Wet 2,4,6-trichloro-1,3,5-triazine (TCT) as an efficient catalyst for the synthesis of 2,4,6-triarylpyridines under solvent-free conditions

Article abstract of DOI:10.1016/j.cclet.2010.06.028

An efficient one-pot synthesis of 2,4,6-triarylpyridines has been described. This involves the three-component reaction of aldehydes, ketones and ammonium acetate in the presence of a catalytic amount of wet 2,4,6-trichloro-1,3,5-triazine (TCT) under solvent-free condition at 130 °C.

Full text of DOI:10.1016/j.cclet.2010.06.028

Available online at www.sciencedirect.com
Chinese Chemical Letters 21 (2010) 1346–1349
www.elsevier.com/locate/cclet
Wet 2,4,6-trichloro-1,3,5-triazine (TCT) as an efficient catalyst
for the synthesis of 2,4,6-triarylpyridines under
solvent-free conditions
b
c
a
Behrooz Maleki a, , Davood Azarifar , Hojat Veisi , Seyede Fatemeh Hojati ,
*
Hafezeh Salehabadi a, Razieh Nejat Yami b
a Department of Chemistry, Sabzevaar Tarbiat Moallem University, Postal Code 397, Sabzevar, Khorasan, Iran
b Department of Chemistry, Bu-Ali Sina University, Zip Code 65178, Hamadan, Iran
c Department of Chemistry, Payame Noor University, Songhor, Kermanshah, Iran
Received 15 March 2010
Abstract
An efficient one-pot synthesis of 2,4,6-triarylpyridines has been described. This involves the three-component reaction of
aldehydes, ketones and ammonium acetate in the presence of a catalytic amount of wet 2,4,6-trichloro-1,3,5-triazine (TCT) under
solvent-free condition at 130 8C.
# 2010 Behrooz Maleki. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: 2,4,6-Triarylpyridines; 2,4,6-Trichloro-1,3,5-triazine; Aldehydes; Ketones; Ammonium acetate
Pyridines have attracted considerable attention due to their wide range biological and pharmacological actives.
Pyridines have been found wide applications in various fields such as in supramoleular chemistry [1–4], in
pharmacology as antimalarial, anesthetic, anticonvulsant, vasodilator and antiepileptic, and in agrochemistry as
fungicides, pesticides and herbicides [5–8]. In addition, pyridines have been used in many natural products including
NAD nucleotides, vitamine B6 and alkaloids [9]. As a result, a continuous interest has been drawn towards the
development of various methods for the synthesis of 2,4,6-triarylpyridines.
The most direct synthetic methods reported so far have been accomplished by reactions that are promoted with
ammonium acetate as a benign source of ammonia. The methods used for the synthesis of these compounds in the
presence of NH4OAc include the reaction of N-phenancylpyridinium [10] or N-phenacylisoquinolinium salts with a,b-
unsaturated ketones [11,12], one-pot reaction of ketones with aldehydes [13–17], michael addition and solid phase
condensation of chalcones [18], reaction of a-benzotriazolylketone with 1,5-diketones [19] and addition reaction of
lithiated b-enaneinophosphonatest to chalcones [20]. Other methods involve the conversion of 2,4,6-triarylpyrylium
salts into 2,4,6-triarylpyridines using aqueous ammonia [21], reaction of v-pyrrolidinoacetophenine with chalcone
using BF3.OEt2 and urea as a benign source of ammonia [22].
* Corresponding author.
E-mail address: maleki@sttu.ac.ir (B. Maleki).
1001-8417/$ – see front matter # 2010 Behrooz Maleki. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.06.028

[(Fig._1)TD$FIG]
B. Maleki et al. / Chinese Chemical Letters 21 (2010) 1346–1349
1347
Fig. 1. The structure of cyanuric chloride.
[(Scheme_1)TD$FIG]
Scheme 1.
Table 1
Optimizing the reaction conditions.
Entry
TCT (mol%)
Temperature (8C)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
10
5
130
130
130
110
120
140
130
5.5
5.5
6
62
64
42
36
52
53
–
3
5
6.5
5.5
5
5
5
–
7
5 (+2 drops of H2O)
130
4
70
a
Isolated yields.
In recent years, 2,4,6-trichloro-1,3,5-triazine called cyanuric chloride (Fig. 1) has been widely used in organic
synthesis because it is stable, non-volatile, inexpensive and commercially available reagent [23–27].
In continuation of our ongoing research on the development of more efficient and environmentally friendly
procedures for some important transformations in organic synthesis [28–30], herein we wish to describe a new and
convenient protocol for the synthesis of 2,4,6-triarylpyridines via a multicomponent reaction of aldehydes and ketones
with ammonium acetate in the presence of wet-TCT under solvent-free condition (Scheme 1).
First of all, we tested the efficiency of our method by choosing the reaction between benzaldehyde (1 mmol),
acetophenone (2 mmol) and ammonium acetate (1.3 mmol) as model reaction in the presence of a catalytic amount of
TCT under solvent-free condition. The effects of temperature and the amount of TCT as the catalyst on the reaction to
achieve suitable reaction conditions in terms of the reaction time and yield were investigated as summarized in Table 1.
As shown in this table, the reaction worked out best (70%) at 130 8C in 4 h when 5 mol% of TCT moisturized with two
drops of water was used as the catalyst compared with dry TCT (Scheme 2). Our attempts to study and optimize the
reaction conditions showed that carrying out the reaction in H2O met with failure; whereas using minute amounts of
H2O to moisten the media gave satisfactory results. It is note worthy that the reaction did not go to complication in
completely dry media. This probably implies that the in situ generation of HCl probably occurs [23–27] in the course
of the reaction along with cyanuric acid as indicated in the mechanism given as Scheme 3. This generated HCl acts as
[(Scheme_2)TD$FIG]
an efficient protic acid catalyst by activating the carbonyl group of the aldehyde or ketone to undergo rapid
Scheme 2.

[(Scheme_3)TD$FIG]
1348
B. Maleki et al. / Chinese Chemical Letters 21 (2010) 1346–1349
Scheme 3.
condensation to yield the expected products 3a–o. It was also observed that, increasing the reaction time or the amount
of the catalyst did not bring about any improvement in the yield. The importance of the catalyst on the reaction was
evaluated by conducting the reaction in the absence of TCT under the same reaction conditions and no formation of the
respective product was detected after 7 h (entry 7). In order to verify the role of HCl which is probably generated upon
moisturizing the TCTwith water, we conducted the reaction under the similar conditions with directly using HCl in the
absence of TCT. A test reaction was performed between 4-chlorobenzaldehyde (1 mmol), acetophenone (2 mmol) and
ammonium acetate (1.3 mmol) in the presence of HCl (one drop) at 130 8C without solvent. It was found that the
generation of 4-(4-chlorophenyl)-2,6-bisphenylpyridine (3b) occurred in 48% after 5 h.
In conclusion, we have developed a convenient, highly efficient and benign synthetic procedure for the synthesis of
2,4,6-triarylpyridines in high yields.
1. Experimental
IR spectra were recorded on a Shimadzu 435-U-04 spectrophotometer (KBr). 1H NMR spectra were obtained using
Jeol FT NMR 90 MHz spectrometer using TMS as an internal reference.
Table 2
TCT-catalyzed solvent-free synthesis of 2,4,6-triarylpyridines.
Productsa
Ar1
Ar2
Time (h)
Yields (%)b
Mp (8C)
Found
Reported
134–135 [14]
3a
3b
3c
3d
3e
3f
C6H5
C6H5
4
70
80
72
64
58
74
76
86
80
70
82
80
78
76
79
133–134
125–126
153–155
178–179
195–196
119–120
154–156
136–138
198–200
112–114
99–100
4-ClC6H4
C6H5
C6H5
5
122–124 [14]
159–160 [14]
176–177 [14]
4-CH3C6H4
4-CH3C6H4
C6H5
5
4-CH3C6H4
4-HOC6H4
2-CH3C6H4
4-MeOC6H4
4-N(CH3)2C6H4
4-ClC6H4
4-ClC6H4
4-MeOC6H4
2-Furyl
5.5
7
197 [14]
C6H5
6
120–122 [18]
155–157 [18]
138–140 [18]
199–201 [18]
115–116 [18]
100–103 [18]
165–166 [18]
113–114 [18]
168–170 [18]
166–167 [15]
3g
3h
3i
4-CH3C6H4
C6H5
7
7
4-CH3C6H4
4-MeOC6H4
C6H5
7.5
6
3j
3k
3l
5.5
6
C6H5
164–165
112–114
172–174
164–166
3m
3n
3o
2-ClC6H4
2-Thienyl
4-BrC6H4
C6H5
5.5
6
C6H5
C6H5
6
a
All the isolated products were characterized on the basis of their physical properties and IR, 1H and 13C NMR spectral analysis and by direct
comparison with authentic materials.
b
Isolated yields.

B. Maleki et al. / Chinese Chemical Letters 21 (2010) 1346–1349
1349
1.1. General procedure for the synthesis of 2,4,6-triarylpyridines
To a stirred mixture of the aldehydes 1 (1 mmol), ketones 2 (2 mmol) and ammonium acetate (1.3 mmol) at room
temperature were added TCT (5 mol%) and H2O (2 drops) and then temperature was raised to 130 8C and maintained
for the appropriate time (Table 2). After the completion of the reaction (as monitored by TLC), the reaction mixture
was diluted with EtOH (96%, 5 mL) and stirred for 2 min at 130 8C. The solvent was evaporated; the remaining solid
products were collected and washed with water to give the crude products. Then, recrystallization from EtOH (96%,
5 mL) provided pure 2,4,6-triarylpyridines.
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