From 1,2,4-triazines towards substituted pyridines and their cyclometallated Pt complexes

Article abstract of DOI:10.1016/j.tetlet.2008.04.138

A new, efficient methodology for the synthesis of substituted thienylpyridines includes the synthesis of 3-thienyl-1,2,4-triazines using simple heterocyclisation followed by easy transformation of the triazine ring to a pyridine through an aza Diels-Alder approach. A variety of substituted pyridines can be easily achieved using cheap, commercially available reagents such as bromoacetylarenes, aroyl hydrazides, norbornadiene, and enamines in various combinations. New thienylpyridines form phosphorescent cyclometallated Pt complexes.

Full text of DOI:10.1016/j.tetlet.2008.04.138

Tetrahedron Letters 49 (2008) 4096–4098
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: http://www.elsevier.com/locate/tetlet
From 1,2,4-triazines towards substituted pyridines and their cyclometallated
Pt complexes
Valery N. Kozhevnikov a,c, , Maria M. Ustinova b,c, Pavel A. Slepukhin a, Amedeo Santoro c,
*
Duncan W. Bruce c, Dmitry N. Kozhevnikov a,b,
*
a Institute of Organic Synthesis, Ural Branch of Russian Academy of Sciences, Kovalevskoy 22, Ekaterinburg 620219, Russia
b Ural State Technical University, Mira 19, Ekaterinburg 620002, Russia
c Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
A new, efficient methodology for the synthesis of substituted thienylpyridines includes the synthesis of
3-thienyl-1,2,4-triazines using simple heterocyclisation followed by easy transformation of the triazine
ring to a pyridine through an aza Diels–Alder approach. A variety of substituted pyridines can be easily
achieved using cheap, commercially available reagents such as bromoacetylarenes, aroyl hydrazides,
norbornadiene, and enamines in various combinations. New thienylpyridines form phosphorescent
cyclometallated Pt complexes.
Received 20 March 2008
Revised 17 April 2008
Accepted 24 April 2008
Available online 27 April 2008
Keywords:
Thienylpyridines
1,2,4-Triazines
Ó 2008 Published by Elsevier Ltd.
Cyclometallated Pt complexes
A significant research effort has focused on the photophysical
and photochemical properties of luminescent cyclometallated Ir
and Pt complexes.1–3 These complexes have found a wide range
of applications such as optical chemosensors,4 photocatalysts,5
molecular photochemical devices for solar energy conversion6
and biological labelling reagents.7 In particular, they are consid-
ered advantageous for application as phosphorescent emitters in
organic light-emitting diodes (OLEDs).8,9 Some cyclometallated
platinum and iridium complexes of 2-(hetero)arylpyridines, which
also contain 1,3-diketonates as auxiliary ligands, were reported to
be strongly emissive, and the nature of the cyclometallating ligand
was found to affect strongly the energy of the emissive state so that
the emission colour could be tuned.10,11 Thus, the photophysical
properties of complexes can be tuned by appropriate ligand design.
It is known that 1,2,4-triazines can be converted into pyridines
through an aza Diels–Alder reaction.12 Thus, a combination of the
wide variety of methods for the synthesis of substituted 1,2,4-tri-
azines, coupled with the aza Diels–Alder reaction with various
dienophiles, allows for the synthesis of different functionalised
pyridines.13–19 In this Letter we report the application of 1,2,4-tri-
azine chemistry in the development of a new, efficient, flexible and
straightforward methodology for the synthesis of ligands capable
of forming cyclometallated complexes with PtII.
The method started with the synthesis of 1,2,4-triazines using
the heterocyclisation reaction described by Saraswathi and Srini-
vasan in 1971, where 2-bromoacetophenone was reacted with
two equivalents of acid hydrazides in the presence of a base to give
3,6-disubstituted-1,2,4-triazines.20 We found that this approach
was not always consistent and in some cases the yields of the de-
sired triazines were far from perfect. Thus, the reactions of bromo-
acetylarenes 1a–d with pyridine-2-carboxylic acid hydrazide 2
resulted in 6-aryl-3-pyridyl-1,2,4-triazines 3a–d in 12–22% yields
(Scheme 1). The low yields (compared with the method21 using
cyclisation of hydrazones of 2-oximinoacetophenones and 2-pyr-
idinecarboxaldehyde) are partly compensated by the fact that
bromoacetylarenes are more readily available than oximinoace-
tophenones (e.g., di- and trimethoxy derivatives). Transformations
of the pyridyltriazines 3 into arylbipyridines 4 via aza Diels–Alder
reactions with 2,5-norbornadiene have been reported.21
Fortunately, synthesis of the desired thienyltriazines was more
successful. Reactions of bromoacetylarenes 1a,b and thienylcarb-
oxylic acid hydrazide 5 in the presence of sodium acetate gave
6-aryl-3-thienyl-1,2,4-triazines 6a,b in 60–65% yields (Scheme
1).22 The best solvent for the reaction was a mixture of ethanol–
acetic acid (3:1). Simple filtration of the resulting crystals from
the reaction mixture gave pure product 6. This synthetic procedure
is very simple and can be performed on a multigram scale. The next
step in the synthesis of the target ligands is the inverse-electron-
demand Diels–Alder reaction. The electron-rich dienophile 1-mor-
pholinocyclopentene reacts readily with electron-deficient 1,2,4-
triazines to give cyclopenteno[c]pyridines 7a,b in 55–82% yields
* Corresponding authors. Tel.: +7 343 3623341; fax: +7 343 3693058 (D.N.K.).
E-mail address: dnk@ios.uran.ru (D. N. Kozhevnikov).
0040-4039/$ - see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2008.04.138

V. N. Kozhevnikov et al. / Tetrahedron Letters 49 (2008) 4096–4098
4097
Ar
12-22%
N
N
H2N
Ar
Ar
O
ii
N
i
NH
+
2
N
N
N
O
N
Br
3a-d
4a-d
1a-d
2
Ar
N
N
H2N
Ar
Ar
O
N
i
iv
80-90%
NH
+
2
S
S
S
41-48%
O
R
R
N
Br
C6H13
1a-d
6a,b (R = H)
9c,d (R = C6H13
5 (R = H)
8 (R = C6H13
10c,d
)
)
iii
55-82%
Ar
Ar
vii
64-84%
Ar = Ph (a)
Ar = 2-Naphthyl (b)
Ar = 3,4-(MeO)2C6H3 (c)
S
Ar
v,vi
S
N
Pt
N
S
O
Pt
Cl
N
Ar = 3,4,5-(MeO)3C6H2 (d)
O
O
S
7a,b
11a,b
12a,b
Scheme 1. Synthesis of substituted thienylpyridines. Reagents and conditions: (i) EtOH/AcOH, NaOAc, reflux, 12 h; (ii) 2,5-norbornadiene, o-xylene, reflux, 12 h; (iii) 1-
morpholinocyclopentene, 220 °C, 0.5 h; (iv) 2,5-norbornadiene, o-xylene, 200 °C, 12 h; (v) K2[PtCl4], AcOH, reflux, 24 h; (vi) DMSO, reflux, 10 min; (vii) Na acac, acetone, rt, 12 h.
(Scheme 1).23 The reaction is performed in the absence of solvent
at high temperature (220 °C). Morpholinocyclopentene must be
used in 3–5-fold excess to compensate for partial decomposition.
To increase the solubility of the thienylpyridines and their com-
plexes, we decided to introduce an aliphatic chain to the molecule.
Thus, the reactions of 5-hexylthiophene-2-carboxylic acid hydra-
zide 8 with 2-bromo-30,40-dimethoxyacetophenone 1c and 2-
bromo-30,40,50-trimethoxyacetophenone 1d under the conditions
described above resulted in hexylthienyltriazines 9c,d (Scheme
1). Transformation of triazines 9 to monocyclic pyridines 10c,d
was performed by heating with 2,5-norbornadiene in o-xylene in
an autoclave at elevated temperatures (200 °C), that allowed the
reaction time to be shortened significantly (12 h) with no adverse
effect on the yield. There were no cross-coupling reactions, and
therefore expensive reagents and complicated reaction conditions
are avoided. All the reactions are easily scalable and can be
performed on multigram scale.
Cyclometallated PtII complexes of cyclopentenopyridines 7a,b
were obtained according to an improved method. Thus, heating
ligands 7a,b with equimolar quantities of K2[PtCl4] in acetic acid
resulted exclusively in the dinuclear bridged complexes, which
had low solubility. Addition of the platinum salt as a water solution
shortened the reaction time. The intermediate dinuclear complex
could be converted easily to a mononuclear DMSO complex by
heating in DMSO for a short-time to yield the mononuclear com-
plexes 11a,b, which could be isolated readily and purified (Scheme
1).24 DMSO complexes 11 are fairly soluble materials and their
reactions with sodium acetylacetonate in acetone proceed quite
easily to give target acac complexes 12a,b in high yields (Scheme
1).25 The reaction time (0.5–2.0 h) in this case is shorter compared
with the synthesis of analogous cyclometallated complexes from
poorly soluble bridged binuclear complexes.
Both DMSO 11 and acac 12 complexes were crystalline com-
pounds. Single crystals of 11a26 and 12b27 suitable for X-ray dif-
fraction crystallography were obtained by slow cooling of the
DMSO solution 11a or slow concentration of the DCM/MeOH solu-
tion 12b. Despite the difference in auxiliary ligands and the aryl
substituents, molecules of both complexes 11a and 12b pack as
centrosymmetric head-to-tail dimers (Figs. 1 and 2). The dimers
Figure 1. Crystal structure of dimer 11a. One of the 11a molecules has been ligh-
tened in colour for clarity. The solvent molecule and hydrogens are omitted. Sele-
cted bond lengths (Å) and angles (°): Pt(1)–C(16) 1.988(5), Pt(1)–N(1) 2.077(3),
Pt(1)–Cl(1) 2.3901(12), Pt(1)–S(2) 2.2035(11) Å, C(16)–Pt(1)–N(1) 80.48(15), Cl(1)–
Pt(1)–S(2) 94.27(4).28
have a plane-to-plane separation of 3.41 Å for 11a and 3.48 Å for
12b indicative of moderate p–p interactions. Short contacts
between the thiophene ring and the aryl group of the molecule
from the next dimer are evidence of moderate p–p interactions
between dimers (see Figs. S1 and S2 in ESI). The shortest distances
between the thiophene and the aryl groups are 3.49 Å for 11a and
3.44 Å for 12b. There are no metal–metal interactions. Each mole-
cule has a square planar geometry that is only slightly distorted
from perfect geometry. There are significant distortions of the
phenyl in 11a (44.6°) and naphthyl in 12b (49.9°) from the plane
of the thienylpyridine moieties because of steric hindrance result-
ing from the ortho-substituent.

4098
V. N. Kozhevnikov et al. / Tetrahedron Letters 49 (2008) 4096–4098
5. Hissler, M.; McGarrah, J. E.; Connick, W. B.; Geiger, D. K.; Cummings, S. D.;
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3108–3116.
8. Yersin, H.; Finkenzeller, W. J. In Highly efficient Efficient OLEDs with
Phosphorescent Materials; Yersin, H., Ed.; Wiley: New York, 2007; pp 1–98.
9. Djurovich, P. I.; Thompsom, M. E. In Highly efficient Efficient OLEDs with
Phosphorescent Materials; Yersin, H., Ed.; Wiley: New York, 2007; pp 131–162.
10. Brooks, J.; Babayan, Y.; Lamansky, S.; Djurovich, P. I.; Tsyba, I.; Bau, R.;
Thompson, M. E. Inorg. Chem. 2002, 41, 3055–3066.
11. Lamansky, S.; Djurovich, P. I.; Murphy, D.; Abdel-Razzaq, F.; Lee, H. E.; Adachi,
C.; Burrows, P. E.; Forrest, S. R.; Thompson, M. E. J. Am. Chem. Soc. 2001, 123,
4304–4312.
12. See for example: Joule, J. A.; Mills, K. Heterocyclic Chemistry; Blackwell Science
Limited: Oxford, 2000; Chapter 5.15.
13. Taylor, E. C.; Macor, J. E. J. Org. Chem. 1989, 54, 1249–1256.
14. Sauer, J.; Heldmann, D. K.; Pabst, G. R. Eur. J. Org. Chem. 1999, 313–321.
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. Fernandez Sainz, Y.; Raw, A.; Taylor, R. J. K. J. Org. Chem. 2005, 70, 10086–
10095.
17. Bromley, W. J.; Gibson, M.; Lang, S.; Raw, S. A.; Whitwood, A. C.; Taylor, R. J. K.
Tetrahedron 2007, 63, 6004–6014.
18. Kozhevnikov, V. N.; Kozhevnikov, D. N.; Rusinov, V. L.; Chupakhin, O. N.; König,
B. Synthesis 2003, 2400–2405.
19. Altuna-Urquijo, M.; Stanforth, S. P.; Tarbit, B. Tetrahedron Lett. 2005, 46, 6111–
6113.
20. Saraswathi, T. V.; Srinivasan, V. R. Tetrahedron Lett. 1971, 12, 2315–2316.
21. Kozhevnikov, V. N.; Kozhevnikov, D. N.; Shabunina, O. V.; Rusinov, V. L.;
Chupakhin, O. N. Tetrahedron Lett. 2005, 46, 1521–1523.
Figure 2. Crystal structure of dimer12b. One of the 12b molecules has been ligh-
tened in colour for clarity. The solvent molecule and hydrogens are omitted. Sele-
cted bond lengths (Å) and angles (°): Pt(1)–C(10) 1.965(8), Pt(1)–N(1) 2.013(5),
Pt(1)–O(1) 1.998(4), Pt(1)–O(2) 2.095(5) Å, C(10)–Pt(1)–N(1) 91.5(2), O(1)–Pt(1)–
O(2) 92.39(18).28
Complexes 12 exhibit phosphorescence in DCM solutions at
room temperature similar to the acac PtII cyclometallated complex
of unsubstituted 2-thienylpyridine (thpy) [Pt(acac)(thpy)].10 How-
ever, the emission maxima of 12a,b are slightly red-shifted
(578 nm for 12a and 587 nm for 12b) compared with the emission
maximum of [Pt(acac)(thpy)] (575 nm).10 Increasing the conjuga-
tion system of the ligand is expected to shift the electronic transi-
tions bathochromically, as observed on changing the phenyl group
to a naphthyl group (12a?12b), which leads to an 11 nm red-shift.
So, changes in the aryl substituent allow tuning of the emission.
Detailed photophysical studies of cyclometallated Pt complexes
of new substituted thienylpyridines will be reported in other work.
In conclusion, an efficient and straightforward method for the
synthesis of aryl-substituted thienylpyridines has been demon-
strated. A wide variety of substituted pyridines can readily be
accessed by using cheap, commercially available reagents, such
as bromoacetylarenes, aroyl hydrazides, norbornadiene, and enam-
ines in various combinations. Different substitution patterns allow
the luminescence of cyclometallated Pt complexes to be tuned
based on these new ligands.
22. Typical procedure for the synthesis of thienyltriazines 6:
A mixture of 2-
bromoacetophenone 1a,b (10 mmol), thiophene-2-carboxylic acid hydrazide
5 (2.84 g, 20 mmol), sodium acetate (1.0 g, 12 mmol), ethanol (30 ml) and
acetic acid (10 ml) was heated under reflux for 12 h. The reaction mixture was
allowed to cool to room temperature and the precipitated solid was filtered off,
washed with ethanol and dried. The product was used in the next step without
further purification.
23. Typical procedure for the preparation of 2-(20-thienyl)cyclopenteno[c]pyridines
7a,b:
A mixture of 6-aryl-3-thienyl-1,2,4-triazine 6 (4.0 mmol) and 1-
morpholinocyclopentene (3 ml, 18.8 mmol) was stirred at 220 °C under an
argon atmosphere for 0.5 h. The reaction mixture was diluted with DCM and
passed through a short column (silica gel, DCM as eluent). The fractions
containing the product were combined, and the solvent was evaporated to
dryness. The residue was treated with ethanol (10 ml), and the solid so formed
was separated by filtration and washed with cold ethanol (5 ml).
24. Typical procedure for the preparation of DMSO Pt complexes 11a,b: To a stirred
solution of
7 (2.2 mmol) in acetic acid (30 ml) was added a solution of
potassium tetrachloroplatinate (415 mg, 1 mmol) in water (1 ml). The reaction
mixture was heated at reflux under nitrogen for 24 h. A precipitated solid of
the chloro-bridged dinuclear intermediate was filtered off, washed with acetic
acid (5 ml), ethanol (5 ml) and dried under vacuum. To this solid was added
DMSO (2 ml) and the mixture was heated under reflux for 10 min. Complex 11
precipitated upon cooling, and the crystals were filtered off and washed with
DMSO (1 ml) and acetone (3 ml) to give pure compounds.
25. Typical procedure for the preparation of acac Pt complexes 12a,b: A mixture of
11a,b (0.1 mmol), sodium acetylacetonate monohydrate (1.0 mmol) and
acetone (10 ml) was stirred at 50 °C for 12 h. The reaction mixture was then
diluted with water (50 ml). The precipitated solid was filtered off and purified
by column chromatography (silica gel, DCM).
Acknowledgements
26. X-ray crystallography of complex 11a. Single crystals of 11a suitable for X-ray
crystallography were obtained by slow cooling of a saturated DMSO solution of
11a. Crystal data for 11a were collected with an Xcalibur 3 CCD (graphite
The authors thank RFBR, the University of York (M.M.U.),
the Royal Society (D.N.K.) and the EU and EPSRC (V.N.K.) for
funding.
monochromator, MoKa):
C20H20ClNOPtS2 C2H6OS, FW = 663.16, triclinic,
a = 7.7173(8) Å, b = 12.3254(11) Å,
c = 13.4726(14) Å,
a = 103.455(11)°,
b = 105.379(9)°, c = 96.111(8)°, V = 1182.2(2) Å3, T = 295(2) K, space group
P ꢀ 1, Z = 2, 9395 reflections were collected, and 5444 independent
reflections were used in all the calculations. Number of parameters 280.
R1 = 0.0280, wR2 = 0.0635. GOOF 1.003. Method SHELXL-97.
Supplementary data
27. X-ray crystallography of complex 12b. Single crystals of 12b suitable for X-ray
crystallography were obtained by slow concentration of a DCM/MeOH solution
of 12b. Crystal data for 12b were collected with an Xcalibur 3 CCD (graphite
Supplementary data (experimental details, spectral data for all
new compounds, and crystal packing of complexes 11a and 12b)
associated with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2008.04.138.
monochromator, MoKa):
C27H23NO2PtS, FW = 620.61, monoclinic, a =
12.3573(13) Å, b = 7.9005(6) Å, c = 23.828(2) Å, a = 90.00°, b = 104.851(8)°,
c = 90.00°, V = 2248.6(3) Å3, T = 295(2) K, space group P21/c, Z = 4, 12197
reflections were collected, and 4520 independent reflections were used in all
the calculations. Number of parameters 289. R1 = 0.0395, wR2 = 0.0882. GOOF
1.007. Method SHELXL-97.
References and notes
28. Crystallographic data (excluding structure factors) for the structures in this
Letter have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication numbers CCDC 668782 11a and 681703 12b.
Copies of the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [fax: +44(0)-1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk].
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