Triazine-based mesoporous covalent imine polymers as solid supports for copper-mediated chan-lam cross-coupling N-arylation reactions

Article abstract of DOI:10.1002/chem.201402365

The synthesis of a novel mesoporous covalent imine polymeric (MCIPs) material, involving simple Schiff-base chemistry, is reported. This highly functionalised nitrogen-rich material acts as a good support for immobilising Cu^II ions, exhibiting excellent catalytic activity in promoting the Chan-Lam cross-coupling reaction between biologically active amines and arylboronic acids. The performance of this catalyst is also evident from its broad substrate scope, high stability, real heterogeneity, mild reaction conditions and reusability without loss of activity. The observed results will provide additional scope on the design and catalytic applications of this emerging class of materials.

Full text of DOI:10.1002/chem.201402365

DOI: 10.1002/chem.201402365
Full Paper
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Covalent Imine Polymers
Triazine-Based Mesoporous Covalent Imine Polymers as Solid
Supports for Copper-Mediated Chan–Lam Cross-Coupling
N-Arylation Reactions
Pillaiyar Puthiaraj[b] and Kasi Pitchumani*[a]
Abstract: The synthesis of a novel mesoporous covalent
imine polymeric (MCIPs) material, involving simple Schiff-
base chemistry, is reported. This highly functionalised nitro-
gen-rich material acts as a good support for immobilising
CuII ions, exhibiting excellent catalytic activity in promoting
the Chan–Lam cross-coupling reaction between biologically
active amines and arylboronic acids. The performance of this
catalyst is also evident from its broad substrate scope, high
stability, real heterogeneity, mild reaction conditions and re-
usability without loss of activity. The observed results will
provide additional scope on the design and catalytic applica-
tions of this emerging class of materials.
Introduction
ing to the synthesis of new materials with diverse applications.
For example, incorporation of catalytically active sites, such as
metals, onto the nitrogen-rich porous-organic-framework surfa-
ces may be beneficial to enhance the catalytic performance, as
well as the stability, of the supported materials.[12]
The creation of pores with desired dimensions, in the form of
frameworks, is a challenging task in materials chemistry.
Among various porous materials, metal–organic frameworks
(MOFs)[1] and porous organic frameworks (POFs)[2] are consid-
ered to be of interest in the fields of gas storage and cataly-
sis.[1,2] In particular, covalently linked POFs have attracted con-
siderable attention as unique and emerging materials. A
number of different types of POFs, such as covalent organic
frameworks (COFs),[3] conjugated microporous polymers
(CMPs),[4] polymers of intrinsic microporosity (PIM),[5] element–
organic frameworks (EOFs),[6] triazine-based organic frame-
works (CTFs),[7] porous polymer networks (PPN),[8] covalent or-
ganic polymers (COP)[9] and porous aromatic frameworks
(PAFs),[10] among others, have been reported. These materials
have advantages, such as relatively high thermal stability, high
specific surface area, low density, ease of synthesis from simple
compounds and retaining their porosity even after boiling in
water for one week.[2–10] In addition, one of the most attractive
aspects of POFs is the promise of tuning structures and prop-
erties through rational chemical design and synthesis. These
properties allow potential applications[8a,10,11] in gas storage, ex-
plosive detection, drug release and catalysis. Consequently, the
development of multifaceted functionality into porous net-
works is one of the frontline areas of research, potentially lead-
The synthesis of porous carbon-based material catalysts has
immense potential in the advancement of sustainable substi-
tutes over existing MOFs, zeolite and metal oxides.[13] Jang
et al. have extensively reported that nitrogen-doped carbon
nanotubes (CNTs) are used to stabilize the palladium nanopar-
ticles,[14] which are used as a catalyst for the Heck reaction and
hydrogenation. Thomas et al. have demonstrated a nitrogen-
rich covalent triazine framework as a good catalytic support
for glycerol oxidation.[15] Recently, Wang et al. have reported
palladium-loaded covalent organic frameworks as catalysts for
[a] Prof. Dr. K. Pitchumani
Centre for Green Chemistry Processes
School of Chemistry, Madurai Kamaraj University
Madurai-625021 (India)
E-mail: pit12399@yahoo.com
[b] P. Puthiaraj
School of Chemistry, Madurai Kamaraj University
Madurai-625021 (India)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402365.
Figure 1. FTIR spectra of 2,4,6-tris(p-formylphenoxy)-1,3,5-triazine (TRIPOD),
p-phenylenediamine (PPD) and MCIP-1.
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Scheme 1. Schematic representation of MCIP-1 and MCIP-2.
Figure 2. FTIR spectra of 2,4,6-tris(p-formylphenoxy)-1,3,5-triazine (TRIPOD),
terephthalodihydrazide (TPH) and MCIP-2.
Suzuki coupling reactions.[11e] Bhaumik et al. have extensively
reported triazine-functionalised mesoporous polymers[12] and
nitrogen-rich porous covalent imine (CIN) frameworks,[16] for
supporting palladium species, as catalysts for CÀC cross-cou-
pling reactions, and acid-group-containing porous organic
polymers as catalysts for the synthesis of 3-benzhydrylindo-
le.[11c] More recently, Zhang et al. have demonstrated the meso-
porous poly(melamine–formaldehyde) material as an efficient
catalyst for chemoselective acetalisation of aldehydes.[17] En-
couraged by these results, herein we report a copper-loaded
mesoporous covalent imine polymer (MCIP) as a unique heter-
ogeneous protocol to achieve the oxidative Chan–Lam cross-
coupling reaction of diverse boronic acids with biologically
active amines.
Figure 3. 13C CP-MAS NMR spectrum of a) MCIP-1 and b) MCIP-2.
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Transition-metal-catalysed CÀN cross-coupling reactions
have immense utility in organic synthesis to develop several
pharmacophore and drug analogues.[18] Generally, these aro-
matic CÀN moieties were synthesised by the aromatic nucleo-
philic substitution of nitrogen nucleophiles with aryl halides, or
the Ullmann coupling reaction,[18] by using stoichiometric
amounts of copper metal at high temperature. Furthermore,
these procedures utilize an expensive and air-sensitive palladi-
um source for CÀN cross-coupling,[19] thus, limiting their appli-
cation in large-scale and laborious catalyst-separation process-
es. Consequently, the development of milder, more environ-
mentally friendly conditions and a cheap and efficient catalyst
is desirable. In this context, Chan–Lam cross-coupling involves
the copper-promoted coupling of amines with wide range of
commercially available arylboronic acids, and has emerged as
a powerful tool for CÀN bond formation under mild reaction
conditions.[20] Though this coupling is reported with nitrogen
nucleophiles,[21] to the best of our knowledge, there is no
report describing the formation of biologically active N-arylfla-
vones from flavones and arylboronic acids. These features
prompted us to study the N-arylation of aminoflavones and
heterocyclic amines by using arylboronic acids to yield biologi-
cally important N-aryl derivatives; the observed results are dis-
cussed below.
both MCIP-1 and MCIP-2 materials. Meanwhile, the aldehyde
(1703 cmÀ1) and amine (3420 and 3358 cmÀ1) bands of MCIP-
1 and MCIP-2 had disappeared completely on comparison with
the spectra of the starting materials (Figure 1 and 2).
The 13C CP-MAS NMR spectral data of MCIP-1 and MCIP-2
(Figure 3) clearly confirmed their chemical structure. The solid-
state NMR spectrum of MCIP-1 shows six peaks at d=122.4,
129.0, 134.5, 148.6, 153.8, and 173.5 ppm (Figure 3a). The peak
at 153.8 ppm corresponds to the carbon atom of the C=N
bond obtained from the condensation reaction of trialdehyde
and diamine. The peak at 173.5 ppm corresponds to the tria-
zine carbon atom. The signals at 122.4, 129.0, 134.5 and
148.6 ppm can be assigned to the carbon atoms of the phenyl
rings. There was no peak present at around 190 ppm. These re-
sults clearly confirm the absence of unreacted aldehyde.
Similarly, in the solid-state NMR spectra of MCIP-2, the char-
acteristic peak of a C=N bond appears at 153.4 ppm (Fig-
ure 3b). Data from the solid-state NMR spectra of MCIP-1 and
MCIP-2 are given in the Supporting Information (Tables S1 and
S2).
FE-SEM describes the morphology of the MCIP-1 and MCIP-2
materials (Figure 4). Images in Figures 4a and 4b clearly indi-
cate that MCIP-1 adopts a sheet-like morphology, whereas
those of MCIP-2 (Figure 4c and 4d) clearly indicate that MCIP-2
adopts a uniform needle-like morphology. These observations
indicate that the condensation of aldehyde and amines leads
Results and Discussion
The imine-functionalised meso-
porous covalent imine polymers
(MCIPs) were synthesised by
Schiff-base chemistry involving
a trialdehyde–triazine derivative
and diamine (Scheme 1). The
synthesised materials were char-
acterized by using FTIR, 13C
cross-polarization
magic-angle
spinning (CP-MAS) NMR spec-
troscopy, Field-emission scan-
ning electron microscopy (FE-
SEM), elemental microanalysis,
powder XRD (PXRD), thermogra-
vimetric analysis (TGA) and nitro-
gen-gas-adsorption studies. The
synthesised MCIP-1 and MCIP-2
materials are insoluble in water
and common organic solvents,
such as DMF, THF, DMSO, ace-
tone, and others.
Fourier transform infrared
(FTIR) spectroscopy of MCIP-
1 and MCIP-2 shows a strong
C=N stretching at 1560 and
1592 cmÀ1, respectively, (Figure 1
and Figure 2), indicating the for-
mation of an imine bond. The
band at 1500 cmÀ1, representing
the triazine ring, is present in Figure 4. FE-SEM images of the synthesised a,b) MCIP-1 and c,d) MCIP-2.
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to a uniform morphology and a certain degree of structural
regularity.
The regularity and crystallinity of the structure of MCIP-
1 and MCIP-2 materials are further confirmed by powder PXRD
analysis (Figure 5). The obtained PXRD pattern of MCIP-1 indi-
cates a partial crystallinity and the set of peaks in the range of
9 to 408, suggests that the framework has a certain degree of
order (Figure 5a). Similarly, the PXRD pattern of MCIP-2 indi-
cates a structure with partial crystallinity and shows a certain
degree of order in the range 10 to 408 (Figure 5b).
The thermal stability of MCIP-1 and MCIP-2 was analysed
TGA under a nitrogen atmosphere (Figure 6). As shown in
Figure 6, MCIP-1 exhibits almost no weight loss below 3008C,
suggesting no loss of guest. The framework decomposition of
MCIP-1 was observed at about 3508C. Subsequently, the
weight gradually decreases, by up to 50% at 6008C. TGA of
Cu/MCIP-1 also demonstrated a good thermal stability up to
2008C. Similarly, Figure 8 clearly shows that MCIP-2 is stable up
to 2508C.
The porosity and surface area of the above materials were
measured by nitrogen adsorption–desorption analysis at 77 K
(Figure 7 and 8). These isotherms are closely related to a type-
IV isotherm, which is indicative of characteristic mesoporous
materials.[22] From the Brunauer–Emmett–Teller (BET) isotherms,
the surface areas are found to be 174 m2 gÀ1 and 187 m2 gÀ1
for MCIP-1 and MCIP-2, respectively. These values are very
close to that of mesoporous materials,[22] but still well within
the values of other materials. Pore-size-distribution plots of
both MCIP-1 and MCIP-2 (insets of Figure 7 and 8) display
a pore width of 32.4 and 44.3 ꢁ, respectively.
As the synthesised MCIP-1 material has large number of ni-
trogen atoms, from the triazine and imine groups, it can be
used as a metal-ion stabiliser. MCIP-1 was stirred with copper-
(II) acetate in CH2Cl2 solvent at room temperature for 48 h to
prepare the copper-loaded MCIP-1 (Cu/MCIP-1) catalyst, which
was characterized by powder XRD (see the Supporting Infor-
mation, Figure S1), energy-dispersive X-ray (EDX), atomic-ab-
sorption spectroscopy (AAS), inductively coupled plasma
atomic-emission spectroscopy (ICP-AES), TGA and X-ray photo-
electron spectroscopy (XPS) analysis. A comparison of the
powder XRD patterns of MCIP-1 and Cu/MCIP-1 shows that the
structure of MCIP-1 was maintained after the treatment with
copper acetate. Elemental analysis by AAS indicated
a 2.58 mmolgÀ1 copper loading in Cu/MCIP-1. From ICP-AES
analysis the copper concentration in Cu/MCIP-1 was found to
be 2.60%. The SEM-EDX results suggest ꢀ2.53 wt% of copper
in Cu/MCIP-1 (see the Supporting Information, Table S3).
XPS spectra (Figure 9a and 9b) show the Cu 2p3/2 core level
of fresh and reused Cu/MCIP-1 catalyst, respectively. The bind-
ing-energy values of the fresh and reused catalyst are summar-
ized in Table 1. Cu 2p3/2 XPS of the fresh Cu/MCIP-1 catalyst ex-
hibits a sharp peak at 934.5Æ0.1 eV and a strong satellite peak
on the higher binding-energy site (above 940 eV), indicating
the existence of divalent copper species, in good agreement
with the characteristic peak of CuII in literature reports.[23] Simi-
larly, the XPS spectrum (of Cu 2p3/2) of the reused Cu/MCIP-
1 catalyst also exhibits a strong binding-energy peak, in the
Figure 5. Powder XRD pattern of a) MCIP-1 and b) MCIP-2.
Figure 6. TGA of MCIP-1, Cu/MCIP-1 and MCIP-2.
same region as the fresh catalyst, with strong satellite peaks.
These results clearly confirm that after completion of the reac-
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Figure 7. Nitrogen adsorption–desorption isotherm of MCIP-1 (solid square:
adsorption; empty circle: desorption). Pore-size distribution of MCIP-
1 (inset).
Figure 9. Cu 2p3/2 core level XPS spectra of a) fresh and b) reused Cu/MCIP-
1.
Table 1. Cu 2p3/2 XPS parameters of fresh, reused Cu/MCIP-1 and report-
Figure 8. Nitrogen adsorption–desorption isotherm of MCIP-2 (solid square:
adsorption; empty circle: desorption). Pore size distribution of MCIP-2
(inset).
ed catalysts.
Catalyst
BE of Cu 2p3/2 [eV]
FWHM [eV]
fresh Cu/MCIP-1
reused Cu/MCIP-1
CuZnAl-HT[23a]
Malachite[23a]
CuO[23b]
934.5Æ1
934.4Æ1
934.6
934.6
933.8
3.8
3.8
3.8
3.3
3.6
1.7
tion, the catalyst retains its original valence (CuII) and provides
a strong support for the structural integrity of the catalyst.
The XPS spectra (Figure 10 and Figure 11) describe the N1s
and O1s core-level spectra of the fresh and reused Cu/MCIP-
1 catalyst. A binding energy of 532.5 eV for the CÀOÀC bond
(O1s core level) is reported in the literature.[24] Interestingly,
the O1s value for the fresh and reused Cu/MCIP-1 catalyst ap-
pears at 531.8Æ1 eV. Similarly, the triazine unit (N1 s core
level) is reported to have a binding energy of 398.9 eV.[25] The
N1s core-level binding energy of the fresh and reused Cu/
MCIP-1 catalyst appears at 400.4Æ1 eV. These values clearly
demonstrate that copper metal binds strongly to nitrogen as
well as oxygen atoms.
Cu metal[23a]
932.7
BE=binding energy; FWHM=full width half maximum.
The catalytic activity of this heterogeneous Cu/MCIP-1 mate-
rial was established in the Chan–Lam cross-coupling reaction
of biologically relevant amines with boronic acids. It is relevant
to note here that the potential industrial applications of this
reaction, using other homogeneous copper catalysts to pro-
duce pharmacologically relevant derivatives, is quite limited
because of the difficulties in separating and recycling the cata-
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Figure 10. N1s core level XPS spectra of a) fresh and b) reused Cu/MCIP-1.
Figure 11. O1s core level XPS spectra of a) fresh and b) reused Cu/MCIP-1.
lyst from the reaction mixture. Catalytic studies are restricted
to Cu/MCIP-1 and are not extended to Cu/MCIP-2 because
amides are known to undergo Chan–Lam N-arylation.
and the desired product was formed in 70% yield (Table 2,
entry 8). When other inorganic bases were used, similar results
were observed (Table 2, entries 9 and 10). Interestingly, when
organic bases, such as NEt3 and pyridine, were used, higher
yields were obtained (Table 2, entries 11 and 12). From a toxicity
point of view, NEt3 is a better choice of base than pyridine for
this cross-coupling reaction. Other solvents, such as methanol,
MeCN, DMF, DMSO and toluene were also employed, but
showed no improvement in yield (Table 2, entries 13–17).
When the reaction was conducted in 1,2-dichloroethane (DCE),
excellent yields were obtained (Table 2, entries 18 and 21).
Water was found to be a poor solvent for this cross-coupling
reaction (Table 2, entry 20). When the reaction was carried out
in the presence of Cu(OAc)2 and organic bases (NEt3 and pyri-
dine), the desired product was obtained in 75 and 80% yields,
respectively (Table 2, entries 19 and 22). When the reaction
was conducted in atmospheric oxygen (in an open flask),
a 78% yield was observed (Table 2, entry 23).
Preliminary studies to screen the catalytic system were car-
ried out by using the reaction of phenylboronic acid with 7-
aminoflavone (Table 2). All reactions were conducted under an
oxygen atmosphere (by using a balloon) at room temperature.
In the absence of a catalyst, with only MCIP-1 and under an
inert atmosphere (absence of oxygen), no product was ob-
tained (Table 2, entries 1, 2 and 24). These results clearly high-
light the specific role of the copper catalyst in the Chan–Lam
cross-coupling N-arylation reaction. When the reactions were
conducted in the presence of other common CuII sources, such
as Cu(OAc)2, CuSO4·5H2O and CuCl2, the desired product was
obtained in 68, 17 and 32% yields, respectively (Table 2, en-
tries 3–5). When CuI sources, such as CuCl and CuI, were used
as catalysts, only trace amounts of the coupled product were
observed (Table 2, entries 6 and 7). Our interest in heterogene-
ous solid catalysts, to increase reactivity and reusability, pro-
moted us to use Cu/MCIP-1 in CH2Cl2, with K2CO3 as a base,
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drawing and electron-donating p- and m- substitu-
ents, providing the corresponding N-arylated fla-
vones in good to excellent yields. Interestingly, halo-
gen-substituted arylboronic acids were also tolerated
in the N-arylation reaction, affording compounds 3 f
and 3g in 80 and 78% yields.
In a further set of experiments, we have investigat-
ed the scope and generality of this method, with re-
spect to 6-aminoflavone (1b). As depicted in Table 4,
compound 1b was easily coupled with arylboronic
acids bearing both electron-donating and electron-
withdrawing substituents. Arylboronic acids with
electron-withdrawing substituents gave a somewhat
lower amount of product than those with electron-
donating groups. It is pertinent to note that the pres-
ence of halogen substituents, as in 3 f, 3g, 4 f and
4g, provides a handle for further structural diversifi-
cations using this metal-catalysed cross-coupling re-
action.
Table 2. Optimisation studies for N-arylation of 7-aminoflavone.[a]
Entry
Catalyst
Base
Solvent
Time [h]
Yield [%][b]
1
2
–
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
K3PO4
NEt3
pyridine
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
pyridine
pyridine
NEt3
NEt3
NEt3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
16
nil
nil
68
17
32
trace
trace
70
MCIP-1
3[c]
4[c]
5[c]
6[c]
7[c]
8
Cu(OAc)2
CuSO4·5H2O
CuCl2
CuCl
CuI
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
Cu(OAc)2
Cu/MCIP-1
Cu/MCIP-1
Cu(OAc)2
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
Cu/MCIP-1
9
10
11
64
65
DCE
CH2Cl2
CH2Cl2
MeOH
MeCN
DMF
DMSO
toluene
DCE
DCE
water
DCE
DCE
DCE
88 (89.5)[h]
12
13
14
15
16
17
18
19[c]
20
21
22[c]
23[d]
24[e]
25
26[f]
27[g]
90 (91.9)[h]
74
62
43
41
47
91 (93.8)[h]
75
25
93 (94.8)[h]
80
The scope of this protocol was further extended to
the coupling reaction of substituted arylboronic acids
with 8-aminoquinoline (1c) to give the correspond-
ing products in good to excellent yield; the results
are summarized in Table 5. Compound 1c was cou-
pled readily with electronically diverse boronic acids.
Interestingly, all the examined substrates underwent
clean conversion to the desired N-arylated aminoqui-
nolines, the only noticeable difference was in the re-
action time. Substituting both electron-donating and
electron-withdrawing groups at the p- and m- posi-
tions gave very good yield. However, o-substituted
arylboronic acid gave a lower yield of product owing
78
nil
DCE
DCE
DCE
DCE
14, 12, 10, 8
12
12
91, 91, 83, 67
91, 91, 76, 49
91, 69, 26
NEt3
NEt3
[a] Reaction conditions: 7-Aminoflavone (0.5 mmol), phenylboronic acid (0.6 mmol),
catalyst (50 mg), solvent (2 mL), base (100 mol%) O2 balloon, room temperature (RT);
[b] Isolated yield based on 7-aminoflavone; [c] 10 mol% of catalyst; [d] Atmospheric
oxygen; [e] N2 atmosphere; [f] Yield of the reaction carried out with 50, 40, 30, 20 mg
of Cu/MCIP-1, respectively; [g] Yield of the reaction carried out with 100, 50, 0 mol%
of base, respectively; [h] Yield obtained by HPLC analysis.
The influence of other experimental parameters, such as re-
action time, amount of catalyst and base, were also optimized.
Increasing the reaction time from 8 to 12 h increased the over-
all yield from 67 to 91% (Table 2, entry 25). The yield of the de-
sired product increased rapidly with an increase in the amount
of the catalyst. On increasing the amount of catalyst to 40 mg,
the product was obtained in excellent yield, but fur-
to steric hindrance.
Based on the above results and previous reports,[20d,21a]
a plausible mechanistic pathway for the present cross-coupling
N-arylation reaction, involving a CuI/CuIII cycle, is depicted in
Scheme 2. The first step involves the coordination of Cu/MCIP-
1 to amine 1 to form a CuII complex, A. The second step in-
ther addition of catalyst had no positive effect on the
overall yield of product (Table 2, entry 26). Table 2,
Table 3. N-Arylation of 7-aminoflavone with various arylboronic acids.[a]
entry 27, shows that the concentration of base plays
an important role in this heterogeneous copper-cata-
lysed Chan–Lam cross-coupling reaction. In the ab-
sence of a base, only 26% yield was obtained after
12 h, and only 69% yield was observed when
50 mol% of base was added. These observations
show that the optimum conditions for this reaction
are the use of Cu/MCIP-1 as a catalyst, in DCE under
an O2 atmosphere (balloon), at room temperature for
12 h.
Entry 7-Aminoflavone (1a) Arylboronic acid (2a–2g) Product (3) Yield [%] TON[b]
1
2
3
4
5
6
7
1a
1a
1a
1a
1a
1a
1a
C6H5B(OH)2 (2a)
4-C2H5-C6H4B(OH)2 (2b)
4-OCH3-C6H4B(OH)2 (2c)
3a
3b
3c
91
93
90
87
89
80
78
54
55
53
51
53
47
46
3-OCH3-C6H4B(OH)2 (2d) 3d
Motivated by these results, we explored the scope
of the cross-coupling reaction of 7-aminoflavone (1a)
with various arylboronic acids (2 a–g). All of the aryla-
tion reactions proceeded cleanly in excellent yields.
As depicted in Table 3, compound 1a was coupled
easily with arylboronic acids bearing electron-with-
3-CH3-C6H4B(OH)2 (2e)
4-Cl-C6H4B(OH)2 (2 f)
4-F-C6H4B(OH)2 (2g)
3e
3 f
3g
[a] Reaction conditions: 7-Aminoflavone (0.5 mmol), boronic acid (0.6 mmol), Cu/
MCIP-1 (40 mg), NEt3 (100 mol%), DCE (2 mL), O2 balloon, RT; Yield based on 7-amino-
flavone. [b] TON=turnover number.
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Table 4. N-Arylation of 6-aminoflavone with various arylboronic acids.[a]
Entry 6-Aminoflavone Arylboronic acid
Products Yield
TON[b]
(1b)
(2a–2g)
(4)
[%]
1
2
3
4
5
6
7
1b
1b
1b
1b
1b
1b
1b
2a
2b
2c
2d
2e
2 f
4a
4b
4c
4d
4e
4 f
93
90
91
89
90
81
77
55
53
54
53
53
48
45
2g
4g
[a] Reaction conditions: 6-Aminoflavone (0.5 mmol), boronic acid
(0.6 mmol) Cu/MCIP-1 (40 mg), NEt3 (100 mol%), DCE (2 mL), O2 balloon,
RT; Yield based on 6-aminoflavone. [b] TON=turnover number.
Table 5. N-Arylation of 8-aminoquinoline with various arylboronic acids.[a]
Entry 8-Aminoquinoline Arylboronic acid (2a– Products Yield TON[b]
(1c)
2j)
(5)
[%]
1
2
3
4
5
6
7
8
9
10
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
2a
2b
2c
2d
2e
2 f
5a
5b
5c
5d
5e
5 f
94
93
90
88
90
84
80
78
76
58
56
55
53
52
53
50
47
46
45
34
2g
5g
3-CN-C6H4B(OH)2 (2h) 5h
3-NO2-C6H4B(OH)2 (2i) 5i
2-Cl-5-OCH3-
5j
C6H4B(OH)2 (2j)
[a] Reaction conditions: 8-Aminoquinoline (0.5 mmol), boronic acid
(0.6 mmol), Cu/MCIP-1 (40 mg), NEt3 (100 mol%), DCE (2 mL), O2 balloon,
RT; Yield based on 8-aminoquinoline. [b] TON=turnover number.
Scheme 2. Plausible mechanistic pathway for Chan–Lam N-arylations.
volves transmetalation of the arylboronic acid, 2, with complex
A, resulting in an arylated CuII complex, B. Complex B then un-
dergoes oxidation to form a CuIII species, C, which undergoes
reductive elimination to form the CuI complex, D, and the N-
arylated products. Subsequently, oxidative addition of 1 and 2
to the CuI complex, D, generates the CuIII species, C, thereby
propagating the CuI/CuIII cycle.
recovered Cu/MCIP-1 was washed three times with CH2Cl2, and
activated under vacuum at room temperature for 1 h. Only
a marginal decrease in the activity of the catalyst was observed
after four cycles.
To verify whether the catalyst is truly heterogeneous, or
whether some metal-leached copper species is present in the
filtrate, Sheldon’s test[26] was performed. The reaction was car-
ried out under the optimized conditions and the Cu/MCIP-
1 catalyst was filtered from the reaction mixture at 67% yield
of desired N-arylation product formation (Table 6). After remov-
al of the Cu/MCIP-1 catalyst, the filtrate was stirred for a further
four hours and no further increase in yield was observed. The
absence of metal leaching was also confirmed by AAS analyses
As recyclability is important for industrial applications, the
reuse performance of Cu/MCIP-1 was also investigated. In this
context, the reusability of Cu/MCIP-1 was investigated in the
Chan–Lam cross-coupling reaction under the optimized condi-
tions, as given in Figure 12. After completion of the reaction,
the products were extracted with CH2Cl2, dried with anhydrous
sodium sulfate, and concentrated under reduced pressure. The
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Conclusion
We have developed two new imine-functionalised MCIPs from
relatively cheap starting materials and industrially important
building blocks by Schiff-base chemistry. This copper-loaded
MCIP-1 material showed excellent catalytic activity in Chan–
Lam cross-coupling N-arylation under mild reaction conditions.
In all cases, removal of the catalyst consists of a simple filtra-
tion. The catalyst is highly stable, shows no metal leaching and
can be reused without loss of catalytic activity. To the best of
our knowledge, the CÀN bond of biologically active flavones
was reported for the first time in a solid catalyst system. The
observed results will provide further motivation for design and
catalytic applications of this novel class of materials. Further
studies of the applications of the MCIP-2 material are currently
underway.
Figure 12. Reusability of Cu/MCIP-1 catalyst.
Experimental Section
Synthesis of MCIP-1
Table 6. Sheldon test.
2,4,6-Tris(p-formylphenoxy)-1,3,5-triazine (TRIPOD) was prepared
according to the published procedure.[27] A round-bottomed flask
fitted with a condenser was charged with TRIPOD (2 mmol) and p-
phenylenediamine (3 mmol) in THF and mesitylene (1:1, 30 mL), at
1208C for 72 h. After the formation of a solid, the reaction mixture
was filtered and the solid washed with methanol, acetone and
CH2Cl2 (each solvent 100 mL) to remove unreacted aldehyde and
diamine. Finally, the product was dried under vacuum to obtain
the desired solvent-free material with 85% yield. Elemental analysis
calcd (%) for C33H24N6O3: C 71.73, H 4.38, N 15.20; found C 69.95, H
4.88, N 13.94.
Catalyst
Yield [%]
8, then 4 h
8 h
67
Reused catalyst
91
Cu/MCIP-1
67
Reaction conditions: 8-Aminoquinoline (0.5 mmol), boronic acid
(0.6 mmol), Cu/MCIP-1 (40 mg), NEt3 (100 mol%), DCE (2 mL), O2 balloon,
RT; yield based on 8-aminoquinoline.
and ICP-AES of the filtrate from the reaction mixture, and also
of the filtrate from a stirred solution of Cu/MCIP-1 in DCE,
under the same reaction conditions. This result was also fur-
ther confirmed by SEM-EDX analysis. The SEM-EDX results sug-
gested ꢀ2.53 and ꢀ2.50% of copper metal was present in
fresh and reused Cu/MCIP-1, respectively (see the Supporting
Information, Figures S2, S3 and Tables S3, S4). These results
demonstrate clearly that Cu/MCIP-1 is truly heterogeneous in
nature.
Synthesis of catalyst (Cu/MCIP-1)
In a typical experiment, a mixture of copper acetate (40 mg) in
CH2Cl2 and MCIP-1 material (500 mg) was stirred at room tempera-
ture for 48 h. After the formation of a greenish-brown solid, the re-
action mixture was filtered and the solid was washed with metha-
nol, acetone and CH2Cl2 to remove any unreacted copper acetate.
The solid was dried under vacuum to obtain the designed solvent-
free catalyst. Powder XRD, EDX and AAS, ICP-AES and X-ray photo-
electron spectroscopy (XPS) analyses of the catalyst suggested the
presence of CuII metal. The stability of the catalyst was confirmed
by TGA. The Cu/MCIP-1 material was dissolved in H2SO4, diluted
and analysed with AAS. The results show that copper content in
Cu/MCIP-1 is 2.58 mmolgÀ1. After the fourth cycle, the copper con-
tent in Cu-MCIP-1 (dissolved in H2SO4) was found to be
To investigate whether any metal leaching did occur, the fol-
lowing control experiment was also performed. Cu/MCIP-
1
(0.040 g) was added to a mixture of 7-aminoflavone
(0.5 mmol), phenylboronic acid (0.6 mmol) and NEt3
(100 mol%), in DCE (2 mL), and the mixture was stirred at
room temperature for 12 h. After completion of the reaction,
the reaction mixture was filtered. The filtrate, and reused Cu/
MCIP-1 (dissolved in H2SO4), were analysed by AAS and ICP-
AES. The results of these analyses showed that the copper con-
centration in the filtrate was below the detectable limit. In the
reused Cu-MCIP-1 (dissolved in H2SO4), the copper concentra-
tion was found to be 2.54 mmolgÀ1 from AAS analysis and
2.59% from ICP-AES analysis. These results clearly show that
that no leaching of copper takes place from the solid to the
liquid phase. These results further prove that catalyst is hetero-
geneous in nature.
2.54 mmolgÀ1
.
Cu/MCIP-1-catalysed Chan–Lam cross-coupling N-arylation
In a typical reaction, a mixture of Cu/MCIP-1 (40 mg), amines
(0.5 mmol) and arylboronic acids (0.6 mmol) was added to 2 mL of
DCE under an oxygen atmosphere (balloon), at room temperature
for 16 h. The progress of the reaction was monitored by TLC analy-
sis. After completion of the reaction, the reaction mixture was
treated with CH2Cl2 (10 mL), the catalyst was removed by filtration
and the filtrate was extracted with distilled water. The organic
layer was then dried over anhydrous sodium sulfate. After the or-
ganic solvent was evaporated under vacuum, the residues were
purified by column chromatography silica gel (60–120 mesh), af-
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Keywords: cross-coupling · copper · covalent imine polymers ·
heterogeneous catalysts · mesoporous materials · Schiff bases
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Received: February 26, 2014
Revised: April 24, 2014
Published online on && &&, 0000
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FULL PAPER
&
Covalent Imine Polymers
P. Puthiaraj, K. Pitchumani*
&& – &&
Triazine-Based Mesoporous Covalent
Imine Polymers as Solid Supports for
Copper-Mediated Chan–Lam Cross-
Coupling N-Arylation Reactions
Immobilising Copper: A novel mesopo-
rous covalent imine polymeric (MCIP)
material, involving simple Schiff-base
chemistry, is reported. This highly func-
tionalised nitrogen-rich material acts as
a good support for immobilising CuII
ions, exhibiting excellent catalytic activi-
ty in promoting the Chan–Lam cross-
coupling reaction between biologically
active amines and arylboronic acids (see
scheme).
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These are not the final page numbers! ÞÞ