Microwave-assisted three-component synthesis of some novel 1-alkyl-1H-indole-2,3-dione 3-(o-alkyloxime) derivatives as potential chemotherapeutic agents

Article abstract of DOI:10.1002/hlca.201000104

A convenient and efficient method for a one-pot conversion of N-alkylisatins to N-alkylisatin O-alkyloximes 7a-7n as potential chemotherapeutic agents is described (Scheme) (isatin=1H-indole-2,3-dione). In this method, the microwave-assisted three-compone

Full text of DOI:10.1002/hlca.201000104

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Helvetica Chimica Acta – Vol. 93 (2010)
Microwave-Assisted Three-Component Synthesis of Some Novel 1-Alkyl-1H-
indole-2,3-dione 3-(O-Alkyloxime) Derivatives as Potential
Chemotherapeutic Agents
by Mohammad Navid Soltani Rad*a), Ali Khalafi-Nezhad*b), Somayeh Babamohammadib), and
Somayeh Behrouza)
a) Department of Chemistry, Faculty of Basic Sciences, Shiraz University of Technology,
Shiraz 71555-313, Iran (phone: þ 98-711-7261392; fax: þ 98-711-7354523; e-mail: soltani@sutech.ac.ir)
b) Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
(phone: þ 98-711-2284822; fax: þ 98-711-2280926; e-mail: khalafi@susc.ac.ir)
A convenient and efficient method for a one-pot conversion of N-alkylisatins to N-alkylisatin O-
alkyloximes 7a – 7n as potential chemotherapeutic agents is described (Scheme) (isatin ¼ 1H-indole-2,3-
dione). In this method, the microwave-assisted three-component reaction of N-alkylisatins 8, hydroxyl-
amine hydrochloride, and diverse alkyl halides in the presence of K2CO3 and Bu4NBr furnishes the
corresponding N-alkylisatin O-alkyloximes under solvent-free condition in short times (2 – 10 min) and
good to excellent yields (62 – 83%). The O-alkylation of in situ generated isatin oximes with alkyl halides
was achieved regioselectively, and (Z)-O-alkyloximes were produced dominantly. PM3 Semi-empirical
quantum-mechanic calculations were performed to rationalize the evidences, and the calculations
indicated a lower heat of formation for the (Z)-O-alkyloximes.
Introduction. – Isatin (¼1H-indole-2,3-dione) is a versatile substrate in organic and
medicinal chemistry, and it has been used extensively for the construction of various
compounds exhibiting a wide spectrum of biological activities [1]. Among isatin
derivatives, oxime and O-alkyloximes of isatin have attracted particular attention
because of their broad range of applications as potential therapeutic agents and
synthetic intermediates [1a – 1c][2]. Isatin oximes and O-alkyloximes display diverse
pharmacological activities such as antiviral [3], anticancer [4], anticonvulsant [5], anti-
HIV [6], anti-inflammatory, as well as anti-asthmatic [7], anti-mycobacterium tuber-
culosis [8], and antidote activity [9]. Moreover, coumarin derivatives of isatin oximes
are used in medicine as fluorescent agents [10]. The structures of several famous isatin
oximes and O-alkyloximes that are used in medicinal chemistry, i.e., of 1 – 6, are shown
in the Figure.
Two general methods have been established for the synthesis of isatin O-
alkyloximes: first, the reaction of isatin with O-alkylhydroxylamines [3b][4d][11]
and second, the reaction of isatin oxime with alkyl halides under various conditions
[3a][12]. However, these methods are accompanied by several drawbacks such as the
nonavailability of structurally diverse O-alkylhydroxylamines, the use of DMF and
DMSO as solvent, tedious workup of the reaction mixture, long reaction times, and low
yields. Moreover, conventional heating methods for the synthesis of O-alkyloximes
ꢀ 2010 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 93 (2010)
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Figure. Structures of several isatin oximes and O-alkyloximes exhibiting biological activities
usually give a mixture of the two geometrical isomers whose separation is cumbersome
and results in a decrease of the overall yield [13].
The multicomponent reactions (MCRs) are most important reactions in organic
synthesis and medicinal chemistry [14]. The MCRs are one-pot processes combining
three or more substrates simultaneously. Due to their ease of operation, atom economy,
and quantitative yields, MCRs have found growing attention. Many important
reactions such as the Biginelli, Mannich, Passerini, and Ugi reactions are well-known
multicomponent reactions [14]. These reactions often involve condensation processes
and ring closure. Indeed, there are only rare reports in which an SN2 type reaction is a
part of MCRs [15].
Microwave-assisted synthesis in organic reactions has been of growing interest as an
efficient, economic, and clean procedure. Microwave irradiation often leads to a
remarkable decrease in reaction time, increased yields, easier workup, compliance with
environmentally benign chemistry, and may enhance the regio- and stereoselectivity of
reactions [16].
Encouraged by the unique biological activities of isatin oximes and O-alkyloxime
derivatives and also in continuation of our ongoing research in oxime chemistry [17] as
well as multicomponent reactions [15], we report a convenient and simple method for
the synthesis of some novel N-alkylated isatin O-alkyloximes 7a – 7n using microwave-
assisted three-component coupling of N-alkylated isatin derivatives, hydroxylamine
hydrochloride and alkyl halides in the presence of K2CO3 and tetrabutylammonium
bromide (Bu4NBr) under solvent-free condition (Scheme, c)). For comparison, we also
examined the multi-step synthesis of the corresponding N-alkylated isatin O-
alkyloximes using both conventional heating and microwave-assisted methods
(Scheme, a) and b), resp.).

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Helvetica Chimica Acta – Vol. 93 (2010)
Scheme
a) DMSO/H2O 9 :1, KOH, r.t., 3 – 5 h. b) K2CO3, MW (100 W), 0.08 – 10 min. c) K2CO3, Bu4NBr,
NH2OH · HCl, MW (300 W), 2 – 10 min.
Results and Discussion. – As shown in the Scheme, the alkylation of isatin was
initially achieved with several alkyl halides to give N-alkylisatins 8a – 8e as the key
intermediates. Several methods for N-alkylation of isatin have been published [3a],
[12a][18], however, using NaH in refluxing DMF gave more satisfactory results
[12a][18a]. Then, the obtained N-alkylisatins 8a – 8e were converted to the oxime
derivatives 9a – 9e by stirring with NH2OH · HCl in the presence of NaOH in EtOH at
room temperature for a day (Scheme). Firstly, the synthesis of isatin O-alkyloximes
7a – 7n was achieved by conventional heating in solution (Scheme, a)). Compounds
9a – 9e reacted with diverse alkyl halides by stirring in 5m KOH/DMSO 1:9 at room
temperature to afford 7a – 7n in moderate yields.

Helvetica Chimica Acta – Vol. 93 (2010)
2457
Since working with DMSO usually is not convenient, and often the extraction of
products from the reaction media is followed by tedious workup procedures, we
employed the microwave irradiation for the preparation of 7a – 7n from 9a – 9e under
solvent-free condition (Scheme, b)). With the aim of optimizing the reaction
conditions, we chose the reaction of N-allylisatin oxime 9a with ethyl 2-bromopropa-
noate under microwave irradiation as a model reaction. The effect of several organic
and inorganic bases, phase-transfer catalysts (PTCs), and irradiation power on the
reaction time and yield of 7j was examined. The results are summarized in Table 1. The
best result was obtained in the presence of K2CO3 (Entry 1), and hence it was the base
of choice for all reactions. Cs2CO3, NaH, and t-BuOK (Entries 2, 3, and 7) also
furnished good yields of 7j, while other bases gave only moderate yields.
Table 1. Effect of Bases, PTCs, and Irradiation Power on the Conversion of N-Allylisatin Oxime 9a into
O-Alkyloxime Ether 7j
Entry
Base
PTC
Irradiation power [Watt]
Time [s]
Yield [%]a)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
K2CO3
Cs2CO3
NaH
CaO
Et3N
–
–
–
–
–
–
–
–
100
100
100
100
100
100
100
100
100
100
100
100
100
100
200
300
400
500
5
5
5
10
10
15
15
15
15
5
5
7
7
15
5
93
82
75
60
64
70
78
69
65
82
93
71
68
60
90
75
75
62
MgO
t-BuOK
DABCOb)
DMAPc)
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
–
Bu4NI
Bu4NBr
Bu4NCl
Bu4NF
Bu4N(HSO4)
–
–
–
–
4
4
4
a) Yield of isolated product. b) 1,4-Diazabicyclo[2.2.2]octane. c) N,N-Dimethylpyridin-4-amine.
We also investigated the role of several tetrabutylammonium salts as phase-transfer
catalysts (PTC) in the model reaction (Table 1). In the presence of PTCs (Table 1,

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Helvetica Chimica Acta – Vol. 93 (2010)
Entries 10 – 14), no distinguishable effect on the reaction was observed, and therefore,
their addition is not necessary. We also studied the effect of microwave power on the
progress of the model reaction (Table 1). The best results were achieved when a power
of 100 or 200 Watt was used. Increment in radiation power did not enhance the yield of
product.
To evaluate the general applicability of this method, the optimized conditions were
applied to synthesize the N-alkylisatin O-alkyloximes 7a – 7n (Scheme). Comparing the
results from the microwave-assisted with those of the solution procedure (Table 2)
revealed that the microwave-assisted reactions (Method b)) proceeded more effi-
ciently, and the desired isatin O-alkyloximes were obtained in good to excellent yields
and after a short reaction time1).
Table 2. Comparison by the Solution (Method a)), Microwave-Assisted (Method b)), and Microwave-
Assisted Three-Component Procedure (Method c)) the Synthesis of Isatin O-Alkyloximes 7a – 7n1)
Method a)
Method b)
Method c)
yield [%]a)
time [h]
yield [%]a)
time [min]
yield [%]a)
time [min]
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
45
58
51
53
48
59
60
60
60
65
62
58
54
51
3
3
4
3
3
4
5
4
3
5
3
3
3
5
70
82
75
78
72
90
87
80
79
93
80
78
75
70
2
3
10
0.5
6
1
6
5
5
0.08
5
6
4
0.5
64
75
62
68
65
77
72
74
70
83
72
69
67
65
8
5
10
4
7
6
8
7
8
3
7
8
5
2
a) Yield of isolated product.
Although the microwave-assisted method is very useful for the preparation of the
O-alkyloximes 7a – 7n from 9a – 9e, the problem usually associated with the oxime
synthesis still remains since accessing pure oximes 9 usually requires the reiteration of
recrystallization which is cumbersome, time-wasting, and eventually leads to a decrease
in the overall yield. Hence, the synchronous oximation of N-alkylisatins and O-
alkylation of in situ generated N-alkylisatin oximes with alkyl halides would be a
1
)
For R and R’, see Scheme.

Helvetica Chimica Acta – Vol. 93 (2010)
2459
suitable and efficient strategy. As there is no report that has exemplified this plan, we
employed this novel method for the synthesis of isatin O-alkyloximes as illustrated in
the Scheme, Method c). So, the synthesis of isatin oxime ethers 7a – 7n was achieved via
a three-component reaction of 8a – 8e, NH2OH · HCl, and alkyl halides in the presence
of K2CO3 and Bu4NBr under microwave-assisted solvent-free conditions.
The first step for the three-component one-pot synthetic approach involved
optimization of the reaction conditions. The choice of the base is of great importance
for the in situ generation of isatin oximes and, therefore, the effect of various organic
and inorganic bases, as well as of different PTCs and irradiation powers on the reaction
of 8a, NH2OH · HCl, and BuBr in the presence of Bu4NBr was studied (Table 3).
According to the results, K2CO3 (Table 3, Entry 1) was the most appropriate base.
Moderate yields of O-alkyloxime 7b were obtained in the presence of Cs2CO3 and t-
BuOK (Entries 2 and 7).
Table 3. The Effect of Bases, PTCs, and Irradiation Power on the Three-Component One-Pot Reaction of
N-Allylisatin 8a into O-Alkyloxime 7b
Entry
Base
PTC
Irradiation power [Watt]
Time [min]
Yield [%]a)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
17
K2CO3
Cs2CO3
NaH
CaO
Et3N
Bu4NBr
Bu4NBr
Bu4NBr
Bu4NBr
Bu4NBr
Bu4NBr
Bu4NBr
Bu4NBr
Bu4NBr
–
Bu4NI
Bu4NCl
Bu4NF
Bu4N(HSO4)
Bu4NBr
Bu4NBr
Bu4NBr
Bu4NBr
300
300
300
300
300
300
300
300
300
300
300
300
300
300
100
200
400
500
5
5
5
75
65
40
37
32
25
67
22
27
n.r.d)
60
60
45
43
35
42
56
40
10
15
10
10
17
17
40
8
MgO
t-BuOK
DABCOb)
DMAPc)
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
8
10
10
25
20
4
4
a) Yield of isolated product. b) 1,4-Diazabicyclo[2.2.2]octane. c) N,N-Dimethylpyridin-4-amine. d) No
reaction.

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Helvetica Chimica Acta – Vol. 93 (2010)
In the absence of PTC, no reaction of the three components was achieved, even
after prolonging the reaction time or enhancing the microwave power, and Bu4NBr
(Table 3, Entry 1) proved to be most efficient, while Bu4NI and Bu4NCl gave moderate
yields of 7b. Lower yields of 7b were obtained when Bu4NF and Bu4N(HSO4) were
used as PTC. The optimal result was attained when 50 mol-% of Bu4NBr were used.
Two roles of Bu4NBr can be considered: i) the molten Bu4NBr (m.p. 102 – 1038) creates
a homogeneous reaction media, and it is assumed to behave as an ionic liquid; ii)
Bu4NBr absorbs the microwave irradiation and increases the temperature of the
reaction media.
We also evaluated the effect of microwave power in the range 100 – 500 W on the
progress of the model reaction (Table 3). The best result was obtained when irradiation
at 300 W was used. Low yields of 7b were obtained at 100 and 200 W; moreover,
irradiation power > 300 W had no distinguishable effect on the progress of the reaction.
The generality and versatility of the three-component one-pot method was
demonstrated by its extension to various structurally diverse alkyl halides, including
primary, secondary, and allylic as well as alicyclic halides (Scheme, Table 2). While
Methods a) and b) required total times of > 1 d for accessing 7a – 7n, only a few
minutes (2 – 10 min) were necessary with Method c).
MCRs can use domino reactions with inseparable intermediates or sequential
reactions with separable intermediates [19]. In our synthetic methodology, the first step
involved the reaction of N-alkylisatin with NH2OH to afford N-alkylisatin oxime as
main intermediate. The oxime anion then attacks the alkyl halides to provide N-
alkylisatin O-alkyloximes. The in situ generation of the N-alkylisatin oximes was
established by TLC comparison of in situ generated N-alkylisatin oximes with the
authentic samples 9a – 9e. Moreover, the intermediate oxime was also isolated at an
early stage of the reaction and characterized by 1H- and 13C-NMR and IR spectroscopy.
Oximes are known to be ambident nucleophiles [20]. The alkylation of an oxime
can be achieved either at the O-atom to afford O-alkyloximes or at the N-atom to
generate nitrones [3a][12a][21]. It is known that various factors can influence the site
of alkylation of oximes [21][22]. However, with the presented method, mainly O-
alkyloximes were obtained, and no nitrones were detected, not even in trace amounts.
All compounds were fully characterized, and their structures were confirmed by
1
elemental analysis, H- and 13C-NMR, and IR spectroscopy. Compounds 7a – 7n were
expected to be formed as two geometrical isomers ((E)- or (Z)-isomer); however, (Z)-
1
isomers were obtained predominantly as their structure was identified in the H- and
13C-NMR spectra by comparing the corresponding chemical-shift values. Indeed, the
amide C(2)¼O of isatin can deshield the nearby atoms in the (Z)-isomer. The minor
(E)-isomer was detected in trace amounts (< 5%). To rationalize the dominant
formation of (Z)-isomers rather than (E)-isomers, PM3 semi-empirical quantum-
mechanic calculations were performed with MOPAC in CS Chem 3D Ultra 8
(Cambridge Soft, 2004) or Hyperchem (Hypercube Inc., Version 7). The results are
summarized in Table 4. The calculated DE for all O-alkyloximes 7a – 7n has a negative
value. There is conformity of the experimental observations and calculated data
(Table 4) establishing the higher stability of the (Z)-isomers and hence predominant
formation of (Z)-products. The biological studies of 7a – 7n are currently under
investigation and will be reported in due course.

Helvetica Chimica Acta – Vol. 93 (2010)
2461
Table 4. Heat of Formation of Isatin O-Alkyloximes 7a – 7n Calculated with PM3
EEa) [kcal/mol]
EZb) [kcal/mol]
DEc) [kcal/mol]
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
28.36148
17.06473
16.22828
53.27466
26.57922
ꢀ 9.74525
4.70148
ꢀ 17.36600
30.70157
ꢀ 50.60039
5.54907
22.31933
11.68065
15.71943
48.32347
22.60886
ꢀ 13.60926
ꢀ 9.03000
ꢀ 23.24679
27.85983
ꢀ 60.19243
ꢀ 2.15372
ꢀ 2.70314
ꢀ 83.29056
ꢀ 87.44306
ꢀ 6.04215
ꢀ 5.38408
ꢀ 0.50885
ꢀ 4.95119
ꢀ 3.97036
ꢀ 3.86401
ꢀ 13.73148
ꢀ 5.88079
ꢀ 2.84174
ꢀ 9.59204
ꢀ 7.70279
ꢀ 11.14231
ꢀ 7.95071
ꢀ 3.43144
8.43917
ꢀ 75.33985
ꢀ 84.01162
a) Heat of formation of the (E)-isomer. b) Heat of formation of the (Z)-isomer. c) DE ¼ EZ ꢀ EE.
In conclusion, a facile and highly efficient synthetic methodology is described for a
three-component one-pot synthesis of novel N-alkylisatin O-alkyloximes 7a – 7n by O-
alkylation of in situ generated N-alkylisatin oximes with alkyl halides under micro-
wave-assisted solvent-free conditions. The selectivity of the reaction, conformity with
environmentally benign chemistry, simple experimental procedure, mild reaction
conditions and relatively high product yield are the advantages of this method. Finally,
to rationalize the experimental evidences, the quantum-mechanical studies confirmed
the considerable preference for (Z)-O-alkyloxime formation.
We thank the Shiraz University of Technology and the Shiraz University Research Councils for partial
support of this work. We are also grateful to Mr. H. Sajedian Fard for recording NMR spectra.
Experimental Part
1. General. All chemicals were obtained from Fluka or Merck. Solvents were purified and dried by
standard procedures, and stored over 3-ꢂ molecular sieves. Microwave oven: MB-245 domestic
microwave oven from Butan Industrial Co. TLC: SILG/UV 254 silica-gel plates. Column chromatography
(CC): silica gel 60 (SiO2; 0.063 – 0.200 mm, 70 – 230 mesh; ASTM). Melting points (M.p.): Bꢀchi-510
apparatus; in open capillaries; uncorrected. IR Spectra: Shimadzu-FT-IR-8300 spectrophotometer; in
cmꢀ1. 1H- and 13C-NMR Spectra: Bruker-Avance-DPX-250 spectrometer; at 250 and 62.5 MHz, resp., d
in ppm, J in Hz. Elemental analyses (CHNS): Perkin-Elmer-240-B micro-analyzer.
2. N-Alkylisatins 8a – 8e: General Procedure. A mixture of isatin (1.47 g, 0.01 mol), appropriate alkyl
halide (0.012 mol), NaH (60% in paraffin wax, 0.4 g, 0.01 mol), and a cat. amounts of Bu4NBr (0.1 g) was
dissolved in dry DMF (30 ml) and then, heated to reflux for 10 h (TLC control). The solvent was
evaporated, the residue dissolved in CHCl3 (150 ml), and the soln. washed with H2O (2 ꢁ 100 ml), dried
(10 g of Na2SO4), and concentrated to afford the crude product which was purified by CC (SiO2).
3. N-Alkylisatin Oximes 9a – 9e: General Procedure. A mixture of the appropriate N-alkylisatin 8a –
8e (0.01 mol), NH2OH · HCl (1.03 g, 0.015 mol), NaOH (0.6 g, 0.015 mol), and H2O (minimum amount
to dissolve NH2OH · HCl and NaOH) was dissolved in EtOH (20 ml), and then the soln. was stirred for
24 h at r.t. Afterwards, the mixture was poured into 20 g of ice/10 g of H2O. The oxime precipitate formed

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Helvetica Chimica Acta – Vol. 93 (2010)
immediately, which was filtered, washed with cold H2O, and dried. Recrystallization from hot MeOH/
H2O afforded pure oximes 9a – 9e which were used for the next step.
4. General Procedure for the Synthesis of N-Alkylisatin O-Alkyloximes 7a – 7n, Method a). An
appropriate alkyl halide (0.013 mol) was added portionwise to a soln. of the appropriate oxime 9a – 9e
(0.01 mol), KOH (0.56 g, 0.01 mol), and H2O (2 ml) in DMSO (20 ml). The mixture was stirred for 3 –
5 h at r.t. (TLC control). Then, the crude product was dissolved in CHCl3 (150 ml), the soln. washed with
H2O (3 ꢁ 200 ml), dried (10 g of Na2SO4), and concentrated to afford the crude product which was
purified by CC (SiO2, AcOEt/hexane 1:5).
Method b). To the appropriate N-alkylisatin oxime 9a – 9e (5 mmol) in a mortar was added K2CO3
(0.69 g, 5 mmol), and the mixture was crushed vigorously to give a homogeneous mass. The mixture was
transferred to a test tube, and then an alkyl halide (6 mmol) was added and mixed with a tiny spatula. The
mixture was then irradiated in the microwave oven at 100 W for several time intervals (5 s). The
irradiation was continued until TLC monitoring indicated no further improvement in the reaction
(Table 2). The crude product was suspended in CHCl3 (100 ml) and washed with H2O (2 ꢁ 100 ml), the
org. layer dried (10 g of Na2SO4) and concentrated, and the crude product purified by CC (SiO2, AcOEt/
hexane 1:5).
Method c). To the appropriate N-alkylisatin 8a – 8e (5 mmol) in a mortar was added a mixture of
K2CO3 (0.69 g, 5 mmol), NH2OH · HCl (0.68g, 10 mmol), and Bu4NBr (2.5 mmol). The mixture was
crushed vigorously to give a homogeneous mass, which was transferred to a test tube, and then an alkyl
halide (6 mmol) was added and mixed with a tiny spatula. The mixture was then irradiated in the
microwave oven at 300 W for several time intervals (1 min). The irradiation was continued until TLC
monitoring indicated no further improvement in the reaction (Table 2). The crude product was
suspended in CHCl3 (100 ml) and washed with H2O (2 ꢁ 100 ml), the org. layer dried (10 g of Na2SO4)
and concentrated, and the crude product purified by CC (SiO2, AcOEt/hexane 1:5).
1-(Prop-2-en-1-yl)-1H-indole-2,3-dione (8a). Purified by CC (SiO2, AcOEt/hexane 1:8). Yield
2.70 g (72%). Red crystals. Rf (AcOEt/hexane 1:8) 0.65. M.p. 172 – 1738. IR (KBr): 3100m, 2964m,
1
2828m, 1715s, 1689s, 1489m. H-NMR (CDCl3): 8.63 – 6.87 (m, 4 arom. H); 5.76 – 5.92 (m, ¼CH); 5.35
(dd, J ¼ 1.8, 5.4, ¼CH2); 4.37 (dd, J ¼ 1.3, 4.0, CH2N). 13C-NMR (CDCl3): 42.00; 110.88; 116.88; 118.63;
123.79; 125.37; 130.31; 138.02; 138.12; 160.31; 180.81. Anal. calc. for C11H9NO2 (187.19): C 70.58, H 4.85,
N 7.48; found: C 70.45, H 4.70, N 7.35.
1-Ethyl-1H-indole-2,3-dione (8b). Purified by CC (SiO2, AcOEt/hexane 1:5). Yield 2.40 g (68%).
Yellow-orange crystals. Rf (AcOEt/hexane 1:5) 0.72. M.p. 162 – 1638. IR (KBr): 3050m, 2945m, 2855m,
1720s, 1689s, 1453m. 1H-NMR (CDCl3): 7.60 – 6.47 (m, 4 arom. H); 3.52 (q, J ¼ 5.0, CH2N); 1.01 (t, J ¼
5.0, Me). 13C-NMR (CDCl3): 12.46; 34.89; 110.11; 117.47; 123.59; 125.29; 138.44; 150.59; 157.80; 183.68.
Anal. calc. for C10H9NO2 (175.18): C 68.56, H 5.18, N 8.00; found: C 68.65, H 5.23, N 7.91.
1-(2-Phenoxyethyl)-1H-indole-2,3-dione (8c). Purified by CC (SiO2, AcOEt/hexane 1:3). Yield
2.90 g (54%). Yellow crystals. Rf (AcOEt/hexane 1:3) 0.58. M.p. > 2508 (dec.). IR (KBr): 3096m,
2925m, 2834m, 1735s, 1689s, 1459m. 1H-NMR (CDCl3): 8.11 – 6.68 (complex, 9 arom. H); 4.11 (t, J ¼ 5.0,
CH2O); 3.96 (t, J ¼ 5.0, CH2N). 13C-NMR (CDCl3): 40.12; 69.09; 111.23; 114.30; 114.53; 117.50; 121.38;
123.78; 125.18; 129.56; 138.33; 151.39; 158.48; 183.18. Anal. calc. for C16H13NO3 (267.28): C 71.90, H 4.90,
N 5.24; found: C 71.83, H 4.75, N 5.10.
Ethyl 2,3-Dihydro-a-methyl-2,3-dioxo-1H-indole-1-acetate (8d). Purified by CC (SiO2, AcOEt/
hexane 1:8). Yield 3.50 g (71%). Yellow crystals. Rf (AcOEt/hexane 1:8) 0.69. M.p. 222 – 2238. IR
(KBr): 3096m, 2822m, 2848m, 1753s, 1732s, 1669s, 1382s, 1062m. 1H-NMR (CDCl3): 7.76 – 6.53 (m, 4
arom. H); 4.84 (q, J ¼ 7.3, MeCHN); 3.93 (q, J ¼ 4.5, MeCH2O); 1.40 (d, J ¼ 7.3, MeCHN); 0.90 (t, J ¼
4.5, MeCH2O). 13C-NMR (CDCl3): 13.99; 14.19; 49.18; 62.04; 111.42; 117.77; 123.81; 125.44; 138.25;
149.44; 157.63; 169.30; 182.66. Anal. calc. for C13H13NO4 (247.25): C 63.15, H 5.30, N 5.67; found: C 63.10,
H 5.22, N 5.56.
1-Cyclopentyl-1H-indole-2,3-dione (8e). Purified by CC (SiO2, AcOEt/hexane 1:8). Yield 3.30 g
(76%). Yellow crystals. Rf (AcOEt/hexane 1:8) 0.69. M.p. 207 – 2088. IR (KBr): 3047m, 2954m, 1720s,
1665s, 1467m. 1H-NMR (CDCl3): 7.85 – 6.61 (m, 4 arom. H); 4.71 – 4.58 (m, NCH); 2.07 – 1.92 (m,
CH2CHCH2); 1.72 – 1.67 (m, CHCH2CH2CH2). 13C-NMR (CDCl3): 24.90; 27.73; 52.99; 111.35; 117.91;

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123.30; 125.43; 138.03; 150.41; 158.06; 183.76. Anal. calc. for C13H13NO2 (215.25): C 72.54, H 6.09, N 6.51;
found: C 72.40, H 5.95, N 6.41.
1-(Prop-2-en-1-yl)-1H-indole-2,3-dione 3-Oxime (9a). Recrystallized from MeOH/H2O. Yield 1.63 g
(80%). Yellow crystals. Rf (AcOEt/hexane 2 :1) 0.62. M.p. 211 – 2128. IR (KBr): 3216 (br.), 3050m,
1
2953m, 1715s, 1604s. H-NMR ((D6)DMSO): 10.26 (s, OH, exchangeable with D2O); 9.08 – 6.90 (m, 4
arom. H); 5.89 – 5.70 (m, ¼CH); 5.14 (dd, J ¼ 1.3, 8.3, ¼CH2); 4.01 (dd, J ¼ 1.4, 7.5, CH2N). 13C-NMR
((D6)DMSO): 41.18; 109.08; 115.56; 116.69; 122.33; 125.96; 130.87; 131.97; 142.05; 143.10; 163.31. Anal.
calc. for C11H10N2O2 (202.21): C 65.34, H 4.98, N 13.85; found: C 65.30, H 4.91, N 13.83.
1-Ethyl-1H-indole-2,3-dione 3-Oxime (9b). Recrystallized from MeOH/H2O. Yield: 1.45 g (76%).
Yellow crystals. Rf (AcOEt/hexane 2 :1) 0.62. M.p. 175 – 1768. IR (KBr): 3234 (br.), 3091m, 2988m,
1
2818m, 1726s, 1653s. H-NMR (CDCl3): 10.39 (s, OH, exchangeable with D2O); 8.40 – 6.77 (m, 4 arom.
H); 3.81 (q, J ¼ 7.0, CH2N); 1.25 (t, J ¼ 7.0, Me). 13C-NMR (CDCl3): 12.74; 34.70; 108.45; 115.79; 123.04;
128.15; 132.00; 143.08; 144.30; 164.14. Anal. calc. for C10H10N2O2 (190.2): C 63.15, H 5.30, N 14.73; found:
C 63.10, H 5.24, N 14.65.
1-(2-Phenoxyethyl)-1H-indole-2,3-dione 3-Oxime (9c). Recrystallized from MeOH/H2O. Yield
2.10 g (74%). Yellow crystals. Rf (AcOEt/hexane 2 :1) 0.66. M.p. 163 – 1648. IR (KBr): 3205 (br.), 3009m,
1
2812m, 1700s, 1646s. H-NMR ((D6)DMSO): 13.44 (s, OH, exchangeable with D2O); 8.51 – 6.54 (m, 9
arom. H); 4.17 (t, J ¼ 5.0, CH2O); 4.08 (t, J ¼ 5.0, CH2N). 13C-NMR ((D6)DMSO): 39.11; 64.87; 109.63;
114.31; 115.14; 120.77; 122.51; 126.71; 129.42; 131.85; 143.20; 157.98; 163.17; 164.31. Anal. calc. for
C16H14N2O3 (282.29): C 68.07, H 5.00, N 9.92; found: C 68.01, H 4.98, N 9.89.
Ethyl 2,3-Dihydro-3-(hydroxyimino)-a-methyl-2-oxo-1H-indole-1-acetate (9d). Recrystallized from
MeOH/H2O. Yield 2.12 g (80%). Yellow crystals. Rf (AcOEt/hexane 2 :1) 0.66. M.p. > 2508 (dec.). IR
(KBr): 3215 (br.), 2956m, 2854m, 1710s, 1680s, 1378s. 1H-NMR ((D6)DMSO): 10.83 (s, OH,
exchangeable with D2O); 7.81 – 6.34 (m, 4 arom. H); 4.80 (q, J ¼ 7.0, MeCHN); 4.56 (q, J ¼ 6.3,
MeCH2O); 1.19 (d, J ¼ 7.0, MeCHN); 1.05 (t, J ¼ 6.3, MeCH2O). 13C-NMR ((D6)DMSO): 15.50; 18.96;
39.25; 50.45; 110.90; 113.63; 115.58; 121.69; 125.70; 130.62; 142.36; 149.94; 163.83. Anal. calc. for
C13H14N2O4 (262.26): C 59.54, H 5.38, N 10.68; found: C 59.50, H 5.30, N 10.62.
1-Cyclopentyl-1H-indole-2,3-dione 3-Oxime (9e). Recrystallized from MeOH/H2O. Yield 1.83 g
(79%). Yellow crystals. Rf (AcOEt/hexane 2 :1) 0.68. M.p. > 2508 (dec.). IR (KBr): 3208 (br.), 3100m,
1
2865m, 1715s, 1674s. H-NMR ((D6)DMSO): 10.26 (s, OH, exchangeable with D2O); 8.38 – 6.93 (m, 4
arom. H); 4.62 – 4.22 (m, CHN); 1.43 – 1.25 (complex, 4 CH2). 13C-NMR ((D6)DMSO): 20.15; 20.28;
42.50; 108.99; 117.32; 120.99; 121.38; 125.95; 137.22; 145.61; 167.28. Anal. calc. for C13H14N2O2 (230.26): C
67.81, H 6.13, N 12.17; found: C 67.79, H 6.10, N 12.10.
(3Z)-1-(Prop-2-en-1-yl)-1H-indole-2,3-dione 3-(O-Ethyloxime) (7a). Purified by CC (SiO2, AcOEt/
hexane 1:5). Yield 0.73 g (64%). Orange oil. Rf (AcOEt/hexane 1:5) 0.66. IR (film): 3049m, 2875m,
1706s, 1670m, 1420m. 1H-NMR (CDCl3): 8.56 – 6.69 (m, 4 arom. H); 5.89 – 5.70 (m, ¼CH); 5.16 (dd, J ¼
1.3, 10.1, ¼CH2); 4.49 (q, J ¼ 3.5, CH2ON); 4.27 (dd, J ¼ 1.5, 4.25, CH2N); 1.44 (t, J ¼ 3.5, Me).
13C-NMR (CDCl3): 14.69; 42.08; 72.94; 108.50; 117.76; 122.95; 124.67; 130.93; 132.17; 140.10; 143.48;
159.95; 163.25. Anal. calc. for C13H14N2O2 (230.26): C 67.81, H 6.13, N 12.17; found: C 67.76, H 6.09, N
12.12.
(3Z)-1-(Prop-2-en-1-yl)-1H-indole-2,3-dione 3-(O-Butyloxime) (7b). Purified by CC (SiO2, AcOEt/
hexane 1:5). Yield 0.96 g (75%). Brown oil. Rf (AcOEt/hexane 1:5) 0.88. IR (film): 3006m, 2931m,
2790m, 1708s, 1699m, 1490m. 1H-NMR (CDCl3): 8.64 – 6.73 (m, 4 arom. H); 5.79 – 5.72 (m, ¼CH); 5.18
(dd, J ¼ 1.4, 10.3, ¼CH2); 4.72 (t, J ¼ 7.5, CH2ON); 4.38 (dd, J ¼ 1.5, 4.3, CH2N); 1.93 – 1.81 (m,
CH2CH2ON); 1.42 – 1.33 (m, MeCH2); 0.89 (t, J ¼ 7.3, Me). 13C-NMR (CDCl3): 13.64; 19.82; 30.51;
41.91; 62.70; 108.50; 117.71; 118.09; 120.74; 122.52; 123.03; 124.79; 131.13; 140.10; 160.10. Anal. calc. for
C15H18N2O2 (258.32): C 69.74, H 7.02, N 10.84; found: C 69.69, H 6.97, N 10.80.
(3Z)-1-(Prop-2-en-1-yl)-1H-indole-2,3-dione 3-(O-Cyclopentyloxime) (7c). Purified by CC (SiO2,
AcOEt/hexane 1:5). Yield 0.52 g (62%). Brown oil. Rf (AcOEt/hexane 1:5) 0.77. IR (film): 3100m,
2941m, 1704s, 1663m. 1H-NMR (CDCl3): 8.70 – 6.72 (m, 4 arom. H); 5.79 – 5.72 (m, ¼CH); 5.20 (dd, J ¼
1.2, 10.5, ¼CH2); 4.34 (dd, J ¼ 1.3, 4.5, CH2N); 3.50 – 3.24 (m, CHON); 2.08 – 1.83 (m, 4 CH2). 13C-NMR
(CDCl3): 25.93; 32.23; 42.28; 70.58; 108.40; 117.71; 118.43; 122.45; 123.00; 124.71; 131.04; 131.27; 139.91;
160.10. Anal. calc. for C16H18N2O2 (270.33): C 71.09, H 6.71, N 10.36; found: C 71.02, H 6.67, N 10.30.

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(3Z)-1-(Prop-2-en-1-yl)-1H-indole-2,3-dione 3-[O-(Prop-2-en-1-yl)oxime] (7d). Purified by CC
(SiO2, AcOEt/hexane 1:5). Yield 0.82 g (68%). Orange crystals. Rf (AcOEt/hexane 1:5) 0.58. M.p. 28 –
298. IR (KBr): 3003m, 2896m, 1703s, 1665m, 1436m. 1H-NMR (CDCl3): 7.90 – 6.71 (m, 4 arom. H); 6.25 –
5.95 (m, CH2¼CHCH2N); 5.82 – 5.66 (m, CH2¼CHCH2O); 5.37 (dd, J ¼ 1.5, 10.2, CH2¼CHCH2O);
5.26 (dd, J ¼ 1.3, 10.5, CH2¼CHCH2N); 4.92 (dd, J ¼ 1.3, 4.75, CH2¼CHCH2O); 4.30 (dd, J ¼ 1.75, 5.12,
CH2¼CHCH2N). 13C-NMR (CDCl3): 42.14; 78.00; 109.29; 115.72; 117.76; 119.03; 122.94; 127.92; 131.06;
132.40; 132.77; 143.61; 143.77; 163.16. Anal. calc. for C14H14N2O2 (242.27): C 69.41, H 5.82, N 11.56;
found: C 69.37, H 5.79, N 11.52.
(3Z)-1-(Prop-2-en-1-yl)-1H-indole-2,3-dione 3-[O-(2-Phenoxyethyl)oxime] (7e). Purified by CC
(SiO2, AcOEt/hexane 1:5). Yield 1.04 g (65%). Yellow-orange crystals. Rf (AcOEt/hexane 1:5) 0.64.
M.p. 49 – 508. IR (KBr): 3023m, 2836m, 1703s, 1656m, 1324s. 1H-NMR (CDCl3): 8.24 – 6.70 (m, 9 arom.
H); 5.81 – 5.66 (m, ¼CH); 5.26 (dd, J ¼ 1.5, 10.3, ¼CH2); 4.76 – 4.68 (m, PhOCH2CH2); 4.30 (dd, J ¼ 1.4,
5.3, CH2N). 13C-NMR (CDCl3): 42.19; 66.28; 75.41; 109.31; 114.53; 117.83; 120.98; 121.11; 123.06; 128.23;
129.43; 131.03; 131.33; 132.55; 143.72; 158.59; 163.14. Anal. calc. for C19H18N2O3 (322.36): C 70.79, H
5.63, N 8.69; found: C 70.70, H 5.59, N 8.65.
2-({[(3Z)-1,2-Dihydro-2-oxo-1-(prop-2-en-1-yl)-3H-indol-3-ylidene]amino}oxy)acetic Acid Benzyl
Ester (7f). Purified by CC (SiO2, AcOEt/hexane 1:5). Yield 1.34 g (77%). Yellow crystals. Rf (AcOEt/
hexane 1:5) 0.65. M.p. 105 – 1068. IR (KBr): 3045m, 2868m, 1733s, 1702s, 1656m, 1324s, 1034m. 1H-NMR
(CDCl3): 8.77 – 6.98 (m, 9 arom. H); 5.88 – 5.72 (m, ¼CH); 5.62 (s, PhCH2O); 5.20 (dd, J ¼ 1.3, 10.0,
¼CH2); 4.36 (dd, J ¼ 1.5, 4.8, CH2N); 4.03 (s, CH2ON). 13C-NMR (CDCl3): 41.96; 66.59; 72.87; 110.37;
115.22; 117.54; 123.32; 128.70; 128.87; 132.03; 133.79; 135.99; 140.84; 144.19; 160.00; 162.23; 165.85;
169.97. Anal. calc. for C20H18N2O4 (350.37): C 68.56, H 5.18, N 8.00; found: C 68.50, H 5.13, N 7.98.
(3Z)-1-(Prop-2-en-1-yl)-1H-indole-2,3-dione 3-{O-[2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)eth-
yl]oxime} (7g). Purified by CC (SiO2, AcOEt/hexane 1:5). Yield 1.35 g (72%). Yellow-orange crystals.
Rf (AcOEt/hexane 1:5) 0.44. M.p. 129 – 1308. IR (KBr): 3027m, 2812m, 1703s, 1679m, 1598m, 1024m.
1H-NMR (CDCl3): 8.27 – 6.64 (complex, 8 arom. H); 5.73 – 5.49 (m, CH2¼CHCH2N); 5.13 (dd, J ¼ 1.25,
8.12, CH2¼CHCH2N); 4.59 (t, J ¼ 5.0, ¼NOCH2CH2N); 4.16 (dd, J ¼ 1.8, 5.7, CH2¼CHCH2N); 4.02 (t,
J ¼ 5.0, ¼NOCH2CH2N). 13C-NMR (CDCl3): 37.28; 42.04; 73.09; 108.51; 115.45; 117.40; 123.30; 124.81;
128.15; 130.85; 131.45; 133.95; 140.16; 140.96; 144.33; 162.84; 167.61. Anal. calc. for C21H17N3O4 (375.38):
C 67.19, H 4.56, N 11.19; found: C 67.16, H 4.53, N 11.16.
(3Z)-1-(Prop-2-en-1-yl)-1H-indole-2,3-dione 3-{O-[4-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)bu-
tyl]oxime} (7h). Purified by CC (SiO2, AcOEt/hexane 1:5). Yield 1.48 g (74%). Yellow-orange crystals.
Rf (AcOEt/hexane 1:5) 0.52. M.p. 97 – 988. IR (KBr): 3025m, 2843m, 1702s, 1686m, 1601m, 1024m.
1H-NMR (CDCl3): 8.55 – 6.71 (m, 8 arom. H); 5.83 – 5.66 (m, CH2¼CHCH2N); 5.26 (dd, J ¼ 1.0, 8.7,
CH2¼CHCH2); 4.75 (t, J ¼ 7.0, ¼NOCH2CH2CH2CH2N); 4.39 (dd, J ¼ 1.7, 5.3, CH2¼CHCH2N); 3.66 (t,
J ¼ 7.0, ¼NOCH2CH2CH2CH2N); 2.00 – 1.89 (m, CH2); 1.79 – 1.69 (m, CH2). 13C-NMR (CDCl3): 25.59;
25.69; 37.29; 42.29; 61.90; 108.55; 109.26; 115.75; 117.76; 123.17; 124.82; 127.79; 131.09; 131.40; 132.02;
133.80; 140.17; 160.03; 168.26. Anal. calc. for C23H21N3O4 (403.43): C 68.47, H 5.25, N 10.42; found: C
68.45, H 5.21, N 10.40.
(3Z)-1-(Prop-2-en-1-yl)-1H-indole-2,3-dione 3-{O-[4-(Naphthalen-2-yloxy)butyl]oxime} (7i). Puri-
fied by CC (SiO2, AcOEt/hexane 1:5). Yield 1.40 g (70%). Yellow-orange oil. Rf (AcOEt/hexane 1:5)
1
0.55. IR (film): 3021m, 2941m, 1707s, 1601m, 1224m. H-NMR (CDCl3): 8.64 – 6.69 (complex, 11 arom.
H); 5.82 – 5.61 (m, CH2¼CHCH2N); 5.16 (dd, J ¼ 1.3, 8.9, CH2¼CHCH2N); 4.82 (t, J ¼ 7.0, ¼NOCH2-
CH2CH2CH2OAr); 4.28 (dd, J ¼ 1.3, 3.7, CH2¼CHCH2N); 4.01 (t, J ¼ 7.0, ¼NOCH2CH2CH2CH2OAr);
2.16 – 2.10 (m, CH2); 1.91 – 1.85 (m, CH2). 13C-NMR (CDCl3): 25.27; 26.32; 42.32; 62.36; 67.12; 106.61;
108.59; 117.80; 119.00; 120.84; 123.11; 123.53; 124.89; 126.23; 126.29; 127.62; 128.95; 129.33; 131.02;
131.19; 131.45; 134.55; 140.20; 159.85; 160.13. Anal. calc. for C25H24N2O3 (400.47): C 74.98, H 6.04, N 7.00;
found: C 74.92, H 6.01, N 6.96.
2-({[(3Z)-1,2-Dihydro-2-oxo-1-(prop-2-en-1-yl)-3H-indol-3-ylidene]amino}oxy)propanoic Acid
Ethyl Ester (7j). Purified by CC (SiO2, AcOEt/hexane 1:5). Yield 1.25 g (83%). Yellow crystals. Rf
(AcOEt/hexane 1:5) 0.48. M.p. 61 – 628. IR (KBr): 3021m, 2973m, 2935m, 1716s, 1702s, 1610m, 1475m,
1354s. 1H-NMR (CDCl3): 8.33 – 6.76 (m, 4 arom. H); 5.86 – 5.71 (m, CH2¼CHCH2N); 5.22 (dd, J ¼ 1.7,
8.2, CH2¼CHCH2N); 4.36 – 4.14 (m, CH2¼CHCH2N, MeCHON, MeCH2O); 1.67 (d, J ¼ 6.7, Me-

Helvetica Chimica Acta – Vol. 93 (2010)
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CHON); 1.18 (t, J ¼ 7.2, MeCH2O). 13C-NMR (CDCl3): 14.01; 14.77; 42.40; 62.20; 67.50; 108.72; 115.50;
117.92; 123.26; 125.23; 131.05; 131.82; 132.20; 143.81; 162.50; 171.20. Anal. calc. for C16H18N2O4 (302.33):
C 63.56, H 6.00, N 9.27; found: C 63.52, H 5.94, N 9.21.
(3Z)-1-Ethyl-1H-indole-2,3-dione 3-[O-(2-Phenoxyethyl)oxime] (7k). Purified by CC (SiO2 ,
AcOEt/hexane 1:5). Yield 1.11 g (72%). Yellow oil. Rf (AcOEt/hexane 1:5) 0.60. IR (film): 3089m,
2973m, 2835m, 1701s, 1625m. 1H-NMR (CDCl3): 8.01 – 6.81 (m, 9 arom. H); 4.26 (t, J ¼ 4.0,
PhOCH2CH2); 3.96 (t, J ¼ 4.0, PhOCH2CH2); 3.72 (q, J ¼ 7.0, MeCH2N); 1.17 (t, J ¼ 7.0, MeCH2N).
13C-NMR (CDCl3): 14.77; 42.40; 60.41; 68.06; 108.50; 113.52; 113.70; 120.08; 123.03; 124.79; 127.36;
128.50; 131.13; 134.10; 157.57; 160.10. Anal. calc. for C18H18N2O3 (310.35): C 69.66, H 5.85, N 9.03; found:
C 69.61, H 5.82, N 9.00.
(3Z)-1-(2-Phenoxyethyl)-1H-indole-2,3-dione 3-[O-(2-Phenoxyethyl)oxime] (7l). Purified by CC
(SiO2, AcOEt/hexane 1:5). Yield 1.38 g (69%). Yellow oil. Rf (AcOEt/hexane 1:5) 0.56. IR (film):
3050m, 2920m, 2835m, 1702s, 1675m. 1H-NMR (CDCl3): 8.21 – 6.72 (complex, 14 arom. H); 4.74 (t, J ¼
4.5, PhOCH2CH2O); 4.28 (t, J ¼ 4.5, PhOCH2CH2N); 4.14 (t, J ¼ 4.5, PhOCH2CH2O); 4.06 (t, J ¼ 4.5,
PhOCH2CH2N). 13C-NMR (CDCl3): 39.81; 65.67; 66.27; 75.42; 109.51; 114.35; 114.72; 121.11; 121.20;
123.08; 124.56; 124.89; 128.15; 129.49; 129.63; 131.47; 132.50; 143.81; 144.62; 162.99. Anal. calc. for
C24H22N2O4 (402.44): C 71.63, H 5.51, N 6.96; found: C 71.59, H 5.48, N 6.92.
Ethyl (3Z)-2,3-Dihydro-a-methyl-2-oxo-3-[(2-phenoxyethoxy)imino]-1H-indole-1-acetate (7m). Pu-
rified by CC (SiO2, AcOEt/hexane 1:5). Yield 1.28 g (67%). Brown oil. Rf (AcOEt/hexane 1:5) 0.49. IR
(film): 3050m, 2973m, 2835m, 1740s, 1705s, 1671m, 1322s. 1H-NMR (CDCl3): 8.79 – 6.74 (m, 9 arom. H);
4.42 (q, J ¼ 4.0, MeCHN); 4.17 (q, J ¼ 7.0, MeCH2O); 3.96 (t, J ¼ 4.0, PhOCH2CH2); 3.85 (t, J ¼ 4.0,
PhOCH2CH2); 1.41 (d, J ¼ 4.0, MeCHN); 1.20 (t, J ¼ 7.0, MeCH2O). 13C-NMR (CDCl3): 14.12; 16.79;
51.27; 61.40; 63.42; 69.11; 111.40; 114.56; 114.65; 115.97; 117.66; 121.10; 121.23; 121.32; 129.54; 132.13;
133.03; 134.28; 158.62. Anal. calc. for C21H22N2O5 (382.41): C 65.96, H 5.80, N 7.33; found: C 65.92, H
5.79, N 7.30.
2-({[(3Z)-1-Cyclopentyl-1,2-dihydro-2-oxo-3H-indol-3-ylidene]amino}oxy)propanoic Acid Ethyl
Ester (7n). Purified by CC (SiO2, AcOEt/hexane 1:5). Yield 1.07 g (65%). Yellow oil. Rf (AcOEt/
hexane 1:5) 0.51. IR (film): 3050m, 2944m, 2841m, 1726s, 1700s, 1664m, 1326s. 1H-NMR (CDCl3): 8.04 –
6.86 (m, 4 arom. H); 5.08 (q, J ¼ 7.0, MeCHON); 4.61 (q, J ¼ 7.0, MeCH2O); 4.20 – 4.11 (m, CHN);
2.11 – 2.09 (m, CH2CHCH2); 1.76 – 1.58 (m, CHCH2CH2CH2); 1.39 (d, J ¼ 7.0, MeCHON); 1.23 (t, J ¼
7.0, MeCH2O). 13C-NMR (CDCl3): 13.90; 14.12; 24.32; 30.91; 43.88; 61.24; 80.01; 110.03; 114.69;
121.38; 122.56; 128.81; 129.55; 132.48; 134.28; 158.62. Anal. calc. for C18H22N2O4 (330.38): C 65.44, H
6.71, N 8.48; found: C 65.40, H 6.69, N, 8.45.
REFERENCES
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1996, 32, 249; c) J. F. M. da Silva, S. J. Garden, A. C. Pinto, J. Braz. Chem. Soc. 2001, 12, 273; d) W. C.
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Received March 14, 2010