Barium chloride dispersed on silica gel nanoparticles: An efficient catalyst for the preparation of 2,4,6-triarylpyridines under solvent-free conditions

Article abstract of DOI:10.3184/174751911X13052141528930

BaCl₂ dispersed on a nano-structural type of silica gel (BaCl₂-nano SiO₂) was found to be an effective catalyst for the rapid and high yielding preparation of substituted 2,4,6-triarylpyridine frameworks by the reaction of various aceto-phenones, benzaldehydes and ammonium acetate. The prepared catalyst was characterised by X-ray diffraction and scanning electron microscopy analysis.

Full text of DOI:10.3184/174751911X13052141528930

294 RESEARCH PAPER
MAY, 294–297
JOURNAL OF CHEMICAL RESEARCH 2011
Barium chloride dispersed on silica gel nanoparticles: an efficient catalyst
for the preparation of 2,4,6-triarylpyridines under solvent-free conditions
Mohammad Reza Mohammad Shafiee* and Raheleh Moloudi
Faculty of Sciences, Islamic Azad University –Najafabad Branch, PO Box: 517, Najafabad, Esfahan, Iran
BaCl2 dispersed on a nano-structural type of silica gel (BaCl2-nano SiO2) was found to be an effective catalyst for the
rapid and high yielding preparation of substituted 2,4,6-triarylpyridine frameworks by the reaction of various aceto-
phenones, benzaldehydes and ammonium acetate. The prepared catalyst was characterised by X-ray diffraction and
scanning electron microscopy analysis.
Keywords: BaCl2-nano SiO2, nano SiO2, barium chloride, 2,4,6-triaryl pyridine, Krohnke pyridines
Compounds containing pyridine rings are of considerable
interest for the synthesis of pharmacological and biologically
active materials. For example, these structures show different
activities such as having anaesthetic, antimalarial, antioxidant,
anticonvulsant, antibacterial and antiparasitic properties.1–3
Therefore, preparation of pyridine derivatives has attracted
considerable attention in recent years.
Despite their importance from a pharmacological and syn-
thetic point of view, comparatively few methods for the prepa-
ration of 2,4,6-triarylpyridines (commonly named as Krohnke
pyridines) have been reported in the literature.4–9 New amongst
these methods is the cyclo-condensation reaction of acetophe-
nones, benzaldehydes and NH4OAc using conventional heat-
ing in the presence of Brønsted and Lewis acid catalysts.10–13
The overall aim of this study was to develop and validate an
efficient protocol for the synthesis and easy purification of
2,4,6-triarylpyridines from the cyclo-condensation reaction of
acetophenones, benzaldehydes and NH4OAc in the presence
of BaCl2-nano SiO2 as an efficient catalyst (Scheme 1).
barium chloride dispersed on silica gel nanoparticles (BaCl2-
nano SiO2). Based on the SEM observation, the BaCl2 particles
dispersed on nano-silica contain irregular shapes with a wide
size distribution.
Preparation of 2,4,6-triaryl pyridines
Initially, we found that catalyst-free and solvent-free reactions
did not yield a product when 4-bromoacetophenone was heated
with 4-chlorobenzaldehyde and ammonium acetate at 120 °C.
Our investigations show that the use of a catalyst is unavoid-
able for this transformation.
When silica gel nanoparticles (particle size 29–43 nm) are
mixed with 10% by weight of hydrated barium chloride
(BaC12.2H2O) dissolved in water, followed by evaporation at
80 °C under high vacuum (0.1 Torr) for 1 h, a dry white powder
is obtained. This powder is an effective catalyst for the
preparation of 2,4,6-triarylpyridine derivatives.
To establish of the most appropriate reaction conditions and
to evaluate the catalytic productivity of BaCl2-nano SiO2 as a
catalyst, firstly a model study was executed on the synthesis of
2,6-bis(4-bromophenyl)-4-(4-chlorophenyl)pyridine (Table 1,
Scheme 2).
Among the solvents tested such as ethanol, n-hexane and
dichloromethane and a solvent-free system, the condensation
of acetophenone, benzaldehyde and ammonium acetate is
more facile and proceeds in the highest yield, under solvent-
free conditions (Table 1, entries 1–4).
Results and discussion
The crystallinity of pure BaCl2-nano SiO2 was examined by
XRD studies. The XRD pattern of BaCl2-nano SiO2 is shown
in Fig. 1. As shown in Fig. 1, the actual phases were silicon
oxide (SiO2) (tetragonal) and BaCl2 (hexagonal). The powder
XRD measurement of BaCl2-nano SiO2 exhibited a diffraction
pattern characteristic of the SiO2 type tetragonal nanopowder
structure with pronounced 22.06, 31.52, 36.18, 38.74, 44.91,
47.12, 48.68, 57.18, 60.41, 62.06, 65.13, 66.98, 68.67, 69.83,
72.79, 74.01, 77.35 and 78.14 peaks (Fig. 1). The peaks at
22.06, 23.09, 29.38, 32.08, 38.74, 39.29, 44.91, 55.94 and
57.18 are believed to arise from the phase of BaCl2 (hexagonal)
(Fig. 1).
Next, the effect of temperature and the amount of catalyst on
the rate of the reaction was investigated (Table 1, entries 4–10).
Finally, we achieved an optimised set of reaction conditions
using 0.08 g of BaCl2-nano SiO2 as the catalyst and 120 °C.
The results are summarised in Table 1.
We then investigated the reaction scope of this catalytic
system and its tolerance of functional groups in the case of
other acetophenone and benzaldehyde derivatives. As shown
The dispersal state of the BaCl2-nano silica was character-
ised by SEM. Figure 2 shows the SEM micrographs of the
Scheme 1 Preparation of 2,4,6-triarylpyridine derivatives.
* Correspondent. E-mail: mohammadreza.mohammadshafiee@
gmail.com

JOURNAL OF CHEMICAL RESEARCH 2011 295
Fig. 1 XRD pattern of BaCl2-nano SiO2.
Table 1 Optimisation of the reaction conditions in the prepara-
tion of 2,6-bis(4-bromophenyl)-4-(4-chlorophenyl)pyridine
Entry Catalyst /g T /°C)
Solvent
CH2Cl2
Time /min Yield /%a
1
2
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.05
0.03
0.01
Reflux
150
150
300
40
85
73
Reflux n-hexane
3
Reflux
120
100
80
Ethanol
84
4
–
–
–
–
–
–
–
91
5
60
87
6
90
85
7
r.t.
480
180
150
210
trace
80
8
9
10
120
120
120
74
62
aIsolated yield.
in Table 2, the optimised reaction conditions were applicable
to various substrates. Whether using various acetophenones or
various benzaldehydes, BaCl2-nano SiO2 efficiently promoted
the reaction with good to excellent yields. The substituent on
the aromatic ring had no noticeable effect on the reaction as
all products were obtained in high yields with short reaction
times.
Conclusion
In conclusion, we have presented a highly efficient and
powerful method for the preparation of 2,4,6-triarylpyridines
catalysed by BaCl2-nano SiO2. The present protocol features
simple operations, short reaction time, environmental friendli-
ness and good yields.
Fig. 2 SEM micrographs of barium chloride dispersed on
silica gel nanoparticles (BaCl2-nano SiO2).
Scheme 2 Preparation of 2,6-bis(4-bromophenyl)-4-(4-chlorophenyl)pyridine using BaCl2-nano SiO2 as catalyst under
solvent-free conditions.

296 JOURNAL OF CHEMICAL RESEARCH 2011
Table 2 Preparation of 2,4,6-triarylpyridine derivatives using BaCl2-nano SiO2
Entry
Acethophenone
Aldehyde
Time /min
Yield /%a
83
m.p. /°C [lit. m.p.]ref
103–105 [103–105]12
1
60
2
3
40
40
91
89
88
87
90
88
86
81
85
94
91
70
166–168
146–148
4
45
149–150
5
110
60
226–228
6
125–127 [125–127]9
202–204 [201–203]11
260–262 [264–265]13
102–104 [100–103]9
157–159 [155–157]9
112–114 [115–116]9
146–148 [143–144]9
199–201 [197]10
7
43
8
65
9
90
10
11
12
95
15
20
13
120
aIsolated yield.
Preparation of silica nanoparticles: Silica nanoparticles were
prepared by the hydrolysis of tetraethyl orthosilicate (TEOS) with
aqueous ethanol catalysed by oxalic acid. Typically, 50 mL of TEOS
and 10 mL oxalic acid (35 w%) were added to a stirred mixture of
50 mL of aqueous ethanol (50%) respectively. The mixture was stirred
at room temperature until a gel was formed and this was subsequently
dried by stirring overnight at 60 °C and 24h at 120 °C to remove the
excess solvents, as well as some of the water, from the pores. The dry
mixture was ground in a mortar and passed through standard sieves.
Finally the xerogel was heated from room temperature to 1400 °C at
a rate of 4 °C/min in an argon flow. The temperature was kept at
1400 °C for 1h to remove organic contaminants. Xerogel particles
29–43 nm in size were used in the next preparation procedure.
Experimental
All reagents were purchased from Merck and Aldrich and used
without further purification. All yields refer to isolated products after
purification. The NMR spectra were recorded on a Bruker Avance
DPX 300 and 400 MHz instruments. The spectra were measured in
DMSO-d6 relative to TMS (0.00 ppm). IR spectra were recorded on
a Perkin-Elmer 781 spectrophotometer. Elemental analysis was per-
formed on a Heraeus CHN–O-Rapid analyser. Melting points were
determined in open capillaries with a BUCHI 510 melting point
apparatus. TLC was performed on silica gel polygram SIL G/UV
254 plates. The powder X-ray diffraction patterns were measured
with Bruker D8 Advance, Bruker, AXS, diffractometer using CuKα
irradiation. Scanning electron micrographs were taken on a Philips
(XL30 model).

JOURNAL OF CHEMICAL RESEARCH 2011 297
Barium chloride dispersed on silica gel (BaCl2-nano SiO2): The
actual procedure for the preparation of BaCl2-nano SiO2 is quite simi-
lar to the procedure for the preparation of SiO2-FeCl3 that was reported
by Tal et al.14 Typically, in a 250 mL flask, barium chloride dihydrate
(BaCl2.2H2O) (1 g) was dissolved in water (50 mL) and silica gel
nanoparticles (10 g) were added to this mixture which was thenvigor-
ously stirred under rotary evaporation until the water had completely
evaporated. This powder was kept in an oven at 100 °C for 1h to give
the active catalyst.
1032, 1006, 981, 818. Found: C, 58.27; H, 3.49; N, 2.86; C24H17Br2NO
requires C, 58.21; H, 3.46; N, 2.83%.
2,6-Bis(4-bromophenyl)-4-(2,4-dichlorophenyl)pyridine (Table 2,
entry 5): 1H NMR (400 MHz, DMSO-d6): δ = 7.59–7.87 (m, 7H), 8.06
(s, 2H), 8.22 (d, J = 8.0 Hz, 4H) ppm; 13C NMR (100 MHz, DMSO-
d6): δ = 120.1, 123.6, 128.3, 129.4, 129.9, 132.3, 132.8, 133.3, 134.7,
136.9, 137.8, 148.3, 155.3 ppm; IR (KBr, cm−1): 1601, 1542, 1478,
1417, 1371, 1259, 1178, 1106, 1070, 1007, 816. Found: C, 51.76;
H, 2.52; N, 2.65 C23H13Br2Cl2N requires C, 51.72; H, 2.45; N, 2.62%.
Typical procedure
We are grateful to the Islamic Azad University –Najafabad
Branch Research Council for the partial support of this
research.
To a mixture of benzaldehyde (1 mmol), 4-bromoacetophenone
(2 mmol) and ammonium acetate (1.3 mmol) was added BaCl2-nano
SiO2 (0.08 g) and the mixture was heated at 120 oC in an oil bath for
the appropriate time (Table 2). The progress of the reaction was mon-
itored by TLC. After completion of the reaction, the mass was cooled
Received 26 February 2011; accepted 17 April 2011
Paper 1100597 doi: 10.3184/174751911X13052141528930
Published online: 1 June 2011
o
to 25 C and the mixture was dissolved in CH2Cl2. The catalyst was
removed by simple filtration. The solvent was then evaporated off and
the solid product was purified by recrystallisation from ethanol.
2,6-bis(4-bromophenyl)-4-(4-chlorophenyl)pyridine (Table 2, entry
2): 1H NMR (300 MHz, DMSO-d6): δ = 7.53 (d, J = 8.5 Hz, 2H), 7.79
(d, J = 8.7 Hz, 4H), 7.94 (d, J = 8.5 Hz, 4H), 7.98 (s, 2H), 8.11 (d, J =
8.6 Hz, 2H) ppm; 13C NMR (75 MHz, DMSO-d6): δ = 123.3, 128.3,
129.8, 131.5, 131.6, 132.7, 134.4, 136.1, 137.2, 143.9, 189.1 ppm; IR
(KBr, cm−1): 1655, 1593, 1487, 1402, 1328, 1215, 1096, 1032, 1006,
982, 814. Found: C, 55.33; H, 2.85; N, 2.84 C23H14Br2ClN requires C,
55.29; H, 2.82; N, 2.80%.
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