Polymer Beads Decorated with Dendritic Systems as Supports for A3 Coupling Catalysts

Article abstract of DOI:10.1007/s10562-020-03301-0

Abstract: The gel type microscopic polymer beads bearing epoxy functionalities were modified using the two-stage procedures in order to decorate their surface with the moieties of the zeroth order PAMAM type dendrimer and different heterocyclic aldehydes (2-pyridinecarboxaldehyde, 2-pyrrolidinecarboxaldehyde, furfural or 2-thiophenecarboxaldehyde). The polymeric supports provided in this manner were then used for the immobilization of copper(II) ions. The resulting materials were characterized using different instrumental techniques (optical microscopy, SEM, FTIR microscopy, DR UV–Vis, ICP-OES, and thermal analysis). They were also used?as catalysts in the model A³ coupling reaction of benzaldehyde, morpholine and phenylacetylene. The best catalytic activity was found for the polymeric catalyst bearing 2-pyridinecarboxaldehyde moieties. It turned out to be effective in the A³ coupling reactions included different benzaldehyde, alkyne, and secondary amine derivatives, as well. It could also be recycled several times without a significant decrease in its activity in the model A³ coupling reaction. Graphic Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s10562-020-03301-0

Catalysis Letters
https://doi.org/10.1007/s10562-020-03301-0
Polymer Beads Decorated with Dendritic Systems as Supports for A3
Coupling Catalysts
Agnieszka Bukowska1 · Karol Bester1 · Maciej Pytel2 · Wiktor Bukowski1
Received: 6 April 2020 / Accepted: 26 June 2020
© The Author(s) 2020
Abstract
The gel type microscopic polymer beads bearing epoxy functionalities were modifed using the two-stage procedures in order
to decorate their surface with the moieties of the zeroth order PAMAM type dendrimer and diferent heterocyclic aldehydes
(2-pyridinecarboxaldehyde, 2-pyrrolidinecarboxaldehyde, furfural or 2-thiophenecarboxaldehyde). The polymeric supports
provided in this manner were then used for the immobilization of copper(II) ions. The resulting materials were characterized
using diferent instrumental techniques (optical microscopy, SEM, FTIR microscopy, DR UV–Vis, ICP-OES, and thermal
analysis). They were also used as catalysts in the model A3 coupling reaction of benzaldehyde, morpholine and phenylacety-
lene. The best catalytic activity was found for the polymeric catalyst bearing 2-pyridinecarboxaldehyde moieties. It turned
out to be efective in the A3 coupling reactions included diferent benzaldehyde, alkyne, and secondary amine derivatives, as
well. It could also be recycled several times without a signifcant decrease in its activity in the model A3 coupling reaction.
Graphic Abstract
Keywords Polymer gels · Polymer modifcation · Polymer supported copper catalysts · A3 coupling
1 Introduction
Functional polymeric materials have found numerous practi-
cal applications. For instance, they are applied as polymeric
sorbents for chromatography [1, 2], ion-exchangers in water
treatment [3], scavenging resins for the fast purifcation of
organic products [4], and supports for the immobilization of
specifc reagents and catalysts [5]. The polymers decorated
with functional groups are also used in diferent biological
applications, e.g. in bioimaging and cancer therapy [6]), and
in materials science [7, 8].
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10562-020-03301-0) contains
supplementary material, which is available to authorized users.
* Agnieszka Bukowska
abuk@prz.edu.pl
1
Faculty of Chemistry, Rzeszów University of Technology,
Powstańców Warszawy 12, 35-959 Rzeszów, Poland
2
Faculty of Mechanical Engineering and Aeronautics,
Various heterogeneous polymerization techniques can
be used for the synthesis of polymers with the suitable
Rzeszów University of Technology, Powstańców Warszawy
12, 35-959 Rzeszów, Poland
Vol.:(0123456789)
1 3

A. Bukowska et al.
functionality. For instance, dispersion, seed, and emulsion
polymerization techniques are useful from the point of view
of preparation of chromatographic sorbents [1] and drug
delivery systems [9]. Suspension polymerization techniques
seem to be interesting particularly in the case of prepara-
tion of polymer beads for sorptive, synthetic and catalytic
applications [4].
species both synthetic (e.g. polyacrylonitrile fbers, poly-
styrene resins) [56–58] and natural organic polymers (e.g.
chitosan) might be used [59, 60].
It is well known that copper ions can promote various
C-N coupling reactions, and their catalytic activity can be
improved by coordinating to diferent multidentate ligands
[34, 47, 61, 62]. Thus, it was expected that the immobiliza-
tion of copper(II) ions on the polymeric supports decorated
with the ligating systems composed of a polyamidoam-
ine (PAMAM) type dendrimer and heterocyclic aldehyde
moieties might provide the novel efective heterogeneous
catalysts for A3 coupling reactions. Herein, we report on the
synthesis of such catalytic systems based on a polymer gel
with epoxy functionalities and their catalytic activity in the
model A3 coupling reactions of aromatic aldehydes, second-
ary amines, and alkynes.
Multicomponent reactions (MCRs), i.e. the reactions
included three or more reactants, are attractive as simple
methods of preparation of organic compounds with the great
molecular diversity. They can be useful as efective synthetic
protocols for obtaining the new libraries of compounds with
the potential biological activity [10–16], natural products
[10, 14–17], agrochemicals [10, 18], substances for the
electronics [19, 20], and also unique polymeric materials
[21–23]. MCRs are characterized by higher atom economy
and require less eforts comparing with the laborious step‐
by‐step procedures of organic synthesis. Hence, the simplic-
ity of MCRs can be especially attractive for the pharmaceuti-
cal industry.
2 Experimental
Although, many multicomponent transformations are
known more than hundred years (e.g. Mannich, Strecker,
Ugi, Passerini and Petasis borono-Mannich reactions),
the modern variants of the classic MCRs and also the new
MCRs are still developed [10, 12, 24–29]. A3 coupling reac-
tions, i.e. the reactions included alkynes, amines, and alde-
hydes, frst discovered in late 1990s, are one of such exam-
ples [30–35]. Propargylamines yielded in the A3 couplings
are important intermediates for the synthesis of numerous
biologically active heterocyclic compounds, e.g. γ-lactams
[36], pyrroles [37], and 2-aminoimidazoles/2-iminoimida-
zoles [38]. For instance, it has been found that the com-
pounds based on propargylamines showed the activity in the
treatment of Parkinson’s and Alzheimer’s diseases [39–41].
To perform the A3 coupling efectively, the selective and
active catalysts are required. Numerous catalytic systems
have been explored in the A3 coupling till now [30–32,
42–60]. Among them copper, silver and gold catalysts seem
to play the most vital role in promoting these transforma-
tions [30, 32, 44–46]. Though the homogeneous version
of A3 couplings shows the high efciency, the difculties
in catalyst reusability and product purifcation cause that,
currently, the various heterogeneous catalysts, including
immobilized metal complexes [30, 34, 47, 48], coordina-
tion compounds [49, 50] and nanocatalysts [30, 32, 51–55]
are examined intensively. The heterogeneous catalysts allow
to limit polluting the fnal products with toxic metal species
when the proper supports are selected. Hence, various multi-
dentate ligands are designed and immobilized onto solid
supports to bond strongly catalytic species on both inorganic
(e.g. mesoporous silica, zeolites, and magnetic particles),
organic (polymers), and hybrid (inorganic–organic) materi-
als. To perform the heterogenization of catalytically active
2.1 General Remarks
All chemicals used in this work were purchased from
Aldrich, Merck or Fluka, and used as received, unless oth-
erwise stated. The epoxy functionalized, low-crosslinked
microscopic polymer beads (GMA resin, 1.40 mmol epoxy
groups per g, 75–150 μm fraction), applied as a matrix for
the preparation of polymer supported copper catalysts,
was synthesized according to the procedure described pre-
viously [63] using the mixture of glycidyl methacrylate
(GMA, 20 mol%), styrene (S, 77 mol%) and diethylene gly-
col dimethacrylate (DEGDMA, 3 mol%). The zeroth order
PAMAM dendrimer based on tris(2-aminoethyl)amine,
methyl acrylate and ethylenediamine (EDA) was prepared
according to the procedure described previously [64].
The loading of copper ions on the polymer supports was
assessed using a Horiba Jobin Yvon Optima 2 ICP-OES
spectrometer (λ=223.008 nm). Samples for the ICP analy-
sis were prepared by mineralizing the beads of the catalysts
in concentrated nitric acid (≥69%, for trace analysis) under
microwave conditions using a Plazmatronika microwave
digestion system. FTIR spectra were recorded in trans-
mission mode using a single bead method [65]. Polymer
beads taken for the FTIR analyses were fattened using a
micro-compression diamond cell. A Thermo Scientific
Nicolet iN10MX microscope equipped with a DLaTGS
detector was used to obtain appropriate spectra in the range
4000–400 cm−1. 64 or 128 scans were used to obtain the
spectral resolution of 0.4 cm–1. DR UV–Vis spectra were
recorded using a Jasco V-670 spectrophotometer equipped
with a Jasco ISN-723 UV–Vis NIR 60 mm integrating
sphere and BaSO4 as a standard. SEM measurements were
performed using a VEGA3 TESCAN scanning electron
1 3

Polymer Beads Decorated with Dendritic Systems as Supports for A3 Coupling Catalysts
microscope equipped with an energy-dispersive (EDS)
detector. A Mettler Toledo (Toledo 822e) instrument was
applied to conduct TGA analyses. Chromatographic analyses
were performed using GC-FID or GC–MS methods. Two
gas chromatographs (Agilent 7890 models) equipped with
autosamplers and capillary columns HP-5 or HP-5+ MS,
respectively, were applied. 1H-NMR and 13C-NMR spectra
were recorded in chloroform-d using a 500 MHz Bruker
Avance spectrometer.
2.3 Catalytic Tests
Aldehyde (1 mmol), amine (1.1 mmol), phenylacetylene
(1.2 mmol), polymer supported catalysts 3 (1 mol.%) and
a solvent (1 mL) were charged to 5 mL vials equipped in
Tefon‐coated cross‐shaped magnetic stir bars. After sealing
the vials, they were placed on a StarFish® Multi‐Experi-
ment Work Station equipped with a stirring hotplate. The
reaction mixtures were gently stirred at 90 °C for the time
indicated. The progress of reactions was followed by gas
chromatography (GC).
2.2 Preparation of Polymer Supported Copper
Catalysts
The fnal reaction mixtures was diluted with ethyl ace-
tate (5 mL) and the catalyst was recovered by fltration. The
resulting organic solutions were concentrated under reduced
pressure. The crude products of A3 coupling reaction were
purifed by column chromatography on silica gel using the
mixtures of hexane and ethyl acetate as eluents. The struc-
ture of fnal products was confrmed by 1H-NMR, 13C-NMR,
FT‐IR and MS spectra (see ESI).
2.2.1 Preparation of Polymeric Supports with Dendritic
Systems
To obtain the polymeric beads with dendritic functionali-
ties (resins 1), GMA resin (2 g) was frst reacted with the
zeroth order PAMAM dendrimer (1.2 eq) in the medium of
DMF-MeOH (3:1 v/v). The reaction was performed accord-
ing to the procedure described previously [66]. The GMA-
PAMAM resin (1, 0.5 g) provided in this manner was next
charged to a PP syringe type reactor equipped with a cotton
flter, a Luer valve and a rubber septum with a needle and
swelled in 2 mL of CH2Cl2. A solution of 1.2 eq. aldehyde
(2-pyridinecarboxaldehyde, PA; pyrrole-2-carboxaldehyde,
PyA; 2-thiophenecarboxaldehyde, TA; or furfural, FA)
in 1 mL MeOH was then added to the swollen polymeric
beads. The reactor was sealed with a septum and placed
on a vibrating shaker. The reaction mixtures were shaken
at ambient temperature for 48 h. After that, the modifed
polymer beads were fltered of and rinsed several times with
CH2Cl2–MeOH mixture (1:1 v/v) to remove the residuals
of unreacted aldehydes. The fnal products (2) bearing the
amine-amide-imine dendritic systems immobilized on poly-
meric beads were dried at 40 °C under reduced pressure.
The recycling experiments were performed in the similar
manner, at 100 °C in 1,4‐dioxane. The beads of recovered
catalyst 3a were washed with THF and dried under reduced
pressure before their reuse.
3 Results and Discussion
3.1 Catalyst Preparation and Characterization
To obtain the new heterogeneous supports with den-
dritic functionalities, the epoxy functionalized polymer
resin (GMA resin) in the form of microscopic beads was
applied as a starting matrix. The resin was frst reacted with
PAMAM, similarly as in Ref. [66], to obtain resin 1 and
the latter was then applied to the synthesis of a series of
polymeric supports 2a–d with amine-amide-imine dendritic
functionalities (Scheme 1). Heterocyclic aldehydes such as
2-pyridinecarboxaldehyde, pyrrole-2-carboxaldehyde, fur-
fural or 2-thiophenecarboxaldehyde were used, respectively,
at the second stage of the modifcation. The condensation
of NH2 groups of immobilized PAMAM moieties with het-
erocyclic aldehydes was performed at room temperature in
the medium of CH2Cl2–MeOH mixture (1:1 v/v). Methyl-
ene chloride delivered advantageous conditions to swell the
hydrophobic polymeric matrix and activate the functional
groups within spherical beads, while methanol facilitated
performing the reaction of condensation under mild condi-
tions. Finally, the beads of resins 2 swollen in CH2Cl2 were
treated with a solution of copper(II) acetate in MeOH at
room temperature to obtain a series of polymer supported
copper(II) complexes 3a–d.
2.2.2 Preparation of Polymer Supported Copper Catalysts
To provide polymer supported copper catalysts 3, resins
2 (0.4 g) were charged to 10 mL glass vials and swelled
preliminarily in 3 mL methylene chloride. After adding
copper(II) acetate solutions in 3 mL methanol (1.0 eq) to
the swollen polymeric beads, the vials were sealed and
placed on a vibrating shaker. The reaction mixtures were
then shaken at ambient temperature for 24 h. to perform the
immobilization of Cu(II) ions. The fnal polymeric materials
were fltered of, washed several times with the mixture of
solvents to remove weakly bonded Cu(II) ions, and, fnally,
dried at 40 °C under reduced pressure.
Each stage of polymer bead modifcation was followed by
visual changes in color of the resulting beads. The starting
1 3

A. Bukowska et al.
Scheme 1 Synthesis of copper
catalysts 3
beads were white. The reaction with PAMAM resulted in
obtaining yellowish beads. As a result of the reaction of
resin 1 with aldehydes, the color of beads changed into yel-
low. Finally, when resins 2 were contacted with the solution
of Cu(CH3COO)2, the beads in green color were provided.
To gain the proof of a course of chemical modifcations,
the FTIR spectra of polymeric beads were recorded after
each stage of transformation. Comparing the spectra of
GMA resin and 1 (Fig. 1), a disappearance of absorption
bands related to epoxy ring stretches (at 910 and 850 cm−1),
and a strong increase in absorption intensity in the range
of 3650–2450 cm−1 with maximum at 3300 cm−1 related
to the stretching vibrations of NH2 (amine), N–H (amine
and amide) and O–H (alcohol) groups were found. The last
fndings pointed out on strong mutual hydrogen bond inter-
actions of NH2, NH and OH groups [67]. Furthermore, a
series of strong bands in the range of 1660–1400 cm−1 were
also observed for 1. They might be related to the vibrations
of amide groups. All fndings proved the successful transfor-
mation of epoxy groups under the infuence of NH2 groups
of PAMAM.
When the FTIR spectra of 2 were compared to the
spectrum of 1, further changes could be observed. In
detail, a well-defned band with the maximum absorption
at 3290 cm−1 in the range characteristic of N–H and OH
stretching vibrations, on the one side, and a series of well
separated bands with diversifed intensity in the absorp-
tion range related to C=N stretching vibration of imines
and amide vibrations (1680–1500 cm−1), on the other side,
were found for 2. The very strong band observed at about
1660 cm−1 is probably a consequence of overlapping the
bands related to the stretching vibrations of C=O (amide)
and C=N (imine) groups. The fndings seemed to prove suc-
cessful performing the condensation of the NH2 groups of
PAMAM and the C=O groups of aldehydes. Finally, the
sorption of copper(II) ions on 2 resulted in further noticeable
changes in the range of 1660–1500 cm−1. For instance, the
blue shifts of the absorption bands from 1658 to 1662 cm−1
and from 1547 to 1562 cm−1 were found comparing the spec-
tra of 2 and 3. The fndings seemed to prove occurring the
complexation interactions between Cu(II) ions and the donor
centers of dendritic ligands immobilized on the polymeric
1 3

Polymer Beads Decorated with Dendritic Systems as Supports for A3 Coupling Catalysts
Fig. 1 The FTIR spectra of GMA resin and the products of its multi-stage modifcation
support. The strong absorption band found at 1565 cm−1
in the spectrum of 3a might be related to the vibrations of
acetate ions [67]. The ions came from Cu(CH3COO)2 used
as a catalyst precursor.
To gain the deeper insight regarding the course of multi-
stage chemical transformation of polymeric beads, the DR
UV–Vis spectra of the resulting beads were also recorded
and compared (Fig. 2). It was found that the beads of GMA
1 3

A. Bukowska et al.
Table 1 Copper contents in
complexes 3
Abbr
% Cu*
mmol/g Cu
3a
3b
3c
3d
5.49
6.31
5.19
5.78
0.86
0.99
0.82
0.91
*Determined using ICP-OES
polymeric bead modifcation, amounted to 0.82–0.99 mmol
Cu (5.19–6.32 wt% Cu). The highest loading was found in
the case of 3b and the lowest for 3c (Table 1).
Comparing the SEM images recorded for GMA resin and
3a (Fig. 3), it was concluded that the multi stage modifca-
tion of GMA resin did not change the morphology of poly-
mer beads. The similar, nonporous, gel-type morphology of
the beads was observed in both cases.
The thermogravimetric analysis performed for 3a
revealed only about 6% weight loss after heating the beads
from 25 to 200 °C (Fig. 4). It could be related to the des-
orption of physically absorbed solvents. The weight loss of
the beads related to thermal degradation intensifed only at
temperature above 200 °C (Fig. 4) and achieved maximal
rate at 405 °C. The fndings have meant that the synthesized
polymer supported complexes are thermal resistant enough
to be applied to the studies of their catalytic activity under
temperature conditions used commonly for A3 coupling
reactions (i.e. at 90–110 °C).
Fig. 2 The DR UV–Vis spectra of polymeric beads
resin and 1 absorbed only in the UV range. The band with
λmax at 266 found for the GMA resin could be related to the
π–π* transitions in styrene aromatic rings and methacrylic
ester moieties and that with λmax at 288 found in the spec-
trum of 1 seemed to prove the presence of immobilized
PAMAM moieties [68]. The immobilization of heterocyclic
aldehyde moieties on 1 provided the imine systems with
C=N bonds conjugated with heterocycle rings. Thus, the
new absorption bands observed for 2 in the visible range of
UV–Vis spectrum (e.g. with λmax at 411 nm for 2a) could be
related to the π–π* transitions in conjugated systems. Finally,
the new absorption bands found in the spectra of 3, e.g. with
λmax at 658 nm for 3a (3b—650; 3c—636; 3d —750 nm),
could be attributed to the d–d transitions of Cu(II) ions in the
pseudo-octahedral environment [67]. Since copper(II) ace-
tate in the solid state absorbs at 880 nm [69], the observed
blue shifts of π–π* transitions bands seemed to prove engag-
ing the imine systems in coordinating Cu(II) ions.
3.2 Catalytic Tests
The catalytic activity of 3 was examined in the model A3
coupling reaction of benzaldehyde (BA), morpholine (MPh)
and phenylacetylene (PhA) (Table 2). The reaction condi-
tions similar to the ones described in Ref. [69] were applied.
The catalysts were used in amount of 1%-mol Cu in relation
to BA and the reactants in the molar proportion of 1:1.1:1.2
(BA:MPh:PhA). The relatively high excess of PhA was
applied to compensate its loss in the side homocoupling
reaction leading to 1,4‐diphenylbutadiyne (DPBD). It is
highly probable that this reaction might accompany the A3
coupling in the presence of copper catalysts [70].
To evaluate quantitatively the particular stages of the
modifcation, the additional elemental analyses were per-
formed for the resulting beads. Based on the values of nitro-
gen percentages, the loadings of PAMAM moieties and NH2
groups being able to react with heterocyclic aldehydes at
the second stage were assessed. The loading of PAMAM
amounted to about 1.3 mmol/g (5.7 wt.% N was found for
1). Further increases in the values of nitrogen percentages
found for 2a and 2b compared to 1, on the one side, and
decreases in the values for 2c and 2d, on the other side,
were the additional proof of occurring the condensation
between the NH2 groups of PAMAM and the C=O groups
of heterocyclic aldehydes. The elemental analysis per-
formed for 3 showed that the loadings of copper ions on
polymer beads, being a consequence of the third stage of
Four organic solvents differing in polarity: diglyme,
1,4-dioxane, ethylene glycol, and toluene, were frst exam-
ined as a reaction medium in the presence of 3a. The time
dependences of BA conversion obtained for this series of
experiments allowed to conclude that ethylene glycol (Fig. 5,
black line) which is a polar, protic solvent with a high dielec-
tric constant (ε = 31.69) turned out to be the least useful
medium for conducting the A3 coupling. Only about 42%
BA was converted in this solvent to propargylamine within
9 h. However, using ethylene glycol as a solvent, a very few
amount of DPBD (~0.5 wt%) has been formed after 24 h.,
1 3

Polymer Beads Decorated with Dendritic Systems as Supports for A3 Coupling Catalysts
Fig. 3 The SEM images of polymer beads: GMA-resin (a), fresh catalyst 3a (b) and recovered catalyst 3a (c)
as well (Table 2, Entry 2). The highest conversion of BA
to propargylamine (~ 87%) was noted for the experiment
performed in 1,4-dioxane (Fig. 5, blue line), i.e. in a non-
polar, aprotic solvent with a low dielectric constant (ε=2,21
[71]). Using this solvent, the yield of DPBD found in the
crude propargylamine after 24 h. was still on the relatively
low level (Table 2, Entry 3). The similar profles of BA
conversion were found for the catalytic experiments con-
ducted in diglyme (an aprotic solvent with a medium value
of dielectric constant, ε = 5.8) or toluene (a nonpolar sol-
vent, ε=2.38) (Fig. 5, orange and green lines, respectively),
although, the former compared to the latter facilitated the
formation of DPBD (Table 2, Entries 4 and 5).
To compare the catalytic activity of the developed
polymer supported complexes, 1,4-dioxane was selected
Fig. 4 Thermogravimetric curve recorded for 3a
Table 2 The efect of solvents on the A3 coupling reaction of benzaldehyde, morpholine and phenylacetylene
O
O
N
catalyst
+
+
CH
O
N
H
Entry
Catalyst
Solvent
Time (h)
Yield of A3 product (%)
Yield of
DPBD
(%)a
1
2
3
4
5
6
7
8
–
1,4-Dioxane
Ethylene glycol
1,4-Dioxane
Diglyme
24
2
0
3a
3a
3a
3a
3b
3c
3d
9/24
9/24
9/24
9/24
9/24
9/24
9/24
42/63
87/98
77/94
73/97
73/97
70/96
56/93
0.5
5.8
7.2
5.2
4.6
5.9
4.7
Toluene
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
aDetermined based on GC analysis
Reaction conditions: benzaldehyde (1 mmol), morpholine (1.1 mmol), phenylacetylene (1.2 mmol), catalyst (1%-mol), solvent (0.5 mL), tem-
perature (90 °C)
1 3

A. Bukowska et al.
the similar level. However, the latter yielded somewhat
more DPBD (Table 2, Entry 7). Despite the differences
in catalytic activity, all the examined polymer supported
copper complexes allowed to obtain the relatively high
yields of propargylamine within 24 h. (Table 2).
A control experiment without any catalyst was also per-
formed, however, as the results of GC analysis showed,
there were no A3 coupling or PhA homocoupling products
in the fnal reaction mixture obtained after its heating at
90 °C for 24 h. Although, about 5% conversion of BA was
noted after that time. The last fnding might be the result of
the equilibrium reaction between BA and secondary amine
resulting in the formation of secondary imine ion. The last
are an intermediate in the A3 coupling reaction. However,
the further transformation of imine ions to the appropriate
propargylamine, being a result of the nucleophilic attack of
activated phenylacetylene molecules on the carbon atom in
C=N+ groups according to the commonly accepted A3 cou-
pling mechanism [72], could not occur without a catalyst.
The lack of any catalyst made the homocoupling of phe-
nylacetylene molecules to diacetylene impossible, as well.
The activity of 3a was also examined in the reactions
included substituted benzaldehydes (six examples) and two
other cyclic secondary amines and substituted phenylacety-
lenes. In all cases, the appropriate propargylamines were
obtained with good or very good yields (Table 3). Compar-
ing the obtained results it was concluded that the exchange
of morpholine (Entry 1) to piperidine (Entry 8) or pyrroli-
dine (Entry 9) resulted in shortening the reaction time with
phenylacetylene and benzaldehyde dramatically. The suit-
able A3 coupling reactions were completed within about 3 h.
The fndings were in agreement with increasing the basicity
of amines. Moreover, it was also found that the yields of the
propargylamines obtained from substituted benzaldehydes in
the reactions with morpholine and phenylacetylene (Entries
2–5) were generally lower than the yield obtained after the
same time for the non-substituted derivative (Entry 1). Both
electron donating (CH3O; Entry 2) and electron acceptor
withdrawing (Cl; Entries 4–6) groups present in the aromatic
ring of benzaldehyde infuenced rather disadvantageously
on the reactivity of benzaldehydes. The particularly nega-
tive efect on the reactivity seemed to have the presence of
Cl atom at position 3 of benzaldehyde (Entry 4 and 6). The
occupied positions 2 or 4 infuenced much less negatively.
The reactivity of 2,6-dichlobenzaldehyde was comparable to
that observed for the non-substituted benzaldehyde (Entry
7). A slight improvement in the yield of the resulting prop-
argylamine was observed only for the reaction with 4-bro-
mobenzaldehyde (Entry 3). Finally, it was also found that
the exchange of phenylacetylene to 4-methyl- or 4-meth-
oxyphenylacetylene was related to decreasing the yields
of the resulting propargylamines. The findings pointed
out on a disadvantageous efect of EDGs on the reactivity
Fig. 5 The efect of solvents on BA conversion in the model A3 cou-
pling catalyzed by 3a
Fig. 6 The activity of catalysts 3 in the model A3 coupling reaction
as an optimal reaction medium. It was found that complex
3a bearing the moieties of 2-pyridinecarboxaldehyde cou-
pled with PAMAM turned out to be clearly more active
than 3b, 3c and 3d, i.e. the complexes with pyrrole-
2-carboxaldehyde, furan-2-carboxaldehyde and thio-
phene-2-carboxaldehyde moieties, respectively (Fig. 6;
Table 3). Probably it is a consequence of much stronger
donor ability of N atom in pyridine ring compared to
the heteroatoms in pyrrole, furan and thiophene moieties.
Among the developed catalysts, as was expected, cata-
lyst 3d having S-donor ligands showed the lowest activity
under the applied reaction conditions (Fig. 6), although
in the presence of this catalyst the yield of DPBD was
lower than observed for 3a (Table 2, Entry 3). The values
of BA conversion found for 3b and 3c after 9 h. were on
1 3

Polymer Beads Decorated with Dendritic Systems as Supports for A3 Coupling Catalysts
of phenylacetylenes. This regularity was observed for the
reactions including both morpholine (Entries 11, 13) and
piperidine (Entries 10, 12). However, in the case of the
reaction with morpholine the observed diferences in the
reactivity of acetylenes were clearly less than for piperidine.
Moreover, although the reactivity of 4-Me- and 4-MeO-sub-
stituted phenylacetylenes in the reaction with morpholine
Table 3 The results of A3
Time
(h)
Yield
(%)a
Aldehyde
Amine
Product
Entry
1
coupling reactions for diferent
aldehydes, amines and alkynes
O
O
O
O
O
N
N
N
9/24
87/98
N
H
2
3
O
O
O
9/24
80/90
N
H
O
O
O
9/24
90/99
N
H
Br
O
Br
O
O
O
4
5
6
N
O
24
63
N
H
Cl
Cl
O
N
O
Cl
24
88
N
H
Cl
Cl
Cl
Cl
O
N
O
Cl
Cl
24
64
N
H
Cl
1 3

A. Bukowska et al.
Table 3 (continued)
O
7
O
O
N
Cl
Cl
9/24
83/100
Cl
N
H
Cl
8
9
O
O
O
N
N
3
3
9
98
99
90
N
H
N
H
10
11
N
N
O
O
N
H
O
O
O
O
O
24
24
24
89
88
92
N
H
12
13
N
N
H
O
O
N
N
H
Reaction conditions: aldehyde (1 mmol), amine (1.1 mmol), phenylacetylene (1.2 mmol), catalyst 3a
(1%-mol), 1,4-dioxane (0.5 mL), temperature (90 °C)
aDetermined based on GC analysis
was comparable, the following sequence of reactivity
PhA>4-MeO>4-Me was observed for piperidine.
Catalyst 3a was recycled in the model reaction of ben-
zaldehyde, phenylacetylene and morpholine. There was not
1 3

Polymer Beads Decorated with Dendritic Systems as Supports for A3 Coupling Catalysts
Fig. 7 The results of catalyst reuse; reaction conditions: benza-
ldehyde (1 mmol), morpholine (1.1 mmol) and phenylacetylene
(1.2 mmol), 1%-mol 3a, 1,4-dioxane (0.5 mL), temperature − 100 °C,
Fig. 8 The heterogeneity test; reaction conditions: benzaldehyde
time—5 h
(1 mmol), morpholine (1.1 mmol) and phenylacetylene (1.2 mmol),
1%-mol 3a, 1,4-dioxane (0.5 mL), temperature − 90 °C, time 9 h
observed a dramatic decrease in its activity under applied
reaction conditions (Fig. 7) even during the ffth use. The
fnal conversion of benzaldehyde after 5 h. decreased from
98% for the fresh catalyst to 90% for the ffth reaction run.
SEM analysis of the recovered catalyst showed that the
physical structure of polymer beads left nearly unchange-
able (Fig. 3c). The fnding pointed out on the good enough
mechanical resistance of the polymeric support under the
applied reaction conditions. Only few mechanical damages
on the rather smooth surface of a single polymer bead could
be found.
concluded that the catalysts presented herein seem to show
the relatively high activity.
4 Conclusion
The gel type microscopic polymer beads obtained by sus-
pension polymerization from the mixture of easily acces-
sible monomers (glycidyl methacrylate (20 mol%), styrene
(77 mol%) and divinylbenzene (3 mol%) and decorated by
using the simple procedures of chemical post-modifcation
with the dendritic moieties bearing the relatively easily
accessible 0th order PAMAM dendrimer and heterocyclic
aldehyde (PA, PyA, TA or FA) moieties turned out to be val-
uable supports for the preparation of heterogeneous catalysts
based on low-cost copper(II) acetate. The catalysts obtained
in that manner were applied successfully in the A3 coupling
reactions included various aldehyde, alkyne and secondary
amine derivatives under the relatively mild reaction condi-
tions. The best catalyst (3a), bearing PA moieties, delivered
the proper alkylamines with the yield of 63–100%. It showed
good recyclability (at least 5 times; 90% yield in the 5th run)
in the model reaction of benzaldehyde, phenylacetylene and
morpholine, as well.
The FTIR spectrum recorded for the recovered catalyst
revealed a decrease in absorption in the range characteristic
of acetate ions (Fig. 1). This fnding indicated that acetate
ions present in the fresh catalyst were removed from the
coordination sphere of copper(II) ions under reaction con-
ditions, probably, as a consequence of coordinative interac-
tions with the reagents and solvent molecules.
An additional hot fltration test was also conducted for
catalyst 3a in the reaction of benzaldehyde, morpholine, and
phenylacetylene (Fig. 8). The catalyst was fltered of from
the reaction mixture after 3 h. The reaction was then con-
tinued with the fltrate. The resulting kinetic data indicated
that the reaction followed mainly a heterogeneous pathway.
Some progress of the reaction which could be observed after
the next 6 h. pointed out that the part of the immobilized
copper(II) ions had been leached to the reaction mixture
under the applied reaction conditions. Using ICP-OES
analysis, it was found about 10% leaching of Cu(II) ions
after the frst run. The observed leaching of Cu(II) from the
polymeric catalyst has been probably responsible for gradual
decreasing in activity found for the recovered catalyst.
Comparing the activity of catalyst 3a with the activity of
other polymer supported copper catalysts examined previ-
ously in the A3 coupling reactions [47, 73, 74] it can be
Open Access This article is licensed under a Creative Commons Attri-
bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes
were made. The images or other third party material in this article are
included in the article’s Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not included in
the article’s Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will
1 3

A. Bukowska et al.
38. Jia J-H, Yu Ch, Xu M, Ma J-W, Jin H-W (2015) Synthesis 47:3473
39. Bolea I, Gella A, Unzeta M (2013) J Neural Transm 120:893
40. Zindo FT, Barber QR, Joubert J, Bergh JJ, Petzer JP, Malan SF
(2014) Europ J Med Chem 80:122
need to obtain permission directly from the copyright holder. To view a
copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
41. Baranyi M, Porceddu PF, Gölöncsér F, Kulcsár SZ, Otrokocsi L,
Kittel Á, Pinna A, Frau L, Huleatt PB, Khoo ML, Chai CHLL,
Dunkel P, Mátyus P, Morelli M, Sperlágh B (2016) Mol Neuro-
degener 11:6
References
1. Sýkora D, Řezanka P, Záruba K, Král V (2019) J Sep Sci 42:89
2. Azzouz A, Kailasa SK, Lee SS, Rascón AJ, Ballesteros E, Zhang
M, Kim K-H (2018) Trends Anal Chem 108:347
3. Villasenõr J, Ríos A (2018) Environ Chem Lett 16:11
4. Tulla-Puche J, Albericio F (2008) The power of functional resins
in organic synthesis. Wiley-VCH, Weinheim
42. Patel SB, Vasava DV (2018) ChemistrySelect 3:471
43. Veisi H, Mohammadi L, Hemmati S, Tamoradi T, Mohammadi P
(2019) ACS Omega 4:13991
44. Patel SB, Vasava DV (2020) Nano-Struct Nano-Objects 21:100416
45. Gholinejad M, Bonyasi R, Najera C, Saadati F, Bahrami M, Das-
varz N (2018) ChemPlusChem 83:431
5. Buchmeiser MR (2003) Polymeric materials in organic synthesis
and catalysis. Wiley-VCH, Weinheim
46. Gholinejad M, Saadati F, Shaybanizadeh S, Pullithadathic B
(2016) RSC Adv 6:4983
6. Zhao W, Li A, Zhang A, Zheng Y, Liu J (2018) ChemMedChem
13:2134
47. Islam MMD, Roy AS, Islam SKM (2016) Catal Lett 146:1128
48. Loukopoulos E, Kallitsakis M, Tsoureas N, Abdul-Sada A, Chil-
ton NF, Lykakis IN, Kostakis GE (2017) Inorg Chem 56:4898
49. Li P, Regati S, Huang HC, Arman HD, Chen BL, Zhao JCG
(2015) Chin Chem Lett 26:6
7. Gokmen MT, Du Prez FE (2012) Prog Polym Sci 37:365
8. Mittal V (2011) Advanced polymer nanoparticles, Synthesis and
Surface Modifcations (CRC Press. Taylor&Francis Group, Boca
Raton
50. Liu L, Tai X, Zhou X, Xin Ch, Yan Y (2017) Sci Rep 7:12709
51. Gholinejad M, Afrasi M, Najera C (2019) Appl Organomet Chem
33:e4760
9. Kim D, Shin K, Kwon SG, Hyeon T (2018) Adv Mater
30:1802309
10. Zarganes-Tzitzikas T, Chandgude AL, Dömling A (2015) Chem
Record 15:981
52. Patel SB, Vasava DV (2020) ChemCatChem 12:631
53. Terra JCS, Moores A, Moura FCC (2019) ACS Sustain Chem Eng
7:8696
11. Taylor AP, Robinson RP, Fobian YM, Blakemore DC, Jones LH,
Fadeyi O (2016) Org Biomol Chem 14:6611
54. Ebrahimiasl S, Behmagham F, Abdolmohammadi S, Kojabad RN,
Vessally E (2019) Curr Org Chem 23:2489
12. Filho JFA, Lemos BC, de Souza AS, Pinheiro S, Greco SJ (2017)
Tetrahedron 73:6977
55. Gholinejad M, Zareh F, Najera C (2018) Appl Organometal Chem
32:e4454
13. Abelraheem EMM, Shaabani S, Dömling A (2018) Drug Discov
Today 29:11
56. Li P, Liu Y, Wang L, Xiao J, Tao M (2018) Adv Synth Catal
360:1673
14. Reguera L, Rivera DG (2019) Chem Rev 119:9836
15. Reguera L, Attorresi CI, Ramírez JA, Beilstein RDG (2019) J Org
Chem 15:1236
57. Hu Q, Shi X-L, Chen Y, Wang F, Weng Y, Duan P (2019) J Ind
Eng Chem 69:387
16. Slobbe P, Ruijter E, Orru RVA (2012) MedChemCommun 3:1189
17. Schaper K, Müller TJJ (2018) Top Curr Chem 376:38
18. Lamberth C (2013) Pest Manag Sci 69:1106
19. Puthumana SSE, Damodaran B (2018) ChemistrySelect 3:2951
20. Zani L, Dessì A, Franchi D, Calamante M, Reginato G, Mordini
A (2019) Coord Chem Rev 392:177
58. Shi X-L, Sun B, Chen Y, Hu Q, Li P, Meng Y, Duan P (2019) J
Catal 372:321
59. Shaabani A, Shadi M, Mohammadian R, Javanbakht S, Nazeri
MT, Bahri F (2019) Appl Organomet Chem 33:e5074
60. Kaur P, Kumar B, Kumar V, Kumar R (2018) Tetrahedron Lett
59:1986
21. Jiang X, Feng Ch, Lu G, Huang X (2015) Sci China Chem
58:1695
61. Monnier F, Taillefer M (2009) Angew Chem Int Ed 48:6954
62. Sambiagio C, Marsden SP, Blacker AJ, McGowan PC (2014)
Chem Soc Rev 43:3525
22. Wu H, Gou Y, Wang J, Tao L (2018) Macromol Rapid Commun
39:1800064
63. Bukowska A, Bukowski W, Noworól J (2007) J Appl Polym Sci
106:3800
23. Sebati W, Ray SS (2018) Catalysts 8:492
24. Zhu EJ, Wang Q, Wang MX (2015) Multicomponent reactions in
organic synthesis. Wiley-VCH Verlag GmbH, Weinheim
25. Herrera ERP, Marques-Lopez E (2015) Multicomponent reactions.
Concepts and applications for design and synthesis. Wiley, New
York
64. Tang MX, Redemann CT, Szoka FC Jr (1996) Biocon Chem 7:703
65. Yan B, Kumaravel G, Anjaria H, Wu A, Petter RC, Jewell CHF
Jr, Wareing JR (1995) J Org Chem 60:5736
66. Bukowska A, Bukowski W, Bester K, Flaga S (2015) RSC Adv
5:49036
26. Afshari R, Shaabani A (2018) ACS Comb Sci 20:499
27. Wu P, Nielsen TE (2018) Drug Discov Today Technol 29:27
28. Giustiniano M, Moni L, Sangaletti L, Pelliccia S, Basso A, Novel-
lino E, Tron GC (2018) Synthesis 50:3549
67. Pretsch E, Bühlmann P, Badertscher M (2009) Structure determi-
nation of organic compounds. Tables of spectral data. Springer,
Berlin
68. Pande S, Crooks RM (2011) Langmuir 27:9609
69. Bukowska A, Bukowski W, Bester K, Hus K (2017) Appl Orga-
nomet Chem 31:e3847
29. Yi J, Badir SO, Alam R, Molander GA (2019) Org Lett 21:4853
30. Yoo WJ, Zhao L, Li CJ (2011) Aldrichchimica Acta 44(2):43
31. Peshkov VA, Pereshivko OP, Van der Eycken EV (2012) Chem
Soc Rev 41:3790
70. Marquez C, Cirujano FG, Smolders S, Van Goethem C, Van-
kelecom I, De Vos D, De Baerdemaeker T (2019) Dalton Trans
48:3946
32. Nasrollahzadeh M, Sajjadi M, Ghorbannezhad F, Sajadi SM
(2018) Chem Rec 18:1
71. Reichardt Ch (2003) Solvents and solvent efects in organic chem-
istry. Wiley-VCH, Weinheim
33. Mo J-N, Su J, Zhao J (2019) Molecules 24:1216
34. Jesin I, Nandi GCH (2019) Europ J Org Chem 14:2704
35. Rokade BV, Barker J, Guiry PJ (2019) Chem Soc Rev 48:4766
36. Shu CH, Liu MQ, Wang SS, Li L, Ye LWJ (2013) Org Chem
78:3292
72. Saha TK, Das R (2018) ChemistrySelect 3:147
73. Kodicherla B, Perumgani PC, Mandapati MR (2014) Appl Orga-
nomet Chem 28:756
37. Ye TY, Selvaraju M, Sun CHM (2017) Org Lett 19:3103
1 3

Polymer Beads Decorated with Dendritic Systems as Supports for A3 Coupling Catalysts
74. Yan S, Pan S, Osako T, Uozumi Y (2019) ACS Sust Chem Eng
7:9097
Publisher’s Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional afliations.
1 3