Highly efficient and easy synthesis of 2,4,6-triarylpyridines catalyzed by pentafluorophenylammonium triflate (PFPAT) as a new recyclable solid acid catalyst in solvent-free conditions

Article abstract of DOI:10.1016/j.cclet.2012.01.035

Pentafluorophenylammonium triflate (PFPAT) was found to be a highly efficient catalyst for the preparation of 2,4,6-triarylpyridines from the reaction of acetophenone derivatives, aromatic aldehydes and ammonium acetate. Present methodology offers several advantages, such as short reaction time, high yields, simple procedure with an easy work-up and the absence of any volatile and hazardous organic solvent. In addition, this catalytic system can act as an active, inexpensive, metal-free, recoverable and recyclable catalyst.

Full text of DOI:10.1016/j.cclet.2012.01.035

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 419–422
www.elsevier.com/locate/cclet
Highly efficient and easy synthesis of 2,4,6-triarylpyridines
catalyzed by pentafluorophenylammonium triflate (PFPAT) as a new
recyclable solid acid catalyst in solvent-free conditions
*
Naser Montazeri , Saber Mahjoob
Department of Chemistry, Faculty of Sciences, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
Received 2 November 2011
Available online 3 March 2012
Abstract
Pentafluorophenylammonium triflate (PFPAT) was found to be a highly efficient catalyst for the preparation of 2,4,6-
triarylpyridines from the reaction of acetophenone derivatives, aromatic aldehydes and ammonium acetate. Present methodology
offers several advantages, such as short reaction time, high yields, simple procedure with an easy work-up and the absence of any
volatile and hazardous organic solvent. In addition, this catalytic system can act as an active, inexpensive, metal-free, recoverable
and recyclable catalyst.
# 2012 Naser Montazeri. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Pentafluorophenylammonium triflate; 2,4,6-Triarylpyridines; Solvent-free conditions; Organocatalyst; Multi-component reaction
Multicomponent reactions (MCRs) have manifested as a powerful tool for the rapid introduction of molecular
diversity. The design and development of MCRs for the generation of heterocycles receive growing interest [1]. MCRs
contribute to the requirements of an environmentally friendly process by reducing the number of synthetic steps,
energy consumption, and waste production. Therefore, discovery for new MCRs and improving already known MCRs
are of substantial interest. One such reaction is the synthesis of 2,4,6-triarylpyridines. Pyridines play a key role in
catalyzing both biological and chemical systems. In many enzymes of living organisms there is the prosthetic pyridine
nucleotide (NADP) that is involved in various oxidation–reduction processes [2]. The pyridine ring is also ubiquitous
in agrochemicals such as fungicides, and herbicides [3]. In view of different biological and chemical applications of
pyridine derivatives, the development of suitable synthetic methodologies for their generation has been a topic of great
¨
interest in recent times. The general method for synthesis of 2,4,6-triarylpyridines (Krohnke pyridine) involves the
reaction of N-phenacylpyridinium salts with a,b-unsaturated ketones in the presence of ammonium acetate [4].
Recently, much effort has been devoted to developing more efficient methods for the synthesis of 2,4,6-
triarylpyridines, for example reaction of chalcones with ammonium acetate [5], solvent-free reaction between
acetophenones, benzaldehydes, and ammonium acetate in the presence of various catalyst, for example cyanuric
chloride [6], HClO4–SiO2 [7], Brønsted-acidic ionic liquid [8], and I2 [9]. However, many of these methods suffer
* Corresponding author.
E-mail address: montazer50@toniau.ac.ir (N. Montazeri).
1001-8417/$ – see front matter # 2012 Naser Montazeri. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2012.01.035

420
N. Montazeri, S. Mahjoob / Chinese Chemical Letters 23 (2012) 419–422
R'
O
O
CH3
PFPAT, 25 mol%
+
H
+
NH4OAc
R
R'
Solvent-free at 120 o
C
N
R
R
4a-n
Scheme 1.
from drawbacks such as expensive catalyst, long reaction time, special care in handling and storing the reagents,
undesired side products in reaction with harsh reagents, using metal oxidants, cumber some product isolation
procedure and environmental pollution. Therefore, a need still exists for further development of versatile reaction
conditions in synthesis of 2,4,6-triarylpyridine using an efficient, reusable, inexpensive, eco-friendly, green, great
selectivity and metal-free catalyst. Tanabe et al. reported the application of pentafluorophenylammonium triflate
(PFPAT) as a novel organocatalyst in organic transformation such as esterification of carboxylic acids with alcohols
[10], C-acylations of enol silyl ethers or ketene silyl (thio)acetals with acid chlorides [11], and Mukaiyama aldol and
Mannich reactions using ketene silyl acetals with ketones and oxime ethers [12]. However, to the best of our
knowledge the use of PFPATas a catalyst in the synthesis of 2,4,6-triarylpyridines has not been reported yet. Recently,
we reported our research findings on the application of PFPAT as catalyst in the synthesis of coumarins via von
pechmann condensation [13]. In continuation, herein, we report the first example of the PFPAT-catalyzed, one-pot
three-component synthesis of 2,4,6-triarylpyridines from a solvent-less reaction of acetophenones, aryl aldehydes, and
ammonium acetate in high yields (Scheme 1).
1. Experimental
1.1. Typical procedure
A mixture of an acetophenone derivative (2 mmol), aryl aldehyde (1 mmol), ammonium acetate (1.3 mmol), and
PFPAT (25 mol% based on aryl aldehyde) was heated on the oil bath at 120 8C for the indicated time. The progress of
the reaction was monitored by TLC. After completion of the reaction mixture was cooled to room temperature and
water was added. The precipitated solid was collected by filtration under suction, washed with cold water, and then
recrystallized from n-hexane to afford pure products 4a–n (Table 2) in high yields. The filtrate was evaporated under
reduced pressure and then washed with n-hexane, dried at 50 8C under vacuum for 1 h and reused in another reaction
with only slight reduction in the catalytic activity. All the products were identified by comparison of spectral data (IR
1
and H NMR), and m.p. with those reported [5a,8].
2. Results and discussion
Solvent-free conditions are especially important for providing an eco-friendly system. The number of publications
reporting solvent-free condition for the heterocyclic synthesis has increased rapidly in recent years [14]. One
advantage of solvent-free reaction, in comparison to the reaction in molecular solvent, is that the compounds formed
are often sufficiently pure to circumvent extensive purification using chromatography. Therefore, due to the increasing
demand in modern organic processes for avoiding expensive purification, we decided to investigate the efficiency of
PFPAT as catalyst in the synthesis of 2,4,6-triarylpyridines under solvent-free conditions. Initially, to optimize the
reaction conditions such as temperature, solvent and amount of catalyst (PFPAT), the reaction between acetophenone,
benzaldehyde, and ammonium acetate was selected as a model. The results are collected in Table 1. Increasing the
reaction temperature and amount of the catalyst up to 120 8C and 25 mol%, respectively under solvent-free conditions,
increased the yield of product 4a (entries 3–7), whereas further increase in both temperature and catalyst amount was
found to have an inhibitory effect on formation of the product (entries 8–11). Interestingly, in the absence of the
catalyst (entry 1) or in the presence of the catalyst at room temperature (entry 2), 4a was obtained in a very trace
amount after 12 h which indicated that the catalyst and temperature should be absolutely necessary for this reaction.

N. Montazeri, S. Mahjoob / Chinese Chemical Letters 23 (2012) 419–422
421
Table 1
Effect of PFPAT amount, temperature, and solvent on the synthesis of 2,4,6-triphenylpyridine (model reaction).a
Entry
Catalyst (mol%)
T (8C)
Solvent
Time (h)
Yield (%)b
1
None
25
20
20
20
25
25
25
30
30
30
25
25
25
25
25
120
None
None
None
None
None
None
None
None
None
None
None
EtOH
MeCN
CH2Cl2
CHCl3
Toluene
12
12
3
Trace
Trace
54
2
r.t.
3
100
4
120
3
66
5
140
2
65
6
100
3
85
7
120
2
89
8
140
2
85
9
100
3
63
10
11
12
13
14
15
16
120
2
87
140
3
85
Reflux
Reflux
Reflux
Reflux
Reflux
10
6
Trace
60
8
63
8
55
5
72
a
2 mmol acetophenone, 1 mmol benzaldehyde and 1.3 mmol ammonium acetate under different conditions.
Isolated yields.
b
On the contrary, lower catalytic activity is observed for various organic solvents such as EtOH, MeOH, MeCN,
CH2Cl2, CHCl3, and toluene under reflux condition and in the presence of 25 mol% of catalyst (Table 1, entries 12–
16).
In order to show generality and scope of this new protocol, we used various substituted acetophenones and
benzaldehydes and the results obtained are summarized in Table 2. All the reaction with substituted benzaldehydes
preceded very cleanly at optimized reaction conditions and no undesirable side-reaction were observed, although the
yields were dependent on the substituent. The results in Table 2 show that electron-withdrawing groups such as nitro,
and chloro at the phenyl ring of benzaldehyde favored the formation of product (Table 2, entries 2 and 3). In contrast,
electron-donating groups gave slightly lower yields (Table 2, entries 4–7). To check the versatility of this method, we
had also studied the various substituted acetophenones and results obtained are summarized in Table 2 (entries 8–14).
All the reaction with substituted acetophenones proceeded very cleanly and no undesirable side-reaction was
observed. Compared to other methodologies reported for the synthesis of 2,4,6-triarylpyridines via one-pot reaction,
Table 2
PFPAT catalyzed synthesis of 2,4,6-triarylpyridines 4a–n.a
Entry
R
R0
Time (h:min)
Productb
Yield [Ref]c
m.p. (8C)
1
H
H
2
2
4a
4b
4c
4d
4e
4f
89
92
91
87
88
86
84
85
87
92
88
86
93
94
130–131
192–193
123–124
127–128
122–124
100–101
193–195
103–105
178–179
199–201
186–187
155–157
175–177
143–144
2
H
4-NO2
4-Cl
3
H
2:15
2:40
2:30
2:50
3
4
H
4-Me
2-Me
4-OMe
4-OH
H
5
H
6
H
7
H
4g
4h
4i
8
4-Br
4-Me
4-Me
4-Me
4-NO2
4-OMe
4-OMe
2:45
2:30
2:10
2:30
2:40
2
9
4-Me
4-Cl
10
11
12
13
14
4j
2-Cl
4k
4l
4-OMe
4-Cl
4m
4n
4-NO2
2
a
Reaction condition: acetophenone 2 mmol, benzaldehyde 1 mmol, ammonium acetate 1.3 mmol, and PFPAT 25 mol% at 120 8C under solvent-
free conditions.
b
All products were characterized by use of IR, and 1H NMR spectral data, and comparison of their melting points with those of authentic samples.
c
Isolated yields based on aromatic aldehyde.

422
N. Montazeri, S. Mahjoob / Chinese Chemical Letters 23 (2012) 419–422
Table 3
Comparison of efficiency of various catalysts in the synthesis of 2,4,6-triphenylpyridine 4a.
Catalyst
Conditions
Time (h)
Yield (%)
Ref.
Cyanuric chloride
Solvent-free; 130 8C
Solvent-free; 120 8C
Solvent-free; 120 8C
Solvent-free; 120 8C
Solvent-free; 120 8C
4
4
3
6
2
70
80
88
56
89
[6]
HClO4–SiO2
[7]
Brønsted-acidic ionic liquid
[8]
I2
[9]
PFPAT
This work
the present methodology offers suitable conditions with respect to reaction times and yields. Some of the results are
summarized in Table 3.
The reusability of the catalyst is one of the most important benefits and makes them useful for commercial
applications, thus the recovery and reusability of PFPAT was investigated. For this purpose, the same model reaction
was again studied under optimized conditions. After the completion of the reaction, the catalyst was easily recovered
according to the procedure mentioned in experimental section and reused for a similar reaction. The catalyst could be
used at least three times with only slight reduction in the catalytic activity (89% for 1st use; 87% for 2nd use; 84% for
3rd use).
3. Conclusion
In conclusion, we have developed a new method for the one-pot three-component synthesis of 2,4,6-triarylpyridines
from aromatic aldehydes, acetophenones, and ammonium acetate using PFPAT as an efficient organocatalyst in good
to excellent yields. Simple experimental procedure, nontoxic, noncorrosive, metal-free, inexpensive solid acid
catalyst, recyclability of the catalyst with no loss in its activity, short reaction times, eco-friendly, great selectivity, and
solvent-free reaction conditions have made this approach distinctly superior over to many other protocols reported
earlier.
Acknowledgment
This research has been supported by the Islamic Azad University, Tonekabon Branch.
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