A New Synthetic Pathway to Triphenylpyridines via Cascade Reactions Utilizing a New Iron-Organic Framework as a Recyclable Heterogeneous Catalyst

Article abstract of DOI:10.1002/ejoc.201900094

A new iron-organic framework, VNU-22 {[Fe₃(BTC)(BPDC)₂]·11.97H₂O}, constructed from BTC^3–, BPDC^2– pillars and infinite [Fe₃(CO₂)₇]_∞ rod SBU, was obtained. The VNU-22 was utilized as a heterogeneous catalyst in the synthesis of 2,4,6-triphenylpyridines via cascade reactions from acetophenones and phenylacetic acids with ammonium acetate as a nitrogen source. This transformation is new. The VNU-22 was more active in the cascade reactions than many homogeneous and heterogeneous catalysts. The framework catalyst was recovered and reutilized without an appreciable decline in its performance. To our best knowledge, this synthetic pathway to 2,4,6-triphenylpyridines was not previously reported, and would attract interests from the chemical industry.

Full text of DOI:10.1002/ejoc.201900094

DOI: 10.1002/ejoc.201900094
Full Paper
Triphenylpyridine Linkers
A New Synthetic Pathway to Triphenylpyridines via Cascade
Reactions Utilizing a New Iron-Organic Framework as a
Recyclable Heterogeneous Catalyst
[
a]
[a]
[a]
[a]
[b]
Son H. Doan, Nhu K. Q. Tran, Phuc H. Pham, Vu H. H. Nguyen, Ngoc N. Nguyen,
[
a]
[c]
[a,c]
[a]
[b]
Phuong T. M. Ha, Shuang Li, Ha V. Le,
Nam T. S. Phan*[
Nhan T. H. Le, Thach N. Tu,* and
a]
Abstract: A new iron-organic framework, VNU-22 {[Fe (BTC)- in the cascade reactions than many homogeneous and hetero-
3
3–
2–
(
BPDC) ]·11.97H O}, constructed from BTC , BPDC pillars and geneous catalysts. The framework catalyst was recovered and
2 2
infinite [Fe (CO ) ] rod SBU, was obtained. The VNU-22 was reutilized without an appreciable decline in its performance. To
3
2 7 ∞
utilized as a heterogeneous catalyst in the synthesis of 2,4,6- our best knowledge, this synthetic pathway to 2,4,6-triphenyl-
triphenylpyridines via cascade reactions from acetophenones pyridines was not previously reported, and would attract inter-
and phenylacetic acids with ammonium acetate as a nitrogen ests from the chemical industry.
source. This transformation is new. The VNU-22 was more active
Introduction
Pyridine derivatives have emerged as one of the most valuable
privileged nitrogen-containing heterocycles, widely found in
a variety of bioactive natural products, pharmaceuticals, agro-
Metal-organic frameworks (MOFs) are highly crystalline and
self-organizing reticular structures, consisting of metal nodes or
clusters, interconnected by multifunctionalized organic link-
ers. The flexibility with which the linkers and the metal-con-
taining units could be diversified has led to the formation of
[
1]
[
9]
[
2]
chemicals, chemosensors, and functional organic polymers.
,4,6-Triphenylpyridines have attracted significant interests, and
[
10]
a large variety of frameworks.
considered as highly versatile materials that find applications in
These networks have been
2
several protocols have been developed for the synthesis of
these heterocyclic structures. Han et al. previously reported a
[
11]
many fields. Exclusive properties such as large surface areas,
changeable pore size, and structural diversity have introduced
Cu(OTf) -catalyzed one-pot formation of 2,4,6-triphenyl-
2
[
12]
MOFs to catalysis community.
have been published with detailed data on characterizations,
Albeit a long series of MOFs
[
3]
pyridines from acetophenones and toluenes. Zhang et al.
demonstrated HOTf-catalyzed one-pot generation of
these heterocycles from acetophenones and benzylamines.
Rohokale et al. synthesized 2,4,6-triphenylpyridines using a
a
[
13]
their application in catalysis are yet limited.
Among numer-
[
4]
ous MOFs, iron-based frameworks have gained noticeable inter-
[
14]
ests.
However, most of these Fe-MOFs possess oxo-centered
[
5]
photoredox catalysis approach. Recently, ketoximes have
been explored in the synthesis of phenylpyridines. Yi et al.
III
[14b]
trimers of octahedral Fe SBUs,
ing Fe -based SBUs are less well-known.
and certainly, MOFs contain-
[
6]
II
[15]
In this research, we
reported a FeCl -catalyzed cyclization of benzaldehydes with
3
would like to report the synthesis of a new iron-organic frame-
work, named VNU-22. Structural analysis verified that this
framework, with the formula of [Fe (BTC)(BPDC) ]·11.97H O
[
7]
ketoximes to achieve 2,4,6-triphenylpyridines. Zhao et al. de-
veloped a FeCl -catalyzed synthesis of these structures from
3
ketoximes and N,N-dialkylanilines.[8] Although fascinating re-
3
2
2
3
–
2–
(
BTC = 1,3,5-benzenetricarboxylate; BPDC = 4,4′-biphenyldi-
carboxylate), composed of BTC and BPDC pillars and the
sults have been achieved, new pathways to access these hetero-
cycles remain to be investigated.
3
–
2–
[
Fe (CO ) ] rod SBU. Moreover, the VNU-22 demonstrated high
3
2 7 ∞
catalytic activity for a new pathway to triphenylpyridines via
cascade reactions between acetophenones and phenylacetic
acids with ammonium acetate as a nitrogen source.
[
a] Faculty of Chemical Engineering, HCMC University of Technology,
VNU-HCM,
2
68 Ly Thuong Kiet, District 10, Ho Chi Minh City, Vietnam
E-mail: ptsnam@hcmut.edu.vn
[
[
b] Center for Innovative Materials and Architectures, VNU-HCM,
Quarter 6, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Vietnam
E-mail: tnthach@inomar.edu.vn
c] Institute of Chemistry–Functional Materials, Technische Universität Berlin,
BA2,
Results and Discussion
Synthesis and Characterization of VNU-22
Hardenbergstraße 40, 10623 Berlin, Germany
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201900094.
Structural analysis indicated that VNU-22 adopt the same topol-
[
16]
ogy with VNU-20 material.
Particularly, this material crystal-
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lized in the orthorhombic space group, Pbcn (No. 60), with 28.07 %; found 28.26 %) (Figure S3). X-ray photoelectron spec-
larger unit cell parameters, a = 25.08246, b = 28.16846, and troscopy measurement of VNU-22 indicated the mixed oxid-
c = 13.73363 Å. Specifically, VNU-22 is built from the sinusoidal ation state of Fe species in the material framework due to the
[
Fe (CO ) ] iron-rod SBU, which consisted of three consecu- feature peaks in the Fe 2p
region, namely at 709.5 and
3
2 7 ∞
3/2
tively distinct octahedral iron centers and connected each other 711 eV, attributed to Fe and FeIII ions, respectively (Figure
II
[
14a,16]
through the sharing edge and vertex (Figure 1b). The sinusoidal S4).
The structural robustness of VNU-22 was further char-
2
–
2
–1
[
Fe (CO ) ] iron-rod metal cluster is finally stitched by BPDC
acterized with BET surface areas of 1029 m g (Figure S5),
3
2 7 ∞
3
–
and BTC linker (Figure 1a, Figure 1e, Figure 1f) to form VNU- which is in good agreement with the simulated surface areas
2
2
–1
2 (1 c, d). Certainly, the replacement of the H NDC by H BPDC calculated using Material Studio 7.0 software (1118 m g ).
2 2
linker directly resulted in the isoreticular expansion of VNU-22.
This leads to the formation of a rectangular channel of 8.0 × 8.6
2
Catalytic Studies
Å constructing from thick walls architecture, composed of infi-
2–
nite rings to rings π–π interaction of BPDC linkers (Figure 1c,
The VNU-22 was subsequently used as a heterogeneous catalyst
for the synthesis of 2,4,6-triphenylpyridine via cascade reactions
between acetophenone and phenylacetic acid with ammonium
acetate as a nitrogen source (Scheme 1). Initially, reaction con-
ditions were screened to improve the yield of the desired prod-
uct (Table 1). The influence of temperature on the yield of het-
erocyclic product was studied (Entries 1–5, Table 1). The reac-
tion conducted at 120 °C afforded 69 % yield (Entry 4, Table 1).
Increasing to 140 °C led to higher yield, however, it was decided
to improve the yield by adjusting other factors. One more issue
to be considered is the VNU-22 catalyst amount (Entries 6–11,
Table 1). Noted that only 10 % yield was detected for the exper-
iment without the VNU-22, thus confirming the need of utilizing
the Fe-MOF catalyst (Entry 6, Table 1). Extending the catalyst
amount provided higher yield. The solvent displayed a remark-
able impact on the transformation (Entries 12–18, Table 1), and
chlorobenzene emerged as the best option (Entry 15, Table 1).
Having these results, several nitrogen sources were explored for
the reaction (Entries 19–23, Table 1), and ammonium acetate
exhibited the best performance with 69 % yield being noticed
Figure 1f).
(
Entry 23, Table 1). Additionally, the yield was improved to 82 %
and 94 % by expanding the amount of ammonium acetate to
and 4 equivalents, respectively (Entries 24–25, Table 1).
3
Figure 1. The 3D architecture of VNU-22 is built from sinusoidal rod
3 2 7 ∞
Fe (CO ) ]
clusters (b) that are joined by BPDC2 and BTC linkers (a, e and
–
3–
[
f) to form the rhombic crystals (c) with structure highlighted by a rectangular
2
window of 8.0 × 8.6 Å (d). Atom colors: Fe, blue, light blue and orange poly-
hedra; C, black; O, red. All H atoms are omitted for clarity.
Additionally, the phase purity of VNU-22 was confirmed by
PXRD analysis with the coincidence between the as-synthesized
and simulated samples (Figure S1). Subsequently, VNU-22 was
activated via CO2 super critical protocol. Following this, the
atomistic connectivity and the structural maintenance after ac-
tivation were confirmed by PXRD (Figure S1) and Fourier trans-
form-infrared (FT-IR) analysis, which evidenced as the existence
of the bands centering at 1612 cm (vC=O stretch of coordi- reaction was subsequently performed utilizing a series of ho-
nated carboxylate) (Figure S2). The elemental microanalysis (EA) mogeneous and heterogeneous catalysts (Table 2). First, many
further confirmed the chemical formula of VNU-22 as iron and copper salts were used as the catalyst for the cascade
Scheme 1. Synthesis of triphenylpyridines via cascade reactions utilizing
VNU-22 catalyst.
In order to emphasize the superiority of the VNU-22, the
–1
[
Fe (BTC)(BPDC) ]·11.97H O (Cal: %C= 41.48; %H = 4.01; reactions between acetophenone and phenylacetic acid with
3 2 2
%
N = 0; found %C = 41.48 %H = 3.54; %N = 0.37). The thermal ammonium acetate as a nitrogen source under standard condi-
stability and structural robustness of VNU-22 were accessed by tions. The reaction afforded more than 50 % yields in the pres-
thermogravimetric analysis (TGA) and nitrogen adsorption ence of FeCl , FeCl , and Fe (SO ) (Entries 1–3, Table 2), while
2
3
2
4 3
measurement at 77 K. Correspondingly, TGA showed the ther- lower yields were detected for the case of Fe(NO ) , Fe(acac) ,
3
3
3
mal stability of up to 250 °C with less than 4.0 % weight loss and Fe(OAc) (Entries 4–6, Table 2). Moreover, it was noted that
2
from room temperature, and the Fe O residual metal oxides, copper and nickel salts exhibited low activity for the transfor-
2
3
which is in consistency with those from model structure (Cal: mation (Entries 7–9, Table 2). Moving to Fe-MOFs, higher yields
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Table 1. Screening reaction conditions.[a]
Entry
Temperature (°C)
VNU-22 [mol-%]
Solvent
Nitrogen source (equiv.)
Yield[b]
1
2
3
4
5
r.t.
80
100
120
140
5
5
5
5
5
PhCl
PhCl
PhCl
PhCl
PhCl
NH
NH
NH
NH
NH
4
4
4
4
4
OAc (1.5)
OAc (1.5)
OAc (1.5)
OAc (1.5)
OAc (1.5)
0
7
11
69
75
6
7
8
9
1
1
120
120
120
120
120
120
0
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
NH
NH
NH
NH
NH
NH
4
4
4
4
4
4
OAc (1.5)
OAc (1.5)
OAc (1.5)
OAc (1.5)
OAc (1.5)
OAc (1.5)
10
30
39
63
67
69
0.5
1.5
2.5
3.5
5
0
1
1
1
1
1
1
1
1
2
3
4
5
6
7
8
120
120
120
120
120
120
120
5
5
5
5
5
5
5
DMF
DMSO
MeNO
PhCl
DCB
NH
4
NH
4
NH
4
NH
4
NH
4
NH
4
NH
4
OAc (1.5)
OAc (1.5)
OAc (1.5)
OAc (1.5)
OAc (1.5)
OAc (1.5)
OAc (1.5)
6
13
5
69
5
0
2
nBuOH
DEG
0
19
20
21
22
23
24
25
120
120
120
120
120
120
120
5
5
5
5
5
5
5
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
NH
NH
4
4
Cl (1.5)
0
HCO
3
(1.5)
24
18
0
69
82
94
urea (1.5)
4 2 2 8
(NH ) S O (1.5)
NH
NH
NH
4
OAc (1.5)
OAc (3)
OAc (4)
4
4
[
a] Reaction conditions: Acetophenone (0.2 mmol); phenylacetic acid (0.3 mmol); solvent (0.5 mL); under oxygen; 12 h; PhCl: chlorobenzene; DMF: N,N′-
dimethylformamide; DMSO: dimethyl sulfoxide; MeNO : nitromethane; DCB: 1,2-dichlorobenzene; DEG: diethylene glycol. [b] GC yield.
2
were obtained for the transformation. The reaction utilizing
VNU-22 catalyst afforded 94 % yield (Entry 10, Table 2), while
Table 2. The one-pot synthesis of 2,4,6-triphenylpyridine utilizing different
catalysts.[
a]
9
1
1 % was also recorded for that using VNU-20 catalyst (Entry
1, Table 2). Other Fe-MOFs such as [Fe O(BDC) ] and
Yield[b]
Entry
Homogeneous catalyst
FeCl
FeCl2
Fe (SO
Fe(NO
Fe(acac)
Heterogeneous catalyst
3
3
1
2
3
4
5
6
7
8
9
3
51
51
51
48
36
48
1
[
Fe O(BPDC) ] offered lower activity (Entries 12–13, Table 2).
3 3
Cu-MOFs should not be used for this reaction (Entries 14–15,
Table 2). Additionally, several superparamagnetic nanoparticles
were tested for the reaction, and low yields of the desired prod-
uct were observed (Entries 16–20, Table 2). The fact that the
VNU-22 was more active than many homogeneous and hetero-
geneous catalysts highlighted the significant aspects of this
iron-organic framework.
To gain more information for the reaction mechanism, sev-
eral control experiments were conducted (Scheme 2). (i) The
reaction did not proceed under an argon atmosphere with no
evidence of product being detected, verifying that that oxygen
was crucial for this transformation. (ii) The reaction did not oc-
cur in the presence of ascorbic acid as antioxidant. (iii) The reac-
tion of phenylacetic acid (2) without acetophenone (1a) was
conducted under standard conditions, and 80 % conversion to
benzaldehyde (4) was recorded (Scheme 2a). (iv) The reaction
between (1a) and 2-hydroxy-2-phenylacetic acid (5) carried out
under standard conditions produced the desired product (3a)
in 82 % yield (Scheme 2b). Noted that 3a was detected in trace
quantity if the experiment was conducted under argon. (v) The
2
4 3
)
)
3 3
3
Fe(OAc)
CuI
2
Cu(OAc)2
Ni(OAc)
19
7
2
1
1
1
0
1
2
VNU-22
VNU-20
94
91
67
69
33
40
11
21
26
13
31
Fe
Fe
3
O(BDC)
O(BPDC)
3
13
3
3
14
15
16
17
Cu(BDC)
Cu (OBA)
2
2
(BPY)
Nano CuFe
Nano NiFe
Nano CoFe O
Nano Fe
Nano Fe
2
O
O
4
2
4
18
2
4
1
2
9
0
2
O
O
3
3
4
[a] Reaction conditions: Acetophenone (0.2 mmol); phenylacetic acid
0.3 mmol); NH OAc (0.8 mmol); catalyst (5 mol-%); chlorobenzene (0.5 mL);
20 °C; under oxygen; 12 h. [b] GC yield.
(
4
1
reaction between (1a) and (4) proceeded to 92 % yield of 3a (1b) and chalcone (6) afforded 3a in 88 % yield (Scheme 2d).
under standard conditions (Scheme 2c). Noted that the reaction Noted that this reaction afforded 10 % yield in the absence of
between (1a) and (4) carried out under argon offered 94 % the Fe-MOF. (vii) The reaction between (1a), (1b), and (2) pro-
yield of 3a. (vi) The reaction between 4-methylacetophenone duced 3 products (3a, 3b, and 3c) in similar yields under stan-
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Scheme 2. Control experiments.
dard conditions (Scheme 2e). These results suggested that (4), imine (C), following by the cyclization to produce 2,4,6-tri-
5), and (6) could be intermediate products in the catalytic phenyl-3,4-dihydropyridine (D). Finally, the aerobic oxidation
cycle. occurred to form the desired product (3a). Certainly, Zhang et
(
On the basis of these observations and the literature, a plau- al. previously demonstrated the generation of 3a from (B) and
sible reaction pathway was proposed (Scheme 3). Initially, the (6) in a HOTf-catalyzed one-pot synthesis of pyridine derivatives
[
4]
iron-catalyzed aerobic oxidation of phenylacetic acid (2) to from acetophenones and benzylamines.
benzaldehyde (4) proceeded via the formation of 2-hydroxy-2- As the synthesis of 2,4,6-triphenylpyridine from acetophen-
phenylacetic acid (5). Indeed, this transformation was well one and phenylacetic acid with ammonium acetate as a nitro-
[
17]
known in the literature. The standard aldol condensation be- gen source utilizing the VNU-22 catalyst was performed in
tween acetophenone (1a) and (4) then occurred to form the chlorobenzene phase, the leaching of iron species during the
corresponding chalcone (6). Simultaneously, (1a) was isomer- experiment must be investigated. Control experiments were
ized to 1-phenylethen-1-ol (A), and the reaction of (A) with subsequently conducted to clarify if the VNU-22 was a truly
ammonium acetate led to the formation of 1-phenylethen-1- heterogeneous catalyst for the transformation or not. The reac-
[
3,4]
amine (B) with water and acetic acid being released.
quently, the condensation between (B) and (6) proceeded to an oxygen atmosphere, with 1.5 equivalents of phenylacetic
generate (1E,2E)-1,3-diphenyl-N-(1-phenylvinyl)prop-2-en-1- acid and 4 equivalents of ammonium acetate, in the presence
Subse- tion was performed in chlorobenzene at 120 °C for 12 h under
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Scheme 3. Plausible reaction pathway.
of 5 mol-% VNU-22 catalyst. Upon completion of the first run, oxygen atmosphere. The presence of Fe(OAc) catalyst afforded
2
the VNU-22 catalyst was removed from the mixture. The reac- 56 % yield of the desired product (Leaching test 2, Figure 2).
tion solution was subsequently transferred to a new reactor, These data suggested that the VNU-22 was a truly heterogene-
and fresh reactants were then added to the mixture. The reactor ous catalyst for the synthesis of 2,4,6-triphenylpyridine.
was consequently heated at 120 °C for 12 h under an oxygen
As mentioned earlier, the VNU-22 was more catalytically ac-
atmosphere. Under these conditions, 14 % yield of the hetero- tive many homogeneous and heterogeneous catalysts in the
cyclic product was detected. It should be noted that the reac- synthesis of 2,4,6-triphenylpyridine from acetophenone and
tion progressed to 10 % yield in the absence of the catalyst phenylacetic acid with ammonium acetate as a nitrogen source.
(
Leaching test 1, Figure 2). In a second experiment, after the To furthermore emphasize its significance, the catalyst recovery
first catalytic run, the VNU-22 catalyst was separated, fresh rea- and reutilization was then explored. The reaction was con-
gents and 10 mol-% Fe(OAc) catalyst were added, and the re- ducted in chlorobenzene at 120 °C for 12 h under an oxygen
2
action was allowed to proceed at 120 °C for 12 h under an atmosphere, with 1.5 equivalents of phenylacetic acid and
Figure 2. Leaching experiment.
Figure 3. Catalyst reutilization studies.
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Figure 4. FT-IR spectra of the fresh (a) and recovered (b) VNU-22 catalyst.
Table 3. The synthesis of 2,4,6-triphenylpyridines utilizing the VNU-22 catalyst.[a]
Figure 5. XRD results of the fresh (a) and recovered (b) VNU-22 catalyst.
[
1
a] Reaction conditions: Acetophenone (0.2 mmol); phenylacetic acid (0.3 mmol); NH
20 °C; under oxygen; 12 h. [b] Isolated yield.
4
OAc (0.8 mmol); VNU-22 catalyst (5 mol-%); chlorobenzene (0.5 mL);
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4
5
equivalents of ammonium acetate, in the presence of atmosphere. Triphenylpyridines were generated via cascade re-
mol-% VNU-22 catalyst. Upon completion of the first run, the actions, including decarboxylation of phenylacetic acids via
3
catalyst was collected using centrifugation, washed thoroughly iron-catalyzed oxidative Csp –H bond activation, condensation,
with anhydrous DMF and chlorobenzene, and evacuated under cyclization, and oxidation. The transformation was dramatically
vacuum at room temperature for 5 h on a Shlenk line. Further adjusted by the solvent, in which chlorobenzene emerged as
catalytic run was subsequently performed utilizing the recov- the best option. The VNU-22 was more active in the synthesis
ered VNU-22 under the same conditions. It was noted that the of 2,4,6-triphenylpyridines than many homogeneous and
VNU-22 catalyst was reutilized several times for the synthesis of heterogeneous catalysts. The framework catalyst was recovered
2,4,6-triphenylpyridine without an appreciable deterioration in and reutilized without an appreciable deterioration in its per-
its performance. Certainly, 87 % yield of 2,4,6-triphenylpyridine formance. The significance that 2,4,6-triphenylpyridines were
th
was recorded for the transformation in the 5 catalytic run un- achieved via cascade reactions using a recyclable catalyst
der standard conditions (Figure 3). Moreover, the recovered should attract interests from the chemical industry.
framework catalyst was characterized by XRD and FT-IR. The
FT-IR spectra of the recovered VNU-22 were similar to those of
the fresh one (Figure 4). Similarly, XRD results of both reutilized
and fresh catalysts revealed that the framework structure was
Experimental Section
maintained, although a slight difference was noticed (Figure 5). Preparation of the Fe-MOF VNU-22: H
BTC (0.021 g, 0.1 mmol),
3
H BPDC (0.12 g, 0.49 mmol), anhydrous FeCl (0.09 g, 0.705 mmol),
The work scope was expanded to the synthesis of 2,4,6-tri-
phenylpyridines utilizing the VNU-22 catalyst (Table 3). The re-
action was performed in chlorobenzene at 120 °C for 12 h un-
der an oxygen atmosphere, with 1.5 equivalents of phenylacetic
acid and 4 equivalents of ammonium acetate, in the presence
of 5 mol-% VNU-22 catalyst. The expected products were then
isolated by column chromatography. In the first series, aceto-
2
2
and anthraquinone (0.12 g, 0.57 mmol) were dissolved into DMF
12 mL). The mixture was then sonicated for 5 min to achieve a
transparent solution. Following this step, the reaction mixture was
distributed into glass tubes, subsequently flamed and sealed under
ambient atmosphere. These tubes were stabilized in an oven at
(
1
80 °C for 72 h, and reddish rhombic crystals of VNU-22 were
formed during the experiment. The product was consequently
phenones containing a substituent on benzene ring were util- treated with DMF (5 × 15 mL), and methanol/water (10 % water, 5 ×
ized for the reaction. Following this protocol, 2,4,6-triphenyl- 15 mL), and dry methanol (5 × 15 mL) for solvent exchange. Finally,
pyridine was obtained in 90 % yield (Entry 1, Table 3). 4-Methy- the solid was exchanged by supercrital CO (four times), and conse-
2
quently activated under vacuum to afford the corresponding frame-
lacetophenone was reactive, affording 4-phenyl-2,6-di-p-tolyl-
pyridine in 89 % yield (Entry 2, Table 3). Moving to haloaceto-
phenone, 2,6-bis(4-chlorophenyl)-4-phenylpyridine (Entry 3,
work (0.064 g, 75 % base on H BTC).
3
Catalytic Studies: To a 12-mL screw-cap vial containing chloro-
Table 3), and 2,6-bis(3-chlorophenyl)-4-phenylpyridine (Entry 4, benzene (0.5 mL) was added acetophenone (24.0 mg, 0.2 mmol),
Table 3) were generated in 88 % and 86 % yields, respectively. phenylacetic acid (40.8 mg, 0.3 mmol), NH4OAc (60.0 mg,
0
0
.8 mmol), VNU-22 catalyst (5 mol-%), and diphenyl ether (17.2 mg,
.1 mmol) as an internal standard. The catalyst amount was calcu-
2
-Chloroacetophenone proceeded more difficultly, though 2,6-
bis(2-chlorophenyl)-4-phenylpyridine (Entry 5, Table 3) was ob-
tained in 72 % yield. Similarly, 2,6-bis(4-bromophenyl)-4-phenyl-
pyridine (Entry 6, Table 3) was produced in 87 % yield for the
case of 4-bromoacetophenone. In the same way, 2,6-bis(3-
methoxyphenyl)-4-phenylpyridine (Entry 7, Table 3), and 2,6-
bis(2-methoxyphenyl)-4-phenylpyridine (Entry 8, Table 3) were
formed in 91 % and 85 % yields, respectively. 3,4-Dihydro-
lated regarding the iron/acetophenone molar ratio. The reaction
tube was back-filled with oxygen and the resulting mixture was
subsequently stirred at 120 °C for 12 h. The reaction yield monitored
by taking aliquots from the reaction mixture, and quenched with
brine. The organic components were consequently extracted into
ethyl acetate (2 mL), dried with anhydrous Na SO , and analyzed
2
4
by GC with reference to diphenyl ether. To isolate the desired prod-
naphthalen-1(2H)-one was also reactive, producing 7-phenyl- uct, after disappearance of the reactant (monitored by TLC), the
5
,6,8,9-tetrahydrodibenzo[c,h]acridine (Entry 9, Table 3) in 82 % mixture was slowly cooled to room temperature and diluted with
ethyl acetate (20 mL), washed with NaHCO solution (5 % in water,
yield. Interestingly, 4-phenyl-2,6-di(thiophen-2-yl)pyridine (En-
try 10, Table 3) was achieved in 87 % yield. In the second series,
phenylacetic acids containing a substituent on benzene ring
were used, and corresponding products were obtained in high
yields (Entries 11–14, Table 3).
3
3
× 5 mL), dried with anhydrous Na SO , and concentrated under
vacuum. The crude product was purified by column chromatogra-
phy with hexane/ethyl acetate solvent system. The product struc-
2 4
1
13
ture was confirmed by GC–MS, H NMR, and C NMR.
CCDC 1837779 (for VNU-22) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
Conclusions
A new iron-organic framework, VNU-22 [Fe (BTC)(BPDC) ]·
3
2
Acknowledgments
3–
2–
1
1.97H O, consisted of mixed-linkers of BTC , BPDC and infi-
2
nite [Fe (CO ) ] rod SBU, was synthesized and characterized by Thach N. Tu acknowledges the Naval International Cooperative
3
2 7 ∞
a variety of techniques. The VNU-22 was subsequently utilized Opportunities in Science and Technology Program through
as a recyclable heterogeneous catalyst in the synthesis of 2,4,6- Project No. N62909-16-1–2146 for VNU-22 synthesis and charac-
triphenylpyridines from acetophenones and phenylacetic acids terization (for Thach N. Tu). Catalytic studies were financially
with ammonium acetate as a nitrogen source under an oxygen supported by the Vietnam National Foundation for Science and
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Full Paper
Triphenylpyridine Linkers
Iron-based Metal-organic framework
(
VNU-22) was utilized as a recyclable
S. H. Doan, N. K. Q. Tran, P. H. Pham,
V. H. H. Nguyen, N. N. Nguyen,
P. T. M. Ha, S. Li, H. V. Le,
heterogeneous catalyst in the synthe-
sis of 2,4,6-triphenylpyridines via cas-
cade reactions.
N. T. H. Le, T. N. Tu,*
N. T. S. Phan* ...................................... 1–9
A New Synthetic Pathway to Tri-
phenylpyridines via Cascade Reac-
tions Utilizing a New Iron-Organic
Framework as a Recyclable Hetero-
geneous Catalyst
DOI: 10.1002/ejoc.201900094
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim