M. Adib et al. / Tetrahedron Letters 47 (2006) 5957–5960
5959
Ar'
Ar'
O
O
+
NH OAc
4
NH2
OH
+ NH OAc
4
Ar
Ar'
Ar
Ar'
_
_
AcOH
AcOH
Ar
NH Ar
_
H O
2
1
3
4
1
Ar'
Ar'
Ar'
Ar'
Ar
Ar'
H
_
_
Ar'CH NH2
H O
NH2
OH
Ar
2
NH2
2
Ar
N
H
Ar
N
Ar
N
Ar
5
6
2
Scheme 1.
1
13
H and C NMR spectra) with those of authentic
2. Constable, E. C.; Housecroft, C. E.; Neuburger, M.;
Phillips, D.; Raithby, P. R.; Schofield, E.; Sparr, E.;
Tocher, D. A.; Zehnder, M.; Zimmermann, Y. J. Chem.
Soc. Dalton Trans. 2000, 2219; Cave, G. W. V.; Hardie, M.
J.; Roberts, B. A.; Raston, C. L. Eur. J. Org. Chem. 2001,
1
7
samples.
Mechanistically, it is reasonable to assume that the first
step may involve condensation of ammonia with a mol-
ecule of chalcone and Michael addition of ammonia to a
second chalcone molecule leading to 2,4-diaryl-1-azadi-
ene 3 and the 1:1 adduct, 4, respectively. Azadiene 3
and adduct 4 probably undergo a formal [4+2] cycload-
dition reaction to form tetrahydropyridine intermediate
3
227; Jetti, R. K. R.; Nagia, A.; Xue, F.; Mak, T. C. W.
Chem. Commun. 2001, 919; Watson, Z. C.; Bampos, N.;
Sanders, J. K. M. New J. Chem. 1998, 1135.
3
. Kim, B. Y.; Ahn, J. B.; Lee, H. W.; Kang, S. K.; Lee,
J. H.; Shin, J. S.; Ahn, S. K.; Hong, C. I.; Yoon, S. S. Eur.
J. Med. Chem. 2004, 39, 433.
5
. Dehydration to dihydropyridine intermediate 6 and
4. Enyedy, I. J.; Sakamuri, S.; Zaman, W. A.; Johnson, K.
M.; Wang, S. Bioorg. Med. Chem. Lett. 2003, 13, 513.
then oxidative aromatization with removal of the benzyl
side chain would yield 2,4,6-triarylpyridine 2. This
oxidative dealkylation has been previously observed.
Isolation of benzylamine from the reaction mixture of
ammonium acetate and 1,3-diphenyl-2-propen-1-one,
5
. Pillai, A. D.; Rathod, P. D.; Franklin, P. X.; Patel, M.;
Nivsarkar, M.; Vasu, K. K.; Padh, H.; Sudarsanam, V.
Biochem. Biophys. Res. Commun. 2003, 301, 183.
. Klime sˇ ov a´ , V.; Svoboda, M.; Waisser, K.; Pour, M.;
Kaustov a´ , J. Il Farmaco 1999, 54, 666.
. Jones, G. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A. R., Rees, C. W., Scriven, E. V. F., Eds.;
Pergamon Press: London, 1996; Vol. 5, pp 168–243,
Chapter 5, and references cited therein.
1
8
6
7
1
a, confirms the proposed mechanism (Scheme 1). A
similar reaction pathway has been proposed for the
reaction between N-(diphenylphosphinyl)-1-ethanimine
and aromatic aldehydes in the formation of 2,4,6-
1
2
triarylpyridines.
8. Katritzky, A. R.; Abdel-Fattah, A. A. A.; Tymoshenko,
D. O.; Essawy, S. A. Synthesis 1999, 2114.
9
. Kr o¨ hnke, F.; Zecher, W. Angew. Chem., Int. Ed. 1962, 1,
26.
In conclusion, we have developed a novel and facile
method for the preparation of 2,4,6-triarylpyridines.
Solvent-free conditions, excellent yields, and a simplified
purification process are the main advantages of this
method. This method appears to have a broad scope
with respect to variation in the pyridine 2-/or 6- and
6
1
0. Kr o¨ hnke, F. Synthesis 1976, 1.
1
1. Potts, K. T.; Cipullo, M. J.; Ralli, P.; Theodoridis, G. J.
Am. Chem. Soc. 1981, 103, 3584; Potts, K. T.; Cipullo, M.
J.; Ralli, P.; Theodoridis, G. J. Am. Chem. Soc. 1981, 103,
3
585.
4
-positions.
12. Kobayashi, T.; Kakiuchi, H.; Kato, H. Bull. Chem. Soc.
Jpn. 1991, 64, 392.
1
1
1
3. Palacios, F.; de Retana, A. M. O.; Oyarzabal, J. Tetra-
hedron Lett. 1996, 37, 4577.
4. Cave, G. W. V.; Raston, C. L. Chem. Commun. 2000,
Acknowledgement
2
199.
This research was supported by the Research Council of
the University of Tehran as research project (6102036/1/
5. Tu, S.; Li, T.; Shi, F.; Fang, F.; Zhu, S.; Wei, X.; Zong, Z.
Chem. Lett. 2005, 34, 732.
0
2).
16. (a) Lombard, R.; Stephan, J.-P. Bull. Soc. Chim. Fr. 1958,
458; (b) Huang, X. Q.; Li, H. X.; Wang, J. X.; Jia, X. F.
1
Chin. Chem. Lett. 2005, 16, 607; (c) Dorofeenko, G. N.;
Krivum, S. V. Zh. Obshch. Khim. 1964, 34, 105.
References and notes
1
7. The procedure for the preparation of 2,4,6-triphenylpyri-
dine 2a is described as an example: A mixture of
1,3-diphenyl-2-propen-1-one, 1a (0.42 g, 2 mmol) and
ammonium acetate (0.16 g, 2.2 mmol) in the presence of
a catalytic amount of acetic acid was stirred at 100 °C
for 4 h (progress of the reaction followed by TLC
1
. Balasubramanian, M.; Keay, J. G. In Comprehensive
Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W.,
Scriven, E. V. F., Eds.; Pergamon Press: London, 1996;
Vol. 5, Chapter 6, pp 245–300, and references cited therein.