A versatile strategy for the synthesis of functionalized 2,2′-bi- and 2,2′:6′,2′-terpyridines via their 1,2,4-triazine analogues

Article abstract of DOI:10.1021/jo0267955

A general synthetic route for the synthesis of functionalized bi- and terpyridines is reported. Functionalized 1,2,4-triazene 4-oxides 7 and 8 - obtained from the reaction of hydrazones 1 with pyridine aldehydes and followed by oxidation - are functionalized by introduction of a cyano group via nucleophilic aromatic substitution. The thus-obtained 5-cyano-1,2,4-triazines 9 and 10 undergo facile inverse-electron-demand Diels-Alder reactions with enamines and alkenes to yield functionalized bi- and terpyridines, respectively. The substituent at position 6 of the 1,2,4-triazene 4-oxides must be aromatic or heteroaromatic in order to allow their facile synthesis, but other substituents and reagents may vary. Each step of the synthetic route allows diversification, which makes the approach particularly useful for the facile synthesis of a large variety of functionalized bi- and terpyridines.

Full text of DOI:10.1021/jo0267955

A Ver sa tile Str a tegy for th e Syn th esis of F u n ction a lized 2,2′-Bi-
a n d 2,2′:6′,2′′-Ter p yr id in es via Th eir 1,2,4-Tr ia zin e An a logu es†
Valery N. Kozhevnikov,*,‡ Dmitry N. Kozhevnikov,*,§ Tatiana V. Nikitina,§
Vladimir L. Rusinov,§ Oleg N. Chupakhin,§ Manfred Zabel,| and Burkhard Ko¨nig*,‡
Ural State Technical University, 620002, Ekaterinburg, Russia, and Institut fu¨r Organische Chemie,
Universita¨t Regensburg, D-93040 Regensburg, Germany
kozhevnikov_v@htf.ustu.ru; dnk@htf.ustu.ru; burkhard.koenig@chemie.uni-regensburg.de
Received December 3, 2002
A general synthetic route for the synthesis of functionalized bi- and terpyridines is reported.
Functionalized 1,2,4-triazene 4-oxides 7 and 8sobtained from the reaction of hydrazones 1 with
pyridine aldehydes and followed by oxidationsare functionalized by introduction of a cyano group
via nucleophilic aromatic substitution. The thus-obtained 5-cyano-1,2,4-triazines 9 and 10 undergo
facile inverse-electron-demand Diels-Alder reactions with enamines and alkenes to yield func-
tionalized bi- and terpyridines, respectively. The substituent at position 6 of the 1,2,4-triazene
4-oxides must be aromatic or heteroaromatic in order to allow their facile synthesis, but other
substituents and reagents may vary. Each step of the synthetic route allows diversification, which
makes the approach particularly useful for the facile synthesis of a large variety of functionalized
bi- and terpyridines.
In tr od u ction
The most common methods of synthesizing function-
alized 2,2′-bipyridines and 2,2′:6′,2′′-terpyridines are
based on the coupling of single pyridine building blocks11
or the formation of the central (rarely both terminal)
pyridine rings starting from the corresponding open-
chain intermediates.12,13
We have recently communicated a new synthetic
strategy for the synthesis of functionalized bi- and
terpyridines via Diels-Alder reaction of their corre-
sponding 1,2,4-triazines.14,15 Herein we describe the scope
and limitation of the method and report the full experi-
mental details. The strategy is based on the high reactiv-
ity of 1,2,4-triazines in nucleophilic substitution reactions
and the possibility of their transformation into pyridines
by the Diels-Alder reaction.16,17 1,2,4-Triazine N-oxides
bearing a pyridine ring at position 3 and any aromatic
substituents at position 6 serve as starting material of
Organic molecules bearing 2,2′-bipyridine and 2,2′:
6′,2′′-terpyridine moieties have a geometry that is favor-
able for the coordination of various metal ions, and
therefore, such molecules are widely used in coordination
chemistry. On the basis of functionalized 2,2′-bipyridine
and 2,2′:6′,2′′-terpyridine ligands and their complexes,
highly sensitive analytical reagents,1 various sensor
systems,2-4 reagents for enantioselective synthesis,5 and
luminescent agents for labeled peptide synthesis6 were
created. 2,2′:6′,2′′-Terpyridines are attractive building
blocks for supramolecular chemistry too.7,8 Due to their
high emission quantum yields, bi-and terpyridines bear-
ing aromatic substituents in the â-position are particu-
larly interesting for photophysical applications.9,10
† Dedicated to Prof. Theodor Troll on the occasion of his 60th
birthday.
‡ Institut fu¨r Organische Chemie, Universita¨t Regensburg, D-93040
Regensburg, Germany. Fax: Int + 49-941-943-1717.
§ Ural State Technical University, 620002, Ekaterinburg, Russia.
Fax: Int + 7-3432-740458.
(9) Loren, J . C.; Siegel, J . S. Angew. Chem., Int. Ed. 2001, 40, 754-
757.
(10) Mutai, T.; Cheon, J .-D.; Arita, S.; Araki, K. J . Chem. Soc.,
Perkin Trans. 2 2001, 1045-1050.
| Zentrale Analytik der NWF IV, Universita¨t Regensburg, 93040
Regensburg, Germany.
(11) Pabst, G. R.; Schmid, K.; Sauer, J . Tetrahedron Lett. 1998, 39,
6691-6694.
(1) Kro¨hnke, F. Synthesis 1976, 1-24.
(12) For a review on methods for terpyridine synthesis, see: Thomp-
son, A. C. Coord. Chem. Rev. 1997, 160, 1-52.
(2) Keefe, M. H.; Benkstein, K. D.; Hupp, J . T. Coord. Chem. Rev.
2000, 205, 201-228.
(13) For a recent paper on terpyridine synthesis, see: Kelly, T. R.;
Lebedev, R. L. J . Org. Chem. 2002, 67, 2197-2205.
(14) Kozhevnikov, D. N.; Kozhevnikov, V. N.; Nikitina, V. T.;
Rusinov, V. L.; Chupakhin, O. N.; Neunhoeffer, H. Mendeleev Commun.
2002, 30-32.
(3) Ait-Haddou, H.; Wiskur, S. L.; Lynch V. M.; Anslyn, E. V. J .
Am. Chem. Soc. 2001, 123, 11296-11297.
(4) Padilla-Tosta, M. E.; Lloris, J . M.; Martinez-Manez, R.; Benito,
A.; Soto, J .; Pardo, T.; Miranda, M. A.; Marcos, M. D. Eur. J . Inorg.
Chem. 2000, 741-748.
(15) Kozhevnikov, D. N.; Kozhevnikov, V. N.; Nikitina, T. V.;
Rusinov, V. L.; Chupakhin, O. N.; Eremenko, I. L.; Aleksandrov, G.
G. Tetrahedron Lett. 2002, 43, 4923-4925.
(5) Chelucci, G.; Cabras, M. A.; Saba, A. J . Mol. Catal. A 1995, 95,
L7-L10.
(6) Saha, A. K.; Kross, K.; Kloszewski, E. D.; Upson, D. A.; Toner,
J . L.; Snow, R. A.; Black, C. D. V.; Desai, V. C. J . Am. Chem. Soc.
1993, 115, 11032-11033.
(16) Kozhevnikov, D. N.; Rusinov, V. L.; Chupakhin, O. N. In
Advances in Heterocyclic Chemistry; Katritzky, A. R., Ed.; Academic
Press: New York, 2002; Vol. 82, pp 61-305.
(7) Ward, M. D. Chem. Soc. Rev. 1995, 121-134.
(8) Schubert, U. S.; Newkome, G.; Goeldel, A.; Pemp, A.; Kersten,
J . L.; Eisenbach, C. D. Heterocycles 1998, 48, 2141-2148.
(17) Neunhoeffer, H. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon Press:
Oxford, 1996; Vol. 6, pp 50-574.
10.1021/jo0267955 CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/07/2003
2882
J . Org. Chem. 2003, 68, 2882-2888

Synthesis of Functionalized 2,2′-Bi- and 2,2′:6′,2′′-Terpyridines
SCHEME 1
SCHEME 2
the sequence. By nucleophilic attack at position 5 another
functional group is introduced, which results in 3-fold
substituted 1,2,4-triazines. A Diels-Alder reaction trans-
forms these precursors into bi- or terpyridines. Depending
on the alkene used as reaction partner, additional
functionality may be introduced at positions 3 and 4 of
the new pyridine rings. Reaction with norbornadiene
leads to bi- and terpyridines showing the same substitu-
tion pattern as the 1,2,4-triazine precursors. Scheme 1
summarizes the key steps of the sequence. With each step
molecular diversity may be introduced, which makes the
approach particularly interesting for library synthesis.
3, (2) both are in the cyclic form as in compound 5, and
(3) one of the 1,2,4-triazines is in the cyclic form, the
second one in the open-chain form as in compound 6
(Scheme 2) (see the Supporting Information for NMR
spectra of compounds 2c and 3b).
Oxidative aromatization proceeded without being af-
fected by the ratio of the ring-chain isomers. The inter-
mediate compounds 2a -e were treated with Pb3O4 in
acetic acid yielding the corresponding 6-aryl-3-(2′-pyr-
idyl)-1,2,4-triazine 4-oxides 7a -e. The same reaction of
3a -c with Pb3O4 resulted in 2,6-bis(6-phenyl-1,2,4-
triazin-3-yl 4-oxide)pyridines 8a -c (Scheme 3).
Resu lts a n d Discu ssion
Syn th esis of 1,2,4-Tr ia zin e 4-Oxid es. A previously
established method18 for the synthesis of 1,2,4-triazine
4-oxides was adapted for preparations reported here. The
reaction of hydrazones of isonitroso acetophenones 1a -e
with pyridine-2-carboxaldehyde or pyridine-2,6-dicarbox-
aldehyde results in 3-aryl-1-hydroxy-6-(2-pyridyl)-1,4,5-
triazahexatrienes 2a -e and 2,6-bis(3-aryl-1-hydroxy-
1,4,5-triazahexatriene-6-yl)pyridine 3a -c (Scheme 2).
The open-chain compounds 2 exist in equilibrium with
their cyclic form of 6-aryl-4-hydroxy-3-(2-pyridyl)-3,4-
dihydro-1,2,4-triazines 4a -e, which is typical for 4-hy-
droxy-3,4-dihydro-1,2,4-triazines.19 As previously shown,19
the ratio of the cyclic (4) and the open-chain isomers (2)
An advantage of this approach over typical methods
for the synthesis of 1,2,4-triazines is the presence of the
N-oxide group in the 1,2,4-triazine ring of the resulting
compounds 7 and 8. This allows the direct introduction
of another substituent by means of a nucleophilic sub-
stitution of hydrogen (SNH).16 The direct cyanation of the
H
1,2,4-triazine 4-oxide has been chosen for SN function-
alization of the bi- and terpyridine precursors 7 and 8.
The reaction proceeds easily. Functional group intercon-
version of the cyano group gives access to many useful
derivatives. The cyano group in 5-cyano-1,2,4-triazines
can readily be substituted by water, various aliphatic
alcohols, amines, or carbanions to give a wide variety of
1,2,4-triazines.16 Furthermore, the electron-withdrawing
cyano group increases the reactivity of the heterocycle
in the inverse electron demand Diels-Alder reaction with
electron rich dienophiles (vide infra). The cyanation of 7
1
can be determined easily by H NMR spectroscopy and
depends on the solvent. Spectra of compounds 3 are more
complicated due to ring-chain isomers: (1) both the 1,2,4-
triazine rings are in the open-chain form as in compound
(18) Kozhevnikov, D. N.; Kozhevnikov, V. N.; Rusinov, V. L.;
Chupakhin, O. N. Mendeleev Commun. 1997, 238-239.
(19) Kozhevnikov, D. N.; Kozhevnikov, V. N.; Rusinov, V. L.;
Chupakhin, O. N.; Sidorov, E. O.; Klyuev, N. A. Rus. J . Org. Chem.
Engl. (Zh. Org. Khim.) 1998, 34, 388-392.
J . Org. Chem, Vol. 68, No. 7, 2003 2883

Kozhevnikov et al.
SCHEME 3
SCHEME 4
and 8 was achieved by reaction with acetone cyanohy-
drine in the presence of triethylamine in dichloromethane,
affording 6-aryl-5-cyano-3-(2′-pyridyl)-1,2,4-triazines 9a-e
and 2,6-bis(6-aryl-5-cyano-1,2,4-triazin-3-yl)-pyridines
10a -c (Scheme 3). The in situ generated cyanide anion
adds to position 5 of the 1,2,4-triazine ring resulting in
the intermediate σ-adducts, which undergo dehydration
to form the aromatic products 9 and 10. The reaction
proceeded smoothly with good yields.
SCHEME 5
Syn th esis of Bi- a n d Ter p yr id in es. The transfor-
mation of cyano-1,2,4-triazines 9 and 10 into bi- and
terpyridines was carried out in practically one step by
Diels-Alder reaction. Bearing in mind that 1,2,4-tri-
azines, are π-deficient heterocycles, particularly if cyano
substituted, we have chosen enamines and norbornadiene
as electron rich dienophiles. The reaction of cyano-1,2,4-
triazine 9a with 1-(1-pyrrolidino)cyclopentene already
proceeds at room temperature, releasing nitrogen. The
intermediate cycloadducts are isolated as a mixture of
two regioisomers 11 and 12. Unaffected by the ratio of
the isomers, the rearomatization by elimination of pyr-
rolidine upon reflux in acetic acid gave 6-cyano-5-phenyl-
2-(2′-pyridyl)-3,4-cyclopentenopyridine 13 (Scheme 4).
The analogous 2-fold reaction of 2,6-bis(cyano-1,2,4-
triazin-3-yl)pyridines 10a ,b with 1-(1-pyrrolidino)cyclo-
pentene or 1-(4-morpholino)cyclopentene gave 2,6-bis(6-
cyano-5-phenyl-3,4-cyclopentenopyridyl-2)pyridines 14a,b
with good yields (Scheme 4). The molecular structure of
the terpyridine 14b was confirmed by X-ray crystal-
lography (see the Supporting Information).
Reaction of the cyanotriazines 9 and 10 with norbor-
nadiene yields unsubstituted bi- and terpyridines. In this
case, the reaction proceeded more slowly than the reac-
tion with enamines. Thus refluxing the compounds 9a -e
with bicyclo[2.2.1]hepta-2,5-diene in toluene resulted in
6-cyano-5-phenyl-2,2′-bipyridine 15a -e. The same reac-
tion of the dinitriles 10a -c yielded 6,6′′-dicyano-5,5′′-
diphenyl-2,2′:6′,2′′-terpyridine 16a -c (Scheme 5). The
cyano group in the 1,2,4-triazine ring facilitates the
inverse-electron-demand Diels-Alder reaction in com-
parison to unsubstituted pyridyl-1,2,4-triazines.
The presence of the cyano group in the bi- and
terpyridines obtained hereby allows further functional
group transformation, if desired. For illustration of this
option, the cyano group of bipyridine 13a was hydrolyzed
in 95% sulfuric acid to give 6-carbomoyl-5-phenyl-2-(2′-
pyridyl)-3,4-cyclopentenopyridine (17). Reflux of the amide
17 in concentrated hydrochloric acid yielded 5-phenyl-2-
(2′-pyridyl)-3,4-cyclopentenopyridine-6-carboxylic acid 18.
Esterification of the acid 18 gave 6-ethoxycarbonyl-5-
phenyl-2-(2′-pyridyl)-3,4-cyclopentenopyridine (19), which
was reduced with sodium borohydride to 6-hydroxymeth-
yl-5-phenyl-2-(2′-pyridyl)-3,4-cyclopentenopyridine (20)
(Scheme 6).
Syn th esis a n d Str u ctu r e of 14a -Ni(NO3)2. The
synthesized bi- and terpyridine ligands are expected to
form complexes with a variety of transition metals.
2884 J . Org. Chem., Vol. 68, No. 7, 2003

Synthesis of Functionalized 2,2′-Bi- and 2,2′:6′,2′′-Terpyridines
SCHEME 6
Con clu sion
Functionalized bi- and terpyridines can be obtained
from 1,2,4-triazine 4-oxides. The sequence of triazine
4-oxide formation, introduction of an additional cyano
group by nucleophilic substitution of hydrogen, and
transformation of the 1,2,4-triazine rings into pyridines
by Diels-Alder reaction tolerates many functional groups.
Most steps result in a high chemical yield. The variety
of substituents is limited by the fact that the substituent
at position 6 of the 1,2,4-triazines must be aromatic or
heteroaromatic. Each step of the synthesis allows diver-
sification, if desired. The presented examples may be well
extended by the use of other nucleophiles or dienophiles.
Functionalized bi- and terpyridines and their metal
complexes are important building blocks for the construc-
tion of chemosensors, self-organized assemblies, or pho-
toactive molecular devices. The synthetic procedure
presented facilitates the preparation of such compounds.
Exp er im en ta l Section
TABLE 1. Absor p tion a n d Em ission Ma xim a a n d
Qu a n tu m Yield s of Com p ou n d s 15a -e a n d 16a -c in a n
Eth a n ol Solu tion
1
Gen er a l Meth od s. H NMR spectra were recorded at 300
MHz and 13C NMR spectra at 75 MHz in CDCl3, unless
otherwise stated. The multiplicity of the 13C signals was
determined using the DEPT technique and quoted as (+) for
CH3 or CH, (-) for CH2, and (Cquat) for quaternary carbons.
Starting hydrazones 1a -e were synthesized according to the
described method.21
a
a,b
compd
λabs
,
nm
λfl,a nm
Φfl
15a
15b
15c
15d
15e
16a
16b
16c
292
295
306
317
304
302
305
313
359
370
408
393
407
355
363
402
0.01
0.10
0.43
0.10
0.58
0.40
0.50
0.60
6-P h en yl-3-(2-p yr id yl)-1,2,4-tr ia zin e 4-Oxid e (7a ). Gen -
er a l P r oced u r e 1 (GP 1). Pyridine 2-carboxaldehyde (1 g, 9.2
mmol) was added to a stirred solution of isonitrosoacetophe-
none hydrazone 1a (1.5 g, 9.2 mmol) in ethanol (10 mL). The
reaction mixture was kept at room temperature for 12 h. The
resulting precipitate was filtered off, washed with ethanol to
give 2a (2.1 g, 8.3 mmol, 90%). Over 1 h at room temperature,
Pb3O4 (5.69 g, 8.3 mmol) was added to the suspension of
intermediate 2a (2.1 g, 8.3 mmol) in acetic acid (11 mL). The
mixture was stirred at room temperature for an additional 3
h and then diluted with water (35 mL). The precipitate was
filtered off, washed with water, and recrystallized from ethanol
a
b
Measured in ethanol solution 10-5 mol/L. Anthracene in
ethanol solution (φ em ) 0.27) was used as standard for determin-
ing emission quantum yields.
However, contrary to less functionalized bi- and terpyr-
idines, the cyano group in the R-(RR′′)-position causes a
steric hindrance. Therefore, complexes of, e.g., two ter-
pyridine molecules binding to one metal atom with coor-
dination number 6 cannot be obtained. This is illustrated
nicely by the nickel complex 14a -Ni(NO3)2, which was
obtained by refluxing dicyanoterpyridine 14a with Ni-
(NO3)2‚6H2O in acetonitrile.15 The molecular structure of
the complex in the crystal was determined by X-ray
crystallography. The Ni(II) atom is bound to the three
nitrogen atoms of the terpyridine ligand and three oxygen
atoms of two nitrate anions with chelate and terminal
coordination. The terpyridine system is almost planar
with a deviation of 0.047 Å of the metal atom from the
average plane of the terpyridine.
Absor p tion a n d Em ission P r op er ties of Cya n o-
bip yr id in es a n d Dicya n oter p yr id in es. Table 1 sum-
marizes the absorption and emission maxima of cyano-
bipyridines 15a -e and dicyanoterpyridines 16a -c in
ethanol. The lowest energy absorption bands of these
compounds are around 300 nm. The emission maxima
and relative quantum yields of 15 and 16 depend strongly
on the aromatic substituents.20 An increase in electron
donor properties of the substituent causes a bathochromic
shift of the emission and an increase in quantum yields.
1
to yield 7a (1.1 g, 54%). Mp: 173-174 °C. H NMR (DMSO-
d6, 250 MHz): δ 7.58 (m, 4H), 8.00 (m, 2H), 8.23 (m, 2H), 8.78
(m, 1H), 9.32 (s, 1H). IR (KBr): ν (cm-1) 1240, 1374, 1424,
1555, 3061. EI MS (70 eV): m/z 250 (23) [M+], 116 (100). Anal.
Calcd for C14H10N4O (250.3): C, 67.19; H, 4.03; N, 22.39.
Found: C, 67.14; H, 4.13; N, 22.42.
6-(4-Meth ylp h en yl)-3-(2-p yr id yl)-1,2,4-tr ia zin e 4-Oxid e
(7b). Following GP1, 1b (2.12 g, 12 mmol) and 2-pyridinecar-
boxaldehyde (1.28 g. 12 mmol) were reacted to yield 2.87 g
(90%) of the intermediate 2b. Compound 2b (2.66 g, 10 mmol)
and Pb3O4 (6.85 g, 10 mmol) gave 1.4 g (5.3 mmol, 52%) of 7b.
1
Mp: 209-210 °C. H NMR: δ 2.43 (s, 3H), 7.36 (m, 2H), 7.48
(m, 1H), 7.92 (m, 3H), 8.21 (br. d, 1H), 8.61 (s, 1H), 8.87 (m,
1H). 13C NMR: δ 21.5 (+), 125.6 (+), 125.9 (+), 127.0 (+), 128.7
(Cquat), 130.2 (+), 131.86 (+), 136.7 (+), 142.6 (Cquat), 147.6
(Cquat), 150.1 (+), 155.4 (Cquat), 157.2 (Cquat). IR (KBr): ν (cm-1
)
1244, 1366, 1420, 1446, 1552, 1581, 3054. EI MS (70 eV): m/z
264 (29) [M+], 248 (5) [M - O+], 130 (100). Anal. Calcd for
C
15H12N4O (264.3): C, 68.17; H, 4.58; N, 21.20. Found: C,
68.03; H, 4.52; N, 20.92.
6-(4-Meth oxyp h en yl)-3-(2-p yr id yl)-1,2,4-tr ia zin e 4-Ox-
id e (7c). According to GP1, 1c (1.13 g, 5.9 mmol) and
2-pyridinecarboxaldehyde (0.63 g. 5.9 mmol) gave 1.64 g (98%)
of the intermediate 2c. In the second step, 2c (1.6 g, 5.7 mmol)
and Pb3O4 (3.89 g, 5.7 mmol) yielded 0.7 g (44%) of 7c. Mp:
1
207-209 °C. H NMR: δ 3.89 (s, 3H), 7.07 (m, 2H), 7.49 (m,
1H), 7.90 (m, 1H), 8.04 (m, 2H), 8.22 (m, 1H), 8.60 (s, 1H),
(21) Dey, B. B. J . Chem. Soc. London 1914, 105, 1039-1046.
J . Org. Chem, Vol. 68, No. 7, 2003 2885
(20) A comparison of the corresponding aryl-substituted bi- and
terpyridines (see ref 9) with the cyano-substituted compounds shows
a bathochromic shift of the emission of 15-25 nm.

Kozhevnikov et al.
8.89 (br.d, 1H). IR (KBr): ν (cm-1) 1244, 1516, 1576, 1603,
2839, 3050. EI MS (70 eV): m/z 280 (29) [M+], 146 (100). Anal.
Calcd for C15H12N4O2 (280.3): C, 64.28; H, 4.32; N, 19.99.
Found: C, 63.86; H, 4.38; N, 20.13.
mixture was heated under reflux until complete conversion of
the starting material was confirmed by TLC (approximately
1 h). Solvents were removed under reduced pressure, and the
residue was dissolved in ethyl acetate and filtered through
silica gel to give 9a (388 mg, 1.5 mmol, 75%). Mp: 128-129
3-(2-P yr id yl)-6-(2-th ien yl)-1,2,4-tr ia zin e 4-Oxid e (7d ).
Following GP1, compound 1d (1.23 g, 7.4 mmol) and 2-pyri-
dinecarboxaldehyde (0.79 g. 7.4 mmol) gave 1.77 g (93%) of
2d . In the second step, 2d (1.62 g, 6.3 mmol) and Pb3O4 (4.3 g,
1
°C. H NMR: δ 7.51 (m, 1H), 7.60 (m, 3H), 7.94 (m, 1H), 8.09
(m, 2H), 8.65 (m, 1H), 8.90 (m, 1H). IR (KBr): ν (cm-1) 1391,
1440, 1580, 2239, 3058. EI MS (70 eV): m/z 259 (4) [M]+, 231
(21) [M - N2]+, 129 (100). Anal. Calcd for C15H9N5 (259.3): C,
69.49; H, 3.50; N, 27.01. Found: C, 69.35; H, 3.47; N, 27.14.
1
6.3 mmol) yielded 680 mg (43%) of 7d . Mp: 202-204 °C. H
NMR: δ 7.32 (m, 1H), 7.62 (m, 1H), 7.96 (dd, 1H), 8.02 (m,
2H), 8.16 (m, 1H), 8.79 (m, 1H), 9.49 (s, 1H). 13C NMR: δ 125.9
(+), 126.2 (+), 129.5 (+), 130.5 (+), 131.6 (+), 132.8 (+), 135.8
(Cquat), 137.1 (+), 148.5 (Cquat), 150.1 (+), 153.5 (Cquat), 156.2
(Cquat). IR (KBr): ν (cm-1) 1240, 1374, 1438, 1561, 3086. EI
MS (70 eV): m/z 256 (29) [M+], 122 (100). Anal. Calcd for
5-Cya n o-6-(4-m et h ylp h en yl)-3-(2-p yr id yl)-1,2,4-t r ia -
zin e (9b). Following GP3, 7b (970 mg, 3.7 mmol) yielded 883
mg (88%) of 9b. Mp: 145-146 °C. 1H NMR: δ 2.48 (s, 3H),
7.44 (m, 2H), 7.54 (m, 1H), 7.98 (m, 1H), 8.07 (m, 2H), 8.69
(br.d, 1H), 8.94 (m, 1H). 13C NMR: δ 21.6 (+), 114.7 (Cquat),
124.5 (+), 126.4 (+), 128.2 (Cquat), 129.0 (+), 130.2 (+), 132.3
(Cquat), 137.6, 143.0 (Cquat), 150.8 (+), 150.8 (Cquat), 157.2 (Cquat),
160.6 (Cquat). IR (KBr): ν (cm-1) 1386, 1578, 1606, 2240, 3049.
EI MS (70 eV): m/z 273 (10) [M]+, 245 (18), [M - N2]+, 141
(100). Anal. Calcd for C16H11N5 (273.3): C, 70.32; H, 4.06; N,
25.63. Found: C, 69.97; H, 4.00; N, 25.63.
C
12H8N4OS (256.3): C, 56.24; H, 3.15; N, 21.86. Found: C,
56.05; H, 3.18; N, 21.64.
6-(2-Na p h th yl)-3-(2-p yr id yl)-1,2,4-tr ia zin e 4-Oxid e (7e).
Following GP1, 1e (1.41 g, 6.6 mmol) and 2-pyridinecarbox-
aldehyde (0.71 g, 6.6 mmol) were reacted to give 1.68 g (84%)
of the intermediate 2e. Compound 2e (1.68 g, 5.6 mmol) and
Pb3O4 (3.81 mg, 5.6 mmol) yielded 0.85 g (51%) of 7e. Mp:
203-205 °C. 1H NMR: δ 7.6 (m, 1H), 7.7 (m, 2H), 8.0 (m, 4H),
8.2 (m, 1H), 8.31 (d, 1H), 8.63 (br.s, 1H), 8.84 (s, 1H), 8.95
(br.d, 1H). IR (KBr): ν (cm-1) 1242, 1348, 1369, 1552, 1580,
2853, 3031. EI MS (70 eV): m/z 300 (48) [M+], 166 (100). Anal.
Calcd for C18H12N4O (300.3): C, 71.99; H, 4.03; N, 18.66.
Found: C, 71.69; H, 4.13; N, 18.54.
5-Cya n o-6-(4-m eth oxyp h en yl)-3-(2-p yr id yl)-1,2,4-tr ia -
zin e (9c). Following GP3, 7c (530 mg, 1.9 mmol) yielded 383
mg (70%) of 9c. Mp: 139-140 °C. 1H NMR: δ 3.93 (s, 3H),
7.02 (m, 1H), 7.15 (m, 2H), 7.58 (m, 1H), 8.20 (m, 2H), 8.70
(m, 1H), 8.97 (m, 1H). 13C NMR (CDCl3, 100 MHz): δ 55.6
(+), 114.8 (Cquat), 115.0 (+), 123.2 (Cquat), 124.5 (+), 126.5 (+),
130.9 (+), 131.6 (Cquat), 138.1 (+), 150.5 (Cquat), 150.5 (+), 156.6
(Cquat), 159.9 (Cquat), 163.1 (Cquat). IR (KBr): ν (cm-1) 1388,
1604, 2232, 3057. EI MS (70 eV): m/z 289 (5) [M]+, 157 (100).
Anal. Calcd for C16H11N5O (289.3): C, 66.43; H, 3.83; N, 24.21.
Found: C, 66.58; H, 4.04; N, 24.70.
2,6-Bis(6-ph en yl-1,2,4-tr iazin -3-yl 4-oxide)pyr idin e (8a).
Gen er a l P r oced u r e 2 (GP 2). A solution of pyridine 2,6-
dicarboxaldehyde (1.35 g, 10 mmol) in ethanol was added to a
stirred solution of isonitrosoacetophenone hydrazone 1a (3.26
g, 20 mmol) in ethanol. The reaction mixture was heated under
reflux for 1 h. The resulting precipitate was separated by
filtration and washed with ethanol to give intermediate 3a
(4.12 g, 97%). To a stirred suspension of 3a (3.50 g, 8.2 mmol)
in glacial acetic (20 mL) acid was added Pb3O4 (11.3 g, 16.5
mmol), and the mixture was kept at room temperature for 5
h. The precipitate was separated by filtration and washed with
acetic acid, water, and ethanol to give 8a (1.14 g, 33%). Mp:
270-273 °C dec. 1H NMR (DMSO-d6, 300 MHz): δ 7.62 (m,
6H), 8.26 (m, 7H), 9.44 (s, 2H). IR (KBr): ν (cm-1) 1244, 1368,
1420, 1555, 3059. EI MS (70 eV): m/z 421 (10) [M+], 102 (100).
Anal. Calcd for C23H15N7O2 (421.4): C, 65.55; H, 3.59; N, 23.27.
Found: C, 65.75; H, 3.39; N, 23.38.
5-Cya n o-6-(2-th ien yl)-3-(2-p yr id yl)-1,2,4-tr ia zin e (9d ).
Following GP3, 7d (450 mg, 1.8 mmol) yielded 335 mg (72%)
1
of 9d . Mp: 197-199 °C. H NMR: δ 7.35 (dd, 1H, J 5.1 Hz,
3.9 Hz), 7.59 (m, 1H), 7.82 (dd, 1H, J 5.1 Hz, 0.8 Hz), 8.02 (m,
1H), 8.45 (dd, 1H, J 3.9 Hz, 0.8 Hz), 8.71 (br.d, 1H), 8.96 (br.d,
1H). 13C NMR: δ 114.7 (Cquat), 124.4 (+), 126.5 (+), 128.8
(Cquat), 129.5 (+), 131.5 (+), 134.1 (+), 134.7 (Cquat), 137.9 (+),
150.6 (Cquat), 150.7 (+), 151.51 (Cquat), 160.0 (Cquat). IR (KBr):
ν (cm-1) 1386, 1420, 1482, 1526, 2231, 3057, 3109. EI MS (70
eV): m/z 265 (9) [M]+, 237 (17), [M - N2]+. Anal. Calcd for
C13H7N5S (265.3): C, 58.86; H, 2.66; N, 26.40. Found: C, 58.49;
H, 2.43; N, 26.51.
5-Cya n o-6-(2-n a p h th yl)-3-(2-pyr id yl)-1,2,4-tr ia zin e (9e).
Following GP3, 7e (430 mg, 1.4 mmol) yielded 394 mg (1.3
mmol, 89%) of 9e. Mp: 169-170 °C. 1H NMR: δ 7.61 (m, 3H),
8.02 (m, 4H), 8.22 (m, 1H), 8.71 (m, 2H), 8.97 (m, 1H). 13C
NMR: δ 114.7 (Cquat), 124.6 (+), 124.8 (+), 126.5 (+), 127.3
(+), 127.9 (+), 128.3 (Cquat), 128.6 (+), 129.3 (+), 129.5 (+),
130.2 (+), 132.7 (Cquat), 132.9 (Cquat), 134.7 (Cquat), 137.7 (+),
150.8 (Cquat), 150.8 (+), 157.2 (Cquat), 160.65 (Cquat). IR (KBr):
ν (cm-1) 1391, 1479, 1578, 2236, 3059. EI MS (70 eV): m/z
309 (7) [M+], 177 (100). Anal. Calcd for C19H11N5 (309.3): C,
73.78; H, 3.58; N, 22.64. Found: C, 73.81; H, 3.88; N, 22.62.
2,6-Bis[6-(4-m eth ylp h en yl)-1,2,4-tr ia zin -3-yl 4-oxid e]-
p yr id in e (8b). Following GP2, 1b (3.54 g, 20 mmol) and 2,6-
pyridinedicarboxaldehyde (1.35 g, 10 mmol) yielded 4.03 g
(89%) of the intermediate 3b. In the second step, 3b (4.0 g,
8.8 mmol) and Pb3O4 (12.10 g, 17.7 mmol) gave 1.34 g (34%)
of 8b. Mp: 303-305 °C. 1H NMR (DMSO-d6, 300 MHz): δ 2.45
(s, 6H), 7.61 (d, 4H, 4-methylphenyl), 8.19 (d, 4H), 2.28-2.31
(m, 3H), 9.46 (s, 2H). IR (KBr): ν (cm-1) 1244, 1366, 1422,
1557, 2920, 3056. EI MS (70 eV): m/z 449 (26) [M+], 116 (78),
130 (100). Anal. Calcd for C25H19N7O2 (449.5): C, 66.81; H,
4.26; N, 21.81. Found: C, 66.43; H, 4.24; N, 21.56.
2,6-Bis(5-cya n o-6-p h en yl-1,2,4-t r ia zin e-3-yl)p yr id in e
(10a ). Following GP3, 8a (700 mg, 1.7 mmol) yielded 460 mg
(63%) of 10a . Mp: 176-177 °C. 1H NMR: δ 7.75 (m, 6H),
0.8.15 (m, 4H), 8.48 (dd, 1H, J 7.8 Hz, J 7.8 Hz), 8.85 (d, 2H,
J 7.8 Hz). IR (KBr): ν (cm-1) 1378, 1441, 2241, 3068. EI MS
(70 eV): m/z 439 (4) [M+], 129 (100). 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.
2,6-Bis-(6-(4-m eth oxyph en yl)-1,2,4-tr iazin -3-yl 4-oxide)-
p yr id in e (8c). Following GP2, 1c (1.4 g, 7.3 mmol) and 2,6-
pyridinedicarboxaldehyde (0.49 g, 3.6 mmol) yielded 1.49 g
(85%) of the intermediate 3c. In the second step, 3c (1.49 g,
3.1 mmol) and Pb2O3 (4.25 g, 6.2 mmol) gave 0.54 g (36%) of
1
8c. Mp: 293-295 °C. H NMR: δ 3.87 (s, 6H), 7.17 (m, 4H),
8.25 (m, 7H), 9.41 (s, 2H). IR (KBr): ν (cm-1) 1244, 1306, 1368,
1421, 1519, 1605, 2841, 3052. EI MS (70 eV): m/z 481 (3) [M]+,
132 (100). Anal. Calcd for C25H19N7O4 (481.5): C, 62.37; H,
3.98; N, 20.36. Found: C, 62.42; H, 4.13; N, 20.67.
2,6-Bis(5-cya n o-6-(4-m eth ylp h en yl)-1,2,4-tr ia zin e-3-yl)-
p yr id in e (10b). Following GP3, 8b (1 g, 2.2 mmol) yielded
1
728 mg (70%) of 10b. Mp: 239-241 °C. H NMR: δ 2.45 (s,
5-Cya n o-6-p h en yl-3-(2-p yr id yl)-1,2,4-tr ia zin e (9a ). Gen -
er a l P r oced u r e 3 (GP 3). To a solution of 1,2,4-triazine-4-
oxide 7a (500 mg, 2.0 mmol) in dichloromethane (10 mL) were
added acetone cyanohydrine (204 mg, 0.22 mL, 2.4 mmol) and
triethylamine (202 mg 0.28 mL, 2.0 mmol). The reaction
6H, CH3), 7.42 (d, 4H), 8.01 (d, 4H), 8.29 (dd, 1H), 8.82 (d,
2H). IR (KBr): ν (cm-1) 1375, 1607, 2240, 3049. EI MS (70
eV): m/z 467 (3) [M+], 141 (100). Anal. Calcd for C27H17N9
(467.5): C, 69.37; H, 3.67; N, 26.96. Found: C, 69.52; H, 3.68;
N, 26.75.
2886 J . Org. Chem., Vol. 68, No. 7, 2003

Synthesis of Functionalized 2,2′-Bi- and 2,2′:6′,2′′-Terpyridines
2,6-Bis(5-cya n o-6-(4-m et h oxyp h en yl)-1,2,4-t r ia zin e-3-
yl)p yr id in e (10c). Following GP3, 8c (350 mg, 0.7 mmol)
yielded 316 mg (87%) of 10c. Mp: 237-239 °C. 1H NMR: δ
3.94 (s, 6H), 7.17 (d, 4H), 8.22 (d, 4H), 8.29 (dd, 1H), 8.89 (d,
2H). IR (KBr): ν (cm-1) 1377, 1603, 2232, 3056. EI MS (70
eV): m/z 499 (7) [M+], 157 (100). Anal. Calcd for C27H17N9O2
(499.5): C, 64.93; H, 3.43; N, 25.24. Found: C, 64.45; H, 3.67;
N, 25.03.
13C NMR: δ 117.2 (Cquat), 122.0 (+), 124.3 (+), 124.9 (+), 128.8
(+), 129.1 (+), 129.6 (+), 131.4 (Cquat), 135.1 (Cquat), 138.1 (+),
138.7 (+), 141.9 (Cquat), 148.6 (+), 153.4 (Cquat), 155.1 (Cquat).
IR (KBr): ν (cm-1) 1437, 1586, 2228, 3056. UV (CH3CN): λmax
(log ꢀ) 290 (4.28). EI MS (70 eV): m/z 257 (100) [M+]. Anal.
Calcd for C17H11N3 (257.3): C, 79.36; H, 4.31; N, 16.33.
Found: C, 79.40; H, 4.56; N, 16.84.
6-Cya n o-5-(4-m eth ylp h en yl)-2,2′-bip yr id in e (15b). Fol-
lowing GP4, 9b (550 mg, 2.0 mmol) yielded 490 mg (90%) of
6-Cya n o-5-p h en yl-2-(2′-p yr id yl)-3,4-cyclop en ten op yr i-
d in e (13). 1-(1-Pyrrolidino)cyclopentene (302 mg, 2.2 mmol)
was added to a solution of 5-cyano-6-phenyl-3-(2-pyridyl)-1,2,4-
triazine 9a (0.52 g, 2.0 mmol) in benzene (10 mL). The reaction
mixture was stirred at room temperature for 1 h and then
heated under reflux for 1 h. The solvent was evaporated in
vacuo and the residue refluxed in acetic acid (3 mL) for 30
min. The precipitated crystals of 13 were filtered off and
washed first with acetic acid and then with ethanol. Yield:
0.58 g (97%). Mp: 192-193 °C. 1H NMR (250 MHz, DMSO-
d6) δ 2.11 (m, 2H), 2.90 (m, 2H), 3.57 (m, 2H), 7.50 (m, 6H),
1
15b. Mp: 187-188 °C. H NMR: δ 2.44 (s, 3H), 7.34 (d, 2H),
7.38 (m, 1H, 7.53 (d, 2H), 7.88 (m, 1H), 7.96 (d, 1H), 8.52 (m,
1H), 8.69 (m, 1H), 8.70 (d, 1H). 13C NMR (CDCl3, 75 MHz): δ
21.3 (+), 117.4 (Cquat), 121.6 (+), 124.1 (+), 124.7 (+), 128.6
(+), 129.8 (+), 131.2 (Cquat), 132.3 (Cquat), 137.4 (+), 138.5 (+),
139.7 (Cquat), 141.8 (Cquat), 149.1 (+), 153.9 (Cquat), 155.6 (Cquat).
IR (KBr): ν (cm-1) 1441, 1583, 2230, 2919, 3019. UV (CH3-
CN): λmax (log ꢀ) 292 (4.56). EI MS (70 eV): m/z 271 (100) [M+].
Anal. Calcd for C18H13N3 (271.3): C, 79.68; H, 4.83; N, 15.49.
Found: C, 79.71; H, 4.90; N, 15.51.
7.94 (m, 1H), 8.32 (m, 1H), 8.67 (m, 1H). IR(KBr): ν (cm-1
)
6-Cyan o-5-(4-m eth oxyph en yl)-2,2′-bipyr idin e (15c). Fol-
lowing GP4, 9c (320 mg, 1.1 mmol) gave 290 mg (92%) of 15c.
1409, 1541, 1572, 2230, 2956, 3059. EI MS (70 eV): m/z 297
(100) [M+]. Anal. Calcd for C20H15N3 (297.36): C, 80.78; H, 5.08;
N, 14.13. Found: C, 80.74; H, 4.98; N, 14.27.
1
Mp: 183-184 °C. H NMR: δ 3.88 (s, 3H), 7.06 (d, 2H), 7.39
(m, 1H), 7.59 (d, 2H), 7.88 (m, 1H), 7.95 (d, 1H, J 8.4 Hz), 8.51
(m, 1H), 8.70 (d, 1H, J 8.4 Hz), 8.70 (m, 1H). 13C NMR: δ 55.4
(+), 114.6 (+), 117.5 (Cquat), 121.7 (+), 124.1 (+), 124.7 (+),
127.4 (Cquat), 130.1 (+), 131.0 (Cquat), 137.5 (+), 138.3 (+), 141.5
(Cquat), 149.0 (+), 153.8 (Cquat), 155.2 (Cquat), 160.7 (Cquat). IR
(KBr): ν (cm-1) 1441, 1518, 1611, 2232, 2843, 2956, 3049. UV
(CH3CN): λmax (log ꢀ) 302 (4.31). EI MS (70 eV): m/z 287 (100)
[M]+, 272 (12), 244 (23). Anal. Calcd for C18H13N3O (287.3):
C, 75.25; H, 4.56; N, 14.62. Found: C, 75.25; H, 4.78; N, 14.82.
2,6-Bis(6-cya n o-5-p h en yl-3,4-cyclop en t en op yr id yl-2)-
p yr id in e (14a ). 1-(4-Morpholino)cyclopentene (178 mg, 1.16
mmol) was added to the solution of the compound 10a (255
mg, 0.58 mmol) in toluene, and the resulting mixture was kept
at room temperature for 1 h and then heated under reflux for
1 h. The solvent was removed in vacuo, and the residue was
heated under reflux in 3 mL of acetic acid. The crystals were
separated by filtration and recrystallized from DMF yielding
14a (230 mg, 77%). Mp: >300 °C dec. 1H NMR (DMSO-d6,
250 MHz) δ: 2.15 (m, 4H), 2.93 (t, 4H), 3.45 (t, 4H), 7.6 (m,
10H), 8.25 (m, 3H). EI/MS (70 eV): m/z 515 (100) [M+]. 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.
Com p lex 14a -Ni(NO3)2.15 A solution of Ni(NO3)2‚6H2O
(84.4 mg, 0.29 mmol) in 3 mL of acetonitrile was added to a
solution of 14a (150 mg, 0.29 mmol) in acetonitrile (5 mL).
The resulting mixture was heated under reflux for 15 min.
Crystals formed after cooling and were separated by filtration,
dissolved 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. C35H25N5-Ni(NO3)2 (698.3).
6-Cya n o-5-(2-th ien yl)-2,2′-bip yr id in e (15d ). Following
GP4, 9d (210 mg, 0.8 mmol) yielded 187 mg (89%) of 15d .
1
Mp: 178-179 °C. H NMR: δ 7.21 (dd, 1H, J 5.2 Hz, 3.8 Hz),
7. 39 (m, 1H), 7.54 (dd, 1H, J 5.2 Hz, 1.1 Hz), 7.80 (dd, 1H, J
3.8 Hz, 1.1 Hz), 7.88 (m, 1H), 8.06 (d, 1H, J 8.5 Hz), 8.50 (br.d,
1H), 8.67 (d, 1H, J 8.5 Hz), 8.70 (m, 1H). 13C NMR: δ 117.5
(Cquat), 121.7 (+), 124.2 (+), 124.8 (+), 128.5 (+), 128.7 (+),
129.4 (Cquat), 134.4 (Cquat), 136.3 (Cquat), 137.6 (+), 137.8 (+),
149.0 (+), 153.5 (Cquat), 155.3 (Cquat). IR (KBr): ν (cm-1) 1449,
1543, 1573, 1587, 2227, 3003. UV (CH3CN): λmax (log ꢀ) 314
(4.32). EI MS (70 eV): m/z 263 (100) [M]+. Anal. Calcd for
C15H9N3S (263.3): C, 68.42; H, 3.45; N, 15.96. Found: C, 68.45;
H, 3.65; N, 16.23.
2,6-Bis(6-cya n o-5-(4-m eth ylp h en yl)-3,4-cyclop en ten o-
p yr id in -2-yl)p yr id in e (14b). 1-(1-Pyrrolidino)cyclopentene
(288 mg, 2.1 mmol) was added to a solution of compound 10b
(470 mg, 1 mmol) in benzene. The resulting mixture was
stirred at room temperature for 1 h and heated under reflux
for 1 h. The solvent was removed in vacuo, the residue was
heated under reflux in 3 mL of acetic acid, and the crystals
obtained were separated by filtration and washed with acetic
acid to give 14b (525 mg, 97%). Mp: 278-279 °C. 1H NMR: δ
2.08 (m, 4H), 2.45 (s, 6H)2.94 (t, 4H), 3.46 (t, 4H), 7.33 (d, 4H),
7.36 (d, 4H), 8.03 (dd, 1H), 8.29 (d, 2H). 13C NMR: δ 21.4 (+),
25.2 (-), 32.6 (-), 34.1 (-), 117.58 (Cquat), 123.8 (+), 128.9 (+),
129.5 (+), 130.1 (Cquat), 131.4 (Cquat), 137.7 (+), 138.4 (Cquat),
139.2 (Cquat), 143.2 (Cquat), 152.2 (Cquat), 155.7 (Cquat). IR
(KBr): ν (cm-1) 1375, 1404, 1544, 1570, 2231, 2871, 2946, 2968,
3026. EI MS (70 eV): m/z 543 (100) [M]+. Anal. Calcd for
6-Cya n o-5-(2-n a p h th yl)-2,2′-bip yr id in e (15e). In accor-
dance with GP4, 9e (200 mg, 0.65 mmol) was reacted to yield
179 mg (90%) of 15e. Mp: 188-190 °C. H NMR: δ 7.40 (m,
1
1H), 7.58 (m, 2H), 7.73 (m, 1H), 7.94 (m, 3H), 8.03 (br.d, 1H),
8.10 (d, 1H), 8.13 (d, 1H), 8.56 (br.d, 1H), 8.72 (m, 1H), 8.76
(d, 1H). 13C NMR: δ 117.3 (Cquat), 121.8 (+), 124.2 (+), 124.8
(+), 125.8 (+), 126.9 (+), 127.3 (+), 127.8 (+), 128.5 (+), 128.6
(+), 129.0 (+), 131.5 (Cquat), 132.5 (Cquat), 133.2 (Cquat), 133.4
(Cquat), 137.6 (+), 138.8 (+), 141.8 (Cquat), 149.0 (Cquat), 153.7
(Cquat), 155.7 (Cquat). IR (KBr): ν (cm-1) 1436, 1541, 2223, 3051.
UV (CH3CN): λmax (log ꢀ) 304 (4.43). EI MS (70 eV): m/z 307
(100) [M]+. Anal. Calcd for C21H13N3 (307.4): C, 82.07; H, 4.26;
N, 13.67. Found: C, 82.08; H, 4.39; N, 13.89.
6,6′′-Dicya n o-5,5′′-d ip h en yl-2,2′,6′2′′-ter p yr id in e (16a ).
Gen er a l P r oced u r e 5 (GP 5). In accordance with GP4,
compound 10a (350 mg, 0.8 mmol) and 20 equiv of bicyclo-
[2.2.1]hepta-2,5-diene (1.47 g, 1.72 mL, 16 mmol) were allowed
to react. Work up in accordance with GP4 yielded 300 mg
(87%) of 16a . Mp: 287-288 °C. 1H NMR: δ 7.56 (m, 6H), 7.67
(m, 4H), 8.03 (d, 2H, J 8.2 Hz), 8.07 (dd, 1H, J 7.9 Hz, J 7.9
Hz), 8.62 (d, 2H, J 7.9 Hz), 8.87 (d, 2H, J 8.2 Hz). 13C NMR:
δ 117.2 (Cquat), 122.5 (+), 124.0 (+), 128.8 (+), 129.1 (+), 129.6
(+), 131.4 (Cquat), 135.2 (Cquat), 138.6 (+), 141.9 (Cquat), 153.5
(Cquat), 155.8 (Cquat). IR (KBr): ν (cm-1) 1436, 1540, 1575, 2230,
3059. UV (CH3CN): λmax (log ꢀ) 301 (4.60). EI MS (70 eV): m/z
435 (100) [M]+. Anal. Calcd for C29H17N5 (435.5): C, 79.98; H,
3.93; N, 16.08. Found: C, 79.87; H, 4.06; N, 15.90.
C
37H29N5 (543.7): C, 81.74; H, 5.38; N, 12.88. Found: C, 81.65;
H, 5.48; N, 12.79.
6-Cya n o-5-p h en yl-2,2′-bip yr id in e (15a ). Gen er a l P r o-
ced u r e 4 (GP 4). A mixture of 5-cyano-6-phenyl-1,2,4-triazine
9a (110 mg, 0.42 mmol) and 10 equiv of bicyclo[2.2.1]hepta-
2,5-diene (386 mg, 0.45 mL, 4.2 mmol) in toluene (10 mL) was
heated under reflux for 12 h. The solvent was evaporated
under reduced pressure, and the residue was stirred with
ethanol (10 mL) for 15 min and separated by filtration to give
15a (103 mg, 95%). Mp: 189-190 °C. 1H NMR: δ 7.43 (m,
1H), 7.54 (m, 3H), 7.63 (m, 2H), 7.93 (m, 1H), 8.00 (d, 1H, J
8.2 Hz), 8.55 (br.d, 1H), 8.72 (m, 1H), 8.78 (d, 1H, J 8.2 Hz).
J . Org. Chem, Vol. 68, No. 7, 2003 2887

Kozhevnikov et al.
6,6′′-Dicya n o-5,5′′-d i(4-m eth ylp h en yl)-2,2′,6′2′′-ter p yr i-
d in e (16b). Following GP5, 10b (570 mg, 1.22 mmol) and
bicyclo[2.2.1]hepta-2,5-diene (2.24 g, 2.63 mL, 24.4 mmol) gave
5H), 7.82 (m, 1H), 8.41 (m, 2H), 8.88 (m, 1H). IR (KBr): ν
(cm-1) 1448, 1547, 1690, 2970, 3055. EI MS (70 eV): m/z 316
(M+, 11), 272 (100) [M+ - CO2]. Anal. Calcd for C20H16N2O2‚
HCl: C, 68.08; H, 4.86; N, 7.94. Found: C, 68.07; H, 4.56; N,
7.73.
1
480 mg (85%) of 16b. Mp: 279-280 °C. H NMR: δ 2.46 (s,
6H), 7.37 (d, 4H), 7.56 (d, 4H), 8.01 (d, 2H, J 8.2 Hz), 8.06 (dd,
1H, J 7.9 Hz, J 7.9 Hz), 8.61 (d, 2H, J 7.9 Hz),8.84 (d, 2H, J
8.2 Hz). 13C NMR: δ 21.3 (+), 117.3 (Cquat), 122.4 (+), 123.9
(+), 128.6 (+), 129.8 (+), 131.3 (Cquat), 132.3 (Cquat), 138.4 (+),
138.5 (+), 139.8 (Cquat), 141.9 (Cquat), 153.5 (Cquat), 155.5 (Cquat).
IR (KBr): ν (cm-1) 1435, 1540, 1575, 2234, 3026. UV (CH3-
CN): λmax (log ꢀ) 304 (4.65). EI MS (70 eV): m/z 463 (100) [M+].
Anal. Calcd for C31H21N5 (463.6): C, 80.33; H, 4.57; N, 15.11.
Found: C, 79.96; H, 4.71; N, 15.13.
6-Eth oxyca r bon yl-5-p h en yl-2-(2′-p yr id yl)-3,4-cyclop en -
ten op yr id in e (19). Carboxylic acid 18 (0.51 g, 1.6 mmol) was
heated under reflux in 5 mL of SOCl2 for 7 h. The solvent was
removed in vacuo, ethanol (15 mL) was added, and the
resulting solution was heated under reflux for 1 h. The mixture
was concentrated in vacuo, and the residue was recrystallized
from ethanol to give 19 (0.47 g, 87%). Mp: 126-127 °C. 1H
NMR (DMSO-d6, 250 MHz) δ 0.97 (t, J 7.5 Hz, 3H), 2.07 (m,
2H), 2.82 (t, J 7.5 Hz, 2H), 3.53 (t, J 7.5 Hz, 2H), 4.03 (q, J 7.5
Hz, 2H), 7.35 (m, 6H), 7.87 (m, 1H), 8.33 (m, 1H), 8.66 (m,
1H). EI MS (70 eV): m/z 344 (3) [M+], 270 (100). Anal. Calcd
for C22H20N2O2 (344.42): C, 76.72; H, 5.85; N, 8.13.: Found:
C, 76.67; H, 5.90; N, 8.17.
6-Hyd r oxym eth yl-5-p h en yl-2-(2′-p yr id yl)-3,4-cyclop en -
ten op yr id in e (20). To a solution of the ester 19 (0.41 g, 1.2
mmol) in ethanol (10 mL) was added NaBH4 (0.23 g, 6 mmol).
The suspension was stirred at room temperature for 1 h and
then heated under reflux for 5 h. The solvent was removed in
vacuo, and the residue was kept at 100 °C for 1 h. Crystals
formed after cooling were filtered off and washed with water
to give 0.27 g of 20 (75%). Mp: 140-141 °C. 1H NMR (DMSO-
d6, 250 MHz) δ 2.03 (m, 2H), 2.70 (t, J 7.4 Hz, 2H), 3.46 (t, J
7.4 Hz, 2H), 4.38 (br.s, 2H), 4.69 (br.s 1H), 7.40 (m, 6H), 7.88
(m, 1H), 8.40 (m, 1H), 8.65 (m, 1H). EI MS (70 eV): m/z 302
(M+, 100). Anal. Calcd for C20H18N2O (302.38): C, 79.44; H,
6.00; N, 9.26. Found: C, 79.44; H, 5.94; N, 9.40.
6,6′′-Dicya n o-5,5′′-d i-(4-m et h oxylp h en yl)-2,2′,6′2′′-t er -
p yr id in e (16c). Following GP5, 10c (150 mg, 0.3 mmol) and
bicyclo[2.2.1]hepta-2,5-diene (552 mg, 0.65 mL, 6 mmol)
yielded 130 mg (87%) of 16c. Mp: 263-264 °C. 1H NMR: δ
3.90 (s, 6H), 7.09 (d, 4H), 7.61 (d, 4H), 8.00 (d, 2H, J 8.2 Hz),
8.05 (dd, 1H, J 7.8 Hz, 7.8 Hz), 8.60 (d, 2H, J 7.8 Hz), 8.83 (d,
2H, J 8.2 Hz). 13C NMR: δ 55.5 (+), 114.6 (+), 117.5 (Cquat),
122.4 (+), 124.0 (+), 127.4 (Cquat), 130.1 (+), 131.1 (Cquat), 138.3
(+), 138.6 (+), 141.6 (Cquat), 153.5 (Cquat), 155.2 (Cquat), 160.8
(Cquat). IR (KBr): ν (cm-1) 1433, 1516, 1609, 2234, 2837, 2955,
3067. UV (CH3CN): λmax (log ꢀ) 312 (4.62). EI MS (70 eV): m/z
495 (100) [M]+. Anal. Calcd for C31H21N5O2 (495.6): C, 75.14;
H, 4.27; N, 14.13. Found: C, 75.33; H, 4.44; N, 14.18.
6-Ca r ba m oyl-5-p h en yl-2-(2′-p yr id yl)-3,4-cyclop en ten o-
p yr id in e (17). Cyanocyclopentenopyridine 13a (0.3 g, 1 mmol)
was dissolved in 1 mL of concentrated sulfuric acid and heated
at 100 °C for 6 h. The mixture was poured onto ice and was
neutralized with concentrated ammonia solution. Precipitated
crystals were filtered off, washed with water, and recrystal-
lized from 2-propanol to give 0.29 g (92%) of 17. Mp: 197-
198 °C. 1H NMR (DMSO-d6, 250 MHz) δ 2.03 (m, 2H), 2.72 (t,
J 7.7 Hz, 2H), 3.50 (t, J 7.7 Hz, 2H), 7.12 (br.s, 1H, amide),
7.32 (m, 6H), 7.72 (br.s, 1H, amide), 8.87 (m, 1H), 8.44 (m,
1H), 8.63-6.67 (m, 1H). IR (KBr): ν (cm-1) 1427, 1577, 1661,
2361, 2953, 3058, 3176, 3400. EI MS (70 eV): m/z 315 (36)
[M]+, 270 (100). Anal. Calcd for C20H17N3O (315.38): C, 76.17;
H, 5.43; N, 13.32. Found: 76.19; H, 5.54; N, 13.30.
Ack n ow led gm en t. We thank the Russian Founda-
tion for Basic Research (Grant No. 02-03-32635), the
U.S. Civilian Research and Development Foundation for
the Independent States of the Former Soviet Union
(SRDF) (Project No. REC-005), and the Fonds der
Chemischen Industrie for support of this research.
V.N.K. is grateful to the Alexander von Humboldt
Foundation for a postdoctoral fellowship.
6-Ca r b oxy-5-p h en yl-2-(2′-p yr id yl)-3,4-cyclop en t en o-
p yr id in e Hyd r och lor id e (18). Carbamoylcyclopentenopyr-
idine 17 (0.19 g, 0.6 mmol) was heated under reflux in 11 M
HCl for 7 h. The crystals formed after cooling were filtered off
and washed with 2 mL of 11 M HCl, yielding 18 (0.16 g, 83%).
Mp: 209-210 °C; 1H NMR (DMSO-d6, 250 MHz) δ 2.04-2.19
(m, 2H), 2.84 (t, J 7.3 Hz, 2H), 3.48 (t, J 7.3 Hz, 2H), 7.39 (m,
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
compound 2c and 3b in DMSO-d6; structure of complex 14b
in the crystal. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O0267955
2888 J . Org. Chem., Vol. 68, No. 7, 2003