Dual solvent-catalyst role of deep eutectic solvents in Hantzsch dihydropyridine synthesis

Article abstract of DOI:10.1080/00397911.2021.1904261

Deep eutectic solvents are a class of new generation green solvents formed from two or more components, which furnish a new homogeneous liquid phase with lower melting point than the individual components. Here, for the first time, dual role of DES as cat

Full text of DOI:10.1080/00397911.2021.1904261

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Dual solvent-catalyst role of deep eutectic solvents
in Hantzsch dihydropyridine synthesis
Shaibuna M. & K. Sreekumar
To cite this article: Shaibuna M. & K. Sreekumar (2021) Dual solvent-catalyst role of deep eutectic
solvents in Hantzsch dihydropyridine synthesis, Synthetic Communications, 51:11, 1742-1753, DOI:
10.1080/00397911.2021.1904261
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2021, VOL. 51, NO. 11, 1742–1753
https://doi.org/10.1080/00397911.2021.1904261
Dual solvent-catalyst role of deep eutectic solvents in
Hantzsch dihydropyridine synthesis
Shaibuna M. and K. Sreekumar
Department of Applied Chemistry, Cochin University of Science and Technology, Cochin, India
ABSTRACT
ARTICLE HISTORY
Received 6 January 2021
Deep eutectic solvents are a class of new generation green solvents
formed from two or more components, which furnish a new homoge-
neous liquid phase with lower melting point than the individual com-
ponents. Here, for the first time, dual role of DES as catalyst and
reaction medium was studied for the synthesis of symmetric dihydro-
pyridine derivatives from aldehyde, ethyl acetoacetate and ammo-
nium acetate. The present article reports the suitability of six DESs for
Hantzsch dihydropyridine synthesis at room temperature. Among this,
DES 2 (ZrOCl2.8H2O and ethylene glycol at 1:2 ratio) was found to be
the catalyst of choice with excellent recyclability. The role of DES in
the present protocol was to activate the reactants through strong
hydrogen bonding interaction and provide suitable medium for the
reaction. The major advantages of DESs for the titled reaction are the
easy preparation, low cost, non-volatility, biodegradability, simple
catalytic process, excellent conversion and the reusability.
KEYWORDS
Deep eutectic solvents;
dihydropyridine derivatives;
Hantzsch pyridine synthesis;
multicomponent reaction
GRAPHICAL ABSTRACT
Introduction
Recently, most of the fields in chemistry have focused on sustainable methods; these
include ILs, deep eutectic solvents and their alternatives.[1] The physicochemical properties
of DESs can be tuned by changing the constituents used and also can have a significant
CONTACT K. Sreekumar
kskpolymer.cusat@gmail.com
Department of Applied Chemistry, Cochin University of
Science and Technology, Cochin, India.
Supplemental data for this article can be accessed on the publisher’s website
ß 2021 Taylor & Francis Group, LLC

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influence on the way these interact with other molecules.[2] DESs are found to be most
efficient in terms of its preparation method, recycling process, biodegradability, toxicity,
cost effectiveness etc. Deep eutectic solvents (DESs) are a new family of green solvents,
based on a hydrogen bond donor (HBD) and a hydrogen bond acceptor (HBA) which
together have a melting point low enough to be used as solvents.[3–6] Some of them show
glass transition temperature instead of melting point and are referred to as low transition
temperature mixtures (LTTMs).[7] DESs have some special properties like wide liquid
range, non-flammability and non-volatility, safe to operate (because they are generally
formed from solids and inflammable liquids and avoid the risk of explosion) which makes
them applicable in diverse fields.[8,9] A prosperous increase was observed in the research
based on deep eutectic solvents in many fields such as polymerization,[10] metal processing
application (like metal electrodeposition, metal electropolishing, metal extraction and the
processing of metal oxides),[11] biomass processing,[12] catalysis,[13]ionothermal synthe-
sis,[14] gas adsorption,[15] nanotechnology,[16] biotransformation etc.[17] Deep eutectic sol-
vents are widely applied as sustainable media as well as catalysts in organic synthesis.
Some recent advances in organic reactions using DESs include DABCO-derived quaternary
ammonium salts for the preparation of terpyridines,[18] synthesis of substituted pyrido-
pyrimidines in low transition temperature mixture (LTTM),[19] synthesis of benzimidazoles
in deep eutectic solvents,[20] synthesis of polymers etc.[21] They are also used in different
organic transformations like cyclization reactions, oxidation reactions, reducing reactions,
addition reactions, multicomponent reactions, replacement reactions and condensation
reactions.[22]
In the present article, the catalytic activity of six deep eutectic solvents (DES 1- DES
6) are reported for the synthesis of symmetric 1,4-dihydropyridine derivatives based on
the physicochemical properties and the nature of the constituents used. To the best of
our knowledge, there are no previous reports on the DES catalyzed synthesis of 1,4-
dihydropyridine derivatives using aldehyde, ethyl acetoacetate and ammonium acetate
(symmetric Hantzsch pyridine synthesis). In 2013, Suhas Pednekar et al reported the
synthesis of polyhydroquinolines (via asymmetric Hantzsch pyridine synthesis) using
aldehyde, dimedone, ethyl acetoacetate and ammonium acetate in the presence of ChCl/
urea (1:2) deep eutectic system at 60 ꢀC.[23] L. Wang et al. in 2014 reported the same
reaction, but with a different composition of DES (ChCl/urea at 1:1 ratio) at 80 ꢀC.[24]
Due to the unprecedented biological and chemical activities of dihydropyridine scaf-
folds, they have revolutionized pharmaceutical research in recent times. They constitute
a well explored scaffold which binds to multiple receptors and are the main fulcrum of
many drugs that have been manufactured and used all over the world.[25] Several 1,4
DHP derivatives were used for the treatment of hypertension, coronary diseases; some of
them are nifedipine, amlodipine, felodipine, Isradipine, Nisoldipine, Nimodipine,
Nicardipine etc. (Fig. 1).[26,27] They act as calcium channel modulators and used for the
treatment of hypertension, as well as precursor to agrochemicals and pharmaceuticals.[28]
1,4-Dihydropyridine skeleton is also present in many vasodilator, bronchodilator, anti-
diabetic, antitumour, antiatheroschlerotic, geroprotective, and hepatoprotective agents.[29]
Different methods are available for the synthesis of DHP derivatives in the
literature; these include the use of catalysts such as BTPPC,[30] Cobalt
Nanoparticles,[31] Fe3O4@chitosan,[32] melamine trisulfonic acid (MTSA),[33] ILOS@Fe/

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M. SHAIBUNA AND K. SREEKUMAR
Figure 1. Selective examples for clinically important 1,4-dihydropyridine derivatives.
[37]
TSPP,[34] Zr-SBA-16,[35] cadmium metal-organic framework,[36] Ti-SBA-15@IL-BF4,
TiO2 NPs,[38] silica-coated Fe3O4 nanoparticles,[39] MgAl2 hydrotalcites (HT),[40]
CoFe2O4@SiO2-NH2-CoII etc.[41] Many of the aforementioned protocols suffer from
major or minor limitations, such as use of expensive and toxic catalyst, tedious reaction
setup, require prolonged reaction times, side product formation, presence of volatile sol-
vents etc. The search for new green and efficient procedures under mild conditions is still
actively continued. This article focuses on the replacement of conventional methods using
renewable deep eutectic solvent in symmetric Hantzsch dihydropyridine synthesis.
Results and discussion
Recently, six DESs (formed from ZrOCl2.8H2O/CeCl3.7H2O with urea, ethylene glycol &
glycerol) were reported and their activities were compared in Kabachnik-Fields reaction for
the synthesis of a-aminophosphonates.[42–44] This manuscript reports the exploration of the
applicability of DESs as catalyst for the synthesis of 1,4-dihydropyridine derivatives via
Hantzsch reaction. A reaction was performed by stirring benzaldehyde (1 mmol), ethyl ace-
toacetate (2 mmol) and ammonium acetate (1.5 mmol) at room temperature under solvent
free and catalyst free condition. Only traces of the product (with impurity) were obtained
after 6h. Later, the same reaction was repeated using DES 1, excellent yield with high pur-
ity was obtained within 30 min at room temperature and this indicated the necessity of a
catalyst in the reaction. Reaction was repeated using some other aldehydes like 4-chloro-
benzaldehyde, 4- bromobenzaldehyde and furfural. In the presence of DES 1, a mixture of
dihydropyridine (1) and dihydropyrimidinone (2) was observed with some aldehydes like
furfural as shown in Scheme 1. The GC profile and mass spectra of the corresponding
dihydropyridine (1) and dihydropyrimidinones (2) are given in Figure 2.
The formation of dihydropyrimidinones (Biginelli product with m/z¼ 250) is due to
the presence of urea in DES 1(mixture of ZrOCl2.8H2O and urea at 1: 5 ratio), which
will act as a coupling agent as well as catalyst in the reaction (over all, a triple role of
DES 1 was observed here, as catalyst, reaction medium and reagent). Separate experi-
ments were conducted using the remaining five DESs (DES 2-DES 6) in the same reac-
tion using furfural (1 mmol), ethyl acetoacetate (2 mmol) and ammonium acetate
(1.5 mmol) at RT. Similar to DES 1, a mixture of dihydropyridine and dihydropyrimidi-
none was observed using DES 4 (CeCl3.7H2O- Urea at 1: 5 ratio) due to the multiple
action of DES as catalyst as well as reagent. Higher yield was observed using DES 2 and
low yield (with impurity) were observed for DES 3, DES 5 and DES 6. Even though, DES
2 is not acidic in the conventional sense (pH ¼ 6.99) compared to DES 5 (pH ¼ 4.44)
and DES 6 (pH ¼ 4.27), its activity may be due to the strong ability to activate the reac-
tants through hydrogen bonding interaction. In addition to this, the lower viscosity of

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Scheme 1. Hantzsch pyridine synthesis in DES 1.
DES 2 may also favor the reaction as it is one of the most important physical properties
of a solvent.[42–43] Both these effects contributed to the better activity of DES 2.
CeCl3.7H2O based deep eutectic solvents (DES 4- DES 6) were found to be less reactive
for the synthesis of dihydropyridine derivatives compared to ZrOCl2.8H2O based DESs
(DES 1- DES 3). The observations are given in Table 1.
DES 1 and DES 4 may create problems in future studies, especially during the studies
based on substrate scope by forming mixture of products (dihydropyridine and dihydro-
pyrimidinone) and recycling. So DES 1 and DES 4 were eliminated from further cata-
lytic activity studies. Single product with higher yield was observed using DES 2
(formed from ZrOCl2.8H2O and ethylene glycol at 1:2 ratio) and was selected for future
optimization studies. In order to find out the optimum catalyst (DES 2) needed for
Hantzsch pyridine synthesis, experiments were conducted under different catalytic con-
ditions (0.2–0.8 mmol of DES 2) using benzaldehyde, ethyl acetoacetate and ammonium
acetate as model substrates for about 30 min (Table 2) at room temperature. An excel-
lent yield was obtained using 0.6 mmol of DES 2 (95%, Table 2, Entry 6) and after that
there was no considerable change in the product yields (Table 2, Entry 7 and 8). The
use of DES 2 at 0.6 mmol was found to be the optimum amount of catalyst (Table 2,
Entry 6) needed for the synthesis of 1,4-dihydropyridine derivatives from benzaldehyde
(1 mmol), ethyl acetoacetate (2 mmol) and ammonium acetate (1.5 mmol) at room
temperature.
Using this optimum catalytic condition, the efficacy and versatility of DES 2 was moni-
tored by repeating the experiment using different varieties of aldehydes and the results are
summarized in Table 3. A variety of aromatic aldehydes were smoothly converted in to
corresponding dihydropyridine derivatives with excellent efficiency (Table 3, Entry 1–10).
Here at first, the reaction was performed using benzaldehyde by doing TLC analysis in
each 5 min. The reaction was completed within 10ꢁ30 min with an yield above 90%
(Table 3). The process was repeated using different substituted benzaldehydes with ethyl
acetoacetate and ammonium acetate and the reaction was monitored by TLC. Excellent
yields were obtained for both electron donating and electron withdrawing substituents
(Table 3, Entry 1–5). Disubstituted aromatic aldehyde (veratraldehyde) was also converted
to the corresponding dihydropyridine derivative with excellent efficiency (Table 3, Entry
6). Further, the activity was checked using heteroaromatic aldehydes like furfural and thio-
phene aldehyde, efficient conversion was observed with DES 2 (Table 3, Entry 7 & 8).
Appreciable yield was obtained for aldehyde with bulky substrate (1-Naphthaldehyde) with
high purity (Table 3, Entry 9). An outstanding yield was observed for cinnamaldehyde
without any side product formation (Table 3, Entry 10).
The ZrOCl2.8H2O/ethylene glycol DES employed played the dual role of catalyst and
solvent, no additional organic solvent was required in the reaction. All the

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M. SHAIBUNA AND K. SREEKUMAR
Figure 2. GC profile and mass spectra of the corresponding dihydropyrimidinone with m/z¼ 250 (1)
and dihydropyridine with m/z ¼ 319 (2).
Table 1. Hantzsch pyridine synthesis using six DESs.
Entry
DES
Mole ratio
Abbreviation
pH
Viscosity (g)/ (mPa.s)
Catalytic activity
1
2
3
4
5
6
Zr: U
Zr: EG
Zr: Gly
Ce: U
Ce: EG
Ce: Gly
1:5
1:2
1:2
1:5
1:2
1:2
DES 1
DES 2
DES 3
DES 4
DES 5
DES 6
2.20
6.93
6.97
4.71
4.44
4.27
52.40
149.50
532.73
195.39
290.40
868.73
Mixture of products
Higher yield and purity
Lower yield
Mixture of products
Lower yield
Lower yield
Reaction conditions: furfural (1 mmol), ethyl acetoacetate (2 mmol) and ammonium acetate (1.5 mmol), RT.
dihydropyridine derivatives were obtained with high purity and the catalyst was
removed from the reaction mixture by simply washing with, since DES was highly
soluble in water. The products were characterized by using TLC, melting point meas-
1
urements, GCMS and H & 13C NMR spectra.

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Table 2. Optimization of catalyst for Hantzsch pyridine synthesis.
Amount of DES 2
Entry
(g)
(mmol)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
–
–
30
30
30
30
30
30
30
30
Trace
60
75
80
82
95
96
96
0.009
0.013
0.019
0.022
0.026
0.031
0.035
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Reaction conditions: benzaldehyde (1 mmol), ethyl acetoacetate (2 mmol) and ammonium acetate (1.5 mmol), RT.
Mechanism of the reaction
A possible mechanism for DES 2 catalyzed Hantzsch dihydropyridine synthesis was pro-
posed in Scheme 2. The main role of DES here was to activate the reactants and inter-
mediates through strong hydrogen bonding interactions.
Here, a hydrogen bonded activated complex was formed by the interaction of DES
with the carbonyl group of aldehyde, which was followed by the formation of
Knoevenagel adduct (intermediate 1) by the nucleophilic attack of one equivalent of
ethyl acetoacetate to this activated complex. Or another ethyl acetoacetate was activated
by DES followed by the ester enamine formation (intermediate 2) by the nucleophilic
attack of ammonia (formed from ammonium acetate) on the carbonyl of ethyl acetoace-
tate. Finally in the presence of DES, cyclocondensation of both Knoevenagel adduct
(intermediate 1) and ester enamine (intermediate 2) took place via Michael type add-
ition yielding the DHP derivative.
Reusability of DES
It is very important to recover and reuse the catalyst in the aspect of green chemistry
and here the reusability of deep eutectic solvent was checked. Highly water soluble deep
eutectic solvents are separated by washing the product with water. The catalyst can be
reused up to five times for the synthesis of dihydropyridine derivatives without remark-
able loss in its activity. The details of the reusability study are given in Table 4 (using
benzaldehyde, ethyl acetoacetate, ammonium acetate as model substrates).
Comparison with previous reports
A detailed comparative study of the present catalyst was performed with some prior
reports using benzaldehyde, ethyl acetoacetate and ammonium acetate as model

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M. SHAIBUNA AND K. SREEKUMAR
Table 3. Synthesis of dihydropyridine derivatives using DES 2.
Entry
R
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
C6H5
20
15
15
15
15
25
25
10
30
10
95
96
90
95
95
97
92
96
95
98
4-Cl-C6H4
4-Br-C6H4
4-MeO-C6H4
4- NO2- C6H4
3,4,-(OMe)2-C6H3
1-Furyl
1-Thienyl
1-Naphthyl
Cinnamyl
9
10
Reaction conditions: benzaldehyde (1 mmol), ethyl acetoacetate (2 mmol) ammonium acetate (1.5 mmol) and DES 2
(0.6 mmol), RT.
substrates, the results are presented in Table 5. To the best of our knowledge, there was
no previous report for the synthesis of symmetric 1,4-dihydropyridine derivatives from
aldehyde, ethyl acetoacetate and ammonium acetate in the presence of deep eutectic sol-
vents. In 2013, S.S. Mansoor et al. reported the synthesis of 1,4-DHPs using melamine
trisulfonic acid (MTSA), but it required prolonged reaction time (4 h) and temperature.
In addition to this, tedious work up process was required for the synthesis of MTSA
(Table 5, Entry 1).
Symmetric dihydropyridines were synthesized using lewis acidic Zr-SBA-16 by R.
Maheswari et al. in 2015. Here also the catalyst preparation required more steps and
time. DHPs were synthesized in the presence of solvents and temperature, also there
was no discussion about the recycling studies (Table 5, Entry 2). Similarly, Cd metal-
organic framework was used as a catalyst for the synthesis of dihydropyridine in 2017
(Table 5, Entry 3). Here the synthesis of the catalyst was more difficult and involved
step by step process. This included (1) preparation of N,N0-(oxybis(4,1-phenylene))-
bis(1-(pyridin-4-yl)methanimine) (OPP), (2) synthesis of f[Cd3(BDC)3(OPP)(DMF)2].
2DMAgn (TMU-33) and (3) synthesis of TMU-33 nanostructures and was the main dif-
ficulty related with this metal organic framework. Titanium incorporated mesoporous
material supported ionic liquid, titanium dioxide nanoparticles, and MgAl2 hydrotalcites
(HT) were also used for the synthesis of Hantzsch esters with excellent yield and recyc-
lability (Table 5, Entry 4-6). But all these methods required difficult preparation process
and the use of organic solvents. A magnetically heterogeneous CoFe2O4@SiO2-NH2-CoII
nanoparticle was reported by Allahresani et al. in 2020 (Table 5, Entry 7). Here also,
the synthesis part was very hard, required five synthesis steps. This included (1) synthe-
sis of CoFe2O4 nanoparticles, (2) synthesis of CoFe2O4@SiO2, (3) synthesis of NH2-Pr
(4) synthesis of NH2-Pr-CoII and (5) synthesis of CoFe2O4@SiO2-NH2-CoII.
The comparison highlights the urgency to introduce a sustainable catalyst for the
easy preparation dihydropyridine derivatives through Hantzsch reaction. Here, DES 2

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Scheme 2. Probable mechanism for Hantzsch pyridine synthesis using DES 2.
(formed from ZrOCl2.8H2O and ethylene glycol at 1:2 ratio) was used as a catalyst for
the synthesis of dihydropyridine derivatives using different aldehydes containing both
electron donating and withdrawing substituents. The main advantages of the present
protocol were the easy method of preparation (formed by simple mixing of the constitu-
ents with gentle heating, the clear and colorless homogeneous mixture was formed with
hundred percentage atom economy), relatively low cost, low toxicity, biodegradability,
eco-friendly, dual role (acts as catalyst as well as reaction medium and no additional

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M. SHAIBUNA AND K. SREEKUMAR
Table 4. Recyclability of the DES 2.
No. of runs
Yield (%)
1
2
3
4
5
95
91
90
88
85
Reaction conditions: benzaldehyde (1 mmol), ethyl acetoacetate (2 mmol) ammonium acetate
(1.5 mmol), RT.
Table 5. Comparison of DES 2 with some prior reports.
Entry
Catalyst
Reaction condition
Yield (%)
Reusability
Ref.
1
2
3
4
5
6
7
8
MTSA
Zr-SBA-16
Cd metal-organic framework
Ti-SBA-15@IL-BF4
TiO2 NPs
MgAl2 hydrotalcites (HT)
CoFe2O4@SiO2-NH2-CoII
DES 2
4h/60 ꢀC
86
77
97
94
92
61
85
95
4 Runs
–
4 Runs
5 Runs
6 Runs
–
33
35
36
37
38
40
41
3h/80 ꢀC/Ethanol
RT/2 h/Ethanol
2h/80 ꢀC/Ethanol
2 h/80 ꢀC/Ethanol
6.5 h/RT/Acetonitrile
2.5h/Reflux/Ethanol
20 min/RT
6 Runs
5 Runs
Present work
Reaction conditions: benzaldehyde, ethyl acetoacetate, ammonium acetate.
organic solvent was required) and recyclability. These attributes make deep eutectic sol-
vents more dominant over other previously reported catalysts for the synthesis of sym-
metric Hantzsch Dihydropyridine Synthesis.
Conclusion
Dual solvent-catalyst activity of six deep eutectic solvents (combination of
ZrOCl2.8H2O/CeCl3.7H2O with urea, ethylene glycol and glycerol) were compared and
a sustainable solvent-free procedure for the multicomponent synthesis of symmetric
dihydropyridine derivatives was developed at room temperature. Among the six DES
(DES 1- DES 6), mixture of both dihydropyridine and dihydropyrimidinones (Biginelli
product) were observed while using DES 1 and DES 4 (ZrOCl2.8H2O/CeCl3.7H2O with
urea at 1:5 ratio). This was due to the presence of urea in the DES mixture, which acted
as a coupling agent as well as a constituent of the catalyst in the reaction and was
removed from further studies. DES 2 (combination of ZrOCl2.8H2O/ethylene glycol at
1:2 ratio) was established as the premier solvent- catalyst system with excellent recyc-
lability. This may be due to the lower viscosity and stronger hydrogen bonding ability
compared to the remaining deep eutectic solvents. Substrate scope was checked by

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repeating the experiment using different aldehydes like monosubstituted and disubsti-
tuted aromatic aldehydes, heteroaromatic aldehydes, unsaturated aldehydes etc.
Excellent conversion was observed for all the aldehydes with high purity. The catalyst
was recovered from the mixture by washing with water and was reused up to 5 catalytic
cycles without much loss in its activity. A detailed comparative study was performed
with some previous reports and the dominance of the described catalyst over others
included simple method of preparation of DES without any additional purification step,
dual activity as catalyst and medium (no need of additional organic solvent), high and
fast catalytic activity, low cost, non volatility, simple reaction condition (reaction per-
formed at room temperature without more experimental setup). In addition to this, the
catalyst could be reused up to five runs without any remarkable loss in its activity and
all these make the procedure attractive.
Experimental section
Preparation of DES
By heating (at 40–60 ꢀC for 10–15 min) a mixture of metal chloride hydrate
(ZrOCl2.8H2O/CeCl3.7H2O) and hydrogen bond donors (urea, ethylene glycol and gly-
cerol) at different molar ratios, clear, colorless, homogeneous liquids were formed. After
cooling, the mixtures could be used for further studies without any purification pro-
cess.[42,43] Full experimental details with recycling process of deep eutectic solvents are
given in the supplementary information.
General procedure for the synthesis of diethyl 2,6-dimethyl-4-phenyl-1,4-
dihydropyridine-3,5-dicarboxylate in DES
A mixture of benzaldehyde (1 mmol), ethyl acetoacetate (2 mmol), ammonium acetate
(1.5 mmol) and DES (0.2–0.8 mmol) was stirred in an RB flask at room temperature for
the time as indicated in Table 3. Completion of the reaction was observed using TLC
with hexane- ethyl acetate (1:1) mixture as developing solvent. After completion of the
reaction, the mixture was washed with distilled water and filtered and analyzed using
1
TLC, melting point measurements, GCMS and H & 13C NMR spectra. General proced-
ure for Hantzsch dihydropyridine synthesis, structure of synthesized products, melting
1
point, NMR data, GC MS and H & 13C NMR spectra of the compounds can be found
in the Supplementary Content section of this article’s Web page.
Spectroscopic data of diethyl 2,6-dimethyl-4-phenyl-1,4-dihydropyridine-3,5
dicarboxylate (P1)
1
White solid (95%); Melting point 157–159 ꢀC; GC-MS (Mþ): 329; H NMR (500 MHz,
DMSO- d6) d ppm: 1.19 (t, 6H), 2.33 (s, 6H), 4.08 (q, 4H), 4.96 (s, 1H), 5.97 (s, 1H,
NH), 7.16–7.33 (m, 5H). 13C NMR (125 MHz, DMSO-d6) d ppm: 14.0, 19.4, 39.6, 59.5,
104.0, 121.8, 129.0, 131.0, 144.4, 146.5, 166.8.

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M. SHAIBUNA AND K. SREEKUMAR
Acknowledgements
The authors gratefully acknowledge IIRBS, Mahatma Gandhi University, Kottayam for NMR ana-
lysis and UGC, India for financial support.
Funding
This work was supported by University Grants Commission.
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