Synthesis of new bis(2-[1,8]naphthyridinyl) bridging ligands with?multidentate binding sites

Article abstract of DOI:10.1016/j.tet.2008.02.017

A series of new 2-[1,8]naphthyridinyl and bis(2-[1,8]naphthyridinyl) bridging ligands with multidentate binding sites were prepared using 2-amino-5-cyano-6-ethoxy-4-phenyl-3-carbaldehyde pyridine as excellent Friedl?nder synthon. Condensation with a serie

Full text of DOI:10.1016/j.tet.2008.02.017

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 3446e3456
www.elsevier.com/locate/tet
Synthesis of new bis(2-[1,8]naphthyridinyl) bridging ligands
with multidentate binding sites
*
Antonio Fernandez-Mato, Gerardo Blanco, Jose M. Quintela , Carlos Peinador
*
´
´
Departamento de Qu´ımica Fundamental, Facultad de Ciencias, Universidad de A Coru~na, 15071 A Coru~na, Spain
Received 16 January 2008; received in revised form 6 February 2008; accepted 7 February 2008
Available online 9 February 2008
Abstract
A series of new 2-[1,8]naphthyridinyl and bis(2-[1,8]naphthyridinyl) bridging ligands with multidentate binding sites were prepared using
2-amino-5-cyano-6-ethoxy-4-phenyl-3-carbaldehyde pyridine as excellent Friedlander synthon. Condensation with a series of acetyl(heteroaryl)-
¨
aromatics provides the corresponding 2-aryl(heteroaryl)-1,8-naphthyridines. Reaction with 1,3-diacetylbenzene, 2,6-diacetylpyridine or 4-tert-
butyl-2,6-diacetylpyridine provides the expected Friedlander product. Similar 2:1 condensation with 1,4-diacetylbenzene, 4,40-diacetylbiphenyl,
¨
1,4- and 1,6-diacetylpyrene, 2,6-diacetylpyrazine or 2,3-butanedione leads to a family of six new bis-1,8-nap ligands. The reaction with cyclic
1,2- or 1,3-diketones affords 3,30-annelated derivatives of all-syn or all-trans planar 2,20-nap, respectively. Examination of the electronic absorp-
tion and emission spectra of the bridging ligands was realized.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
(nap), although less basic than 2,20-bipyridine (bpy), can
also function as a bidentate ligand where the nitrogen lone
pairs are now fixed nearly parallel and coplanar in a 1,3 rela-
tionship. The functionalized derivatives of nap at positions 2
and 7 with, at least, a donor atom or group (X¼O, N, P),
such as X-nap I and X2-nap II, introduce multiple coordina-
tion possibilities, and the ability to act as polynucleating
ligands gathering several metal centres (Fig. 1).4 Coordinating
substituents on positions 2 and 7 of the napy ring, such as III
(pynap) and IV (bpnap) (Fig. 1), gave rise to polydentate, cav-
ity-shaped molecules able to coordinate two metal centres in
the cavity.5 Novel multidentate dinucleating ligands based
Bridging ligands have received much interest recently due
to their ability to couple metal centres in a covalent manner
resulting in polymetallic complexes that often possess new
and interesting properties as, for example, photosynthetic
mimics, molecular devices and electrocatalysts. Heteroaro-
matic nitrogen ligands find extended applications in several
important research and technological fields, including asym-
metric catalysis, DNA binding, use as diagnostic agents and
drugs, tumour targeting, nonlinear optical materials and other
applications in electrooptical and photonic devices.1 Currently,
there is enormous interest in the design and preparation of poly-
dentate ligands capable of self-assembly processes.2 Among
the polydentate ligands, the 1,8-naphthyridine molecule has
received wide attention because of its ability to function as
an effective ligand. The naphthyridines and their derivatives
exhibit various types of biological activity, and their organic
chemistry has been frequently reviewed.3 1,8-Naphthyridine
X
N
N
X
N
N
X
I
II
N
N
N
N
N
N
N
III
IV
* Corresponding authors.
E-mail address: capeveqo@udc.es (C. Peinador).
Figure 1.
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.02.017

A. Ferna´ndez-Mato et al. / Tetrahedron 64 (2008) 3446e3456
3447
Ph
on 1,8-naphthyridine have been prepared with the aim of
mimicking the coordination environment of dinuclear metallo-
hydrolases that perform the hydrolysis of biologically impor-
tant substrates such as DNA, RNA and peptides.6
Ph
N
NC
CHO
NH2
NC
+
RCOCH3
EtO
N
EtO
N
R
1
2a-l
3a-l
The Friedlander condensation, in which an aromatic a,b-
¨
unsaturated b-aminoaldehyde or ketone is condensed with an
aldehyde or ketone containing at least one methylene group
a to the carbonyl, represents a versatile and straightforward
approach to the pyridine nucleus especially when it is incorpo-
rated into annulated derivatives such as quinoline and 1,8-nap-
2a R =
2b R =
3a (93%)
2g R =
N
3g (93%)
3h (83%)
N
3b (95%) 2h R =
N
H
thyridine.7 The Friedlander reaction of o-aminoaldehydes to
N
¨
2c R =
2d R =
3c (97%)
3d (97%)
2i R =
2j R =
3i (86%)
3j (80%)
prepare quinolines was extensively reviewed by Cheng and
Yan in 1982.8 Caluwe et al.9 and Thummel et al.10 have dem-
onstrated the use of this method for the regioselective intro-
O
S
duction of 1,8-naphthyridine units. Friedlander reactions are
¨
generally carried out either by refluxing an aqueous or alco-
holic solution of reactants in the presence of acids or bases
or may take place by heating the reactants at high tempera-
tures in the absence of catalyst. In recent years, modified
methods have been employed and chlorotrimethylsilane,11
Lewis acids,12 iodine,13 a combination of acidic catalysts
and microwave irradiation14 and ionic liquids15 have all
been found to be effective for this conversion.
2e R =
2f R =
3e (98%)
2k R =
2l R =
3k (82%)
3l (88%)
S
N
3f (87%)
N
Scheme 1.
We previously reported a highly efficient and regioselective
synthesis of substituted pyrazinothienopyrimidinones and bis-
(pyrazinothienopyrimidinyl)benzenes of interest as potential
biologically active compounds or pharmaceuticals, as well as
in their use as appropriate phenanthroline-like ligands.16 In
this context, as part of a programme of investigating the syn-
thesis and study of new bridging ligands and their use as
chelating ligands, we directed our attention to the synthesis
of novel multidentate nitrogen based ligands and, herein, we
disclose that the b-enaminoaldehyde 1 is an excellent
(20-nap)benzene 4 and the 4,40-disubstituted biphenyl analogue
ligand 5. In fact, the aminoaldehyde 1 then undergoes double
Friedlander condensation with 1,4-diacetylbenzene to provide
¨
1,4-di(1,8-naphthyridyn-20-yl)-benzene 4 (Fig. 2). In an analo-
gous fashion, the condensation of 1 with 4,40-diacetylbiphenyl
provides the homologated biphenyl-bridged system 5 in 77%
yield. Other diketones will condense in a similar 2:1 fashion,
and thus, when 1,4-diacetylpyrene or 1,6-diacetylpyrene,
Ph
Ph
Friedlander building block17 for the preparation of a variety
¨
CN
OEt
N
N
NC
EtO
of functionalized derivatives of nap at positions 2 and 7,
including annelated cavity-shaped molecules derivatives of
substituted bis-1,8-naphthyridines.
N
N
N
N
4 (88%)
5 (77%)
Ph
Ph
2. Results and discussion
CN
NC
EtO
N
N
OEt
The prerequisite heterocyclic aminoaldehyde used as start-
ing material for the preparation of the title condensed
1,8-naphthyridine derivatives can be readily prepared by
LiAlH4 reduction of 2-amino-3,5-dicyano-6-ethoxy-4-phenyl-
pyridine,18 which is easily accessible from malononitrile and
benzaldehyde.19 First, the initial objective was the synthesis
of 2-aryl and 2-heteroaryl derivatives 3ael. Thus, the base-
catalyzed reaction of the b-aminoaldehyde 1 with aryl and
heteroaryl methyl ketones 2ael provides the corresponding
2-aryl and 2-heteroaryl-1,8-naphthyridines in very good yields
of 80e98% (Scheme 1). The series of 2-aryl(heteroaryl) deriva-
tives 3ael would help to investigate the p-stacking effect of
this aromatic substituent with a pyridine of one of the auxiliary
bpy ligands in Ru(bpy)2 complexes.10b,20
Ph
CN
EtO
NC
N
N
N
N
OEt
Ph
6 (60%)
N
N
N
Ph
N
Ph
NC
OEt
EtO
CN
The Friedlander reaction of 1 with a variety of diketones
¨
7 (67%)
Figure 2.
occurs readily under basic conditions leading polyaza cavities
of bis-1,8-naphthyridine. Thus, we have prepared 1,4-bis-

3448
A. Ferna´ndez-Mato et al. / Tetrahedron 64 (2008) 3446e3456
accomplished according to a published procedures,21 is con-
densed with the b-enaminoaldehyde 1, the analogous corre-
sponding 1,4- or 1,6-di(1,8-naphthyridyn-20-yl)-pyrenes, 6
and 7, are prepared in 60 and 67% yield, respectively. These
four systems provide an interesting series of ligands wherein
the orientation between metals bound at the two 1,8-naphthyr-
idine sites will be controlled by the bridging group. This group
will also strongly influence any electronic communication
between the metal centres through the p-framework.10b
This synthesis could also be adapted to the preparation of
analogues having their terminal 1,8-naphthyridine groups
linked. Thus, 2,3-butanedione condenses in a similar 2:1 fash-
ion, and provides 2,20-bis[1,8]-naphthyridine 9 as a multiden-
tate ligand (Scheme 2). The reaction of 2,3-butanedione with 1
in a 1:1 molar ratio in ethanol, under a catalytic alkaline con-
ditions (10% ethanolic potassium hydroxide), gives 2-acetyl-
1,8-naphthyridine 8. Formation of 9 was confirmed by using
and 7, the pyrene protons may be explained by their character-
istic coupling patterns and chemical shifts. For the isomer 7
H4¼H5 and H9¼H10 and the signals of these protons appear
as a singlets at d¼8.48 and 8.20, respectively. For this isomer,
H3¼H6sH2¼H7 and thus H3 and H6, as well as H2 and H7,
appear as doublets at d¼8.39 and 8.35, respectively. For the
isomer 6, H4¼H9sH3¼H8sH2¼H7sH5¼H10 appear as
doublets at d¼8.50 (J¼9.3 Hz), 8.36 (J¼8.0 Hz), 8.32
(J¼8.0 Hz) and 8.16 (J¼9.3 Hz), respectively.
All the ligands are shown in their all-syn planar conforma-
tion, which would be the one providing the greatest interaction
between two bond metal centres and emphasize potential
cooperativity on metal binding. The free ligands in solution,
however, more likely exist in conformations that would mini-
mize HeH and nitrogen lone pairelone pair repulsions about
single bonds.24 Rotation about the single bond connecting the
terminal nap to the linker would provide other conformations
of the ligands. Furthermore, molecule 5 has other single bonds
in the linker, which would afford additional conformational
freedom. Binding two metals will, in every case, restrict this
rotational freedom. The fused pyridine rings serve to sterically
congest the coordinating pocket of the molecule in its syn
conformation and limit the types of complexation which can
occur.25
Reactions of heterocyclic aminoaldehydes with cyclic dike-
tones are especially valuable for the construction of polycon-
densed heterocyclic compounds for which in many cases
alternate annelation methods are not readily available. The
direction of annelation and the position of the heteroatom(s)
are in general uniquely defined by the participating functional
groups. As shown in Scheme 3, 1,2-cyclohexanedione pro-
vides direct accessibility of the 3,30-annelated 2,20-bis[1,8]-
naphthyridine 12. This 3,30-ethylene-bridged system 12 is
a cavity-shaped molecule with sp2-hybridized nitrogen atoms
an alternative way involving Friedlander condensation of ace-
¨
tylnaphthyridine 8 with 1 under the same reaction conditions.
Similarly, the dinap-pyrazine 11 was synthesized by a double
Friedlander condensation using an appropriate diacetyl diazine
¨
precursor and 2 equiv of a,b-enaminonitrile 1 (Scheme 2). The
diacetylpyrazine 10 was prepared by the free radical acetyl-
ation of pyrazine using acetaldehyde and tert-butylhydroperox-
ide in the presence of ferric sulfate.22 The condensation with 1
proceeded smoothly to afford 80% of the expected 2,5-dinap-
pyridazine 11.
O
Ph
NC
(1:1)
O
EtO
N
N
O
8
1
O
O
Ph
Ph
(2:1)
Ph
Ph
(1:1)
O
O
1
NC
N
N
CN
OEt
NC
EtO
N
N
CN
OEt
N
N
N
N
EtO
12 (76%)
Ph
O
9 (66%)
N
O
O
(1:1)
O
EtO
NC
NC
EtO
N
N
1
Ph
N
N
N
10
O
N
N
13
CN
OEt
N
Ph
1
N
11 (80%)
OEt
OEt
Scheme 2.
CN
Ph
CN
Ph
N
N
O
O
All bridging ligands 4, 5, 9 and 11 were readily character-
1
ized by H NMR. The 2-nap moieties gave very similar and
N
N
(1:2)
DDQ
1
characteristic patterns in the aromatic region. Thus, the H
N
N
NMR spectra show two doublets at d¼8.04e8.17 and 8.20e
8.86 (J¼8.4e8.6) due to either one protons of the naphthyr-
idine skeletons. The central ring was distinguished by either
one singlet, d¼8.40 for 4 and 10.02 for 11, or one multiplet,
d¼7.85e7.92 for 5. The deshielding of these protons was con-
sistent with their proximities to nitrogen.23 For the ligands 6
N
N
Ph
OEt
Ph
OEt
CN
14 (65%)
CN
15 (60%)
Scheme 3.

A. Ferna´ndez-Mato et al. / Tetrahedron 64 (2008) 3446e3456
3449
Figure 3. Crystal structure of compound 14 showing the atom labelling scheme and 50% probability thermal ellipsoids. Solvent molecules and hydrogen atoms
have been omitted for clarity.
at every nonbridgehead position on the ‘bay region’. Thus, the
double condensation reaction of 1,2-cyclohexanedione with 1
in a 1:2 molar ratio proceeds to form exclusively polyaza
cavity-shaped molecule 12 in a good manner. However, the
analogous reaction with 1,2-cyclopentanedione has thus far
been unsuccessful.
are observed. The structural determination of 14 was unequiv-
ocally established by the X-ray structure determination of a
monocrystal (Fig. 3).
With a view towards modifying the size, shape and dentic-
ity of the binding pocket, we have undertaken in the prepara-
tion of polyaza ligands in which nitrogens are situated inside a
molecular cavity potentially capable of polynuclear metal
coordination. These ligands consist of two terminal moieties
of 1,8-naphthyridine connected by an intervening aromatic
or heteroaromatic species. Thus, the cavity-shaped molecules
Annelation reactions of b-diketones with 1 are greatly facil-
itated by the presence of a double activated a-methylene group
and, as expected, only one directed ring closure is observed.
Thus, the base-catalyzed condensation of nicotinaldehyde 1
with 1,3-cyclohexanedione provides tricyclic ketone 13 or
annelated bisnap 14, depending on the molar ratio of the reac-
tants. Treatment of the annelated ketone 13 with nicotinalde-
hyde 1 likewise resulted in the formation of the pentacyclic
bisnaphthyrine 14 in 65% yield. Compound 14 could be
oxidized to the fully aromatic derivative 15 with 2,3-di-
chloro-5,6-dicyano-1,4-benzoquinone (DDQ) in refluxing
THF. Bisnap molecule 12 can be considered as a 3,30-ethyl-
ene-bridged derivative of all-syn planar 2,20-bis[1,8]-naphthyr-
ine 9, and the latter ligands 14 and 15 as a 3,30-dimethylene-
bridged or a 3,30-ethene-bridged derivative of all-trans planar
2,20-nap 9, respectively. The steric requirements of both
ligands 9 and 12 are very similar, and differences in the prop-
erties of their metal complexes could be mostly attributed to
electronic differences from the greater electronegativity of
2,20-bis[1,8]-naphthyridine 12.26
19aec were synthesized by a double Friedlander condensation
¨
using 1,3-diacetylbenzene (18a), 2,6-diacetylpyridine (18b)
or 4-tert-butyl-2,6-diacetylpyridine (18c)27 precursors and
2 equiv of 2-amino-3-pyridinecarbaldehyde 1 (Scheme 4).
R
R
1
X
Ph
N
N
Ph
X
O
O
N
N
NC
CN
18a-c
OEt
OEt
19a X = CH, R = H (92%)
19b X = N, R = H (77%)
19c X = N, R = C(CH3)3 (93%)
Scheme 4.
Further unambiguous identification for 12e15 was obtained
from 1H NMR, 13C NMR, MS and elemental analyses. It should
be noted that when the bridge contains more than one methy-
lene unit a conformational inversion of the non-planar ring is
possible, providing an interconvertible pair of enantiomers
via twisting about the 3,30-bond.10a As has been previously
noted for other bridged similar compounds,10 the 3,30-ethylene
system of 12 is conformationally mobile on the NMR time scale
and a singlet is observed at d¼3.80 as expected for 4 equiv pro-
tons flanked by two napthyridine groups. For the ethylene
bridge of 14, the CH2 groups are non-equivalent and two signals
1,2,3,4,5,6,7,8-Octahydroacridine-2,8-dione 2028 may be
considered as a bridged derivative of 19a. Although it could
be condense with 1 to provide the highly congested naphthyr-
idine derivative 22, solubility problems thwarted the character-
ization of this compound. That compound was detected in the
1H NMR and mass spectra of the crude material but unfortu-
nately separation and purification have been unsuccessful
(Scheme 5). Also, an analogous 2:1 reaction with 5,6,7,8-tet-
rahydro-8-quinolone 21a or 5,6,7,8-tetrahydro-8-quinazolone
21b29 to provide the ethylene bridged parent ligands 23 and

3450
A. Ferna´ndez-Mato et al. / Tetrahedron 64 (2008) 3446e3456
the dinuclear complex of 7 can still rotate freely about the
biphenyl linkage. In addition, we have also compared rigid
cavity-shaped molecules, as 12, and the mononuclear pyrene
analogue 3f of the compounds 6 and 7.
N
N
Ph
N
N
Ph
O
O
20
N
N
NC
CN
Since the spectroscopic and electronic properties of metal
complexes will depend to a great extent on ligand structure,
it was of interest to measure their absorption and emission
properties for these systems. These properties were recorded
in CH2Cl2, and that data are compiled in Tables 1 and 2,
and several interesting correlations can be made involving
the energies of these absorptions and structure. The strongest
correlation in these data involves different compounds aryl
or heteroaryl substituted or with different central linkers
between the terminal napy moieties.
OEt
OEt
22
X
N
1
X
Ph
O
21a,b
N
N
CN
OEt
N
23 X = CH
24 X = N
Scheme 5.
Table 1
Photophysical data for naphthyridine derivatives 3a
24 was also unsuccessful (Scheme 5). Once again, by solubil-
ity problems we have never been able to isolate such interest-
ing bridged bisnaphthyridines although these compounds were
Absorptiona lmax [nm] (log 3)
Emissionb lcm
[nm] 298 K
1
3a
3b
3c
3d
3e
3f
3g
3h
3i
234 (5.07), 350 (4.85), 365 (4.91)
232 (5.39), 372 (5.04)
380
410
detected in the H NMR spectra of the crude materials.
The functionalized derivatives of 1,8-naphthyridine and
1,8-bisnaphthyridines prepared in this work introduce multiple
coordination possibilities, and the ability to act as polynuclea-
ting ligands gathering by binding two or more metal atoms. On
the other hand, several of the prepared ligands have a variety
of different denticities available. Although it is possible for
1,8-naphthyridine to act as a chelating bidentate ligand, for
the 2-(pyrid-20-yl)-1,8-naphthyridine motif found in molecules
as, for example, 3f or 11 it is far more likely that bidentate
metal binding will involve N1 of naphthyridine and the pyr-
idine (or pyridazine) nitrogen. This would leave one nitrogen
of the naphthyridine uncomplexed and available to facilitate
other chemistry. This property has been exploited by Thummel
et al. in studies aimed at the photooxidation of water assisted
by photosensitized intramolecular proton transfer.30
To attain better electronic communication between linked
ligands, substantial attention has been paid to the conjugating
ability of the linker. Linkers with one or more p-bonds are com-
mon, while the inclusion of a tetrahedral centre such as an sp3-
carbon atom can serve as an insulating junction.32 Conjugated
p-systems as linkers pose further problems, the most important
of which is the potential orthogonality between any two adja-
cent p-links. Such an orthogonal junction can also behave as
an insulator, as has been noted with polyene and polyphenylene
linkers.32 In this context, the pyrene nucleus is of considerable
current interest as part of a ligand system due to the promising
symmetry and electronic structure of this polynuclear aromatic
compound.33 Consequently, we sought to use of benzene,
pyrene, phenylene, pyridine or pyrazine molecule as a linker
in bridging ligand design. The availability of diacetylbenzenes,
2,6-diacetylpyridine, 2,6-diacetylpyrazine, 4,40-diacetylbi-
phenyl, 2,3-butanedione and several isomers of diacetylpyrene
led us to prepare and study the family of bridging ligands 4e7,
9, 11 and 19 reported here. Although the ligands experience free
rotation about the bond connecting nap to the linker, the incor-
poration of a metal centre unit rigidifies the system, for exam-
ple, as [Ru(bpy)2]2þ by inhibiting this rotation. Nevertheless,
241 (4.43), 266 (4.41), 366 (4.32), 410 (4.57)
235 (5.41), 264 (5.50), 375 (5.18)
236 (5.04), 271 (4.65), 351 (4.53), 400 (4.68)
235 (4.99), 277 (5.06), 350 (4.61), 366 (4.72)
274 (4.37), 370 (4.31), 387 (4.22)
236 (5.34), 287 (5.22), 350 (5.00)
236 (4.67), 393 (4.75)
440, 490
420, 470
440, 480
390, 480
420
330, 480
475
410
3j
3k
3l
275 (5.05), 367 (4.47), 379 (4.62)
230 (5.40), 365 (5.38), 383 (5.50)
274 (5.56), 372 (5.21), 388 (5.31)
420
420
a
CH2Cl2 (10ꢀ5 M) at 25 ꢁC.
Excited to the long-wavelength absorption maximum.
b
The phenyl derivative 3a shows a long-wavelength absorp-
tion at 365 nm, while the heteroaryl species show absorptions
at somewhat lower energies consistent with increased electro-
negativity due to the additional heteroatom(s). The aryl deriva-
tives 3aee show long-wavelength absorptions in the range
365e410 nm, and this long-wavelength region of the UV
absorption spectra of 3a, 3c and 3d is shown in Figure 4.
Table 2
Photophysical data for bisnaphthyridine derivativesa
Absorptiona lmax [nm] (log 3)
Emissionb lcm
[nm] 298 K
4
233 (5.31), 291 (3.87), 386 (5.84)
232 (5.40), 333 (5.49), 384 (5.54)
231 (5.63), 288 (4.57), 328 (4.50), 418 (4.68)
230 (5.56), 294 (4.51), 372 (4.52), 416 (4.59)
369 (3.74), 376 (3.83), 388 (3.85)
232 (5.11), 378 (5.10), 394 (5.13)
249 (4.60), 377 (4.34), 391 (4.37), 415 (4.37)
248 (4.98), 378 (4.89), 398 (5.06)
232 (5.25), 391 (5.11)
410
5
410, 440
530
480
6
7
9
390
450
11
12
14
15
19a
19b
a
450
440
410
495
235 (5.10), 286 (4.72), 353 (4.91), 369 (5.05)
242 (5.58), 352 (5.37), 371 (5.54)
430
CH2Cl2 (10ꢀ6 M) at 25 ꢁC.
Excited to the long-wavelength absorption maximum.
b

A. Ferna´ndez-Mato et al. / Tetrahedron 64 (2008) 3446e3456
3451
Figure 5. Absorption spectra (top) of 4e7 measured in 10ꢀ6 M CH2Cl2 solu-
tions at room temperature and the emission spectra (bottom) for 4e7.
Figure 4. Absorption spectra (top) of 3a,cee measured in 10ꢀ5 M CH2Cl2
solutions at room temperature and the emission spectra (bottom) for 3cee.
moieties. The existence of the pyridazine subunit causes
a bathochromic shift and an increase in intensity. The emission
shifts (Fig. 5) to 410 nm for 4, 440 nm for 5 and 530 nm for 6,
in the fluorescence spectra, newly reflects a steady progression
to lower energy with increasing delocalization of the system
with the 16p-electron of the central pyrene ring providing
better delocalization of the excited state. The Stokes shift is
the difference between the absorption and emission maxima
and, to some extent, provides a measure of geometric changes
that occur upon electronic excitation. For 4e7, and 11 we
observe values of 24e112 nm, which are consistent with the
more longitudinal organization of the molecule.31
Increasing delocalization causes a bathochromic shift and in-
crease in intensity. Where the absorption spectrum gives infor-
mation about the excited-state population of a molecule, the
emission spectrum addresses the depopulation of this state.
The long emission shifts to 380 nm for 3a, 410 nm for 3b,
490 nm for 3c, 470 nm for 3d and 480 nm for 3e reflecting
a steady progression to lower energy with increasing delocal-
ization of the system. The shortest maximum emission for 3d
is consistent with the angular structure of the phenanthrene
moiety. Figure 4 shows the emission spectra for 3cee.
The ligands 4e7, 9 and 11 show low energy absorption
bands in the range of 386e418 nm and several interesting cor-
relations can be made involving the energies of these absorp-
tions and structure. The strongest correlation that one finds in
these data involves ligands having similar linkers between the
terminal nap moieties. First, the bisnap derivative 4 shows
long-wavelength absorption at 386 nm while the dimeric
pyrene species 6 and 7 show absorptions at somewhat lower
energies (418 and 416 nm, respectively), consistent with the
symmetry and electronic structure of the pyrene moiety.31
The ligand involving pyridazine 11 absorbs at longer wave-
length (394 nm) than their benzene counterparts 4, which
agrees with increased electronegativity due to the additional
nitrogen atoms. Figure 5 compares electronic absorption spec-
tra for systems having an aromatic linker between the nap
For the two ligands involving 1,8-naphthyridine 9 and 12,
the one 2,20-bis[1,8]-naphthyrine 9 absorbs at 27 nm shorter
wavelength than their one all-syn planar 3,30-dimethylene-
bridged derivative 12. This difference can be explained by
considering the planar conformations available for the ligands.
Conformational mobility about the 2,20 bond provides less
delocalization and the least coplanar system 9 absorbs at
shortest wavelength. Finally, rotation about the single bonds
connecting the terminal nap to the linker that would mini-
mize nitrogenenitrogen lone pair repulsions could explain
shortest wavelength emission for 19b than their isoster deriv-
ative 19a.
Future work will investigate the metal binding properties of
these new ligands. Preliminary results indicate an interesting
Ru and Pt complexes.

3452
A. Ferna´ndez-Mato et al. / Tetrahedron 64 (2008) 3446e3456
3. Experimental section
3.1. General
3.2.3. 7-(Anthracen-20-yl)-3-cyano-2-ethoxy-4-phenyl-1,8-
naphthyridine (3c)
Recrystallized from ethanol; yield (93%); yellow crystals;
mp: 285e287 ꢁC. IR (KBr) 2226 (CN), 1583, 1486 cmꢀ1
.
All reagents used were commercial grade chemicals from
freshly opened containers. Merk 60 HF254þ366 foils were used
for thin layer chromatography and Merk 60 (230e400 mesh)
silica gel for flash chromatography. NMR spectra were obtained
in a Bruker Avance 500 equipped with a dual cryoprobe for 1H
and 13C and a Bruker Avance 300 spectrometers. TMS was used
as an internal reference. IR spectra were recorded as potassium
bromide disks. Mass spectrometry experiments were carried
out in a Fision VG-Quattro spectrometer. Electronic spectra
were measured on a Perkin Elmer Lambda 900 spectrophotom-
eter. Fluorescence spectra were obtained with a Hitachi F-2000
luminescence spectrometer. Melting points were measured
using Stuart Scientific SMP3 apparatus and are uncorrected.
Microanalyses were performed by the elemental analyses
1H NMR (CDCl3, 300 MHz) d: 1.58 (t, 3H, J¼7.1 Hz, CH3),
4.87 (q, 2H, J¼7.1 Hz, OCH2), 7.50e7.64 (m, 7H, ArH),
7.98e8.08 (m, 4H, ArH), 8.17 (d, 1H, J¼9.0 Hz), 8.36 (dd,
1H, J¼1.7, 7.2 Hz), 8.47 (s, 1H), 8.60 (s, 1H), 8.90 (s, 1H).
13C NMR (CDCl3, 75 MHz) d: 14.0, 63.7, 114.1, 116.3,
118.2, 128.6, 130.8, 131.5, 131.6, 132.2, 134.3, 136.6,
157.8, 160.0, 162.4. MS (FAB) m/z 452 [(MH)þ, 100], 451
(52), 424 (24), 391 (33), 341 (19), 289 (25). Anal. Calcd for
C31H21N3O: C, 82.46; H, 4.69; N, 9.31. Found: C, 82.59; H,
4.66; N, 9.26.
3.2.4. 3-Cyano-2-ethoxy-7-(phenanthren-20-yl)-4-phenyl-
1,8-naphthyridine (3d)
CH2Cl2ehexane, 8:2; yield (97%); white solid; mp: 284e
285 ꢁC. IR (KBr) 2226 (CN), 1583, 1480, 1414 cmꢀ1 1H
.
~
general service of the University of A Coruna.
NMR (CDCl3, 300 MHz) d: 1.59 (t, 3H, J¼7.1 Hz, CH3),
4.86 (q, 2H, J¼7.1 Hz, OCH2), 7.49e8.09 (m, 11H), 8.47e
8.54 (m, 1H), 8.73e8.88 (m, 4H). 13C NMR (CDCl3,
75 MHz) d: 13.0, 64.0, 98.9, 115.0, 124.5, 128.5, 128.7,
128.9, 130.6, 130.8, 131.9, 132.0, 135.4, 137.3, 155.0,
163.3, 163.6. MS (FAB) m/z 452 [(MH)þ, 90], 391 (35).
Anal. Calcd for C31H21N3O: C, 82.46; H, 4.69; N, 9.31.
Found: C, 82.79; H, 4.76; N, 9.16.
3.2. 7-Aryl (or heteroaryl)-3-cyano-2-ethoxy-4-phenyl-1,8-
naphthyridines 3ael. General procedure
A solution of 1 (0.75 mmol), a suitable aryl or heteroaryl
methyl ketone 2 (0.75 mmol) and a catalytic amount of 10%
ethanolic potassium hydroxide in ethanol (10 mL) was re-
fluxed until all starting material had disappeared as checked
by TLC (15 mine24 h). After cooling, the precipitates were
collected by filtration and recrystallized from ethanol or puri-
fied by medium-pressure chromatography on silica gel.
3.2.5. 3-Cyano-2-ethoxy-4-phenyl-7-(pyren-10-yl)-1,8-
naphthyridine (3e)
Recrystallized from ethanol; yield (98%); yellow crystals;
mp: 275e276 ꢁC. IR (KBr) 2936, 2854, 2224 (CN), 1584,
3.2.1. 3-Cyano-2-ethoxy-4,7-diphenyl-1,8-
naphthyridine (3a)
CH2Cl2ehexane, 1:1; yield (93%); white solid; mp: 204e
1481, 1409 cmꢀ1 1H NMR (CDCl3, 300 MHz) d: 1.59 (t,
.
206 ꢁC. IR (KBr) 2231 (CN), 1587, 1382 cmꢀ1 1H NMR
.
3H, J¼7.1 Hz, CH3), 4.89 (q, 2H, J¼7.1 Hz, OCH2), 7.49e
7.71 (m, 5H, ArH), 7.81 (d, 1H, J¼8.0 Hz, H-6), 8.03e8.46
(m, 9H, ArH), 8.47 (d, 1H, J¼8.0 Hz, H-5). 13C NMR
(CDCl3, 75 MHz) d: 14.5, 64.0, 98.8, 115.0, 118.2, 123.5,
124.8, 125.5, 127.5, 129.1, 129.2, 129.4, 129.8, 132.6,
136.6, 156.9, 158.1, 164.3. MS (FAB) m/z 476 [(MH)þ,
100], 446 (30), 391 (20). Anal. Calcd for C33H21N3O: C,
83.35; H, 4.45; N, 8.84. Found: C, 83.49; H, 4.36; N, 9.01.
(CDCl3, 300 MHz) d: 1.56 (t, 3H, J¼7.1 Hz, CH3), 4.82 (q,
2H, J¼7.1 Hz, 2OCH2), 7.48e7.63 (m, 8H, ArH), 7.80 (d, 1H,
J¼8.6 Hz, H-6), 8.01 (d, 1H, J¼8.6 Hz, H-5), 8.2e8.23 (m,
2H, ArH). 13C NMR (CDCl3, 75 MHz) d: 14.7, 64.4, 98.9,
114.8, 116.9, 118.8, 128.4, 128.8, 130.4, 130.8, 133.5, 137.4,
138.4, 156.2, 158.5, 163.0. MS (FAB) m/z 352 [(MH)þ, 14],
341 (8), 308 (8), 289 (15). Anal. Calcd for C23H17N3O: C,
78.61; H, 4.88; N, 11.96. Found: C, 78.43; H, 4.91; N, 12.06.
3.2.6. 3-Cyano-2-ethoxy-4-phenyl-7-(pyrid-20-yl)-1,8-
naphthyridine (3f)
Recrystallized from ethanol; yield (94%); yellow solid; mp:
244e246 ꢁC. IR (KBr) 2991, 2229 (CN), 1593, 1474,
1440 cmꢀ1 1H NMR (CDCl3, 300 MHz) d: 1.60 (t, 3H,
.
3.2.2. 3-Cyano-2-ethoxy-7-(naphth-20-yl)-4-phenyl-1,8-
naphthyridine (3b)
CH2Cl2ehexane, 3:7; yield (95%); orange solid; mp: 215e
217 ꢁC. IR (KBr) 2231 (CN), 1573, 1424 cmꢀ1
.
1H NMR
(CDCl3, 300 MHz) d: 1.55 (t, 3H, J¼7.1 Hz, CH3), 4.82 (q,
2H, J¼7.1 Hz, OCH2), 7.49e7.64 (m, 12H, ArH), 7.67 (d, 1H,
J¼8.4 Hz, H-6), 8.10 (d, 1H, J¼8.4 Hz, H-5). 13C NMR
(CDCl3, 75 MHz) d: 14.3, 64.2, 99.0, 114.4, 116.5, 122.9,
125.2, 126.0, 126.8, 128.3, 128.4, 128.5, 128.6, 129.0, 129.3,
129.8, 130.2, 130.8, 133.1, 136.3, 137.4, 155.8, 158.4, 162.6,
164.9. MS (FAB) m/z 402 [(MH)þ, 100], 391 (9), 375 (14),
372 (22), 219 (18). Anal. Calcd for C27H19N3O: C, 80.78; H,
4.77; N, 10.47. Found: C, 80.89; H, 4.66; N, 10.36.
J¼7.1 Hz, CH3), 4.83 (q, 2H, J¼7.1 Hz, OCH2), 7.38e7.65
(m, 6H, ArHþPy), 7.85e7.98 (m, 1H, Py), 8.09 (d, 1H,
J¼7.8 Hz, H-6), 8.53 (d, 1H, J¼7.8 Hz, H-5), 8.74e8.82 (m,
2H, Py). 13C NMR (CDCl3, 75 MHz) d: 14.3, 64.0, 98.9,
114.3, 117.6, 118.5, 122.7, 124.9, 128.9, 129.2, 130.0,
132.9, 136.8, 137.0, 148.7, 154.7, 155.9, 158.2, 161.0,
162.4. MS (FAB) m/z 353 [(MH)þ, 100], 325 (26), 289 (10).
Anal. Calcd for C22H16N4O: C, 74.98; H, 4.58; N, 15.90.
Found: C, 74.89; H, 4.76; N, 16.01.

A. Ferna´ndez-Mato et al. / Tetrahedron 64 (2008) 3446e3456
3453
3.2.7. 3-Cyano-2-ethoxy-4-phenyl-7-(pyrid-40-yl)-1,8-
naphthyridine (3g)
Recrystallized from ethanol; yield (93%); yellow crystals;
3.2.11. 3-Cyano-2-ethoxy-4-phenyl-7-(thien-20-yl)-1,8-
naphthyridine (3k)
CH2Cl2eEtOH, 9:1; yield (82%); yellow solid; mp: 218e
220 ꢁC. IR (KBr) 2982, 2232 (CN), 1583, 1525, 1374 cmꢀ1
.
mp: 227e228 ꢁC. IR (KBr) 2220 (CN), 1590, 1565 cmꢀ1
.
1H NMR (CDCl3, 300 MHz) d: 1.60 (t, 3H, J¼7.1 Hz, CH3),
4.83 (q, 2H, J¼7.1 Hz, OCH2), 7.47e7.52 (m, 2H, ArH),
7.63e7.66 (m, 3H, ArH), 7.84 (d, 1H, J¼7.8 Hz, H-6),
8.06e8.14 (m, 2H, Py), 8.53 (d, 1H, J¼7.8 Hz, H-5), 8.80e
8.83 (m, 2H, Py). 13C NMR (CDCl3, 75 MHz) d: 14.3, 64.4,
114.1, 117.7, 118.3, 121.9, 129.1, 129.3, 130.4, 132.9,
135.3, 139.9, 145.2, 150.6, 158.4, 160.0. MS (FAB) m/z 353
[(MH)þ, 100], 325 (53). Anal. Calcd for C22H16N4O: C,
74.98; H, 4.58; N, 15.90. Found: C, 74.95; H, 4.61; N, 15.94.
1H NMR (CDCl3, 300 MHz) d: 1.56 (t, 3H, J¼7.1 Hz, CH3),
4.85 (q, 2H, J¼7.1 Hz, OCH2), 7.16e7.21 (m, 1H, thienyl),
7.47e7.67 (m, 7H, ArHþthienylþH-6), 7.70e7.93 (m, 2H,
thienylþH-5). 13C NMR (CDCl3, 75 MHz) d: 14.4, 63.9, 98.0,
114.3, 116.5, 128.1, 128.4, 129.0, 129.3, 130.1, 131.2, 134.5,
137.8, 144.2, 156.3, 163.1. MS (FAB) m/z 358 [(MHþ), 100],
330 (27), 289 (47). Anal. Calcd for C21H15N3OS: C, 70.57; H,
4.23; N, 11.76. Found: C, 70.75; H, 4.11; N, 11.72.
3.2.12. 3-Cyano-2-ethoxy-4-phenyl-7-(thiazol-20-yl)-1,8-
naphthyridine (3l)
Recrystallized from ethanol; yield (88%); yellow crystals;
mp: 248e250 ꢁC. IR (KBr) 3106, 2972, 2222 (CN), 1574,
1425, 1327 cmꢀ1 1H NMR (CDCl3, 300 MHz) d: 1.59 (t,
.
3H, J¼7.1 Hz, CH3), 4.83 (q, 2H, J¼7.1 Hz, OCH2), 7.47e
7.66 (m, 6H, ArHþthiazolyl), 8.02e8.11 (2H, m,
thiazolylþH-6), 8.28 (d, 1H, J¼8.0 Hz, H-5). 13C NMR
(CDCl3, 75 MHz) d: 14.1, 64.2, 97.0, 111.2, 114.7, 115.8,
117.0, 122.9, 124.0, 129.2, 129.3, 130.6, 137.0, 144.0,
154.8, 157.9, 163.6. MS (EI) m/z 358 (Mþ, 90), 331 (30),
289 (55). Anal. Calcd for C20H14N4OS: C, 67.02; H, 3.94;
N, 15.63. Found: C, 67.15; H, 4.01; N, 15.74.
3.2.8. 3-Cyano-2-ethoxy-4-phenyl-7-(pyrazin-20-yl)-1,8-
naphthyridine (3h)
Recrystallized from ethanol; yield (83%); white crystals;
mp: 264e265 ꢁC. IR (KBr) 2986, 2225 (CN), 1591,
1474 cmꢀ1 1H NMR (CDCl3, 300 MHz) d: 1.58 (t, 3H,
.
J¼7.1 Hz, CH3), 4.80 (q, 2H, J¼7.1 Hz, OCH2), 7.52e7.74
(m, 5H, ArH), 7.85 (d, 1H, J¼7.8 Hz, H-6), 8.47 (d, 1H,
J¼7.8 Hz, H-5), 8.78e8.80 (m, 2H, Py), 9.8 (s, 1H, Py). 13C
NMR (CDCl3, 75 MHz) d: 14.3, 64.4, 114.0, 117.7, 118.3,
121.9, 129.1, 130.4, 132.9, 135.5, 139.9, 145.2, 150.6,
158.4, 161.2. MS (EI) m/z 354 (Mþ, 19), 326 (4), 289 (16),
219 (5). Anal. Calcd for C21H15N5O: C, 71.38; H, 4.28; N,
19.82. Found: C, 71.35; H, 4.41; N, 19.72.
3.3. 1,4-Di(1,8-naphthyridyn-20-yl)-aryl(heteroaryl)ligands
4e7, 9, 11, 12, 14 and 19aec. General procedure
3.2.9. 3-Cyano-2-ethoxy-4-phenyl-7-(pyrrol-20-yl)-1,8-
naphthyridine (3i)
A
solution of 1 (0.90 mmol), a suitable diketone
CH2Cl2ehexane, 1:1; yield (85%); yellow solid; mp: 180e
182 ꢁC. IR (KBr) 2982, 2232 (CN), 1583, 1525, 1374 cmꢀ1. 1H
NMR (CDCl3, 300 MHz) d: 1.54 (t, 3H, J¼7.1 Hz, CH3), 4.73
(q, 2H, J¼7.1 Hz, OCH2), 6.34e6.38 (m, 1H, pyrrolyl), 6.94e
6.99 (m, 1H, pyrrolyl), 7.04e7.07 (m, 1H, pyrrolyl), 7.43e7.61
(m, 6H, ArHþH-5), 7.72 (d, 1H, J¼8.7 Hz, H-6), 10.3 (br s, 1H,
NH). 13C NMR (CDCl3, 75 MHz) d: 14.3, 63.9, 97.0, 111.2,
114.7, 115.7, 117.0, 122.9, 128.9, 129.3, 130.7, 133.2, 154.8,
156.1, 157.8, 163.0. MS (EI) m/z 340 (Mþ, 100), 325 (12),
312 (67), 295 (7), 284 (16). Anal. Calcd for C21H16N4O: C,
74.10; H, 4.74; N, 16.46. Found: C, 74.15; H, 4.61; N, 16.51.
(0.45 mmol) and a catalytic amount of 10% ethanolic potas-
sium hydroxide in ethanol (10 mL) was refluxed until all start-
ing material had disappeared as checked by TLC (2e30 h).
After cooling, the precipitates were collected by filtration
and purified by medium-pressure chromatography on silica
gel using CH2Cl2 as eluent. For 12, 19a and 19b, the precip-
itate was filtered off and washed with EtOH. For 15, the solid
was purified by eluting with CH2Cl2eAcOEt 9:1.
3.3.1. 1,4-Di[(60-cyano-70-ethoxy-50-phenyl)-1,8-
naphthyridin-20-yl]benzene (4)
From 1,4-diacetylbenzene. Reaction time 10 h; yield (88%);
white solid; mp: >300 ꢁC. IR (KBr) 2996, 2237 (CN), 1618,
3.2.10. 3-Cyano-2-ethoxy-7-(fur-20-yl)-4-phenyl-4-1,8-
naphthyridine (3j)
1
1513, 1493, 1431, 1396 cmꢀ1. H NMR (CDCl3, 300 MHz) d:
Recrystallized from ethanol; yield (80%); yellow crystals;
mp: 233e235 ꢁC. IR (KBr) 3140, 2229 (CN), 1581,
1.58 (t, 6H, J¼7.1 Hz, 2CH3), 4.68 (q, 4H, J¼7.1 Hz, 2OCH2),
7.48e7.65 (m, 10H, 2C6H5), 7.89 (d, 2H, J¼7.8 Hz, H-3), 8.01
(d, 2H, J¼7.8 Hz, H-4), 8.40 (s, 4H, C6H4). 13C NMR (CDCl3,
75 MHz) d: 14.1, 63.8, 99.0, 115.0, 118.0, 125.5, 128.4, 129.1,
133.3, 136.6, 156.0, 158.2, 161.9, 163.1. MS (FAB) m/z 625
[(MH)þ, 20], 460 (14), 289 (50). Anal. Calcd for C40H28N6O2:
C, 76.91; H, 4.52; N, 13.45. Found: C, 76.89; H, 4.63; N, 13.24.
1492 cmꢀ1 1H NMR (CDCl3, 300 MHz) d: 1.55 (t, 3H,
.
J¼7.1 Hz, CH3), 4.81 (q, 2H, J¼7.1 Hz, OCH2), 6.63 (1H,
dd, J¼3.5, 1.7 Hz, furyl), 7.45e7.65 (m, 7H, ArHþfuryl),
7.76 (d, 1H, J¼8.6 Hz, H-6), 7.96 (d, 1H, J¼8.6 Hz, H-5).
13C NMR (CDCl3, 75 MHz) d: 14.3, 64.1, 97.3, 112.8,
113.2, 116.7, 129.0, 129.3, 130.1, 137.0, 145.2, 152.7,
153.7, 155.9, 157.6, 160.7, 162.8, 163.3, 167.5. MS (FAB)
m/z 342 [(MHþ), 100], 341 (21), 314 (15), 289 (20). Anal.
Calcd for C21H15N3O2: C, 73.89; H, 4.43; N, 12.31. Found:
C, 73.75; H, 4.41; N, 12.52.
3.3.2. 4,40-Di[(60-cyano-70-ethoxy-50-phenyl)-1,8-
naphthyridin-20-yl]biphenyl (5)
From 4,40-diacetylbiphenyl. Reaction time 2 h; yield
(77%); white solid; mp: >300 ꢁC. IR (KBr) 2980, 2229

3454
A. Ferna´ndez-Mato et al. / Tetrahedron 64 (2008) 3446e3456
1
(CN), 1610, 1583, 1478, 1431, 1381 cmꢀ1. H NMR (CDCl3,
300 MHz) d: 1.56 (t, 6H, J¼7.1 Hz, 2CH3), 4.65 (q, 4H,
J¼7.1 Hz, 2OCH2), 7.44e7.67 (m, 10H, 2C6H5), 7.85e7.92
(m, 8H, biphenyl), 8.04 (d, 2H, J¼7.8 Hz, H-3), 8.38 (d, 2H,
J¼7.8 Hz, H-4). 13C NMR (CDCl3, 75 MHz) d: 14.1, 63.8,
99.0, 114.0, 117.0, 118.0, 125.5, 128.4, 129.1, 133.3, 136.6,
139.9, 142.1, 156.1, 158.4, 161.9, 163.1. MS (FAB) m/z 701
[(MH)þ, 14], 663 (98), 647 (70), 607 (13), 289 (64). Anal.
Calcd for C46H32N6O2: C, 78.84; H, 4.60; N, 11.99. Found:
C, 78.94; H, 4.71; N, 11.87.
3.3.6. 2,5-Di[(60-cyano-70-ethoxy-50-phenyl)-1,8-
naphthyridin-20-yl]pyrazine (11)
From 2,5-diacetylpyrazine. Reaction time 20 h; yield
(78%); white solid; mp: >300 ꢁC. IR (KBr) 2962, 2225
1
(CN), 1584, 1568, 1328 cmꢀ1. H NMR (CDCl3, 300 MHz)
d: 1.60 (t, 6H, J¼7.1 Hz, 2CH3), 4.85 (q, 4H, J¼7.1 Hz,
2OCH2), 7.50e7.66 (m, 10H, 2C6H5), 8.16 (d, 2H,
J¼8.6 Hz, H-3), 8.58 (d, 2H, J¼8.6 Hz, H-4), 10.2 (s, 2H, pyr-
azine). 13C NMR (CDCl3, 75 MHz) d: 14.1, 64.1, 99.7, 114.0,
118.2, 119.0, 128.9, 129.1, 130.2, 132.7, 137.5, 143.3, 149.9,
155.3, 158.3, 158.9, 162.2. MS (EI) m/z 627 [(MH)þ, 10],
613 (15), 607 (15), 460 (50). Anal. Calcd for C38H26N8O2:
C, 72.83; H, 4.18; N, 17.88. Found: C, 72.96; H, 4.21; N,
17.78.
3.3.3. 1,6-Di[(60-cyano-70-ethoxy-50-phenyl)-1,8-
naphthyridin-20-yl]pyrene (6)
From 1,4-diacetylpyrene. Reaction time 10 h; yield (60%);
yellow solid; mp: >300 ꢁC. IR (KBr) 2226 (CN), 1583, 1329,
1294 cmꢀ1 1H NMR (CDCl3, 300 MHz) d: 1.57 (t, 6H,
.
3.3.7. 6,60-Dicyano-7,70-diethoxy-3,30-dimethylene-5,50-
diphenyl-2,20-bi-1,8-naphthyridine (12)
J¼7.1 Hz, 2CH3), 4.85 (q, 4H, J¼7.1 Hz, 2OCH2), 7.56e
7.68 (m, 10H, 2C6H5), 7.84 (d, 2H, J¼8.4 Hz, H-3), 8.16 (d,
2H, J¼9.3 Hz, pyrene), 8.17 (d, 2H, J¼8.4 Hz, H-4), 8.32
(d, 2H, J¼8 Hz, pyrene), 8.36 (d, 2H, J¼8 Hz, pyrene), 8.50
(d, 2H, J¼9.3 Hz, pyrene). 13C NMR (CDCl3, 75 MHz) d:
14.4, 64.3, 99.1, 114.4, 116.5, 123.6, 125.0, 125.2, 125.5,
128.3, 128.5, 129.0, 129.1, 129.3, 130.2, 131.7, 133.2, 135.2,
136.5, 155.9, 158.5, 162.8, 165.1. MS (EI) m/z 749 [(MH)þ,
40], 391 (30), 289 (55). Anal. Calcd for C50H34N6O2:
C, 79.98; H, 4.56; N, 11.99. Found: C, 80.05; H, 4.51; N,
11.84.
From 1,2-cyclohexanedione. Reaction time 2 h; yield
(76%); yellow solid; mp: >300 ꢁC. IR (KBr) 3323, 2227
(CN), 1586, 1476, 1412, 1331 cmꢀ1 1H NMR (CDCl3,
.
300 MHz) d: 1.56 (t, 6H, J¼7.1 Hz, 2CH3), 3.08 (s, 4H,
2CH2), 4.83 (q, 4H, J¼7.1 Hz, 2OCH2), 7.47e7.64 (m, 10H,
2C6H5), 7.85 (s, 2H, H-4). 13C NMR (CDCl3, 75 MHz) d:
14.3, 14.4, 27.1, 31.8, 64.1, 64.4, 99.2, 99.5, 114.2, 114.3,
117.1, 129.1, 130.2, 155.0, 162.4, 165.8. MS (FAB) m/z 575
[(MH)þ, 33], 413 (26), 391 (83), 363 (60). Anal. Calcd for
C36H26N6O2: C, 75.25; H, 4.56; N, 14.62. Found: C, 75.37;
H, 4.57; N, 14.48.
3.3.4. 1,8-Di[(60-cyano-70-ethoxy-50-phenyl)-1,8-
3.3.8. 3,11-Dicyano-2,10-diethoxy-4,12-diphenyl-6,7-
dihydrobenzo[1,2-b:3,4-b0]1,8-binaphthyridine (14)
From 1,3-cyclohexanedione. Reaction time 3 h; yield
(65%); white solid; mp: 239e241 ꢁC. IR (KBr), 2229 (CN),
naphthyridin-20-yl]pyrene (7)
From 1,6-diacetylpyrene. Reaction time 3 h; yield (66%);
yellow solid; mp: >260 ꢁC (dec). IR (KBr) 2227 (CN), 1582,
1479, 1327 cmꢀ1. 1H NMR (CDCl3, 300 MHz) d: 1.56 (t, 6H,
J¼7.1 Hz, 2CH3), 4.82 (q, 4H, J¼7.1 Hz, 2OCH2), 7.54e
7.66 (m, 10H, 2C6H5), 7.82 (d, 2H, J¼8.4 Hz, H-3), 8.13 (d,
2H, J¼8.4 Hz, H-4), 8.20 (s, 2H, pyrene), 8.35 (d, 2H,
J¼7.9 Hz, pyrene), 8.39 (d, 2H, J¼7.9 Hz, pyrene), 8.48 (s,
2H, pyrene). 13C NMR (CDCl3, 75 MHz) d: 14.3, 64.5, 98.7,
114.3, 116.4, 123.7, 125.0, 125.2, 125.6, 128.1, 128.5, 129.0,
129.1, 130.3, 133.2, 134.2, 136.4, 156.0, 158.5, 162.8, 165.0.
MS (EI) m/z 749 [(MH)þ, 25], 748 (9), 391 (20). Anal. Calcd
for C50H34N6O2: C, 79.98; H, 4.56; N, 11.99. Found: C,
79.83; H, 4.74; N, 11.88.
1
1569, 1476, 1413, 1329 cmꢀ1. H NMR (CDCl3, 300 MHz)
d: 1.53 (t, 3H, J¼7.1 Hz, CH3), 1.55 (t, 3H, J¼7.1 Hz, CH3),
3.14 (t, 2H, J¼6.9 Hz, CH2), 3.43 (t, 2H, J¼6.9 Hz, CH2),
4.69 (q, 2H, J¼7.1 Hz, CH2), 4.78 (q, 2H, J¼7.1 Hz,
CH2), 7.43e7.68 (m, 10H, 2C6H5), 7.78 (s, 1H, H-4), 9.11
(s, 1H, H-13). 13C NMR (CDCl3, 75 MHz) d: 14.3, 14.4,
27.1, 31.8, 64.1, 64.4, 99.2, 99.5, 114.2, 114.3, 117.1, 117.5,
127.1, 129.1, 129.2, 129.6, 129.7, 130.2, 130.5, 132.9,
135.1, 155.0, 155.8, 156.2, 157.8, 159.5, 162.4, 163.1,
165.8. MS (FAB) m/z 575 [(MH)þ, 43], 391 (19), 307 (36),
289 (19). Anal. Calcd for C36H26N6O2: C, 75.25; H, 4.56;
N, 14.62. Found: C, 75.38; H, 4.67; N, 14.78.
3.3.5. 6,60-Dicyano-7,70-diethoxy-5,50-diphenyl-2,20-bi-1,8-
naphthyridine (9)
From 1,3-butanedione. Reaction time 20 h; yield (66%);
white solid; mp: >300 ꢁC. IR (KBr) 2928, 2225 (CN), 1584,
1478, 1323 cmꢀ1 1H NMR (CDCl3, 300 MHz) d: 1.57 (t,
.
6H, J¼7.1 Hz, 2CH3), 4.59 (q, 4H, J¼7.1 Hz, 2OCH2),
7.45e7.66 (m, 10H, 2C6H5), 8.15 (d, 2H, J¼8.6 Hz, H-3),
8.86 (d, 2H, J¼8.6 Hz, H-4). 13C NMR (CDCl3, 75 MHz) d:
13.5, 63.0, 98.7, 115.0, 120.0, 129.3, 130.6, 136.2, 155.0,
159.6. MS (EI) m/z 549 [(MH)þ, 24], 460 (37), 391 (100).
Anal. Calcd for C34H24N6O2: C, 74.44; H, 4.41; N, 15.32.
Found: C, 74.40; H, 4.44; N, 15.38.
3.3.9. 1,3-Di[(60-cyano-70-ethoxy-50-phenyl)-1,8-
naphthyridin-20-yl]benzene (19a)
From 1,3-diacetylbenzene. Reaction time 1 h; yield (92%);
white solid; mp: >300 ꢁC. IR (KBr) 2922, 2224 (CN), 1667,
1586, 1375 cmꢀ1 1H NMR (CDCl3, 300 MHz) d: 1.57 (t,
.
6H, J¼7.1 Hz, 2CH3), 4.83 (q, 4H, J¼7.1 Hz, 2OCH2),
7.51e7.71 (m, 10H, 2C6H5), 7.74 (1H, t, J¼7.8 Hz, H-5),
7.97 (d, 2H, J¼7.9 Hz, H-4, H-6), 8.08 (d, 2H, J¼7.9 Hz,
H-30), 8.38 (d, 2H, J¼7.9 Hz, H-40), 9.01 (s, 1H, H-2). 13C
NMR (CDCl3, 75 MHz) d: 14.3, 64.2, 98.9, 114.4, 116.8,
118.7, 127.8, 129.0, 129.3, 129.5, 130.2, 133.1, 137.3,

A. Ferna´ndez-Mato et al. / Tetrahedron 64 (2008) 3446e3456
3455
138.8, 155.9, 158.3, 162.1, 162.8. MS (EI) m/z 624 (Mþ, 10),
623 (11), 424 (20), 262. Anal. Calcd for C40H28N6O2: C,
76.91; H, 4.52; N, 13.45. Found: C, 76.98; H, 4.41; N, 13.58.
formed was filtered off and recrystallized from ethanol/acetone
to give white crystals (0.28 g, 84%). Mp: 281e282 ꢁC. IR
1
(KBr) 2232 (CN), 1696 (CO), 1584, 1420, 1332 cmꢀ1. H
NMR (CDCl3, 300 MHz) d: 1.55 (t, 6H, J¼7.1 Hz, CH3),
2.22e2.30 (m, 2H, H-8), 2.75 (t, 2H, J¼6.5 Hz, H-9), 3.37 (t,
2H, J¼6.5 Hz, H-7), 4.81 (q, 4H, J¼7.1 Hz, OCH2), 7.45e
7.64 (m, 5H, C6H5), 8.60 (s, 1H, H-5). 13C NMR (CDCl3,
75 MHz) d: 14.3, 21.3, 33.1, 38.6, 64.7, 79.3, 99.8, 113.8,
116.7, 126.1, 129.2, 130.7, 132.4, 137.5, 157.0, 160.2, 163.8,
168.7, 196.4. MS (EI) m/z 343 (Mþ, 39), 342 (100), 316 (18),
315 (79), 287 (47). Anal. Calcd for C21H17N3O2: C, 75.45; H,
4.99; N, 12.24. Found: C, 75.47; H, 5.10; N, 12.14.
3.3.10. 2,6-Di[(60-cyano-70-ethoxy-50-phenyl)-1,8-
naphthyridin-20-yl]pyridine (19b)
From 2,6-diacetylpyridine. Reaction time 20 h; yield
(77%); white solid; mp: >300 ꢁC. IR (KBr) 2979, 2224
(CN), 1584, 1569, 1485, 1383 cmꢀ1 1H NMR (CDCl3,
.
300 MHz) d: 1.59 (t, 6H, J¼7.1 Hz, 2CH3), 4.85 (q, 4H,
J¼7.1 Hz, 2OCH2), 7.49e7.65 (m, 10H, 2C6H5), 8.15 (m,
3H), 8.69 (d, 2H, J¼7.8 Hz, H-30), 8.93 (d, 2H, J¼7.8 Hz,
H-40). 13C NMR (CDCl3, 75 MHz) d: 14.3, 63.6, 99.0,
114.0, 116.3, 118.0, 125.0, 128.4, 129.1, 130.6, 133.3,
136.6, 139.9, 154.2, 158.1, 163.4. MS (FAB) m/z 626
[(MH)þ, 100], 670 (23), 460 (14), 391 (52), 345 (8). Anal.
Calcd for C39H27N7O2: C, 74.87; H, 4.32; N, 15.67. Found:
C, 74.69; H, 4.50; N, 15.62.
3.6. 3,11-Dicyano-2,10-diethoxy-4,12-diphenylbenzo-
[1,2-b:3,4-b0]1,8-binaphthyridine (15)
A solution of 14 (57 mg, 0.1 mmol) and DDQ (30 mg,
0.12 mmol) in THF (5 mL) was refluxed for 2 h. Alter cooling,
the solid formed was filtered off and purified by flash chroma-
tography on silica gel with CH2Cl2eAcOEt 9:1 to give a white
solid (34 mg, 60%). Mp: >300 ꢁC. IR (KBr) 2986, 2227 (CN),
1649, 1580, 1487, 1332 cmꢀ1. 1H NMR (CDCl3, 300 MHz) d:
1.54e1.58 (m, 6H, 2CH3), 4.64 (q, 2H, J¼7.0 Hz, OCH2),
4.72 (q, 2H, J¼7.0 Hz, OCH2), 7.45e7.63 (m, 10H, 2C6H5),
8.01 (d, 1H, J¼8.6 Hz, H-6), 8.30 (d, 1H, J¼8.6 Hz, H-7),
8.60 (s, 1H, H-5), 9.20 (s, 1H, H-13). 13C NMR (CDCl3,
75 MHz) d: 14.2, 14.4, 27.1, 64.1, 64.9, 94.0, 99.5, 107.8,
114.1, 114.3, 117.4, 121.9, 129.0, 129.1, 129.4, 130.2,
132.5, 133.0, 136.5, 139.6, 139.8, 150.6, 157.9, 158.2,
161.2. Anal. Calcd for C36H24N6O2: C, 75.51; H, 4.22; N,
14.68. Found: C, 75.62; H, 4.17; N, 14.53.
3.3.11. 2,6-Di[(60-cyano-70-ethoxy-50-phenyl)-1,8-
naphthyridin-20-yl]-4-tert-butyl-pyridine (19c)
From 4-tert-butyl-2,6-diacetylpyridine. Reaction time 30 h;
yield (93%); mp: >300 ꢁC. IR (KBr) 2980, 2226 (CN), 1585,
1
1571, 1330 cmꢀ1. H NMR (CDCl3, 300 MHz) d: 1.57 (s, 9H,
3CH3), 1.60 (t, 6H, J¼7.1 Hz, 2CH3), 4.82 (q, 4H, J¼7.1 Hz,
2OCH2), 7.51e7.64 (m, 10H, 2C6H5), 8.11 (d, 2H, J¼8.6 Hz,
H-30), 8.67 (d, 2H, J¼8.6 Hz, H-40), 8.87 (s, 2H). 13C NMR
(CDCl3, 75 MHz) d: 14.2, 64.0, 98.9, 114.2, 117.6, 118.9, 121.2,
128.8, 129.2, 130.1, 132.9, 136.9, 139.9, 154.1, 154.4, 155.4,
163.8. MS (FAB) m/z 682 [(MH)þ, 100], 670 (23), 681 (12),
626 (7), 429 (8), 345 (12), 460. Anal. Calcd for C44H39N7O2: C,
75.73; H, 5.63; N, 14.05. Found: C, 75.88; H, 5.47; N, 14.21.
4. Crystallographic material
3.4. 7-Acetyl-3-cyano-2-ethoxy-4-phenyl-1,8-
naphthyridine (8)
Crystallographic data (excluding structural factors) for 14
have been deposited in the Cambridge Crystallographic Data
Center as supplementary publication number CCDC 674102.
Copies of the data may be obtained, free of charge, on appli-
cation to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK
(fax: þ44 1223 33603 or e-mail: deposit@ccdc.cam.ac.uk).
A catalytic amount of 10% ethanolic potassium hydroxide
was added to a solution of 1 (0.27 g, 1 mmol) and 1,3-butane-
dione (103 mg, 1,2 mmol) in ethanol (10 mL) and the mixture
was heated under reflux for 8 h until all starting material had
disappeared as checked by TLC (2e30 h). After cooling, the
precipitate was collected by filtration and washed with EtOH
to give 160 mg (50%) of white solid. Mp: >300 ꢁC (dec).
Acknowledgements
IR (KBr) 2225 (CN), 1780 (CO), 1585, 1570, 1335 cmꢀ1
.
We thank to FEDER, MCyT (CTQ2006-04728) and the
Xunta de Galicia, Spain (Grants PGI-DIT04PXIC10307PN
and PGIDIT06PXIB103224PR) for financial support. A.F.-M.
acknowledges a predoctoral fellowship from the University of
1H NMR (CDCl3, 300 MHz) d: 1.48 (t, 3H, J¼7.1 Hz, CH3),
3.49 (s, 3H, CH3), 4.78 (q, 4H, J¼7.1 Hz, 2OCH2), 7.47e
7.78 (m, 5H, C6H5), 8.17 (d, 2H, J¼8.6 Hz, H-6), 8.84 (d,
2H, J¼8.6 Hz, H-5). Anal. Calcd for C19H15N3O2: C, 71.91;
H, 4.76; N, 13.24. Found: C, 71.80; H, 4.74; N, 13.35.
~
A Coruna.
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