590j.
(7) (a) Tang, S.; Peng, P.; Pi, S.-F.; Liang, Y.; Wang, N.-X.; Li,
J.-H. Org. Lett. 2008, 10, 1179. (b) Tang, S.; Peng, P.;
Wang, Z.-Q.; Tang, B.-X.; Deng, C.-L.; Li, J.-H.; Zhong, P.;
Wang, N.-X. Org. Lett. 2008, 10, 1875. (c) Peng, P.; Tang,
B.-X.; Pi, S.-F.; Liang, Y.; Li, J.-H. J. Org. Chem. 2009, 74,
3569.
(8) Miura, T.; Toyoshima, T.; Takahashi, Y.; Murakami, M.
Org. Lett. 2009, 11, 2141.
(9) Bararjanian, M.; Hosseinzadeh, S.; Balalaie, S.; Bijanzadeh,
H. R.; Wolf, E. Tetrahedron Lett. 2011, 52, 3329.
deposit@ccdc.cam.ac.uk].
(12) General Procedure for the Synthesis of Oxyindolyl
Enaminone: To a stirred solution of isatylidene
malononitrile 1 (1.0 mmol) and α-azido ketone 2 (1.25
mmol) in EtOH (5 mL), was added piperidine (1.0 mmol).
Stirring was continued at r.t. for appropriate times as
mentioned in Table 2. After the reaction was complete as
indicated by TLC, solvent was removed under vacuum and
the crude product was purified by column chromatography
on silica gel (Merck, 100–200 mesh, EtOAc–PE, 25:75).
(Z)-3-(1-Amino-2-oxo-2-phenylethylidene)indolin-2-one
(5a): brown solid; mp 246–248 °C. IR (KBr): 3413, 3260,
2925, 1665, 1616, 1461, 1324, 1210, 1005, 783, 724, 669,
581, 513 cm–1. 1H NMR (500 MHz, DMSO-d6 + CDCl3):
δ = 6.45 (d, J = 7.65 Hz, 1 H, ArH), 6.52 (t, J = 7.65 Hz, 1
H, ArH), 6.75–6.78 (m, 2 H, ArH), 7.42 (d, J = 7.65 Hz, 2 H,
ArH), 7.65 (t, J = 7.65 Hz, 1 H, ArH), 7.72 (br s, 1 H, D2O
exchangeable, NH), 7.99 (d, J = 7.65 Hz, 2 H, ArH), 9.01 (br
s, 1 H, D2O exchangeable, NH), 9.81 (s, 1 H, D2O
exchangeable, NH). 13C NMR (125 MHz, DMSO-d6): δ =
94.2, 109.4, 117.9, 120.4, 122.9, 123.6, 129.3, 130.1, 134.0,
135.1, 136.8, 154.5, 171.1, 192.0. Anal. Calcd for
C16H12N2O2: C, 72.72; H, 4.58; N, 10.60. Found: C, 72.82;
H, 4.56; N, 10.62. HRMS (ESI): m/z calcd for C16H12N2O2:
265.0972 [M + H]+; found: 265.0977.
(Z)-3-(1-Amino-2-oxo-2-phenylethylidene)-1-(prop-2-
ynyl)indolin-2-one (5c): orange solid; mp 220–222 °C. IR
(KBr): 3407, 3285, 2931, 1665, 1616, 1464, 1352, 724, 679,
583 cm. 1H NMR (500 MHz, DMSO-d6): δ = 3.18 (s, 1 H,
≡CH), 4.62 (s, 2 H, CH2), 6.46 (d, J = 7.65 Hz, 1 H, ArH),
6.68 (t, J = 7.65 Hz, 1 H, ArH), 6.96 (t, J = 7.65 Hz, 1 H,
ArH), 7.00 (d, J = 7.65 Hz, 1 H, ArH), 7.59 (t, J = 7.65 Hz,
2 H, ArH), 7.73 (t, J = 7.65 Hz, 1 H, ArH), 8.00 (d, J = 7.65
Hz, 2 H, ArH), 8.64 (br s, 1 H, D2O exchangeable, NH), 8.99
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 1950–1954

1954
J. Kamalraja et al.
LETTER
(br s, 1 H, D2O exchangeable, NH). 13C NMR (125 MHz,
DMSO-d6): δ = 28.0, 73.9, 78.9, 91.4, 108.6, 117.0, 121.1,
121.9, 123.4, 129.6, 129.7, 130.1, 133.5, 135.5, 155.5,
167.2, 191.5. Anal. Calcd for C19H14N2O2: C, 75.48; H, 4.67;
N, 9.27. Found: C, 75.44; H, 4.63; N, 9.23. HRMS (ESI): m/z
calcd for C19H14N2O2: 303.1128 [M + H]+; found: 303.1142.
(Z)-Ethyl 2-[3-(1-Amino-2-oxo-2-phenylethylidene)-2-
oxoindolin-1-yl]acetate (5d): pale orange solid; mp 230–
232 °C. IR (KBr): 3404, 3294, 2924, 1714, 1668, 1624,
1496, 1365, 728, 588 cm–1. 1H NMR (500 MHz, DMSO-d6):
δ = 1.18 (t, J = 6.05 Hz, 3 H, Me), 4.12 (q, J = 7.65 Hz, 2 H,
CH2), 4.63 (s, 2 H, CH2), 6.46 (d, J = 7.65 Hz, 1 H, ArH),
6.66 (t, J = 5.35 Hz, 1 H, ArH), 6.91 (t, J = 6.10 Hz, 2 H,
ArH), 7.60 (t, J = 7.65 Hz, 2 H, ArH), 7.74 (t, J = 7.65 Hz,
1 H, ArH), 8.00 (d, J = 2 H, ArH), 8.61 (br s, 1 H, D2O
exchangeable, NH), 8.90 (br s, 1 H, D2O exchangeable, NH).
13C NMR (125 MHz, DMSO-d6): δ = 14.6, 41.0, 61.5, 92.0,
108.7, 117.4, 121.3, 122.3, 123.8, 130.1, 134.0, 135.9,
137.4, 155.7, 168.5, 169.0, 192.0. Anal. Calcd for
279.1128 [M + H]+; found: 279.1133.
(Z)-3-[1-Amino-2-(naphthalen-2-yl)-2-oxoethylidene]-1-
(prop-2-ynyl)indolin-2-one (5i): bright orange solid; mp
246–248 °C. IR (KBr): 3410, 3297, 3054, 2931, 1669, 1619,
1468, 1357, 1278, 1183, 669, 582 cm–1. 1H NMR (500 MHz,
CDCl3): δ = 2.23 (t, J = 2.3 Hz, 1 H, ≡CH), 4.63 (d, J = 2.3
Hz, 2 H, CH2), 5.61 (br s, 1 H, D2O exchangeable, NH),
6.69–6.74 (m, 2 H, ArH), 7.00–7.05 (m, 2 H, ArH), 7.53 (t,
J = 8.05 Hz, 1 H, ArH), 7.63 (t, J = 8.05 Hz, 1 H, ArH), 7.86–
7.94 (m, 3 H, ArH), 8.14 (d, J = 8.55 Hz, 1 H, ArH), 8.57 (s,
1 H, ArH), 9.1 (br s, 1 H, D2O exchangeable, NH). 13C NMR
(125 MHz, CDCl3-d6): δ = 28.7, 71.9, 77.7, 95.6, 108.6,
119.0, 121.8, 121.9, 123.8, 124.5, 127.4, 128.0, 129.6,
129.9, 130.2, 132.5, 134.0, 136.6, 137.1, 153.4, 168.5,
191.7. Anal. Calcd for C23H16N2O2: C, 78.39; H, 4.58; N,
7.95. Found: C, 78.43; H, 4.63; N, 7.91. HRMS (ESI): m/z
calcd for C23H16N2O2: 353.1285 [M + H]+; found: 353.1290.
(Z)-3-[1-Amino-2-(4-chlorophenyl)-2-oxoethylidene]-
indolin-2-one (5k): orange solid; mp 236–238 °C. IR (KBr):
3317, 3158, 2925, 2854, 1664, 1614, 1469, 1359, 1279,
1182, 785, 749, 477 cm–1. 1H NMR (500 MHz, DMSO-d6):
δ = 6.38 (d, J = 7.65 Hz, 1 H, ArH), 6.59 (t, J = 7.65 Hz, 1
H, ArH), 6.79 (d, J = 7.65 Hz, 1 H, ArH), 6.85 (t, J = 7.65
Hz, 1 H, ArH), 7.65 (d, J = 8.45 Hz, 2 H, ArH), 7.99 (d, J =
8.45 Hz, 2 H, ArH), 8.38 (br s, 1 H, D2O exchangeable, NH),
9.02 (br s, 1 H, D2O exchangeable, NH), 10.47 (s, 1 H, D2O
exchangeable, NH). 13C NMR (125 MHz, DMSO-d6): δ =
79.6, 93.4, 109.7, 117.5, 120.6, 123.9, 130.3, 131.9, 132.8,
137.1, 140.8, 154.4, 170.6, 191.1. Anal. Calcd for
C20H18N2O4: C, 68.56; H, 5.18; N, 8.00. Found: C, 68.52; H,
5.16; N, 8.06. HRMS (ESI): m/z calcd for C20H18N2O4:
351.1339 [M + H]+; found: 351.1345.
(Z)-3-(1-Amino-2-oxo-2-phenylethylidene)-1-benzyl-
indolin-2-one (5e): brown solid; mp 233–235 °C. IR (KBr):
3410, 3281, 3057, 1663, 1619, 1464, 741, 700, 600 cm–1. 1H
NMR (500 MHz, DMSO-d6): δ = 5.00 (s, 2 H, CH2), 6.46 (d,
J = 8.4 Hz, 1 H, ArH), 6.62 (t, J = 3.85 Hz, 1 H, ArH), 6.84
(d, J = 7.65 Hz, 2 H, ArH), 7.27–7.37 (m, 5 H, ArH), 7.59 (t,
J = 7.65 Hz, 2 H, ArH), 7.73 (t, J = 7.65 Hz, 1 H, ArH), 8.02
(d, J = 7.65 Hz, 2 H, ArH), 8.61 (br s, 1 H, D2O
C16H11ClN2O2: C, 64.33; H, 3.71; N, 9.38. Found: C, 64.39;
H, 3.67; N, 9.32.
(Z)-Ethyl 2-{3-[1-Amino-2-(4-chlorophenyl)-2-
exchangeable, NH), 9.00 (br s, 1 H, D2O exchangeable, NH).
13C NMR (125 MHz, DMSO-d6): δ = 42.6, 92.1, 109.0,
117.4, 121.2, 122.4, 123.8, 127.5, 127.7, 129.1, 130.1,
130.2, 134.0, 135.9, 137.9, 137.9, 155.7, 168.6, 192.1. Anal.
Calcd for C23H18N2O2: C, 77.95; H, 5.12; N, 7.90. Found: C,
77.89; H, 5.18; N, 7.92. HRMS (ESI): m/z calcd for
oxoethylidene]-2-oxoindolin-1-yl}acetate (5l):
bright orange solid; mp 221–223 °C. IR (KBr): 3347, 3194,
2925, 1743, 1663, 1613, 1469, 1368, 1275, 1174, 1092,
1016, 754, 593, 539 cm–1. 1H NMR (500 MHz, DMSO-d6):
δ = 1.18 (t, J = 7.3 Hz, 3 H, Me), 4.12 (q, J = 6.85 Hz, 2 H,
CH2), 4.63 (s, 2 H, CH2), 6.45 (d, J = 7.65 Hz, 1 H, ArH),
6.68 (t, J = 7.65 Hz, 1 H, ArH), 6.89–6.93 (m, 2 H, ArH),
7.67 (d, J = 8.4 Hz, 2 H, ArH), 8.0 (d, J = 7.6 Hz, 2 H, ArH),
8.59 (br s, 1 H, D2O exchangeable, NH), 8.94 (br s, 1 H, D2O
exchangeable, NH). 13C NMR (125 MHz, DMSO-d6): 14.6,
41.0, 61.5, 92.0, 108.7, 117.4, 121.4, 122.1, 123.9, 130.3,
131.9, 132.7, 137.5, 140.9, 155.0, 169.0, 191.0. Anal. Calcd
for C20H17ClN2O4: C, 62.42; H, 4.45; N, 7.28. Found: C,
62.48; H, 4.51; N, 7.21. HRMS (ESI): m/z calcd for
C20H17ClN2O4: 385.0950 [M + H]+; found: 385.0955.
(13) McEwen, W. E.; Conrad, W. E.; VanderWerf, C. A. J. Am.
Chem. Soc. 1952, 74, 1168.
C23H18N2O2: 355.1441 [M + H]+; found: 355.1457.
(Z)-3-(1-Amino-2-oxo-2-phenylethylidene)-5-methyl-
indolin-2-one (5g): orange solid; mp 210–212 °C. IR (KBr):
3423, 3154, 1665, 1618, 1481, 1326, 791, 718, 671, 587 cm–1.
1H NMR (500 MHz, DMSO-d6): δ = 1.94 (s, 3 H, Me), 6.20
(s, 1 H, ArH), 6.65–6.68 (m, 2 H, ArH), 7.58 (t, J = 7.65 Hz,
2 H, ArH), 7.72 (t, J = 7.65 Hz, 1 H, ArH), 7.98 (d, J = 7.65
Hz, 2 H, ArH), 8.33 (br s, 1 H, D2O exchangeable, NH), 9.01
(br s, 1 H, D2O exchangeable, NH), 10.32 (s, 1 H, D2O
exchangeable, NH). 13C NMR (125 MHz, DMSO-d6): δ =
21.5, 93.3, 109.4, 118.2, 123.2, 124.4, 128.9, 130.0, 130.1,
134.1, 134.9, 135.8, 154.9, 170.8, 192.2. Anal. Calcd for
C17H14N2O2: C, 73.37; H, 5.07; N, 10.07. Found: C, 73.41;
H, 5.11; N, 10.03. HRMS (ESI): m/z calcd for C17H14N2O2:
Synlett 2012, 23, 1950–1954
© Georg Thieme Verlag Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or
emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.
However, users may print, download, or email articles for individual use.