Synthesis of functionalized 1,2,3-triazole derivatives of 2-indolones from Morita-Baylis-Hillman adducts of isatin via "'click chemistry"

Article abstract of DOI:10.1002/jhet.168

(Chemical Equation Presented) A short and efficient regioselective synthesis of a number of 1,4-disubstituted-1,2,3-triazole derivatives of oxindoles from N-terminal alkyne and alkynyl ether derivatives of Morita-Baylis-Hillman (MBH) adducts of isatin wit

Full text of DOI:10.1002/jhet.168

September 2009
Synthesis of Functionalized 1,2,3-Triazole Derivatives
of 2-Indolones from Morita-Baylis-Hillman Adducts of Isatin via
‘‘Click Chemistry’’
919
Ponnusamy Shanmugam,* Mumusamy Damodiran, Kodirajan Selvakumar,
and Paramasivan T. Perumal*
Division of Organic Chemistry, Central Leather Research Institute, Adyar, Chennai,
Tamil Nadu 600 020, India
*E-mail: shanmu196@rediffmail.com
Received February 28, 2009
DOI 10.1002/jhet.168
Published online 2 September 2009 in Wiley InterScience (www.interscience.wiley.com).
A short and efficient regioselective synthesis of a number of 1,4-disubstituted-1,2,3-triazole deriva-
tives of oxindoles from N-terminal alkyne and alkynyl ether derivatives of Morita-Baylis-Hillman
(MBH) adducts of isatin with in situ generated alkyl azide and copper(I) iodide as a catalyst in 1:1 mix-
ture of t-BuOH:water as a solvent system has been achieved. The synthetic procedure tolerates most of
the functional groups present in the MBH adducts and circumvents the problems associated with the
isolation of potentially toxic and explosive organic azides.
J. Heterocyclic Chem., 46, 919 (2009).
INTRODUCTION
reported for the synthesis of 1,2,3-triazoles and 1,3-dipo-
lar cycloaddition of azides to alkynes [19–21]. Recently,
Sharpless and coworkers have reported a high yielding
synthesis of triazoles using a Cu(I) catalyst with an
excellent 1,4-regioselectivity. The metal-catalyzed reac-
tion discovered simultaneously and independently in the
Sharpless and Meldal laboratories [22] constitutes a sub-
stantial improvement of the classical Huisgen-type ther-
mal 1,3-dipolar cycloaddition, which usually afford a
mixture of 1,4- and 1,5-disubstituted triazoles. Fokin and
coworkers have developed a multicomponent variant for
the synthesis of trizoles both in conventional [23] and
microwave irradiation [24] methods. Although N-propar-
gyl isatins obtained from Friedel-Crafts alkylation of 2-
napthol with isatin have been used for the 1,3-dipolar
cycloaddition with alkyl azides [25], however, the reac-
tion with N-alkyne and N-alkynyl ether derivatives of
MBH adducts of isatin are unknown. Thus, herein, we
report an efficient, safe, and one-pot synthesis of 1,4-dis-
ubstituted-1,2,3-triazole derivatives of oxindoles from
the 1,3-dipolar cycloaddition reaction of N-propargyl
MBH adduct of isatin with in situ generated alkyl azide
and copper iodide as catalyst in 1:1 mixture of t-BuOH
and water as a solvent. The reaction condition was fully
compatible and environmentally benign. A detailed study
Oxindoles derivatized as 1,2,3-triazole are elegant
synthetic targets in organic synthesis due to their signifi-
cant biological activities [1]. Recently, click chemistry
has been emerged as a fast and efficient method for the
synthesis of novel diverse chemical entities and the gen-
eration of large number of drug-like molecules with tria-
zole scaffolds [2]. The triazole scaffolds are considered
as significant synthetic targets due to their significant bi-
ological activities, such as antibacterial [3], anti-HIV
[4], and anti-allergic [5]. Hence, a number of synthetic
routes have been developed for the preparation of these
structural frameworks [6–9]. As a result, there has been
considerable interest in developing efficient synthetic
methods for these compounds with oxindole as core
structure. The Morita-Baylis-Hillman (MBH) adduct and
their derivatives, such as halides, acetates, ethers, etc.
play an important role as synthons for a number of
potential synthetic intermediates and natural product
syntheses [10]. As part of our on going research on
novel synthetic applications of MBH adducts [11–13],
particularly for the construction of novel oxindole deriv-
atives [14–18], we were interested to explore the synthesis
of title compounds using the versatile ‘‘click chemistry’’
reaction methodology. Several methods have been
C
V
2009 HeteroCorporation

920
P. Shanmugam, M. Damodiran, K. Selvakumar, and P. T. Perumal
Vol 46
Scheme 1
on the 1,3-dipolar cycloaddition reaction of N-terminal
alkynes 3 and 5 with alkyl azides to afford highly func-
tionalized triazole derivatives is the subject matter of
this article (Scheme 1).
tuted the Cu(I) catalyzed alkyne–azide [3þ2]-cycloaddi-
tion furnished pharmaceutically important 1,4-disubsti-
tuted 1,2,3-triazole indolones in excellent yields
(Scheme 1, Table 1). This investigation offers a mild
and efficient method for the preparation of 1,2,3-tria-
zoles using CuI as catalyst for the 1,3-dipolar cycloaddi-
tion of terminal alkynes with alkyl azides. The copper(I)
readily inserts into terminal alkynes in the presence of a
base, which proceeds via the intriguing six-membered
ring [22,27]. The triazole was formed in a regioselective
manner, with no contamination of 1,5-regioisomer. To
demonstrate the methodology applicable to a variety of
substrates having bromo, fluorine, and alkyl substitu-
tions, synthesis of several triazole derivatives of oxin-
doles have been achieved and the results are collected
in Table 1. The structure of 1,4-disubstituted 1,2,3-tria-
zoles obtained is in good agreement with those
described in the previous reports on the synthesis of
substituted triazoles via three component coupling reac-
tion [28]. The results revealed that the reaction was de-
pendent on the nature of substituents on the isatin as
evident from the comparison of the yields of products
(4a–k and 6a–c) due to electronic effects. The yields of
the products decreased when electron donating groups
were present on the isatin (entries 3 and 4). The yield of
the products increased when electron-withdrawing
groups were present on the isatin (entries 5, 6, 9, and
10). The substitution in ester group from Me ! Et !
Bu (entries 6, 7, 8, 10, and 11) afforded decreased yields.
RESULTS AND DISCUSSION
The starting material N-terminal alkynes of isatin
were prepared from the alkylation reaction of isatin with
propargyl bromide and CaH2 as a base in DMF at 60ꢀC
for 1 hr. Further, the corresponding MBH adducts were
prepared following reported procedure [26]. The other
substrate namely, N-propargyl ether derivative of MBH
adduct was prepared from the N-methylated MBH
adduct of isatin with propargyl alcohol and cerium am-
monium nitrate (CAN) in acetonitrile at room tempera-
ture [11].
Initially, we carried out a reaction of alkyne 3 with
1.2 equivalents of sodium azide, 2.6 equivalents of trie-
thylamine, and 2.2 equivalents of benzyl bromide in the
presence of 2.5 mol % CuI in PEG-400. The reaction
did not proceed and attempts to carry out the reaction
with other solvent such as H2O also did not yield fruit-
ful results. However, the use of
a mixture of
tBuOH:H2O (1:1 v/v) as solvent drove the reaction to
form the desired 1,4-disubstituted 1,2,3-bistriazole prod-
uct in excellent yield (Scheme 1, Table 1, entry 1). The
click chemistry reaction, under mild conditions, consti-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Table 1
Table 1
(Continued)
Synthesis of 1,2,3-triazole derivatives of oxindole.
Entry Substrate (R2)
Product
Yield (%)a
75
Entry Substrate (R2)
H
Product
Yield (%)a
8
Br
1
2
3
4
5
80
82
73
71
82
9
F
86
88
77
79
82
80
H
10
11
12
13
F
Me
Me
Br
F
H
F
6
Br
84
14
F
7
Br
78
a Isolated yield.

922
P. Shanmugam, M. Damodiran, K. Selvakumar, and P. T. Perumal
Vol 46
122.7, 122.3, 122.6, 124.4, 128.0, 128.2, 128.9, 129.0, 131.0,
141.2, 164.3, 176.1. MS (EI) m/z 372 (Mþ).
All the new compounds were characterized thoroughly
1
by spectroscopic methods (IR, H, 13C NMR, and ESI-
mass spectra).
Methyl
2-(1-((1-benzyl-1H-1,2,3-triazol-4-y2l)methyl)-3-
hydroxy-2-oxoindolin-3-yl) acrylate (4b). White solid: Rf
(60% EA/hexane) 0.25; IR (KBr): 3383, 1718, 1612, 1490,
It is noteworthy that these reactions were efficiently
performed in a neutral aqueous solution (water:tBuOH)
at an ambient temperature (RT). Molar equivalents of the
halide, sodium azide, and alkyne were used in the mild
1,3-dipolar cycloaddition reaction. The method avoid the
problems associated during the isolation of organic
azides, and complements the reported method for the
preparation of 1,2,3-triazoles. The operational simplicity
of this method makes it attractive for preparative applica-
tions as well as a library compounds for drug discovery.
In conclusion, we have demonstrated an efficient syn-
thetic procedure for the synthesis of highly functional-
ized 1,2,3-triazole derivatives of 2-indolones via a cop-
per(I) catalyzed 1,3-dipolar cycloaddition of N-terminal
alkyne derivative of MBH adduct of isatin with in situ
generated alkyl azides. Further studies on this reagent
system are in progress.
1
1327, 1171 cmꢂ1; H NMR (CDCl3/TMS, 300.1 MHz): d 3.32
(brs, 1H), 3.49 (s, 3H), 4.92 (d, J ¼ 15.8 Hz, 1H), 5.17 (d, J
¼ 15.8 Hz, 1H), 5.45 (AB quartet, J ¼ 13.7 Hz, 2H), 6.46 (s,
1H), 6.57 (s, 1H), 6.97–7.32 (m, 9H), 7.36 (s, 1H); 13C NMR
(CDCl3/TMS, 75.3 MHz): 36.0, 51.8, 54.2, 76.0, 109.8, 122.9,
123.1, 123.7, 128.0, 128.1, 128.7, 129.0, 129.4, 130.2, 134.4,
139.0, 142.9, 143.1, 164.9, 176.0. MS (EI) m/z 405 (Mþ).
2-(1-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-3-ydroxy-5-
methyl-2-oxoindolin-3-yl)acrylonitrile (4c). White solid: Rf
(60% EtOAc/hexane) 0.34; IR (KBr): 3371, 2221, 1719, 1608,
1
1483, 1330, 1169 cmꢂ1; H NMR (CDCl3/TMS, 300.1 MHz):
d 2.30 (s, 1H), 4.37 (brs, 1H), 4.88 (d, J ¼ 15.7 Hz, 1H), 5.06
(d, J ¼ 15.7 Hz, 1H), 5.40 (AB quartet, J ¼ 13.8 Hz, 2H),
6.16 (s, 1H), 6.40 (s, 1H), 6.90 (d, J ¼ 7.9 Hz, 1H), 7.13–7.19
(m, 4H), 7.29–7.34 (m, 3H), 7.51 (s, 1H); 13C NMR (CDCl3/
TMS, 75.3 MHz): 20.9, 33.0, 36.0, 54.2, 54.8, 76.5, 105.3,
110.1, 117.9, 122.6, 122.8, 125.2, 127.0, 128.0, 128.7, 129.0,
131.2, 131.3, 139.5, 142.9, 176.0. MS (EI) m/z 386 (Mþ).
Methyl 2-(1-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-3-hydroxy-
5-methyl-2-oxoindolin-3-yl)acrylate (4d). White solid: Rf
(60% EA/hexane) 0.25; IR (KBr): 3387, 1721, 1612, 1492,
EXPERIMENTAL
1
1322, 1168 cmꢂ1; H NMR (CDCl3/TMS, 300.1 MHz): d 2.03
(brs, 1H), 2.62 (s, 3H), 3.48 (s, 3H), 5.01 (AB quartet, J ¼
12.4 Hz, 2H), 5.38 (d, J ¼ 14.8 Hz, 1H), 5.45 (d, J ¼ 14.8
Hz, 1H), 6.49 (s, 1H), 6.56 (s, 1H), 6.82 (d, J ¼ 7.8 Hz, 1H),
6.95–7.11 (m, 3H), 7.24–7.31 (m, 4H), 7.64 (s, 1H). 13C NMR
(CDCl3/TMS, 125 MHz): 20.9, 36.0, 51.8, 54.2, 75.8, 109.5,
122.8, 124.4, 127.8, 127.9, 128.0, 128.3, 128.6, 129.01, 129.2,
130.4, 132.7, 134.4, 138.9, 140.6, 143.0, 164.9, 176.6. MS
(EI) m/z 419 (Mþ).
General. IR measurements were done as KBr pellets for
solids using PerkinElmer Spectrum RXI FTIR. The 1H and
13C NMR spectra were recorded in CDCl3 with, Bruker
500 MHz and Bruker 300.1 MHz high resolution NMR spec-
trometer. CDCl3 was used as the solvent for the NMR spectral
measurements and spectra were recorded in ppm with TMS as
internal standard. Multiplicities are abbreviated as follows: sin-
glet (s), doublet (d), triplet (t), multiplet (m), and broad (br).
The mass were analyzed by using a Electrospray Ionization
method with Thermo Finnigan Mass spectrometer. Melting
points were determined in capillary tubes and are uncorrected.
Analytical TLC was performed on precoated plastic sheets of
silica gel G/UV-254 of 0.2-mm thickness (Macherey-Nagel,
Germany).
2-(1-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-5-bromo-3-
hydroxy-2-oxoindolin-3-yl)acrylonitrile (4e). White solid: Rf
(60% EA/hexane) 0.25; IR (KBr): 3381, 1614, 1495, 1323,
1
1166 cmꢂ1; H NMR (CDCl3/TMS, 300.1 MHz): d 2.00 (brs,
1H), 4.90 (d, J ¼ 15.8 Hz, 1H), 4.99 (d, J ¼ 15.7 Hz, 1H),
5.41 (AB quartet, J ¼ 14.3 Hz, 2H), 6.20 (s, 1H), 6.44 (s, 1H),
6.91 (d, J ¼ 8.8 Hz, 1H), 7.07–7.14 (m, 2H), 7.30–7.35 (m,
3H), 7.42–7.44 (m, 2H), 7.50 (s, 1H); 13C NMR (CDCl3/TMS,
75.3 MHz): 35.3, 52.1, 54.2, 76.1, 112.0, 122.1, 122.6, 126.2,
126.9, 128.0, 128.7, 128.6, 128.9, 130.2, 132.7, 133.9, 138.4,
142.2, 142.7, 175.4. MS (EI) m/z 450 (Mþ), 452 (M þ 2).
Typical experimental procedure (4b). A mixture of N-pro-
pargyl derivative of MBH adduct (100 mg, 0.35 mmol), so-
dium azide (27 mg, 0.42 mmol), benzyl bromide (66 mg, 0.38
mmol), triethylamine (92 mg, 0.91 mmol), and CuI (2.5 mol
%) in 3 mL of t-butanol:water (1:1) was stirred at room tem-
perature for 6 h. After completion of the reaction (monitored
R
Methyl
bromo-3-hydroxy-2-oxoindolin-3-yl)
solid: Rf (60% EtOAc/hexane) 0.30; IR (KBr): 3371, 2221,
1719, 1608, 1483, 1330, 1169 cmꢂ1 1H NMR (CDCl3/TMS,
2-(1-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-5-
V
by TLC), the catalyst was filtered off through a pad of celite
acrylate (4f). White
and the product was extracted with ether (2 ꢁ 20 mL). The
combined organic layer was dried (anhyd. Na2SO4), filtered,
and removed under vacuum. The crude product was purified
by silica gel column chromatography using hexane–ethyl ace-
tate (7:3) solvent mixture to afford pure triazole derivatives.
2-(1-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-3-hydroxy-2-
oxoindolin-3-yl)acrylonitrile (4a). White solid: Rf (60% EA/
;
300.1 MHz): d 2.03 (s, 1H), 3.51 (s, 1H), 4.85 (d, J ¼ 15.8 Hz,
1H), 5.09 (d, J ¼ 15.9 Hz, 1H), 5.41 (AB quartet, J ¼ 12.5 Hz,
2H), 6.51 (s, 1H), 6.58 (s, 1H), 6.82 (d, J ¼ 8.2 Hz, 1H), 7.26–
7.43 (m, 7H), 7.61 (s, 1H); 13C NMR (CDCl3/TMS, 75.3
MHz): 35.8, 51.8, 54.2, 76.5, 111.3, 122.1, 122.8, 126.8, 126.9,
128.0, 128.4, 128.6, 128.9, 129.1, 132.7, 134.2, 138.4, 142.0,
142.4, 165.4, 175.4. MS (EI) m/z 483 (Mþ), 485 (M þ 2).
Ethyl 2-(1-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-5-bromo-
3-hydroxy-2-oxoindolin-3-yl)acrylate (4g). White solid: Rf
(60% EA/hexane) 0.25; IR (KBr): 3369, 1724, 1617, 1484,
hexane) 0.25; IR (KBr): 3378, 1612, 1487, 1332, 1177 cmꢂ1
;
1H NMR (CDCl3/TMS, 300.1 MHz): d 2.39 (brs, 1H), 4.86 (d,
J ¼ 15.8 Hz, 1H), 5.10 (d, J ¼ 15.9 Hz, 1H), 5.38 (AB quar-
tet, J ¼ 14.2 Hz, 2H), 6.13 (s, 1H), 6.39 (s, 1H), 6.74–7.13
(m, 4H), 7.26–7.31 (m, 5H), 7.54 (s, 1H). 13C NMR (CDCl3/
TMS, 75.3 MHz): 34.9, 52.5, 54.2, 76.2, 108.9, 112.1, 114.3,
1
1318, 1183 cmꢂ1; H NMR (CDCl3/TMS, 300.1 MHz): d 1.09
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2009
Synthesis of Functionalized 1,2,3-Triazole Derivatives of 2-Indolones from
Morita-Baylis-Hillman Adducts of Isatin via ‘‘Click Chemistry’’
923
(t, J ¼ 3.24 Hz, 3H), 2.03 (brs, 1H,), 3.95 (q, J ¼ 4.5, 11.8
Hz, 2H), 4.92 (d, J ¼ 15.8 Hz, 1H), 5.09 (d, J ¼ 15.9 Hz,
1H), 5.45 (AB quartet, J ¼ 11.9 Hz, 2H), 6.48 (s, 1H), 6.60
(s, 1H), 6.79–7.01 (m, 3H), 7.26–7.38 (m, 5H), 7.60 (s, 1H).
MS (EI) m/z 266 (Mþ);13C NMR (CDCl3/TMS, 125 MHz):
13.8, 14.1, 22.6, 22.9, 29.6, 34.6, 52.7, 54.3, 61.1, 75.7, 111.4,
115.7, 122.8, 125.0, 127.0, 128.1, 128.2, 128.7, 129.0, 135.2,
138.4, 142.0, 164.3, 175.4. MS (EI) m/z 497 (Mþ), 499
(M þ 2).
1H), 6.35–6.98 (m, 9H), 7.38 (s, 1H); 13C NMR (CDCl3/TMS,
75.3 MHz): 30.1, 52.3, 53.9, 68.1, 74.2, 112.2, 114.9, 116.3,
125.9, 127.6, 128.1, 128.5, 129.4, 133.0, 135.5, 138.3, 138.6,
164.7, 177.1. MS (EI) m/z 402 (Mþ).
2-(1-(((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy) methyl)-5-
fluoro-3-hydroxy-2-oxoindolin-3-yl)acrylonitrile (6b). White
solid: Rf (60% EA/hexane) 0.29; IR (KBr): 3382, 1621, 1486,
1112 cmꢂ1 1H NMR (CDCl3/TMS, 300.1 MHz): d 4.63 (d,
;
J ¼ 13.2 Hz, 1H), 4.72 (d, J ¼ 13.1 Hz, 1H), 5.06 (d, J ¼ 11.4
Hz, 1H), 5.36 (AB quartet, J ¼ 9.8 Hz, 2H), 5.53 (d, J ¼ 11.4
Hz, 1H), 5.84 (brs, 1H), 6.25 (s, 1H), 6.58 (s, 1H), 6.78–6.81 (m,
4H), 7.00–7.12 (m, 4H), 7.35 (s, 1H); 13C NMR (CDCl3/TMS,
75.3 MHz): 35.7, 53.2, 53.9, 69.7, 76.1, 111.5, 113.4, 115.8,
116.1, 123.3, 128.6, 128.1, 128.7, 128.9, 132.4, 134.7, 137.9,
138.3, 144.0, 164.4, 175.6. MS (EI) m/z 420 (Mþ).
Butyl 2-(1-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-5-bromo-
3-hydroxy-2-oxoindolin-3-yl)acrylate (4h). White solid: Rf
(60% EA/hexane) 0.25; IR (KBr): 3383, 1718, 1612, 1490,
1
1327, 1171 cmꢂ1; H NMR (CDCl3/TMS, 300.1 MHz): d 0.88
(t, J ¼ 7.2 Hz, 3H), 1.19–1.29 (m, 4H), 3.89 (t, J ¼ 6.9 Hz,
2H), 4.08 (brs, 1H), 4.91 (d, J ¼ 15.6 Hz, 1H), 5.08 (d, J ¼
15.9 Hz, 1H), 5.44 (AB quartet, J ¼ 12.1 Hz, 2H), 6.47 (s,
1H), 6.61 (s, 1H), 6.84 (d, 1H, J ¼ 8.1 Hz), 7.24–7.38 (m,
7H), 7.61 (s, 1H). MS (EI) m/z 266 (Mþ);13C NMR (CDCl3/
TMS, 125 MHz): 13.6, 18.9, 19.0, 29.6, 30.2, 36.0, 43.3, 54.3,
64.9, 75.7, 111.4, 115.7, 122.8, 127.0, 128.1, 128.2, 128.6,
128.7 (C), 129.0, 129.3, 132.6, 134.3, 138.4, 142.0, 164.4,
175.5. MS (EI) m/z 525 (Mþ), 527 (M þ 2).
Methyl2-(1-(((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy) methyl)-
5-fluoro-3-hydroxy-2-oxoindolin-3-yl) acrylate (6c). White solid:
Rf (60% EA/hexane) 0.29; IR (KBr): 3386, 1722, 1617, 1483,
1110 cmꢂ1 1H NMR (CDCl3/TMS, 300.1 MHz): d 3.50 (s,
;
3H), 4.60 (d, J ¼ 12.6 Hz, 1H), 4.68 (d, J ¼ 12.8 Hz, 1H),
5.11 (d, J ¼ 11.2 Hz, 1H), 5.29 (d, J ¼ 11.3 Hz, 1H), 5.40–
5.51 (m, 2H), 5.71 (s, 1H, br), 6.61 (s, 1H), 6.83 (s, 1H),
6.83–6.93 (m, 3H), 7.30–7.36 (m, 3H), 7.14–7.17 (s, 2H), 7.42
(s, 1H); 13C NMR (CDCl3/TMS, 75.3 MHz): 14.8, 35.9, 51.8,
53.9, 69.7, 75.8, 110.5, 111.7, 115.8, 116.1, 123.3, 127.9,
128.4, 128.6, 128.9, 131.4, 134.2, 138.1, 138.3, 144.0, 164.8,
176.9. MS (EI) m/z 453 (Mþ).
2-(1-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-5-fluoro 3-
hydroxy-2-oxoindolin-3-yl)acrylonitrile (4i). White solid: Rf
(60% EtOAc/hexane) 0.32; IR (KBr): 3386, 2243, 1726, 1619,
1
1490, 1343, 1171 cmꢂ1; H NMR (CDCl3/TMS, 300.1 MHz):
d 2.02 (brs, 1H), 4.89 (d, J ¼ 15.8 Hz, 1H), 4.99 (d, J ¼ 15.8
Hz, 1H), 5.40 (d AB quartet, J ¼ 13.3 Hz, 2H), 6.17 (s, 1H),
6.43 (s, 1H), 6.96–7.09 (m, 3H), 7.22 (d, J ¼ 3.3 Hz, 1H),
7.26–7.34 (m, 4H), 7.51 (s, 1H); 13C NMR (CDCl3/TMS, 75.3
MHz): 35.8, 52.0, 54.2, 76.5, 109.2, 112.4, 115.5, 122.1 122.7,
123.5, 128.0, 128.7, 129.0, 131.9, 134.0, 140.1, 141.8, 142.5,
143.3, 173.8. MS (EI) m/z 390 (Mþ).
Acknowledgments. M. D. and K. S. thanks UGC and CSIR
(New Delhi) for the award of a Senior Research Fellowships. Fi-
nancial support (SR/S1/OC-38/2005) from the DST (New Delhi)
is gratefully acknowledged. Thanks to Mrs. Viji and Mrs. Sou-
mini Mathew for providing mass and NMR data, respectively.
Methyl 2-(1-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-5-flu-
oro-3-hydroxy-2-oxoindolin-3-yl)acrylate (4j). White solid: Rf
(60% EtOAc/hexane) 0.28; IR (KBr): 3362, 2217, 1722, 1612,
REFERENCES AND NOTES
1
1490, 1334 cmꢂ1; H NMR (CDCl3/TMS, 300.1 MHz): d 3.50
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(s, 3H), 4.65 (brs, 1H), 4.86 (d, J ¼ 15.9 Hz, 1H), 5.08 (d, J
¼ 15.9 Hz, 1H), 5.41 (AB quartet, J ¼ 10.0 Hz, 2H), 6.46 (s,
1H), 6.51 (s, 1H), 6.83–6.95 (m,3H), 7.21 (d, J ¼ 3.0 Hz, 1H),
7.26–7.39 (m, 3H), 7.62 (s, 1H); 13C NMR (CDCl3/TMS, 75.3
MHz): 35.9, 51.8, 54.2, 75.9, 110.1, 122.8, 128.0, 128.3,
128.6, 128.9, 129.2, 129.7, 130.0, 134.3, 138.5, 139.0, 142.5,
143.2, 164.7, 175.7. MS (EI) m/z 423 (Mþ).
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(60% EA/hexane) 0.31; IR (KBr): 3371, 1718, 1630, 1469,
1
1318, 1183 cmꢂ1; H NMR (CDCl3/TMS, 300.1 MHz): d 1.07
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(t, 3H, J ¼ 7.1 Hz), 2.48 (brs, 1H), 3.92 (q, J ¼ 4.3, 11.2 Hz,
2H), 4.85(d, J ¼ 15.9 Hz, 1H), 5.04 (d, J ¼ 15.9 Hz, 1H),
5.39 (AB quartet, J ¼ 9.3 Hz, 2H), 6.44 (s, 1H), 6.50 (s, 1H),
6.82–6.92 (m, 5H), 7.28–7.34 (m, 3H), 7.64 (s, 1H); 13C NMR
(CDCl3/TMS, 75.3 MHz): 14.2, 22.4, 33.8, 51.8, 53.9, 62.0,
75.5, 96.0, 99.2, 109.6, 113.8, 113.9, 115.4, 122.4, 128.3,
128.6, 128.8, 129.0, 129.4, 134.2, 138.4, 142.0, 164.1, 172.0.
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2-(1-(((1-benzyl-1H-1,2,3-triazol-4-l)methoxy)methyl)-3-
hydroxy-2-oxoindolin-3-yl) acrylonitrile (6a). White solid: Rf
(60% EA/hexane) 0.29; IR (KBr): 3377, 1615, 1473, 1117
cmꢂ1 1H NMR (CDCl3/TMS, 300.1 MHz): d 3.43 (s, 1H,
;
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