Amine-functionalized hyper-crosslinked polyphenanthrene as a metal-free catalyst for the synthesis of 2-amino-tetrahydro-4H-chromene and pyran derivatives

Article abstract of DOI:10.1016/j.apcata.2017.03.009

The hyper-crosslinked microporous polyphenanthrene spheres were fabricated simply by the polymerization of phenanthrene using bromomethyl methyl ether as a bridging agent in the absence of any templates. The organic spheres were subjected to amine-functionalizing on the periphery of them using unreacted bromomethyl groups. The amine-functionalized microporous polyphenthrene could be employed as a highly effective and stable solid basic catalyst for the syntheses of functionalized 2-amino-tetrahydro-4H-chromene and pyran derivatives. The significant features of these reactions are high product yields, environmental benignity, short reaction time, broad substrate scope, and non-requirement of toxic solvents. Furthermore, the catalyst can be reused up to four times without significant loss of activity.

Full text of DOI:10.1016/j.apcata.2017.03.009

Accepted Manuscript
Title: Amine-functionalized hyper-crosslinked
polyphenanthrene as a metal-free catalyst for the synthesis of
2-amino-tetrahydro-4H-chromene and pyran derivatives
Authors: Reddi Mohan Naidu Kalla, Anuraj Varyambath, Mi
Ri Kim, Il Kim
PII:
S0926-860X(17)30108-4
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.apcata.2017.03.009
APCATA 16168
To appear in:
Applied Catalysis A: General
Received date:
Revised date:
Accepted date:
21-12-2016
1-3-2017
9-3-2017
Please cite this article as: Reddi Mohan Naidu Kalla, Anuraj Varyambath, Mi Ri
Kim, Il Kim, Amine-functionalized hyper-crosslinked polyphenanthrene as a metal-free
catalyst for the synthesis of 2-amino-tetrahydro-4H-chromene and pyran derivatives,
Applied Catalysis A, General http://dx.doi.org/10.1016/j.apcata.2017.03.009
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

Amine-functionalized hyper-crosslinked polyphenanthrene as a metal-free
catalyst for the synthesis of 2-amino-tetrahydro-4H-chromene and pyran
derivatives
Reddi Mohan Naidu Kalla, Anuraj Varyambath, Mi Ri Kim, and Il Kim*
BK21 PLUS Centre for Advanced Chemical Technology, Department of Polymer science and
Engineering, Pusan National University, Busan, Republic of Korea.
*Corresponding author
E-mail: ilkim@pusan.ac.kr
Graphical abstract
Highlights
 ▶Supported organo base-catalyzed syntheses of chromenes and pyrans are introduced.
1

 ▶The reactions are eco-friendly, economically viable and versatile.
 ▶ The catalyst is reusable without losing its catalytic activity.
ABSTRACT: The hyper-crosslinked microporous polyphenanthrene spheres were fabricated
simply by the polymerization of phenanthrene using bromomethyl methyl ether as a bridging agent
in the absence of any templates. The organic spheres were subjected to amine-functionalizing on
the periphery of them using unreacted bromomethyl groups. The amine-functionalized
microporous polyphenthrene could be employed as a highly effective and stable solid basic catalyst
for the syntheses of functionalized 2-amino-tetrahydro-4H-chromene and pyran derivatives. The
significant features of these reactions are high product yields, environmental benignity, short
reaction time, broad substrate scope, and non-requirement of toxic solvents. Furthermore, the
catalyst can be reused up to four times without significant loss of activity.
Keywords: Base catalyst, Carbon sphere, Chromenes, Multi-component reactions, Pyrans,
Supported catalyst.
1. Introduction
The microporous organic polymers (MOPs) with pores smaller than 2 nm have attracted
considerable interest due to their potential applications in the areas of catalysis, gas storage,
molecular separation, conductivity [1]. Various synthetic methodologies and further chemical
modifications of MOPs are widely reported [2–4].Over the past few years, researchers have
developed variety of MOPs that are composed of non-metallic elements such as C, H, O, N, and
B, including polymers of intrinsic micro porosity [5], covalent organic frameworks [6], and
2

conjugated microporous polymers [7]. The monomers used for these materials usually carry
ethynyl [8] or stereo-controlled structures [9], which require tedious synthesis and purification
using expensive catalysts [10].
Hyper-crosslinked microporous organic polymers (HMOPs) are a subclass of porous polymers,
which are mainly synthesized by a hyper-crosslinking of small organic molecules by
Friedel−Crafts alkylation reaction with external cross linker [11,12]. For example, the HMOPs
were prepared by the post-cross linking reaction of styrene or styrene-divinylbenzene polymer in
solution or a highly swollen state Davankov resin [13]. However, this method yielded HMOPs
with humdrum polymeric matrices of non-uniform pores, and needed fussy synthesis processes.
Recently we have fabricated highly uniform HOMPs based on a simple Friedel-Crafts alkylation
of aromatic hydrocarbons including naphthalene, anthracene, phenanthrene, pyrene and coronene,
showing good performance as super capacitor materials [14]. Since the resultant HMOPs are
chemically and thermally stable and bear halogen functional groups on the surface, they can be
easily functionalized without losing their morphology.
Currently, functionalized polymer materials with high surface area are receiving significant
interest in the fields of adsorption, catalysis, sensor technology, and chromatography [7b,15].
Functionalization of the polymer material peripheral surface provides an efficient barrier against
oxidation and acid erosion. Various methods have been developed for functionalization including
post-modification, copolymerization of skeleton molecules with functional groups, and self-
polymerization of functional organic groups. These supports have advantages like high chemical
and hydrothermal stabilities and easy tailoring of active sites [16]. For the functionalization on the
surface of porous polymers Xiao et al. employed sulfonic acid functionalized porous polymer for
esterifications and Friedel–Crafts acylation reactions [17], Copper et al. reported the post-
3

modification of amine functionalized conjugated microporus polymers for gas sorption [18], and
Wang et al. studied organic polymers functionalized with Tröger’s base and 4-(N,N-
dimethylamino)pyridine as the heterogeneous organocatalyst, showing reasonable catalytic
activity in the addition reaction of diethyl zinc to 4-chlorobenzaldehyde and the acylation of
alcohols and phenols [19,20].
Recent reports on ethylenediamine (EDA)–functionalized grapheneoxide (GO) indicate good
catalytic activity in hydrolysis, Knoevenagelcondensation (KC) [21,22], and Henry-Michael
reactions [23]. In view of the above, herein we report for the first time the synthesis of a HMOP
featuring EDA covalently bonded to the bromomethylated HMOPs via condensation reaction. The
unreacted bromomethyl groups can further chemically modified with EDA (Fig. 1). Phenanthrene
(Ph) was chosen as starting material in this study due to its low cost and ready availability. The
resultant polyphenanthrene PPh@EDA samples showed good catalytic activity for the preparation
of biologically potent functionalized 2-amino-tetrahydro-4H-chromene and pyran derivatives.
EDA is a liner with two nitrogen atoms, and its functionalization by various reduction
condensation reactions, together with ionic liquids and various acids, is prominent in catalysis and
other applications [24].
Recently, various important biologically potent heterocyclic compounds have been synthesized
under solvent-free conditions via multicomponent reactions (MCRs) [25]. MCRs are an elegant
and powerful tool for organic synthesis as compared to multistep reactions, due to the one-pot
formation of several new bonds (e.g., C–C, C–N, C–O, and C–S). The advantages of MCRs are
high atom economy, avoidance of time-consuming protection and deprotection processes,
4

simplicity, and shorter reaction time. Therefore, academic and industrial research is mainly
focused on various organic transformations utilizing one-pot MCRs.
Derivatives of 2-amino-tetrahydro-4H-chromene and pyran, representing the main structural unit
of most oxygen-containing heterocyclic compounds, are formed through one-pot Knoevenagel-
Michael cyclocondensation. In addition, many natural products exhibiting anti-tumor/cancer,
antiviral, antibacterial, antifungal, anticoagulant, antileishmanial, antiallergenic, and diuretic
activities contain chromene moieties [26]. For example, 2-amino-tetrahydro-4H-chromene
derivatives A, B, and C are valuable compounds (Fig. 2) [27–30]. Compound A is a tumor
antagonist that exhibits binding activity for the surface pocket of cancer-implicated Bcl-2 proteins
and induces apoptosis in follicular lymphoma-B and leukemia HL-60 cells. Compound B is an
inhibitor of the insulin-regulated amino peptidase (IRAP), enhancing memory and learning
functions, while compound C and its derivatives are antibacterial agents.
Furthermore, these compounds are used in other applications, such as fluorescence markers [31],
laser dyes [32], pigments [33], optical brighteners [34], cosmetics, and pH-sensitive fluorescent
materials for the visualization of biomolecules [35] and biodegradable agrochemicals [36]. Owing
to their important properties, various methods for preparing 2-amino-tetrahydro-4H-chromenes
and pyrans have been developed, e.g., methods utilizing microwaves [37], PPA-SiO2 [38],
meglumine [39], MgO [40], triethylamine [41], urea [42], ionic liquids [43], and Fe3O4
nanoparticles (NPs) supported by multi-walled carbon nanotubes [44]. However, the majority of
these methods suffer from certain drawbacks such as long reaction times, expensive non-reusable
catalysts, toxic solvents, and tedious work-up procedures. Hence, a search for more broad, feasible,
clean, efficient, and high-yielding routes to this class of O-heterocycles remains a valid exercise.
5

The important goals of green chemistry include the avoidance of organic solvents, toxic reagents,
and the reduction of costs associated with organic synthesis. In view of these goals and our
sustained interest in the development of efficient, economical, and novel methodologies [45–47],
we herein report the use of easily accessible PPh@EDA as an environmentally benign and
recyclable solid basic catalyst for high-yielding and solvent-free synthesis of chromenes and
pyrans (Scheme 1).
2. Experimental
2.1. Materials and instrumentation
Aromatic hydrocarbons such as Ph (98%, Sigma-Aldrich), and Co (>95%, TCI), Bromomethyl
methyl ether (BMME, >95%, TCI), various substituted aldehydes, (Sigma-Aldrich Co.)
malononitrile (Fisher Scientific UK Ltd), cyclicketones and acyclic ketones (TCI), anhydrous zinc
bromide (ZnBr2, 98%, Acros), were used as received. All experiments were performed under
solvent-free conditions. Pre-coated silica gel plates (Merck Chemicals) were developed with
iodine, and were used for analytical thin-layer chromatography (TLC). Melting points were
uncorrected and determined using a digital Stuart SMP3 apparatus (Bibby Scientific Limited,
Staffordshire, UK). 1H NMR (400 MHz), and 13C NMR (100 MHz), spectra were recorded using
a Varian INOVA 400 NMR spectrometer at room temperature. Chemical shift values are quoted
relative to Me4Si. Data are presented as follows: chemical shift (ppm), multiplicity (s= singlet, d
= doublet, dd = doublet of doublets, t = triplet, m = multiplet), and coupling constant J(Hz). Solid
13C NMR spectra were obtained on a Bruker Avance 500 NMR spectrometer. Fourier-transform
(FT) IR spectra were recorded at r.t. using a Shimadzu IR Prestige 21 spectrometer. The spectra
were obtained, using KBr disks, in the range 4500–500 cm−1. The XRD analysis was performed
by using an automatic Philips powder diffractometer with nickel-filtered Cu Kα radiation. The
6

diffraction pattern was collected in the 2 range of 0-80οin steps of 0.02ο and counting times of 2 s
step−1. The microstructures of the samples were investigated using an S-3000 scanning electron
microscope (SEM; Hitachi, Japan) and thermo gravimetric analysis measured by TGA N-1000
(Scinco, Seoul, and Republic of Korea).X-ray photoelectron spectroscopy (XPS) analysis was
performed in a Theta Probe AR-XPS system with a monochromatic Al Kα X-ray source (1486.6
eV). The Brunauer-Emmett-Teller (BET) and the Density-Functional-Theory (DFT) methods
(Nova 3200e system, Quantachrome Instrument, USA) were used to investigate the BET specific
surface area and pore size distribution of the samples. Elemental analyses were obtained on GmbH
elemental analyzer.
2.2. Synthesis of bromomethylatedpolyphenanthrene, PPh@CH2Br.
Phenanthrene (1 g, 5.6 mmol)and anhydrous ZnBr2 (1.3 g, 5.7 mmol) were dissolved in
dichloroethane (80 mL)in a 100 mL flask, and bromomethyl methyl ether (BMME) (1.4 g, 11.2
mmol) was added to the solution under an atmosphere of nitrogen. The mixture was stirred for 18
h at 70 °C, and the resulting polymer was thoroughly washed with water and methanol. After
extraction with methanol in
a
Soxhlet extractor for 24 h, the synthesized
bromomethylatedpolyphenanthrene (PPh@CH2Br) polymer was collected and dried overnight
under vacuum at 110 °C. The addition of BMME introduced methylene crosslinking bridges
between PPh rings, and the bromine content of the non-cross linked part (–CH2Br) was determined
by calorimetrically [48].
2.3.Functionalization of PPh@CH2Br with EDA.
PPh@CH2Br (0.6 g) was dissolved in CH2Cl2 (15 mL) in a 25 mL flask and EDA (1.8 mL) was
added slowly at r.t. The mixture was stirred for 12 h at r.t. The resulting EDA–functionalized
7

polymer was centrifuged, washed with CH2Cl2 (10 mL), and dried at 80 °C for 4h. The EDA
functionalized PPh@EDA was designated as PPh@EDA–0.2, PPh@EDA–0.4, and PPh@EDA–
0.6, where the 0.2, 0.4, and 0.6 represent the amount (mL) of EDA used during the preparation of
the PPh@EDA samples.
2.4. General procedure for the preparation of 2-amino-tetrahydro-4H-chromene and pyran
derivatives 1–42.
p–methoxybenzaldehyde 1{11} (1 mmol), MN 2{1} (1 mmol), dimedone 3{1}(1 mmol), and
PPh@EDA (10 mg) were mixed at r.t. under solvent-free conditions with stirring. The reaction
progress was monitored by TLC (hexane:EA = 6:4). When the reaction was complete, EA (8 mL)
was added, and the reaction mixture was centrifuged for 30 min at 6000 rpm. The solvent was
decanted and concentrated using a rotary evaporator. The crude product was purified by
recrystallization from EtOH (10 mL). This procedure was used for all title compounds. In the re-
usability tests, PPh@EDA was washed with EA (2 × 8 mL) and dried under vacuum at 80 °C for
1
13
1h. Detailed spectral data for all the compounds, H and C NMR are given in the Supporting
Information (SI).
3. Results and Discussion
3.1. Characterization of PPh@EDA.
To assess the extent of EDA incorporation onto PPh bearing bromide groups on the periphery
(PPh@CH2Br), Fourier transform infrared (FT-IR) spectra of individual PPh@CH2Br and
PPh@EDA samples were recorded (Fig. 3(A)). The characteristic peaks of PPh@CH2Br are due
to the C–H wagging vibration at 1190 cm–1 and the C–Br stretching vibration at 750 cm–1 of the
CH2Br moiety. For PPh@EDA, the broad peak at 3441 cm−1 corresponds to the both –NH and –
NH2 group, and the new peak at 1344 cm−1 is attributed to the C–N bond [21].In addition,
8

depending on the amount of the amine, the peak intensities of –NH, –NH2 and C–Br changes due
to the reaction between amine and uncroslinked bromine. The C–Br stretching vibrations nearly
disappeared, indicating the occurrence of amination to produce PPh@EDA. In addition the C–N
bond of PPh@EDA is clearly shown in solid state 13C NMR spectrum Fig. S1 in the SI.
X-ray powder diffraction (XRD) spectra of PPh@CH2Br and PPh@EDA samples are shown in
Fig. 3(B). Generally, carbon materials exhibit a (002) reflection peak at 2θ=26.6°[49].The shift of
the latter to lower angles (2θ=23.3°) indicates C–N bond formation as a result of EDA
functionalization of PPh [22].The thermal stabilities of PPh@CH2Br and PPh@EDA were
measured by thermo gravimetric analysis (TGA, Fig. 3(C)). The weight loss in the range of 300–
370 °C is due to the pyrolysis of labile oxygen-containing functional groups, producing CO and
CO2. Furthermore, the thermal stability threshold of PPh@EDA is below 300°C, which is lower
than that of PPh@CH2Br due to earlier degradation of ethylene moieties. The surface morphology
of PPh@CH2Br and PPh@EDA was investigated using scanning electron microscopy (SEM). The
observed microsphere sizes (30 µm) were uniform (Fig. 3(D)), attributed to the uniform
bromomethylation layer on the surface of aromatic hydrocarbons during polymerization. The
morphology of PPh@EDA was similar to that of PPh@CH2Br (Fig. 3(D)), indicating no change
of surface morphology in the reaction of the polymer with EDA.
The textured morphology of the HMOPs sample was further investigated by nitrogen adsorption-
desorption. In all cases, the nitrogen absorption-desorption isotherms were type IV curves (Fig.
3(E)). The BET surface area of PPh@EDA-0.6and PPh@EDA-0.4was estimated as 552 m2/g and
556 m2/g indicating good porosity of the PPh@EDA samples. The total pore volume of PPh@EDA
was measured to be 0.38 cm3g−1. In addition, as shown DFT calculations derived from the pore
size distribution showed that peak value observed at 9.2 A0 and 9.6 A0 for PPh@EDA-0.6 and
9

PPh@EDA-0.4. This suggests that the size of the micropores arises from spherical structures
formed by regular crosslinking on surface of the polymer.
X-ray photoelectron spectroscopy (XPS) is a quantitative surface analysis technique, used to
determine empirical formulae, elemental composition (at parts per thousand ranges), and the
chemical and electronic states of the elements present in the sample. Fig. 4 shows the C1s, N1s,
and O1s regions of the PPh@EDA XPS spectra. The C1s region shows three distinct carbon
environments at 284.5, 284.7, and 284.9 eV, corresponding to sp2 C, (C–C/C=C), and C–N
functionalities, respectively [17]. Figure 4(D) clearly shows that the N1s spectra can be fitted by
two curves with binding energies of 398.6 and 399.7 eV, assigned to –C–NH and CH2–NH2,
respectively [50]. The presence of these two peaks indicates that the condensation of EDA with
PPh@CH2Br results in the formation of C–N bonds. Element analysis of PPh@EDA showed that
the amounts of C, H and N are 85.98, 5.60 and 1.78 wt%, respectively.
3.2. PPh@EDA-catalyzed synthesis of functionalized 2-amino-tetrahydro-4H-chromenes and
pyrans.
The characterizations above confirm the successful functionalization of EDA into the HMOP of
PPh matrix and the importance of aromatic hydrocarbons are widespread components of many
materials, such as petroleum and tars. Generally the aromatic hydrocarbons present in mixtures,
occurring both naturally and as byproducts of fuel processing operations. Phenanthrene is a
polycyclic aromatic hydrocarbon (PAH) compounds that consists of sp2-hybridized carbon atoms,
forming a uniform hexagon, similar to graphite. These PAHs, since they are assembled from
aromatic rings in a periodic fashion, possess extraordinary and often unique electronic properties,
and also it shows low bond gaps, will inspire research on solar cell devices, semiconductors,
10

molecular sensors, and UV stabilizer/absorbers. By using this material we study the catalytic
activity for the synthesis of 2-amino-tetrahydro-4H-chromenes and pyrans through MCRs. It
requires extensive reaction times, high temperatures, and high catalyst loading to promote the
formation of the desired product. Reactions taking place under solvent-free (neat) conditions have
attracted significant interest, since they are cost-effective, easy to handle, require simple workup
procedures, and lead to high yields. Recently, we have synthesized various biologically potent
organic compounds under solvent-free conditions [51–54]. One-pot three-component reactions of
p-methoxy benzaldehyde, malononitrile (MN), and dimedone (1 mmol each) were first attempted
using catalyst-free, acidic (Heterogeneous and Lewis acids) and basic (liquid and solid) catalysts
at room temperature (r.t.) under solvent-free conditions. We found that the solid basic PPh@EDA
catalyst was best suited for the formation of target 2-amino-tetrahydro-4H-chromenesin good
yields, preventing the occurrence of Knoevenagel condensation (KC) (Scheme 2).
Initially, the reaction between p-methoxybenzaldehyde, MN, and dimedone was conducted in
absence of catalyst at r.t. for 14 h under solvent-free conditions; however, no product was observed
(Table 1, entry 1). Later, acidic catalysts such as AlCl3, FeCl3, CuCl2,silicotungstic acid (STA),
phospho sulfonic acid (PSA), and tungstosulfonic acid (TSA) were used at r.t. for 5h,furnishing
yields below 50% and requiring tedious workup procedures (entries 2–7). Subsequently, basic
catalysts containing primary, secondary and tertiary nature were employed. At first, the same
reaction was conducted in presence of 4-ethylmorpholine as catalyst (3 mol %). After 1h, the
reaction mixture contained both the KC and the targeted 2-amino-tetrahydro-4H-chromene
products in a ratio of 0.5:1, estimated from the corresponding 1H NMR spectrum (Fig. S3, SI). No
11

changes were observed when the reaction was continued for 8 h under the same conditions (entries
8–10).
Based on these results, we tried to find a suitable basic catalyst for the selective formation of 2-
amino-tetrahydro-4H-chromenes and pyrans over the KC product. Various basic catalysts, such as
t
triethylamine, butylamine, tetramethylethylenediamine (TMEDA), pyrrolidine, piperidine, and
diethylamine (DEA) furnished the desired 2-amino-tetrahydro-4H-chromenes and pyrans in
excellent yields, without the formation of KC product (Table 1, entries 11–16). The Jeffamine
-amine groups
provided the desired products with good yields without forming intermediates (entries 17–19);
however, the reaction systems involving these polymers are homogeneous and it needs tedious
protocols to purify and separate them after the reaction. We have also employed solid polymers
containing primary amine, poly(ethylene glycol) methyl ether amine (MPEG2000–NH2;
MW=2000) and tertiary amine, poly(dimethyl amino ethyl methacrylate) (PDMAEMA) for the
synthesis of targeted compounds. These two catalysts also show good activities (entries 20 and
21), but again the separation of these polymers is not easy.
The same reaction conducted in presence of resin such as Amberlite IRA–410 gives good yield
but it takes long time for completion of the reaction (entries 22). In order to circumvent this
problem, we have prepared microporus PPh@EDA as a solid basic catalyst and applied it for the
selective formation of 2-amino-tetrahydro-4H-chromenes and pyrans. Initial trials to use
PPh@CH2Br for the reaction show only negligible catalytic activity. To increase the rate of the
reaction and yield of the product, we substituted the bromine groups for EDA with various amount
of amine (0.2, 0.4, and 0.6 mL). Comparing all the three PPh@EDA samples, PPh@EDA–0.6
12

showed the best catalytic activity for the targeted compounds (entries 26–31), indicating that the
number of basic sites has a significant effect on the catalytic performance. The optimal molar
loading of PPh@EDA was determined in a model reaction using 1.8, 3, 3.6, 4.8, 6, and 7.8 mol %
of PPh@EDA under neat conditions, producing the target compound in 80, 82, 87, 91, 95, and 95%
yield, respectively. The yields gradually increased with increasing catalyst loading up to 6 mol %,
with no enhancement of the product yield observed at higher loadings (entries 26–31).
Subsequently, the reaction progress under solvent and solvent-free conditions (Table 2) was
compared. The reaction preceded smoothly in both polar and non-polar solvents, such as ethanol,
isopropanol, methanol, THF, CH2Cl2, CHCl3, and 1,4-dioxane. Both solvent groups led to the
effective formation of target compounds, but the reaction times required were long (entries 2–8).
The scope and limitations of this catalytic method were investigated using diverse aldehydes
1{1−20}, alkylmalonates 2{1, 2}, and cyclic ketones 3{1,2}; acyclic ketoesters {3–5} were
selected for library validation (Fig. 5). First, the reaction of p-methoxybenzaldehyde 1 {11}, MN
2 {1}, and dimedone 3{1} was examined. As shown in Table 3, this MCR produced a good yield
of the desired product in a short time. The nature of substrate and the position of functional groups
in the aromatic ring of the aldehyde had a small effect on product yield and reaction time.
Aromatic aldehydes with electron-donating groups (OMe, OEt) in the para-position reacted
faster and gave better yields compared to the ones with the above groups in the ortho-position, due
to steric hindrance. The same effects were also observed for aldehydes with alkyl groups (Me or
iPr). While halogen-substituted aldehydes furnished good yields and fast reaction rates, those
substituted at the 2-position reacted slower than the ones substituted at 3-and 4-positions. 2-chloro-
6-fluorobenzaldehyde gave yields smaller than those of other halogen-substituted aldehydes, due
13

to the electro-negativity of the fluorine substituent. Reactions of aldehydes bearing a highly
electron-withdrawing nitro group were relatively slow and furnished the products in low yields,
due to the electron deficiency of the substrate. Furthermore, heterocyclic and aliphatic aldehydes
also gave good yields and short reaction times. We found that the reaction with ethyl cyanoacetate
was slower than that with MN, due to the lower reactivity of the former. Subsequently, activated
compounds with enolizable C−H bonds, such as cyclohexane-1,3-dione, containing a reactive α-
methylene group, were also evaluated. Furthermore, the reaction was extended to compounds
containing acyclic ketoester moieties, such as methylacetoacetate, ethylacetoacetate, and
tbutylacetate, the reactions of which proceeded smoothly, with total avoidance of KC (Table 3,
entries 26–41).
In addition, the merits of microporus PPh@EDA were compared with those of other reported
amine containing various porous and nonporous catalysts for the synthesis of 2-amino-4H-
chromenes and pyrans (Table 4). Aghayanet al. [55] developed for the synthesis of tetrahydro-
chromenes in presence of mesoporous amino-functionalized MCM–41 catalyst that is active only
at high temperatures, leading to the formation of by products. Recently Morsali [56] reported the
synthesis of tetrahydro−chromenes by using amine−functionalized metal−organic framework
(MOF–NH2) that is active in organic solvents and needs long reaction time (4 h) to complete the
reaction at reflux condition. Liao et al. [57] also reported the use of amino–appended β–
cyclodextrins supramolecular catalyst (β–CD–NH2) for the preparation of 2-amino-4H-chromenes
needing longer reaction time than PPh@EDA. Siddiqui et al.[58] used chitosan as a catalyst for
the synthesis of 2-amino-4H-pyrans, requiring 1.5 h to achieve 89% yield. Comparing to above-
mentioned catalysts, the PPh@EDA has obvious advantages for the synthesis of 2-amino-4H-
14

chromenes and pyrans in that it does not require harsh reaction conditions, solvents and laborious
work-up procedures and that it is recyclable. Such an attractive features of PPh@EDA are related
with the hyper-cross-linked micropore structure of it. The presence of interconnected micropores
may result in (i) a beneficial mass transfer from side to side; (ii) a large surface area available for
interaction of the molecules with the active sites [59,60]. These micropores present a good
platform for the catalysis to carry on in a particular pathway leading to the desired products by
virtue of its decreased retention times.
Finally, the recyclability of PPh@EDA was examined for the preparation of functionalized 2-
amino-tetrahydro-4H-chromene 4{11,1,1}. PPh@EDA was simply recovered by adding ethyl
acetate (EA) to the reaction mixture. The insoluble catalyst was separated by centrifugation,
washed twice with EA (2 × 8 mL), and dried under vacuum at 60 °C, showing good reusability for
up to 4 cycles the catalytic activity was slightly decreased due to the recovery percentage of the
catalyst might be loss during recovery (Fig. 6), and also the recycled catalyst was characterized by
using FT-IR, TGA and SEM is similar to that of fresh catalyst (Fig. S2, SI).
All synthesized compounds were identified by FT-IR, 1H, and 13C NMR spectroscopies. The IR
spectra of compounds 1–42 showed the expected absorption bands at 3425–3119, 2346–2356, and
1
1750–1650 cm−1, attributed to NH2, CN, and C=O stretching vibrations, respectively [39]. In H
NMR spectra, the Ar–CH proton signal appeared as a singlet at 5.16–3.38 ppm, and the NH2 signal
appeared as a broad singlet at 4.75–4.42 ppm. The remaining proton signals were in agreement
with the ones previously reported. In 13C NMR spectra, the Ar–CH carbon signal at 40.4 ppm
confirmed the formation of target compounds.
A plausible reaction mechanism for the formation of functionalized 2-amino-tetrahydro-4H-
chromenes and pyrans in the presence of PPh@EDA is shown in Scheme 3. Initially, the aldehyde
15

carbonyl group reacts with malononitrile to form the KC product. Subsequently, the enol form of
active methylene compounds undergoes Michael addition to the KC product and forms the desired
2-amino-tetrahydro-4H-chromenes after cyclization.
4. Conclusions
We have reported active, stable and recyclable micropores PPh@EDA systems highly effective
solid base catalysts for the synthesis of 2-amino-tetrahydro-4H-chromenes and pyrans. This
catalyst is applicable for broad substrate scope and the reactions involving PPh@EDA catalyst are
characterized by operational simplicity, good yields, mild reaction conditions, short reaction times,
easy recovery and recycling of catalyst, chromatography–free purification, and no use of
hazardous and expensive organic solvents. Thus, 4{11,1,1} compound was obtained at 95% yield
by reacting p-methoxybenzaldehyde 1{11} (1 mmol), MN 2{1} (1 mmol), and dimedone 3{1}(1
mmol) at r.t. under solvent-free conditions by using PPh@EDA (10 mg) as a catalyst in an hour.
In addition the catalyst was recyclable 4 times without losing its activity. Evidently PPh@EDA is
an environmentally friendly and commercially tangible catalyst for the preparation of diverse
libraries of 2-amino-tetrahydro-4H-chromene and pyran derivatives.
16

Justification
We summarize the contribution of this research as follows.
i) A diversity of 2-amino-tetrahydro-4H-chromene and pyrans were synthesized with high
yields in a short time by using amine-functionalized polyphenanthrene spheres as a catalyst for the
first time. All compounds were fully characterized by IR, 1H and 13C NMR.
ii) An efficient and green method was employed for the synthesis of these derivatives.
iii) The amine-functionalized polyphenanthrene catalyst was a found to be more suitable for
the synthesis of targeted compounds compared with the reported methods.
Acknowledgements
This work was supported by the Basic Science Research Program through the National Research
Foundation of Korea (2015R1D1A1A09057372). The authors also thank the BK21 PLUS Program
for partial financial support.
References
[1] R. Dawson, A.I. Cooper, D.J. Adams, Prog. Polym. Sci. 37 (2012) 530–563.
[2] S. Xu, Y. Luo, B. Tan, Macromol. Rapid Commun. 34 (2013) 471–484.
[3] G. Jonathan, M.J.F. Jean, S. Frantisek, Small, 5 (2009) 1098–111.
[4] J. Jiang, A.I. Cooper, M. Schroder, Microporous Organic Polymers: Design, Synthesis, and
Function. Functional Metal-Organic Frameworks: Gas Storage, Separation and Catalysis;
Springer, 2010.
17

[5] G. Cheng, B. Bonillo, R.S. Sprick, D.J. Adams, T. Hasell, A.I. Cooper,Adv. Funct. Mater. 24
(2014) 5219–5224.
[6] Q. Fang, Z. Zhuang, S. Gu, R.B. Kaspar, J. Zheng, J. Wang, S. Qiu, Y.Yan, Nat. Commun.5
(2014) 4503.
[7] R. Dawson, A. Laybourn, Y.Z. Khimyak, D.J. Adams, A.I. Cooper, Macromolecules, 43 (2010)
8524–8530.
[8] S. Yuan, B. Dorney, D. White, S. Kirklin, P. Zapol, L. Yu, D. Liu, Chem. Commun.46 (2010)
4547–4549.
[9] X.D. Zhuang, F. Zhang, D.Q. Wu, N. Forler, H.W. Liang, M. Wagner, D. Gehrig, M.R. Hansen,
F. Laquai, X.L. Feng, Angew. Chem., Int. Ed. 52 (2013) 9668–9672.
[10] B. Li, Z. Guan, W. Wang, X. Yang, J. Hu, B. Tan, T. Li,Adv. Mater.24 (2012) 3390–3395.
[11] P. Samanta, P. Chandra, S.K. Ghosh, Beilstein J. Org. Chem.12 (2016) 1981–1986.
[12] B. Li, R. Gong, W. Wang, X. Huang, W. Zhang, H. Li, C. Hu, B. Tan,Macromolecules,44
(2011) 2410–2414.
[13] M.P. Tsyurupa, V.A. Davankov, React. Funct. Polym.66 (2006) 768–779.
[14] X. Huang, S. Kim, M.S. Heo, J.E. Kim, H. Suh, I. Kim, Langmuir, 29 (2013) 12266–12274.
[15] K.E. Maly, J. Mater. Chem.19 (2009) 1781–1787.
[16] Q. Sun, Z. Dai, X. Meng, F.-S. Xiao, Chem. Soc. Rev.44 (2015) 6018–6034.
[17] F. Liu, X. Meng, Y. Zhang, L. Ren, F. Nawaz, F.-S.Xiao, J. Catal.271 (2010) 52–58.
[18] S. Jiang, J. Bacsa, X. Wu, J.T.A. Jones, R. Dawson, A. Trewin, D.J. Adams, A.I. Cooper,
Chem. Commun. 47 (2011) 8919–8921.
[19] X. Du, Y. Sun, B. Tan, Q. Teng, X. Yao, C. Su, W. Wang, Chem. Commun.46 (2010) 970–
972.
18

[20] Y. Zhang, Y. Zhang, Y.L. Sun, X. Du, J.Y. Shi, W.D. Wang, W. Wang, Chem. Eur. J.18
(2012) 6328–6334.
[21] F. Zhang, H. Jiang, X. Li, X. Wu, H. Li. ACS Catal.4 (2014) 394–401.
[22] B. Xue, J. Zhu, N. Liu, Y. Li, Catal .Commun.64 (2015) 105–109.
[23] F. Zhang, H. Jiang, X. Wu, Z. Mao, H. Li. ACS Appl. Mater. Interfaces.7 (2015) 1669–1677.
[24] N.H. Kim, T. Kuil, J.H. Lee, J. Mater. Chem.A1 (2013) 1349–1358.
[25] R.V.A. Orru, M. de Greef, Synthesis, 10 (2003) 1471–1499.
[26] L. Bonsignore, G. Loy, D. Secci, A. Calignano, Eur. J. Med. Chem.28 (1993) 517–520.
[27] M.N. Erichsen, T.H.V. Huynh, B. Abrahamsen, J.F. Bastlund, C. Bundgaard, O. Monrad, A.B.
Jensen, C.W. Nielsen, K. Frydenvang, A.A. Jensen, L. Bunch, J. Med. Chem.53 (2010) 7180−7191.
[28] W. Kemnitzer, J. Drewe, S. Jiang, H. Zhang, C.C. Grundy, D. Labreque, M. Bubenick, G.
Attardo, R. Denis, S. Lamothe, H. Gourdeau, B. Tseng, S. Kasibhatla, S.X. Cai, J. Med. Chem.51
(2008) 417−423.
[29] M. Mahmoodi, A. Aliabadi, S. Emami, M. Safavi, S. Rajabalian, A.M. Mohagheghi, A.
Khoshzaban, A.S. Kermani, N. Lamei, A. Shafiee, A. Foroumadi, Arch. Pharm. Chem. Life
Sci.343 (2010) 411−416.
[30] D. Kumar, V.B. Reddy, S. Sharad, U. Dube, S. Kapur, Eur. J. Med.Chem.44 (2009)
3805−3809.
[31] E.R. Bissell, A.R. Mitchell, R.E. Smith, J. Org. Chem.45 (1980) 2283−2287.
[32] G.A. Reynolds, K.H. Drexhage, Opt. Commun.13 (1975) 222−225.
[33] G.P. Ellis, “Chromenes, Chromanones, and Chromones,” in The Chemistry of Heterocyclic
Compounds Chromenes, A. Weissberger andE.C. Taylor, Eds., Wiley, NY, USA, 1977.
19

[34] H. Zollinger, Color Chemistry: Syntheses, Properties, and Applications of Organic Dyes and
Pigments, VHCA, Zurikh, Switzerland, 3rd edn, 2003.
[35] C.G. Knight, T.J. Stephens, J.Bio.Chem.258 (1989) 683−687.
[36] E.A.A. Hafez, M.H. Elnagdi, A.G.A. Elagamey, F.M.A.A. El-Taweel, Heterocycles, 26 (1987)
903−907.
[37] S. Santra, M. Rahman, A. Roy, A. Majee, A. Hajra, Org. Chem. Int.2014, 1−8.
[38] A. Davoodnia, S. Allameh, S. Fazli, N. Tavakoli-Hoseini, Chem. Pap.65 (2011) 714−720.
[39] R.-Y. Guo, Z.-M. An, L.-P. Mo, ACS Comb. Sci.15 (2013) 557−563.
[40] M. Seifi, H. Sheibani, Catal. Lett.126 (2008) 275−279.
[41] M.H. Elnagdi, R.M. Abdel-Motaleb, M. Mustafa, M.F. Zayed, E.M. Kamel, J. Heterocycl.
Chem.24 (1987) 1677−1681.
[42] G. Brahmachari, B. Banerjee, ACS Sustainable Chem. Eng.2 (2014) 411−422.
[43] Y. Peng, G. Song, Catal .Commun.8 (2007) 111−114.
[44] A. Fallah-Shojaei, K. Tabatabaeian, F. Shirini, S.Z. Hejazi, RSC Adv. 4 (2014) 9509−9516.
[45] R.M.N. Kalla, H. Park, H.R. Lee, H. Such, I. Kim, ACS Comb. Sci.17 (2015) 691−697.
[46] R.M.N. Kalla, S.J. Byeon, M.S. Heo, I. Kim, Tetrahedron, 69 (2013) 10544−10551.
[47] R.M.N. Kalla, V.J. Johnson, H. Park, I. Kim, Cat. Commun.57 (2014) 55–59.
[48] B. Niyazi, K. Bunyamin, Eur. Polym. J. 43 (2007) 4719–4725.
[49] R. Bissessur, P.K.Y. Liu, S.F. Scully, Synth. Met.156 (2006) 1023–1027.
[50] T. Ramanathan, F.T. Fisher, R.S. Ruoff, L.C. Brinson, Chem. Mater. 17 (2005) 1290–1295.
[51] K.R.M. Naidu, S.I. Khalivulla, S. Rasheed, S. Fakurazi, P. Arulselvan, O. Lasekan, F. Abas,
Int. J. Mol. Sci.14 (2013) 1843–1853.
20

[52] K.R.M. Naidu, B.S. Krishna, M A. Kumar, P. Arulselvan, S.I. Khalivulla, O. Lasekan,
Molecules, 17 (2012) 7543–7555.
[53] R.M.N. Kalla, M.R. Kim, I. Kim, Tetrahedron Lett.56 (2015) 717–720.
[54] R.M.N. Kalla, M.R. Kim, Y.N. Kim, I. Kim, New J. Chem.40 (2016) 687–693.
[55] M. Mirza-Aghayan, S. Nazmdeh, R. Boukherroub, M. Rahimifard, A.A. Tarlani, M.
Abolghasemi-Malakshah, Synth.Commun.43 (2013) 1499–1507.
[56] V. Safarifard, S. Beheshti, A. Morsali, Cryst. Eng.Commun. 17 (2015) 1680–1685.
[57] Y. Ren, B. Yang, X. Liao, Catal. Sci. Technol.6 (2016) 4283–4293.
[58] P.R. Rahila, I. Afshan S. Hozeyfa R. Siddiqui, Chemistryselect, 1 (2016) 1300–1304.
[59] V. Meynen, P. Cool, E.F. Vansant, Microporous Mesoporous Mater.104 (2007) 26–38.
[60] S. van Donk, A.H. Janssen, J.H. Bitter, K.P. de Jong, Catal. Rev. - Sci. Eng.45 (2003) 297–
319.
21

Fig. 1. Schematic synthesis of hyper-crosslinked polyaromatic spheres and ethylenediamine-
functionalized polymer spheres (PPh@EDA).
Fig. 2. Examples of representative 2-amino-tetrahydro-4H-chromene derivatives HA 14-1(A),
IRPA inhibitor (B), and Antibacterial Agents (C).
22

Fig. 3. (A) FT-IR spectra of PPh@CH2Br (a), PPh@EDA–0.2 (mL) (b), PPh@EDA–0.4 (mL) (c),
and PPh@EDA–0.6 (mL) (d); (B) XRD patterns of PPh@CH2Br (a) and PPh@EDA (b); (C) TGA
thermograms of PPh@CH2Br (a) and PPh@EDA (b); SEM images of PPh@CH2Br (a) and
PPh@EDA (b); and (E) nitrogen adsorption and desorption isotherms (a) and pore size distribution
(b) of PPh@EDA.
23

Fig. 4. XPS curves: full spectrum of PPh@EDA (A), with corresponding C1s (B), O1s (C), and
N1s (D) regions.
24

Fig. 5. Reagents used to study the reaction scope.
25

Fig. 6. Effect of PPh@EDA recycling on the yield of 2-amino-tetrahydro-4H-chromenes and
pyrans.
Scheme 1. Synthesis of a series of novel 2-amino-tetrahydro-4H-chromenes and pyrans.
26

Scheme 2. Possible products formed during the one-pot synthesis of 2-amino-tetrahydro-4H-
chromenes and pyrans.
Scheme 3. A plausible mechanism for the formation of 2-amino-tetrahydro-4H-chromenes in
presence of PPh@EDA.
27

Table 1.Effect of various catalysts on the synthesis of 2-amino-tetrahydro-4H-chromenes and
pyrans.a
Yield (%)b
Catalyst amount
(%)
Entry catalyst
Time (h)
KC
4
1
2
3
4
5
6
7
8
Catalyst free
AlCl3
FeCl3
CuCl2
STA
PSA
TSA
4-ethylmorpholine
4-ethylmorpholine
4-ethylmorpholine
Triethylamine
Tertiary butyl amine
TEMDA
-
14
3
4
3.5
5
5
5
1
4
8
nrc
45
50
50
30
45
40
80
85
90
86
88
90
91
90
91
92
90
89
86
85
86
45
80
83
80
82
87
91
95
95
3 (mol %)
3 (mol %)
3 (mol %)
3(mol %)
3 (mol %)
3 (mol %)
3 (mol %)
3 (mol %)
3 (mol %)
3 (mol %)
3 (mol %)
3 (mol %)
3 (mol%)
3 (mol%)
3 (mol%)
3 (mol %)
3 (mol %)
3 (mol %)
3 (mol %)
3 (mol %)
3 (mg)
–
–
–
–
–
–
20
15
10
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
1
0.5
0.5
0.5
1
0.5
0.5
0.7
1
1
1.5
2
6
3
Pyrrolidine
Piperidine
Diethylamine
Jeffamine (230)
Jeffamine (400)
Jeffamine (2000)
MPEG2000–NH2
PDMAEMA
Amberlite IRA–410
PPh@CH2Br
PPh@EDA–0.2
PPh@EDA–0.4
PPh@EDA–0.6
PPh@EDA–0.6
PPh@EDA–0.6
PPh@EDA–0.6
PPh@EDA–0.6
PPh@EDA–0.6
3 (mg)
0.6 (mol %)
1.2 (mol %)
1.8 (mol %)
3 (mol %)
3.6 (mol %)
4.8 (mol %)
6 (mol %)
7.8 (mol %)
2
1.5
1.4
1
1
1
1
28

aExperimental conditions: p-methoxybenzaldehyde = 1 mmol, malononitrile =
1 mmol, dimedone = 1 mmol, and catalyst = 10 mg at r.t. and neat condition.
bIsolated Yields.
cNoreaction.
29