A new route to 6,6″-dicyano-2,2′:6′,2″-terpyridines and their complexes with Ni(II)

Article abstract of DOI:10.1016/S0040-4039(02)00951-6

A new methodology for the synthesis of functionalised 2,2′:6′,2″-terpyridine systems is suggested: sequential synthesis of the heterocyclic assemblies based on the 1,2,4-triazine ring, direct introduction of the cyano group in the 1,2,4-triazine ring and

Full text of DOI:10.1016/S0040-4039(02)00951-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4923–4925
A new route to 6,6%%-dicyano-2,2%:6%,2%%-terpyridines and their
complexes with Ni(II)
Dmitry N. Kozhevnikov,a,* Valery N. Kozhevnikov,a,* Tatiana V. Nikitina,a Vladimir L. Rusinov,a
Oleg N. Chupakhin,a Igor L. Eremenkob and Grigory G. Aleksandrovb
aUrals State Technical University, 620002 Ekaterinburg, Russia
bInstitute of General and Inorganic Chemistry, Moscow, Russia
Received 26 March 2002; revised 7 May 2002; accepted 17 May 2002
Abstract—A new methodology for the synthesis of functionalised 2,2%:6%,2%%-terpyridine systems is suggested: sequential synthesis
of the heterocyclic assemblies based on the 1,2,4-triazine ring, direct introduction of the cyano group in the 1,2,4-triazine ring and
the transformation of the latter to a pyridine ring via an aza-Diels–Alder reaction. © 2002 Elsevier Science Ltd. All rights reserved.
Organic molecules bearing the 2,2%:6%,2%%-terpyridine
moiety have a geometry is favourable for accepting
various metal centres, therefore such molecules are used
widely in coordination chemistry. Based on compounds
of this series and their complexes, highly sensitive ana-
lytical reagents,1 various sensor systems,2 reagents for
enantioselective synthesis,3 and luminescent agents for
labelled peptide synthesis4 were created. Besides,
2,2%:6%,2%%-terpyridines are attractive building blocks for
supramolecular chemistry.5
In the present paper we describe a new methodology
for the synthesis of functionalised terpyridines, based
on the direct introduction of substituents into a 1,2,4-
triazine ring followed by transformation of the latter
into the pyridine ring. In planning such an approach we
proceeded from the following points: (a) 1,2,4-triazine
4-oxides are very electrophilic heterocycles, that allow
the direct introduction to the 1,2,4-triazine ring of
various nucleophiles including the formation of a new
CꢀC bond;7 (b) 1,2,4-triazines react relatively easier
with electron rich dienophiles in an inverse electron
demand aza-Diels–Alder reaction resulting in their
transformation into pyridines.8 In this situation, suc-
cessful realisation of the suggested methodology
depends on the synthesis of heterocyclic assemblies
based on 1,2,4-triazines. To achieve this aim we used
the method for the synthesis of the 1,2,4-triazine 4-
The most common methods for the synthesis of the
2,2%:6%,2%%-terpyridines are by means of combination of
single pyridine blocks or formation of the central
(rarely both terminal) pyridine rings starting from the
corresponding open-chain intermediates (for a review
see Ref. 6).
Scheme 1. Reagents and conditions: (i) EtOH, rt, 12 h; (ii) Pb3O4/AcOH, rt; (III) NEt3, CHCl3, reflux.
* Corresponding authors. Tel.: +7-3432-740458; fax: +7-3432-740458; e-mail: dnk@htf.ustu.ru
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00951-6

4924
D. N. Kozhe6niko6 et al. / Tetrahedron Letters 43 (2002) 4923–4925
oxides described earlier.9 Thus, condensation of two
molecules of the hydrazone of isonitrozoacetophenone
with pyridine-2,6-dicarboxaldehyde in ethanol followed
by oxidative aromatisation of the intermediate with
Pb3O4 in acetic acid resulted in the formation of 2,6-
bis(4-oxid-6-phenyl-1,2,4-triazin-3-yl)pyridine 1.10 The
presence of the N-oxide group opens a way for func-
tionalisation of the 1,2,4-triazine rings of 1 via nucle-
ophilic substitution of hydrogen.7 Cyanide anion was
chosen as a nucleophile, since the introduction of the
cyano group in the heterocycle allows further modifica-
tions of potential ligands via typical nitrile transforma-
tions. We decided not to use the cyanide ion itself in
this reaction with 1, but instead used its synthetic
equivalent—acetone cyanohydrin in the presence of
triethylamine,11 affording 2,6-bis(5-cyano-6-phenyl-
1,2,4-triazin-3-yl)pyridine 2 (Scheme 1).12 The reaction
proceeded in good yield, hence the 1,2,4-triazines seem
to be useful building-blocks for the preparation of
oligopyridine systems.
purification by the elimination of pyrrolidine by reflux
in acetic acid to afford 2,6-bis(6-cyano-5-phenyl-3,4-
cyclopentenopyridyl-2)-pyridine L2 (Scheme 2).14 The
presence of two aliphatic rings in the molecule L2
increases the solubility in comparison with terpyridine
L1, thereby facilitating the synthesis of complexes with
transition metals.
Refluxing of ligand L2 with Ni(NO3)2·6H2O in acetoni-
trile led to the formation of a complex of molecular
formula of this complex L2Ni(NO3)2.15 The geometry
was established by X-ray analysis (Fig. 1).16 The Ni(II)
atom adepts a strained octahedral environment formed
by three nitrogen atoms of the ligand L2 and three
oxygen atoms of the nitrate anions with chelate and
One characteristic feature increasing the attraction of
1,2,4-triazines is the possibility of their facile transfor-
mation into a pyridine ring in one step as result of the
inverse electron demand Diels–Alder reaction.8 Thus,
refluxing dinitrile 2 with 2,5-norbornadiene in toluene
yielded 6,6%%-dicyano-5,5%%-diphenyl-2,2%:6%,2%%-terpyridine
L1 (Scheme 2).13
It is appropriate to use in this reaction more electron-
rich dienophiles such as enamines. For instance, treat-
ment of dinitrile 2 with 1-pyrrolidinocyclopentene
proceeded with loss of nitrogen resulting in an interme-
diate cycloadduct, which was aromatised without
Scheme 2. Reagents and conditions: (iv) toluene, reflux, 6 h;
(v) toluene, reflux, 1 h; (vi) AcOH, reflux, 1 h.
Figure 1. Geometry of the complex L2Ni(NO3)2.

D. N. Kozhe6niko6 et al. / Tetrahedron Letters 43 (2002) 4923–4925
4925
terminal coordination. The terpyridine system is almost
planar, and deviation of the metal atom from the
average plane of the terpyridine is 0.047 A. Torsion
angles between the planes of the phenyl substituents
and the terpyridine fragment are from 59.3 to 65.4°.
11. Chupakhin, O. N.; Rusinov, V. L.; Ulomsky, E. N.;
Kozhevnikov, D. N.; Neunhoeffer, H. Mendeleev Com-
mun. 1997, 66–67.
,
12. 2,6-Bis(5-cyano-6-phenyl-1,2,4-triazin-3-yl)-pyridine
2.
Acetone cyanohydrine (3.9 ml, 43 mmol) and triethyl-
amine (1.5 ml, 10 mmol) were added to a suspension of
compound 2 (4.5 g, 10 mmol) in chloroform. After 30
min at reflux, followed by evaporation in vacuo, purifica-
tion by column chromatography and recrystallisation
from ethyl acetate the product 2 was obtained. Yield 2.7
g (58%). Mp 176–177°C. 1H NMR (DMSO-d6), l: 7.75
(m, 6H), 8.15 (m, 4H), 8.48 (dd, 1H, J3 7.8 Hz, J3 7.8
Hz), 8.85 (d, 2H, J3 7.8 Hz). EI/MS (m/z) 439 (M+, 4%).
Anal. calcd for C25H13N9 (439.4): C, 68.33; H, 2.98; N,
28.69. Found C, 67.93; H, 2.71; N, 28.39%.
In conclusion, suggested methodology of sequential
synthesis of the heterocyclic assemblies based on the
1,2,4-triazine ring, direct introduction of the cyano
group via nucleophilic substitution of hydrogen and
transformation of the 1,2,4-triazine rings into pyridine
rings by way of the aza-Diels–Alder reaction is a conve-
nient method for the synthesis of functionalised
2,2%:6%,2%%-terpyridines. It has to be noted that such
molecules are good acceptors for nickel atoms and,
perhaps, for other d-block elements.
13. 5,5%%-Diphenyl-6,6%%-dicyano-2,2%:6%2%%-terpyridine L1.
A
mixture of compound 2 (680 mg, 1.5 mmol) and bicy-
clo[2.2.1]hepta-2,5-diene (1.3 ml, 12 mmol) in toluene (10
ml) were refluxed for 6 h. The crystals formed were
filtered off and recrystallised from acetic acid to give 260
mg (40%) of the terpyridine L1. Mp 296–297°C. 1H NMR
(DMSO-d6), l: 7.6 (m, 6H), 7.75 (m, 4H), 8.22 (dd, 1H,
J3 7.8 Hz, J3 7.8 Hz), 8.3 (d, 2H, J3 8.0 Hz), 8.5 (d, 2H,
J3 7.8 Hz), 8.93 (d, 2H, J3 8.0 Hz); EI/MS (m/z) 435
(M+, 100%). Anal. calcd for C29H17N5 (435.5): C, 79.98;
H, 3.93; N, 16.08. Found C, 79.60; H, 3.75; N, 16.35%.
14. 2,6-Bis(6-cyano-5-phenyl-3,4-cyclopentenopyridyl-2)-pyri-
dine L2. 1-Morpholinocyclopentene (0.1 ml, 1.16 mmol)
was added to a solution of compound 2 (255 mg, 0.58
mmol) in toluene, the resulting mixture was kept at room
temperature for 1 h, then refluxed additionally for 1 h.
The solvent was removed in vacuo, and the residue was
refluxed in 3 ml of acetic acid. The crystals formed were
filtered off and recrystallised from DMF yielding 230 mg
(77%) of the ligand L2. Mp >300°C (dec.). 1H NMR
(DMSO-d6), l: 2.15 (m, 4H), 2.93 (t, 4H), 3.45 (t, 4H),
7.6 (m, 10H), 8.25 (m, 3H); EI/MS (m/z) 515 (M+,
100%). Anal. calcd for C35H25N5 (515.6): C, 81.53; H,
4.89; N, 13.58. Found C, 81.62; H, 4.81; N, 13.60%.
15. Complex L2Ni(NO3)2 was obtained as follows. A solution
of Ni(NO3)2·6H2O (84.4 mg, 0.29 mmol) in 3 ml of
acetonitrile was added to a solution of ligand L2 (150 mg,
0.29 mmol) in acetonitrile (5 ml). The resulting mixture
was refluxed for 15 min. The crystals formed after cooling
were filtered off, redissolved in hot acetonitrile and kept
at room temperature for 12 h resulting in green crystals,
suitable for X-ray analysis. Yield 152 mg, 75%. Mp
>300°C. Anal. calcd for C35H25N5*Ni(NO3)2 (698.3) C,
60.20; H, 3.61; N, 14.04. Found C, 59.33; H, 3.64; N,
13.82%.
Acknowledgements
The authors thank the RFBR (grant no. 02-03-32635)
and CRDF (project REC-005) for financial support.
References
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10. 2,6-Bis(4-oxide-6-phenyl-1,2,4-triazin-3-yl)-pyridine
1.
Pyridine-2,6-dicarboxaldehyde (3.5 g, 26 mmol) and the
hydrazone of isonitrosoacetophenone (8.5 g, 52 mmol)
were dissolved in 50 ml of ethanol and kept overnight at
room temperature. The crystals formed were filtered off,
dried and suspended in 150 ml of acetic acid. Lead(IV)
oxide (34.2 g, 50 mmol) was added to the resulting
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room temperature. The crystals of the product were
filtered off and recrystallised from DMF. Yield 5.6 g,
16. CCDC 182870 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/conts/retrieving.
html (or from the CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336033; e-mail: deposit@
ccdc.cam.ac.uk
1
52%. Mp >270°C (dec.). H NMR (DMSO-d6) l 7.6 (m,
6H), 8.25 (m, 7H), 9.43 (s, 2H); EI/MS (m/z) 421 (M+,
10%). Anal. calcd for C23H15N7O2 (421.4): C, 65.55; H,
3.58; N, 23.26. Found C, 65.75; H, 3.39; N, 23.38%.