2-Aminoethanesulfonic acid: An efficient organocatalyst for green synthesis of spirooxindole dihydroquinazolinones and novel 1,2-(dihydroquinazolin-3(4H)isonicotinamides in water

Article abstract of DOI:10.1080/00397911.2019.1692868

A facile and efficient one-pot procedure for the preparation of spirooxindole dihydroquinazolinone derivatives and new N-(4-oxo-2-phenyl-1,2-dihydroquinazolin-3(4H)-yl)isonicotinamides from reaction between isatoic anhydride, isoniazid and substituted ald

Full text of DOI:10.1080/00397911.2019.1692868

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
2-Aminoethanesulfonic acid: An efficient
organocatalyst for green synthesis of
spirooxindole dihydroquinazolinones and novel
1,2-(dihydroquinazolin-3(4H)isonicotinamides in
water
Asha V. Chate, Priyanka P. Rudrawar, Giribala M. Bondle & Jaiprakash N.
Sangeshetti
To cite this article: Asha V. Chate, Priyanka P. Rudrawar, Giribala M. Bondle & Jaiprakash N.
Sangeshetti (2019): 2-Aminoethanesulfonic acid: An efficient organocatalyst for green synthesis
of spirooxindole dihydroquinazolinones and novel 1,2-(dihydroquinazolin-3(4H)isonicotinamides in
water, Synthetic Communications, DOI: 10.1080/00397911.2019.1692868
To link to this article: https://doi.org/10.1080/00397911.2019.1692868
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https://doi.org/10.1080/00397911.2019.1692868
2-Aminoethanesulfonic acid: An efficient organocatalyst for
green synthesis of spirooxindole dihydroquinazolinones
and novel 1,2-(dihydroquinazolin-3(4H)isonicotinamides
in water
Asha V. Chatea, Priyanka P. Rudrawara, Giribala M. Bondlea, and
Jaiprakash N. Sangeshettib
aDepartment of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, India;
bDepartment of Quality Assurance, Y. B. Chavan College of Pharmacy, Rafiq Zakaria Campus,
Aurangabad, India
ABSTRACT
ARTICLE HISTORY
Received 18 July 2019
A facile and efficient one-pot procedure for the preparation of spi-
rooxindole dihydroquinazolinone derivatives and new N-(4-oxo-2-
phenyl-1,2-dihydroquinazolin-3(4H)-yl)isonicotinamides from reaction
between isatoic anhydride, isoniazid and substituted aldehydes cata-
lyzed by 2-aminoethanesulfonic acid (taurine) is describe. This new
protocol has the advantages of environmental friendliness, good
yields, and convenient operation. The reaction proceeds efficiently
using water as green solvent and nontoxic catalysts that could be
efficiently reused. Together with this simple workup procedure, use
of the organocatalyst, and water as solvent without the need of col-
umn chromatographic purification, are the notable features of this
methodology, which make this protocol a very efficient and green
alternative to the traditional methods.
KEYWORDS
2-Aminoethanesulfonic acid
(taurine); 2,3-
dihydroquinazolin-4(1H)-
ones; multicomponent
reaction; spirooxindole
GRAPHICAL ABSTRACT
CONTACT Asha V. Chate
chateav@gmail.com
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada
University, Aurangabad, Maharashtra 431004, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
A. V. CHATE ET AL.
Introduction
On the ground of environmental concerns, chemists and researchers are switching their
interest towards synthetic processes which incorporate the environmentally benign
reagents for the synthesis of highly privileged scaffolds and this has emerged as a phe-
nomenally recommended platform.[1] Within this context, Chemical reactions in the
presence of organocatalysis[2] have gained widespread attention as a result of the effi-
ciency and selectivity for many reactions. Novel methods employing organic molecules
are advantageous from both a practical and an environmental standpoint.
Recently, the commercially available and inexpensive amino acid such as taurine (2-
aminoethanesulfonic acid) has been elegantly used to catalyze some organic reaction. 2-
Aminoethanesulfonic acid is ubiquitous sulfur-containing amino acids in nature, which
can be extracted from many biological organisms.[3] For the existence of the –SO3H
group, taurine has the potential to function as proton-acid catalysts in the oxidation of
sulfides to sulfoxides employing aqueous hydrogen peroxide as oxidant. Some different
applications of taurine derivatives comprise nanosensors,[4] organogelators,[5] or water-
soluble dyes.[6] In addition to this, they improve water solubility and are capable to
form H-bonds while their strong inductive effect can be utilized to tune pKa values of
adjacent or remote amino groups.[7] On the other hand the structural and electronic
properties might mimic transition states to tetrahedral intermediates.[8] Besides being 2-
aminoethanesulfonic acid is a readily available and environmentally benign catalyst.
These features make 2-aminoethanesulfonic acid not only an alternative catalyst for a
transition-metal free approach but also a good choice in strategies of catalytic chemistry
for some organic transformation. Several groups have studied the organic transform-
ation using taurine of sul-fonic acids.[9]
Over the past few decades, multicomponent reactions (MCRs) have gained consider-
able interest in both academia and industry owing to exceptional synthetic efficiency,
intrinsic atom-economy, high reactivity, and procedural simplicity.[10] These strategies
were subsequently replaced by the cascade/domino or multicomponent reaction, which
allow the formation of complex molecular architectures under ambient conditions and
without the need of protecting groups and purification of intermediates.[11,12] In add-
ition, they are recognized as processes with minimal waste generation. In this way, mul-
ticomponent or cascade reactions fall under the category of green chemical
transformations. The development of new organocatalyst for the construction of struc-
turally and stereochemically diverse compounds by MCRs approach would be signifi-
cant and extremely useful.[13]
Nitrogen-containing heterocycles are among the most common structural motifs in
bioactive compounds.[14] In particular, 2,3-Dihydroquinazolinone is increasingly attract-
ive scaffolds, which play a key role in various cellular processes. Furthermore, quinazoli-
none skeleton is frequently found in various natural products.[15,16] They also possess a
wide range of pharmacological activities such as antitumor, analgesic, antiviral, and
antimicrobial activities.[17–20] In addition, these compounds can be easily oxidized to
the corresponding 4(3 H)-quinazolinones,[21,22] which are important biologically active
heterocyclic compounds. Spiro compounds contain two rings fused at a central spiro
atom, and they possess a unique 3 D conformation. Chemists are fascinated with spiro-
cycles for more than a hundred years, since there is an impressive number of spirocyclic

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3
Figure 1. Some natural and synthesized bioactive molecules contained quinazolinone or spirooxindole
scaffolds.
representatives, in natural product synthesis,[23] such as Marcfortine B, Spirotryprostatin
B, and Cyclopiamine B.[24] Considering the intriguing molecular architecture and potent
biological activities, various protocols have been developed to synthesize this class of
molecules.[25,26] It is notable that spirooxindole dihydroquinazolinone derivatives com-
bine two pharmacophoric subunit into one molecule, leads to the design of new hybrid
architectures. Furthermore, quinazolinone skeleton with spirocyclic compound (Fig. 1).
is frequently found in various natural products and significant role in medicinal chemis-
try for their biological activity as antibacterial, antiinflammatory, anticancer and
laxatives.[27,28]
Among the different strategies reported for the preparation of 2,3-dihydroquinazoli-
nones,[29–37] the organocatalytic synthesis via cascades has attracted particular interest,
however, the reported methods suffered from some inconveniences such as corrosive
solvent, special reactor and narrow substrate scope, etc. Therefore, keeping in mind the
importance of 2,3-Dihydroquinazolinones and spirooxindole moiety, and atom econom-
ical approaches for the construction of the spirooxindole dihydroquinazolinones scaffold
are still in demand, we herein wish to report a convenient, clean, facile, and organocata-
lytic practical method for the synthesis of spirooxindole dihydroquinazolinones
molecular skeletons and a new series of functionalized N-(4-oxo-2-phenyl-1,2-dihydro-
quinazolin-3(4H)-yl)isonicotinamides in water at heating conditions, the overall results
are summarized in (Scheme 1).
Result and discussion
During the course of our initial investigation reaction of isatoic anhydride (1), aniline
(2a), and isatin (3a) was used as the standard model reaction in a one-pot manner to
investigate experimental conditions including catalysts and solvents (Scheme 2). Initially
standard model reaction was carried out without the aids of any catalyst in the presence

4
A. V. CHATE ET AL.
Scheme 1. The pathway for synthesis of 3’-phenyl-1’H-spiro[indoline-3,2’-quinazoline]-2,4’(3’H)-dione
4a–r and N-(4-oxo-2-phenyl-1,2-dihydroquinazolin-3(4H)-yl)isonicotinamide 7a–j derivatives.
Scheme 2. Standard model reaction.
of suitable solvent under heating conditions, thereby isolating the desired product 4a in
trace amount yield after the prolong reaction time. Then we performed the same reac-
tion of isatoic anhydride (1), aniline (2a), and isatin (3a) in water at 80 ꢀC in the pres-
ence of 15 mol% of catalyst 2-aminoethanesulfonic acid (taurine) gave the desired
product 4a in 90% yield (Scheme 2). We also tried different catalyst such as
KAl(SO4)2ꢁ12H2O, b–CD, and Tris-buffer afforded the moderate yield as compare to
taurine (Table 1, entries 1–3) under similar reaction conditions but no appreciable
increment in product yield was observed. Then it was thought worthwhile to study the
reaction in the presence of organocatalyst like taurine (Table 1, entries 1–3). This sug-
gests that the presence of organocatalyst is pivotal for the catalytic efficiency. The best
result was obtained with the 2-aminoethanesulfonic acid which gave 90% yield of 4a
(Table 1, entry 4), hence we decided to use 2-aminoethanesulfonic acid for further opti-
mization studies.
Further to investigate the solvent effect on the above reaction, various solvent such as
protic and aprotic solvents have been used for model reaction. Obviously, protic

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Table 1. Optimization studies for the synthesis of spirooxindole dihydroquina-
zolinones using different catalyst.a
Entry
Catalyst
Time (hr)
Yieldb (%)
1.
2.
3.
4.
KAl(SO4)2.12H2O
b-CD
Tris buffer
Taurine
3–4
2–3
4–6
2–3
65
88
55
90
aAll reactions were carried out using isatoic anhydride (1), aniline (2a) and isatin (3a), and
solvent under reflux condition.
bIsolated yield.
Table 2. Optimization of solvent study for the synthesis of spirooxindole
dihydroquinazolinones.a
Entry
Taurine (mol%)
Solvent
CH3CN
Toluene
Chloroform
methanol
Ethanol
EtOH:H2O (9:1)
EtOH:H2O (1:9)
Water
Condition (Reflux)
Yieldb (%)
1.
2.
3.
4.
5.
6.
7.
8.
15
15
15
15
15
15
15
15
2–3 hr
2–3 hr
2–3 hr
2–3 hr
2–3 hr
2–3 hr
2–3 hr
2–3 hr
65
78
61
66
70
76
80
90
aAll reactions were carried out using isatoic anhydride (1), aniline (2a) and isatin (3a) taurine
and solvent under reflux condition.
bIsolated yield.
Table 3. The effect of amount of taurine in the preparation of 4a by isatoic
anhydride (1), aniline (2) and isatin (3) in water.a
Entry
Solvent
Mol% of Taurine
Time (hr)
Yieldb (%)
1.
2.
3.
4.
5.
Water
Water
Water
Water
Water
–
5
10
15
20
9–10
7–8
5–6
2–3
2–3
–
55
67
90
90
aAll reactions were carried out using isatoic anhydride (1), aniline and isatin, taurine and
solvent under reflux condition.
bIsolated yield.
solvents were better for the reaction, especially when EtOH:H2O (9:1) was applied
(Table 2, entry 6), Encourage by this result, we carried on with examining the effect of
solvents using different ratio EtOH:H2O (1:9) and H2O. It was clear that the highest
yield of product 3a was achieved when the reaction was performed in water (Table 2,
entry 8). From green chemistry perspective, water is considered as a safe and uniquely
redox-stable green solvent which facilitates typical solvation and molecular assembly
processes, leading to the remarkable modes of reactivity and selectivity of a wide variety
of organic reactions.[38–44] In order to establish the correct concentration of catalyst for
the above model reaction, the model reaction was further performed by changing the
concentration of taurine in 5, 10, 15 and 20 mol% respectively for 2–3 h. Increasing the
catalyst loading slightly improve the yield, the highest yield of 90% when 15 mol% of 2-
aminoethanesulfonic acid was used (Table 3, entry 4). On the other hand, the yield
of the compound 4a was not significantly improve when the amount of

6
A. V. CHATE ET AL.
2-aminoethanesulfonic acid catalyst increase to 20 mol% (Table 3, entry 5). Finally,
15 mol% of catalyst was concluded to be ample to catalyze the above conversion.
To explore the temperature effect, initially above model reaction performed at
ambient temperature and achieved the desired product in very low yield increasing
the reaction temperature to 80 ꢀC resulted in high yield of the desired product.
Further increase in temperature was detrimental for the reaction as several byprod-
ucts were observed.
With the optimized conditions in hand, to check the generality as well as effective-
ness of this newly developed protocol, a number of functionalized aromatic anilines
were reacted with isatin and isatoic anhydride using identical reaction conditions; all of
these eighteen entries underwent the reaction smoothly, affording the corresponding 30-
phenyl-10H-spiro[indoline-3,20-quinazoline]-2,40(30H)-diones 4b–r (Table 4, entries
2–18) in excellent yields ranging from 75% to 90% at heating condition within 2–4 hr.
Inspired by these results, we then replace aniline with isoniazid and isatin with aldehyde
and carried out a similar set of one reactions from the mixture of this isatoic anhydride,
isoniazid with aldehyde in water using 15 mol% of 2-aminoethanesulfonic acid at heat-
ing condition. To our delight, the reaction produces the expected product in 90% yield
respectively within 2–4 hr (Scheme 3). We then extended this methodology in synthesiz-
ing nine more new N-(4-oxo-2-phenyl-1,2-dihydroquinazolin-3(4H)-yl)isonicotinamide
derivatives 7b–j from one pot reaction of isatoic anhydride, isoniazid with functional-
ized aromatic aldehydes using identical reaction conditions; all of them underwent the
reaction in a facile manner, affording the desired products 7b–j (Table 5, entries 2–10)
with excellent yields ranging from 85% to 94% within 2.5 ꢂ 4 hr. All the synthesized
1
compounds were well characterized by spectral H NMR, IR, 13C NMR, Mass spectra
and elemental analysis data.
For the industrial applications through a green chemistry approach, recyclability of
catalysts is highly desirable. We evaluated the reusability of 2-aminoethanesulfonic
acid for both the reactions of spirooxindole dihydroquinazolinones and N-(4-oxo-2-phe-
nyl-1,2-dihydroquinazolin-3(4H)-yl)isonicotinamides. The 2-aminoethanesulfonic acid
could be easily recovered and reused for at least three runs without any significant
impact on the yield of the products (Fig. 2). The purification of 2-aminoethanesulfonic
acid catalyst after the recycling was confirmed by IR spectra shown in (Fig. 3).
Experimental
Materials and methods
All the chemicals used were of laboratory grade. Melting points of all the synthesized
compounds were determined in open capillary tube and are uncorrected. Progress of
the reaction was monitored by thin layer chromatography on Merck’s silica plates
and visualization was accomplished by iodine/ultraviolet light. IR spectra were
obtained on a Bruker ALPHA (Eco-ATR) spectrometer. 1H NMR spectra of were
recorded with an NMR predict proton DMSO (BRUKER/TOPSPIN) spectrometer
operating at 700 MHz using DMSO solvent and trimethylsilane (TMS) as the internal
standard and chemical shift in d ppm and 13C NMR at 176 MHz, DMSO, Mass spec-
tra were recorded on a Waters (BRUKER/TOPSPIN) (ESI-MS and APCI-MS)

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Table 4. 2-Aminoethanesulfonic acid catalyzed one-pot synthesis of spirooxindole dihydroquinazoli-
nonesa 4a–r.
Sr. No.
1.
Entry
Product
Time (hr)
2.5
Yieldb (%)
4a
90
2.
3.
4b
4c
3
4
81
82
4.
4d
4
85
5.
6.
4e
4f
4
86
90
4.5
7.
8.
4g
4h
4
3
87
90
(continued)

8
A. V. CHATE ET AL.
Table 4. Continued.
Sr. No.
9.
Entry
Product
Time (hr)
3.5
Yieldb (%)
86
4i
10.
11.
12.
4j
4.5
89
75
87
4k
5
4l
6
13.
14.
15.
4m
4n
4o
6
89
90
88
6.5
6.5
16.
4p
5.5
90
(continued)

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9
Table 4. Continued.
Sr. No.
17.
Entry
Product
Time (hr)
6
Yieldb (%)
89
4q
18.
4r
6
88
aAll reactions were carried out using isatoic anhydride (1), aniline 2 (a–r) and isatin (3a), taurine and solvent under
reflux condition.
bIsolated yield.
Scheme 3. Synthesis of 2,3-dihydroquinazolinones.
Instrument and elemental analysis were recorded on CHNS autoanalyser
Thermofischer (FLASH EA1112 SERIES).
General procedure for synthesis of 1’H-spiro[indoline-3,2’-quinazoline]-2,4’(3’H)-dio-
nes 4a–r
A equimolar mixture of isatoic anhydride (1.0 mole), aniline (1.0 mole), and isatins
(1.0 mole) was taken in 10 mL water in 100 mL round bottom flask and 15 mol% of
taurine catalyst was added to this reaction mixture. The reaction content was heated for
the appropriate time given in (Table 4). After the completion of reaction, which was
monitored by TLC, the reaction mixture was allowed to cool and 10 mL of water was
added and stirred for 3 min. During this time, the product was precipitated and subse-
quently separated by filtration. The separated product was washed with water for several
times. After drying, the pure product was obtained; there was no need for further puri-
fication by column chromatography or addition of any organic solvent. Furthermore,
water was evaporated from the filtrate to recycle and recovered the taurine catalyst. The
recovered taurine reused for same transformation 2–3 consecutive runs without any sig-
1
nificant loss in yield and activity. The products were characterized by M. P., FT-IR, H
NMR, 13C NMR, Mass spectra and elemental analysis and are good agreement with the
reported compounds.[39]

10
A. V. CHATE ET AL.
Table 5. Synthesis of new 2,3-dihydroquinazolinonesa derivatives7a–j.
Sr. No.
1.
Entry
Product
Time (hr)
2.5
Yieldb (%)
90
7a
2.
3.
4.
7b
7c
7d
3.5
85
87
93
4
3.5
5.
6.
7e
3.5
4.5
86
90
7f
7.
7g
3
88
(continued)

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11
Table 5. Continued.
Sr. No.
8.
Entry
7h
Product
Time (hr)
4
Yieldb (%)
94
9.
7i
4
87
10.
7j
2.5
90
aAll reactions were carried out using isatoic anhydride (1), isonizid (5) and aldehyde 6 (a–j), taurine and solvent under
reflux condition.
bIsolated yield.
92
90
88
86
Catalyst recovery
Yield
84
82
80
Fresh
Run 1
Run 2
Run 3
Figure 2. Reuse and recovery of 2-aminoethanesulfonic acid (taurine) and its effect on yield.
Spectral analysis of 3’-phenyl-1’H-spiro[indoline-3,2’-quinazoline]-2,4’(3’H)-dione (4a)
IR (ATR) ꢀmax cmꢂ1: 3243 (NH), 3059 (NH), 1735 (C¼O), 1706 (C¼O), 1454, 1326
1
1
(Ar–H). H NMR 700 MHz, DMSO): d 10.29 (s, CONH); H NMR (400 MHz, DMSO)
d 10.77 (s, 1 H), 7.77 (dd, J ¼ 7.7, 1.5 Hz, 1 H), 7.67 (s, 1 H), 7.53 (d, J ¼ 7.2 Hz, 1 H),
7.31 (ddd, J ¼ 8.1, 7.4, 1.6 Hz, 1 H), 7.27 (t, J ¼ 7.4 Hz, 2 H), 7.17 (ddd, J ¼ 9.0,
4.9,1.2 Hz, 2 H), 7.15–6.99 (m, 2 H), 6.95 (t, J ¼ 7.6, 0.9 Hz, 1 H), 6.91–6.87 (m, 1 H),
6.76 (d, J ¼ 8.1 Hz, 1 H), 6.63 (d, J ¼ 7.7 Hz, 1 H);13C NMR (100 MHz, DMSO-d6): d

12
A. V. CHATE ET AL.
3500
3000
2500
2000
1500
1000
Wavenumber cm-1
Figure 3. FT-IR spectral analysis of the fresh 2-aminoethanesulfonic acid (green) and after 3rd time
reused catalyst (blue).
175.66, 164.56, 146.10, 131.79, 128.60, 127.69, 127.40, 127.29, 126.47, 117.75, 115.57,
114.08, 110.57, 75.33. Elemental Analysis Calcd. For C21H15N3O2: C, 73.89; H, 4.43; N,
12.31; Found: C, 73.85; H, 4.46; N, 12.35; LC-MS (ESI, m/z): 342.18 (M þ 1).
General procedure for synthesis of N-(4-oxo-2-phenyl-1,2-dihydroquinazolin-3(4H)-
yl)sonicotinamide 7a–j
A equimolar mixture of isatoic anhydride (1.0 mole), isoniazid (1.0 mole), aldehyde
(1.0 mole) was taken in 10 mL water in 100 mL round bottom flask and 15 mol% of
taurine catalyst was added to this reaction mixture. The reaction content was heated for
the appropriate time given in (Table 5). After the completion of reaction, which was
monitored by TLC, the reaction mixture was allowed to cool and 10 mL of water was
added and stirred for 3 min. During this time, the product was precipitated and subse-
quently separated by filtration. The separated product was washed with water for several
times. After drying, the pure product was obtained; there was no need for further puri-
fication by column chromatography or addition of any organic solvent. Furthermore,
water was evaporated from the filtrate to recycle and recovered the taurine catalyst. The
recovered taurine reused for same transformation 2–3 consecutive runs without any sig-
nificant loss in yield and activity. The obtained new products were characterized by
1
M. P., FT-IR, H NMR, 13C NMR, Mass spectra and elemental analysis.
N-(4-oxo-2-phenyl-1,2-dihydroquinazolin-3(4H)-yl)isonicotinamide (7a)
1
IR (ATR) ꢀmax cmꢂ1: 3303, 3189, 3038, 1793, 1651, 1600, 1492, 1402, 1287, 1052; H
NMR (400 MHz, CDCl3): d 8.65–8.80 (dd, J ¼ 9.2 Hz, 2 H, Ar–H), 8.38–8.48 (dd, 2 H,

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13
Scheme 4. A plausible mechanism for the product formation of 3’-phenyl-1’H-spiro[indoline-3,2’-
quinazoline]-2,4’(3’H)-dione.
Ar–H), (8.16 (s, 1 H, -NH), 7.94–7.57 (m, 4 H, Ar–H), 7.54–7.11 (m, J ¼ 2.8, 5.2, 3.6 Hz,
5 H, Ar–H), 6.35 (s, 1 H, -CH), 5.35 (s, 1 H, -NH); 13C NMR (125 MHz, DMSO): d
164.42, 158.92, 150.02, 149.64, 149.13, 145.02, 143.11, 132.12, 129.71, 126.53, 124.12,
121.13, 118.19, 112.92, 85.21; Elemental Analysis Calcd. For C20H16N4O2: C, 69.76; H,
4.68; N, 16.27; Found: C, 69.75; H, 4.72; N, 16.23; LC-MS (ESI, m/z): 344.3 (M þ 1).
Reaction mechanism
According to the relevant literature,[36] the plausible pathway for 2-aminoethanesulfonic
acid catalyzed these one-pot three component reactions was suggested in (Scheme 4).
2-Aminoethanesulfonic acid (taurine) acts as a bifunctional donor–acceptor reagent in
which the isatoic anhydride (1) carbonyl site is activated by taurine to give intermediate
8, which could facilitate nucleophilic attack of aniline (2a) on the carbonyl unit.
Nucleophilic addition of aniline (2a) to isatoic anhydride 1, followed by decarboxylation,
produced 2-aminobenzamide 9, condensation of 9 with protonated isatin, prepared using
taurine, gave imine 10, which underwent intramolecular cyclization to afford product 4a.
The plausible pathway for 2-Aminoethanesulfonic acid (taurine) catalyzed these
one-pot three component reactions was suggested in (Scheme 5). First, the isatoic anhy-
dridewas activated by 2-aminoethanesulfonic acid in the protic solvent, then the N-
nucleophilic attack isoniazid (5) to the isatoic anhydride formed intermediate 8 with
the decarbonylation. Next, the imine intermediate 9 was given by nucleophilic attack of
aldehyde that promoted by 2-aminoethanesulfonic acid. Finally, the product 7a formed
from 9 by intermolecular cyclization.
Conclusion
In summary, we have developed a novel, simple and efficient protocol for the synthesis
of 1’H-spiro[indoline-3,2’-quinazoline]-2,4’(3’H)-diones 4a–r and new N-(4-oxo-2-

14
A. V. CHATE ET AL.
Scheme 5. A plausible mechanism for the formation of N-(4-oxo-2-phenyl-1,2-dihydroquinazolin-
3(4H)-yl)isonicotinamide.
phenyl-1,2-dihydroquinazolin-3(4H)-yl)isonicotinamide 7a–j derivatives using 2-aminoe-
thanesulfonic acid (taurine) as a recyclable heterogeneous organocatalyst. Additionally
the use of readily available and inexpensive catalyst 2-aminoethanesulfonic acid (taur-
ine) make this system highly atom economical which makes the overall synthesis, is
applicable in the quick access to relevant pharmaceutical molecules in one pot. This
reaction is expected to open a new convenient and versatile route to access the structur-
ally important spirooxindole dihydroquinazolinones family. The catalyst could be recov-
ered and recycled without a significant loss in the catalytic activity, which is one of the
most important limitations associated with the use of homogeneous catalysts.
The supplementary information provides full experimental procedures and character-
ization of all compounds in this article.
Acknowledgments
The authors are thankful to Professor Charansingh H. Gill for his invaluable discussions and
guidance. The authors are thankful to the Department of Chemistry for providing the necessary
facilities for completing this work.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
The authors are also thankful to the Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad for providing funding through [MRP-STAT/VI/RG/Dept/219-20/325-26].

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