A multicomponent reaction as a versatile tool for the synthesis of spirooxindoles using N-alkylisatins; efficient catalysis by ZnO nanoparticles

Article abstract of DOI:10.3184/174751917X14815427219086

An efficient and green protocol for the synthesis of functionalised spirooxindole derivatives is described. This involves the reaction of in situ-generated keto-enaminones with N-alkylisatins in the presence of isothiocyanates.

Full text of DOI:10.3184/174751917X14815427219086

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 41 JANUARY, 7–11
RESEARCH PAPER 7
A multicomponent reaction as a versatile tool for the synthesis of
spirooxindoles using N-alkylisatins; efficient catalysis by ZnO nanoparticles
Ali Varasteh Moradi*
Department of Chemistry, Gorgan Branch, Islamic Azad University, Gorgan, Iran
An efficient and green protocol for the synthesis of functionalised spirooxindole derivatives is described. This involves the reaction of in
situ-generated keto-enaminones with N-alkylisatins in the presence of isothiocyanates.
Keywords: oxindole derivatives, 1,3-dicarbonyl compounds, three-component reaction, isothiocyanates, N-alkylisatin
Isatin is an endogenous compound identified in humans that
has a wide range of biological activities. Isatin has antiogenic,
sedative and anticonvulsant activities and acts as a potent
antagonist on atrial natriuretic peptide receptors in vitro.1 A
range of substituted N-alkylisatins have been synthesised and
their cytotoxicity evaluated against several cancer cell lines in
vitro. Structure–activity relationship studies have indicated that
the introduction of an aromatic ring with a one or three carbon
atom linker at N1 enhances the activity.2 Multicomponent
reactions (MCRs) are important in medicinal and
pharmaceutical chemistry3–6 and are one of the best procedures
for the synthesis of heterocyclic compounds with biological
activity and high molecular complexity.7–10 The spirooxindole
system is the core structure of a variety of medicinal agents
and natural products.11,12 In fact, spirooxindole derivatives have
been described with different biological activities, ranging from
anti-tumour, anti-microbial, anti-HIV and antipyretic agents
to sodium channel blockers and antimalarials.13–15 Compared
with the usual stepwise approaches, MCRs are notable because
of their ability to provide powerful synthetic processes with
advantages in terms of time, cost and waste minimisation.16–22
Both academic and industrial groups utilise MCRs because
of their great versatility to find potent biologically active
compounds for various applications.23–27 Also, in recent years,
green chemistry has become very important.28–29 The chief aims
of green chemistry are the expansion of cleaner and more benign
chemical processes by replacement of volatile and dangerous
reagents and solvents with environmentally compatible
compounds, therefore increasing process selectivity.30–37
Results and discussion
In this paper, we show an efficient synthesis of oxindole
derivatives in 85–95% yield via the reaction of N-alkylisatins 1,
isothiocyanates 2, 1,3-dicarbonyl compounds 3 and pyrrolidine
4 in the presence of ZnO nanoparticles (ZnO-NPs)38–40 under
solvent-free conditions at 50 °C (Scheme 1).
The starting step for our experiments was to optimise the
reaction conditions, such as solvent, catalyst and reaction
time, for the generation of spirooxindole derivatives (Table 1).
The results indicated that simple mixing of an N-alkylisatin
1 (2 mmol), an isothiocyanate 2 (2 mmol) and an enamine
produced by the reaction of a 1,3-dicarbonyl compound 3
and pyrrolidine 4, is an efficient method for preparation of
spirooxindole derivatives 5 in good yields.
In the optimised reaction conditions, the temperature of
the reaction mixture is 50 °C and the reaction was performed
under solvent-free conditions in the presence of ZnO-NPs. The
ZnO nanostructure was prepared according to the literature
procedure.38 Under these conditions, oxindole derivatives
5 were produced in good yield. In these reactions, some
alternative catalysts, such as ZnO nanorods (ZnO-NR), ZnO
nanosheets (ZnO-NS), commercial ZnO (CM-ZnO), TiO2-NPs,
CuO-NPs and KF/clinoptilolite NPs (KF/CP NPs), were also
used. Amongst these catalysts, ZnO-NPs were the best for these
O
R''
NR'
O
O
S
O
O
R'
N
C
S
ZnO-NPs (10 mol%)
Solvent-free, 50 oC, 5 h
+
+
O
+
O
R''
N
H
N
R
N
R
5
1
2
4
3
1, 2, 3, 5
R
R’
R’’
Yield of 5/%
a
b
c
d
e
f
Me
Me
Et
Bn
Bn
Me
Et
4-MeOC6H4
4-MeC6H4
4-O2NC6H4
4-MeOC6H4
tBu
Me
OEt
Me
Me
Me
OEt
Me
Me
92
85
87
90
92
93
95
85
tBu
g
h
tBu
4-BrC6H4
Bn
Scheme 1 Reaction of N-alkylisatins, isothiocyanates, 1,3-dicarbonyl compounds and pyrrolidine in the presence of ZnO nanoparticles.
* Correspondent. E-mail: avmoradi@yahoo.com

8 JOURNAL OF CHEMICAL RESEARCH 2016
Table 1 Optimisation of reaction conditions of compound 5a
The structures of compounds 5a–h were assigned by IR,
1H NMR, 13C NMR and mass spectral data. For example,
Entry Solventa
Catalyst
–
T/°C
90
50
90
80
50
80
90
r.t.
r.t.
50
80
r.t.
r.t.
50
70
50
50
50
50
50
50
50
50
50
–
Time/h
10
8
Yield/%b
15
56
57
40
40
10
10
–
10
25
25
5
80
92
92
75
68
35
47
78
65
38
28
–
1
the H NMR spectrum of 5a displayed two singlets for the
1
DMF
methyl protons at δ 2.23 and 2.28 ppm, one singlet at δ 3.32
2
3
4
5
Toluene
Toluene
CH3CN
CH3CN
EtOH
ZnO-NPs
ZnO-NPs
ZnO-NPs
ZnO-NPs
ZnO-NPs
ZnO-NPs
–
ZnO-NPs
ZnO-NPs
ZnO-NPs
–
for the NMe protons and a singlet for the methoxy protons at
8
3.78 ppm along with signals from the aromatic moiety. The 13
C
10
10
12
12
6
6
6
6
5
NMR spectrum of 5a showed a signal for the spiro carbon at
91.6 ppm and two signals for the carbonyl groups at 164.6 and
192.4 ppm in agreement with the proposed structure. Moreover
the mass spectra of 5a exhibited the molecular ion peak at the
appropriate m/z value.
Mechanistically, it is possible that the reaction involves
the initial formation of enaminone 6 from the reaction of
1,3-dicarbonyl compounds 3 and pyrrolidine 4 (Scheme 1).
The enaminone 6, as a nucleophile, subsequently reacts with
isothiocyanate 2 in the presence of ZnO-NPs to produce
enaminone 7.41,42 After that, nucleophilic attack of 7 on the
carbonyl group of N-alkylisatin 1 leads to the zwitterionic
species 8. Finally, intramolecular cyclisation of 8 generates
intermediate 9 which, following elimination of pyrrolidine, is
converted to product 5.
For confirmation of the mechanism of the reaction,
one derivative of 7 was isolated and then reacted with an
N-alkylisatin in the presence of ZnO-NPs (Scheme 3). After
separation of compound 7a and subsequent reaction with
N-methylisatin 1a, product 5a was generated.
In this study, the reaction of isothiocyanates with
N-alkylisatins and enaminones in the presence of a catalytic
amount of ZnO-NPs at 50 °C under solvent-free conditions has
been investigated and shown to provide a facile synthesis of
some functionalised spirooxindoles.
6
7
EtOH
8
H2O
9
H2O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
H2O
H2O
Solvent-free
Solvent-free ZnO-NPs
Solvent-free ZnO-NPs
Solvent-free ZnO-NPs
Solvent-free ZnO-NR
Solvent-free ZnO-NS
Solvent-free TiO2-NPs
Solvent-free CuO-NPs
Solvent-free KF/CP NPs
Solvent-free ZnCl2
Solvent-free ZnI2
EtOH
H2O
Solvent-free CM-ZnO
Solvent-free CM-ZnO
5
5
5
12
10
10
10
8
12
12
12
12
15
12
ZnCl2
ZnCl2
37
45
50
aThe amount of solvent was 5 mL.
bIsolated yield for reaction under solvent-free conditions
Experimental
reactions. The amount of catalyst is 10 mol%. Using a catalyst
loading of more than 10 mol% decreased the yield of product.
It was found that ZnO-NPs can be reused five times without
significant loss of activity. The catalyst was filtered off after
each run and washed completely with ethyl acetate. It was then
dried at room temperature for 24 h and employed for the next
catalytic cycle.
All chemicals used in this work were prepared by Fluka (Buchs,
Switzerland) and were used without further purification. N-alkylisatins
were synthesised using a literature procedure.43 An Electrothermal
9100 apparatus was employed for measurement of melting points.
Elemental analyses for C, H and N were performed with Heraeus
CHN–O-Rapid analyser. Mass spectra were recorded on a Finnigan-
MAT 8430 spectrometer operating at an ionisation potential of 70 eV.
O
R''
H
N
NR'
+
_
O
+
1
N
S
O
_
2
+
O
N
S
3 +
4
ZnO-NPs
R''
O
R''
N
H N
R'
R
8
7
6
O
R''
O
S
R''
H
NR'
NR'
N
O
N
S
_
O
H
O
O
N
R
N
R
5
9
Scheme 2 Proposed mechanism for the formation of 5.

JOURNAL OF CHEMICAL RESEARCH 2016 9
N
S
O
2a
+
O
N
4
3a +
Me
H N
Me
OMe
7a
6a
O
S
Me
O
N
OMe
O
S
N
O
_
ZnO-NPs (10 mol%)
OMe
N
H
+
O
O
Me
N
N
Me
Me
1a
7a
5a
Scheme 3 Confirmation of the reaction mechanism for the formation of 5.
Measurement of IR spectra was performed using a Shimadzu IR-460
spectrophotometer. 1H and 13C NMR spectra were evaluated with
a Bruker DRX-500 Avance spectrometer at 500.1 and 125.8 MHz,
respectively. 1H NMR and 13C NMR spectra were obtained for
solutions in CDCl3 using TMS as an internal standard.
free conditions. After 30 min, the N-alkylisatin (2 mmol) was added
to the mixture. Then, the reaction mixture was stirred for 5 h at 50 °C
under solvent-free conditions. After completion of the reaction (TLC),
ethyl acetate (5 mL) was poured into the reaction mixture. The catalyst
was removed by filtration. The solvent was evaporated and the residue
was purified by column chromatography (hexane:EtOAc 5:1) to afford
5.
Preparation of ZnO nanoparticles
ZnO-NPs were prepared according to the literature procedure.37 To a
stirred solution of sodium hydroxide (0.44 g) in distilled water (75 mL)
at room temperature, zinc acetate dihydrate (0.6 g) was added and the
solution was heated for 1.5 h at 80 °C. Then, the solution was cooled
at room temperature and the precipitate was collected by filtration and
washed with distilled water and ethanol (96%) several times. ZnO-NPs
were air dried at room temperature for 24 h.
1-Methyl-1, 3- dihydro-2H-indol-2-one-spiro-1- {4- [(4-
methoxyphenyl)imino]-6-methyl-4H-1,3-oxathiin-5-yl}-1-ethanone
(5a): Yellow powder; m.p. 152–154 °C; yield 0.75 g (92%); IR (KBr)
(υmax cm−1): 1738, 1725, 1695, 1578, 1465, 1385, 1298; MS (EI) m/z
1
(%): 408 (M+, 15), 365 (82), 43 (100); H NMR (500 MHz, CDCl3):
δ 2.23 (3 H, s, CH3), 2.28 (3 H, s, CH3), 3.32 (3 H, s, NMe), 3.78 (3
H, s, MeO), 6.87 (2 H, d, J = 7.5 Hz, 2 × CH ), 7.12 (1 H, t, J = 7.8 Hz,
CH), 7.22 (2 H, d, J = 7.5 Hz, 2 × CH), 7.32 (1 H, d, J = 7.6 Hz, CH),
7.68 (1 H, t, J = 7.8 Hz, CH), 7.92 (1 H, d, J = 7.8 Hz, CH); 13C NMR
(125.7 MHz, CDCl3): δ 28.2 (Me), 28.6 (NMe), 29.3 (Me), 55.7 (MeO),
91.6 (C), 115.3 (2 CH), 119.4 (CH), 123.6 (2 CH), 124.2 (CH), 125.7
(CH), 130.2 (C), 131.4 (C), 132.7 (CH), 144.2 (C), 150.2 (C), 156.8
(C=N), 157.6 (C), 164.6 (C=O), 166.2 (C), 192.4 (C=O). Anal. calcd
for C22H20N2O4S (408.47): C, 64.69; H, 4.94; N, 6.86; found: C, 64.78;
H, 5.06; N, 6.95%.
Preparation of compounds (7a) and (5a)
To a magnetically stirred of acetylacetone 3a (0.50 g, 5 mmol),
pyrrolidine
4 (0.35 g, 5 mmol) was added. After 30 min,
4-methoxyphenyl isothiocyanate 2a (0.83 g, 5 mmol) was added
under solvent-free conditions. After completion of the reaction (TLC,
AcOEt:hexane 1:6), the reaction mixture was purified by column
chromatography on silica gel (Merck 230–400 mesh) using n-hexane–
EtOAc as the eluent to afford pure compound 7a.
1-Methyl-1,3-dihydro-2H-indol-2-one-spiro-{ethyl-6-methyl-4-
[(4-methylphenyl)imino]-6-methyl-4H-1,3-oxathiine}-5-carboxylate
(5b): Yellow powder; m.p. 164–166 °C; yield 0.72 g (85%); IR (KBr)
(υmax cm−1): 1740, 1728, 1697, 1583, 1467, 1392, 1285; MS (EI) m/z (%):
422 (M+, 15), 349 (82), 73 (100); 1H NMR (500 MHz, CDCl3): δ 1.28
(3 H, t, J = 7.4 Hz, CH3), 2.34 (3 H, s, Me), 2.40 (3 H, s, CH3), 3.43 (3
H, s, NMe), 4.22 (2 H, q, J = 7.4 Hz, CH2O), 6.92 (2 H, d, J = 7.6 Hz,
2 × CH ), 7.09 (1 H, t, J = 7.6 Hz, CH), 7.18 (1 H, d, J = 7.6 Hz, CH),
7.25 (2 H, d, J = 7.6 Hz, 2 × CH), 7.73 (1 H, t, J = 7.8 Hz, CH), 7.83
(1 H, d, J = 7.8 Hz, CH); 13C NMR (125.7 MHz, CDCl3): δ 14.2 (Me),
21.4 (Me), 21.8 (Me), 28.6 (NMe), 61.2 (CH2O), 92.4 (C), 119.6 (CH),
120.6 (C), 122.3 (2 CH), 123.5 (CH), 125.8 (CH), 129.2 (2 CH), 131.8
(C), 132.6 (CH), 134.6 (C), 148.7 (C), 149.5 (C), 155.2 (C=N), 163.4
(C=O), 164.6 (C=O), 175.2 (C). Anal. calcd for C23H22N2O4S(422.49):
C, 65.38; H, 5.25; N, 6.63; found: C, 65.47; H, 5.36; N, 6.72%.
2-Acet yl-N1- (4 -methox yphenyl) -3- (1-pyrrolidinyl) -2-
butenethioamide (7a): Yellow oil; yield 0.75 g (95%); IR (KBr)
(υmax cm−1): 1720, 1687, 1547, 1478, 1363, 1227; MS (EI) m/z (%): 318
(M+, 10), 275 (76), 43 (100); 1H NMR (500 MHz, CDCl3): δ 2.08 (3 H,
s, CH3), 2.15 (4 H, m, 2 × CH2), 2.38 (3 H, s, CH3), 3.52 (4 H, m, 2 ×
CH2), 3.78 (3 H, s, MeO), 7.04 (2 H, d, J = 7.4 Hz, 2 × CH ), 7.15 (2 H, d,
J = 7.4 Hz, 2 × CH); 13C NMR (125.7 MHz, CDCl3); δ 14.2 (Me), 26.3
(2 CH2), 27.2 (Me), 49.5 (2 CH2), 55.6 (MeO), 103.6 (C), 115.6 (2 CH),
117.2 (2 CH), 143.6 (C), 155.6 (C), 161.4 (C), 176.3 (C=S), 189.6 (C=O).
Anal. calcd for C17H22N2O2S(318.44): C, 64.12; H, 6.96; N, 8.80; found:
C, 64.26; H, 7.08; N, 8.93%.
To a magnetically stirred solution of 7a (0.64 g, 2 mmol),
N-methylisatin 1a (0.32 g, 2 mmol) and ZnO-NPs (10 mol%) were
added at 50 °C under solvent-free conditions. After completion of the
reaction (monitored by TLC), ethyl acetate (5 mL) was poured into the
reaction mixture. The catalyst was removed by filtration. The solvent
evaporated from the mixture and the residue was purified by column
chromatography (hexane:EtOAc 5:1) to afford compound 5a.
1-Ethyl-1,3-dihydro-2H-indol-2-one-spiro-1-{4-[(4-nitrophenyl)
imino]-6-methyl-4H-1,3-oxathiin-5-yl}-1-ethanone (5c): Yellow
powder; m.p. 178–180 °C; yield 0.76 g (87%); IR (KBr) (υmax cm−1):
1742, 1722, 1685, 1574, 1452, 1364, 1252; MS (EI) m/z (%): 437
1
(M+, 20), 394 (68), 43 (100); H NMR (500 MHz, CDCl3): δ 1.38
Preparation of compounds (5a–h); general procedure
To a magnetically stirred mixture of the 1,3-dicarbonyl compound 3
(2 mmol) and pyrrolidine 4 (2 mmol), the appropriate isothiocyanate 2
(2 mmol) and ZnO-NPs (10 mol%) were added at 50 °C under solvent-
(3 H, t, J = 7.5 Hz, CH3), 2.26 (3 H, s, Me), 2.34 (3 H, s, CH3), 4.36
(2 H, q, J = 7.5 Hz, NCH2), 6.95 (1 H, t, J = 7.8 Hz, CH ), 7.28 (1 H,
d, J = 7.6 Hz, CH), 7.34 (2 H, d, J = 7.8 Hz, 2 × CH), 7.62 (1 H, t,

10 JOURNAL OF CHEMICAL RESEARCH 2016
J = 7.6 Hz, CH), 7.82 (1 H, d, J = 7.8 Hz, CH), 8.34 (2 H, d, J = 7.8 Hz,
2 × CH); 13C NMR (125.7 MHz, CDCl3): δ 13.6 (Me), 28.4 (Me), 28.8
(Me), 41.7 (NCH2), 93.6 (C), 122.2 (CH), 123.6 (2 CH), 124.2 (CH),
126.3 (2 CH), 126.8 (CH), 130.2 (C), 131.8 (C), 132.6 (CH), 148.2 (C),
150.2 (C), 156.2 (C), 156.8 (C=N), 164.8 (C=O), 166.3 (C), 192.6
(C=O). Anal. calcd for C22H19N3O5S (437.47): C, 60.40; H, 4.38; N,
9.61; found: C, 60.52; H, 4.49; N, 9.73%.
1-Benzyl-1, 3- dihydro-2H-indol-2- one-spiro-1- {4- [(4-
methoxyphenyl)imino]-6-methyl-4H-1,3-oxathiin-5-yl}-1-ethanone
(5d): Yellow powder; m.p. 183–185 °C; yield 0.87 g (90%); IR (KBr)
(υmax cm−1): 1745, 1727, 1687, 1575, 1457, 1376, 1268; MS (EI) m/z (%):
484 (M+, 10), 441 (72), 43 (100); 1H NMR (500 MHz, CDCl3): δ 2.28
(3 H, s, Me), 2.35 (3 H, s, CH3), 3.78 (3 H, s, MeO), 4.86 (2 H, s, NCH2),
6.94 (2 H, d, J = 7.6 Hz, 2 × CH), 7.15 (1 H, t, J = 7.8 Hz, CH), 7.23 (2
H, d, J = 7.6 Hz, 2 × CH), 7.23 (1 H, d, J= 7.8 Hz, CH), 7.26–7.38 (5 H,
m, 5 × CH), 7.68 (1 H, t, J = 7.6 Hz, CH), 7.92 (1 H, d, J = 7.6 Hz, CH);
13C NMR (125.7 MHz, CDCl3): δ 29.2 (Me), 29.8 (Me), 52.3 (NCH2),
55.7 (MeO), 92.5 (C), 115.2 (2 CH), 121.6 (CH), 122.6 (2 CH), 123.2
(2 CH), 124.2 (CH), 125.8 (CH), 127.2 (CH), 128.6 (2 CH), 130.2 (C),
132.2 (C), 132.7 (CH), 137.3 (C), 144.2 (C), 150.4 (C), 156.7 (C=N),
157.5 (C), 164.6 (C=O), 166.5 (C), 193.4 (C=O). Anal. calcd for
C28H24N2O4S (484.57): C, 69.40; H, 4.99; N, 5.78; found: C, 69.52; H,
5.12; N, 5.89%.
2, 10), 532 (M+, 10), 490 (68), 43 (100); 1H NMR (500 MHz, CDCl3):
δ 2.23 (3 H, s, Me), 2.28 (3 H, s, CH3), 4.85 (2 H, s, NCH2), 6.95 (1
H, t, J = 7.6 Hz, CH), 7.15 (2 H, d, J = 7.8 Hz, 2 × CH), 7.24 (1 H, d,
J = 7.6 Hz, CH), 7.23–7.34 (5 H, m, 5 × CH), 7.65 (1 H, t, J = 7.6 Hz,
CH), 7.94 (1 H, d, J = 7.6 Hz, CH); 13C NMR (125.7 MHz, CDCl3): δ
28.4 (Me), 28.6 (Me), 52.5 (NCH2), 92.7 (C), 118.7 (C), 121.7 (CH),
122.7 (2 CH), 123.9 (CH), 125.4 (2 CH), 125.8 (CH), 126.2 (CH),
128.8 (2 CH), 130.4 (C), 132.3 (C), 132.8 (2 CH), 133.2 (CH), 136.7
(C), 150.6 (C), 151.8 (C), 156.7 (C=N), 164.7 (C=O), 165.8 (C), 193.7
(C=O). Anal. calcd for C27H21BrN2O3S (533.44): C, 60.79; H, 3.97; N,
5.25; found: C, 60.82; H, 4.12; N, 5.37%.
Acknowledgements
I gratefully acknowledge financial support from the Islamic
Azad University of Gorgan.
Received 7 October 2016; accepted 15 November 2016
Paper 1604364 doi: 10.3184/174751917X14815427219086
Published online: 16 January 2017
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1
(100), 43 (100); H NMR (500 MHz, CDCl3): δ 1.28 (9 H, s, Me3C),
2.24 (3 H, s, CH3), 2.33 (3 H, s, CH3), 4.87 (2 H, s, NCH2), 7.04 (1 H,
t, J = 7.5 Hz, CH), 7.18 (1 H, d, J = 7.6 Hz, CH), 7.23–7.38 (5 H, m,
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132.6 (CH), 137.2 (C), 151.2 (C), 161.6 (C=N), 163.6 (C), 164.8 (C=O),
193.4 (C=O). Anal. calcd for C25H26N2O3S (434.55): C, 69.10; H, 6.03;
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6-methyl-
11 R.T. Brown, Indoles, the monoterpenoid indole alkaloids, Wiley, New
York, 1983, Vol. 25.
4-(tert-butylimino)-6-methyl-4H-1,3-oxathiine]-5-carboxylate
(5f): Yellow powder; m.p. 145–147 °C; yield 0.72g (93%); IR (KBr)
(υmax cm−1): 1745, 1725, 1683, 1582, 1466, 1385, 1273; MS (EI) m/z (%):
388 (M+, 15), 331 (82), 57 (100); 1H NMR (500 MHz, CDCl3): δ 1.29
(9 H, s, Me3C), 1.32 (3 H, t, J = 7.4 Hz, CH3), 2.34 (3 H, s, CH3), 3.28
(3 H, s, NCH3), 4.25 (2 H, q, J = 7.4 Hz, CH2O), 7.06 (1 H, t, J = 7.6 Hz,
CH), 7.15 (1 H, d, J = 7.5 Hz, CH), 7.72 (1 H, t, J = 7.5 Hz, CH), 7.83 (1
H, d, J = 7.6 Hz, CH); 13C NMR (125.7 MHz, CDCl3): δ 14.2 (Me), 21.4
(Me), 28.6 (NMe), 29.7 (Me3C), 55.3 (Me3C), 61.2 (CH2O), 91.7 (C),
119.4 (CH), 120.3 (C), 124.3 (CH), 126.2 (CH), 131.6 (C), 132.7 (CH),
150.7 (C), 159.5 (C=N), 163.4 (C=O), 164.7 (C=O), 173.4 (C). Anal.
calcd for C20H24N2O4S (388.48): C, 61.83; H, 6.23; N, 7.21; found: C,
61.92; H, 6.34; N, 7.32%.
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1-Ethyl-1,3-dihydro-2H-indol-2-one-spiro-1-[4-(tert-butylimino)-
6-methyl-4H-1,3-oxathiin-5-yl]-1-ethanone (5g): Yellow powder; m.p.
147–149 °C; yield 0.71g (95%); IR (KBr) (υmax cm−1): 1743, 1728, 1688,
1587, 1469, 1386, 1274; MS (EI) m/z (%): 372 (M+, 10), 315 (86), 57
1
(100); H NMR (500 MHz, CDCl3): δ 1.27 (9 H, s, Me3C), 1.37 (3 H,
t, J = 7.4 Hz, CH3), 2.26 (3 H, s, CH3), 2.32 (3 H, s, CH3), 4.32 (2 H, q,
J = 7.4 Hz, NCH2), 7.08 (1 H, t, J = 7.5 Hz, CH), 7.33 (1 H, d, J = 7.5 Hz,
CH), 7.58 (1 H, t, J = 7.5 Hz, CH), 7.84 (1 H, d, J = 7.5 Hz, CH); 13C NMR
(125.7 MHz, CDCl3): δ 13.8 (Me), 28.3 (Me), 28.7 (Me), 29.2 (Me3C),
41.8 (NCH2), 56.7 (Me3C), 93.4 (C), 122.3 (CH), 124.6 (CH), 125.8
(CH), 129.2 (C), 131.7 (C), 132.3 (CH), 150.8 (C), 161.2 (C=N), 163.8
(C), 164.8 (C=O), 193.5 (C=O). Anal. calcd for C20H24N2O3S (372.48):
C, 64.49; H, 6.49; N, 7.52; found: C, 64.58; H, 6.57; N, 7.64%.
1-Benzyl-1,3-dihydro-2H-indol-2-one-spiro-1-{4-[(4-bromophenyl)
imino]-6-methyl-4H-1,3-oxathiin-5-yl}-1-ethanone (5h): Yellow
powder; m.p. 196–198 °C; yield 0.91 g (85%); IR (KBr) (υmax cm−1):
1742, 1725, 1698, 1586, 1487, 1382, 1292; MS (EI) m/z (%): 534 (M+ +

JOURNAL OF CHEMICAL RESEARCH 2016 11
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