PEG-400 catalyzed reaction for the synthesis of 2, 4, 6-Triarylpyridines and crystal structure of 2,4,6-tris(4'-chlorophenyl)pyridine

Article abstract of DOI:10.2174/157017810790796228

An efficient and rapid procedure for synthesizing triarylpyridine compounds under mild reaction conditions has been described. Meanwhile, the crystal structure of 2,4,6-tris(4'-chlorophenyl)pyridine was obtained and determined by X-ray single-crystal diffraction. The procedure is operationally simple, giving good to high product yields.

Full text of DOI:10.2174/157017810790796228

172
Letters in Organic Chemistry, 2010, 7, 172-177
PEG-400 Catalyzed Reaction for the Synthesis of 2, 4, 6-Triarylpyridines
and Crystal Structure of 2,4,6-tris(4’-chlorophenyl)pyridine
Qingpeng He*, Jianyong Wang and Ruokun Feng
Department of Chemistry & Chemical Engineering, Liaocheng University, Liaocheng, 252059, P. R. China
Received July 24, 2009: Revised December 25, 2009: Accepted January 01, 2010
Abstract: An efficient and rapid procedure for synthesizing triarylpyridine compounds under mild reaction conditions has
been described. Meanwhile, the crystal structure of 2,4,6-tris(4’-chlorophenyl)pyridine was obtained and determined by
X-ray single-crystal diffraction. The procedure is operationally simple, giving good to high product yields.
Keyword: 2, 4, 6-Triarylpyridines, phase transfer catalyst, crystal structure.
2,4,6-Triarylpyridines are prominent synthons in
supramolecular chemistry, with their ꢀ-stacking ability along
with directional ꢀ-bonding capacity. In particular, they also
are important because of their optical properties [1]. In
addition, the excellent thermal stabilities of these pyridines
have instigated a growing interest for their use as monomeric
building blocks in thin films and organometallic polymers
[2].
400 under microwave irradiation and solvent-free conditions.
The experiment results are summarized in Scheme 1 and
Table 1 [11].
Under microwave irradiation, the reaction of an aldehyde
with an aromatic ketone in the presence of ammonium
acetate and PEG-400 completed within 5-7 min and yielded
3a–3p in 83–95% yields (Scheme 1). While for the formation
of compound 3a, in microwave irradiation heating mode in
the absence of the PEG-400, the reaction time is 8 min and
the yield is only 78%, which indicates this reaction can be
promoted by the PEG-400.
Recent studies have highlighted the biological activity of
triarylpyridines, providing impetus for further studies in
utilizing this scaffold in new therapeutic drug classes [3].
Since Kröhnke original report on the synthesis of 2, 4, 6-
triarylpyridines [4], there has been a plethora of research
targeting their syntheses [5-9]. In general, conventional
methods used in the synthesis of substituted pyridines use
volatile organic solvents and display only moderate to low
yields. Although great success has been obtained, many of
these processes suffer from drawbacks such as drastic
reaction conditions, long reaction time, low product yields,
tedious work-up procedures, the use of toxic metal salts as
catalysts, and relatively expensive reagents. Hence, the
search for the better method, especially the readily available
and green catalysts, is still being actively pursued.
As seen from Table 1, the various aromatic aldehydes
and acetophenone (Table 1, entries 1, 5, 9, 13) were
converted to the corresponding triarylpyridines in excellent
yields under the solvent-free conditions. The results clearly
show that a substituent on the phenyl ring, whether electron-
donating or electron-withdrawing, did not show any
significant effect on the product yields, whereas the
substituted acetophenones slightly affect product yields. The
use of methyl substituted acetophenone rather increased the
yield (Table 1, entries 2), The use of Cl, Br substituted
acetophenones led to a little low yield (Table 1, entries 3,4)
under the similar conditions. Furthermore, the crystal
structure of 2,4,6-tris(4’-chlorophenyl)pyridine was obtained
and the structure of 2,4,6-tris(4-chlorophenyl)pyridine was
confirmed by X-ray diffraction crystallography. In (I) (Fig.
1), the bond lengths and angles are normal and comparable
to those observed reported in the compound [12]. The crystal
packing demonstrates no significantly short intermolecular
contacts.
Nevertheless there are no reported simple ‘one-pot’
procedures for the synthesis of triarylpyridines compounds
under phase transfer catalyst. As a non-toxic, inexpensive,
thermally stable, recoverable and biologically acceptable
reagent, polyethylene glycol (PEG) represents a very
attractive medium for organic reactions[10]. To the best of
our knowledge, the synthesis of triarylpyridines using PEG-
400 as catalyst has not so far been reported.
In conclusion, we have developed a new and simple
procedure for the one-pot synthesis of triarylpyridines
mediated by PEG-400 under solvent-free and microwave
irradiation conditions. The reaction here has the following
advantages: milder conditions, shorter reaction times,
environmentally benign and good yields. Our work showed
that substantial progress could be made in organic reactions
under solvent-free conditions, which have great potential in
reducing chemical pollution.
In this letter, we report a green and one-pot method for
the synthesis of triarylpyridines in good to excellent yields
by the condensation of various aromatic aldehydes,
substituted acetophenones with NH4OAc catalyzed by PEG-
*Address correspondence to this author at the Department of Chemistry &
Chemical Engineering, Liaocheng University, Liaocheng, 252059, P. R.
China; Tel: +86-635-8239077; Fax: +86-635-8239121;
E-mail: heqp2008@163.com
1570-1786/10 $55.00+.00
© 2010 Bentham Science Publishers Ltd.

PEG-400 Catalyzed Reaction for the Synthesis
Letters in Organic Chemistry, 2010, Vol. 7, No. 2
173
R1
PEG-400
Solvent-free/MW
R1
CHO
R2
COCH3
NH4OAc
+
+
2
N
1
R2
2
R2
R2=H, CH3, Cl,Br,OCH3
R1=H, CH3, Cl,OCH3
3
Scheme 1.
Fig. (1).
Table 1. Synthesis of 2, 4, 6- Triarylpyridines with Various Aromatic Aldehydes, Substituted Acetophenones with NH4OAc
Catalyzed by PEG-400 Under Microwave Irradiation and Solvent-Free Conditionsa
Productb
Entry
R1
R2
Time (Min)
Yield (%)c
3a
1
H-
H
5
90 [13]
N
3b
2
H-
CH3
5
94 [13]
N
H3C
CH3

174 Letters in Organic Chemistry, 2010, Vol. 7, No. 2
He et al.
(Table 1). Contd…..
Yield (%)c
Productb
Entry
R1
R2
Time (Min)
3c
3
H-
Cl
6
87 [13]
N
Cl
Cl
3d
4
H-
Br
7
83 [13]
N
Br
Br
CH3
3e
5
CH3-
H
5
91 [13]
95 [13]
89 [14]
N
CH3
6
CH3-
CH3
3f
5
N
H3C
CH3
CH3
3g
7
CH3-
Cl
6
N
Cl
Cl
CH3
3h
8
CH3-
Br
6
85
N
Br
Br

PEG-400 Catalyzed Reaction for the Synthesis
Letters in Organic Chemistry, 2010, Vol. 7, No. 2
175
(Table 1). Contd…..
Productb
Entry
R1
R2
Time (Min)
Yield (%)c
Cl
3i
9
Cl-
H
6
91 [6]
N
Cl
3j
10
Cl-
CH3
6
93
N
CH3
H3C
Cl
3k
11
12
13
Cl-
Cl
Br
H
7
7
5
86
N
Cl
Cl
Cl
3l
Cl-
85
N
Br
Br
OCH3
3m
CH3O-
92 [15]
N
OCH3
3n
14
CH3O
CH3
5
95 [15]
N
H3C
CH3

176 Letters in Organic Chemistry, 2010, Vol. 7, No. 2
He et al.
(Table 1). Contd…..
Yield (%)c
Productb
OCH3
Entry
R1
R2
Time (Min)
3o
15
CH3O
CH3O
Cl
5
87 [8]
N
Cl
Cl
OCH3
3p
16
Br
6
86
N
Br
Br
aReaction conditions: aromatic aldehydes (5 mmol), substituted acetophenones (10 mmol) and NH4OAc(5 mmol), PEG-400 (2 mmol) under microwave irradiation (375W) and
solvent-free conditions.
bAll the compounds was characterized by 1H-NMR, 13C-NMR, MS.
cIsolated yield.
1
ACKNOWLEDGEMENTS
3l: Mp 286-288˚C H NMR (200M Hz, CD3Cl) ꢀ = 8.04
(d, J=7.2, 4H), 7.80 (s, 2H), 7.65-7.52 (m, 8H); 13C NMR
(100M Hz, CD3Cl) ꢀ = 156.53, 149.29, 137.96, 137.00,
135.45, 131.88, 129.38, 128.60, 128.32, 126.94,116.83; MS
(m/e, %): 481 (M++4, 47.32), 499 (M++2, 58.49), 497 (M+,
53.12), 462 (M+-Cl, 14.73);
The work was supported by the Natural Science
Foundation of China (Grant 20671048), the Foundation of
Liaocheng University (Grant No.X071013).
3p: Mp 293-295˚C 1H NMR (200M Hz, CD3Cl) ꢀ = 8.28
(d, J=8.4, 4H), 7.96 (s, 2H), 7.80-7.16 (m, 8H), 3.98 (s, 3H);
13C NMR (100M Hz, CD3Cl) ꢀ = 162.3, 156.2, 148.6, 139.2,
130.8, 129.0, 128.5, 128.4, 127.4, 117.1, 114.4, 55.6; MS
(m/e, %): 499 (M++4, 51.23), 497 (M++2,100), 495 (M+,
48.74), 416 (M+-Br, 20.41)
DATA FOR SELECTED COMPOUNDS
1
3a; Mp 133-135˚C (lit[13]136-137˚C) H NMR (400M
Hz, CD3Cl) ꢀ = 8.13 (d, J=8.6, 4H), 7.82 (s, 2H), 7.76-7.43
(m, 11H); 13C NMR (100M Hz, CD3Cl) ꢀ =157.45, 150.15,
139.52, 139.01, 129.08, 129.01, 128.94, 128.67, 127.14,
127.10, 117.08; MS (m/e, %): 307 (M+, 100), 230 (M+-C6H5,
21.3), 77 (C6H5, 18.21).
3h: Mp 258-260˚C 1H NMR (200M Hz, CD3Cl) ꢀ = 8.05
(d, J=8.4, 4H), 7.84 (s, 2H), 7.80-7.31 (m, 8H), 2.44 (s, 3H);
13C NMR (100M Hz, CD3Cl) ꢀ = 156.28, 150.40, 139.36,
138.20, 132.33, 131.87, 129.87, 128.61, 126.94, 123.56,
116.84, 21.26; MS (m/e, %): 481(M++4, 43.22), 479
(M++2,100), 477 (M+, 48.80), 464 (M+- CH3, 20.90)
3j: Mp 193-195˚C 1H NMR (200M Hz, CD3Cl) ꢀ = 8.08
(d, J=8.2, 4H), 7.82 (s, 2H), 7.69-7.29 (m, 8H), 2.47 (s, 6H);
13C NMR (100M Hz, CD3Cl) ꢀ = 157.47, 148.79, 139.13,
137.57,136.52, 135.04, 129.40, 129.24, 128.42, 126.98,
116.20, 21.31; MS (m/e, %): 371 (M++2, 34.39), 369 (M+,
100), 334 (M+-Cl, 21.39);
3k; Mp 271-273˚C 1H NMR (400M Hz, CD3Cl) ꢀ = 8.12
(d, J=7.2, 4H), 7.81 (s, 2H), 7.68-7.46 (m, 8H); 13C NMR
(100M Hz, CD3Cl) ꢀ = 156.48, 149.35, 137.46, 137.03,
135.45, 129.40, 128.94, 128.41, 128.35, 116.81; MS (m/e,
%): 411 (M++2, 58.49), 409 (M+, 100), 374 (M+-Cl, 30.51).
The crystal data of the compound 3k: orthorhombic
system , space group Pnma, a = 1.8811(2) nm, b = 2.1663(3)
nm, c = 4.7237(8) nm, ꢀ = 90.00°, ꢁ = 90.00°, ꢂ = 90.00°, Dc
= 1.410 g.cm-3, V = 1.9249(5) nm-3, Z = 4.
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