Multicomponent reaction for the synthesis of pyridine derivatives based on triphenylamine

Article abstract of DOI:10.3184/174751911X12964930076449

A facile preparation of pyridine derivatives based on triphenylamine through a multicomponent reaction from 3-cyanoacetylindoles, ammonium acetate and a 1,3-diarylpropenone either by conventional heating or microwave irradiation is described. The three-co

Full text of DOI:10.3184/174751911X12964930076449

74 RESEARCH PAPER
FEBRUARY, 74–76
JOURNAL OF CHEMICAL RESEARCH 2011
Multicomponent reaction for the synthesis of pyridine derivatives based
on triphenylamine
Li-Jun Genga,b, Guo-Liang Fengb, Jiu-Gao Yua* and Hong-Li Zhangb
aDepartment of Chemistry, School of Science, Tianjin University, Weijin Road, Tianjin 300072, P. R. China
bSchool of Science, Hebei University of Science andTechnology, 70Yuhua East Road, Shijiazhuang 050018, P. R. China
A facile preparation of pyridine derivatives based on triphenylamine through a multicomponent reaction from 3-cya-
noacetylindoles, ammonium acetate and a 1,3-diarylpropenone either by conventional heating or microwave irradia-
tion is described. The three-component reaction afforded good yields and involved a simple procedure.
Keywords: multicomponent reaction, pyridine derivatives, triphenylamine, chalcone
Table 1 The synthesis of 4b in different solvents under
Since the publication of the Strecker reaction in 1850 consid-
ered as the beginning of the multicomponent reaction (MCR)
story,1 there has been considerable interest in one-pot multi-
component reactions due to their diversity, efficiency and rapid
access to complex and highly functionalised organic mole-
cules.2,3 In the past decade there have been tremendous devel-
opments in three- and four-component reactions4,5 and great
efforts have been and still are being made to find and develop
new MCRs.6,7 During the past few years, the synthesis and
application of triphenylamine derivatives have been of great
interest for chemists and material scientists8,9 because these
compounds are quite interesting due to their intrinsic photo-
physical and redox properties: they exhibit relatively intense
luminescence and undergo reversible oxidation processes
which make them suitable as hole carriers.10,11
Due to our interest in multicomponent syntheses and triphe-
nylamine,12 we have synthesised novel compounds containing
triphenylamine and pyridine groups using a three-component
reaction (Scheme 1). To the best of our knowledge, these
compounds have not been reported previously.
In order to realise our plan, the starting compound chalcone
1 was prepared according to the procedure described by
Mauricio et al.13 The synthesis of 3-cyanoacetylindoles 2 was
carried out by a similar method to that the literature.14 How-
ever, when 2-nitroindole or 5-nitroindole were used, we failed
to get the expected product owing to the lower reactivity of the
nitroindoles.
refluxing
Entry
Solvent
Time/h
Yield/%a
1
2
3
4
5
6
MeOH
5
40
50
55
71
42
76
EtOH
5
HOAc
5
Glycol
4.5
6
water
HOAc/Glycol(1: 2)
5
a Isolated yield.
We also carried out the reaction at different temperatures
ranging from 90 to 140 °C under microwave irradiation with
HOAc/glycol (1: 2) as the solvent. The yield of product 4b was
increased and the reaction time was shortened when the tem-
perature was increased. The yields, however, reached a maxi-
mum when the temperature was further increased to 120 and
140 °C, microwave irradiation at 120 °C gave the highest yield.
Under these optimised conditions, a series of 3-cyanoacetyl-4-
(4-diphenylaminophenyl)-2-(indol-3-yl)-6-phenylpyridine
derivatives 4 was synthesised (Table 2).
Table 2 Synthesis of compounds 4a–g under conventional
heating and microwave irradiation
Entry R
Product
Conventional
heating
Microwave
irradiation
Time/h Yielda/% Time/min Yielda/%
Choosing an appropriate solvent was of crucial importance
for the successful synthesis. In our initial study, we investi-
gated the efficacy of different solvents under refluxing for the
reaction of chalcone 1, 3-cyanoacetyl-5-methoxylindole 2b
and ammonium acetate. The results are summarised in Table 1.
Excellent results were obtained with HOAc/glycol (1:2)
(Table 1. entry 6) as the solvent, and so this solvent was used
in the succeeding experiments.
1
2
3
4
5
6
7
H
4a
4b
4c
4d
4e
4f
5
5
5
5
5
5
5
75
76
70
72
69
71
74
12
12
15
12
15
15
12
83
85
77
82
75
81
82
5-OCH3
2-CH3
7-CH3
2-C6H5
5-Br
1-CH3
4g
a Isolated yield.
Scheme 1
* Correspondent. E-mail: jgyu2010@126.com

JOURNAL OF CHEMICAL RESEARCH 2011 75
and tetramethylsilane (TMS) as internal reference. IR spectra was
obtained on a Nicolet FT-IR 6700 spectrophotometer using KBr
pellets. Elementary analyses were performed by a Carlo-Erba
EA1110 CNNO-S analyser. Microwave reactions were carried out in
a Xianghu XH-100B microwave oven.
Conventional heating: A mixture of chalcone 1 (0.75 g, 2 mmol),
3-cyanoacetylindole 2 (2 mmol) and ammonium acetate 3 (0.62 g,
8 mmol) in HOAc (3 mL) and glycol (6 mL) were refluxed for 5 h.
After the completion of the reaction (followed by TLC), the mixture
was allowed to cool to room temperature and was extracted with
dichloromethane, washed with H2O (3×10 mL) and the organic layer
dried over MgSO4 and concentrated under reduced pressure. The
crude product was chromatographed on silica gel (200–300 mesh)
using a mixture of petroleum ether and dichloromethane as eluent to
afford the pure product 4.
As shown in Table 2, firstly, the reaction proceeded smoothly
with a wide range of functionalised 3-cyanoacetylindoles,
including those containing methyl, bromo, methoxyl and
phenyl substituents. The electronic effects of the substituents
on the 3-cyanoacetylindoles have no significant influence on
the reaction yield. Secondly, microwave irradiation exhibited
several advantages over conventional heating by significantly
reducing reaction times and improving the reaction yield.
The structures of 4a–g were confirmed by spectroscopic
studies and elemental analyses as exemplified for compound
4a as follows. The IR spectrum of 4a showed absorptions
at 2223 and 3296 cm−1 for CN and NH functional groups,
respectively. The aryl protons gave rise to signals in the range
δ 7.07–8.38 ppm, and a signal at δ 11.81 confirmed the
presence of the indolyl NH group in 1H NMR spectrum.
Based on the above results, a possible mechanism was pro-
posed (Scheme 2). 3-Cyanoacetylindole reacted with ammo-
nia from ammonium acetate to give intermediate 5, which
further reacted with the corresponding chalcone to yield 6.
Michael addition product 6 was then cyclised to afford the
Hantzsch dihydropyridine derivative 7 with elimination of
water, finally dehydrogenation of 7 presumably involving
aerial oxidation led to the formation of the highly substituted
pyridine derivative 4.
Microwave irradiation: A mixture of chalcone 1 (0.75 g, 2 mmol),
3-cyanoacetylindole 2 (2 mmol) and ammonium acetate 3 (0.62 g,
8 mmol) in HOAc (3 mL) and glycol (6 mL) were irradiated for appro-
priate minutes at 120 °C. The product isolation was similar to that of
conventional method.
3-Cyanoacetyl-4-(4-diphenylaminophenyl)-2-(indol-3-yl)-6-
phenylpyridine (4a): Yellow powder; m.p. 278–279 °C; IR (KBr) ν
3296(NH), 3034, 2223(CN), 1590, 1572, 1509, 1492, 1435, 1271,
1
1233 cm−1; H NMR (500 MHz, DMSO-d6): δ (ppm) 11.81 (s, 1H),
8.38-8.33 (m, 4H), 7.94 (s, 1H), 7.75 (d, J = 8.5 Hz, 2H), 7.59–7.54
(m, 4H), 7.40 (t, J = 7.5 Hz, 4H), 7.24–7.22 (m, 2H), 7.18–7.15
(m, 6H), 7.07 (d, J = 8.5 Hz, 2H). Anal. Calcd for C38H26N4: C, 84.73;
H, 4.87; N, 10.40. Found: C, 84.62; H, 4.90; N, 10.41%.
In conclusion, we have demonstrated the efficiency of
the synthesis of 3-cyanoacetyl-4-(4-diphenylaminophenyl)-2-
(indol-3-yl)-6-phenylpyridine derivatives involving a three-
component condensation of a 1,3-diarylpropenone, a 3-
cyanoacetylindole and ammonium acetate under conventional
heating ormicrowave irradiation in a simple one-pot procedure.
High efficiency and short reaction times were the advantages
of this protocol.
3-Cyanoacetyl-4-(4-diphenylaminophenyl)-2-(5-methoxyindol-3-
yl)-6-phenylpyridine (4b):Yellow powder; m.p. 247–248 °C; IR (KBr)
ν 3311(NH), 3037, 2921, 2212(CN), 1588, 1524, 1509, 1484, 1436,
1
1283, 1238 cm−1; H NMR (500 MHz, DMSO-d6): δ (ppm) 11.70
(s, 1H), 8.41–8.39 (m, 3H), 8.08 (d, J = 2.5 Hz, 1H), 7.92 (s, 1H),
7.74 (d, J = 7.0 Hz, 2H), 7.59–7.55 (m, 3H), 7.44 (d, J = 8.5 Hz, 1H),
7.40 (t, J = 7.5 Hz, 4H), 7.18–7.15 (m, 5H), 7.08–7.07 (m, 2H), 6.90
(dd, J = 8.5 Hz and J = 2.5 Hz, 1H), 5.76 (s, 1H), 3.82 (s, 3H). Anal.
Calcd for C39H28N4O: C, 82.37; H, 4.96; N, 9.85. Found: C, 82.22;
H, 4.90; N, 9.93%.
Experimental
Melting points were recorded on an electrothermal digital melting
point apparatus and are uncorrected. H NMR spectra were deter-
mined on a Varian VXP-500s spectrometer using DMSO-d6 as solvent
3-Cyanoacetyl-4-(4-diphenylaminophenyl)-2-(2-methylindol-3-yl)-
6-phenylpyridine (4c): Yellow powder; m.p. 238–239 °C; IR (KBr) ν
3396(NH), 3054, 2862, 2218(CN), 1570, 1525, 1460 cm−1; 1H NMR
1
Scheme 2

76 JOURNAL OF CHEMICAL RESEARCH 2011
1
ν 3045, 2961, 2213(CN), 1576, 1532, 1480, 1369 cm−1; H NMR
(500 MHz, DMSO-d6): δ (ppm) 11.60 (s, 1H), 8.30 (dd, J = 8.5 Hz
and J = 2.0 Hz, 2H), 8.06 (s, 1H), 7.78 (d, J = 8.5 Hz, 2H), 7.66 (d,
J = 7.5 Hz, 1H), 7.57–7.53 (m, 3H), 7.42-7.38 (m, 5H), 7.18–7.12
(m, 7H), 7.10–7.07 (m, 3H), 2.60 (s, 3H). Anal. Calcd for C39H28N4:
C, 84.76; H, 5.11; N, 10.14. Found: C, 84.73; H, 5.17; N, 10.20%.
3-Cyanoacetyl-4-(4-diphenylaminophenyl)-2-(7-methylindol-3-yl)-
6-phenylpyridine (4d): Pale yellow powder; m.p. >300 °C; IR (KBr)
ν 3304(NH), 3046, 2968, 2216(CN), 1572, 1548, 1492, 1440 cm−1;
1H NMR (500 MHz, DMSO-d6): δ (ppm) 11.80 (s, 1H), 8.35–8.33
(m, 3H), 8.20 (d, J = 8.0 Hz, 1H), 7.94 (s, 1H), 7.75 (d, J = 9.0 Hz,
2H), 7.61–7.55 (m, 3H), 7.42–7.39 (m, 4H), 7.18–7.11 (m, 7H), 7.08–
7.04 (m, 3H), 2.55 (s, 3H). Anal. Calcd for C39H28N4: C, 84.76;
H, 5.11; N, 10.14. Found: C, 84.83; H, 5.06; N, 10.18%.
3-Cyanoacetyl-4-(4-diphenylaminophenyl)-6-phenyl-2-(2-phenyl-
indol-3-yl) pyridine (4e): Yellow powder; m.p. 254–255 °C; IR (KBr)
ν 3338(NH), 3054, 2965, 2214(CN), 1570, 1537, 1509, 1456 cm−1;
1H NMR (500 MHz, DMSO-d6): δ (ppm) 11.98 (s, 1H), 8.19–8.17
(m, 2H), 8.09 (s, 1H), 7.68 (d, J = 7.5 Hz, 1H), 7.57–7.35 (m, 15H),
7.24 (t, J = 7.5 Hz, 1H), 7.17–7.12 (m, 7H), 7.00 (d, J = 8.5 Hz, 2H).
Anal. Calcd for C44H30N4: C, 85.97; H, 4.92; N, 9.11. Found: C, 85.85;
H, 5.03; N, 9.17%.
(500 MHz, DMSO-d6): δ (ppm) 8.38–8.33 (m, 4H), 7.95 (s, 1H), 7.75
(d, J = 6.5 Hz, 2H), 7.61–7.55 (m, 4H), 7.40 (t, J = 7.5 Hz, 4H), 7.32
(t, J = 4.0 Hz, 1H), 7.27 (d, J = 6.5 Hz, 1H), 7.18–7.08 (m, 6H), 7.06
(s, 2H), 2.50 (s, 3H). Anal. Calcd for C39H28N4: C, 84.76; H, 5.11;
N, 10.14. Found: C, 84.73; H, 5.17; N, 10.20%.
Received 28 September; accepted 1 December 2010
Paper 1000376 doi: 10.3184/174751911X12964930076449
Published online: 10 February 2011
References
1
2
3
4
A. Strecker, Liebigs Ann. Chem., 1850, 75, 27.
A. Nefzi, J.M. Ostresh and R.A. Houghten, Chem. Rev., 1997, 97, 449.
L.A.Thompson, Curr. Opin. Chem. Biol., 2000, 4, 324.
M. Li, W.L. Yang, L.R. Wen and F.Q. Li, Eur. J. Org. Chem., 2008,
2751.
S. Kumar, P. Sharma, K.K. Kapoor and M.S. Hundal, Tetrahedron, 2008,
64, 536.
M.C. Bagley, J.W. Cale and J. Bower, Chem. Commun., 2002, 1682.
D. Dallinger, N.Y. Gorobets and C.O. Kappe, Org. Lett., 2003, 5, 1205.
G. Chen, H.Y. Wang, Y. Liu, X.P. Xu and S.J. Ji, Dye Pigm., 2010, 85,
194.
5
6
7
8
2-(5-Bromoindol-3-yl)-3-cyanoacetyl-4-(4-diphenylaminophenyl)-
6-phenylpyridine (4f): Yellow powder; m.p. 271–272 °C; IR (KBr)
ν 3334(NH), 2968, 2889, 2216(CN), 1580, 1566, 1539, 1502,
9
K.J. Jiang, Y.L. Sun, K.F. Shao and L.M. Yang, Chem. Lett., 2004, 33, 50.
1
1443 cm−1; H NMR (500 MHz, DMSO-d6): δ (ppm) 12.00 (s, 1H),
10 B. Lim, J.T. Hwang, J.Y. Kim, J. Ghim, D. Vak,Y.Y. Noh, S.H. Lee, K. Lee,
A.J. Heeger and D.Y. Kim, Org. Lett., 2006, 21, 4703.
11 J.Y. Li, C. Ma, J.X. Tang, C.S. Lee and S. Lee. Chem. Mater., 2005, 17,
615.
12 L.J. Geng, G.L. Feng and J.G. Yu, J. Chem. Res., 2010, 34, 333.
13 C. Mauricio, S. Macarena and F. Gabriela, Bioorg. Med. Chem., 2007, 15,
3356.
8.62 (d, J = 2.0 Hz, 1H), 8.46 (d, J = 3.0 Hz, 1H), 8.34–8.32 (m, 2H),
7.96 (s, 1H), 7.75 (dd, J = 6.5 Hz and J = 2.0 Hz, 2H), 7.62–7.57 (m,
3H), 7.54 (d, J = 8.5 Hz, 1H), 7.42–7.37 (m, 5H), 7.18–7.16 (m, 6H),
7.07 (d, J = 7.0 Hz, 2H). Anal. Calcd for C38H25N4Br: C, 73.91;
H, 4.08; N, 9.07. Found: C, 74.03; H, 4.07; N, 9.20%.
3-Cyanoacetyl-4-(4-diphenylaminophenyl)-2-(1-methylindol-3-yl)-
6-phenylpyridine (4g): Yellow powder; m.p. 255–256 °C; IR (KBr)
14 J. Slatt, I. Romero and J. Bergman, Synthesis, 2004, 2760.

Copyright of Journal of Chemical Research is the property of Science Reviews 2000 Ltd. and its content may
not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written
permission. However, users may print, download, or email articles for individual use.