Facile synthesis of triarylpyrimidines with microwave-irradiated reactions of N-phenacylpyridinium chloride

Article abstract of DOI:10.1080/00397910601031843

In a system of ammonium acetate and acetic acid under microwave irradiation, N-phenacylpyridinium chloride 1 reacted with 2 mol of aromatic aldehydes 2a-h to give 2,4,6-triarylpyrimidine 3a-h, reacted with pyridinecarboxaldehyde 4a-c and acetophenone 5 to yield bipyridine derivatives 6a-c. The structure of the products was characterized with 1H NMR, 13C NMR, IR, and mass spectroscopy. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910601031843

This article was downloaded by: [University of Illinois Chicago]
On: 28 October 2014, At: 21:03
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Facile Synthesis of Triarylpyrimidines
with Microwave‐Irradiated Reactions of
N‐Phenacylpyridinium Chloride
a b
a
a
a
Ping Wu
, Xi‐Mei Cai , Qi‐Fang Wang & Chao‐Guo Yan
a
College of Chemistry and Chemical Engineering, Yangzhou University ,
Yangzhou, China
b
Yangzhou Polytechnic College , Yangzhou, China
Published online: 25 Jul 2007.
To cite this article: Ping Wu , Xi‐Mei Cai , Qi‐Fang Wang & Chao‐Guo Yan (2007) Facile Synthesis of
Triarylpyrimidines with Microwave‐Irradiated Reactions of N‐Phenacylpyridinium Chloride, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:2,
223-229, DOI: 10.1080/00397910601031843
To link to this article: http://dx.doi.org/10.1080/00397910601031843
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

w
Synthetic Communications , 37: 223–229, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601031843
Facile Synthesis of Triarylpyrimidines with
Microwave-Irradiated Reactions of
N-Phenacylpyridinium Chloride
Ping Wu
College of Chemistry and Chemical Engineering, Yangzhou University,
China and Yangzhou Polytechnic College, Yangzhou, China
Xi-Mei Cai, Qi-Fang Wang, and Chao-Guo Yan
College of Chemistry and Chemical Engineering, Yangzhou University,
China
Abstract: In a system of ammonium acetate and acetic acid under microwave
irradiation, N-phenacylpyridinium chloride 1 reacted with 2 mol of aromatic
aldehydes 2a–h to give 2,4,6-triarylpyrimidine 3a–h, reacted with pyridinecarboxal-
dehyde 4a–c and acetophenone 5 to yield bipyridine derivatives 6a–c. The structure of
1
13
the products was characterized with H NMR, C NMR, IR, and mass spectroscopy.
Keywords: aldehyde, condensation, microwave irradiation, pyridine, pyrimidine
INTRODUCTION
Because of the aromatic character of the pyridine heterocycle, its basicity, and
the electron-attracting influence of the nitrogen atom, pyridinium cations can
behave as nucleophiles and 1,3-dipoles and show a great variety of synthetic
uses such as reactions with alkenes substituted with electron-withdrawing
[
1]
groups. Pyridinium cations with stronger electron-withdrawing carbonyl,
cyano, and nitro groups increase the activity of methylene group and have
[
2–4]
many more versatile applications.
N-Phenacylpyridinium bromide in
Address correspondence to Chao-Guo Yan, College of Chemistry and Chemical
Engineering, Yangzhou University, Yangzhou 225002, China. E-mail: cgyan@yzu.
edu.cn
2
23

2
24
P. Wu et al.
the presence of a base is known to undergo Knoevenagel condensation with
[
5,6]
[7,8]
aldehydes,
Michael addition to a,b-unsaturated carbonyl compounds,
[9]
and dipolar cycloaddition with activated alkenes. It was thus worthwhile
to investigate new reactions and synthetic applications of this kind of salt
with an emphasis on multicomponent reactions (MCRs), which offer signifi-
cant advantages and are of increasing importance in organic and medical
chemistry. Herein we report the reaction results of some one-pot reactions
of N-phenacylpyridium chloride with aromatic aldehydes and ketones under
microwave irradiation conditions.
RESULTS AND DISCUSSION
N-Phenacylpyridinium chloride 1 was easily prepared by refluxing the
benzene solution of phenacyl chloride and pyridine for 2 h. Early in 1963,
F. Kronke et al. reported one example of the reaction of N-phenacylpyridi-
nium bromide with p-nitrobenzaldehyde to give 2,4-bis-(p-nitrophenyl)-6-
[
10]
phenylpyrimidine.
But until now, there have been no other reports
about this kind of reaction. The first microwave-irradiation reaction we
tested is the reaction of N-phenacylpyridinium chloride 1 with 2 mol of
aromatic aldehydes 2a–g in a mixture of ammonium acetate and acetic
acid (Scheme 1). After irradiating 2–4 min, 2,4,6-triarylpyrimidine 3a–i
were synthesized in satisfactory yields (54–82%). Under microwave
irradiation, all aromatic aldehydes even bearing electron-donating methyl
and methoxy groups form pyrimidine smoothly. When 3- or
4-pyridinecarboaldehyde was used in the reaction, the 2,4-pyrdinyl groups
were introduced on the pyrimidine, which shows this reaction procedure
has wide scope and is a facile synthetic route to pyrimidine compared
[
11]
with the other method.
Evidently the reaction mechanism was as
follows (Scheme 2): N-phenacylpyridinium chloride reacts with 1 mol of
aldehyde and ammonia via a Mannich-type reaction to give substituted
aminopropiophenone, which then reacts with the ammonia and second
molecular aldehyde and cyclizes to form a tetrahydropyrimidine ring. The
latter pyrolyzes smoothly to give triarylpyrimidine.
Scheme 1. Ar ¼ Ph, p-ClC
6
H
4
,
p-CH
3
OC
6
H
4
,
m-NO
2
C
6
H
4
,
2 6 4
p-NO C H ,
p-CH C H , 3-py, 4-py.
3 6 4

Triarylpyrimidines
225
Scheme 2.
1
The analytical data of 3a–h is listed in Table 1. In H NMR spectroscopy,
-H of pyrimidine usually appears as one singlet peak at 7.90 ppm. The proton
5
signals of the triaryl group show a couple of splitting peaks of 8.50–7.50 ppm
with o-H at the lower field and m-, p-H at the higher field. But it is very diffi-
culty to elucidate each peak because there are three aryl groups with few
1
3
differences. In C spectra, C-2 of pyrimidine shows one peak at about
1
1
60 ppm, and other aromatic carbons show a couple of peaks at 100–
40 ppm. These peaks overlap very heavily, and they are not listed in Table 1.
With the initial success of this reaction, we set out to determine the scope
and variability of the procedure. It is generally recognized that chalcone was
easily formed from the condensation of aromatic aldehydes with acetophe-
[12]
none under mild basic conditions, and in fact there are several reports
about the aldol condensation under microwave conditions. We realized that
aromatic aldehydes could react with acetophenone to give chalcone in situ
in the previously described microwave-irradiation procedure. Equivalent
molar ratios of 2-, 3-, or 4-pyridinecarboaldehyde 5a–c and p-chloroacetophe-
none 5 were used to react with N-phenacylpyridinium chloride 1 in a mixture
of ammonium acetate and acetic acid (Scheme 3). Under microwave
irradiation the five-component mixture reacted smoothly to give 2,4,6-triaryl-
pyridine 6a–c in high yields (84–92%). Here the formation of 2,4,6-triaryl-
pyridine is a typical multicomponent domino reaction. The reaction
proceeds via pyridinecarboaldehyde, reacted first with acetophenone to form
a,b-unsaturated ketone, which in turn reacted with N-phenacylpyridinium
chloride to give 1,5-diketone derivatives, then cyclized with ammonium,
and finally eliminated pyridine cation to form the triarylpyridines
(Scheme 4). This method allows freely selective introduction of variously sub-
stituted aryl groups into the 2-, 4-, and 6-position of pyridine and also provides
one practical synthetic routes for bipyridine derivatives with two aryl groups
1
on one pyridine ring. In H NMR, the proton signals of 3,5-H in triarylpyridine
usually show one peak at about 7.90 ppm.

Table 1. Physical data of 2,4,6-triarylpyrimidines 3a–g and bipyridines 6a–c
Yield
(%)
1
21
)
Entry
Ar
Mp (8C)
H NMR (CDCl ppm)
3
IR (KBr Disk, cm
3
a
Ph
54
148.5
8.74 (d, J ¼ 6.6 Hz, 1H, PhH), 8.30 (d, J ¼ 6.0 Hz, 2H, PhH)
2924(w), 2854(w), 1569(s)
1526(s), 1494(m), 1396(m)
1361(m), 1174(m), 1072(w)
1027(w), 866(w), 749(s)
8
7
7
.21 (d, J ¼ 7.2 Hz, 2H, PhH), 7.90 (s, 1H, 5-PyH)
.75 (d, J ¼ 7.2 Hz, 1H, PhH), 7.56 (m, 8H, PhH)
.46 (d, J ¼ 7.2 Hz, 1H, PhH)
3b
p-ClC
6
H
4
71
188.2
8.64 (d, J ¼ 8.4 Hz, 2H, ArH), 8.25 (d, J ¼ 7.2 Hz, 2H, ArH)
2924(s), 2854(m), 1591(m)
1526(vs), 1490 (s), 1385(m)
1361(m), 1093(m), 768(m)
8
7
7
.21 (d, 2H, J ¼ 8.4 Hz, ArH), 7.96 (s, 1H, 5-PyH)
.56 (s, 3H, PhH), 7.53 (d, J ¼ 8.4 Hz, 2H, ArH)
.50 (d, J ¼ 8.4 Hz, 2H, PhH)
3
3
c
p-CH
3
OC
6
H
4
65
82
147–148
206.5
8.15–8.18 (m, 4H, ArH), 7.769 (s, 2H)
2922(w), 2856(w), 1607(vs)
1518(s), 1357 (m), 1182(m)
1064(w), 953(w), 813(m)
7
.66 (d, J ¼ 6.0 Hz, 2H), 7.51–7.45 (m, 4H)
7
.03 (d, J ¼ 6.0 Hz, 2H), 3.88 (s, 3H, OCH )
3
d
m-NO C H
6 4
9.52 (s, 1H), 9.06 (m, 2H), 8.70 (d, J ¼ 7.2 Hz, 1H)
3092(w), 2860(w), 1579(m)
1530(vs), 1351(vs), 1089(w)
878(w), 730(m), 685(m)
2
8
8
7
.43 (d, J ¼ 7.8 Hz, 1H), 8.40 (d, J ¼ 7.8 Hz, 1H)
.33 (s, 2H), 8.15 (s, 1H), 7.81 (t, J ¼ 7.2 Hz, 1H)
.75 (t, J ¼ 7.2 Hz, 1H), 7.62 (s, 3H, PhH)
3
e
p-NO C H
6 4
78
230
8.90 (d, J ¼ 7.8 Hz, 2H, ArH), 8.46 (d, J ¼ 7.8 Hz, 4H, ArH)
2925(w), 2853(w), 1572(s)
1532(s), 1344(vs), 1108(w)
1012(w), 858(m), 743(m)
2
8
.41 (d, J ¼ 7.8 Hz, 2H, ArH), 8.32 (s, 2H, PhH)
8
.17 (s, 1H, 5-PyH), 7.62 (s, 3H, PhH)

3
3
f
p-CH
3-py
3
C
6
H
4
80
61
166–168
226
8.64 (d, J ¼ 7.8 Hz, 2H, ArH), 8.31 (d, J ¼ 7.2 Hz, 2H, ArH)
3027(w), 2915(w), 1571(s)
1524(vs), 1444(w), 1358(s)
1239(w), 1178(m), 1110(w)
1024(w), 824(m), 764(s)
8
7
2
.22 (d, J ¼ 7.8 Hz, 2H, ArH), 7.99 (s, 1H, 5-PyH)
.59-7.56(m, 3H, ArH), 7.39–7.36 (m, 4H, ArH)
3
.48 (s, 6H, CH )
g
9.90 (s, 1H, PyH), 9.47 (s, 1H, PyH)
3064(w), 2924(w), 2854(w)
1590(vs), 1528(s), 1483(w)
1253(w), 1193(w), 765(m)
8
8
8
.95 (d, J ¼ 7.8 Hz, 1H, PyH), 8.79 (m, 2H, PyH)
.60 (d, J ¼ 7.8 Hz, 1H, PyH), 8.30 (s, 2H, PyH)
.09 (s, 1H, 5-PyH), 7.59 (s, 3H, PhH), 7.53–7.49 (m, 2H, PhH)
3
h
a
4-py
2-Py
74
88
.250
8.87 (d, J ¼ 11.4 Hz, 4H, PyH), 8.57 (s, 2H, PyH)
3032(w), 2923(w), 2854(w)
1583(vs), 1557(m), 1525(m)
1367(m), 1062(w), 765(m)
8
8
.31 (s, 2H, PyH), 8.21–8.16 (m, 1H, PyH)
.15 (d, 2H, PhH), 7.61 (s, 3H, PhH)
6
160
8.80 (d, J ¼ 3.6 Hz, 1H, PyH), 8.29 (s, 2H, 3,5-PyH)
3089(w), 3061(w), 2926(w)
2855(w), 1604(s), 1550(s)
1495(m), 1472(m), 1385(m)
1093(m), 1013(m), 837(m)
8
7
7
.23 (d, J ¼ 7.2 Hz, 4H), 7.92 (d, J ¼ 7.8 Hz, 1H)
.86 (t, J ¼ 7.8 Hz, 1H), 7.52 (t, J ¼ 7.8 Hz, 2H)
.474 (m, 3H), 7.381 (t, J ¼ 3.6 Hz, 1H)
6
6
b
c
3-Py
4-Py
92
84
144
201
9.02 (s, 1H), 8.75 (s, 1H), 8.18–8.16 (m, 4H)
3039(w), 2925(w), 1545(s)
1486(m), 1427 (m), 1384(s)
1091(m), 1014(m), 831(m)
8
7
.084 (s, 1H), 7.890 (s, 1H), 7.849 (s, 1H)
.60-7.50 (m, 6H)
8.79 (s, 2H), 8.18 (d, J ¼ 7.2 Hz, 2H)
3036(w), 2923(w), 1590(vs)
1536(s), 1493(s), 1400(m)
1086(m), 1012(m), 778(s)
8
.16 (d, J ¼ 7.2 Hz, 2H), 7.90 (s, 1H)
7
.86 (s, 1H), 7.66 (s, 2H), 7.54–7.49(m, 5H, PhH)

2
28
P. Wu et al.
Scheme 3.
EXPERIMENTAL
General Procedure for the Preparation of Pyrimidine 3a–h
To a 50-mL of flask, N-phenacylpyridinium chloride (1.0 mmol, 0.225 g),
aromatic aldehyde (2.2 mmol), ammonium acetate (3.0 g), and acetic aid
(
2.0 mL) were added. The mixture was put in the microwave (Lin-Jiang
microwave reactor LWMC-201, Nanjing) and heated for about 2–4 min
130 W). After cooling, the reaction mixture was diluted with 50 mL of
(
water, and the resulting precipitate was collected with filtration. The crude
product was recrystallizated with ethanol to give the pure solid sample
3a–h for analysis with FeLiegen high pressure liquid chromatography/
mass spectrometer (HPLC/MS), H NMR, and IR.
1
General Procedure for the Preparation of Bipyridines 6a–c
To a 50-mL flask, N-phenacylpyridinium chloride (1.2 mmol, 0.280 g),
pyridinecarbaldehyde (1.0 mmol), p-chloroacetophenone (1.0 mmol),
ammonium acetate (3.0 g), and acetic aid (2.0 mL) were added. The mixture
Scheme 4.

Triarylpyrimidines
229
was put in the microwave (Lin-Jiang microwave reactor LWMC-201, Nanjing)
and heated for about 2–4 min (130 W). After cooling, the reaction mixture was
diluted with 50 mL of water, and the resulting precipitate was collected with
filtration. The crude product was recrystallizated with ethanol to give the
1
pure solid sample 6a–c for analysis with HPLC/MS, H NMR, and IR.
REFERENCES
1
2
. Kowalkowska, A.; Sucholbiak, D.; Jonczyk, A. Generation and reactions of
ammonium ylide in basic two-phase systems. Eur. J. Org. Chem. 2005, 925.
. Risitano, F.; Grassi, G.; Foti, F.; Bilardo, C. Pyridinium N-ylides and arylmethy-
lene azol-5-ones: Reaction cascade leading to an unusual spiroiosxazolineone ring.
Tetrahedron 2000, 56, 9674.
3
. Vo, N. H.; Eyermann, C. J.; Hodge, C. N. Transformations of resin-bound pyridi-
nium ylides, I: A stereoselective synthesis of 2,2,3-trisubstituted cyclopropane-
carboxylates. Tetrahedron Lett. 1997, 38, 7951.
4
5
6
7
. Papageorgiou, C. D.; Ley, S. V.; Graut, M. J. Organic-catalyst-mediated cyclopro-
panation reaction. Angew. Chem. Int. Ed. 2003, 42, 828.
. Krohnke, F. New methods of preparative organic chemistry: Syntheses using pyri-
dinium salts. Angew. Chem. Int. Ed. 1963, 2 (5), 225.
. Krohnke, F.; Zecher, W. Synthesis using the Michael addition of pyridium salts.
Angew. Chem. Int. Ed. 1962, 1 (12), 626.
. Ghosh, C. K.; Sahana, S. Benzopyrans: Part 34—reactions of 3-substituted 1-ben-
zopyran-4-ones with N-phenacylpyridinium bromide. Ind. J. Chem. 1996, 35B,
203.
8
9
. Brahambhatt, D. I.; Raolji, G. B.; Pandya, S. U.; Pandya, U. R. A facile synthesis
of some 3-(2-pyridyl)-coumarins. Ind. J. Chem. 1999, 38B, 212.
. Katritsky, A.; Grzeskowiak, N.; Alvarez-Builla, J. Preparation of tetrahydroindo-
lizines from pyrinium and isoquinolinium ylides. J. Chem. Soc. Perkin Trans. 1
1
981, 1180.
0. Krohnke, F.; Schmidt, E.; Zecher, W. Neue Pyrimidin-Synthesen, Chem. Ber.
963, 1163.
1. M u¨ ller, T. J.; Braun, R.; Ansorge, M. A novel three-component one-pot pyrimidine
synthesis based upon a coupling-isomerization sequence. Org. Lett. 2000, 2 (13),
1
1
1
1967.
12. Varma, R. S.; Dahiya, R.; Kumar, S. Microwave-assisted Henry reaction: Solvent-
less synthesis of conjugated nitroalkenes. Tetrahedron Lett. 1997, 38, 5131.