Polymeric imidazolium ionic liquid-tagged manganese Schiff base complex: an efficient catalyst for the Biginelli reaction

Article abstract of DOI:10.1007/s11164-020-04230-8

Abstract: In this study, a new organometallic catalyst including polymeric imidazolium ionic liquid-functionalized Mn(III) Schiff base complex (PIL-SB-Mn(III)) was prepared and characterized using various analyses like FTIR, H-NMR, FE-SEM, EDX, TGA, and ICP-OES. Then, the applications of catalyst were tested in the synthesis of 3,4-dihydropyrimidine-2(1H)-one/thiones under solvent-free conditions. This polymeric ionic liquid catalyst can carry out the Biginelli reaction in less than an hour in good to excellent yields. The recovered catalyst has been characterized by FTIR and EDX analyses; heterogeneous nature of this catalyst has been confirmed successfully. Graphic abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-020-04230-8

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04230-8
Polymeric imidazolium ionic liquid‑tagged manganese
Schif base complex: an efcient catalyst for the Biginelli
reaction
Mahboobeh‑Sadat Mashhoori1 · Reza Sandaroos1 ·
Ali Zeraatkar Moghaddam1
Received: 15 May 2020 / Accepted: 1 August 2020
© Springer Nature B.V. 2020
Abstract
In this study, a new organometallic catalyst including polymeric imidazolium ionic
liquid-functionalized Mn(III) Schif base complex (PIL-SB-Mn(III)) was prepared
and characterized using various analyses like FTIR, H-NMR, FE-SEM, EDX, TGA,
and ICP-OES. Then, the applications of catalyst were tested in the synthesis of
3,4-dihydropyrimidine-2(1H)-one/thiones under solvent-free conditions. This poly-
meric ionic liquid catalyst can carry out the Biginelli reaction in less than an hour in
good to excellent yields. The recovered catalyst has been characterized by FTIR and
EDX analyses; heterogeneous nature of this catalyst has been confrmed successfully.
Graphic abstract
Keywords Polymer · Ionic liquid · Schif base · Biginelli reaction ·
3,4-Dihydropyrimidine-2-one
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-020-04230-8) contains supplementary material, which is available to authorized users.
*
Mahboobeh-Sadat Mashhoori
M.Mashhoori2015@birjand.ac.ir
*
Reza Sandaroos
R_Sandaroos@birjand.ac.ir
1
Department of Chemistry, Faculty of Science, University of Birjand, P.O. Box 97175-615,
Birjand, Iran
Vol.:(0123456789)
1 3

M.-S. Mashhoori et al.
Introduction
Recently, discovering the more sustainable catalytic system is the most important
challenge in modern chemistry. In current research, multicomponent reactions
(MCRs) are presented as a strong method to synthesis of a wide variety of organic
compounds in a very fast and easy manner without the separation and purifcation of
any intermediate [1–7]. Simple procedure, high atom economy and time-saving are
the major advantages of MCRs. Combining of MCRs with separable and reusable
catalysts is an attractive path to avoid the waste produced in regular syntheses and
decrease the efect of chemistry on the environment [8–10].
Ionic liquids (ILs) are a new class of ionic, salt-like materials which are liquid at
room temperature or even below 0 °C. To date, these ionic compounds have been
used in diferent applications like organic synthesis [11, 12], industrial processing
[13], catalysis [14–16], nano-chemistry [17, 18] and other [19, 20]. These worth-
while materials can act as a solvent in organic synthesis, and usually they have been
efcient and essential in several reactions to improve the yields of the reaction and
also inducing selectivity [21–23]. Schif bases complexes are well-known inorganic
compounds that they have diferent biological and pharmaceutical properties such
as antiviral [24], anticancer [25], antifungal [26] and antibacterial [27]. These inor-
ganic complexes are increasingly applied as efcient catalysts due to their unbeliev-
able catalytic activity in plenty of organic reactions [28–30].
The Biginelli reaction is one of the MCRs carried out from three-components
condensation reaction of aromatic and aliphatic aldehydes with 1,3-dicarbonyl com-
pounds and urea/thiourea to produce 3,4-dihydropyrimidine-2(1H)-one/thiones [31,
32]. The products of Biginelli reaction are extremely signifcant in organic synthe-
sis, because they have various pharmacological and biological properties like anti-
infammatory, antibacterial, antiviral, anti-HIV activity and anticancer [33–38]. The
synthesis of 3,4-dihydropyrimidine-2(1H)-one/thiones has been traditionally done
under Brønsted and Lewis acidic catalysts such as para-toluene sulfonic acid [39],
trifuoroacetic acid [40], trifuoromethanesulfonic acid [41], TiCl3 [42], ZrCl4 [43],
FeCl3·6H2O [44], CoCl2·6H2O [45], and some heterogeneous catalytic systems like
silica-supported materials [46–49], supported magnetic nanoparticles [50] and car-
bon-based materials [51, 52]. However, most of these Brønsted and Lewis acidic
catalytic systems are not eco-friendly and have some drawbacks like using toxic sol-
vents and harmful conditions and problems in recyclability of catalyst and also prod-
uct separation and purifcation. To overcome these restrictions, introducing new and
applicable methods is still recommended.
In this study, a new heterogeneous polymer catalyst (PIL-SB-Mn(III)) has been
synthesized by the covalent bonding of polymeric ionic liquid to salicylaldehyde,
followed by complex formation via the reaction with manganese acetate (Scheme 1).
Furthermore, the catalytic application of this Schif bases complex catalyst has
been investigated in the synthesis of 3,4-dihydropyrimidine-2(1H)-one/thiones
through the three-component condensation reaction of diferent aldehydes with
various 1,3-dicarbonyl compounds and urea or thiourea in solvent-free conditions
(Scheme 2).
1 3

Polymeric imidazolium ionic liquid‑tagged manganese Schif…
Scheme 1 Synthesis of PIL-SB-Mn(III) catalyst
Scheme 2 Synthesis of 3, 4-dihydropyrimidin-2-ones in the presence of PIL-SB-Mn(III) catalyst
Experimental
Chemicals and instruments
All solvents were purchased from Merck and were dried by standard procedures.
N-Vinyl imidazole (VIM), azobisisobutyronitrile (AIBN), 3-bromopropylamine
hydrobromide, salicylaldehyde and manganese acetate were purchased from
1
Sigma-Aldrich. HNMR, spectra were recorded on a Bruker Avance DPX-250
using deuterated DMSO as solvent and TMS as internal standard. FTIR spectra
were recorded on a PerkinElmer FTIR spectrometer (KBr tablets). The morphol-
ogy and elementary analysis (EDS) of the catalyst were determined by using FE-
SEM-FEI Nova nanoSEM 450 instrument. Thermogravimetric analysis (TGA)
was performed on a Q600 TA instrument at 30–700 °C with a heating gradient
of 20 °C min−1 in argon atmosphere. ICP-OES analysis was performed using a
simultaneous VISTA-PRO instrument.
1 3

M.-S. Mashhoori et al.
Preparation of ionic liquid (IL)
To fask that contains an ethanolic solution of 3-bromopropylamine hydrobromide
(10 mmol, 2.2 g) was added N-Vinyl imidazole (10 mmol, 0.8 mL) and refuxed
under argon atmosphere for 24 h. Then, the reaction mixture was cooled to room
temperature and the solvent removed by rotary. The obtained viscous liquid was
changed to white-yellow sediment after washing with dry acetonitrile, ethyl ether
and chloroform and dried in a vacuum oven for 12 h at 60 °C. Melting point:
1
123–124 °C. H-NMR (300 MHz, DMSO, TMS) δ (ppm) = 2.2 (m, 2H, –CH2),
2.9 (m, 2H, –CH2), 4.4 (t, 2H, –CH2), 5.4 (dd, 1H, –CH vinyl), 6.0 (dd, 1H, –CH
+
vinyl), 7.3 (dd, 1H, –CH vinyl), 7.9 (m, 3H, –NH3 ), 8.0 (s, 1H, –CH), 8.3 (s, 1H,
–CH), 9.61 (s, 1H, –CH) (Fig. 1). FTIR (KBr): νmax = 3416, 3058, 2984, 1656,
1601, 1569, 1549, 1492, 1446, 1371, 1176, 1147, 1058, 830 cm−1.
Preparation of polymeric ionic liquids (PIL)
The polymerization reaction was carried out by reaction of the ionic liquid monomer of
vinyl imidazolium salt (10 mmol, 3.2 g) in the presence of AIBN initiator (10 mol%)
and the mixture of ethanol/water (40 mL, 3:1 v/v) for 24 h under argon atmosphere.
After completion of the reaction, the reaction mixture was cooled to room temperature
and after removal of the solvent with rotary, the obtained product was washed with dry
Fig. 1 1H-NMR spectrum of IL
1 3

Polymeric imidazolium ionic liquid‑tagged manganese Schif…
tetrahydrofuran and acetone. The desired polymer is obtained by adding dry ethanol
1
and dried in a vacuum oven for 12 h at 60 °C. H-NMR (300 MHz, DMSO, TMS)
δ (ppm)=3.47 (m, 2H, –CH2), 4.58 (m, 2H, –CH2), 5.40 (d, 1H, –CH), 5.81 (d, 1H,
–CH), 7.13 (m, 1H, –CH), 7.66 (s, 1H, –CH), 7.81 (s, 1H, –CH), 9.18 (s, 1H, –CH)
(Fig S1 B in SM). FTIR (KBr): νmax =3416, 3152, 2924, 2867, 1637, 1618, 1568,
1505, 1470, 1163, 624, 502 cm−1.
Preparation of PIL‑functionalized Schif base (PIL‑SB)
Salicylaldehyde (10 mmol, 1.12 mL) dropwise was added to the ethanolic polymer
solution (10 mmol, 3.23 g). Then, the aqueous solution of sodium hydroxide (10 mmol,
0.4 g) was added to the solution and refuxed in argon atmosphere for 8 h. After com-
pletion of the reaction, the reaction was cooled to room temperature and the solvent
was evaporated with rotary. Finally, after washing the residue with ethyl ether and
1
water and drying in vacuum oven for 12 h at 60 °C, the product was obtained. H-
NMR (300 MHz, DMSO, TMS) δ (ppm)=3.47 (m, 2H, –CH2), 4.58 (m, 2H, –CH2),
5.40 (d, 1H, –CH), 5.81 (d, 1H, –CH), 7.13 (m, 1H, –CH), 7.66 (s, 1H, –CH), 7.81 (s,
1H, –CH), 9.18 (s, 1H, –CH) (Fig S1 C in SM). FTIR (KBr): νmax =3424, 3416, 3152,
2914, 2867, 1631, 1618, 1568, 1505, 1470, 1287, 1163, 1100, 762 cm−1.
Preparation of polymeric IL‑functionalized SB Manganese complex (PIL‑SB‑Mn)
PIL-SB-Mn(III) catalyst was prepared according to the method described as follows.
To the ethanolic solution of PIL-SB (10 mmol, 3.3 g), Mn (OAc)2·4H2O (5.0 mmol,
1.2 g) dissolved in ethanol was added and the mixture was refuxed for 4 h at 80 °C.
Then, LiCl (5.0 mmol, 0.2 g) was added and refux was contained for further 2 h. After
completion of the reaction, the reaction mixture was cooled to room temperature and
the synthesized precipitate was separated by centrifugation, washed successively with
ethanol and fnally dried at 60 °C for 12 h in vacuum oven to obtain the greenish solid
product. FTIR (KBr): νmax =3424, 3416, 3152, 2914, 2867, 1631, 1618, 1568, 1505,
1470, 1287, 1163, 1100, 762 cm−1.
Typical procedure for synthesis of 3,4‑dihydropyrimidin‑2(1H)‑ones
A mixture of aromatic aldehyde 1 (1.0 mmol), urea/thiourea 2 (1.5 mmol), diketone
3 (1.0 mmol), and PIL-SB-Mn(III) catalyst (1.0 mol%) was heated at 60 °C in sol-
vent-free condition for the appropriate time mentioned in Table 2. The progress of
the reaction was monitored by thin-layer chromatography (ethyl acetate/n-hexane,
4:1). Upon completion of the reaction, hot ethanol (10 mL) was added to reaction
mixture and the catalyst was separated from the reaction mixture by centrifugation.
The solvent evaporated under reduced pressure and the crude product was purifed
by recrystallization with ethanol to give compounds 4a–z in good to excellent yields
(Table 2).
1 3

M.-S. Mashhoori et al.
Spectral data of products
Ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4a):
white solid, Mp=207–208 °C, 1H-NMR (DMSO-d6, 300 MHz): δ (ppm) 1.10 (3H,
CH3, t), 2.28 (3H, CH3, s), 4.00 (2H, CH2, q), 5.18 (1H, CH, s), 7.22–7.34 (3H, ArH,
m), 7.36–7.37 (2H, ArH, m), 7.82 (1H, NH1, s), 9.26 (1H, NH1, s); IR (KBr, νmax
/
cm−1): 3245.11, 3113.28, 2979.01, 1725.27, 1699.43, 1648.39, 1221.47, 1090.60,
699.40.
Ethyl
6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
1
(4b): Yellow solid, Mp=205–207 °C, H-NMR (DMSO-d6, 300 MHz): δ (ppm)
1.19 (3H, CH3, t), 2.26 (3H, CH3, s), 4.18 (2H, CH2, q), 5.42 (1H, CH, s), 7.24–7.34
(3H, ArH, m), 7.36–7.37 (2H, ArH, m), 8.97 (1H, NH1, s), 9.98 (1H, NH, s); IR
(KBr, νmax/cm−1): 3243.21, 3118.70, 2980.63, 1728.04, 1703.88, 1648.61, 1221.19,
1089.05, 781.41.
Ethyl 4-(4-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-car-
1
boxylate (4c): White solid, Mp=205–206 °C, H-NMR (DMSO-d6, 300 MHz): δ
(ppm) 1.12 (3H, CH3, t), 2.27 (3H, CH3, s), 3.73 (3H, OCH3, s), 4.00 (2H, CH2,
q), 5.12 (1H, CH, s), 6.90 (2H, ArH, d), 7.18 (2H, ArH, d), 7.74 (1H, NH, s), 9.22
(1H, NH, s); IR (KBr, νmax/cm−1): 3242.83, 3112.54, 2956.13, 2835.11, 1705. 32,
1512.32, 1223.09, 1089.50, 791.91.
Ethyl
4-(4-methoxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimi-
1
dine-5-carboxylate (4d): Yellow solid, Mp=170–173 °C, H-NMR (DMSO-d6,
300 MHz): δ (ppm) 1.12 (3H, CH3, t), 2.27 (3H, CH3, s), 3.73 (3H, OCH3, s), 4.00
(2H, CH2, q), 5.22 (1H, CH, s), 6.90 (2H, ArH, d), 7.18 (2H, ArH, d), 9.78 (1H, NH,
s), 10.37 (1H, NH, s); IR (KBr, νmax/cm−1): 3244.72, 3115.53, 2979.48, 17,059.44,
1649.05, 1223.03, 1088.93, 784.29.
Ethyl
6-methyl-2-oxo-4-(o-tolyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate
1
(4e): Yellow solid, Mp=207–208 °C, H-NMR (DMSO-d6, 300 MHz): δ (ppm)
1.10 (3H, CH3, t), 2.30 (6H, 2CH3, d), 4.01 (2H, CH2, q), 5.14 (1H, CH, s), 6.90
(2H, ArH, d), 7.07 (1H, ArH, m), 7.24 (2H, ArH, m), 7.32 (1H, ArH, m), 7.82 (1H,
NH, s), 9.19 (1H, NH, s); IR (KBr, νmax/cm−1): 3236.05, 3117.81, 2982.52, 2926.52,
1704.67, 1651.99, 1225.79, 1090.45, 767.76, 700.39.
Ethyl
4-(4-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (4l): Yellow solid, Mp=209–211 °C, 1H-NMR (DMSO-d6,
300 MHz): δ (ppm) 1.11 (3H, CH3, t), 2.27 (3H, CH3, s), 4.00 (2H, CH2, q), 5.16
(1H, CH, s), 7.26 (2H, ArH, d), 7.42 (2H, ArH, d), 7.81 (1H, NH, s), 9.28 (1H, NH,
s); IR (KBr, νmax/cm−1): 3243.21, 3118.70, 2980.63, 2853.92, 1728. 04, 1703.88,
1648.61, 1221.19, 1089.05, 781.41.
Ethyl 4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-car-
1
boxylate (4m): White solid, Mp=230–232 °C, H-NMR (DMSO-d6, 300 MHz): δ
(ppm) 1.16 (3H, CH3, t), 2.27 (3H, CH3, s), 4.05 (2H, CH2, q), 5.12 (1H, CH, s),
6.90 (2H, ArH, d), 7.18 (2H, ArH, d), 7.74 (1H, NH, s), 9.22 (2H, NH and OH,
s); IR (KBr, νmax/cm−1): 3251.38, 3120.98, 2982.03, 1697. 93, 1456.76, 1225.09,
1094.45, 777.82.
Ethyl
4-(3-bromophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-
5-carboxylate (4n): White solid, Mp=185–187 °C, 1H-NMR (DMSO-d6,
1 3

Polymeric imidazolium ionic liquid‑tagged manganese Schif…
300 MHz): δ (ppm) 1.12 (3H, CH3, t), 2.29 (3H, CH3, s), 4.01 (2H, CH2, q), 5.18
(1H, CH, s), 7.37 (4H, ArH, m), 7.85 (1H, NH, s), 9.22 (1H, NH, s); IR (KBr, νmax
/
cm−1): 3233.30, 3119.57, 2976.76, 2929.40, 1705. 51, 1653.91, 1226.19, 1090.96,
767.69.
Results and discussion
Preparation and characterization of the catalyst
This new polymeric ionic liquid-functionalized manganese Schif base complex
(PIL-SB-Mn(III)) was prepared according to Scheme 1. Firstly, the ionic liquid
(IL) was prepared by the nucleophilic reaction of N-vinyl imidazole and 3-bromo-
propylamine hydrobromide. Then, the synthesized ionic liquid was polymerized by
using azobisisobutyronitrile (AIBN) as the initiator to form polymeric IL (PIL) and
followed by the reaction with salicylaldehyde to form the ionic liquid-functionalized
Schif base (PIL-SB). Finally, in order to prepare the manganese complex, the pre-
pared polymeric ionic liquid Schif base (PIL-SB) was added to the ethanolic solu-
tion of Mn (OAc)2·4H2O and LiCl with vigorous stirring and desired catalyst was
produced (PIL-SB-Mn(III)). The structure of synthesized catalyst was characterized
by various analyses like FTIR, H-NMR, ICP, TGA, FE-SEM and EDS.
The FTIR spectrum of all steps for preparation of catalyst is shown in Fig. 1. In
the frst FTIR spectrum of prepared imidazolium ionic liquid (Fig. 2, black), the
peaks at 1178 and 1147 cm−1 are attributed to the stretching vibrations of C–N
bond of imidazole ring and the sharp peaks at 1551 and 1658 cm−1 are assigned
to C=N and C=C of this fve-membered ring. The stretching vibrations of C–H
bond of ring and alkyl chain appear at 3063 and 2984 cm−1, respectively. The broad
band at around 3416 cm−1 was ascribed to the N–H stretching vibration of amine
Fig. 2 FTIR spectra of IL (pink), PIL (red), PIL-SB (blue), PIL-SB-Mn(III) (purple). (Color fgure
online)
1 3

M.-S. Mashhoori et al.
moiety [53]. After polymerization reaction of ionic liquid, there are not any signif-
cant changes or new peaks in FTIR spectrum (Fig. 2, red) [54]. The third spectrum
belongs to the FTIR spectrum of papered polymeric ionic liquid-functionalized
Schif base (Fig. 2, blue). In this fgure, the appeared absorption peak at 1630 cm−1
is assigned to the formation of imine bond in Schif base molecule and broad peak
at 3415 is attributed to the stretching vibration of O–H group on the aldehyde mol-
ecule [55]. In fnal spectrum related to polymeric ionic liquid-functionalized Schif
base manganese complex (PIL-SB-Mn(III)), Fig. 2, green), the C=N stretching fre-
quency and O–H stretching vibration were shifted to the lower wave number (1614,
3412 cm−1), which confrm successful coordination of nitrogen and oxygen to the
metal center. Also, the stretching vibration of the OH group at 3412 cm−1 is becom-
ing weak after coordinating with manganese ion [56, 57].
Scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy
(EDX) analyses were applied for better perception of the morphology and elemen-
tal analysis of catalyst (PIL-SB-Mn(III)). SEM photograph of catalyst demonstrates
irregular structure for the polymeric catalyst in micrometer size (Fig. 3), and EDX
graph confrms the successful linkage of Schif base manganese (III) complex on the
polymeric imidazolium ionic liquid by the presence of all metallic and nonmetallic
elements involved in the catalyst like carbon, nitrogen, oxygen, bromine, chlorine
and manganese (Fig. 4). Furthermore, the best technique for confrmation of catalyst
preparation particularly complex moiety is inductively coupled plasma atomic emis-
sion spectroscopy (ICP-OES) analysis. This technique gives the amount of manga-
nese in fresh and reused catalysts. These amounts are 1.091 mmol (6.05 wt%) and
1.065 mmol (5.91 wt%) on 1.0 g of fresh and reused catalysts (PIL-SB-Mn(III)),
respectively. This result demonstrates that approximately no leaching of manganese
took place during the reaction and confrms the successful coordination of metal ion
on the Schif base molecule. The molecular weight of the synthesized polymeric
catalyst was measured by GPC analysis, and its amount 12,500 g/mol was reported.
Fig. 3 SEM image of PIL-SB-Mn(III) catalyst
1 3

Polymeric imidazolium ionic liquid‑tagged manganese Schif…
Fig. 4 EDX graph of PIL-SB-Mn(III) catalyst
The thermogravimetric (TGA) is another method for evaluation of the chemical
structure of the catalyst. Thus, the TGA of the PIL-SB and fnal catalyst (PIL-SB-
Mn) has been analyzed. As depicted in Fig. 5, there are three main weight losses
in the TGA plot of PIL-SB. The frst decrease in the weight of catalyst (about 5%)
in the temperature between 40 and 120 °C is attributed to the removal of absorbed
water to the PIL-SB. Then, the second weight loss about 40% that began from
150 °C and continued to about 500 °C is assigned to the decomposition of organic
moieties of catalyst like ionic liquid part, and third weight losses after 500 °C (about
10%) are related to the complete decomposition of molecule (Fig. 5a). The TGA
plot of fnal catalyst (PIL-SB-Mn) is similar to the previous plot with small changes
about 5% that are probably attributed to the decomposition of organometallic com-
plex (Fig. 5b) [54, 58].
In order to optimize the overall process, the reaction of benzaldehyde, ethyl
acetoacetate and urea has been chosen as a model reaction. The infuence of
several critical reaction conditions like the amount of catalyst, solvent and
Fig. 5 Thermogravimetric analysis of a PIL-SB and b PIL-SB-Mn(III) catalyst
1 3

M.-S. Mashhoori et al.
solvent-free condition, temperature and time has been analyzed on the Biginelli
reaction (Table 1). First of all, the reaction was carried out without the catalyst,
while other factors were constant; no product was observed after 3 h (entry 1).
After that, the efect of the amount of catalyst (entries 2–5) was tested on reac-
tion yield and time and 1.0 mol% of catalyst was the optimum amount (entry
4). Then, to investigate the infuences of the solvent, a wide variety of solvents
(entries 6–13) and solvent-free condition were applied in 1.0 mol% of catalyst
for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones. The reaction in
solvent-free conditions proceeds better than solvent (entry 4), although yield of
the reaction in acetonitrile was good (entry 10). Another factor for checking the
yield and time of the reaction was temperature which was important and efective.
Thus, the efect of this factor was analyzed on the model reaction as well (entries
14–17). The reaction in mild temperature (60 °C) was done in the highest amount
of yield and shorter time. Eventually, in order to fnd out the best time to pro-
gress the reaction, the time was optimized too (entries 18–20). The best yield was
Table 1 Optimization of the reaction conditions for Biginelli reaction
Entry
Condition
Catalyst (mol%)
Tempera- Time (min)
ture (°C)
Yield (%)a
TONb
TOFc
1
2
3
4
5
6
7
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
CHCl3
CH2Cl2
Toluene
THF
CH3CN
EtOH
MeOH
H2O
Solvent-free
Solvent-free
Solvent-free
Solvent-free
solvent-free
solvent-free
solvent-free
–
60
60
60
60
60
60
60
60
60
60
60
60
60
rt
40
80
100
60
60
60
180
60
30
15
15
15
15
15
15
15
15
15
15
15
15
15
15
5
–
–
–
30
0.1
0.5
1.0
3.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
30
61
95
94
35
40
44
60
85
80
73
76
55
72
95
94
68
84
92
30
61
95
94
35
40
44
60
85
80
73
76
55
72
95
94
68
84
92
122
380
376
140
160
176
240
340
320
292
304
220
288
380
376
816
504
184
8
9
10
11
12
13
14
15
16
17
18
19
20
10
30
Benzaldehyde (1.0 mmol), ethyl acetoacetate (1.0 mmol), urea (1.5 mmol) and PIL-SB-Mn(III)
aIsolated yield
bTurnover numbers (TONs) defned as mmol of products reacted per mmol of catalyst
cTurnover frequencies (TOFs) defned as mmol of products reacted per mmol of catalyst per hour
1 3

Polymeric imidazolium ionic liquid‑tagged manganese Schif…
Table 2 Synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones in the presence of PIL-SB-Mn(III) cata-
lyst
Entry
R
X
1,3-Diketone
Product Time (min) Yield (%)a Melting point
Found
Reported [ref]
1
2
3
4
5
6
7
8
H
H
O
S
O
S
O
O
S
O
S
O
O
O
O
O
O
S
O
S
O
S
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Dimedone
Dimedone
Dimedone
Dimedone
Dimedone
Dimedone
Dimedone
Dimedone
Dimedone
4a
4b
4c
4d
4e
4f
4g
4h
4i
15
15
20
30
45
30
30
15
15
30
30
15
30
45
30
30
20
20
20
20
30
30
45
45
45
95
94
86
85
90
84
80
94
94
85
90
92
88
86
88
85
92
92
93
90
87
88
82
80
80
207–208 209–210 [59]
205–207 206–208 [60]
205–206 203–204 [59]
170–173 173–174 [59]
207–208 207–208 [59]
226–227 225–226 [59]
210–212 210–212 [60]
206–208 207–208 [60]
202–204 204–205 [60]
206–207 227–229 [60]
197–198 195–197 [60]
209–211 210–212 [60]
230–232 232–233 [60]
185–187 185–186 [61]
290–292 290–292 [61]
282–284 283–285 [59]
300–302 302–304 [59]
295–297 295–297 [59]
4-OCH3
4-OCH3
2-CH3
3-NO2
3-NO2
4-NO2
4-NO2
2-Cl
3-Cl
4-Cl
4-OH
3-Br
H
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
H
4-NO2
4-NO2
4-Cl
4-Cl
3-Cl
> 300
> 300 [59]
4t
295–297 295–296 [62]
276–278 278–280 [62]
270–272 271–272 [62]
249–249 248–249 [59]
238–241 240–241 [59]
266–268 267–268 [63]
O
S
O
S
4u
4v
4w
4x
4y
3-Cl
3-OCH3
3-OCH3
H
Dimedone
O
1,3-Cyclohexan-
edione
26
H
S
1,3-Cyclohexadione 4z
45
75
258–260 258–259 [63]
Reaction conditions: aromatic aldehydes (1.0 mmol), 1,3-diketones (1.0 mmol), urea/thiourea (1.5 mmol)
and PIL-SB-Mn(III) (1.0 mol%) in solvent-free condition at 60 °C
aIsolated yield
obtained after about 15 min and more, and less than of this time, the yield of the
reaction was decreased. Thus, the best condition for the synthesis of 3,4-dihydro-
pyrimidin-2(1H)-ones/thiones was 1.0 mol% of catalyst in solvent-free condition
at 60 °C (entry 4).
After optimization reaction conditions, the scope of the Biginelli reaction was
investigated by the reaction of diferent aromatic aldehydes, three 1,3-diketones
(ethyl acetoacetate, dimedone and 1,3-cyclohexanedione) and urea or thiourea in
the presence of 0.01 g of catalyst in solvent-free condition at 60 °C (Table 2). All
aromatic aldehydes with electron-donating and electron-withdrawing groups reacted
1 3

M.-S. Mashhoori et al.
well in Biginelli reaction and gave good to excellent isolated yields. In the case of
1,3-diketones, ethyl acetoacetate (entries 1–14) has the better yield and reacts in
shorter reaction time compare to dimedone (entries 15–24) and 1,3-cyclohexanedi-
one (entries 25, 26). The reaction also has the better condition, when we used urea
compare to thiourea for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones.
Investigation of the reaction mechanism is a signifcant way to understand the
efect of catalyst on the Biginelli reaction. For this purpose, a plausible mechanism
for condensation of aromatic aldehyde, urea and 1,3-diketone in the presence of
PIL-SB-Mn(III) as a Lewis acid catalyst for the synthesis of 3,4-dihydropyrimidin-
2(1H)-ones/thiones is proposed in Scheme 3. As shown in this scheme, in the frst
step, the Lewis acid catalyst can active the aldehyde to attack the urea and produce
intermediate A and after loss of one molecule water, the intermediate B is formed.
In this step, one molecule of 1,3-dicarbonyl is attacked to intermediate B in which
the carbonyl parts are activated with catalyst and intermediate C is created and fol-
lowed by loss of one molecule of water, the product is obtained (D).
Regarding the principle of green chemistry, reusability and recyclability of
the catalyst are highly preferable. Therefore, the reusability of prepared catalyst
(PIL-SB-Mn(III)) for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones
was also tested (Fig. 6). So, upon completion the reaction, hot ethanol was added
to the reaction mixture and the catalyst was separated by centrifugation, dried in
vacuum for 12 h and reused in next catalytic cycles under the optimum condi-
tions. The recycled catalyst was successfully reused for fve times, and the reac-
tion yields were only decreased less than 5% in these fve times using of catalyst.
Also, the FTIR spectrum of the fresh and recovered catalyst (PIL-SB-Mn(III))
was compared and there was no change in the structure of catalyst and approxi-
mately the spectrums were similar (Fig. 7). These results confrm the structure of
catalyst is stable after several times using.
To evaluate catalyst stabilization and metal leaching, the hot fltration test was
performed in the model reaction under the optimized conditions. So, the mixture
Scheme 3 Proposed mechanism for synthesis of 3,4-dihydropyrimidin-2(1H)-ones
1 3

Polymeric imidazolium ionic liquid‑tagged manganese Schif…
Fig. 6 Recycling test of PIL-SB-Mn(III) catalyst for synthesis of 3,4-dihydropyrimidin-2(1H)-ones
of benzaldehyde (1.0 mmol), ethyl acetoacetate (1.0 mmol), urea (1.5 mmol) and
PIL-SB-Mn(III) (1.0 mol%) was stirred at 60 °C under the solvent-free condition
for 8 min. After proceeding the reaction about 50%, the catalyst was separated
from the reaction mixture by centrifugation and then the reaction was continued
for further reaction time (7 min). No increase in conversion was observed after
catalyst separation. This result evidently shows that no leaching of Mn ion took
place during the reaction and confrms the successful coordination of manganese
ion on the Schif base moiety and in agreement with ICP analysis.
It is necessary to compare the merit of our synthesized catalyst (PIL-SB-Mn(III))
with other catalytic systems published in previous works for better understanding of
our methodology. Thus, the results of our catalyst for the synthesis of 3,4-dihydropy-
rimidin-2(1H)-ones/thiones were fnally compared with some other heterogeneous
catalysts (Table 3). As seen in this table, our prepared heterogeneous organometallic
Fig. 7 FTIR spectra of PIL-SB-Mn(III) catalyst fresh (blue) and reuse (yellow). (Color fgure online)
1 3

M.-S. Mashhoori et al.
Table 3 Comparison of catalytic activity of PIL-SB-Mn(III) catalyst with other heterogeneous catalysts
in Biginelli reaction
Entry Catalyst
Conditions
Time (min) Yield (%)a References
1
2
3
4
5
6
7
SSA, [bmim]Brb
Uranyl acetate, succinimide
[bmim]FeCl4
Nano-AL2O3-SO3H
Fe3O4@MCM-41-OB(OH)2 Ultrasonic, 50 °C
Solvent-free, 100 °C 60
68
95
90
87
95
96
95
[64]
[65]
[66]
[67]
Solvent-free, 90 °C
Solvent-free, 90 °C
240
120
Solvent-free, 120 °C 5.0
30
[68]
GaCl3
PIL-SB-Mn(III)
Solvent-free, 80 °C
360
[69]
Solvent-free, 60 °C
15
This workc
aIsolated yield
bIonic liquid silica sulfuric acid
cBenzaldehyde (1.0 mmol), ethyl acetoacetate (1.0 mmol), urea (1.5 mmol) and PIL-SB-Mn(III)
(1.0 mol%)
catalyst (PIL-SB-Mn(III)) is more efcient than other catalysts regarding yield and
time.
Conclusion
For the frst time, a novel polymeric organometallic catalyst (PIL-SB-Mn(III) has
been prepared and after full characterization, its applications were investigated for
the synthesis of diferent derivatives of 3,4-dihydropyrimidin-2(1H)-ones/thiones
via Biginelli reaction. The main advantages of this method are the use of polymeric
ionic liquid Schif base manganese complex for synthesis of 3,4-dihydropyrimidin-
2(1H)-ones/thiones with good to excellent yields and short reaction time in solvent-
free condition and mild temperature (60 °C). Moreover, the catalyst could separate
from the reaction mixture by centrifuging and be reused more than fve times with-
out any signifcant decrease in catalytic activity.
Acknowledgements The authors gratefully acknowledge the partial support of this study by University of
Birjand, Birjand, Iran.
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