An efficient route to 5,5″-diaryl-2,2′:6′,2″- terpyridines through 2,6-bis(1,2,4-triazin-3-yl)pyridines

Article abstract of DOI:10.1016/j.tetlet.2005.01.020

A new route to substituted 2,2′:6′,2″-terpyridines based on a new method for the synthesis of substituted 2,6-bis(1,2,4-triazin-3-yl) pyridines and their inverse electron demand Diels-Alder reaction is shown to be an efficient strategy for the synthesis of structurally diverse terpyridine ligands.

Full text of DOI:10.1016/j.tetlet.2005.01.020

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1521–1523
An efficient route to 5,500-diaryl-2,20:60,200-terpyridines through
2,6-bis(1,2,4-triazin-3-yl)pyridines
Valery N. Kozhevnikov,* Dmitry N. Kozhevnikov, Olga V. Shabunina,
Vladimir L. Rusinov and Oleg N. Chupakhin
Urals State Technical University, Department of Organic Chemistry, Ekaterinburg 620002, Russia
Received 20 October 2004; revised 18 December 2004; accepted 6 January 2005
Available online 25 January 2005
Abstract—A new route to substituted 2,20:60,200-terpyridines based on a new method for the synthesis of substituted 2,6-bis(1,2,4-
triazin-3-yl)pyridines and their inverse electron demand Diels–Alder reaction is shown to be an efficient strategy for the synthesis
of structurally diverse terpyridine ligands.
Ó 2005 Elsevier Ltd. All rights reserved.
2,20:60,200-Terpyridines (tpy) are undoubtedly among the
most widely used ligands in coordination and supra-
molecular chemistry.1 In particular, the photophysical
properties of terpyridine metal complexes and of terpy-
ridines themselves are especially interesting.2,3 Among
terpyridines, 2,20:60,200-terpyridines bearing aromatic
substituents at the b-positions of the peripheral pyridine
rings exhibit the best luminescent properties with emis-
sion quantum yields (Uf) of upto 0.85, due to the effects
of aromatic substituents making the bipyridines attrac-
tive as chromophores and ÔantennaeÕ.4,5 Other applica-
tions include template synthesis of catenands based on
5,500-bis(4-hydroxyphenyl)-2,20:60,200-terpyridine.6 How-
ever, the study of these interesting and useful com-
pounds has been hampered by inefficient chemical
synthesis. Cross-coupling approaches or modified
Kro¨hnke syntheses are limited by inaccessible starting
compounds, multi-step procedures and low yields.6,7
are interesting compounds in their own right due to
their application in the separation of lanthanides and
actinides in the management of nuclear wastes.9
Here we report a new strategy for the synthesis of 5,500-
diaryl-2,20:60,200-terpyridines 1 based on the conversion
of 1,2,4-triazines into pyridines via an aza-Diels–Alder
reaction.8 The main stepof our strategy is original
involving easily synthesized key intermediates—2,6-
bis(1,2,4-triazin-3-yl)pyridines bearing aryl substituents
at position 6 of the peripheral 1,2,4-triazine rings. It
should be noted that 2,6-bis(1,2,4-triazin-3-yl)pyridines
Scheme 1. Reagents and conditions: (i) i-PrONO, EtONa, EtOH,
10 °C, then AcOH; (ii) N2H4–H2O, EtOH, rt; (iii) pyridine-2,6-
dicarboxaldehyde, AcOH, reflux (1 min); (iv) 2,5-norbornadiene,
xylene, 48 h; (v) 1-(4-morpholino)cyclo-pentene, dioxane, reflux, 6 h.
Keywords: Terpyridines; Bistriazinylpyridines.
*
Corresponding author. Tel.: +7 343 375 4501; fax: +7 343 374
0458; e-mail: dnk@htf.ustu.ru
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.01.020

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V. N. Kozhevnikov et al. / Tetrahedron Letters 46 (2005) 1521–1523
Table 1. Bistriazinylpyridines 2a–e, terpyridines 1a,c and 6a,e produced via Scheme 1
Procedure Yield (%) Mp( °C)
1H NMR spectra, d
Formula
Calculated (%)
Found (%)
C
H
N
2a
2b
2c
2d
A
A
A
A
66
85
68
65
>290
(CF3COOD) 7.80 (m, 6H), 8.33 (m, 4H), 8.86
(t, J = 8.5 Hz,1H), 9.32 (d, J = 8.5 Hz, 2H),
10.04 (s, 2H)
C23H15N7
C25H19N7
C25H19N7O2
70.94 3.88 25.18
70.92 3.83 25.20
260–262
>290
(CF3COOD) 2.58 (s, 6H), 7.60 (m, 4H), 8.22
(m, 4H), 8.80 (t, J = 8.4 Hz, 1H), 9.25
(d, J = 8.4 Hz, 2H), 10.03 (s, 2H)
71.93 4.59 23.49
71.81 4.45 23.61
(CF3COOD) 4.09 (s, 6H), 7.34 (m, 4H), 8.38
(m, 4H), 8.78 (t, J = 8.0 Hz, 1H), 9.22
(d, J = 8.0 Hz, 2H), 10.02 (s, 2H)
66.81 4.26 21.81
66.70 4.20 21.98
>290
(CF3COOD) 7.92 (m, 4H), 8.19 (m, 4H), 8.89
(t, J = 8.1 Hz, 1H), 9.33 (d, J = 8.1 Hz, 2H),
9.98 (s, 2H)
C23H13Br2N7 50.48 2.39 17.92
50.41 2.42 17.78
2e
1a
A
B
73
80
>290
(DMSO-d6) 8.49 (m, 4H), 8.57 (t, J = 7.8 Hz, 1H),
8.61 (m, 4H), 8.78 (d, J = 7.8 Hz, 2H), 9.75 (s, 2H)
C23H13N9O4
C27H19N3
57.62 2.73 26.29
57.53 2.79 26.17
218–220
(CDCl3) 7.45 (m, 2H), 7.53 (m, 4H), 7.68 (m, 4H),
7.99 (t, J = 7.6 Hz, 1H), 8.07 (dd, J = 8.2, 2.4 Hz,
2H), 8.46 (d, J = 7.6 Hz, 2H), 8.72 (dd, J = 8.2, 0.9 Hz,
2H), 8.90 (dd, J = 2.4, 0.9 Hz, 2H)
84.13 4.97 10.90
84.05 5.02 10.72
1c
B
65
281–282
(DMSO-d6/CCl4) 3.85 (s, 6H), 7.05 (m, 4H), 7.67
C29H23N3O2
78.18 5.20
78.24 5.25
9.43
9.35
(lit.6 280) (m, 4H), 8.02 (t, J = 7.8 Hz, 1H), 8.12 (dd, J = 8.2,
2.4 Hz, 2H), 8.46 (d, J = 7.8 Hz, 2H), 8.65
(d, J = 8.2 Hz, 2H), 8.90 (d, J = 2.4 Hz, 2H)
6a
6e
C
C
75
55
102–104
283–285
(DMSO-d6) 2.06 (m, 4H), 3.04 (t, J = 7.0 Hz, 4H),
3.39 (t, J = 7.0 Hz, 4H), 7.50 (m, 10H), 8.04
(t, J = 7.1 Hz, 1H), 8.20 (d, J = 7.1 Hz, 2H), 8.48 (s, 2H)
C33H27N3
85.13 5.85
9.02
85.01 5.70
9.19
(DMSO-d6/CCl4) 2.08 (m, 4H), 3.08 (t, J = 7.4 Hz,
4H), 3.42 (t, J = 7.4 Hz, 4H), 7.83 (m, 4H), 8.04
(t, J = 7.2 Hz, 1H), 8.23 (d, J = 7.2 Hz, 2H),
8.35 (m, 4H), 8.57 (s, 2H)
C33H25N5O4
71.34 4.54 12.61
71.25 4.32 12.70
We devised a new method for the synthesis of 2,6-bis(6-
aryl-1,2,4-triazin-3-yl)pyridines 2 starting from readily
available acylarenes 3 bearing various substituents on
the aryl moiety, for example, bromine, methyl, methoxy
or nitro groups. Nitrosation of 3 yielded the correspond-
ing 1-aryl-2-oximino-1-ethanones 4 after which treat-
ment with hydrazine hydrate resulted in the formation
of 1-aryl-1-hydrazono-2-oximinoethanes 5 in good
yields. Condensation of hydrazones 5 with pyridine-
2,6-dicarboxaldehyde followed by dehydration of the
intermediates (4-hydroxy-3,4-dihydro-1,2,4-triazines)10
by briefly refluxing in acetic acid gave the bistriazinyl-
pyridines 2.11 The aryl substituents of the starting
ketones 3 appear at position 6 of the 1,2,4-triazines 2
not position 5, as in typical 1,2,4-triazine synthesis
from arylglyoxals.12
Inverse electron demand aza-Diels–Alder reactions14,15
of 2 with eneamines as dienophiles were used to
extend the substituent diversity. Bistriazinylpyridines
2a,e reacted with 1-(4-morpholino)cyclopentene more
readily than with norbornadiene (refluxing in dioxane
instead of xylene) yielding terpyridines 6a,e with
fused five-membered rings (Scheme 1).16 The solubility
of the arylterpyridines was increased in this way
(Table 1).
In conclusion, the structural diversity is achieved by vari-
ation of three independent components: acylarenes and
dienophiles (substituents in peripheral pyridines), as well
as pyridinedicarboxaldehyde (substituents on the pyri-
dine). Good yields of all intermediates and products,
accessible starting compounds and a relatively easy
experimental procedure, together combine to make a
useful route for creating libraries of terpyridines suitable
for any application.
Conversion of bistriazinylpyridines 2 into terpyridines 1
was achieved by aza-Diels–Alder reaction with the
strained dienophile—2,5-norbornadiene—following a
typical procedure.8 The reaction proceeded slowly and
at high temperature (refluxing in xylene) to give 5,500-di-
aryl-2,20:60,200-terpyridines 1 cleanly and in good yields.13
The reaction needs a long time to go to completion due
to the very low solubility of bistriazinylpyridines 2.
Acknowledgements
The authors thank the Russian Foundation for Basic
Research (grant no. 04-03-96106) for financial support.

V. N. Kozhevnikov et al. / Tetrahedron Letters 46 (2005) 1521–1523
1523
solution of pyridine-2,6-dicarboxaldehyde (1.35 g, 10
mmol) in acetic acid (10 mL). The mixture was heated to
reflux and allowed to cool to room temperature. The
precipitate was filtered off, washed with water and
recrystallized from DMSO to give 2.
References and notes
1. Constable, E. C. In Comprehensive Supramolecular Chem-
istry; Lehn, J.-M., Ed.; Pergamon, 1996; Vol. 9, pp 213–
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12. Neunhoeffer, H. In Comprehensive Heterocyclic Chemistry
II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.;
Pergamon: Oxford, 1996; Vol. 6, pp 50–574.
13. Procedure B. A mixture of 2,6-bis(6-aryl-1,2,4-triazin-3-
yl)pyridine 2c (0.67 mmol), 2,5-norbornadiene (1.33 g,
13.4 mmol) and o-xylene (30 mL) was refluxed for 48 h
and then cooled to room temperature. The precipitate was
filtered off, washed with benzene and recrystallized from
acetic acid to give the terpyridine 1.
14. Rykowski, A.; Branowska, D.; Kielak, J. Tetrahedron
Lett. 2000, 41, 3657–3658.
15. Kozhevnikov, V. N.; Kozhevnikov, D. N.; Nikitina, T. V.;
Rusinov, V. L.; Chupakhin, O. N.; Zabel, M.; Koenig, B.
J. Org. Chem. 2003, 68, 2882–2888.
16. Procedure C. A mixture of 2,6-bis(6-aryl-1,2,4-triazin-3-
yl)pyridine 2 (1.0 mmol), 1-(4-morpholino)cyclo- pentene
(612 mg, 4 mmol) and 1,4-dioxane (20 mL) was heated at
reflux for 6 h. Then acetic acid (2 mL) was added and the
reaction mixture was heated at reflux for 30 min, cooled to
room temperature and made basic with aqueous 2 M
NaOH. The precipitate was filtered off, washed with water
and recrystallized from ethanol to give 6.
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11. Procedure A. To a solution of 1-hydrazono-2-oximino-1-
arylethane 5 (20 mmol) in AcOH (30 mL) was added a