An efficient green approach for the synthesis of novel triazolyl spirocyclic oxindole derivatives via one-pot five component protocol using DBU as catalyst in PEG-400

Article abstract of DOI:10.1016/j.tetlet.2016.05.084

We have described an efficient one-pot five component reaction of acetylacetone, aryl azides, aromatic aldehydes, isatin and L-proline using DBU as catalyst in PEG-400 at 80?°C for the construction of novel heterocyclic triazolyl spirocyclic oxindole derivatives. Structures of all synthesized novel compounds have been confirmed by spectral and X-ray studies. Crystal packing of compound 6i has also been reported. Green solvent, less reaction time, easy work up and high yields are the salient features of the present protocol. The same reaction has also been reported by stepwise reactions including a one-pot three component reaction.

Full text of DOI:10.1016/j.tetlet.2016.05.084

Accepted Manuscript
An efficient green approach for the synthesis of novel triazolyl spirocyclic ox-
indole derivatives via one-pot five component protocol using DBU as catalyst
in PEG-400
Sudesh Kumari, Harjinder Singh, Jitender M. Khurana
PII:
S0040-4039(16)30617-7
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.05.084
TETL 47703
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
19 April 2016
14 May 2016
22 May 2016
Please cite this article as: Kumari, S., Singh, H., Khurana, J.M., An efficient green approach for the synthesis of
novel triazolyl spirocyclic oxindole derivatives via one-pot five component protocol using DBU as catalyst in
PEG-400, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.05.084
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
An efficient green approach for the synthesis of novel Leave this area blank for abstract info.
triazolyl spirocyclic oxindole derivatives via one-pot
five component protocol using DBU as catalyst in
PEG-400
Sudesh Kumari, Harjinder Singh and Jitender M. Khurana*
Five
components
in one pot
Ar'-CHO
O
Ar'
O
O
Ar
DBU (10 mol%)
PEG-400, 80oC
N
HOOC
N
O
N
N
N
N
H
O
Ar-N3
H
N
O
H
Short reaction time
High yields of products

1
Tetrahedron Letters
An efficient green approach for the synthesis of novel triazolyl spirocyclic
oxindole derivatives via one-pot five component protocol using DBU as catalyst
in PEG-400
Sudesh Kumari, Harjinder Singh and Jitender M. Khurana*
Department of Chemistry, University of Delhi, Delhi-110007
*Email:- jmkhurana1@yahoo.co.in, jmkhurana@chemistry.du.ac.in
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
We have described an efficient one-pot five component reaction of acetylacetone, aryl azides,
aromatic aldehydes, isatin and L-proline by using DBU as catalyst in PEG-400 at 80oC for the
construction of novel heterocyclic triazolyl spirocyclic oxindole derivatives. Structures of all
synthesized novel compounds have been confirmed by spectral and X-ray studies. Crystal
packing of compound 6i has also been reported. Green solvent, less reaction time, easy work up
and high yields are the salient features of the present protocol. The same reaction has also been
reported by stepwise reactions including a one-pot three component reaction.
Available online
Keywords:
Spirooxindole
1,2,3-triazole
[3+2] cycloaddition
Azomethine ylides
Multicomponent reaction
2009 Elsevier Ltd. All rights reserved.
Spirocyclic oxindoles1 are important heterocycles with diverse
biological activities including antibacterial, antifungal,
anticonvulsant, antiviral and antiproliferative.2 They acts as
potent inhibitors of monoamine oxidase in human urine, rat
tissues3 and acetylcholinesterase,4 They also act as antagonist of
in vitro receptor binding by atrial natriuretic peptide5 and possess
a wide range of CNS activities.6 Spiro oxindole ring system also
occurs in nature as a part of some natural products with diverse
biological activities such as paraherquamide A which possesses
N
N
O
O
H
H
O
H
O
O
H
O
N
N
NH
N
OH
O
O
O
O
N
N
N
MeO
Spirotryprostatin A
H
H
Spirotryprostatin B
OMe
Paraherquamide A
O
O
O
F
S
O
N
O
Me
Me
Me
F
N
HN
N
Ph
O
H
N
Boc
O
N
H
F
Antimalarial
Luminescent spirooxindole
Antituberculosis
antiparasitic
activity
and
antinematodal
properties,7
N
spirotryprostatins A and B8 which possess anti-mitotic and anti-
cancer properties etc. (Figure 1). 1,2,3-Triazoles are another
privileged nitrogenous heterocycles with a plethora of biological
activities including antiHIV,9 antimicrobial,10 antiviral,11
antiproliferative,12 antibiotics,13 insecticides14 and fungicidal.15
Fluconazole16 is a well-known antifungal drug consisting of
1,2,3-triazole ring, while Tazobactum17 is a broad spectrum
antibiotic for treatment of various infections (Figure 1).
N
O
H
O
OH
C8H17
N
S
N
N
N
N
N
F
N
N
O
OH
O
F
Fluoconazole
Tazobactum
Figure 1: Some biologically active compounds containing
spirooxindole and 1,2,3-triazole core structure.
Multicomponent reactions (MCRs) offer valuable strategies for
the synthesis of complex molecules with several advantages e.g.
elimination of intermediate steps, diversity, high efficiency,

2
Tetrahedron
selectivity and minimal waste production.18 Polyethylene glycol
NO2
NO2
N3
CHO
O
(PEG-400) and modified polyethylene glycol derivatives have
become popular alternate reaction media due to their non-
toxicity, bio-compatibility and bio-degradability compared to
other ‘neoteric solvents’ such as ionic liquids, super-critical
fluids and micellar systems.19 1,8-Diazabicyclo[5.4.0]undec-7-
ene (DBU), regarded as a non-nucleophilic, strong tertiary amine
base has been widely used as an effective corrosion free catalyst
in many organic transformations in recent years.20
O
O
HOOC
O +
+
+
+
N
N
N
N
H
H
N
NO2
3a
NO2
2a
N
O
1
4
5
N
O
H
6a
Scheme 1: Model reaction for synthesis of 2'-(5-methyl-1-(4-
nitrophenyl)-1H-1,2,3-triazole-4-carbonyl)-1'-(4-nitrophenyl)-
1',2',5',6',7',7a'-hexahydrospiro[indoline-3,3'-pyrrolizin]-2-one
(6a)
The above reaction was then repeated in glycerol, ethylene glycol
and 1,4-dioxane as solvents under otherwise identical conditions.
The reactions were complete in 120 min, 100 min and 90 min
and gave 74%, 75% and 87% yield of product 6a, respectively
(Table 1, entries 3, 4 and 5). The same reaction was then
explored in PEG-400 under otherwise identical conditions. The
reaction was found to be complete in 40 min and gave 93% yield
of the desired product 6a (Table 1, entry 6). Thus, the best results
were obtained when this five-component reaction was attempted
in PEG-400, and hence PEG-400 was chosen as suitable solvent
for further exploration of this reaction. To determine the effect of
bases other than DBU over this model reaction, the five-
component model reaction was attempted using K2CO3 (10
mol%), DABCO (10 mol%) and piperidine (10 mol%) as base
catalyst in PEG-400 at 80oC. This gave desired product 6a in
Therefore, in continuation of our research interest in the synthesis
of potentially bioactive heterocyclic compounds with diverse
applications,21 we decided to investigate the synthesis of novel
conjugates consisting of spirocyclic oxindole and 1,2,3-triazoles
in a single matrix through MCR approach under green
conditions.
The present manuscript reports a new, diversity oriented and
highly efficient green protocol for the synthesis of novel 1,2,3-
triazole tethered spirooxindole derivatives namely 2'-(5-methyl-
1-aryl-1H-1,2,3-triazole-4-carbonyl)-1'-aryl-1',2',5',6',7',7a'-
hexahydrospiro[indoline-3,3'-pyrrolizin]-2-ones via one-pot five
component condensation of acetylacetone, aryl azides, aromatic
aldehydes, isatin and L-proline using DBU as organocatalyst in
PEG-400 at 80oC.
The optimized reaction conditions for this proposed five-
component reaction were established by attempting model
reaction for the synthesis of 6a (Scheme 1) comprising
acetylacetone (1) (1.0 mmol), 4-nitrophenyl azide (2a) (1.0
mmol), 4-nitrobenzaldehyde (3a) (1.0 mmol), isatin (4) (1.0
mmol) and L-proline (5) (1.0 mmol) under different reaction
conditions as shown in Table 1. First, the model reaction of
acetylacetone (1) (1.0 mmol), 4-nitrophenyl azide (2a) (1.0
mmol), 4-nitrobenzaldehyde (3a), isatin (4) and L-proline (5) was
carried out using DBU (10 mol%) as base in H2O and EtOH at
80oC. The progress of the reactions was monitored by TLC
(eluent: ethyl acetate: petroleum ether, 40:60, v/v) and reactions
were found to be incomplete even after 300 min. After work-up
and separation by column chromatography, desired product 2'-(5-
methyl-1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carbonyl)-1'-(4-
nitrophenyl)-1',2',5',6',7',7a'-hexahydrospiro[indoline-3,3'-
pyrrolizin]-2-one (6a) was obtained in 37% and 42% yield
respectively (Table 1, entries 1 and 2).
70%, 72% and 45%, respectively (Table 1, entries 7-9). The
effect of temperature and catalyst loading on the reaction time
and yield of the product was also examined. The above reaction
using DBU (10 mol%) in PEG-400 was therefore attempted at
higher temperature (100oC), lower temperature (60oC), lower
loading of catalyst (5%) and higher loading of catalyst (15%).
There was no significant effect on the product yield and time of
reaction under these conditions (entries 10-13).
Thus, condensation of five-components in one-pot using DBU
(10 mol%) in PEG-400 at 80oC were chosen as optimum
reaction conditions for further study of scope of this reaction.
Subsequently, reactions were attempted with differently
substituted azides and aromatic aldehydes under the optimized
conditions. All the reactions were facile and complete in less than
60 min with both electron rich and electron deficient aryl azides
and aldehydes affording the desired products 6a-6o in high yields
(Scheme 2).24 All the results have been compiled in Table 2.
1
Structural assignments have been made on the basis of H NMR,
13C NMR, IR and mass spectra.

3
1
symmetric stretch). The H NMR spectrum of 6a showed a
Table 1: Optimization for the synthesis of 2'-(5-methyl-1-(4-
nitrophenyl)-1H-1,2,3-triazole-4-carbonyl)-1'-(4-nitrophenyl)-
1',2',5',6',7',7a'-hexahydrospiro[indoline-3,3'-pyrrolizin]-2-one
(6a)a
sharp singlet at δ 10.41 for NH proton, twelve aromatic protons
in the range of δ 8.40-6.57, one methine proton appeared as
doublet at δ 4.95 (3J= 10.68 Hz, vicinal coupling) and two
methine protons as multiplets at δ 4.16-4.11 and δ 4.01-3.96,
three protons of methyl group appeared as a sharp singlet at δ
2.13, two CH2 groups appeared as multiplets at δ 1.94-1.83 and δ
1.74-1.65 and third CH2 group showed two multiplets at δ 2.90-
2.84 and δ 2.41-2.38 for each proton. Three methylene carbons in
the 13C NMR appeared at δ 48.8, 28.2, 25.9 and three methine
carbons appeared at δ 71.4, 66.2 and 51.1. One methyl carbon
appeared at δ 9.70 and quaternary carbon at δ 72.5. Eighteen
aromatic and two olefinic carbons appeared in the range of δ
109.9 to 149.2. Two carbonyl carbons appeared at δ 192.6 and
179.9. (Peak at δ 179.9 is due to oxindole carbonyl carbon). The
position of peaks for methyl, methylene, methine and quaternary
carbons were assigned by DEPT spectra of compound 6a. The
two- dimensional NMR spectra of HMBC and COSY
correlations are useful in the signal assignment of 6a, and various
characteristic signals are shown in figure 2. The mass spectrum
of 6a showed a molecular ion peak at m/z 580.1932 [M+H]+.
From the C-H HMBC, the correlation between the H of C-3
interacting with spiro carbon C4 at δ 72.5 suggests the formation
of product 6a proceeding via Path a (See proposed pathway,
Scheme 4). In case of Path b, the correlation should appear
between the H of C-2 and spiro carbon C4 at δ 72.5, but no such
interaction is observed in HMBC.
S. No.
Solvent
Catalyst
Catalyst
(mol %)
10
Temp.
(oC)
80
Time
(min)
300
Yield
(%)
1.
2.
3.
4.
H2O
EtOH
DBU
DBU
DBU
DBU
37b
10
10
10
80
80
80
300
120
100
42b
Glycerol
74
Ethylene
glycol
75
5.
1,4-
DBU
10
80
90
87
Dioxane
PEG-400
6.
7.
DBU
K2CO3
DABCO
Piperidine
DBU
10
10
10
10
10
10
5
80
80
80
80
100
60
80
80
40
90
90
300
40
70
60
40
93
70
72
45b
90
85
88
91
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
8.
9.
10.
11.
12.
13.
DBU
DBU
DBU
15
aReaction was carried out between acetylacetone (1) (1.0 mmol), 4-
nitrophenyl azide (2a) (1.0 mmol), 4-nitrobenzaldehyde (3a) (1.0 mmol),
isatin (4) (1.0 mmol) and L-proline (5) (1.0 mmol) bIncomplete reaction
Ar'
O
Ar
O
O
N
N
DBU (10 mol%)
PEG-400, 80oC
HOOC
+
Ar-N3
2a-2c
+
Ar'-CHO
3a-3c
+
O +
N
N
N
N
O
H
H
N
O
1
H
4
5
6a-6o
Scheme 2: Synthesis of compounds 6a-6o
Table 2: Synthesis of 2'-(5-methyl-1-aryl-1H-1,2,3-triazole-4-
carbonyl)-1'-aryl-1',2',5',6',7',7a'-hexahydrospiro[indoline-
3,3'-pyrrolizin]-2-one
derivatives
(6a-6o)
using
multicompoenent approacha
Products
Ar
Ar’
Time
Yield
(%)
93
87
89
91
86
88
92
88
89
90
86
89
91
87
88
(min)
40
55
50
45
60
55
45
55
50
40
55
50
40
55
50
6a
6b
6c
6d
6e
6f
4-(NO2)C6H4
4-(NO2)C6H4
4-(NO2)C6H4
4-(CH3)C6H4
4-(CH3)C6H4
4-(CH3)C6H4
4-BrC6H4
4-(NO2)C6H4
4-(CH3)C6H4
4-BrC6H4
The structure of compound 6i has been further confirmed by the
single crystal X-ray diffraction analysis. Single crystal of
compound 6i suitable for X-ray diffraction was obtained by
vapour diffusion of petroleum ether into chloroform solution of
compound at room temperature. The crystal packing shows eight
4-(NO2)C6H4
4-(CH3)C6H4
4-BrC6H4
6g
6h
6i
4-(NO2)C6H4
4-(CH3)C6H4
4-BrC6H4
4-BrC6H4
molecules in
a single unit cell (Figure S1, Electronic
4-BrC6H4
supplementary information). The structural resolution of 6i
showed two disordered molecules of chloroform solvent located
in the crystal. The crystal chemical unit of compound 6i contains
two molecules which are chemically identical but not related by
crystallographic symmetry, each different molecule is coloured
differently in crystal packing (Figure S2, Electronic
supplementary information).
6j
3-Cl-4-FC6H3
3-Cl-4-FC6H3
3-Cl-4-FC6H3
7-Chloroquinoline
7-Chloroquinoline
7-Chloroquinoline
4-(NO2)C6H4
4-(CH3)C6H4
4-BrC6H4
6k
6l
6m
6n
6o
4-(NO2)C6H4
4-(CH3)C6H4
4-BrC6H4
aAll the reactions were carried out by using DBU (10 mol%) as catalyst in
PEG-400 at 80oC
IR spectra of compound 6a revealed peaks at 3306 cm-1 (N-H
stretch), 1715 cm-1 (carbonyl stretch), 1660 cm-1 (amide C=O
stretch), 1516 cm-1 (N-O asymmetric stretch) and 1347 cm-1 (N-O

4
Tetrahedron
H
H
in PEG-400 in presence of DBU gave 1-(5-methyl-1-aryl-1H-
H
H
H
H
H
d 4.01-3.96, 1H, m, -CH; 13C = 71.4
d 4.16-4.11, 1H, m, -CH; 13C = 51.1
1,2,3-triazol-4-yl)-3-(4-nitrophenyl)prop-2-en-1-one (8) in 92 %
yield. The reaction of 8 (1.0 mmol) with isatin (4) (1.0 mmol)
and L-proline (5) (1.0 mmol) in PEG-400 at 80oC gave the
desired products 6a-6o (Table S2, Electronic supplementary
N
NO2
H
O
N
N
N
N
H
H
13C = d 72.5
13C = d 179.9
O
H
1
H
N
H
NO2
NO2
H
H
H
O
2
3
d 2.13, 3H, s, -CH3
;
13C = 9.7
C-H HMBC
N
N
4
N
H
information).
N
O
H
H
O
H
O
Ar'
H
H
H
H
NO2
H
Ar'
Ar
H
N
O
O
N
a
N
N
b
c
13C = d 192.6
d 4.95, 1H, d, J = 10.68 Hz, -CH; 13C = 66.2
d 10.41, 1H, s, N-H
Ar-N3
N
H
+
N
N
N
NO2
O
N
H
N
N
O
Ar
Ar
N
O
N
H
H
N
N
N
H
1
2
7
8
6a-6o
O
H
H
Scheme 3: Sequential synthesis of 6a-6o (a) PEG-400, DBU (10
mol%), 80oC; (b) aromatic aldehydes (3), PEG-400, DBU (10
mol %), 0oC to rt; (c) Isatin (4), L-Proline (5), PEG-400, 80oC.
NO2
H
H-H COSY
Figure 2: HMBC and COSY correlations of 6a and various
characteristic 1H and 13C NMR peaks
The above sequential reactions required longer reaction time and
gave poorer overall yields compared to the above five component
process as obvious from Table 2 and S2. It is also clear that DBU
is required only for the synthesis of chalcones and has no further
role in the synthesis of spiroheterocycles.
Compound 6i shows four chiral centres, with ‘R’ configuration at
C2 position, ‘S’ configuration at C23 position, ‘R’ configuration
at C24 position and ‘R’ configuration at C25 position as observed
from the crystal structure (Figure S3, Electronic supplementary
information). The crystal data including the structure refinement
are listed in Table S1 (Electronic supplementary information).
A plausible reaction mechanism for the formation of triazole
containing spiro-oxindole derivatives 6 is depicted in Scheme 3.
The triazole 7, formed by [3+2] cycloaddition of acetylacetone
and azide in presence of DBU undergoes aldol condensation with
aromatic aldehydes to give the chalcone derivative 8.
Condensation of isatin and L-proline to give 9 followed by
decarboxylation of spiro compound22 gives the ylide 10. The
chalcone 8 can undergo [3+2] cycloaddition with ylide 10 by two
ways, path a and path b to give either the product 6 or 11
respectively. In case of path a, the secondary orbital interaction23
between the double bond of triazole ring and carbonyl group of
isatin in the transition state stabilize the intermediate and results
in the formation of 6 but in case of path b no such stabilization
by secondary orbital interaction is observed as shown in scheme
3. Therefore formation of only 6 was observed instead of 11. The
formation of 6 was confirmed by HMBC and X-ray analysis as
discussed earlier. The reaction of preformed chalcone 8a with
isatin and L-proline in PEG-400 at 80oC further confirms the
proposed pathway.
Figure 3: ORTEP diagram of compound 6i (CCDC 1455726)
We have also carried out the sequential synthesis of 6a-6o in
three steps including one-pot three component reaction as
depicted in Scheme 3 to demonstrate the advantages of
multicomponent reaction for the synthesis of target molecules
over sequential process. The reaction of acetylacetone (1) and
aryl azides (2) in presence of DBU (10 mol%) in PEG-400 at
80oC gave 1-(5-methyl-1-aryl-1H-1,2,3-triazol-4-yl)ethanone (7)
in 95% yield, which on condensation with aromatic aldehydes (3)
We also examined the recyclability of the catalyst and solvent by
using reactions for the synthesis of 6a, 6e and 6i. The
recyclability of DBU-(PEG-400) system was tested by six run
recycling experiment by changing substrates from one cycle to
another cycle. The product was separated from the reaction
mixture by simple filtration.

5
O
O
Ar'
Supplementary data
O
O
DBU
N
DBU
N
Supplementary data associated with this article can be found, in
the online version, of this article
Ar-N3
+
N
Ar-CHO
N
N
N
Ar
7
Ar
8
References and notes
O
H
O
N
N
1. (a) Singh, G. S.; Desta, Z. Y. Chem. Rev. 2012, 112, 6104; (b)
Liu, Y.; Wang, H.; Wan, J. Asian J. Org. Chem. 2013, 2, 374.
2. Silva, J. F. M.; Garden, S. J.; Pinto, A. C. J. Braz. Chem. Soc.
2001, 12, 273.
COOH
N
O
O
-CO2
H
O
O
N
N
N
H
H
9
10
N
NH
N
8 + 10
Ar'
O
3. Glover, V.; Halket, J. M.; Watkins, P. J.; Clow, A.; Goodwin,
B. L.; Sandler, M. J. Neurochem. 1998, 51, 656.
Ar'
O
Path b
Path a
O
O
N
H
N
4. Kumar, R.; Bansal, R. C.; Mahmood, A. Biog. Amines 1993, 9,
281.
N
N
N
Ar
N
N
Ar
Secondary orbital interaction
5. Medvedev, A. E.; Clow, A.; Sandler, M.; Glover, V. Biochem.
Pharmacol. 1996, 52, 385.
Ar
N
6. (a) Bhattacharya, S. K.; Mitra, S. K.; Acharya, S. B.
Psychopharmacology 1991, 5, 202; (b) Bhattacharya, S. K.;
Glover, V.; McIntyre, I.; Oxenkrug, G.; Sandler, M. Neurosci.
Lett. 1982, 92, 218.
O
Ar'
Ar
N
N
N
N
N
N
Ar'
N
O
Not formed
N
O
O
N
H
H
11
6
7. Yamazaki M.; Okuyama, E. Tetrahedron Lett. 1981, 22, 135.
8. (a) Cui, C.-B.; Kakeya, H.; Osada, H. Tetrahedron 1996, 52,
12651; (b) Wang, H.; Ganesan, A. J. Org. Chem. 2000, 65, 4685.
9. Velazquez, S.; Alvarez, R.; Perez, R.; Gago, F.; Camarasa, M.
J. Antivir. Chem. Chemother. 1998, 9, 481.
Scheme 4: Plausible mechanism for the synthesis of 6
This allows quick recovery of catalyst and solvent for reuse in
the next run. The results of recycling experiment are shown in
Table S3 (in supplementary information). All reactions were
complete in 40-65 min and afforded the products in 93-81%
yield. The catalyst showed no substantial reduction in activity.
Therefore this system can act as an excellent recyclable reaction
medium cum catalyst for synthesis of triazole tethered
spirooxindoles in high yields.
10. Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn, M.
R.; Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grega, K. C.;
Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer, R. J.;
Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.;
Stapert, D.; Yagi, B. H. J. Med. Chem. 2000, 43, 953.
11. Jordao, A. K.; Ferreira, V. F.; Souza, T. M.; Faria, G. G.;
Machado, V.; Abrantes, J. L.; Souza, M. C.; Cunha, A. C.
Bioorg. Med. Chem. 2011, 19, 1860.
In conclusion, we have developed an efficient, clean approach for
the synthesis of novel structurally diverse triazolyl spirocyclic
oxindole derivatives by one-pot five component condensation of
acetylacetone, aryl azides, aromatic aldehydes, isatin and L-
proline using DBU as catalyst in PEG-400 at 80oC. All the
reactions were facile and gave high yields by simple work-up.
All the compounds were characterized by 1H NMR, 13C NMR, IR
and Mass spectra.
12. Agalave, S. G.; Maujan, S. R.; Pore, V. S. Chem. Asian J.
2011, 6, 2696.
13. Kume, M.; Kubota, T.; Kimura, Y.; Nakashimizu, H.;
Motokawa, K.; Nakano, M. J. Antibiot. 1993, 46, 177.
14. Boddy, I. K.; Briggs, G. G.; Harrison, R. P.; Jones, T. H.;
O’Mahony, M. J.; Marlow, I. D.; Roberts, B. G.; Willis, R. J.;
Bardsley, R. J. Pestic. Sci. 1996, 48, 189.
Acknowledgement
15. Buechel, K. H.; Gold, H.; Frohberger, P. E.; Kaspers, H.
German Patent 2407305, 1975; Chemical Abstracts, 1975, 83,
206.
S.K. thank C.S.I.R., New Delhi, India for the grant of Junior and
Senior Research Fellowship, H.S. thank UGC, New Delhi, India
for the grant of Junior and Senior Research Fellowship. The
authors also acknowledge DU-DST for providing HRMS-LC
analysis.
16. Goodman, J. L.; Winston, D. J.; Greenfield, R. A.;
Chandrasekar, P. H.; Fox, B.; Kaizer, H; Shadduck, R. K.; Stiff,
T. C. S. P.; Friedman, D. J.; Powderly, W. G.; Silber, J .L.;

6
Tetrahedron
Horowitz, H.; Lichtin, A.; Wolff, S. N.; Mangan, K. F.; Silver,
mmol) and L-proline (5) (1.0 mmol) was dissolved in PEG-400
(10 ml) in a 50 mL round-bottomed flask and 10 mol% of DBU
catalyst was added to this reaction mixture. The reaction contents
were stirred magnetically in a pre-heated oil-bath maintained at
80oC. The progress of the reaction was monitored by TLC (Ethyl
acetate: Petroleum ether, 40:60, v/v). After completion of the
reaction, the reaction mixture was allowed to cool at room
temperature and quenched with water (~10 mL). The solid
formed was filtered and washed with water. The crude material
was purified by flash chromatography over silica gel (230-400
mesh) to afford pure products. The products were characterized
by 1H NMR, 13C NMR, IR and Mass spectra. Product 6i was also
analyzed by X-ray diffraction studies.
S. M.; Weisdorf, D.; Ho, W. G.; Gilbert, G.; Buell, D. N. Engl. J.
Med. 1992, 326, 845.
17. Sanders Jr., W. E.; Sanders, C. C. Infect Dis. 1996, 22, 107.
18. Chanda, A.; Fokin, V. V. Chem. Rev. 2009, 109, 725.
19. Chen, J.; Spear, S. K.; Huddleston, J. G.; Rogers, R. D. Green
Chem. 2005, 7, 64.
20. (a) Shieh, W. C.; Dell, S.; Repic, O. J. Org. Chem. 2002, 67,
2188; (b) Zhao, G. L.; Shi, Y. L.; Shi, M. Org. Lett. 2005, 7,
4527; (c) Price, K. E.; Aboussafy, C.; Lillie, B. M.; McLaughlin,
R. W.; Mustakis, J.; Hettenbach, K. W.; Hawkins, J. M.;
Vaidyanathan, R. Org. Lett. 2009, 11, 2003; (d) Ying, A. G.; Liu,
L.; Wu, G. F.; Chen, G.; Chen, X. Z.; Ye, W. D. Tetrahedron
Lett. 2009, 50, 1653; (e) Ando, K.; Yamada, K. Green Chem.
2011, 13, 1143.
21. Rajeswari, M.; Sindhu, J.; Singh, H.; Khurana, J. M. RSC
Advan. 2015, 5, 39686; (b) Sindhu, J.; Singh, H.; Khurana, J. M.
Mol. Divers. 2014, 18, 345; (c) Sindhu, J.; Singh, H.; Khurana, J.
M.; Sharma, C.; Aneja, K. R. Chin. Chem. Lett. 2015, 26, 50; (d)
Singh, H.; Sindhu, J.; Khurana, J. M.; Sharma, C.; Aneja, K. R.
RSC Adv. 2014, 4, 5915; (e) Singh, H.; Sindhu, J.; Khurana, J. M.
RSC Adv. 2013, 3, 22360; (f) Singh, H.; Kumari, S.; Khurana, J.
M. Chin. Chem. Lett. 2014, 25, 1336; (g) Sindhu, J.; Singh, H.;
Khurana, J. M.; Sharma, C.; Aneja, K. R. Chin. Chem. Lett.
2015, 26, 50.
22. (a) Kanchithalaivan, S.; Sumesh, R. V.; Kumar, R. R. ACS
Comb. Sci. 2014, 16, 566; (b) Rizzi, G. P. J. Org. Chem. 1970,
35, 2069; (c) D’Souza, A. M.; Spiccia, N.; Basutto, J.; Jokisz, P.;
Wong, L. S.–M.; Meyer, A. G.; Holmes, A. B.; White, J. M.;
Ryan, J. H. Org. Lett. 2011, 13, 486; (d) Aly, M. F.; El-Nagger,
G. M.; El- Emary, T. I.; Grigg, R.; Metwally, S. A. M.;
Sivagnanam, S. Tetrahedron 1994, 50, 895; (e) Coldham, I.;
Hufton, R. Chem. Rev. 2005, 105, 2765.
23. (a) Srinu, L.; Thennarasu, S.; Perumal, P. T. Tetrahedron
Lett. 2012, 53, 7052; (b) Apeloig, Y.; Matzner, E. J. Am. Chem.
Soc. 1995, 117, 5375; (c) Arrieta, A.; Cossio, F. P. J. Org. Chem.
2001, 66, 6178; (d) Liu, H.; Dou, G.; Shi, D. J. Comb. Chem.
2010, 12, 633.
24. General procedure for the synthesis of 2'-(5-methyl-1-aryl-
1H-1,2,3-triazole-4-carbonyl)-1'-aryl-1',2',5',6',7',7a'-
hexahydrospiro[indoline-3,3'-pyrrolizin]-2-one derivatives (6a-
6o):
An equimolar mixture of acetylacetone (1) (1.0 mmol), aryl
azides (2) (1.0 mmol), aromatic aldehydes (3), isatin (4) (1.0

7
An efficient green approach for the
synthesis of novel triazolyl spirocyclic
oxindole derivatives via one-pot five
component protocol using DBU as
catalyst in PEG-400
Sudesh Kumari, Harjinder Singh and Jitender
M. Khurana*
Department of Chemistry, University of Delhi,
Delhi-110007
*Email:- jmkhurana1@yahoo.co.in,
jmkhurana@chemistry.du.ac.in
Graphical abstract
Five
components
in one pot
Ar'-CHO
O
Ar'
O
O
Ar
DBU (10 mol%)
PEG-400, 80oC
N
HOOC
N
O
N
N
N
N
H
O
Ar-N3
H
N
O
H
Short reaction time
High yields of products

8
Tetrahedron
Highlights:
 DBU catalysed synthesis of fused
heterocyclic triazolyl spirocyclic oxindoles
 High yield of products and short reaction
time
 Structure has been characterized by X-ray
crystallography
 Recyclability of DBU-PEG-400 system