Tetrahedron

Letters
Tetrahedron Letters 46 (2005) 1791–1793

An efficient route to 5-(hetero)aryl-2,4 0- and 2,2 0-bipyridines

through readily available 3-pyridyl-1,2,4-triazines
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 9 December 2004; revised 18 January 2005; accepted 25 January 2005

Abstract—A new route to substituted bipyridines based on a new method for the synthesis of substituted 3-pyridyl-1,2,4-triazines
and their aza-Diels–Alder reactions is shown to be an efficient strategy for the preparation of structurally diverse bipyridine ligands.
Ó 2005 Elsevier Ltd. All rights reserved.

2,2 0 -Bipyridines (bpy) are undoubtedly among the most 6-position of the 1,2,4-triazine ring. It should be noted
widely used ligands in coordination and supramolecular that 3-pyridyl-1,2,4-triazines are interesting compounds
chemistry.1,2 In particular, the photophysical properties in their own right due to their application in transition
of their metal complexes are of special interest. It was metal analysis11 or in the separation of lanthanides
shown in numerous studies that the transition metal and actinides in the management of nuclear waste.12
bpy complexes find various applications: from catalysis3
and photocatalysis4 to chemosensors5 and luminescent We devised a new method for the synthesis of 6-aryl-3-
probes for biomolecular systems.6 Among bipyridines, (2-pyridyl)-1,2,4-triazines 2 starting from readily avail-
5-aryl-2,2 0 -bipyridines (arbpy) exhibit the best lumines- able acylarenes 3 bearing various substituents on the
cent properties with emission quantum yields (Uf) up aryl moiety, for example, fluoro-, chloro-, bromo-,
to 0.80, due to the effect of the aromatic substituents methyl-, methoxy- or nitrophenyl. Nitrosation of 3
making the bipyridines attractive as chromophores and yielded the corresponding 1-aryl-2-oximino-1-ethanones
ÔantennaeÕ.7 Strong fungicidal activity of 5-aryl-2,2 0 - 4, then treatment with hydrazine hydrate resulted in the
bipyridines against different plant diseases is another formation of 1-aryl-1-hydrazono-2-oximinoethanes 5 in
application to be described.8 However, the study of good yields. Condensation of hydrazones 5 with pyri-
these interesting and useful compounds is hampered dine-2-carboxaldehyde gave 1-aryl-2-oximino-1-(2-pyr-
by inefficient chemical synthesis. The typical Kroehnke idylmethylenehydrazono)ethanes 6 in excellent yields.
synthesis was modified to prepare 5-substituted-2,2 0 - The open-chain compounds 6 exist in equilibrium with
bipyridines giving mixtures of isomers and poor yields.8 the cyclic 6-aryl-4-hydroxy-3-(2-pyridyl)-3,4-dihydro-
Alternative cross-coupling9 approaches are limited by 1,2,4-triazines 7 (the ring-chain isomerism of 4-hydro-
inaccessible starting compounds. xy-3,4-dihydro-1,2,4-triazines is described elsewhere13).
Dehydration of the dihydrotriazines 7 after brief reflux-
In this letter we report an efficient strategy for the syn- ing in acetic acid yielded the aromatic pyridyltriazines 2.
thesis of 5-(hetero)aryl-2,2 0 -bipyridines 1 based on the The aryl substituents of the starting ketones 3 appear ex-
conversion of 3-(2-pyridyl)-1,2,4-triazines to substituted actly at the defined 6-position of the 1,2,4-triazines 2 and
bpys via an aza-Diels–Alder reaction.10 The key-step of not the 5-position as in 1,2,4-triazine synthesis from
our strategy is the regiospecific and easy synthesis of 3- arylglyoxals.14 Isolation of the intermediates 6 and 7
pyridyl-1,2,4-triazines bearing an aryl substituent at the from the reaction mixtures can be omitted to make the
synthetic procedure easier.15

Keywords: Bipyridines; Polypyridines; 1,2,4-Triazines; Ligands. Conversion of triazines 2 to arbpys 1 was achieved by
* Corresponding author. Tel.: +7 343 3754501; fax: +7 343 aza-Diels–Alder reactions with a strained dienophile—
3740458; e-mail: dnk@htf.ustu.ru 2,5-norbornadiene—following a typical procedure.10

0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.01.135
1792 V. N. Kozhevnikov et al. / Tetrahedron Letters 46 (2005) 1791–1793

Ar O Ar O Ar N Ar N Ar N iv
i ii NH2 iii N N
HN
N N 65-85%
55-70% N 50-70% N 93-98% N
OH OH OH OH
3a-j 4a-j 5a-j
6a-j 7a-j
Ar N Ar
N v
N N
N 85-95% N

2a-j 1a-j

vi 70-90%

Ar = C6H5 (a), 4-CH3-C6H4 (b),

Ar
4-CH3O-C6H4 (c), 4-F-C6H4 (d),
N 4-Cl-C6H4 (e), 4-Br-C6H4 (f),
N 4-NO2-C6H4 (g), 4-pyridyl (h),
2-pyridyl (i), 2-thienyl (j)
8h

Scheme 1. Reagents and conditions: (i) i-PrONO, EtONa, EtOH, 10 °C, then AcOH; (ii) N2H4–H2O, EtOH, rt; (iii) pyridine-2-carboxaldehyde,
EtOH; (iv) AcOH, reflux; (v) 2,5-norbornadiene, xylene, reflux, 8–15 h; (vi) morpholinocyclopentene, dioxane, reflux.

The reaction proceeded slowly and at high temperature

(refluxing in xylene) to give 5-aryl-2,2 0 -bipyridines 1 in
high yields.

Starting from acylheteroarenes, for example, acetylthio-

phene, 2- or 4-acetylpyridines, 3-(2-pyridyl)-1,2,4-tri-
azines 2h–j15 bearing heteroaromatic substituents at
the 6-position were obtained by this method. Next, the
cycloaddition step gave 5-heteroaryl-2,2 0 -bipyridines
1h–j.16

Additional substituent diversity was achieved using ene-

amines as dienophiles in inverse electron demand aza-
Diels–Alder reactions17,18 Pyridyltriazine 2h reacted
with morpholinocyclopentene more readily than with Scheme 2. Reagents and conditions: (iv) AcOH, reflux; (v) 2,5-
norbornadiene (refluxing in dioxane instead of xylene) norbornadiene, xylene, reflux.
yielding 8h possessing a fused five-membered ring
(Scheme 1).19
In conclusion it should be noted, that the good yields of
Finally, the arbpys diversity could be extended by vary- all intermediates and final products, multi-gram scale,
ing the substituents in the starting pyridinecarboxalde- cheap and accessible starting compounds and relatively
hydes, for example, 5-tolyl-6 0 -hydroxymethyl-2,2 0 - easy experimental procedure make these substituted
bipyridine 9b was obtained from 6-hydroxymethylpyr- bipyridines readily available compounds. Substituent
idine-2-carboxaldehyde (Scheme 2). diversity is achieved by variation of three independent
components: the acyl(hetero)arenes, dienophiles and
Not only 2,2 0 - but 2,4 0 -bipyridines could be obtained pyridinecarboxaldehyde.
by our method. The condensation of pyridine-4-carbox-
aldehyde with hydrazones 5 followed by dehydration
of the intermediates resulted in the formation of 6-aryl- Acknowledgements
3-(4-pyridyl)-1,2,4-triazines 10, then refluxing with nor-
bornadiene yielded 5-aryl-2,4 0 -bipyridines 11 (Scheme The authors thank the Russian Foundation for Basic
2). Researches (grant no. 04-03-96106) for financial
support.
It is noteworthy, that the reactions could be easily scaled
up to produce multi-gram quantities of arbpys 1 (we
obtained 5 g of the arbpy 1b from one operation). The Supplementary data
relatively harsh conditions (long time (up to 15 h) and
high temperatures (refluxing in xylene) of the reaction Supplementary data associated with this article can be
with norbornadiene did not affect the yields or purities found, in the online version, at doi:10.1016/j.tetlet.
of the arbpys 1. 2005.01.135.
 V. N. Kozhevnikov et al. / Tetrahedron Letters 46 (2005) 1791–1793 1793

References and notes with water and recrystallized from ethanol to afford a
yellow crystalline solid (2.66 g, 68%), mp 193–194 °C, 1H
1. von Zelewsky, A. Stereochemistry of Coordination Com- NMR (250 MHz, DMSO-d6): d = 7.64 (ddd, 1H, J 7.5,
pounds; Wiley: Chichester, 1996. 4.7, 1.1 Hz), 8.09 (ddd, 1H, J 7.8, 7.8, 1.8 Hz), 8.26 (m,
2. Constable, E. C. In Comprehensive Supramolecular Chem- 2H), 8.52 (br d, 1H, J 7.9 Hz), 8.85 (m, 3H), 9.65 (s, 1H);
istry; Lehn, J.-M., Ed.; Pergamon, 1996; Vol. 9, pp 213–252. C13H9N5 (235.25) calcd C, 66.37; H, 3.86; N, 29.77. Found
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3170. 16. 5-(4-Pyridyl)-2,2 0 -bipyridine 1h. A mixture of 3-(2-pyr-
4. Ziessel, R. In Photosensitization and Photocatalysis Using idyl)-6-(4-pyridyl)-1,2,4-triazine 2h (730 mg, 3.1 mmol),
Inorganic and Organic Compounds; Kalyanasundaram, bicyclo[2.2.1]hepta-2,5-diene (1.58 mL, 15.5 mmol) and
K., Grätzel, M., Eds.; Kluwer Academic: Dordrecht, o-xylene (30 mL) was refluxed for 10 h and cooled to
1993, pp 217–246. room temperature. The resulting precipitate was filtered
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Rev. 2000, 205, 201–228. product (638 mg, 88%), mp 185–187 °C, 1H NMR
6. Saha, A. K.; Kross, K.; Kloszewski, E. D.; Upson, D. A.; (250 MHz, DMSO-d6): d = 7.48 (ddd, 1H, J 7.6, 4.9,
Toner, J. L.; Snow, R. A.; Black, C. D.; Decai, V. C. 1.2 Hz), 7.85 (m, 2H), 7.98 (ddd, 1H, J 7.9, 7.9, 1.8 Hz),
J. Am. Chem. Soc. 1993, 115, 11032–11033. 8.37 (dd, 1H, J 8.2, 2.1 Hz), 8.45 (m, 1H), 8.52 (dd, 1H,
7. Loren, J. C.; Siegel, J. S. Angew. Chem., Int. Ed. 2001, 40, J 8.2, 0.6 Hz), 8.70 (m, 3H), 9.13 (dd, 1H, J 2.1, 0.6 Hz);
754–757. C15H11N3 (233.28) calcd C, 77.23; H, 4.75; N, 18.01.
8. Kelly-Basetti, B. M.; Cundy, D. J.; Pereira, S. M.; Sasse, Found C, 77.25; H, 4.72; N, 17.96.
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289–295. mixture of 3-(2-pyridyl)-6-(4-pyridyl)-1,2,4-triazine 2h
12. Kolarik, Z.; Mullich, U.; Gassner, F. Solvent Extr. Ion (400 mg, 1.7 mmol), 1-morpholinocyclopentene (0.3 mL,
Exch. 1999, 17, 23–32. 287 mg, 1.8 mmol) and 1,4-dioxane (20 mL) was refluxed
13. Kozhevnikov, D. N.; Rusinov, V. L.; Chupakhin, O. N. In for 24 h. Then acetic acid (2 mL) was added and the
Adv. Heterocycl. Chem.; Katritzky, A. R., Ed.; Academic, reaction mixture was heated at reflux for 1 h, cooled to
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Oxford, 1996; Vol. 6, pp 50–574. ethanol–water (1:1) to give the titled compound (320 mg,
15. 3-(2-Pyridyl)-6-(4-pyridyl)-1,2,4-triazine 2h. To a solution 79%), mp 154–155 °C, 1H NMR (250 MHz, DMSO-d6):
of 1-hydrazono-2-oximino-1-(4-pyridyl)ethane 5h (2.74 g, d = 2.02 (p, 2H, J 7.6 Hz), 3.04 (t, 2H, J 7.6 Hz), 3.43 (t,
16.7 mmol) in AcOH (10 mL) was added 2-pyridinecar- 2H, J 7.6 Hz), 7.42 (ddd, 1H, J 7.3, 4.9, 1.2 Hz), 7.61 (m,
boxaldehyde (1.79 g, 16.7 mmol). The mixture was stirred 2H), 7.94 (ddd, 1H, J 7.9, 7.9, 1.8 Hz), 8.31 (ddd, 1H, J
at room temperature for 1 h, heated to reflux, allowed to 7.9, 0.9, 0.9 Hz), 8.59 (s, 1H), 8.70 (m, 3H); C18H15N3
cool to room temperature and then diluted with water (273.34) calcd C, 79.10; H, 5.53; N. 15.37. Found C, 79.15;
(10 mL). The resulting precipitate was filtered off, washed H, 5.42; N, 15.36.