Activation of the NC-H bond of Morita-Baylis-Hillman adducts of N-substituted isatins with cerium ammonium nitrate (CAN) and alcohol (ROH)

Article abstract of DOI:10.1139/V09-020

A study on the activation of the NC-H bond of Morita-Baylis-Hillman adducts of N-substituted isatin with cerium ammonium nitrate (CAN) and saturated and unsaturated alcohols have been carried out. The choice of a Morita-Baylis- Hillman adduct for this stu

Full text of DOI:10.1139/V09-020

591
Activation of the NC–H bond of Morita–Baylis–
Hillman adducts of N-substituted isatins with
cerium ammonium nitrate (CAN) and alcohol (ROH)
Ponnusamy Shanmugam and Vadivel Vaithiyanathan
Abstract: A study on the activation of the NC–H bond of Morita–Baylis–Hillman adducts of N-substituted isatin with cerium
ammonium nitrate (CAN) and saturated and unsaturated alcohols have been carried out. The choice of a Morita–Baylis–
Hillman adduct for this study is screened with a number of adducts. A comparative and reactivity pattern study on NC-H
activation of Morita–Baylis–Hillman adducts of N-substituted isatin derivatives viz. N-methyl, N-ethyl, N-methyl acetate,
N-benzyl, N-propargyl, and N-isopropyl isatins have been carried out. Effect of aryl ring substitution has also been inves-
tigated. A plausible mechanism for the formation of the ether products has been outlined.
Key words: cerium ammonium nitrate (CAN), Morita–Baylis–Hillman adduct, N-CH activation, functionalised ethers, ni-
tration.
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Resume : On a effectue une etude sur l’activation, par le nitrate d’ammonium cerique (NAC), de la liaison NC-H d’adduits
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Morita–Baylis–Hillman d’isatine N-substituee et d’alcools satures et non satures. Le choix de l’adduit Morita–Baylis–Hill-
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man pour cette etude est evalue avec un certain nombre d’adduits. On a aussi realise une etude comparative et une etude de
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patron de reactivite sur l’activation NC-H d’adduits Morita–Baylis–Hillman d’isatines N-substituees, entre autre par des grou-
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pes N-methyle, N-ethyle, N-methylacetate, N-benzyle, N-propargyle et N-isopropyle. On a aussi etudie l’effet de la substitu-
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tion sur les groupes aryles. On propose un mecanisme plausible pour la formation d’ethers comme produits.
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Mots-cles : NAC, adduit de Morita–Baylis–Hillman, activation NC-H, ethers fonctionnalises, nitration.
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[Traduit par la Redaction]
ROH (alcohol).27 In continuation of the work, a detailed
study on NC-H activation of various MBH derivatives of N-
substituted isatins with CAN as a one electron oxidant and
with a number of alcohols as reagents was carried out. The
details of this study are the subject matter of this paper.
Introduction
The C–H bond activation method is one of the challeng-
ing synthetic routes in organic synthesis.1–12 Activation of
C–H bonds particularly by oxidative processes1–5 and by or-
ganometallic reagents6–12 has been of great interest to or-
ganic chemists in recent years. Cerium(IV) ammonium
nitrate (CAN) has emerged as a versatile reagent for a num-
ber of synthetic transformations.13,14 The synthetic flexibility
of isatin and its derivatives has led to the extensive use of
this compound in synthetic organic chemistry.15 Recently,
the Morita–Baylis–Hillman (MBH) reaction has emerged as
an important carbon–carbon bond, forming reactions that, in
general, afford densely functionalized molecular frame
works and the reaction is considered as atom economic.16–19
As part of our ongoing research in the area of novel
synthetic methodologies based on MBH adducts,20–26 we
have reported the preliminary results on activation of the
NC–H bond of MBH adducts of N-methylisatin with CAN/
Results and discussion
Optimization of the NC-H activation and choice of MBH
adducts of isatin
The optimization studies were initiated using the MBH ad-
duct of N-methylisatin (1) as a model substrate. The prelimi-
nary study and results are shown in Table 1. Initially, adduct
1 was treated with 2 equiv. of CAN and excess methanol
(10 mL) to afford the NC-H activated product 2 in trace
amount (5%) (Table 1, entry 1). Repeating the reaction with
3 equiv. of CAN and MeOH (5 mL) for 12 h afforded 2 in a
slightly improved yield (10%, Table 1, entry 2). Fine-tuning
of the reaction conditions is shown in Table 1. Thus, the op-
timum condition was found as 4 equiv. of CAN and MeOH
(1.6 mL, 40 equiv.) and CH3CN (0.5 mL) and at room tem-
perature (RT) for 24 h (Table 1, entry 4).
Further, to examine the selectivity and structural require-
ments of N-methyl isatin derivatives for NC-H activation, we
chose different isatin derivatives (1, 4–9), as shown in Fig. 1.
Under the optimized condition, MBH adducts 1, 4, and 5
of N-methyl isatin afforded the ether products 2, 10, and 12
in 24%–66% yields and the nitrated compound 3, 11, and 13
in trace-30% yields, respectively (Table 2, entries 1–3). In-
Received 22 August 2008. Accepted 12 January 2009. Published
on the NRC Research Press Web site at canjchem.nrc.ca on
31 March 2009.
P. Shanmugam1,2 and V. Vaithiyanathan. Chemical Sciences
and Technology Division, National Institute for Interdisciplinary
Science and Technology, Trivandrum 695019, Kerala, India.
1Corresponding author (e-mail: shanmu196@rediffmail.com).
2Present address: Organic Chemistry Division, Central Leather
Research Institute (CLRI), Adyar, Chennai 600 020, India.
Can. J. Chem. 87: 591–599 (2009)
doi:10.1139/V09-020
Published by NRC Research Press

592
Can. J. Chem. Vol. 87, 2009
Table 2. NC-H activation reactions of isatin derivatives.
Table 1. Optimization of the NC-H activation of 1 with CAN/
MeOH.
Products
Yield (%)
Entry
Substrate Ether (A) Nitrates (B)
A
B
1
2
3
4
5
6
7
1
4
5
6
7
8
9
2
3
66
50
24
—
—
—
—
30
30
Trace
15
—
10
12
—
—
—
—
11
13
14
—
—
—
Yield (%)
—
—
MeOH
(mL)
CH3CN
(mL)
CAN
(equiv.) (h)
Time
Entry
2
3
1
2
3
4
10.0
5.0
3.0
1.6
—
—
3.0
0.5
2.0
3.0
4.0
4.0
12
12
24
24
5
—
—
35
30
Fig. 2. Choice of different sources of MBH adduct of isatin deriva-
tives for NC-H activation.
10
20
66
Fig. 1. A Choice of different isatin derivatives (1, 4–9) for C-H ac-
tivation.
Fig. 3. Choice of different MBH adducts having a methyl NC-H
source.
terestingly, the simple N-methyl isatin 6 yielded only the ni-
trated product 14 in 15% yields. Other N-methylisatin deriva-
tives such as the bromo-derived adduct (7), oxime derivative
of N-methyl isatin (8), and N-methyl-3-spirocyclopropyl-2-
indolone (9) did not yield any NC-H activated ether prod-
uct or nitrated product. The results of the preliminary in-
vestigation are summarized in Table 2. Hence, the study
showed that the MBH adduct of N-methyl isatin was the
most suitable substrate for NC-H activation reaction.
Excellent preliminary results on NC-H activation of MBH
adduct of N-methyl isatin prompted us to investigate a sys-
tematic activation study of various N-substituted MBH ad-
ducts of isatin derivatives. Thus, we chose various MBH
adducts with different N-alkyl substitutions such as methyl,
methylene, and methine, which in principle generate 1ꢀ, 2ꢀ,
and 3ꢀ radical cation intermediates during the NC-H activa-
tion process (Fig. 2).
actions afforded the NC-H activated ethers 10 and 16–23
along with nitrated products 3 and 11 in moderate yield
(Table 3, entries 1–9). Notably, the reaction of MBH adduct
1 with 2ꢀ- and 3ꢀ-alcohols (isopropanol and t-butanol) did
not yield any NC-H activated product and only the nitrated
product 3 was obtained in good yields (Table 3, entries 10
and 11). However, the reactions with allyl alcohol/CAN and
cinnamyl alcohol/CAN did not afford the NC-H activated
product. Only alcohol oxidation was observed during the
course of the reaction (Table 3, entries 12 and 13). All the
new compounds were characterized by spectroscopic (IR, 1H,
and 13C NMR) and HRMS data. The results are summar-
ized in Table 3.
NC-H activation study of primary methyl radical sources
To investigate the NC-H activation via primary radical
cation intermediates, MBH adducts 1, 3, 4, and 15 were
chosen (Fig. 3.) and the details are discussed in the follow-
ing section.
Effect of aryl ring substitution on NC-H activation of MBH
adducts 15 and 3
To circumvent nitration and to check the effect of substi-
tution at the aryl ring, we examined the activation study
with MBH adduct 15 with CAN and alcohols such as meth-
anol, ethanol, homopropargyl alcohol, and t-butanol. The re-
actions underwent smoothly at an enhanced rate (1.5–2 h)
and afforded the NC-H activated compounds (24–27) in
good yields (Table 3, entries 14–17). Investigation on the ef-
fect of substitution and to understand the reactivity pattern
NC-H activation of MBH adducts of N-methyl isatin 1 and 4
As discussed earlier, during the optimization study the
MBH adduct 1 with CAN/MeOH afforded the products 2
(ether) and 3 (nitrate). This observation prompted us to fur-
ther explore the study using adducts 1 and 4 with various
saturated and unsaturated 1ꢀ alcohols (R4OH)/CAN. The re-
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Shanmugam and Vaithiyanathan
Table 3. Results of NC-H activation study of primary methyl radical sources.
593
Products
Yield (%)
NC-H
activation (A)
Nitration
(B)
—
—
3
—
—
—
11
11
11
3
Entry
1
2
3
4
5
6
7
8
MBHA
1
1
1
1
1
1
4
4
4
1
1
1
1
Alcohol (R4)
EtOH
Time (h)
24
24
24
24
24
24
24
24
24
24
24
24
A
B
16
17
18
19
20
21
10
22
23
—
—
—
—
24
25
26
27
—
—
52
51
58
55
67
59
50
53
57
—
—
—
—
52
51
58
55
—
—
—
—
25
—
—
—
30
27
35
54
65
—
—
—
—
—
—
—
—
Propargyl
Homopropargyl
Ethane-1,2-diol
Propane-1,3-diol
Benzyl alcohol
MeOH
EtOH
9
Propargyl
Isopropanol
t-Butanol
Allyl alcohol
Cinnamyl
MeOH
EtOH
Homopropargyl
t-BuOH
10
11
12
13
14
15
16
17
18
19
3
—
—
—
—
—
—
—
—
24
15
15
15
15
3
2.0
2.0
1.0
1.5
48
EtOH
MeOH
3
48
of adducts due to electron withdrawing substitution, the re-
actions with 5-nitro substituted adduct 3 in methanol and
ethanol were tested (Table 3, entries 18 and 19). No NC-H
activation was found even after allowing the reaction to pro-
ceed for a longer period of time (48 h) and with an excess
of CAN (6 equiv.); only starting material was recovered
quantitatively.
Fig. 4. Choice of different MBH adducts having a methylene NC-H
source.
NC-H activation study of secondary methylene radical
sources
Scheme 1. Synthesis of MBH adducts 28–35.
To inspect and understand the NC-H activation reaction,
which proceeded through a secondary radical intermediate,
MBH adducts 28–35 were chosen (Fig. 4).
A general synthesis of MBH adducts 28–35 is shown in
Scheme 1. Accordingly, N-alkylation of isatin was carried
out with CaH2 and alkyl halide in DMF at 60 8C to afford
N-alkyl isatins in excellent yield. The MBH adducts forma-
tion of N-alkyl isatins with methyl acrylate and DABCO
(1,4-diazabicyclo[2.2.2]octane) in methanol afforded the de-
sired MBH adducts (28–35) in excellent yield.
and no NC-H activated product was observed (Table 4,
entry 1). Experiments with other alcohols such as ethanol,
propargyl alcohol, and propane-1,3-diol provided only ni-
trated compound 36 and no NC-H activated product was ob-
served in all the cases (Table 4, entries 2–4). The structure
of nitrated compound 36 was analyzed by spectroscopic
studies. The number of aromatic protons and chemical shifts
were the tool for detection of nitration. Accordingly, in the
aromatic region, a doublet at d 6.97 due to ortho coupling
(J = 8.6 Hz, 1H), meta coupled doublet at d 8.04 (J =
Activation study of MBH adducts 28 and 29 of N-ethyl
isatin
Activation reaction of adduct 28 with CAN/MeOH in
CH3CN for 24 h provided only the nitrated compound 36
Published by NRC Research Press

594
Can. J. Chem. Vol. 87, 2009
Table 4. Results of the NC-H activation study of secondary methylene radical sources.
Products
Yield (%)
NC-H
activation (A)
Nitration
(B)
3
Entry
1
2
3
4
5
6
7
8
MBHA
28
28
28
28
29
29
30
30
30
31
31
32
32
33
34
34
Alcohol (R4)
MeOH
Time (h)
24
24
24
24
48
48
24
24
24
24
24
24
24
24
24
24
A
—
—
—
B
—
—
—
—
37
38
39
40
41
42
43
—
—
44
—
—
45
56
49
45
55
—
—
—
—
—
—
—
—
—
—
—
—
—
EtOH
36
36
36
—
—
—
—
—
—
—
—
—
—
—
—
—
Propargyl alcohol
Propane-1,3-diol
MeOH
EtOH
MeOH
—
Trace
Trace
58
49
55
47
54
—
—
47
—
—
85
EtOH
9
Propargylol
Benzylol
Homopropargylol
MeOH
EtOH
MeOH
EtOH
MeOH
MeOH
10
11
12
13
14
15
16
17
35
2
2.3 Hz, 1H), and one doublet of doublet at d 8.31 (J = 8.6,
2.3 Hz, 1H) due to ortho and meta couplings appeared. The
alkyl and olefin region were similar to that of starting mate-
rial 28. To demonstrate and to check the effect of electron
donating substitution at the aryl ring on NC-H activation,
another adduct (29) was selected. Reactions in methanol
and ethanol were carried out (Table 4, entries 5 and 6). To
our surprise, we found only a trace of NC-H activated prod-
Activation study on MBH adduct of N-benzyl and
propargyl derivatives of isatin 32–35
Having surprising results obtained from adducts 30 and
31, we were interested in surveying the NC-H activation of
highly functionalized MBH adducts 32–33 and 34–35 of N-
benzyl and N-propargyl isatins, respectively. The desired ad-
ducts 32–33 and 34–35 were synthesized using standard pro-
cedure described earlier (Scheme 1).
The adduct 32 with CAN/methanol and CAN/ethanol
under optimized reaction conditions yielded neither NC-H
activated product nor nitrated derivative and the starting ma-
terial was recovered quantitatively (Table 4, entries 12 and
13). However, the 5-bromo MBH adduct 33 afforded the de-
sired NC-H activated product (44) in good yield (Table 4,
entry 14). In the case of adduct (34), the reaction mixture
became complex (TLC) with CAN/methanol and CAN/etha-
nol mixture and no NC-H activated and nitrated product was
obtained (Table 4, entries 15 and 16), while the adduct 35
provided an excellent yield of NC-H activated product 45 in
2 h (Table 4, entry 17).
1
uct formation (37, 38) as evidenced from its H NMR of
crude reaction mixture at regular intervals for 48 h.
Activation study of MBH adduct of N-methyl/ethyl acetate
isatin 30 and 31
Since, the compound 28 with electron releasing substitu-
tion at a to the NC-H bond did not yield any C-H activation
products, we considered checking electron withdrawing sub-
stitution at a to the NC-H bond for NC-H activation of MBH
adduct such as 30. In contrast to the substrates 28 and 29,
activation of adduct 30 with CAN/methanol under optimized
reaction condition provided a good yield of NC-H activated
product 39 (Table 4, entry 7). The presence of -OMe group
due to NC-H activation in the product 39 was confirmed
from its 1H NMR spectrum. Thus, the methoxy protons
were observed at d 3.63 as a singlet and the methine proton
was observed as a singlet at d 5.96. The reactions with etha-
nol and propargyl alcohol were also tested and the respective
NC-H activated products (40 and 41) were isolated in moder-
ate to good yields (Table 4, entries 8 and 9). Similarly, reac-
tions of adduct 31 with benzyl alcohol and homopropargyl
alcohol afforded the corresponding NC-H activated products
42 and 43, respectively (Table 4, entries 10 and 11).
NC-H activation study of tertiary methine radical source
N-isopropyl isatin (46)
For a comparative study on N-alkyl series of isatin deriv-
atives, we chose the MBH adduct of N-isopropyl isatin (46)
as substrate, which is believed to precede the NC-H activa-
tion via a tertiary radical intermediate (Fig. 5). Adduct 46
was prepared under standard procedure described earlier.
The NC-H activation of adduct 46 with CAN/MeOH,
under optimized condition did not yield any NC-H activated
product, instead only a moderate yield of nitrated product 47
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Shanmugam and Vaithiyanathan
595
Fig. 5. Choice of MBH adducts having methine NC-H source.
Fig. 6. Effect of substitution and magnitude of lone pair availability
on nitrogen.
Scheme 2. A plausible mechanism for ether formation.
Fig. 7. Selectivity reason for NC-H activation towards MBH ad-
ducts alone.
was obtained. Similarly, reactions with ethanol, propargyl
alcohol, and propane-1,3-diol furnished only nitrated com-
pound 47. The results are collected in Tables 2 and 3. The
structure of nitrated compound 47 was confirmed from its
proton NMR data. Thus, the aromatic protons in 47 showed
an ortho coupled doublet at d 7.10 (J = 8.7 Hz, 1H), a meta
coupled doublet at d 8.03 (J = 2.3 Hz, 1H), and ortho-meta
coupled doublet of doublet at d 8.28 (J = 2.3, 8.7 Hz, 1H).
The alkyl and olefin region were similar to that of starting
material 46.
with nitrogen lone pair, averts the reactivity of the adduct
3. A pictorial representation for substitution effect and mag-
nitude of nitrogen lone pair is shown in Fig. 6. The nitration
mechanism of the aromatic ring with CAN is well known in
the literature.31
The selectivity reason for NC-H activation towards MBH
adducts alone may be due to the conformation favoured by
H-bonding in the adduct structure, which brings more avail-
ability of lone pair on nitrogen atom and avoids resonance
with the adjacent carbonyl group. However, the highly pla-
nar structure in the compounds 6–9 allows the nitrogen lone
pair to be in resonance with the adjacent carbonyl group.
Hence, no NC-H activation happened with simple isatin de-
rivatives (Fig. 7).
A plausible mechanism of N-CH activation/nitration
A plausible mechanism for the formation of the ether
products is delineated in Scheme 2. In the first step, the
MBH adduct A is oxidized by CAN to form a radical cat-
ion28–30 B. Further oxidation of radical cation B and libera-
tion of H+ by CAN produce a cation intermediate C, which
is quenched by alcohol to afford the NC-H activated ether
product. The proposed mechanism is supported from the re-
sults obtained in the studies. It should be noted that for com-
parison among MBH adducts 1, 15, and 3, only adduct 15
underwent NC-H activation in 1.5–2.0 h whilst adduct 1
took 24 h for NC-H activation and adduct 3 did not provide
any NC-H activation product with a clear indication of di-
rect involvement of the nitrogen lone pair in the reaction
mechanism.
The reactivity nature of MBH adducts 28–35 and 46 to-
wards NC-H activation can be explained based on the effect
of bulky substitution, which reduces the availability of lone
pair on the nitrogen atom, which prevents the first step oxi-
dation and less approach possibility by bulky reagent Ce(IV)
towards nitrogen in adducts 28, 32, 34, and 46. The 5-bromo
substitution, which increases the electron density on nitro-
gen, is clearly found from the reactivity of adducts 29 (trace
of NC-H activation, 48 h), 33 (47% NC-H activation, 24 h),
and 35 (85% NC-H activation, 2 h). However, quite the op-
posite occurs; the nitro substituent, having direct resonance
Conclusion
In conclusion, we have carried out a novel study on NC-H
activation of various Morita–Baylis–Hillman adducts of N-
substituted isatin with a number of alcohols using CAN as a
single electron oxidizing agent. A plausible mechanism of
the reaction is proposed. It is noteworthy that the com-
pounds obtained here are highly functionalized and can be
used for further synthetic manipulations. Further studies us-
ing the reagent system for novel synthetic methods are in
progress in our laboratory.
Experimental
General consideration
Analytical thin layer chromatography was performed on
silica gel TLC plates. Purification by gravity column chro-
Published by NRC Research Press

596
Can. J. Chem. Vol. 87, 2009
matography was carried out using silica gel (100–200 mesh).
Mixture of ethyl acetate and hexane and pure ethyl acetate
were used as eluent as required. IR spectra were run on a
Nicolet (impact 400D FT-IR) spectrophotometer. NMR
spectra were obtained using chloroform-d as solvent on
Bruker DPX 300 MHz NMR spectrometer. Chemical shifts
are given in d scale with TMS as the internal reference.
HRMS were measured on the JMS 600 JEOL mass spec-
trometer. Yields refer to quantities obtained after chroma-
tography. Solvents used are reagent grade and were purified
before use according to the literature procedure.32
Methyl 2-(3-hydroxy-2-oxo-1-(prop-2-ynyl) indolin-3-
yl)acrylate (34)
Colourless waxy solid. Rf = 0.34 (25% EtOAc–Hexanes).
nmax(CH2Cl2, cm–1): 3425, 2131, 1718, 1611. 1H NMR
(CDCl3) dH: 2.28 (1H, t, J = 2.2 Hz), 3.59 (3H, s), 4.07
(1H, s), 4.51–4.58 (2H, m), 6.44 (1H, s), 6.57 (1H, s), 7.04–
7.09 (2H, m), 7.18 (1H, d, J = 6.48 Hz), 7.35 (1H, t, J =
7.6 Hz). 13C NMR (CDCl3) dC: 29.5, 52.1, 72.6, 76.1, 76.6,
109.6, 123.3, 123.9, 128.1, 129.2, 130.2, 138.9, 142.5,
164.9, 175.4. Anal. calcd. for C15H13NO4: 271.0845; found:
271.0841.
Methyl 2-(3-hydroxy-1-isopropyl-2-oxoindolin-3-yl)acrylate
(46)
General experimental procedure for alkylation of isatin
A mixture of isatin (1 mmol), alkyl bromide/iodide
(1.5 mmol), and calcium hydride (3 mmol) in DMF was
stirred at 60 8C for 1 h. After completion of the reaction
(monitored by TLC), the crude mixture was diluted with
water, neutralized with 2 N HCl and extracted using ethyl
acetate. The organic layer was separated, dried (Na2SO4),
and concentrated in vacuo. The crude product obtained was
purified by silica gel chromatography using EtOAc–hexane
(20:80) as eluent to afford the desired N-alkylisatin deriva-
tives.
Colourless waxy solid. Rf = 0.42 (25% EtOAc–Hexanes).
1
nmax (CH2Cl2, cm–1): 3353, 1699, 1611. H NMR (CDCl3)
dH: 1.52 (6H, d, J = 8.15 Hz), 3.55 (1H, br s), 3.61 (3H, s),
4.58 (1H, sept, J = 7.0 Hz), 6.42 (1H, s), 6.56 (1H, s), 7.02
(2H, d, J = 7.7 Hz), 7.17 (1H, d, J = 6.6 Hz), 7.30 (1H, t,
J = 6.8 Hz). 13C NMR (CDCl3) dC: 19.1 (2C), 43.3, 51.8,
75.8, 109.7, 122.3, 124.0, 127.6, 129.8 (2C), 139.3, 143.1,
164.8, 176.1. Anal. calcd. for C15H17NO4: 275.1158; found:
275.1152.
General experimental procedure for NC-H activation
A mixture of MBH adduct (1 mmol), 4 equiv. of cerium
ammonium nitrate (4 mmol), and 40 equiv. of ROH
(1.6 mL) in CH3CN (0.5 mL) was allowed to stir at RT for
2–48 h. The progress of reaction was monitored by TLC.
After completion of the reaction, the solvent was removed
under reduced pressure. The crude reaction mixture was ex-
tracted with dichloromethane and washed with water and
brine. The organic layer was separated, dried (Na2SO4), and
concentrated in vacuo. The crude mixture was purified by
silica gel column chromatography using gradient elution
with hexane and hexane and EtOAc to afford pure function-
alized ethers and aromatic nitrated products.
General procedure for the preparation of MBH adducts
A mixture of N-alkyl isatin (1 mmol), methyl acrylate
(1.5 mmol), and DABCO (0.02 mmol) in MeOH (5 mL)
was stirred at RT for 3–4 d. After completion of the reaction
(monitored by TLC), the reaction mixture was diluted with
ethyl acetate. The organic layer was washed successively
with 0.2 N HCl, water, and brine. The organic layer was
separated, dried (Na2SO4), and concentrated in vacuo. The
crude product obtained was purified by silica gel column
chromatography using EtOAc–hexane (20:80) as eluent to
afford the desired MBH adducts of N-alkyl isatin.
Spectral data of MBH adducts 28, 30, 34, and 46
Methyl 2-(1-ethyl-3-hydroxy-2-oxoindolin-3-yl)acrylate (28)
Colourless solid. Mp 148–150 8C. Rf = 0.48 (25%
EtOAc–Hexanes). nmax (CH2Cl2, cm–1): 3341, 1723, 1615.
1H NMR (CDCl3) dH: 1.32 (3H, t, J = 7.2 Hz), 2.45 (1H,
brs), 3.62 (3H, s), 3.74 (2H, q, J = 7.2 Hz), 6.41 (1H, s),
6.56 (1H, s), 6.88 (1H, d, J = 7.8 Hz), 7.05 (1H, t, J =
6.7 Hz), 7.19 (1H, d, J = 6.4 Hz), 7.32 (1H, t, J = 7.7 Hz).
13C NMR (CDCl3) dC: 12.4, 52.3, 64.5, 70.5, 110.4, 123.6,
124.1, 128.0, 129.1, 130.72, 139.2, 143.3, 165.3, 176.5.
Anal. calcd. for C14H15NO4: 261.1001; found: 261.1000.
Spectral data for NC-H activated compounds
Methyl 2-(3-hydroxy-1-(methoxy methyl)-2-oxoindolin-3-
yl)acrylate (2)
Waxy solid. Rf = 0.35 (20% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3386, 1716, 1085, 1063. H NMR (CDCl3)
dH: 2.57 (1H, bs), 3.41 (3H, s), 3.65 (3H, s), 5.13 (1H, d, J =
11.1 Hz), 5.17 (1H, d, J = 11.1 Hz), 6.42 (1H, s), 6.59 (1H,
s), 7.06–7.10 (2H, m), 7.20 (1H, d, J = 7.5 Hz), 7.32 (1H, t,
J = 7.5 Hz). 13C NMR (CDCl3) dC: 52.5, 53.2, 70.5, 76.6,
110.4, 123.7, 124.1, 127.8, 129.1, 130.6, 139.5, 143.3,
164.8, 176.9. Anal. calcd. for C14H15NO5: 277.0950; found:
277.0947.
Methyl 2-(1-methylene carbomethoxy-3-hydroxy-2-
oxoindolin-3-yl)acrylate (30)
Colourless waxy solid. Rf = 0.29 (25% EtOAc–Hexanes).
nmax (CH2Cl2, cm–1): 3350, 1716, 1615, 1087, 1063. 1H
NMR (CDCl3) dH: 3.64 (3H, s), 3.78 (3H, s), 4.41 (1H, brs),
4. 41 (1H, d, J = 17.6 Hz), 4.61 (1H, d, J = 17.6 Hz), 6.44
(1H, s), 6.59 (1H, s), 6.74 (1H, d, J = 7.8 Hz), 7.06 (1H, t, J
= 7.4 Hz), 7.06–7.34 (2H, m). 13C NMR (CDCl3) dC: 41.4,
52.1, 52.7, 76.0, 108.6, 123.4, 124.1, 128.3, 129.4, 130.3,
138.5, 142.9, 165.2, 168.2, 176.0. Anal calcd. for
C15H15NO6: 305.0899; found: 305.0896.
2-(3-Hydroxy-1-(methoxymethyl)-2-oxoindolin-3-
yl)acrylonitrile (10)
Waxy solid. Rf = 0.44 (20% EtOAc–Hexanes). nmax
(CH2Cl2, cm–1): 3376, 2209, 1726, 1614, 1087. H NMR
1
(CDCl3) dH: 3.36 (3H, s), 4.07 (1H, s), 5.10 (1H, d, J =
10.9 Hz), 5.19 (1H, d, J = 10.9 Hz), 6.21 (1H, s), 6.39 (1H, s),
7.12 (1H, d, J = 7.7 Hz), 7.17 (1H, t, J = 8.1 Hz), 7.41 (2H, d,
J = 7.5 Hz). 13C NMR (CDCl3) dC: 52.1, 70.7, 76.7, 110.8,
Published by NRC Research Press

Shanmugam and Vaithiyanathan
597
115.5, 123.2, 123.9, 124.8, 126.8, 128.1, 131.5, 142.5, 176.3.
Anal. calcd. for C13H12N2O3: 244.0848; found: 244.0836.
129.4, 130.5, 139.0, 143.1, 165.4, 177.2. Anal. calcd. for
C16H19NO6: 321.1212; found: 321.1205.
Methyl 2-(1-((benzyloxy)methyl)-3-hydroxy-2-oxoindolin-3-
yl)acrylate (21)
Methyl 2-(1-(ethoxymethyl)-3-hydroxy-2-oxoindolin-3-
yl)acrylate (16)
Waxy solid. Rf = 0.29 (20% EtOAc–Hexanes). nmax
Waxy solid. Rf = 0.43 (20% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3314, 1716, 1617, 1083, 1055. H NMR
1
(CH2Cl2, cm–1): 3382, 1716, 1089, 1053. H NMR (CDCl3)
(CDCl3) dH: 2.67 (1H, bs), 3.62 (3H, s), 4.36 (1H, d, J =
11.6 Hz), 4.72 (1H, d, J = 11.6 Hz), 5.24 (1H, d, J =
11.1 Hz), 5.32 (1H, d, J = 11.1 Hz), 6.47 (1H, s), 6.59 (1H,
s), 7.08–7.35 (9H, m). 13C NMR (CDCl3) dC: 52.1, 70.1,
70.7, 76.4, 110.3, 123.5, 123.8, 127.8 (2C), 128.2(2C),
128.3 (2C), 128.7, 130.5, 137.5, 138.9, 143.0, 165.0, 176.6.
Anal. calcd. for C20H19NO5: 353.1263; found: 353.1254.
dH: 1.20 (3H, t, J = 6.9 Hz), 2.67 (1H, bs), 3.65 (5H, m),
5.17 (1H, d, J = 11.1 Hz), 5.22 (1H, d, J = 11.1 Hz), 6.43
(1H, s), 6.58 (1H, s), 7.05–7.13 (2H, m), 7.20 (1H, d, J =
7.2 Hz), 7.35 (1H, t, J = 7.2 Hz). 13C NMR (CDCl3) dC:
15.1, 52.3, 64.6, 70.5, 76.6, 110.4, 123.6, 124.1, 128.0,
128.9, 130.6, 139.2, 143.2, 165.2, 176.9. Anal. calcd. for
C15H17NO5: 291.1107; found: 291.1088.
2-(1-(Ethoxymethyl)-3-hydroxy-2-oxoindolin-3-yl)
acrylonitrile (22)
Methyl 2-(3-hydroxy-2-oxo-1-((prop-2-ynyloxy)methyl)
indolin-3-yl)acrylate (17)
Waxy solid. Rf = 0.34 (20% EtOAc–Hexanes). nmax
(CH2Cl2, cm–1): 3378, 2917, 2185, 1732, 1613, 1487, 1097.
1H NMR (CDCl3) dH: 1.19 (3H, t, J = 7.2 Hz), 1.90 (1H,
bs), 3.57 (2H, q, J = 7.2 Hz), 5.15 (1H, d, J = 11.1 Hz),
5.25 (1H, d, J = 11.1 Hz), 6.21 (1H, s), 6.36 (1H, s), 7.14–
7.22 (2H, m), 7.40–7.45 (2H, m). 13C NMR (CDCl3) dC:
15.0, 64.8, 70.7, 76.8, 111.1, 115. 6, 123.3, 124.6, 124.9,
126.5, 128.6, 131.6, 142.0, 175.5. Anal. calcd. for
C14H14N2O3: 258.1004; found: 258.0992.
Waxy solid. Rf = 0.37 (20% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3390, 2210, 1716, 1615, 1087, 1064. H
NMR (CDCl3) dH: 2.48 (1H, t, J = 2.4 Hz), 2.67 (1H, bs),
3.63 (3H, s), 4.28 (2H, d, J = 2.4 Hz), 5.20 (1H, d, J =
11.2 Hz), 5.37 (1H, d, J = 11.2 Hz), 6.48 (1H, s), 6.59 (1H,
s), 7.05–7.20 (3H, m), 7.35 (1H, t, J = 7.6 Hz). 13C NMR
(CDCl3) dC: 30.5, 52.3, 56.3, 70.3, 75.5, 78.6, 110.7, 123.6,
124.2, 128.1, 129.1, 130.5, 139.3, 143.2, 165.3, 176.9. Anal.
calcd. for C16H15NO5: 301.0950; found: 301.0941.
2-(3-Hydroxy-2-oxo-1-[(prop-2-yloxy)methyl] indolin-3-
yl)acrylonitrile (23)
Methyl 2-(1-[(but-3-ynyloxy)methyl]-3-hydroxy-2-
oxoindolin-3-yl)acrylate (18)
Waxy solid. Rf 0.42 = (20% EtOAc–Hexanes). nmax
Waxy solid. Rf = 0.47 (20% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3390, 2305, 1733, 1614, 1073. H NMR
(CH2Cl2, cm–1): 3406, 1716, 1614, 1089, 1050. H NMR
1
(CDCl3) dH: 1.80 (1H, bs), 2.48 (1H, t, J = 2.4 Hz), 4.21
(2H, d, J = 2.4 Hz), 5.24 (1H, d, J = 11.1 Hz), 5.36 (1H, d,
J = 11.1 Hz), 6.21 (1H, s), 6.37 (1H, s), 7.10–7.29 (2H, m),
7.42 (2H, d, J = 7.5 Hz). 13C NMR (CDCl3) dC: 30.6, 56.4,
69.5, 75.8, 78.7, 110.9, 115.7, 123.1, 125.0, 126.9, 128.8,
131.6, 132.6, 141.9, 174.9. Anal. calcd. for C15H12N2O3:
268.0848; found: 268.0840.
(CDCl3) dH: 1.80 (1H, bs), 1.95 (1H, t, J = 2.4 Hz), 2.46
(2H, td, J = 6.6, 2.4 Hz), 3.63 (3H, s), 3.66 (2H, t, J =
6.6 Hz), 5.20 (1H, d, J = 11.1 Hz), 5.28 (1H, d, J =
11.1 Hz), 6.46 (1H, s), 6.59 (1H, s), 7.05–7.20 (3H, m),
7.35 (1H, t, J = 7.8 Hz). 13C NMR (CDCl3) dC: 19.8, 30.4,
52.3, 66.9, 69.5, 70.6, 81.3, 110.5, 123.7, 124.1, 126.2,
127.9, 130.7, 139.2, 143.1, 165.2, 176.9. Anal. calcd. for
C17H17NO5:315.1107; found: 315.1101.
Methyl 2-(5-bromo-3-hydroxy-1-(methoxymethyl)-2-
oxoindolin-3-yl)acrylate (24)
Methyl 2-(1-((2-hydroxyethoxy)methyl)-3-hydroxy-2-
oxoindolin-3-yl)acrylate (19)
Waxy solid. Rf = 0.47 (20% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3376, 1710, 1079, 1060. H NMR (CDCl3)
Waxy solid. Rf = 0.23 (20% EtOAc–Hexanes). nmax
dH: 3.40 (3H, s), 3.58 (1H, s), 3.65 (3H, s), 5.09 (1H, d, J =
11.0 Hz), 5.16 (1H, d, J = 11.0 Hz), 6.47 (1H, s), 6.62 (1H,
s), 6.97 (1H, d, J = 8.3 Hz), 7.30 (1H, d, J = 1.8 Hz), 7.46
(1H, dd, J = 8.3, 1.8 Hz). 13C NMR (CDCl3) dC: 52.5, 53.1,
70.6, 76.7, 111.8, 116.1, 126.8, 128.3, 130.8, 133.2, 138.6,
142.1, 164.7, 174.4. Anal. calcd. for C14H14BrNO5:
355.0055; found: 355.0051.
(CH2Cl2, cm–1): 3416, 1716, 1614, 1085, 1065. H NMR
1
(CDCl3) dH: 2.67 (2H, bs), 3.62 (3H, s), 3.69–3.75 (4H, m),
5.21 (1H, d, J = 11.1 Hz), 5.28 (1H, d, J = 11.1 Hz), 6.50
(1H, s), 6.60 (1H, s), 7.05–7.26 (3H, m), 7.34 (1H, t, J =
6.6 Hz). 13C NMR (CDCl3) dC: 52.4, 59.7, 66.1, 70.5, 76.3,
110.1, 123.5, 123.9, 128.3, 129.4, 130.6, 139.0, 143.2,
165.3, 175.6. Anal. calcd. for C15H17NO6: 307.1056; found:
307.1047.
Methyl 2-(5-bromo-1-(ethoxymethyl)-3-hydroxy-2-
oxoindolin-3-yl)acrylate (25)
Methyl 2-(1-[(3-hydroxypropoxy)methyl]-3-hydroxy-2-
oxoindolin-3-yl)acrylate (20)
Waxy solid. Rf = 0.45 (20% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3379, 1715, 1084, 1062. H NMR (CDCl3)
Waxy solid. Rf = 0.28 (20% EtOAc-Hexanes). nmax
dH: 1.19 (3H, t, J = 7.8 Hz), 1.89 (1H, bs), 3.45–3.63 (5H,
m), 5.13 (1H, d, J = 11.1 Hz), 5.19 (1H, d, J = 11.1 Hz),
6.47 (1H, s), 6.60 (1H, s), 7.00 (1H, d, J = 8.3 Hz), 7.28
(1H, d, J = 1.9 Hz), 7.46 (1H, dd, J = 8.3, 1.9 Hz). 13C
NMR (CDCl3) dC: 14.8, 52.1, 64.4, 70.4, 76.2, 111.8, 116.0,
127.1, 128.3, 130.8, 133.2, 138.6, 142.1, 164.7, 174.3. Anal.
calcd. for C15H16BrNO5: 369.0212; found: 369.0201.
1
(CH2Cl2, cm–1): 3418, 1716, 1613, 1086, 1055. H NMR
(CDCl3) dH: 1.73 (2H, quintet, J = 7.2 Hz), 3.11 (2H, bs),
3.48–3.80 (7H, m), 5.14 (1H, d, J = 11.4 Hz), 5.21 (1H, d,
J = 11.4 Hz), 6.55 (1H, s), 6.60 (1H, s), 7.03–7.16 (3H,
m),7.33 (1H, t, J = 7.5 Hz). 13C NMR (CDCl3) dC: 32.6,
52.4, 59.8, 66.2, 70.5, 76.3, 110.1, 123.6, 123.9, 128.4,
Published by NRC Research Press

598
Can. J. Chem. Vol. 87, 2009
1
Methyl 2-(5-bromo-1-((but-3-ynyloxy)methyl)-3-hydroxy-2-
oxoindolin-3-yl)acrylate (26)
(CH2Cl2, cm–1): 3396, 1717, 1084, 1065. H NMR (CDCl3)
dH: 1.19 (3H, t, J = 7.17 Hz), 3.51 (1H, s), 3.64 (3H, s), 4.24
(2H, q, J = 7.17 Hz), 4.72 (1H, d, J = 11.8 Hz), 4.91 (1H, d,
J = 11.8 Hz), 6.03 (1H, s), 6.44 (1H, s), 6.64 (1H, s), 7.01
(1H, t, J = 7.5 Hz), 7.18 (2H, t, J = 7.6 Hz), 7.27–7.39 (6H,
m). 13C NMR (CDCl3) dC: 14.4, 52.6, 62.9, 70.7, 76.5,
112.3, 114.6, 124.4, 128.7 (2C), 128.8 (2C), 129.3 (2C),
130.7 (2C), 136.7, 141.5, 165.6, 167.2, 177.8. Anal. calcd.
for C21H20NO5: 366.1341; found: 366.1326.
Waxy solid. Rf = 0.39 (20% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3390, 2210, 1716, 1085, 1063. H NMR
(CDCl3) dH: 1.94 (1H, t, J = 2.4 Hz), 2.46 (2H, td, J = 6.7,
2.4 Hz), 3.61–3.76 (5H, m), 5.18 (1H, d, J = 11.2 Hz), 5.18
(1H, d, J = 11.2 Hz), 5.25 (1H, d, J = 11.2 Hz), 6.48 (1H,
s), 6.62 (1H, s), 7.01 (1H, d, J = 8.3 Hz), 7.29 (1H, d, J =
1.7 Hz), 7.46 (1H, dd, J = 8.3, 1.7 Hz). 13C NMR (CDCl3)
dC: 19.3, 30.4, 52.5, 67.3, 69.5, 70.5, 81.1, 110.9, 116.2,
127.1, 128.3, 130.7, 133.2, 138.5, 143.0, 164.8, 176.3. Anal.
calcd. for C17H16BrNO5: 393.0212; found: 393.0203.
Methyl 2-(3-hydroxy-1-(methyl 2-(but-3-ynyloxy)acetate)-2-
oxoindolin-3-yl)acrylate (43)
Waxy solid. Rf = 0.46 (20% EtOAc–Hexanes). nmax
(CH2Cl2, cm–1): 3388, 2210, 1718, 1615, 1087, 1064. H
1
Methyl 2-(1-(t-butoxymethyl)-5-bromo-3-hydroxy-2-
oxoindolin-3-yl)acrylate (27)
NMR (CDCl3) dH: 1.24 (3H, t, J = 7.20 Hz), 1.90 (1H, t, J
= 2.5 Hz), 3.56 (1H, s), 3.63 (3H, s), 4.13–4.28 (4H, m),
6.01 (1H, s), 6.54 (1H, s), 6.62 (1H, s), 7.06–7.29 (4H, m).
13C NMR (CDCl3) dC: 13.9, 19.3, 31.6, 62.5, 66.9, 69.7,
76.0, 78.2, 80.2, 111.7, 123.6, 124.0, 128.1, 128.8, 130.3,
138.4, 140.9, 164.7, 165.9, 176.2. Anal. calcd. for
C18H18NO5: 328.1185; found: 328.1183.
Waxy solid. Rf = 0.47 (20% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3376, 1710, 1079, 1060. H NMR (CDCl3)
dH: 1.23 (9H, s), 3.58 (1H s), 3.65 (3H, s), 5.07 (1H, d, J =
10.8 Hz), 5.30 (1H, d, J = 10.8 Hz), 6.38 (1H, s), 6.58 (1H,
s), 7.02 (1H, d, J = 8.3 Hz), 7.29 (1H, d, J = 1.9 Hz), 7.46
(1H, dd, J = 8.3, 1.9 Hz). 13C NMR (CDCl3) dC: 28.4, 29.7,
65.3, 75.1, 76.3, 109.8, 114.3, 117.1, 121.5, 127.1, 128.3,
133.1, 138.4, 159.0, 164.9. Anal. calcd. for C17H20BrNO5:
397.0525; found: 397.0523.
Methyl 2-(5-bromo-3-hydroxy-1-(methoxy(phenyl) methyl)-
2-oxoindolin-3-yl)acrylate (44)
Waxy solid. Rf = 0.39 (20% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3382, 1717, 1085, 1057. H NMR (CDCl3)
Methyl 2-(3-hydroxy-1-(methyl 2-methoxyacetate)-2-
oxoindolin-3-yl)acrylate (39)
dH: 2.15 (1H, s), 3.45 (3H, s), 3.66 (3H, s), 6.48 (1H, s),
6.53 (1H, s), 6.58 (1H, s), 7.19–7.45 (8H, m). 13C NMR
(CDCl3) dC: 52.1, 53.4, 65.4, 76.4, 110.3, 123.5, 124.3,
127.8 (2C), 128.1 (2C), 128.2 (2C), 128.7, 131.3, 137.4,
139.0, 143.0, 164.5, 175.5. Anal. calcd. for C20H18BrNO5:
431.0368; found: 431.0357.
Waxy solid. Rf = 0.44 (20% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3420, 1718, 1606, 1051. H NMR (CDCl3)
dH: 1.90 (1H, bs), 3.59 (3H, s), 3.63 (3H, s), 3.79 (3H, s),
5.96 (1H, s), 6.55 (1H, s), 6.63 (1H, s), 7.04–7.10 (2H, m),
7.17–7.32 (2H, m). 13C NMR (CDCl3) dC: 46.9, 52.1, 56.9,
76.0, 79.7, 111.4, 123.6, 123.8, 128.1, 128.7, 130.5, 138.6,
140.8, 164.7, 166.9, 176.3. Anal. calcd. for C16H17NO7:
335.1005; found: 335.1001.
Methyl 2-(5-bromo-3-hydroxy-1-(1-methoxyprop-2-ynyl)-2-
oxoindolin-3-yl)acrylate (45)
Waxy solid. Rf = 0.48 (20% EtOAc–Hexanes). nmax
(CH2Cl2, cm–1): 3396, 2212, 1714, 1089, 1055. H NMR
1
Methyl 2-(3-hydroxy-1-(methyl 2-ethoxyacetate)-2-
oxoindolin-3-yl)acrylate (40)
(CDCl3) dH: 2.61 (1H, d, J = 2.1 Hz), 3.48 (3H, s), 3.61
(3H, s), 3.79 (1H, s), 6.12 (1H, d, J = 2.1 Hz), 6.38 (1H, s),
6.43(1H, s), 7.27 (1H, d, J = 8.3 Hz), 7.32 (1H, d, J =
1.9 Hz), 7.46 (1H, dd, J = 8.3, 1.9 Hz). 13C NMR (CDCl3)
dC: 52.3, 55.9, 56.4, 72.3, 75.1, 75.8, 114.1, 116.4, 126.9,
128.6, 130.9, 132.9, 138.3, 139.5, 164.5, 175.3. Anal. calcd.
for C16H14BrNO5: 379.0055; found: 379.0043.
Waxy solid. Rf = 0.42 (20% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3421, 1727, 1615, 1056. H NMR (CDCl3)
dH: 1.28 (3H, t, J = 7.2 Hz), 3.97 (1H, bs), 3.65 (3H, s), 3.79
(3H, s), 4.25 (2H, q, J = 7.2 Hz), 6.02 (1H, s), 6.44(1H, s),
6.59 (1H, s), 7.06–7.31 (4H, m). 13C NMR (CDCl3) dC: 14.8,
52.1, 53.7, 62.4, 76.0, 79.7, 110.6, 123.6, 123.8, 127.8,
128.7, 130.4, 137.9, 141.5, 165.5, 166.9, 176.2. Anal. calcd.
for C17H19NO7: 349.1162; found: 349.1155.
Spectral data for nitrated derivatives
Methyl 2-(1-ethyl-3-hydroxy-5-nitro-2-oxoindolin-3-
yl)acrylate (36)
Methyl 2-(3-hydroxy-1-(methyl 2-(prop-2-ynyloxy)acetate)-
2-oxoindolin-3-yl)acrylate (41)
Waxy solid. Rf = 0.48 (20% EtOAc–Hexanes). nmax
Waxy solid. Rf = 0.48 (25% EtOAc–Hexanes). nmax
(CH2Cl2, cm–1): 3294, 2120, 1712, 1610, 1051. H NMR
(CH2Cl2, cm–1): 3348, 1706, 1611. H NMR (CDCl3) dH:
1
1
(CDCl3) dH: 2.54 (1H, t, J = 2.4 Hz), 3.57 (1H, bs), 3.63
(3H, s), 3.81 (3H, s), 4.46 (2H, d, J = 2.4 Hz), 6.24 (1H, s),
6.57 (1H, s), 6.62 (1H, s), 7.07–7.13 (2H, m), 7.19–7.34
(2H, m). 13C NMR (CDCl3) dC: 22.3, 41.5, 52.2, 55.9, 62.7,
75.9, 77.9, 109.3, 111.5, 123.7, 124.1, 128.1, 130.3, 138.7,
140.8, 165.9, 176.1, 176.5. Anal. calcd. for C18H17NO7:
359.1005; found: 359.0996.
1.32 (3H, t, J = 7.23 Hz), 2.2 (1H, bs), 3.62 (3H, s), 3.77–3.9
(2H, m), 6.58 (1H, s), 6.67 (1H, s), 6.97 (1H, d, J = 8.6 Hz),
8.04 (1H, d, J = 2.3 Hz), 8.31 (1H, dd, J = 2.3 Hz, J = 8.6 Hz).
13C NMR (CDCl3) dC: 12.1, 43.6, 52.3, 76.1, 109.6, 120.32,
122.3, 123.1, 128.7, 129.9, 144.4, 144.7, 164.8, 176.1. Anal.
calcd. for C14H14N2O6: 306.0852; found: 306.0841.
Methyl 2-(3-hydroxy-1-isopropyl-5-nitro-2-oxoindolin-3-
yl)acrylate (47)
Methyl 2-(3-hydroxy-1-(methyl 2-(benzyloxy)acetate)-2-
oxoindolin-3-yl)acrylate (42)
Waxy solid. Rf = 0.43 (20% EtOAc–Hexanes). nmax
Waxy solid. Rf = 0.49 (25% EtOAc–Hexanes). nmax
1
(CH2Cl2, cm–1): 3351, 1709, 1612. H NMR (CDCl3) dH:
Published by NRC Research Press

Shanmugam and Vaithiyanathan
599
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ar030002z. PMID:14730991.
1.55 (6H, d, J = 8.1 Hz), 3.47 (1H, s), 3.63 (3H, s), 4.58–4.63
(1H, m), 6.56 (1H, s), 6.67 (1H, s), 7.1 (1H, d, J = 8.7 Hz),
8.03 (1H, d, J = 2.3 Hz), 8.28 (1H, dd, J = 2.3, J = 8.7 Hz).
13C NMR (CDCl3) dC: 19.1 (2C), 43.3, 51.8, 75.8, 109.7,
122.3, 124.0, 127.6, 129.8 (2C), 140.4, 143.2, 164.8, 176.1.
Anal. calcd. for C15H16N2O6: 320.1008; found: 320.1008.
Acknowledgements
(15) da Silva, J. F. M.; Garden, S. J.; Pinto, A. C. J. Braz. Chem.
The authors thank Professor T. K. Chandrashekar, Direc-
tor, for providing infrastructure facilities. Financial support
(SR/S1/OC-38/2005) from the Department of Science Tech-
nology (DST, New Delhi) is gratefully acknowledged. V.V.
thanks the Council of Scientific and Industrial Research
(CSIR, New Delhi) for the award of Senior Research Fellow-
ship (SRF). Thanks are due to Mrs. Viji and Mrs. Soumini
Mathew for providing HRMS and NMR data, respectively.
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