Aqueous hydrotropic solution: green reaction medium for synthesis of pyridopyrimidine carbonitrile and spiro-oxindole dihydroquinazolinone derivatives

Article abstract of DOI:10.1007/s11164-019-03801-8

Abstract: From the green chemistry point of view, water is one of the most sustainable solvents for chemical transformations, but there are some limitations to its use as a reaction medium due to the lack of solubility of organic compounds. To overcome this difficulty, we used aqueous hydrotropic solution, which increases the solubility of organic compounds in water by?200-fold. We report an environmentally efficient method for synthesis of pyridopyrimidine carbonitriles and spiro-oxindole dihydroquinazolinones by using 50?% aqueous sodium p-toluene sulfonate (NaPTS) solution at ambient reaction condition. The merits of the present protocol include short reaction time, excellent product yield?with high purity, easy workup procedure and reusability of reaction medium. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-019-03801-8

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-03801-8
Aqueous hydrotropic solution: green reaction
medium for synthesis of pyridopyrimidine carbonitrile
and spiro‑oxindole dihydroquinazolinone derivatives
Audumbar Patil, et al. [full author details at the end of the article]
Received: 23 November 2018 / Accepted: 11 March 2019
© Springer Nature B.V. 2019
Abstract
From the green chemistry point of view, water is one of the most sustainable sol-
vents for chemical transformations, but there are some limitations to its use as a
reaction medium due to the lack of solubility of organic compounds. To overcome
this difculty, we used aqueous hydrotropic solution, which increases the solubility
of organic compounds in water by 200-fold. We report an environmentally efcient
method for synthesis of pyridopyrimidine carbonitriles and spiro-oxindole dihydro-
quinazolinones by using 50 % aqueous sodium p-toluene sulfonate (NaPTS) solution
at ambient reaction condition. The merits of the present protocol include short reac-
tion time, excellent product yield with high purity, easy workup procedure and reus-
ability of reaction medium.
Graphical abstract
Keywords Multicomponent reaction · Hydrotropic solution ·
Dihydroquinazolinone · Green reaction medium · Spiro-oxindole
Vol.:(0123456789)
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A. Patil et al.
Introduction
Multicomponent reactions (MCRs) play an important role in synthetic medicinal
and organic chemistry [1]. Due to their high atom economy and short reaction
time, they are one of the most powerful tools in the modern drug discovery pro-
cess [2]. These reactions proceed in one pot to form complex structures in a sin-
gle operation by formation of new C–C and C–N bonds [3]. Recently, a number
of researchers have synthesized various heterocyclic molecules by using green
methodologies [4, 5].
From the green chemistry prospective, carrying out organic transformations in
aqueous medium remains a great challenge. As a universal solvent, it is desirable
to use water as a reaction medium due to its safe, harmless and environmentally
benign nature [6], but most organic compounds are insoluble in water. To over-
come this difculty, we have carried out reactions in hydrotropes [7]. The term
“hydrotropes” refers to a class of water-soluble surface-active compounds with
amphiphilic character and hydrophobic regions that enhance the solubility of
organic reactants and nonpolar compounds in aqueous phase at higher concentra-
tion [8]. They can increase the solubility of organic compounds up to 200-fold in
water [9]. They usually comprise hydrophilic and hydrophobic moieties, with the
latter typically being too small to induce micelle formation [10, 11].
Pyrido[2,3-d]pyrimidine and spiro-oxindole derivatives are an important class
of heterocyclic compounds [12], being the main components of some naturally
occurring products. These compounds have attracted increasing interest in recent
years due to their useful biological and pharmacological properties [13, 14].
Pyrido[2,3-d]pyrimidine and spiro-oxindole derivatives exhibit intriguing biolog-
ical activities such as antitumor, antiallergic, antifolate, antimicrobial, antibacte-
rial [15], antiinfammatory [16], analgesic, antihypertensive [17], tuberculostatic
and anticonvulsant [18] efects. In addition, pyridopyrimidines is very important
class of annelated uracils (Fig. 1) [19] with biological signifcance because of
their connection with the purine pyridine system [20, 21].
Dihydroquinazolin-4(3H)-ones exhibit a broad spectrum of biological and
pharmaceutical activities [22]. Spiro-oxindole fused quinazolinone compounds
show antimalarial, antibacterial, anticancer and antimycobacterial activities [23,
24]. The heterocyclic spiro-oxindole ring system is a widely distributed structural
framework [25] that is present in a number of pharmaceuticals (Fig. 2) and natu-
ral products, including cytostatic alkaloids such as spirotryprostatins A and B and
strychnophylline [26, 27].
Due to the versatile biological activities of pyridopyrimidine carbonitrile
and spiro-oxindole derivatives, they have become important targets of synthetic
organic chemistry. In this context, a number of methods have been reported for
synthesis of these fused heterocycles [28]. Recently reported methods for syn-
thesis of pyrido[2,3-d]pyrimidine carbonitrile include use of triethanolamine in
water at 80 °C [29], glycerol [30], in dimethylformamide (DMF) under micro-
wave irradiation [31], nanocrystalline MgO in water [32], sulfonic acid-func-
tionalized SBA-15 [33], 1,4-diazabicyclo[2.2.2]octane (DABCO)-functionalized
1 3

Aqueous hydrotropic solution: green reaction medium for…
NH2
N
R
N
O
N
HN
O
N
O
N
H
OH
O
N
N
O
Cl
N
O
O
NH2
N
NH2
NH2
N
N
O
N
N
N
H
N
Fig. 1 Biologically active pyridopyrimidine derivatives
CH3
O
O
O
O
N
O
O
NH
O
NH
N
N
H
O
O
N
N
H
N
H
Br
Chorismate mutase inhibitior
CB2 receptor inhibitor
IRAP inhibitior
Cytotoxicity
Fig. 2 Biologically active spiro-oxindole quinazolinone molecules
ionic liquid [34], Fe3O4 nanoparticles in EtOH at 40 °C [35] and Al-HMS-20 in
EtOH at room temperature [36]. Meanwhile, synthesis of spiro-oxindole deriva-
tives has been reported using diferent catalytic systems, such as alum in ethanol
[37], SnCl2·H2O in ethanol under refux condition [38], ethylenediamine in water
under refux condition [39], [HMIm]HSO4 at 100 °C [40], bentonite under ultra-
sound irradiation [23], nano-CuO in ethanol [24], acetic acid under microwave
irradiation [41], Fe3O4GO–SO3H in solvent-free condition at 100 °C [42], nano-
CeO2 in water–ethanol (1:1) system [22] and cetyltrimethylammonium bromide
(CTAB) in water [26] based on the cosolvent efect [43–46]. However, reported
methods sufer from one or more limitations such as use of volatile solvents or
homogeneous catalysts, long reaction time and unsatisfactory yield. To overcome
these difculties and in continuation of our interest in the synthesis of bioactive
molecules [47–51], we developed and describe herein one-pot three-component
synthesis of pyrido[2,3-d]pyrimidine carbonitrile by reaction of aldehyde, malon-
onitrile and 6-amino-1,3-dimethyluracil and spiro-oxindole dihydroquinazolinone
using isatin, aniline and isatoic anhydride in 50 % aqueous hydrotropic medium
at 28 °C.
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A. Patil et al.
Scheme 1 Synthesis of pyrido[2,3-d]pyrimidine carbonitrile
Table 1 Optimization of various hydrotropes
Entry
Hydrotrope
Time (min)
Yielda (%)
1
2
3
4
Sodium benzene sulfonate (NaBS)
Sodium p-xylene sulfonate (NaXS)
Sodium p-toluene sulfonate (NaPTS)
Sodium cumene sulfonate (NaCS)
120
90
25
70
56
65
92
70
Reaction conditions: benzaldehyde (1 mmol), malononitrile (1 mmol) and 6-amino-1,3-dimethyluracil
(1 mmol) in 5 mL aq. hydrotropic solution (50 % w/v) stirred at 28 °C
aIsolated product yield
Results and discussion
Initially, to optimize the reaction conditions, including temperature, solvent and
catalyst, we carried out the reaction of benzaldehyde (1a), malononitrile (2) and
6-amino-1,3-dimethyluracil (3) as model reaction (Scheme 1). To identify a suit-
able hydrotrope for synthesis of pyrido[2,3-d]pyrimidine carbonitrile, we carried
out the model reaction using diferent hydrotropes such as sodium benzene sul-
fonate (NaBS), sodium p-xylene sulfonate (NaXS), sodium p-toluene sulfonate
(NaPTS) and sodium cumene sulfonate (NaCS). Comparatively, higher activity
was observed with NaPTS based on the results presented in Table 1, due to its
overall planar structure and presence of more balanced hydrophobic and hydro-
philic regions generating microunits.
Based on the reaction time and product yield, we considered that the sodium
salt p-toluene sulfonate (NaPTS) was the best hydrotrope for synthesis of
pyrido[2,3-d]pyrimidine carbonitrile. After choosing the suitable hydrotrope, we
screened the model reaction using diferent concentrations of aqueous NaPTS
hydrotropic solution (Table 2, entries 1–8), noting that 50 % aqueous NaPTS gave
the maximum yield of the pyridopyrimidine derivative 4a. Further increase in the
concentration of NaPTS above 50 % failed to increase the product yield. After
optimization of the concentration of NaPTS, we carried out the reaction at difer-
ent temperatures (Table 2, entries 9–12), observing the maximum product yield
at 28 °C. At higher temperature, rate of micelle formation decreses which inturn
result in product yield decrement.
1 3

Aqueous hydrotropic solution: green reaction medium for…
Table 2 Optimization of
Entry
Hydrotrope
Temperature Time (min)
Yielda (%)
reaction conditions for synthesis
of pyridopyrimidine derivatives
concentration (°C)
(% w/v)
1
2
3
4
5
6
7
8
H2O
28
28
28
28
28
28
28
28
40
60
80
100
150
120
100
80
65
50
25
30
30
30
–
5 % NaPTS
10 % NaPTS
20 % NaPTS
30 % NaPTS
40 % NaPTS
50 % NaPTS
60 % NaPTS
50 % NaPTS
50 % NaPTS
50 % NaPTS
50 % NaPTS
40
54
66
75
80
92
90
88
84
80
78
9
10
11
12
30
30
Reaction conditions: benzaldehyde (1 mmol), malononitrile
(1 mmol) and 6-amino-1,3-dimethyluracil (1 mmol) in 5 mL aq.
hydrotropic solution (% w/v) stirred at various temperatures
aIsolated product yield
After optimization of the reaction conditions, we explored the scope of the
reaction for diferent substituted aldehydes (Scheme 2; Table 3, entries 1–18). It
was observed that aldehydes bearing electron-withdrawing as well as electron-
releasing groups underwent the reaction smoothly to aford desired pyridopyrimi-
dine derivatives in excellent yield.
Our next task was to explore the scope of NaPTS for synthesis of spiro-oxin-
dole dihydroquinazolinone derivatives. For this purpose, we reacted isatoic anhy-
dride (5) and isatin (6) with various structurally diverse anilines 7a–o to obtain
a series of spiro-oxindole dihydroquinazolinone derivatives 8a–o (Scheme 3;
Table 4). It was found that various anilines with electron-releasing and elec-
tron-withdrawing substituents gave corresponding spiro-oxindole dihydroquina-
zolinone derivatives in good to excellent yield. However, in case of nitroaniline,
Scheme 2 General reaction for synthesis of pyridopyrimidine carbonitrile derivatives
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A. Patil et al.
Table 3 Synthesis of pyrido[2,3-d]pyrimidine carbonitrile derivatives
Entry
Aldehyde
Product
Time (min)
Yielda (%)
M.p. (°C) obs. [lit.] [Ref.]
1
2
3
4
5
6
7
8
R=H
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
92
92
88
90
86
95
94
92
88
90
86
85
88
89
86
91
88
92
240–243 [242–245] [30]
226–228 [227–229] [30]
221–224 [221–223] [33]
216–218 [215–217] [33]
261–162 [160–162] [30]
226–228 [225–227] [33]
221–224 [221–223] [30]
216–218 [215–217] [33]
302 [>300] [30]
281–282 [280–281] [33]
244–246 [245–247] [30]
242–244 [241–243] [30]
235–237 [234–236] [33]
236–238 [235–237] [30]
266–268 [229–230] [33]
198–200 [197–199] [30]
291–292 [290–292] [33]
266–268 [229–230] [30]
R=4-CH3
R=3-CH3
R=2-CH3
R=4-N(CH3)2
R=4-OCH3
R=3-OCH3
R=2-OCH3
R=3-NO2
R=4-NO2
R=4-F
R=2-Cl
R=4-Cl
R=4-Br
R=4-CN
R=2-OH
R=3-OH
R=4-OH
9
10
11
12
13
14
15
16
17
18
Reaction conditions: aldehyde (1 mmol), malononitrile (1 mmol), and 6-amino-1,3-dimethyluracil
(1 mmol) in 5 mL aq. NaPTS solution (50 % w/v) stirred at 28 °C
aIsolated product yield
Scheme 3 General reaction for synthesis of spiro-oxindole dihydroquinazolinone derivatives
no product formation was observed, which might be due to the strong electron-
withdrawing character of nitro group (Table 4, entry 9).
Recyclability
Recovery and reuse of catalysts is highly preferable for a green process. Thus, the
reusability of the catalyst was investigated using the reaction of benzaldehyde, malo-
nonitrile and 6-amino-1,3-dimethyluracil as model reaction (Scheme 1). After reaction
1 3

Aqueous hydrotropic solution: green reaction medium for…
Table 4 Synthesis of spiro-oxindole dihydroquinazolinone derivatives
Entry
Aniline
Product
Time (min)
Yielda (%)
M.p. (°C) obs. [lit.] [Ref.]
1
2
3
4
5
6
7
8
R=H
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
30
30
30
30
30
30
30
30
–
30
30
30
30
30
30
88
87
86
90
89
86
92
88
–
86
82
88
84
89
85
250–252 [251–253] [37]
278–280 [280–282] [37]
272–276 [274–276] [39]
270–272 [271–273] [37]
276–280 [278–280] [43]
275–276 [274–276] [43]
268–270 [269–271] [37]
294–296 [295–297] [40]
–
248–252 [250–252] [40]
292–294 [293–295] [40]
262–264 [264–266] [37]
294–298 [295–296] [39]
212–214 [213–215] [37]
190–194 [190–192] [37]
R=2-CH3
R=3-CH3
R=4-CH3
R=2-OCH3
R=3-OCH3
R=4-OCH3
R=4-CH2CH3
R=2-NO2
R=2-Cl
R=3-Cl
R=4-Cl
R=4-F
R=4-Br
9
10
11
12
13
14
15
R=benzylamine
Reaction conditions: isatoic anhydride (1 mmol), isatin(1 mmol) and aniline (1 mmol) in 5 mL of aq.
NaPTS solution (50 % w/v) stirred at 28 °C
aIsolated product yield
completion, the reaction mixture was fltered and the fltrate was washed with ethyl
acetate; the obtained NaPTS, after evaporating the aqueous layer, was reused directly
in the next run. It was found that the catalyst could be recycled fve times with only a
slight decrease in product yield.
Plausible reaction mechanism
A plausible reaction mechanism for the synthesis of pyrido[2,3-d]pyrimidine carboni-
trile derivatives is shown in Scheme 4. The SO3H group of NaPTS donates a proton
to the carbonyl carbon of aldehyde and increases the electrophilicity of the carbonyl
carbon and activates the aldehyde 1. This aldehyde reacts with malononitrile 2 to form
intermediate 4, followed by Knoevenagel condensation to produce benzylidene malon-
onitrile 5. Michael addition of 6-amino-1,3-dimethyluracil 3 with intermediate 5 gives
intermediate 6. NaPTS donates another proton to intermediate 6 to form intermediate 7,
which undergoes cyclization to form intermediate 8, followed by aromatization to give
the desired product 10.
1 3

A. Patil et al.
Scheme 4 Plausible reaction mechanism
Conclusions
We describe a protocol based on an efcient multicomponent domino approach for
synthesis of pyridopyrimidine and spiro-oxindole dihydroquinazolinone derivatives
by one-pot reaction in aqueous NaPTS medium. The reactions show broad substrate
scope with no side-product observed. This green synthesis shows various attractive
features such as environmentally friendly reaction medium, fast reaction rate which
enables the reaction to complete within 25–30 min and convenient workup proce-
dure requiring only simple fltration.
Experimental
General
The diferent substrates used for synthesis of various derivatives were purchased from
both Sigma-Aldrich and Alfa Aesar and used without any further purifcation. TLC
was carried out using silica gel G 60 F254 plates (Merck). The melting points of prod-
ucts were determined in open capillary tubes and are uncorrected. 1H and 13C nuclear
magnetic resonance (NMR) and distortionless enhancement by polarization trans-
fer (DEPT)-135 spectra were recorded on a Bruker-Avance 300 MHz and 75 MHz
1 3

Aqueous hydrotropic solution: green reaction medium for…
spectrometer using tetramethylsilane (TMS) as internal standard and CDCl3/dimethyl
sulfoxide (DMSO)-d6 as solvent.
General procedure for synthesis of pyridopyrimidine carbonitrile derivatives
In a round-bottomed fask, a mixture of 2.5 g sodium salt p-toluene sulfonic acid and
5 mL water was stirred for 15 min at 28 °C to obtain 50 % aq. NaPTS solution. Then,
substituted aldehyde (1 mmol), malononitrile (1 mmol) and 6-amino-1,3-dimethylura-
cil (1 mmol) were added to 50 % aq. NaPTS solution and stirred for required time as
indicated in Table 3. Reaction progress was monitored by thin-layer chromatography
(TLC). After reaction completion, 10 mL water was added to the reaction mixture and
solid product was separated by fltration. The obtained product was washed with water
and recrystallized from ethanol to yield pyridopyrimidine carbonitrile derivatives. The
synthesized compounds were identifed by comparison of physical and spectral data
(1H NMR, 13C NMR, MS and FT-IR).
General procedure for synthesis of spiro‑oxindole dihydroquinazolinone
In a round-bottomed fask, a mixture of 2.5 g sodium salt p-toluene sulfonic acid and
5 mL water was stirred for 15 min at 28 °C to obtain 50 % aq. NaPTS solution. Then,
various substituted aniline (1 mmol), isatoic anhydride (1 mmol) and isatin (1 mmol)
were added to 50 % aq. NaPTS solution and stirred for required time as indicated in
Table 4. Reaction progress was monitored by thin-layer chromatography (TLC). After
reaction completion, 10 mL water was added to the reaction mixture and solid product
was separated by fltration. The obtained product was washed with water and recrystal-
lized from ethanol to yield pyridopyrimidine carbonitrile derivatives. The synthesized
compounds were identifed by comparison of physical and spectral data (1H NMR, 13
C
NMR, MS and FT-IR).
Spectral data of selected compounds
7‑Amino‑1,3‑dimethyl‑2,4‑dioxo‑5‑phenyl‑1,2,3,4‑tetrahydropyrido[2,3‑d]
pyrimidine‑6‑carbonitrile (4a)
White solid; m.p.: 240–243 °C (lit. 242–245 °C) [30]; IR (KBr, vmax/cm−1): 3350.72,
3190.42, 3117.30, 2158.16, 1689.55, 1371.18, 1252.64 and 1174.04. 1H NMR
(300 MHz, CDCl3, ppm): δ 3.08 (s, 3H), 3.38 (s, 3H), 7.12-7.28 (m, 5H), 7.38 (s,
2H-NH2). 13C NMR (75 MHz, CDCl3): δ 162.43, 158.40, 151.42, 149.94, 144.70,
130.44, 129.49, 128.82, 127.66, 126.36, 119.58, 29.14, 28.42 ppm. MS: C16 H13N5O2,
m+=307.
1 3

A. Patil et al.
7‑Amino‑5‑(4‑methoxyphenyl)‑1,3‑dimethyl‑2,4‑dioxo‑1,2,3,4‑tetrahydropyrido[2,3
‑d]pyrimidine‑6‑carbonitrile (4f)
White solid; m.p.: 226–228 °C (lit. 225–227 °C) [33]; IR (KBr, vmax/cm−1):
3342.72, 3286.38, 3172.12, 2956.20 2191.70, 1684.79, 1648.30, 1361.98, 1248.04
1
and 1054.14. H NMR (300 MHz, CDCl3, ppm): δ 3.10 (s, 3H), 3.42 (s, 3H), 3.92
(s, 3H), 6.85 (d, 2H, J=6.3 Hz), 7.16 (d, 2H, J=6.0 Hz) 7.32 (s, 2H–NH2). 13C
NMR (75 MHz, CDCl3): δ 161.14, 159.31, 158.15, 151.02, 150.72, 137.24, 129.35,
119.33, 114.06, 59.58 30.18, 28.76 ppm. MS: C17 H15N5O3, m+ =337.
7‑Amino‑1,3‑dimethyl‑5‑(3‑nitrophenyl)‑2,4‑dioxo‑1,2,3,4‑tetrahydropyrido[2,3‑d]
pyrimidine‑6‑carbonitrile (4i)
White solid; m.p.: >300 °C (lit. >300 °C) [30]; IR (KBr, vmax/cm−1): 3373.85,
1
3306.68, 3184.42, 2196.46, 1683.76, 1391.18, 1232.64 and 1194.04. H NMR
(300 MHz, CDCl3, ppm): δ 3.48 (s, 3H), 3.78 (s, 3H), 5.92 (s, 2H-NH2), 7.23-8.40
(m, 4H). 13C NMR (75 MHz, CDCl3): δ 158.80, 158.01, 157.15, 154.82, 150.02,
147.94, 137.70, 132.14, 127.45, 124.02, 122.66, 114.56, 30.28, 28.26 ppm. MS: C16
H12N6O4, m+ =352.
7‑Amino‑5‑(4‑chlorophenyl)‑1,3‑dimethyl‑2,4‑dioxo‑1,2,3,4‑tetrahydropyrido[2,3‑d]
pyrimidine‑6‑carbonitrile (4m)
White solid; m.p.: 235–237 °C (lit. 234–236 °C) [33]; IR (KBr, vmax/cm−1):
3393.05, 3326.28, 3198.47, 2205.76, 1688.71, 1399.88, 1252.61, 1194.04 and
1
850.23. H NMR (300 MHz, DMSO-d6, ppm): δ 3.16 (s, 3H), 3.52 (s, 3H), 7.29
(d, 2H, J=6.6 Hz), 7.51 (d, 2H, J=6.0 Hz), 7.88 (s, 2H-NH2). 13C NMR (75 MHz,
DMSO-d6): δ 161.09, 160.98, 159.11, 158.78, 152.92, 150.43, 135.91, 132.01,
130.11, 128.07, 118.22, 101.52, 89.35, 31.42, 29.62 ppm. MS: C16 H12Cl N5 O2,
(m+2)=341.
3′‑Phenyl‑1′H‑spiro[indoline‑3,2′‑quinoline]‑2,4′(3′H)‑dione (8a)
White solid; m.p.: 250–252 °C (lit. 251-253 °C) [37]; IR (KBr, vmax/cm−1):
1
3690.18, 3225.30, 2840.20, 1721.12, 1615.36, 1480.70, 1340.30 and 750.25. H
NMR (300 MHz, DMSO-d6, ppm): δ 10.43 (s, 1H), 7.72–7.54 (m, 2H), 7.31 (t, 1H,
J=6.3 Hz), 7.19 (t, 2H, J=7.5 Hz and 5.1 Hz) 7.14 (d, 1H, J=6.9 Hz), 7.00–6.90
(m, 4H), 6.77(d, 1H, J=7.2 Hz), 6.70 (d, 2H, J=8.1 Hz), 6.63 (d, 1H, J=7.8 Hz).
13C NMR (75 MHz, DMSO-d6): δ 174.05, 162.02, 146.60, 141.65, 138.00, 133.64,
130.79, 127.60, 126.61, 126.59, 126.46, 126.26, 126.00, 122.14, 117.65, 114.51,
110.08, 76.35. MS: C21 H15 N3 O2, m+ =341.
3′‑(p‑Tolyl)‑1′H‑spiro[indoline‑3,2′‑quinoline]‑2,4′(3′H)‑dione (8d)
White solid; m.p.: 270–272 °C (lit. 271–273 °C) [37]; IR (KBr, vmax/cm−1):
3830.40, 3640.26, 3148.52, 1723.24, 1630.51, 1515.80, 1468.70, 1340.78, 1176.28
1 3

Aqueous hydrotropic solution: green reaction medium for…
1
and 548.97. H NMR (300 MHz, DMSO-d6, ppm): δ 10.44 (s, 1H), 7.73 (d, 1H,
J=7.8 Hz), 7.63 (s, 1H), 7.58 (d, 1H, J=7.2 Hz), 7.35 (t, 1H, J=7.8 Hz), 7.27
(t, 1H, J=7.8 Hz), 7.05 (d, 2H, J=8.2 Hz), 6.98 (t, 1H, J=7.5 Hz), 6.93 (d, 2H,
J=7.8 Hz), 6.82–6.70 (m, 2H), 6.65 (d, 1H, J=7.8 Hz), 2.30 (s, 3H); 13C NMR
(75 MHz, DMSO-d6): δ 178.74, 165.43, 149.90, 145.63, 139.82, 137.44, 134.59,
130.70, 127.45, 126.40, 122.20, 117.62, 114.35, 110.10, 72.45, 22.56; MS: C22
H17N3O2, m+ =355.
3′‑(4‑Methoxyphenyl)‑1′H‑spiro[indoline‑3,2′‑quinoline]‑2,4′(3′H)‑dione (8g)
White solid; m.p.: 268–270 °C (lit. 269–271 °C) [37]; IR (KBr, vmax/cm−1): 3650.40,
1
3289.42, 1720.30, 1589.34, 1350.04, 1240.08 and 748.25. H NMR (300 MHz,
DMSO-d6, ppm): δ 10.40 (s, 1H), 7.68–7.62 (m, 1H), 7.57 (s, 1H), 7.55 (d, 1H,
J=7.2 Hz), 7.32–7.24 (m, 1H), 7.12 (d, 1H, J=1.2 Hz), 6.93 (d, 1H, J=0.9 Hz),
6.88 (d, 2H, J=7.2 Hz), 6.76–6.72 (m, 3H), 6.70 (d, 1H, J=7.8 Hz), 6.65 (d,1H,
J=7.5 Hz), 3.60 (s, 3H): 13C NMR (75 MHz, DMSO-d6): δ 175.84, 172.45, 161.21,
157.12, 146.09, 140.59, 133.57, 130.60, 127.50, 126.53, 122.43, 115.03, 76.05,
54.43; MS: C22 H17N3O3, m+ =371.
Acknowledgements The authors would like to thank the Department of Chemistry, Shivaji University,
Kolhapur, for providing research facilities.
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maps and institutional afliations.
Afliations
Audumbar Patil1 · Ananda Mane1 · Siddharth Kamat1 · Trushant Lohar1 ·
Rajashri Salunkhe1
*
Rajashri Salunkhe
rsschem1@gmail.com
1
Department of Chemistry, Shivaji University, Kolhapur 416004, India
1 3