5-Acylmethyl-3-(2-pyridyl)-1,2,4-triazines: Synthesis and complexes with Cu(II)

Article abstract of DOI:10.1007/s11178-006-0022-z

5-Acylmethyl-3-(2-pyridyl)-1,2,4-triazines are easily prepared from accessible 3-(2-pyridyl)-1,2,4-triazine 4-oxides by reaction of the latter with acetophenone or trifluoroacetone in the presence of NaH. The compounds obtained behaved as efficient ligand

Full text of DOI:10.1007/s11178-006-0022-z

Russian Journal of Organic Chemistry, Vol. 41, No. 11, 2005, pp. 1702-1705. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 11, 2005,
pp. 1736-1739.
Original Russian Text Copyright Ó 2005 by Prokhorov, Kozhevnikov, Rusinov, Matern, Nikitin, Chupakhin, Eremenko, Aleksandrov.
Dedicated to Academician of the Russian Academy of Sciences N.S.Zefirov
on occasion of his70th anniversary
5-Acylmethyl-3-(2-pyridyl)-1,2,4-triazines: Synthesis
and Complexes with Cu(II)
A.M. Prokhorov1, D.N. Kozhevnikov1,2, V.L. Rusinov1,A.I. Matern1,
M.M. Nikitin1, O.N. Chupakhin2, I.L. Eremenko3, and G.G. Aleksandrov3
1Ural State Technical University, Yekaterinburg, 620002 Russia
e-mail: dnk@htf.ustu.ru
2Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences,Yekaterinburg, Russia
3Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
Received May 21, 2005
Abstract—5-Acylmethyl-3-(2-pyridyl)-1,2,4-triazines are easily prepared from accessible 3-(2-pyridyl)-1,2,4-triazine
4-oxides by reaction of the latter with acetophenone or trifluoroacetone in the presence of NaH. The compounds
obtained behaved as efficient ligands in reaction with CuCl2 furnishing dimeric neutral complexes with Cu(II)
whose structure was investigated by means of X-ray diffraction analysis.
A considerable interest to heterocyclic substances
containing both pyridine and 1,2,4-triazine rings is due to
their pronounced ability to form coordination compounds
with transition metals. For instance, derivatives of pyridyl-
1,2,4-triazine are used as sensitive analytical reagents for
iron ions [1, 2]. 2,6-Bis(5,6-dialkyl-1,2,4-triazin-3-yl)-
pyridines are selective extractants applied to partitioning
of actinides and lanthanides in the course of recovery of
the used nuclear fuel [3, 4]. An opportunity was also
demonstrated [5, 6] of transforming pyridyl-1,2,4-triazines
into functionalized polypyridines (bi- and terpyridines),
ligands extensively used in the coordination, analytical,
and supramolecular chemistry [7, 8].
5-acylmethyl-3-(2-pyridyl)-1,2,4-triazines I that alongside
the bidentate heterocyclic ensemble possessed a chelating
carbonyl group in the side chain.
We selected as the starting compounds the substances
we had described before [10], 6-aryl-3-(2-pyridyl)-1,2,4-
triazine 4-oxides II–IV.
It was established that compounds II–IV readily
reacted with carbanions generated from acetophenones
or from trifluoroacetone. The reaction occurred [12] as
the carbanion addition to the C5 atom of the triazine ring
followed by auto-aromatization of the intermediate sH-
adducts through water elimination to furnish in 50–85%
yields the products of aromatic substitution: 5-phenacyl-
or 5-trifluoroacetylmethyl-3-(2-pyridyl)-1,2,4-triazines Ia–
Ig (see the scheme).
Up till now the most widely used preparation method
for pyridyl-1,2,4-triazines consisted in the cyclization of
pyridylamidrazones with diketones [9]. The disadvantage
of this method lies in a limited possibility to vary sub-
stituents and consequently in restricted optimization of
the useful properties. We recently developed a sufficiently
simple procedure for the synthesis of 3-pyridyl-1,2,4-
triazine ligands involving the preparation of 3-(2-pyridyl)-
1,2,4-triazine 4-oxides and the functionalization of the
heterocyclic ensemble via a nucleophilic substitution of
a hydrogen in the 1,2,4-triazine ring [10]. The presence
of the N-oxide group significantly facilitates these
reactions [11].
As an independent synthesis of these compounds we
performed the previously described cyano group
substitution in a series of 5-cyano-1,2,4-triazines [13].
For instance, the reaction of acetophenone carbanion with
3-(2-pyridyl)-6-phenyl-5-cyano-1,2,4-triazine (V) obtained
by direct cyanation [14] of 1,2,4-triazine 4-oxide (II)
resulted in compound Ia (see the scheme). This reaction
may be regarded as an alternative method of synthesis
for ligands I, although it is less preferable primarily not
because of the additional cyanation stage but due to lower
yields caused by the tarring of the reaction mixture.
The target of this study was the development of
synthetic methods for new heterocyclic N,N,O-ligands,
1070-4280/05/4111-1702Ó2005 Pleiades Publishing, Inc.

5-ACYLMETHYL-3-(2-PYRIDYL)-1,2,4-TRIAZINES
1703
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I, R = Ph (a), 4-ClC6H4 (b), tolyl (c), 4-FC6H4 (d), CF3 (e–g);Ar = Ph (Ia–Ie, II), 4-ClC6H4 (If, III), 4-MeOC6H4 (Ig, IV). Reagents
and conditions: i, RCOCH3, NaH, THF, –20°C, 20 min, then triazine ii, –20°C, 3 h; ii, HOAc; iii, acetone cyanohydrin, NEt3,
CH2Cl2, 20°C.
metrical dimer (see the figure). The chelating part of the
ligand (pyridine and triazine rings, and also carbonyl-
methylene fragment) is exactly planar. The Cu(II) atom
in the complex VI is pentacoordinate, the coordination
sites form a square pyramid with the N, N, O atoms and
a bridging Cl in the base of the pyramid, and the other
bridging Cl in its vertex. The distance between the copper
The elemental analyses of compounds Ia–Ig obtained
are in agreement with the calculated data, and in the mass
spectra the peak of the molecular ion is observed. In
solution the compounds apparently exist as 5-(2-R-2-
hydroxyethenyl)-1,2,4-triazines A which is evidenced by
1
the presence in the H NMR spectrum of a broadened
one-proton singlet in the downfield region (15 ppm) and
of a one-proton singlet of a methine proton at 6.2 ppm,
and also by the absence in the IR spectrum of compound
Ie of the absorption band from the stretching vibrations
of the carbonyl group. On the other hand we cannot totally
exclude the existence of the third form, 5-acylmethylene-
4H-1,2,4-triazines C. Form B is excluded for the 1H NMR
spectrum lacks a two-proton singlet from the methylene
gtoup.
°
atoms in the dimer is 3.442 A, exceeding the sum of the
°
van der Waals radii (2.7 A). Besides the structure of
complex VI contains two very long Cu–Cl bonds
°
(2.7173 A) exceeding the sum of the atomic radii of
°
–
Cu(II) and Cl (2.54 A).
Thus the data obtained in the present study suggest
that the 5-acylmethyl-3-pyridyl-1,2,4-triazines are of
interest as accessible efficient ligands for transition
metals.
In any event whatever the form of existence the anions
of triazines I behave as N,N,O-ligands and efficiently
chelate Cu(II). For instance, triazine Ia reacts with
copper(II) chloride dihydrate in acetonitrile forming
complex VI. We succeeded in obtaining single crystals
of complex VI and therefore we were able to study it by
means of FAB mass spectrometry and X-ray diffraction
analysis. The neutral complex VI obtained is a centrosym-
EXPERIMENTAL
1H NMR spectra were registered on a spectrometer
Bruker WM-250 (250 MHz), solvent DMCO-d6–CCl4,
1:1, internal reference TMS Mass spectra were measured
on Varian MAT-311A instrument, ionization by electron
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

PROKHOROV et al.
1704
5-(4-Methylphenacyl)-3-(2-pyridyl)-6-phenyl-
1,2,4-triazine (Ic). Yield 0.27 g (75%), mp 147–148°C.
1H NMR spectrum, d, ppm: 2.35 s (3H, CH3), 6.21 s
(1H, COCH), 7.19–7.73 m (10Harom), 8.06 m (1H, Py),
8.51 m (1H, Py), 8.89 m (1H, Py), 15.34 br.s (1H, NH).
Found, %: C 75.59; H 4.97; N 15.26. C23H18N4O.
Calculated, %: C 75.39; H 4.95; N 15.29.
2
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1
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1
1
1
3-(2-Pyridyl)-6-phenyl-5-(4-fluorophenacyl)-
1
&X
1,2,4-triazine (Id). Yield 0.13 g (50%), mp 216–218°C.
1
1
–1
IR spectrum (KBr), cm : 559, 681, 697, 803, 875, 1113,
&O
1
1
1137, 1190, 1213, 1409, 1564, 3064, 3084. H NMR
2
spectrum, d, ppm: 6.45 s (1H, COCH), 7.01–8.15 m
(10H), 8.56 m (1H, Py), 8.81 m (1H, Py), 8.89 m (1H,
Py), 15.34 br.s (1H, NH). Mass spectrum, m/z (Irel, %):
344 (14) [M]+. Found, %: C 71.12; H 4.07; N 15.20.
C22H15FN4O. Calculated, %: C 71.34; H 4.08; N 15.13.
3-(2-Pyridyl)-5-trifluoroacetylmethyl-6-phenyl-
1,2,4-triazine (Ie). Yield 0.25 g (70%), mp 214–215°C.
1H NMR spectrum, d, ppm: 5.78 s (1H, COCH), 7.61–
7.78 m (5H, Ph), 7.80 m (1H, Py), 8.17 m (1H, Py),
8.59 m (1H, Py), 8.90 m (1H, Py), 14.50–15.50 br.s (1H,
NH). Found, %: C 59.31; H 3.22; N 16.27. C17H11F3N4O.
Calculated, %: C 59.31; H 3.22; N 16.27.
Structure of complex VI according to X-ray diffraction study.
Lengths of some bonds (A): Cu1–Cl1 2.252, Cu1–N4 2.041,
Cu1–N3 1.954, Cu1–O1 1.937, Cu1–Cl1a 2.717, Cu1–Cu1a 3.442.
beam. IR spectra were obtained on Fourier IR spectrom-
eter Perkin Elmer Spectrum I. Cyanotriazine V was
prepared by known procedure [15].
6-(4-Methoxyphenyl)-3-(2-pyridyl)-5-trifluoro-
acetylmethyl-1,2,4-triazine (If). Yield 0.14 g (60%),
mp 236–238°C. 1H NMR spectrum, d, ppm: 3.85 s (3H,
CH3), 5.76 s (1H, COCH), 7.70–7.81 m (4H, Ph),
7.82 m (1H, Py), 8.21 m (1H, Py), 8.57 m (1H, Py),
8.89 m (1H, Py), 14.50-15.50 br.s (1H, NH). Found, %:
C 57.58; H 3.61; N 14.97. C18H13F3N4O2. Calculated,
%: C 57.76; H 3.50; N 14.97.
Synthesis of 1,2,4-triazines I. In 5 ml of anhydrous
THF was dispersed 1.2 mmol of sodium hydride, then
1.4 mmol of acetophenone or trifluoroacetone was added.
In 20 min the dispersion obtained was poured to a disper-
sion of 1 mmol of 1,2,4-triazine 4-oxide II in 20 ml of
THF cooled to –20°C, and the mixture was stirred for
3 h. Then 1.2 mmol of acetic acid was added, the solvent
was removed at a reduced pressure, and the residue was
extracted with toluene. On distilling off toluene from the
extract the residue was treated with acetonitrile; the
arising bright-yellow precipitate was filtered off and
recrystallized from toluene.
3-(2-Pyridyl)-5-trifluoroacetylmethyl-6-(4-
chlorophenyl)-1,2,4-triazine (Ig). Yield 0.25 g (50%),
1
mp 241–243°C. H NMR spectrum, d, ppm: 5.80 s (1H,
COCH), 7.69–7.79 m (4H, Ph), 7.82 m (1H, Py), 8.33 m
(1H, Py), 8.59 m (1H, Py), 8.90 m (1H, Py), 14.50–
15.50 br.s (1H, NH). Found, %: C 53.99; H 3.00; N 14.75.
C18H13F3N4O2. Calculated, %: C 53.91; H 2.66; N 14.79.
3-(2-Pyridyl)-5-phenacyl-6-phenyl-1,2,4-triazine
1
(Ia). Yield 0.3 g (85%), mp 155–156°C. H NMR
spectrum, d, ppm: 6.25 s (1H, COCH), 7.48–7.80 m (11H),
8.14 m (1H, Py), 8.54 m (1H, Py), 8.95 m (1H, Py),
15.39 br.s (1H, NH). Found, %: C 74.79; H 4.47; N 15.86.
C22H16N4O. Calculated, %: C 74.98; H 4.58; N 15.90.
Synthesis of complex VI. To a solution of 26 mg
(0.15 mmol) of copper(II) chloride dihydrate in 30 ml of
acetonitrile was added at stirring at room temperature
a solution of 53 mg (0.15 mmol) of ligand Ia in 30 ml of
acetonitrile. The mixture obtained was left standing for
3 days at slow evaporation of the solvent. The separated
crystals were filtered off. Yield 0.114 g (80%). Mass
spectrum FAB, m/z (Irel, %): 417 [Cu(Ia)]+. Found, %:
C 58.31; H 3.52; N 12.27. C44H30Cl2Cu2N8O2. Calculat-
ed, %: C 58.54; H 3.57; N 12.41.
3-(2-Pyridyl)-6-phenyl-5-(4-chlorophenacyl)-
1,2,4-triazine (Ib). Yield 0.3 g (80%), mp 151–152°C.
1H NMR spectrum, d, ppm: 6.21 s (1H, COCH), 7.45–
7.79 m (10Harom), 8.12 m (1H, Py), 8.53 m (1H, Py),
8.89 m (1H, Py), 15.42 br.s (1H, NH). Found, %: C 74.79;
H 4.47; N 15.86. C22H15ClN4O. Calculated, %: C 68.31;
H 3.91; N 14.48.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

5-ACYLMETHYL-3-(2-PYRIDYL)-1,2,4-TRIAZINES
1705
1998, vol. 39, p. 6691.
X-ray diffraction analysis was carried out on a dif-
fractometer Nonius Cad-4, MoKa radiation, graphite
monochromator (w-scanning), 293 K. The structure was
solved by the direct method SIR-97 and refined by the
6. Kozhevnikov, V.N., Kozhevnikov, D.N., Shabunina, O.V.,
Rusinov, V.L., and Chupakhin, O.N., Tetrahedron Lett.,
2005, vol. 46, p. 1191.
7. Lehn, J.-M., Supramolecular Chemistry - Concepts and
Perspectives, VCH: Weinheim, Germany, 1995.
8. Chelucci, G. and Thummel, R.P., Chem. Rev., 2002, vol. 102,
p. 3129.
9. Pabst, G., Pfuller, O., and Sauer, J., Tetrahedron, 1999,
vol. 55, p. 5047.
10. Kozhevnikov, V.N., Kozhevnikov, D.N., Nikitina, T.V.,
Rusinov, V.L., Chupakhin, O.N., Zabel, M., and Koenig, B.,
J. Org. Chem., 2003, vol. 68, p. 2882.
11. Kozhevnikov, D.N., Rusinov, V.L., and Chupakhin, O.N.,
Usp. Khim., 1998, vol. 67, p. 707.
12. Kozhevnikov, D.N., Prokhorov, A.M., Kovalev, I.C.,
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Khim., 2003, p. 1504.
least-squares
procedure
SHELXL-97.
C44H30Cl2Cu2N8O2. M 900.74, a 9.145(4), b 9.804(4),
°
c 12.096(7) A, a 66.03(4), b 76.65(4), g 88.03(4)°, V
°
–1
962.0(8) A3, Z 1, Dcalc 1.555 g/cm3, m 1.295 cm . Space
group P-1(bar). Number of measured reflections 5311.
Number of reflections with I > 2s(I) 5213. R 0.0377.
The structure of complex VI and the length values of
some bonds are given on the figure.
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RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005