"On water" synthesis of spiro-indoles via Schiff bases

Article abstract of DOI:10.1007/s00706-011-0697-x

A fast, efficient, and clean "on water" synthesis of new Schiff bases and their conversion to spiro compounds under microwave irradiation, as well as in water, is reported. Indol-2,3-diones were reacted separately with various heterocyclic and aromatic am

Full text of DOI:10.1007/s00706-011-0697-x

Monatsh Chem (2012) 143:1187–1194
DOI 10.1007/s00706-011-0697-x
ORIGINAL PAPER
‘‘On water’’ synthesis of spiro-indoles via Schiff bases
•
Siva S. Panda Subhash C. Jain
Received: 13 May 2011 / Accepted: 29 November 2011 / Published online: 10 January 2012
Ó Springer-Verlag 2012
Abstract A fast, efficient, and clean ‘‘on water’’ syn-
thesis of new Schiff bases and their conversion to spiro
compounds under microwave irradiation, as well as in
water, is reported. Indol-2,3-diones were reacted separately
with various heterocyclic and aromatic amines in water at
room temperature to obtain corresponding Schiff bases in
high purity and yield. These were then converted into
corresponding spiro compounds using mercaptoacetic acid
under microwave irradiation in neat conditions as well as in
water on refluxing. Hence, a green synthetic protocol is
developed to synthesize new molecules with improved
profile under ecofriendly conditions, in which no wastes or
side-products are formed.
because of their anti-inflammatory, fungistatic, bacterio-
static, and anticonvulsant activities [8, 9]. On the other
hand, benzothiazoles have also found application as
potential therapeutic agents for various diseases [10] and
also as enzyme inhibitors [11], plant growth regulators
[12], fluorescent material [13], and dyes [14].
Encouraged by the above-cited literature reports, an
idea was developed to introduce separately benzothiazole
as well as indazole moiety into the above-mentioned
spiro[indole-thiazolidine] under ecofriendly conditions,
in order to improve its biological properties and
broaden the activity spectrum of the resulting new spiro
compounds.
Typically, synthesis of Schiff bases and spiro-indoles
employs various organic solvents and reagents under
different conditions [15–21]. Some reactions involve high
temperatures, use of catalyst, and hazardous organic
solvents. Therefore, development of a simple and effi-
cient protocol under mild conditions for construction of
these heterocycles has been advocated. Tight legislation
to maintain greenness requires us to prevent generation
of waste, avoid use of auxiliary substances (e.g., organic
solvents, additional reagents), and minimize energy
requirements. In this context, use of water as the reaction
medium offers several advantages [22–24] as: (1) it is
cheap, nonflammable, nontoxic, and safe to use; (2) it
eliminates the additional efforts required to make the
substrates/reagents dry before use and thus reduces/
eliminates consumption of drying agents, energy, and
time; (3) the unique physical and chemical properties of
water often increase reactivity or selectivity, unattainable
in organic solvents; and (4) the product may be easily
isolated by filtration. All these inspired us to continue
our focus on the aspect of ‘‘on water’’ heterocycle
synthesis.
Keywords Schiff bases ꢀ Spiro compounds ꢀ
Cycloadditions ꢀ Green chemistry ꢀ Water ꢀ Microwave
Introduction
Indoles are an important class of nitrogen heterocycles,
being used as key building blocks for synthesis of many
pharmaceuticals. Spiro-indoles and Schiff bases are known
to exhibit diverse biological activities [1–7]. Of these,
spiro[indole-thiazolidines] have attracted our attention
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-011-0697-x) contains supplementary
material, which is available to authorized users.
S. S. Panda ꢀ S. C. Jain (&)
Department of Chemistry, University of Delhi,
Delhi 110007, India
e-mail: jainsc48@hotmail.com
123

1188
S. S. Panda, S. C. Jain
Results and discussion
any metallic impurities from tap water catalyzing such
reactions. The Schiff base was obtained in 92% yield,
and no appreciable rate retardation was observed. All the
reactions were carried out in tap water to avoid the effort
and energy consumption needed to prepare distilled
water.
As a part of our continuing interest in synthesis of new
spiro heterocycles of medicinal interest by molecular
modification [25–29], we have now developed a protocol
for synthesis of Schiff bases by stirring 1H-indol-2,3-dione
with different aromatic and heterocyclic amines in water at
room temperature to afford the corresponding Schiff bases
as colored solids in excellent yield (Table 1). For 3a, the
infrared (IR) spectrum showed a characteristic absorption
band at 1,613 cm-1 for C=N stretching, thus indicating the
To find out if water provides a kinetic advantage over
other solvents, the progress of the reaction of 5-methyl-1H-
indol-2,3-dione with 6-aminobenzothiazole was monitored
in various solvents. Since 6-aminobenzothiazole and the
corresponding Schiff base had close Rf values, the con-
sumption of 5-methyl-1H-indol-2,3-dione was taken as a
measure of reaction completion.
formation of a Schiff base. H and 13C nuclear magnetic
1
resonance (NMR) data provided the final evidence for the
formation of a Schiff base.
Complete consumption of 5-methyl-1H-indol-2,3-
dione, as observed on high-performance thin-layer chro-
matography (HP-TLC), took place after 9, 8, 7, 5, 5, 4,
and 3 h in methanol, tetrahydrofuran, ethanol, acetic acid,
dimethyl sulfoxide, dimethyl formamide, and water,
respectively. A graphical representation of the time
required for complete consumption of 5-methyl-1H-indol-
2,3-dione and the yield of each reaction is given in
Figs. 1 and 2.
The cyclocondensation of the Schiff base with mer-
captoacetic acid was accelerated by microwave irradiation
(70 W) at 100 °C for 5 min in a CEM Discover Focussed
Microwave Synthesis System, and the desired product was
obtained in 5 min in very good yield. The same reaction
was also carried out in water under traditional refluxing
condition to obtain the desired product in good yield
(Table 2). For 5a, two one-proton characteristic doublets at
d = 4.04 and 4.20 ppm (J = 15.6 Hz) in 1H and a peak at
32.8 ppm in 13C NMR for the methylene group of the
newly formed thiazolidinone ring supported the formation
of spiro[indole-thiazolidine]-2,40-diones.
Spiro-indoles were synthesized by microwave irradia-
tion of a homogeneous mixture of Schiff base and
mercaptoacetic acid without using any solvent, catalyst, or
supporting material. This reaction was completed in 5 min.
The above reaction was also carried out in presence of
solvents such as methanol, dimethyl formamide, and tol-
uene along with supporting materials such as silica or
K-10 clay, but no significant difference was observed
either in the yield or in the purity of the compound, as
compared with one prepared under neat condition
(Scheme 1).
Thus, we have introduced herein a highly selective and
efficient method for constructing Schiff bases and spiro-
indoles without using any catalyst. In general, after
completion of the reactions, the Schiff bases were settled
down on standing and were isolated in pure form after
filtration and air drying, whereas spiro-indoles were pre-
cipitated out upon neutralization by sodium bicarbonate.
The isolated products were obtained in pure form (by
spectral data) and did not require any further additional
efforts for purification. To generalize the methodology we
have prepared a number of known and unknown Schiff
bases and spiro-indoles by following the ecofriendly
methodology.
We have also carried out the above reaction in water
under traditional refluxing condition and under microwave
irradiation under dry condition on large scale. It proceeds
nearly to completion in water, while some amount of
reactants are left when carried out under dry condition
under microwave irradiation, indicating that ‘‘on water’’
synthesis is more efficient than under dry condition on
small as well as large scale.
To ensure that no metal ion is leaching out from the
glass reaction vessel and is responsible for providing
catalytic assistance, the reaction of 1H-indol-2,3-dione
(3 mmol) with 4-methylaniline (3 mmol) was also car-
ried out in a plastic vessel in water for 5 h, and the
corresponding Schiff base was obtained in 94% yield.
Further, the reaction of 5-fluoro-1H-indol-2,3-dione with
4-methylaniline was carried out separately in distilled
water, tap water, and saturated brine solution. No sig-
nificant difference was observed either in the reaction
time or in the product yield. The Schiff base was
obtained in 94%, 95%, and 94% yield, respectively, after
4 h at room temperature. Further, we carried out the
reaction in deionized water to rule out the possibility of
In conclusion, we describe herein a fast, efficient,
cleaner, and greener methodology for ‘‘on water’’ syn-
thesis of Schiff bases and spiro-indoles. The advantages
such as (1) no requirement of additional reagent/catalyst,
(2) nonflammable and nontoxic reaction medium, (3)
high yield, (4) virtually no waste generation, and (5)
ease of product isolation/purification fulfill the triple
bottom-line philosophy of green chemistry and make the
present methodology environmentally benign. This pro-
tocol is associated with readily available starting
materials, mild conditions, easy operation, and a broad
range of substrates.
123

‘‘On water’’ synthesis of spiro-indoles via Schiff bases
1189
Table 1 Synthesis of 3-(heteroaryl/arylimino)-5-substituted indoline-2-ones 3a-3u
O
N
R
R1
R1
Water, rt
O
+
H2N R
O
N
N
H
H
1
2a 2g
3a 3u
-
-
1a
1b
: R = H
1
: R = F
1c: R1 = CH3
Prod.
1
2
Time/h
3.0
Yield/%
98
M.p./°C
3a
1a
248–250
N
S
H2N
2a
3b
3c
3d
1b
1c
1a
2a
2a
3.5
3.0
3.5
96
98
91
259–261
146–147
[280 [29]
H2N
N
N
H
2b
3e
3f
1b
1c
1a
2b
2b
4.0
4.5
0.5
95
92
98
[280 [29]
266–267
3g
129–131 [28]
CH3
N
H3C
H2N
N
2c
O
3h
3i
1b
1c
1a
1b
1c
1a
1b
1c
1a
1b
1c
1a
1b
1c
2c
2c
0.5
0.5
4.0
5.0
5.0
4.0
4.5
4.5
5.0
4.0
4.0
4.5
4.0
4.0
96
94
92
91
90
90
90
90
94
95
96
92
96
98
141–142 [30]
153–155 [31]
183–184 [32]
154–155 [33]
142–144
3j
Aniline (2d)
3k
3l
2d
2d
3m
3n
3o
3p
3q
3r
3s
4-Fluoroaniline (2e)
210–211 [8]
220–221 [33]
275–276 [34]
261–262 [35]
249–250
2e
2e
4-Methylaniline (2f)
2f
2f
241–243 [35]
251–253 [35]
245–247
4-Methoxyaniline (2g)
3t
2g
2g
3u
221–222 [34]
123

1190
S. S. Panda, S. C. Jain
Table 2 Synthesis of 30-(heteroaryl/aryl)spiro[3H-indol-3,20-thiazolidine]-2,40(1H)-diones 5a-5u
O
N R
O
S
HSCH2COOH
R1
R1
N R
O
4
Water, reflux
N
N
H
H
3a-3u
5a-5u
Prod.
R
R1
Time/h
Yield/%
M.p./°C
5a
5b
5c
H
4.0
6.0
4.0
90
88
88
294–296
302–304
273–274
N
S
F
CH3
5d
5e
5f
H
4.0
6.0
6.0
85
89
82
[280 [29]
[280 [29]
181–182
F
N
CH3
N
H
5g
5h
5i
H
5.0
6.0
5.0
89
88
88
305–307 [29]
307–309 [31]
305–306 [30]
CH3
N
F
H3C
N
CH3
O
5j
C6H5-
H
6.0
6.0
6.0
4.5
6.0
4.0
4.0
5.0
4.0
5.0
4.0
5.0
82
85
87
82
83
88
82
80
82
85
90
82
230–231 [32]
265–266 [15–19]
86–88
5k
5l
F
CH3
H
5m
5n
5o
5p
5q
5r
5s
4-F-C6H4-
244–246 [8]
180–182 [15–19]
193–195
F
CH3
H
4-CH3-C6H4-
123–125
F
102–104
CH3
H
[280 [36]
210–211 [37]
196–197
4-CH3O-C6H4-
5t
F
5u
CH3
201–203
120
98
100
80
60
40
20
0
10
85
9
81
80
9
8
7
6
5
4
3
2
1
0
8
71
68
65
7
5
5
4
3
MeOH
THF
EtOH
AcOH
DMSO
DMF
Water
MeOH
THF
EtOH
AcOH
DMSO
DMF
Water
Solvent
Solvent
Fig. 1 Time required for complete consumption of 5-methyl-1H-
indol-2,3-dione during its reaction with 6-aminobenzothiazole
Fig. 2 Schiff base formation during reaction of 5-methyl-1H-indol-
2,3-dione with 6-aminobenzothiazole using various solvents
123

‘‘On water’’ synthesis of spiro-indoles via Schiff bases
1191
Scheme 1
O
N
R
O
R1
R1
Water, rt
O
+
H2N
R
N
H
N
2a-2g
R = heteroaryl, aryl
H
1a: R1 = H
1b: R1 = F
3a-3u
1c: R1 = CH3
MW / water, reflux
HSCH2COOH
4
O
S
R1
N
R
O
N
H
5a-5u
7.30 (dd, J = 7.7, 7.6 Hz, 1H), 7.77 (s, 1H), 8.14 (d,
J = 8.4 Hz, 1H), 9.32 (s, 1H), 11.00 (s, 1H, NH, D2O
exchangeable) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 110.9, 111.3, 119.6, 121.7, 124.8, 125.8, 135.1, 146.3,
148.4, 151.3, 158.9, 163.9 (C-2) ppm; MS: m/z = (ES?)
280.13 [M? ? 1], (ES-) 278.13 [M? - 1].
Experimental
Melting points were determined in a capillary tube in sul-
furic acid bath. IR spectra were recorded on a Shimadzu
model IR-435 spectrophotometer. 1H and 13C NMR spectra
were recorded on a Bruker AC-400 (400 MHz for 1H,
100 MHz for 13C) in DMSO-d6. Elemental analyses were
performed on a PerkinElmer series 11 CHNS/O analyzer
2400 and were within 0.4% of calculated values. Mass
spectra were recorded on a Micromass Quattro MicroTM
instrument. A CEM Discover Focussed Microwave Syn-
thesis System was used for microwave irradiation.
Substituted 1H-indol-2,3-diones 1b-1c were prepared by
literature procedures starting from the corresponding ani-
lines [28].
3-(Benzothiazol-6-ylimino)-5-fluoro-1,3-dihydro-2H-
indole-2-one (3b, C15H9FN3OS)
ꢀ
IR (KBr): m = 3,183, 2,929, 1,721, 1,620, 1,474, 1,306,
1
1,263, 1,194, 852, 826, 635 cm-1; H NMR (400 MHz,
DMSO-d6): d = 6.88 (m, 2H), 7.22-719 (m, 2H), 7.80 (s,
1H), 8.16 (d, J = 8.4 Hz, 1H), 9.34 (s, 1H), 11.04 (s, 1H,
NH, D2O exchangeable) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 111.2, 113.3, 116.5, 123.0, 124.5, 135.5,
144.0, 147.7, 155.5, 159.0, and 163.9 (C-2) ppm; MS:
m/z = (ES?) 298.18 [M? ? 1], (ES-) 296.13 [M? - 1].
Typical procedure for synthesis of 3-(heteroaryl/
aryl)imino-5 substituted 1,3-dihydro-2H-indole-2-ones
3-(Benzothiazol-6-ylimino)-1,3-dihydro-5-methyl-2H-
indole-2-one (3c, C16H11N3OS)
ꢀ
IR (KBr): m = 3,338, 2,923, 1,739, 1,623, 1,484, 1,304,
Substituted isatin (1.0 mmol) and heterocyclic or aromatic
amine (1.0 mmol) were taken in a 50-cm3 round-bottom
flask and stirred in 10 cm3 tap water. The progress of the
reaction was monitored by TLC. Upon completion of
the reaction, the solvent was removed by filtration and the
Schiff base isolated. All the compounds were characterized
by their spectral data [IR, NMR, and mass spectrometry
(MS)], and for known compounds these were compared
with literature values.
1,259, 1,205, 1,120, 854, 806, 652 cm-1 1H NMR
;
(400 MHz, DMSO-d6): d = 2.22 (s, 3H, CH3), 6.77 (m,
2H), 7.08 (d, J = 1.6 Hz, 1H), 7.29 (s, 1H), 7.36 (d,
J = 7.6 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 8.84 (s, 1H),
10.90 (s, 1H, NH, D2O exchangeable) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 20.5 (CH3), 104.2, 112.5,
115.4, 118.2, 123.5, 125.3, 132.5, 135.7, 139.2, 145.2,
147.8, 149.0, 149.6, 159.9, 185.0 (C-2) ppm; MS:
m/z = (ES?) 294.14 [M? ? 1], (ES-) 292.11 [M? - 1].
3-(Benzothiazol-6-ylimino)-1,3-dihydro-2H-indole-2-one
(3a, C15H9N3OS)
1,3-Dihydro-3-(1H-indazol-5-ylimino)-5-methyl-2H-
indole-2-one (3f, C16H12N4O)
ꢀ
IR (KBr): m = 3,167, 2,918, 1,723, 1,613, 1,463, 1,341,
1
1,220, 854, 751, 639 cm-1; H NMR (400 MHz, DMSO-
ꢀ
IR (KBr): m = 3,189, 2,924, 1,738, 1,616, 1,485, 1,307,
1,209, 956, 831, 651 cm-1; H NMR (400 MHz, DMSO-
1
d6): d = 6.30 (d, J = 7.6 Hz, 1H), 6.65 (d, J = 7.6 Hz,
1H), 6.88 (d, J = 7.2 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H),
d6): d = 1.94 (s, 3H, CH3), 6.46 (s, 1H), 6.80 (d,
123

1192
S. S. Panda, S. C. Jain
J = 7.9 Hz, 1H), 7.09 (m, 2H), 7.34 (s, 1H), 7.63 (d,
J = 8.7 Hz, 1H), 8.01 (s, 1H), 10.74 (s, 1H, NH, D2O
exchangeable), 13.00 (s, 1H, NH, D2O exchangeable) ppm;
13C NMR (100 MHz, DMSO-d6): d = 21.3 (CH3), 109.0,
111.2, 116.7, 119.7, 123.6, 126.1, 131.1, 134.6, 144.0,
155.6, 164.6 (C-2) ppm; MS: m/z = (ES?) 277.12
[M? ? 1], (ES-) 275.14 [M? - 1].
filtered, washed with water, and dried to obtain the desired
product.
Alternate method:
A
mixture of 3-indolylimine
(1.0 mmol) and mercaptoacetic acid (1.2 mmol) was mixed
with 10 cm3 water in a round-bottom flask. The contents
were refluxed for 4–5 h. The progress of the reaction was
monitored by TLC. After completion of the reaction, the
reaction mixture was neutralized by NaHCO3. The precip-
itate was filtered, washed with water, and dried to obtain the
desired product.
1,3-Dihydro-5-methyl-3-(phenylimino)-2H-indole-2-one
(3l, C15H12N2O)
ꢀ
IR (KBr): m = 3,288, 2,926, 1,745, 1,628, 1,492, 1,307,
1,198, 1,129, 831, 692 cm-1; 1H NMR (400 MHz, DMSO-
d6): d = 2.23 (s, 3H, CH3), 6.19 (s, 1H), 6.75 (m, 2H), 6.89
(d, J = 7.9 Hz, 1H), 7.02 (d, J = 8.1 Hz, 1H), 7.28 (m,
2H), 7.36 (d, J = 7.9 Hz, 1H), 10.60 (s, 1H, NH, D2O
exchangeable) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 21.1 (CH3), 109.5, 111.5, 114.1, 112.7, 118.8, 122.9,
143.4, 159.1, 164.1 (C-2) ppm; MS: m/z = (ES?) 237.19
[M? ? 1] (ES-) 235.19 [M? - 1].
30-(Benzothiazol-6-yl)spiro[3H-indole-3,20-thiazolidine]-
2,40(1H)-dione (5a, C17H11N3O2S2)
ꢀ
IR (KBr): m = 3,167, 2,851, 1,727, 1,689, 1,470, 1,401,
1,339, 1,224, 1,185, 855, 764, 622 cm-1 1H NMR
;
(400 MHz, DMSO-d6): d = 4.04 (d, J = 15.6 Hz, 1H),
4.20 (d, J = 15.6 Hz, 1H), 6.71 (d, J = 7.6 Hz, 1H), 6.97
(dd, J = 7.6, 7.6 Hz, 1H), 7.14 (d, J = 6.8 Hz, 1H), 7.17
(d, J = 7.6 Hz, 1H), 7.57 (d, J = 7.2 Hz, 1H), 7.89 (s,
1H), 7.97 (d, J = 8.8 Hz, 1H), 9.37 (s, 1H), 10.77 (s, 1H,
NH, D2O exchangeable) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 32.8 (S-CH2), 70.1 (spiro carbon), 111.1,
123.3, 124.9, 126.7, 127.0, 131.7, 133.9, 134.5, 142.0,
152.9, 158.5, 172.5 (C-2), 176.6 (thiazolidine C=O) ppm;
MS: m/z = (ES?) 354.15 [M? ? 1], (ES-) 352.15
[M? - 1].
5-Fluoro-1,3-dihydro-3-[(4-methylphenyl)imino]-2H-
indole-2-one (3q, C15H11FN2O)
ꢀ
IR (KBr): m = 3,432, 2,926, 1,748, 1,621, 1,475, 1,300,
1
1,187, 834, 652 cm-1; H NMR (400 MHz, DMSO-d6):
d = 2.23 (s, 3H, CH3), 6.20 (d, J = 8.0 Hz, 1H), 6.96 (m,
2H), 7.16 (m, 2H), 7.30 (m, 2H), 10.95 (s, 1H, NH, D2O
exchangeable) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 22.5 (CH3), 109.5, 111.1, 112.9, 113.6, 116.1, 124.3,
142.8, 154.1, 158.8, 164.4 (C-2) ppm; MS: m/z = (ES?)
255.10 [M? ? 1], (ES-) 253.16 [M? - 1].
30-(Benzothiazol-6-yl)-5-fluorospiro[3H-indole-3,20-
thiazolidine]-2,40(1H)-dione (5b, C17H10FN3O2S2)
ꢀ
IR (KBr): m = 3,449, 2,926, 1,734, 1,691, 1,486, 1,357,
1
1,181, 887, 635 cm-1; H NMR (400 MHz, DMSO-d6):
5-Fluoro-1,3-dihydro-3-[(4-methoxyphenyl)imino]-2H-
indole-2-one (3t, C15H11FN2O2)
d = 4.04 (d, J = 15.6 Hz, 1H), 4.18 (d, J = 15.2 Hz, 1H),
6.71 (d, J = 8.0 Hz, 1H), 7.02 (d, J = 7.8 Hz, 1H), 7.19
(d, J = 7.6 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.84 (s,
1H), 8.01 (d, J = 7.6 Hz, 1H), 9.39 (s, 1H), 10.79 (s, 1H,
NH, D2O exchangeable) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 32.8 (S-CH2), 70.3 (spiro carbon), 112.3,
114.8, 118.5, 123.5, 124.0, 127.0, 133.7, 134.6, 138.1,
153.0, 157.5, 158.6, 159.9, 172.4 (C-2), 176.5 (thiazolidine
C=O) ppm; MS: m/z = (ES?) 372.17 [M? ? 1], (ES-)
370.12 [M? - 1].
ꢀ
IR (KBr): m = 3,434, 2,928, 1,739, 1,605, 1,474, 1,251,
1
1,186, 1,032, 820, 773, 655 cm-1; H NMR (400 MHz,
DMSO-d6): d = 3.83 (s, 3H, OCH3), 6.92 (d, J = 8.1 Hz,
2H), 7.05 (m, 2H), 7.17 (m, 1H), 7.29 (d, J = 8.1 Hz, 1H),
6.42 (d, J = 6.8 Hz, 1H), 10.93 (s, 1H, NH, D2O
exchangeable) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 55.5 (OCH3), 109.5, 111.9, 112.7, 113.6, 116.4, 119.8,
123.7, 143.4, 154.3, 158.8, 164.1 (C-2) ppm; MS:
m/z = (ES?) 271.26 [M? ? 1], (ES-) 269.22 [M? - 1].
30-(Benzothiazol-6-yl)-5-methylspiro[3H-indole-3,20-
thiazolidine]-2,40(1H)-dione (5c, C18H13N3O2S2)
Typical procedure for synthesis of 30-(heteroaryl/
aryl)spiro[3H-indole-3,20-thiazolidine]-2,40(1H)-
diones
ꢀ
IR (KBr): m = 3,182, 1,729, 1,689, 1,491, 1,467, 1,348,
1,203, 1,169, 860, 815, 694, 637 cm-1
;
1H NMR
(400 MHz, DMSO-d6): d = 2.18 (s, 3H, CH3), 4.01 (d,
J = 15.6 Hz, 1H), 4.17 (d, J = 15.6 Hz, 1H), 6.59 (d, J =
8.0 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H), 7.14 (d,
J = 8.8 Hz, 1H), 7.39 (s, 1H), 7.89 (s, 1H), 7.98 (d, J =
8.4 Hz, 1H), 9.37 (s, 1H), 10.67 (s, 1H, NH, D2O
exchangeable) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 21.0 (CH3), 32.8 (S-CH2), 70.2 (spiro carbon), 110.9,
123.3, 123.9, 125.0, 126.7, 127.4, 132.0, 132.4, 134.0,
A dried heavy-walled Pyrex tube containing a small stir bar
was charged with 3-indolylimine (1.0 mmol) and mercap-
toacetic acid (1.2 mmol) without any solvent. The contents
were subjected to microwave irradiation (70 W) at 100 °C
for 5 min in cooling mode. A sticky solid was formed,
which was treated with saturated solution of sodium
bicarbonate to remove excess acid. The solid left was
123

‘‘On water’’ synthesis of spiro-indoles via Schiff bases
1193
134.6, 139.5, 152.8, 158.4, 172.6 (C-2), 176.5 (thiazolidine
C=O) ppm; MS: m/z = (ES?) 368.19 [M? ? 1], (ES-)
366.19 [M? - 1].
70.4 (spiro carbon), 112.1, 114.3, 115.9, 117.9, 118.4,
127.3, 130.6, 138.8, 152.3, 154.4, 171.8 (C-2), 176.2
(thiazolidine C=O) ppm; MS: m/z = (ES?) 311.19
[M? ? 1], (ES-) 309.21 [M? - 1].
30-(1H-Indazol-5-yl)-5-methylspiro[3H-indole-3,20-
thiazolidine]-2,40(1H)-dione (5f, C18H14N4O2S)
5-Fluoro-30-(4-methylphenyl)spiro[3H-indole-3,20-
thiazolidine]-2,40(1H)-dione (5q, C17H13FN2O2S)
ꢀ
IR (KBr): m = 3,424, 2,926, 1,720, 1,685, 1,494, 1,380,
1
1,209, 942, 812, 633 cm-1; H NMR (400 MHz, DMSO-
IR (KBr): m = 3,449, 2,928, 1,734, 1,682, 1,487, 1,365,
ꢀ
d6): d = 2.38 (s, 3H, CH3), 3.88 (d, J = 15.3 Hz, 1H), 4.29
(d, J = 15.3 Hz, 1H), 6.60 (d, J = 8.9 Hz, 1H), 6.81 (s,
1H), 6.96 (d, J = 8.3 Hz, 1H), 7.02 (d, J = 8.8 Hz, 1H),
7.30 (s, 1H), 7.42 (d, J = 7.9 Hz, 1H), 7.76 (s, 1H), 10.33
(s, 1H, NH, D2O exchangeable), 13.08 (s, 1H, NH, D2O
exchangeable) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 21.4 (CH3), 33.1 (S-CH2), 68.1 (spiro carbon), 111.4,
121.3, 126.9, 127.6, 131.7, 139.6, 143.2, 172.8 (C-2), 174.3
(thiazolidine C=O) ppm; MS: m/z = (ES?) 351.11
[M? ? 1], (ES-) 349.14 [M? - 1].
1,273, 1,234, 1,190, 816, 697, 624 cm-1
;
1H NMR
(400 MHz, DMSO-d6): d = 2.19 (s, 3H, CH3), 3.86 (d,
J = 15.2 Hz, 1H), 4.16 (d, J = 15.2 Hz, 1H), 6.71 (m,
1H), 6.92 (m, 3H), 7.03 (m, 2H), 7.22 (d, J = 7.1 Hz, 1H),
10.61 (s, 1H, NH, D2O exchangeable) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 20.3 (CH3), 33.1 (S-CH2),
69.8 (spiro carbon), 109.7, 111.8, 124.8, 127.2, 128.3,
129.0, 130.5, 131.9, 132.4, 139.2, 173.1 (C-2), 176.1
(thiazolidine C=O) ppm; MS: m/z = (ES?) 329.19
[M? ? 1], (ES-) 327.17 [M? - 1].
5-Methyl-30-phenylspiro[3H-indole-3,20-thiazolidine]-
2,40(1H)-dione (5l, C17H14N2O2S)
5-Fluoro-30-(4-methoxyphenyl)spiro[3H-indole-3,20-
thiazolidine]-2,40(1H)-dione (5t, C17H13FN2O3S)
ꢀ
ꢀ
IR (KBr): m = 3,447, 2,925, 1,734, 1,687, 1,493, 1,363,
IR (KBr): m = 3,447, 2,922, 1,734, 1,688, 1,493, 1,363,
1
1,207, 817, 757, 694 cm-1; H NMR (400 MHz, DMSO-
1,207, 817, 757, 694, 635 cm-1 1H NMR (400 MHz,
;
d6): d = 2.19 (s, 3H, CH3), 3.91 (d, J = 15.5 Hz, 1H), 4.15
(d, J = 15.4 Hz, 1H), 6.65 (d, J = 7.9 Hz, 1H), 6.98 (m,
3H), 7.25 (m, 4H), 10.62 (s, 1H, NH, D2O exchangeable)
ppm; 13C NMR (100 MHz, DMSO-d6): d = 21.1 (CH3),
32.6 (S-CH2), 69.8 (spiro carbon), 109.7, 111.8, 124.8,
127.0, 127.9, 128.3, 129.4, 130.5, 132.2, 139.2, 172.2 (C-
2), 176.5 (thiazolidine C=O); MS: m/z = (ES?) 311.22
[M? ? 1], (ES-) 309.22 [M? - 1].
DMSO-d6): d = 3.70 (s, 3H, OCH3), 3.95 (d, J = 15.3 Hz,
1H), 4.17 (d, J = 15.3 Hz, 1H), 6.74 (m, 2H), 6.82 (d,
J = 8.9 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 7.42 (d,
J = 7.8 Hz, 1H), 10.66 (s, 1H, NH, D2O exchangeable)
ppm; 13C NMR (100 MHz, DMSO-d6): d = 32.5 (S-CH2),
55.4 (OCH3), 70.1 (spiro carbon), 111.8, 113.9, 114.6,
117.6, 118.0, 127.1, 129.9, 138.0, 157.0, 159.2, 171.9 (C-
2), 176.5 (thiazolidine C=O) ppm; MS: m/z = (ES?)
350.11 [M? ? 1], (ES-) 348.10 [M? - 1].
30-(4-Fluorophenyl)-5-methylspiro[3H-indole-3,20-
thiazolidine]-2,40(1H)-dione (5o, C17H13FN2O2S)
30-(4-Methoxyphenyl)-5-methylspiro[3H-indole-3,20-
thiazolidine]-2,40(1H)-dione (5u, C18H16N2O3S)
ꢀ
IR (KBr): m = 3,441, 2,928, 1,731, 1,689, 1,490, 1,354,
1
1,247, 1,198, 1,065, 810, 751, 694, 632 cm-1; H NMR
IR (KBr): m = 3,447, 2,923, 1,734, 1,687, 1,501, 1,373,
ꢀ
(400 MHz, DMSO-d6): d = 2.31 (s, 3H, CH3), 3.96 (d,
J = 15.0 Hz, 1H), 4.11 (d, J = 15.0 Hz, 1H), 6.84 (m,
2H), 6.92 (d, J = 8.8 Hz, 2H), 7.17 (d, J = 8.8 Hz, 2H),
7.29 (d, J = 8.0 Hz, 1H), 10.60 (s, 1H, NH, D2O
exchangeable) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 21.2 (CH3), 32.2 (S-CH2), 70.0 (spiro carbon), 112.1,
114.5, 116.6, 117.9, 118.0, 127.4, 130.2, 138.4, 152.0,
165.2, 171.9 (C-2), 176.5 (thiazolidine C=O) ppm; MS:
m/z = (ES?) 329.23 [M? ? 1], (ES-) 327.18 [M? - 1].
1,205, 811, 735, 678, 635 cm-1
;
1H NMR (400 MHz,
DMSO-d6): d = 2.21 (s, 3H, CH3), 3.79 (s, 3H, OCH3),
3.95 (d, J = 15.0 Hz, 1H), 4.15 (d, J = 15.0 Hz, 1H), 6.79
(m, 2H), 6.82 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 7.8 Hz,
2H), 7.28 (m, 1H), 10.66 (s, 1H, NH, D2O exchangeable)
ppm; 13C NMR (100 MHz, DMSO-d6): d = 21.5, 32.5 (S-
CH2), 55.6 (OCH3), 70.2 (spiro carbon), 112.1, 113.7,
114.6, 117.5, 118.4, 128.0, 129.7, 139.3, 157.0, 164.2,
171.8 (C-2), 176.2 (thiazolidine C=O) ppm; MS:
m/z = (ES?) 341.17 [M? ? 1], (ES-) 339.11 [M? - 1].
30-(4-Methylphenyl)spiro[3H-indole-3,20-thiazolidine]-
2,40(1H)-dione (5p, C17H14N2O2S)
Acknowledgments Authors are grateful to UGC (New Delhi) for
financial assistance.
ꢀ
IR (KBr): m = 3,440, 2,926, 1,739, 1,680, 1,495, 1,363,
1,237, 932, 827, 757, 691, 629 cm-1; 1H NMR (400 MHz,
DMSO-d6): d = 2.23 (s, 3H, CH3), 3.90 (d, J = 15.1 Hz,
1H), 4.15 (d, J = 15.1 Hz, 1H), 6.80 (m, 2H), 6.89 (d,
J = 8.2 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 7.31 (m, 2H),
10.58 (s, 1H, NH, D2O exchangeable) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 21.2 (CH3), 32.3 (S-CH2),
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