A novel one-pot synthesis of annulated 2,2'-bipyridine ligands by inverse electron demand Diels-Alder reaction of 5,5'-bi-1,2,4-triazines

Article abstract of DOI:10.1016/S0040-4039(00)00436-6

The Diels-Alder reaction of 5,5'-bi-1,2,4-triazines with cyclic enamines in the absence of a solvent leads to a range of symmetrical, annulated 2,2'- bipyridines in good yield. When the reaction is carried out in boiling dioxane only 5-(heteroaryl)1,2,4-triazines are formed. The latter, bearing methylsulfanyl substituents, are oxidized with potassium permanganate to the corresponding methylsulfonyl derivatives, which easily undergo Diels-Alder reactions with different enamines to give unsymmetrical, annulated 2,2'- bipyridines. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00436-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3657–3659
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A novel one-pot synthesis of annulated 2,2 -bipyridine ligands by
inverse electron demand Diels–Alder reaction of
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,5 -bi-1,2,4-triazines
∗
Andrzej Rykowski, Danuta Branowska and Joanna Kielak
Institute of Chemistry, University of Podlasie, 3-go Maja 54, 08-110 Siedlce, Poland
Received 6 January 2000; accepted 13 March 2000
Abstract
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The Diels–Alder reaction of 5,5 -bi-1,2,4-triazines with cyclic enamines in the absence of a solvent leads to
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a range of symmetrical, annulated 2,2 -bipyridines in good yield. When the reaction is carried out in boiling
dioxane only 5-(heteroaryl)1,2,4-triazines are formed. The latter, bearing methylsulfanyl substituents, are oxidized
with potassium permanganate to the corresponding methylsulfonyl derivatives, which easily undergo Diels–Alder
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reactions with different enamines to give unsymmetrical, annulated 2,2 -bipyridines. © 2000 Elsevier Science Ltd.
All rights reserved.
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Keywords: bi-1,2,4-triazines; enamines; Diels–Alder reaction; annulated 2,2 -bipyridines.
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,2 -Bipyridine ligands are widely used in coordination and supramolecular chemistry. Their an-
nulated derivatives incorporated into larger macropolycyclic structures are particularly attractive since
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they form stable luminescent complexes with a variety of lanthanide cations. The latter can be used as
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markers for modern medical applications. Although there are several methods to synthesize annulated
bipyridines with benzo fusion, only a limited number of reports have appeared regarding their analogues
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with attached cycloalkene rings. More recent approaches employ cobalt(I)-catalyzed [2+2+2] cyclo-
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additions between 5-hexynenitrile and 1,3-diynes or the double intramolecular Diels–Alder reaction
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of α,β-unsaturated hydrazones with 1,3-dialkynes. This intramolecular Diels–Alder reaction has a
broad substrate scope with respect to the unsaturated hydrazones; however, the preparation of the latter
compounds requires multistep synthesis. In this communication we present a more straightforward
approach to cycloalkenobipyridines which involves the use of intermolecular Diels–Alder reactions of
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,5 -bi-1,2,4-triazines.
Inverse electron demand Diels–Alder reactions of monocyclic 1,2,4-triazines with electron rich dieno-
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philes have become useful tools in the preparation of novel pyridines and bipyridines. We have applied
∗
Corresponding author. E-mail: rykowski@ap.siedlce.pl (A. Rykowski)
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040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00436-6
tetl 16716

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this methodology to the direct synthesis of a range of symmetrical and unsymmetrical, annulated 2,2 -
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bipyridines from easily available 5,5 -bi-triazines 1a–b and cyclic enamines.
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Heating 3,3 -bis(methylthio)-5,5 -bi-1,2,4-triazine 1a with 1-pyrrolidino-1-cyclopentene 2a in the
absence of a solvent at 130°C gives 1,1 -bis(methylthio)-3,3 -bi(cyclopenta[c]pyridine) 3a in 68% yield.
Also, the six- and seven-membered enamines (2b and 2c) react efficiently with 1a at a higher temperature
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giving directly 3b and 3c in 56 and 70% yields, respectively. Oxidation of 2,2 -bipyridines 3a–c with
potassium permanganate under phase transfer catalysis conditions provides a series of methylsulfonyl
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derivatives 3d–f in good yield. The same order of reactivity is observed on treatment of 3,3 -bis(methyl)-
5
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,5 -bi-1,2,4-triazine 1b with the cyclic enamines 2a–c. However, the yield of the biisoquinoline
derivative 3h formed in the reaction of 1b with 2b is much lower than those of bipyridines 3g and 3i
Scheme 1, Table 1).
(
Scheme 1.
Table 1
a
b
Yields and melting points of compounds 3–6
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It has been found that 5,5 -bi-1,2,4-triazines 1a–b undergo [4+2] cycloadditions with cyclic enamines
by a different pathway if the reactions are carried out in an appropriate solvent. When 1a and 1b are
reacted with 2a–c in boiling dioxane only 5-(heteroaryl)-1,2,4-triazines 4a–f are formed in excellent
yield. The compounds 4a–c bearing a methylsulfanyl substituent are oxidized easily with potassium
permanganate to the corresponding methylsulfonyl derivatives 5a–c. The reaction of these compounds
with different enamines is completed within 1 hour at room temperature leading to unsymmetrical,
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annulated 2,2 -bipyridines 6a–c (Scheme 2, Table 1).
Scheme 2.

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In summary, we have described a new, simple method to gain access to annulated 2,2 -bipyridines with
cycloalkene rings.
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