Facile access to polymer supported zinc–salen complex: highly efficient heterogeneous catalyst for synthesizing hydantoins, thiohydantoins and Schiff bases in aqueous medium

Article abstract of DOI:10.1007/s11164-017-3215-x

The synthesis of polymer supported zinc–salen complex (PS-Zn–salen) is described. The mononuclear zinc(II)–salen complex was characterized by Fourier-transform NMR spectroscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectrophotometry (FT-IR), thermogravimetric analysis, scanning electron microscopy, surface area and pore size distribution by Brunauer–Emmett–Teller. The synthesized PS-Zn–salen complex used as a recyclable heterogeneous catalyst for the efficient synthesis of hydantoins, thiohydantoins and Schiff bases in an aqueous medium. The isolated yields of hydantoins, thiohydantoins and Schiff bases achieved up to 89, 95 and 94%, respectively. In spite of conventional heterogeneous catalysts, current PS-Zn–salen complex shows thermal stability up to 280?°C. Moreover, the catalyst could be recovered easily by simple filtration and reused for next run with slightly declining its activity up to six successive runs. The FT-IR spectrum of recycle catalyst after 6th run confirmed that the catalyst was stable during the course of a reaction. The leaching of metal from the PS-Zn–salen is negligible, which was confirmed by AAS and hot filtration test.

Full text of DOI:10.1007/s11164-017-3215-x

Res Chem Intermed
https://doi.org/10.1007/s11164-017-3215-x
Facile access to polymer supported zinc–salen complex:
highly efcient heterogeneous catalyst for synthesizing
hydantoins, thiohydantoins and Schif bases in aqueous
medium
Kamlesh Rudreshwar Balinge1 · Avinash Ganesh Khiratkar1 ·
Prashant Narayan Muskawar2 · K. Thenmozhi1 · Pundlik Rambhau Bhagat1
Received: 26 September 2017 / Accepted: 17 November 2017
© Springer Science+Business Media B.V., part of Springer Nature 2017
Abstract The synthesis of polymer supported zinc–salen complex (PS-Zn–salen)
is described. The mononuclear zinc(II)–salen complex was characterized by Fourier-
transform NMR spectroscopy, energy-dispersive X-ray spectroscopy, Fourier trans-
form infrared spectrophotometry (FT-IR), thermogravimetric analysis, scanning
electron microscopy, surface area and pore size distribution by Brunauer–Emmett–
Teller. The synthesized PS-Zn–salen complex used as a recyclable heterogeneous
catalyst for the efcient synthesis of hydantoins, thiohydantoins and Schif bases in
an aqueous medium. The isolated yields of hydantoins, thiohydantoins and Schif
bases achieved up to 89, 95 and 94%, respectively. In spite of conventional heteroge-
neous catalysts, current PS-Zn–salen complex shows thermal stability up to 280 °C.
Moreover, the catalyst could be recovered easily by simple fltration and reused for
next run with slightly declining its activity up to six successive runs. The FT-IR
spectrum of recycle catalyst after 6th run confrmed that the catalyst was stable dur-
ing the course of a reaction. The leaching of metal from the PS-Zn–salen is negligi-
ble, which was confrmed by AAS and hot fltration test.
Keywords PS-Zn–salen · Aqueous medium · Hydantoins · Thiohydantoins · Schif
bases
Electronic supplementary material The online version of this article (https://doi.org/10.1007/
s11164-017-3215-x) contains supplementary material, which is available to authorized users.
*
Pundlik Rambhau Bhagat
drprbhagat111@gmail.com
1
2
Department of Chemistry, School of Advanced Sciences, VIT, Vellore 632014, India
Department of Chemistry, Amolakchand Mahavidyalaya, Yavatmal 445002, India
1 3

K. R. Balinge et al.
Introduction
The compound hydantoin, or imidazolidine-2,4-dione, was frst separated by Nobel
laureate Adolph von Baeyer in 1861 from the hydrogenolysis of allantoin and several
acyclic structures [1]. Hydantoins have several uses in current organic synthesis and
much important analogue in a number of therapeutic agents, which have an exten-
sive array of biological activities [2]. The most conversant medicinal application of
a hydantoin is as the drug phenytoin, which has a controlling efect on the central
nervous system (CNS), and has been used by people with epilepsy as an anticon-
vulsant to prevent psychomotor epilepsy for more than 60 years. Merrit and Putnam
frst recognized that phenytoin was active against induced seizures in cats, subse-
quently becoming accessible for medical use and has been functional as the fore-
most drug for the treatment of tonic–clonic seizures [2, 3]. Additionally, hydantoin
derivatives have synthetic value, e.g. as precursors to α-amino acid and pyruvic acid
derivatives [4–6]. Also, it has been observed primarily that these are undesired by-
products in the production of peptides [7, 8]. The fosphenytoin is a sodium channel
antagonist and nilutamide, an androgen antagonist, used in the treatment of epilepsy
and anticancer therapy, respectively [9].
Thiohydantoins are closely associated analogues of hydantoins containing sul-
phur atom and have a large number of medicinal and industrial applications [10, 11].
There are various routes of synthesis for hydantoin and its derivatives, depending on
the choice of starting materials [12, 13]. Usually, phenytoin and its derivatives are
synthesized by the well-known Bucherer–Bergs reaction [14].
In the preceding decades, many homogeneous catalytic methodologies were
described to obtain hydantoin and their derivatives. Ghandi [15] has demonstrated
a facile and suitable synthetic route to obtain some asymmetrical 1,3-diarylsubsti-
tuted 4,5-dihydroxy-2-imidazolidinones by the reaction of aqueous glyoxal with
N-heteroaryl-N′-phenylureas using formic acid. Here in the same year, a process
for the synthesis of enantiomerically pure hydantoins from optically pure α-amino
amides [16]. Another novel synthetic approach for the synthesis of 2-hydantoins has
been developed by using unprotected amino acids under acylation conditions with
potential applications towards the preparation of diferent heterocyclic compounds
from peptides [17]. Under ambient condition, Chandrashekar et al. [18] attempted to
synthesize the prodrug fosphenytoin sodium via imidate ester. Subsequently, several
homogeneous approaches were established to synthesize hydantoin and its deriva-
tives using aldehyde extracted from almond kernels [19], α1-adrenoceptor antago-
nists using 2-methoxyphenylpiperazine [20], treating methyl phenyl acetate with
di-tert-butyldiaziridinone [21], eco-friendly dialkylphosphate-mediated solvent-
free condition [22], various amine-alkyl terminal fragments at N1-position [23] and
2-thiohydantoin-asparagine from N-acetyl-2-thiohydantoin-asparagine [24]. Like-
wise, hybrids sandwiched between phenytoin and thiosemicarbazide, 1,3,4-oxadia-
zole, 1,3,4-thiadiazole or 1,2,4-triazole, have shown anticonvulsant activity [25].
Moreover, the diferent products of N-(2,4-dioxo 4,4-diphenyl imidazolidin-4-yl)
benzamides capable of anti-HIV and antiviral agents were described [26]. Recently,
5-substituted-3-(alkoxycarbonyl)alkyl-hydantoin products were synthesized by
1 3

Facile access to polymer supported zinc–salen complex: highly…
mechanochemistry from amino esters or dipeptides, through one-pot or two-step
cyclization reaction containing aminoacid unsymmetrical urea and carboxy-imida-
zolyl-dipeptide ester intermediates [27].
Furthermore, syntheses of hydantoin and thiohydantoin derivatives using micro-
wave activation [28–31] and ultrasound-activation [32] have also been successfully
reported. Conversely, the homogenous reactions employed for the preparation of
hydantoins and thiohydantoins confnes their practical application in product refning
from the reaction mixture. In order to develop more environmentally benign meth-
ods for the synthesis of hydantoins, heterogeneous catalytic systems have become an
active area of research in recent years. The synthesis of phenytoin (5,5-diphenylhy-
dantoin) was carried out using MgAl calcined hydrotalcites under eco-friendly con-
ditions with appreciable conversion (80–95%) and selectivity (90–95%) [33]. Safari
et al. [34] incorporated magnetic Fe3O4 nanoparticles as a heterogeneous catalyst for
the synthesis of 5,5-disubstituted hydantoins. Consecutively, the researchers have
developed a simple magnetic Fe3O4–chitosan nanoparticles for the large scale prepa-
ration of 5,5-diphenylhydantoins and 5,5-diphenyl-2-thiohydantoins, with low cata-
lyst loading, reusability, and ease of operation [35]. With the hope of meeting a few
principles of green chemistry, the same group designed renewable hybrid Fe3O4-chi-
tosan nanocatalysts to synthesize 5-substituted hydantoins with high yields in short
duration [36].
Among diferent heterogeneous catalysts, Zn–salen complex has received a
remarkable attentions due to their prospective use in various felds, such as enanti-
oselective alkynylation of ketones [37], CO2 fxation with epoxides at atmospheric
pressure [38], detection of H2O2 in cells [39], photo catalyst for the activation of
molecular oxygen to degrade organic pollutants in aqueous solution under visible
light irradiation (λ ≥ 420 nm) [40]. However, Zn–salen complexes were used in
quantitative analysis of applications, viz. fuorometry, as solvent extraction reagents
and as solid phase extraction sorbents [41].
From the literature survey, Co-salen complexes immobilized onto the HEMA-
resin [42], polystyrene supported salen type bis-thiopseudourea Pd(II)-complex [43]
and reusable salen Mn(III) complexes are reported [44] for the various applications,
but there is no report on polymer supported zinc–salen complex (PS-Zn–salen) for
the preparation of phenytoins. In our previous work, we exploited some polymer-
supported benzimidazolium based ionic liquid for efcient adsorption of hexavalent
chromium [45] and the PS-Zn–salen complexes for one pot oxidative esterifca-
tion of aldehyde to carboxylic ester [46]. In the continuation of our work, we have
revealed the facile access to polymer supported zinc–salen complex: Highly efcient
heterogeneous catalyst for hydantoins, thiohydantoins and Schif bases synthesis in
aqueous medium.
1 3

K. R. Balinge et al.
Experimental
Materials
All chemicals were used reagent grade with the highest purity available. ZnCl2,
4-vinylbenzyl chloride, DMSO-d6, CDCl3 were purchased from Sigma Aldrich
(India). 4-Hydroxybenzaldehyde, formaldehyde and other aldehydes, Azobisisobu-
tyronitrile (AIBN) were obtained from Avra synthesis Pvt. Ltd. and ethanol from
Changshu Yangyuan chemical China. Chloroform, acetonitrile, urea, thiourea, and
potassium thiocyanate from SDFCL and THF procured from Spectrochem Pvt. Ltd.
and used as received unless otherwise mentioned.
Characterization techniques
NMR spectra were recorded in DMSO-d6 and CDCl3 on a Bruker spectrometer
operating at 400 MHz and chemical shifts are given in ppm downfeld from TMS
(δ = 0.00). Surface morphology and the elemental composition of the complex
were investigated by scanning electron microscope (SEM) along with energy dis-
persive X-ray (EDX) spectroscopy (Carl Zeiss EVO/18SH, UK). An accelerating
voltage of 10 kV was applied to obtain SEM images. The sample was coated with
carbon tape, and gold particles were sputtered over the sample using a gold sput-
ter coater, after which the polymeric material was directly analyzed using the scan-
ning electron microscope. FT-IR spectra were obtained from IR Afnity Shimadzu
using the KBr pellet method. Thermal stability of PS-Zn–salen was confrmed using
TGA thermo analyser SII, 7200 (Seiko, Japan). Atomic absorption spectrometer
(AA240, Varian, Victoria, Australia) was used to determine leaching Zn in reac-
tion. Brunauer–Emmett–Teller (BET) surface area was measured at the temperature
of 77 K liquid N2 using a Quantachrome NOVA-1000 instrument analyser. Specifc
surface area, average pore diameter and pore volume are measured using N2 adsorp-
tion–desorption isotherms. Before analysis, samples were degassed at 150 °C for
5 h under vacuum for the removal of moisture and unwanted adsorbents from the
sample.
Synthesis and characterization of PS‑Zn–salen complex
Synthesis of polyvinyl benzyl chloride (PVBC) 1a, poly 1‑(4‑sec‑butyl)
benzyl)‑1H‑benzo[d]imidazole, 1b and 5‑(chloromethyl)‑2‑hydroxybenzaldehyde 1c
The synthesis of compounds 1a, 1b were carried out according to Khiratkar et al
[47] and 1c according to Naik et al. [48], and the characterization data of the cor-
responding compounds match with the literature reports.
1a: 1H NMR (400 MHz, CDCl3) δ = 7.08 (Ar–H, br), 6.5 (Ar–H, br), 4.56 (CH2–
Cl, br), 1.71 (br), 1.60 (br), 1.42 (br), 0.95 (br). 13C NMR (100 MHz, CDCl3)
1 3

Facile access to polymer supported zinc–salen complex: highly…
145.56, 134.97, 128.57, 46.37, 40.36, 31.60, 25.28. FT-IR (KBr) in cm−1: 3024,
2922, 2848, 1610, 1510, 1442, 1221, 1265, 1109, 1018, 912, 823, 707, 669, 559.
1b: 1H NMR (400 MHz, CDCl3) δ = 7.99 (NCHN, br), 7.7 (Bim–H, br), 7.19
(Bim–H, br), 6.6 (Ar–H, br), 6.17 (Ar–H, br), 4.95 (Bim–CH2–Ar, br), 1.84 (br),
1.48 (br), 1.25 (br), 0.84 (br). 13C NMR (100 MHz, CDCl3) 143.85, 143.09, 133.95,
128.03, 127.27, 122.97, 122.35, 120.37, 110.06, 67.99, 48.33, 29.71, 25.62. FT-IR
(KBr) in cm−1: 2918, 1492, 1363, 1330, 1259, 1197, 1178, 844, 817, 738, 634, 574.
1c: 1H NMR (400 MHz, CDCl3) δ = 11.08 (s, 1H, Ph-CHO), 9.90 (s, 1H, Ph–
OH), 7.6–7.55 (m, 2H, arom.), 7.02–7.00 (d, J = 8.89 Hz, 1H, CH arom), 4.6 (s,
2H, –CH2–).13C NMR (100 MHz, CDCl3) 196.19, 161.64, 137.64, 133.64, 118.33,
45.24. FT-IR (KBr) in cm−1: 3203, 3243, 2875, 1647, 1579, 1481, 1379, 1259,
1186, 1145, 1080, 991, 876, 766, 717, 667, 572, 497.
Synthesis of 1‑(4‑(sec‑butyl)benzyl)‑3‑(3‑formyl‑4‑hydroxybenzyl)‑1H‑benzo[d]
imidazol‑3‑ium chloride (IL) 1d
A mixture of poly 1-(4-sec-butyl)benzyl)-1H-benzo[d]imidazole (20 mmol, 5.28
gm) and 5-(chloromethyl)-2-hydroxybenzaldehyde (20 mmol, 3.4 gm) was put into a
100-mL round bottom fask in acetonitrile medium. The mixture was stirred at room
temperature for 24 h. The precipitated compound was then washed with diethyl ether
to obtain white powder of 1d. Yield: 68%.
1H NMR (400 MHz, DMSO-d6) δ = 10.25 (CH=O, s), 8.4 (C–NH–C, s), 8.1–7.5
(Bim H, br), 7.2–6.2 (Ar, br), 5.8 (CH2, br), 5.5 (CH2, br), 2, 1.23, 1.09, 0.85 (ali-
phatic proton). FT-IR (KBr) in cm−1: 3396, 2926, 1614, 1556, 1487, 1442, 1371,
1282, 1249, 1188, 744, 632.
Synthesis of 3,3′‑((((1E,1′E)‑(ethane‑1,2‑dylbis(azanylylidene))
bis(methanylylidene))bis(4‑hydroxy‑3,1‑phenylene))bis (methylene))
bis(1‑(4‑(sec‑butyl)benzyl)‑1H‑benzo[d]imidazol‑3‑ium) chlorideie [salen ligand]
1e
The salen ligand was prepared by slightly changing the procedure from Morris et al.
[49]. A solution of 1, 2-diethyl amine (7.5 mmol, 0.45 gm) and IL (1d) (15 mmol,
6.51 gm) in ethanol was stirred for 30 min at room temperature and refuxed for 2 h.
The ligand was isolated by fltration and purifed by repeated washing with ethanol
to remove unreacted amine. The product was then dried under vacuum to acquire the
yellow powder of salen ligand 1e.
1H NMR (400 MHz, DMSO-d6) δ = 13.18 (OH, br), 10.26 (CH=O, s), 8.5
(C–NH–C, s), 8.4–7.5 (Bim H, br), 7.2–6.8 (Ar, br), 5.6 (CH2, br), 5.5 (CH2, br),
3.5, 2, 1.23, 1.09, 0.85 (aliphatic proton). FT-IR (KBr) in cm−1: 3354, 3053, 3024,
2968, 2920, 2850, 1631, 1558, 1494, 1423, 1369, 1334, 1284, 1188, 742, 634, 574.
1 3

K. R. Balinge et al.
Synthesis of Zn–salen complex 1f
The Zn–salen complex was prepared by slight modifcation of the method of Mor-
ris et al. [49]. Initially salen ligand 1e (1 mmol, 0.892 g) in 10 mL ethanol was put
into a 100-mL fask followed by drop-wise charging of ZnCl2 (1 mmol, 0.136 g)
carried out at room temperature for 1 h. The mixture was then refuxed at 75–80 °C
for 2 h. The product was easily separated after the reaction. The product was repeat-
edly washed with ethanol and dried in a hot air oven to get a yellow fne powder of
Zn–salen complex 1f (Fig. 1).
General procedure for synthesis of Aryl thiourea derivatives 2a–2f
The library of aryl thiourea derivatives 2a–2f was prepared according to the litera-
ture [50], and the products were confrmed by FT-IR analysis (Supplementary data).
General procedure for the synthesis of hydantoin and thiohydantoin
derivatives (3a–j) catalyzed by (1f)
Slightly altering the process from the literature for preparation of hydantoin and
thiohydantoin derivatives was achieved by refuxing a mixture of benzil (1 mmol,
210 mg), urea or thiourea derivative (1.5 mmol), in aqueous ethanol (H2O/EtOH,
7:3) in the presence of 10 mg catalyst at 65 °C for 4 h. The reaction progress was
monitored by TLC (petroleum ether:ethyl acetate, 7:3 v/v). After the completion of
the reaction, the heterogeneous catalyst was separated by fltration and the fltrate
was acidifed with concentrated HCl to precipitate the desired product. The resulting
solids were recrystallized from aqueous ethanol to give pure products [35].
1
(3a) 5,5‑Diphenylimidazolidine‑2,4‑dione (Yield = 65%); H NMR (400 MHz,
DMSO-d6) δ = 11.06 (s, 1H), 9.27 (s, 1H), 7.41–7.31(m, 10H). 13C NMR (100 MHz,
DMSO-d6) 174.70, 155.86, 139.84, 128.39, 127.91, 126.48, 70.12. FT-IR (KBr) in
cm−1: NH (3265, 3194), C=O (1770, 1710). GC–MS m/z: calcd. for C15H12N2O2:
252.0899, found 252.1824.
(3b) 1‑Methyl‑5,5‑diphenylimidazolidine‑2,4‑dione (Yield = 51%); 1H NMR
(400 MHz, DMSO-d6) δ = 9.64 (s, 1H), 7.40–7.35 (m, 10H), 2.94 (s, 3H). 13C
NMR (100 MHz, DMSO-d6) 173.28, 155.49, 139.62, 128.50, 128.12, 126.64, 69.18,
24.49. FT-IR (KBr) in cm−1=NH (3280), C=O (1770, 1695).
1
(3c) 1,3‑Dimethyl‑5,5‑diphenylimidazolidine‑2,4‑dione (Yield = 89%); H NMR
(400 MHz, DMSO-d6) δ = 7.02–6.8 (m, 10H), 6.5 (s, 6H). 13C NMR (100 MHz,
DMSO-d6) 169.28, 138.02, 127.23, 127.20, 126.91, 92.28, 25.65,FT-IR (KBr) in
cm−1=C=O (1739), C=S (1178).
(3d) 5,5‑Diphenyl‑2‑thioxoimidazolidin‑4‑one (Yield
=
95%); 1H NMR
(400 MHz, DMSO-d6) δ = 12.13 (s, 1H), 11.30 (s, 1H), 7.42–7.31 (m, 10H). 13C
1 3

Facile access to polymer supported zinc–salen complex: highly…
Fig. 1 Preparation of polymer supported Zinc-centered salen complex (1f)
NMR (100 MHz, DMSO-d6) 181.32, 175.15, 138.35, 128.72, 128.39, 126.55, 72.95.
FT-IR (KBr) in cm−1: NH (3251, 3155), C=O (1745, 1722), C=S (1155). GC–MS
m/z: calcd. for C15H12N2OS: 268.0670 and found 268.1799.
(3e) 1,5,5‑Triphenyl‑2‑thioxoimidazolidin‑4‑one (Yield
=
83%); 1H NMR
(400 MHz, DMSO-d6) δ = 11.92 (s, 1H), 7.52–7.42 (m, 13H), 7.34 (d, J = 9.72 Hz,
2H). 13C NMR (100 MHz, DMSO-d6) 181.01, 173.13, 138.13, 134.94, 128.98,
1 3

K. R. Balinge et al.
128.91, 128.85, 128.66, 126.76, 71.86. FT-IR (KBr) in cm−1=NH (3294), C=O
(1737), C=S (1172).
(3f) 1‑(4‑Chlorophenyl)‑5,5‑diphenyl‑2‑thioxoimidazolidin‑4‑one (Yield = 76%);
1H NMR (400 MHz, DMSO-d6) δ = 12 (s, 1H), 7.59 (d, J = 8.63 Hz, 2H), 7.50–
7.40 (m, 12H). 13C NMR (100 MHz, DMSO-d6) 180.61, 172.94, 138.01, 133.94,
131.74, 130.78, 128.90, 128.70, 129.79, 71.96. FT-IR (KBr) in cm−1=NH (3319),
C=O (1735), C=S (1176).
(3g) 5,5‑Diphenyl‑2‑thioxo‑1‑(p‑tolyl)imidazolidin‑4‑one (Yield = 39%); 1H NMR
(400 MHz, DMSO-d6) δ = 11.89 (s, 1H), 7.50–7.41 (m, 10H), 7.32 (d, J = 8.51 Hz,
2H), 7.20 (d, J = 8.51 Hz, 2H), 2.36 (s, 3H). 13C NMR (100 MHz, DMSO-d6)
181.19, 173.18, 138.64, 138.17, 138, 129.48, 128.90, 126.75, 71, 20. FT-IR (KBr) in
cm−1=NH (3153), C=O (1747), C=S (1172).
(3h) 1‑(4‑Fluorophenyl)‑5,5‑diphenyl‑2‑thioxoimidazolidin‑4‑one (Yield = 88%);
1H NMR (400 MHz, DMSO-d6) δ = 11.95 (s, 1H), 7.50–7.40 (m, 12H), 7.37 (t,
J = 8.8 Hz, 2H). 13C NMR (100 MHz, DMSO-d6) 180.91, 173.09, 163.17, 160.72,
138.07, 131.31, 128.89, 126.70, 116.02, 71.88. FT-IR (KBr) in cm−1=NH (3221),
C=O (1734), C=S (1153).
(3i) 1‑(4‑bromophenyl)‑5,5‑diphenyl‑2‑thioxoimidazolidin‑4‑one (Yield = 74%);
1H NMR (400 MHz, DMSO-d6) δ = 11.97 (s, 1H), 7.73 (d, J = 8.74 Hz, 2H), 7.50–
7.40 (m, 10H), 7.35 (d, J = 8.74 Hz, 2H). 13C NMR (100 MHz, DMSO-d6) 180.53,
172.87, 137.99, 132.18, 131.99, 131.07, 128.90, 128.69, 126.77, 122.27, 71.96.
FT-IR (KBr) in cm−1=NH (3315), C=O (1735), C=S (1174).
(3j) 1‑(naphthalen‑1‑yl)‑5,5‑diphenyl‑2‑thioxoimidazolidin‑4‑one (Yield = 54%)
1H NMR (400 MHz, DMSO-d6) δ = 12.10 (s, 1H), 8.12–8.06 (m, 2H), 7.68
(d, J = 8.07 Hz, 1H), 7.58–7.44 (m, 13H), 7.29 (d, J = 8.51 Hz, 1H). 13C NMR
(100 MHz, DMSO-d6) 181.38, 173.45, 138.33, 138.09, 133.77, 129.96, 129.78,
129.36, 129.11, 128.73, 128.34, 127.36, 126.91, 126.56, 125.67, 121.26, 72.44.
FT-IR (KBr) in cm−1=NH (3151), C=O (1762), C=S (1178).
General procedure for synthesis of Schif bases 4a–4i catalyzed by (1f)
Varying the procedure from the literature, 10 mg catalyst was added to a solution
of ethylenediamine (1 mmol, 60 mg) and 2 mmol of benzaldehyde derivative in
10 mL distilled water and refuxed at 80 °C for 2 h. The reaction mixture was poured
onto ice, and the resulting precipitate was dissolved in ethyl acetate and the catalyst
was separated by fltration. Evaporate of EtOAc to get Schif bases, which can be
further recrystallized using ethanol [51].
(4a) 2,2′‑((1E,1′E)‑(Ethane‑1,2‑diylbis(azanylylidene))bis (methanylylidene))diphe‑
1
nol (Yield = 79%); H NMR (400 MHz, CDCl3) δ = 13.19 (s, 2H), 8.35 (s, 2H),
1 3

Facile access to polymer supported zinc–salen complex: highly…
7.30–7.21 (m, 4H), 6.94 (d, J = 8.35 Hz, 2H), 6.8 (t, J = 7.75 Hz, 2H), 3.93 (S,
4H). 13C NMR (100 MHz, CDCl3) 166.52, 161.02, 132.41, 131.50, 118.69, 118.65,
116.97, 59.77. GC–MS m/z: calcd. for C16H16N2O2: 268.1212 and found 268.2494.
(4b) 3,3′‑((1E,1′E)‑(Ethane‑1,2‑diylbis(azanylylidene))bis (methanylylidene))diphe‑
nol (Yield = 86%); 1H NMR (400 MHz, DMSO-d6) δ = 9.4 (s, 2H), 8.23 (s, 2H),
7.22 (t, J = 7.6 Hz, 2H), 7.14 (s, 2H), 7.10 (d, J = 7.34 Hz, 2H), 6.8 (d, J = 8.09 Hz,
2H), 3.82 (s, 4H). 13C NMR (100 MHz, DMSO-d6) 161.89, 157.54, 137.44, 129.59,
119.28, 117.79, 113.64, 60.87.
(4c) (1E,1′E)‑N,N′‑(Ethane‑1,2‑diyl)bis(1‑p‑tolylmethanimine) (Yield = 70%);1H
NMR (400 MHz, CDCl3) δ = 8.24 (s, 2H), 7.59 (d, J = 7.31 Hz, 4H), 7.19 (d,
J = 7.63 Hz, 4H), 3.94 (s, 4H), 2.36 (s, 6H). 13C NMR (100 MHz, CDCl3) 162.84,
141.12, 133.92, 129.56, 128.36, 62, 21.76.
(4d)
(1E,1′E)‑N,N′‑(Ethane‑1,2‑diyl)bis(1‑(4‑methoxyphenyl)
methan‑
1
imine) (Yield = 70%); H NMR (400 MHz, CDCl3) δ = 8.20 (s, 2H), 7.64 (d,
J = 8.56 Hz, 4H), 6.90 (d, J = 8.53 Hz, 4H), 3.91 (t, 4H), 3.82 (s, 4H). 13C NMR
(100 MHz, CDCl3) 162.03, 161.71, 129.76, 129.35, 114.07, 61.86, 55.47.
(4e)
(1E,1′E)‑N,N′‑(Ethane‑1,2‑diyl)bis(1‑(3,4,5‑trimethoxy‑phenyl)methan‑
1
imine) (Yield = 88%); H NMR (400 MHz, CDCl3) δ = 8.29 (s, 2H), 7.07 (s,
4H), 4.07 (s, 4H), 4.00 (s, 12H), 3.9 (s, 6H). 13C NMR (100 MHz, CDCl3) 162.21,
153.34, 140.30, 131.61, 105.08, 61.44, 60.82, 56.12.
(4f)
5,5′‑((1E,1′E)‑(Ethane‑1,2‑diylbis(azanylylidene))bis(methanylylidene))bis(2
1
ethoxyphenol) (Yield = 78%); H NMR (400 MHz, DMSO-d6) δ = 9.14 (s, 2H),
8.16 (s, 2H), 7.22 (s, 2H), 7.07 (d, J = 8.30 Hz, 2H), 6.95 (d, J = 7.92 Hz, 2H),
3.79 (s, 6H), 3.33 (t, 4H). 13C NMR (100 MHz, DMSO-d6) 172.55, 184.28, 134.55,
134.35, 133.22, 26.33.
(4g)
(1E,1′E)‑N,N′‑(Ethane‑1,2‑diyl)bis(1‑(4‑bromophenyl)
methan‑
1
imine) (Yield = 92%); H NMR (400 MHz, CDCl3) δ = 8.20 (s, 2H), 7.56 (d,
J = 8.35 Hz, 4H), 7.52 (d, J = 8.35 Hz, 4H), 3.9 (s, 4H). 13C NMR (100 MHz,
CDCl3) 161.56, 135.11, 131.95, 129.62, 125.21, 61.55.
(4h)
(1E,1′E)‑N,N′‑(Ethane‑1,2‑diyl)bis(1‑(4‑chlorophenyl)
methan‑
imine) (Yield = 76%); H NMR (400 MHz, CDCl3) δ = 8.22 (s, 2H), 7.62 (d,
J = 7.70 Hz, 4H), 7.36 (d, 7.70 Hz, 4H), 3.95 (s, 4H). 13C NMR (100 MHz, CDCl3)
161.62, 136.95, 134.90, 129.18, 61.75.
(4i)
(1E,1′E)‑N,N′‑(Ethane‑1,2‑diyl)bis(1‑(4‑nitrophenyl)
methan‑
1
imine) (Yield = 75%) H NMR (400 MHz, CDCl3) δ = 8.37 (s, 2H), 8.25 (d,
J = 7.62 Hz, 4H), 7.87 (d, J = 7.64 Hz, 4H), 4.06 (s, 4H). 13C NMR (100 MHz,
CDCl3) 160.66, 149.40, 141.72, 129.09, 124.20, 61.78, 30.04.
1 3

K. R. Balinge et al.
Results and discussion
Catalyst characterization
Fourier transform infrared (FT‑IR) spectroscopy
The FT-IR spectra of the IL (1d), salen ligand (1e) are compared with that of Zn–salen
complex (1f) (Fig. 2) to defne the coordination sites that may be involved in chela-
tion. The most signifcant IR spectral bands in (1d) and (1e) for (O–H) appeared
at 3396 cm−1 and 3354 cm−1, respectively. Similarly, stretching bands observed
at 1656 cm−1 is due to (aldehyde C=O) in IL (1d) and 1631 cm−1 for (C=N) in the
ligand (1e). The formation of Schif base Zn(II)-complex is evidenced by the disap-
pearance of (O–H) stretching band in (1f). Conclusive evidence of the bonding is
also shown by the appearance of the new band in the region (532 and 416 cm−1) in
the spectrum of the complex due to (Zn–O) and (Zn–N) stretching vibrations. For
the Schif base, the (C=N–) stretching of salen ligand (1e) is observed as a strong
band at 1631 cm−1. This band undergoes a small shift on complexation (~ 9); such
a small shift has been observed at 1622 cm−1 (1f), which revealed that azomethine
nitrogen is involved in coordination to the metal [52–54].
Scanning electron microscopy (SEM) images and energy dispersive X‑ray analysis
(EDX)
The surface morphology and elemental analysis of polymer supported Zn–salen
complex was characterized by SEM/EDX as shown in Fig. 3. The scanning elec-
tron micrograph (SEM) images were reported for polymer supported salen ligand
(A) and polymer supported Zn–salen complex (C). The polymer supported Zn–salen
complex showed morphological changes (A and C) that indicate the formation of
the desired complex. The surface of polymer supported Zn–salen complex reveal
Fig. 2 FT-IR spectrum of 1d,
1e and 1f
532
416
1622
3354
1631
3396
Zn-salen (1f)
1656
Salen ligand (1e)
IL (1d)
4000 3500 3000 2500 2000 1500 1000 500
-1
Wavenumber (cm
)
1 3

Facile access to polymer supported zinc–salen complex: highly…
Fig. 3 SEM/EDX of polymer supported salen ligand (a/b) and polymer supported Zn–salen complex
(1f) (c/d)
micron sized particles deposited over the surface (Fig. 3c). The comparative spec-
trum of energy-dispersive X-ray spectroscopy, ligand (B) and a metal complex (D)
confrmed the presence of Zn in the metal complex (D).
Thermal analysis
Thermal stability of PS-salen (1e) and PS-Zn–salen (1f) were studied using TGA
under a nitrogen atmosphere with a heating rate of 10 °C min−1 over a temperature
range of 30–800 °C (Fig. 4). There is negligible weight loss in 1f (4.250%) com-
pared to 1e (8.5%) below 120 °C indicating the presence of physically adsorbed sol-
vent. Weight loss of 62.56% 1e, 36.48% 1f in the region of 235–470 and 280–550,
respectively, may be due to a salen group of the ligand and the complex begins to
crumble. The observations clearly indicate the stability of PS-Zn–salen is more
compared to the PS-salen ligand. Further weight loss in both 1e and 1f perceived
to decomposition of poly 1-(4-sec-butyl)benzyl)-1H-benzo[d] imidazole. From TGA
analysis it is observed that the weight loss is negligible up to 280 °C in 1f and is
found to be thermally stable; therefore, it is concluded that the polymer supported
Zn–salen complex (1f) catalyst is suitable for high-temperature reaction.
1 3

K. R. Balinge et al.
Fig. 4 Thermogravimetric
analysis (TGA) thermogram of
PS-salen (1e) and PS-Zn–salen
(1f)
100
80
60
40
20
0
PS-Zn-salen (1f)
PS-salen (1e)
0
100 200 300 400 500 600 700 800
Temperature (°C)
BET analysis
Specifc surface area and pore size distribution of the Zn–salen complex was meas-
ured using adsorption and desorption isotherm of nitrogen molecules. The BET
specifc surface area of synthesized Zn–salen complex was found to be 4.783 m2/g
(Fig. 5). The total pore volume and average pore diameter of Zn–salen complex was
0.015 cc/g and 1.562 nm, respectively (Fig. 6).
Catalytic activity of polymer supported Zn–salen complex
Owing to our curiosity in the progress of more ecological catalytic reaction con-
ditions and our interest in the green chemistry of ILs [55, 56], we report here
new results under heterogeneous catalysis to support the formation of hydantoin/
Fig. 5 BET isotherm of PS-Zn–
10
salen
8
6
4
2
0
0.0
0.2
0.4
0.6
0.8
1.0
Relative pressure (p/po)
1 3

Facile access to polymer supported zinc–salen complex: highly…
0.0030
Fig. 6 Pore diameter and pore
volume of PS-Zn–salen
0.0025
0.0020
0.0015
0.0010
0.0005
0.0000
0
5
10
15
20
25
30
35
40
Pore diameter (nm)
thiohydantoin/Schif bases in an aqueous medium. To begin our study, we examined
the synthesis of hydantoins and thiohydantoins using benzil and urea/thiouera deriv-
atives (Scheme 1) and Schif bases (Scheme 2) by reacting ethylenediamine with
aromatic aldehydes in the presence of polymer supported Zn–salen complex under
a variety of reaction conditions. The results are summarized in Tables 1 and 2 show-
ing the optimization of the amount of catalyst, temperature, time on the synthesis
of 5,5-diphenyl-2-hydantoin (Scheme 3) and Schif bases, respectively (Scheme 4).
Initially, in order to optimize the reaction parameters such as amount of cata-
lyst, temperature and time, we carried out the model reaction for the synthesis of
5,5-diphenyl-2-hydantoin by reacting benzil with urea under diferent conditions
shown in Table 1. A control reaction was attempted to test the necessity of a catalyst
Scheme 1 Synthesis of 5,5-diphenylhydantoins and 5,5-diphenyl-2-thiohyd-antoins
Scheme 2 Synthesis of Schif bases
1 3

K. R. Balinge et al.
Table 1 Optimization of the
amount of catalyst, temperature
and time on 5,5-diphenyl-2-
hydantoin catalyzed by (1f)
Entry Catalyst
amount
Solvent
Tem-
Time (min) Yielda (%)
perature
(°C)
(mg)
1
2
3
4
5
6
7
8
0
10
5
30% EtOH 65
30% EtOH 65
30% EtOH 65
30% EtOH 65
30% EtOH 65
30% EtOH 65
30% EtOH RT
30% EtOH 45
30% EtOH 55
30% EtOH 65
30% EtOH 75
30% EtOH 85
30% EtOH 65
30% EtOH 65
30% EtOH 65
30% EtOH 65
30% EtOH 65
240
240
240
240
240
240
240
240
240
240
240
240
60
20
31b
57
65
65
64
23
35
47
65
60
57
48
56
61
65
63
10
15
20
10
10
10
10
10
10
10
10
10
10
10
9
10
11
12
13
14
15
16
17
120
180
240
300
Reaction condition: benzil (1 mmol, 210 mg), urea (1.5 mmol,
90 mg), aqueous ethanol (30%)
aIsolated yield of product
bIn presence of 1e
by stirring the reagents in the absence of the catalyst. It is worth emphasizing that
reactions accomplished 65% yield in the presence of catalyst, but in the absence of
catalyst, gave poor results (yield 20%; Table 1, entry 1). Likewise, the reaction car-
ried out with ligand (1e) does not show much progress in the product (Table 1, entry
2). The amount of catalyst loading was tested on the model reaction (Table 1, entries
3–6). The optimal amount of the catalyst was 10 mg (Table 1, entry 4). However,
it is exciting to note that there is no change in yields irrespective of loading more
amount of the catalyst (Table 1, entries 5–6). Thus, it was evident that the amount of
catalyst plays an important role in the formation of products.
With the optimized amount of catalyst (10 mg) in hand, we examined reaction
(Scheme 3) using benzil and urea at diferent temperatures and time in aqueous
ethanol (30%). We also investigated the reaction using the ratio of benzil to urea
1.0:1.5 between the reagents toward a more efcient and greener process to yield
the corresponding 5,5-diphenyl-2-hydantoin (65% yield) at 65 °C Table 3. The yield
improved as the reaction temperature was raised from room temperature to 65 °C. At
65 °C, moderate yield (65%) of product was obtained in moderate yield of 65% in
240 min (Table 1, entries 7–10). A further increase in temperature did not improve
the product yield, but somewhat decreased it (Table 1, entries 11 and 12). It is worth
1 3

Facile access to polymer supported zinc–salen complex: highly…
Table 2 Optimization of
catalyst amount, temperature
and time on the synthesis of the
catalyzed Schif base (1f)
Entry Catalyst
amount
Solvent Tem-
Time (min) Yielda (%)
perature
(mg)
(°C)
1
2
3
4
5
6
7
8
0
5
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
80
80
80
80
RT
45
55
65
70
75
80
85
90
80
80
80
80
80
80
120
120
120
120
120
120
120
120
120
120
120
120
120
30
43
87
94
94
65
71
73
77
83
89
94
94
92
79
86
90
94
91
89
10
15
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
9
10
11
12
13
14
15
16
17
18
19
60
90
120
150
180
Reaction condition: 4-bromobenzaldehyde (2 mmol, 370 mg), ethyl-
enediamine (1 mmol, 60 mg), H2O (10 mL)
aIsolated yield of product
Scheme 3 Synthesis of 5,5-diphenyl-2-hydantoin
Scheme 4 Synthesis of Schif base
1 3

K. R. Balinge et al.
Table 3 Efect of ratio of
benzil to urea on the synthesis
of 5,5-diphenylhydantoins
catalyzed by (1f)
Entry
Benzil:urea
Yielda
(%)
1
2
3
1:1
1:1.5
1:2
50
65
64
Reaction condition: benzil (1 mmol, 210 mg) and urea, dil. NaOH
(3 mL), aqueous ethanol (10 mL) and Cat. (10 mg). refux at 65 °C
for 4 h
aIsolated yield of product
mentioning that the catalytic activity enhances with increasing duration of the reac-
tion from 60 min to 240 min (Table 1, entries 13–16) but remained almost the same
with a variation of time from 240 to 300 min (Table 1, entry 17). Thus the formation
of hydantion proceeded smoothly in the presence of aqueous ethanol, 10 mg cat.,
and 65 °C in 240 min. and gave the desired product in admirable yield. Similarly
optimization of all the parameters like amount of catalyst, temperature and time for
the synthesis of Schif bases catalyzed by 1f, were carried out and summarized in
Table 2. Further, to examine the substrate choice of this reaction, urea with difer-
ent substituents were used under the above-optimized conditions. From the results
shown in Table 4, it is apparent that the reactions progressed efectively and gave the
desired products in good to excellent yields in 240 min.
A variety of substituted urea and thiourea, with either electron-donating or
electron-withdrawing groups, provided encouraging results in this reaction. For
example, methyl and dimethyl urea aforded the corresponding hydantoin products
in appreciable yields (Table 4, entries 2 and 3). Thiourea (Table 4, entry 4), phenyl
(Table 4, entry 5) and halo phenyl sub-stituted thiourea were equally responsive to
these conditions providing thiohydantoins in 74 to 88% yield (Table 4, entries 6, 8
and 9). P-tolylthiourea 1-naphthyl thiourea could also be achieved using this meth-
odology, albeit in signifcantly lower yields indicating the admirable catalytic activ-
ity of catalyst (Table 4, entry 7 and 10). The efect of various electron-donating or
electron-withdrawing groups on synthesis of Schif base derivatives summarized in
Table 5.
A plausible mechanism for the hydantoin, thiohydantoin catalyzed by
PS-Zn–salen complex is shown in Scheme 5. Initially, (1f) as a Lewis acid, and OH
group of the base through hydrogen bonding activated the carbonyl group of benzil
for the nucleophilic substitution of urea that leads to the formation of corresponding
intermediate (I). The ring closure of this intermediate, via the electrophilic nitrogen
atom of urea ofered an intermediate (II). The stability of the intermediate (II) con-
trols the selectivity of the main product (hydantoin/thiohydantoin) in the presence
of (1f). Furthermore, the catalyst prevents the reaction pathway (b) and follows the
reaction pathway (a). In the presence of KOH as a catalyst, the pathway (b) might be
possible [33]. Therefore, the selectivity of the major product depends on the com-
petitive paths (a) and (b).
1 3

Facile access to polymer supported zinc–salen complex: highly…
Table 4 Synthesis of 5,5-diphenylhydantoins and 5,5-diphenyl-2-thiohydantoins catalyzed by (1f)
1 3

K. R. Balinge et al.
Table 4 (continued)
Reaction condition: benzil (1 mmol, 210 mg), urea/thiourea derivatives (1.5 mmol), Dil. NaOH (3 mL),
aqueous ethanol (10 mL) and Cat. (10 mg). Refux at 65 °C for 4 h
aIsolated yield of product
Stability and recyclability
In continuation of our eforts to develop an efcient and environmentally benign
protocol for the organic synthesis, our aim was to provide, improved, water-tol-
erant and recoverable catalyst. The recyclability of the catalyst was studied using
the above model reaction. After separation of the product, by fltration, the catalyst
was washed with ethanol and reused in the next run without further purifcation.
A mixture of benzil and thiourea in (1:1.5) ratio was added to the aqueous ethanol
(30%) and stirred under the same conditions. The data listed in (Fig. 7) indicated
that the Zn–salen catalyst was successfully used in six successive runs and presented
steady activity to aford an average yield of 88.5% with no signifcant loss of per-
formance. Compared with the traditional solvents and catalysts, the easy reusability
is also a prominent property of the complex for environmental protection and com-
mercial reasons. High stability of complex 1f was further confrmed by using FT-IR
and showed that the structure of the catalyst stayed intact during the catalysis even
after six runs (Fig. 8). Therefore, the present PS-Zn–salen complex is very attrac-
tive for the synthesis of hydantoins, thiohydantoins and Schif bases. Moreover yield
obtained in an aqueous medium using 1f catalyst, towards condensation reaction is
better than or analogous to the literature reports with respect to catalyst loading and
duration of reaction (Table 6).
Leaching studies
To determine the degree of leaching of Zn from the heterogeneous catalyst, the cata-
lyst was removed by fltration and the Zn content of the fltrate was determined by
AAS. During the course of reactions, only 0.184 ppm of Zn was lost into solution
after the frst run. After the 6th recycle loss of 1.155 ppm of Zn was observed, which
shows the average amount of leaching of Zn per cycle is about 0.192 ppm.
To defne whether the catalyst is truly functioning as heterogeneous or if it is
just a reservoir for more active soluble Zinc species, we have performed a hot fltra-
tion test [57]. This test includes fltering of the solid catalyst during some point of
the reaction at the optimized temperature. The substrates (urea and benzil) allowed
reacting at reaction temperature with Ps-Zn–salen for 1 h, fltering the catalyst and
continued the reaction in the fltrate. We found that after hot fltration of the cata-
lyst, there is no acceptable change in conversion of product. On the basis of these
outcomes, we may conclude that the catalysis reaction is indeed heterogeneous in
nature and the leached zinc species did not catalyzed the reaction.
1 3

Facile access to polymer supported zinc–salen complex: highly…
Table 5 Synthesis of Schif bases catalyzed by (1f)
1 3

K. R. Balinge et al.
Table 5 (continued)
Reaction condition: aldehydes (2 mmol), ethylenediamine (1 mmol, 60 mg), Cat. (10 mg), H2O (10 mL),
refux at 80 °C for 2 h
aIsolated yield of product
Scheme 5 Possible reaction pathway for the synthesis of hydantoin/thiohydantoin
Fig. 7 Recyclability of catalyst
(1f) recovers up to 6th run
100
80
60
40
20
0
95%
94%
91%
88%
84%
79%
1
2
3
4
5
6
Recycle time
1 3

Facile access to polymer supported zinc–salen complex: highly…
(6thrun)
(4rdrun)
Fig. 8 FT-IR spectrum of cata-
lyst (1f) recovers up to 6th run
(2ndrun)
(1strun)
(1f)
1622
532
416
4000 3500 3000 2500 2000 1500 1000
500
-1
Wavenumber (cm )
Table 6 Comparison of (1f) with other catalysts in the synthesis of 5,5-diphenylhydantoins and
5,5-diphenyl-2-thiohydantoins
Entry Catalyst
Catalyst dosage (in mg) Time Solvent
Yield (%)
1.
2.
3.
4.
5.
CuCl-P(n-Bu)3
Dialkylphosphate
Mg/Al-3calcined
Fe3O4–chitosan NPs 45 mg
PS-Zn–salen (1f) 10 mg
5 mol%
Reactnt:Cat (1:2)
50 mg
12 h
1 h
24 h
CHCl3
Solvent less
MeOH
79 [21]
92 [22]
73 [33]
8 min H2O:EtOH (1:2) 99 [35]
4 h H2O:EtOH (7:3) 95 (Present work)
Conclusions
In conclusion, we have successfully synthesized a new polymer supported Zn–salen
(PS-Zn–salen) complex. The existence of organic functionalities in the complex was
clearly quantifed by Fourier transform infrared spectrophotometry (FT-IR), energy-
dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and
Fourier transform NMR spectroscopy (FT-NMR). The heterogeneous catalyst shows
high thermal stability up to 280 °C and has displayed admirable activity in the syn-
thesis of hydantoins, thiohydantoins and Schif bases in an aqueous medium. It
could be reused six times with slightly decline the activity, representing a robust
solid catalyst. The stability of the catalyst was further confrmed by FT-IR analy-
sis, which revealed that the Zn–salen complex catalyzed the condensation reac-
tions without deterioration of the ordered structure. The high yield of condensation
compounds (up to 95%), the use of a relatively low catalyst, the easy work up, an
environmentally benign protocol, mild reaction conditions, high atom economy,
shorter reaction times are the advantages of this protocol over the other procedures
1 3

K. R. Balinge et al.
reported. Other studies of its applicability in synthetic conversions are currently on-
going in our laboratory.
Acknowledgements The authors thank VIT Vellore for providing “VIT SEED GRANT” for carrying
out this research work and SIF DST-VIT-FIST for NMR, GC–MS, FT-IR and SEM/EDX VIT University,
Vellore for providing necessary facility to bring this article to this level. We are also thankful to the Dean,
School of Advanced Sciences, and all the Scholars of our Research Laboratory, “Smart Materials Labora-
tory for Bio-Sensing and Catalysis” VIT University Vellore, who have encouraged the authors during this
period.
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