New pyrrolopyridazine derivatives as blue organic luminophors

Article abstract of DOI:10.1016/j.tet.2005.08.038

New pyrrolopyridazine derivatives were synthesized as potential blue organic luminophors. Three different classes of pyrrolopyridazine derivatives were made, for example, aryl groups directly connected to the core PPY (pyrrolo[1,2-b]pyridazine-5,6,7-tricarboxylic acid trimethyl ester) moiety, aryl groups connected to the PPY via a vinylene linker and aryl groups connected to the PPY via an acetylene linker. Their optical and electrochemical properties were productively compared. One of the derivatives 2 showed a relative quantum yield as high as 0.9. Compound 8 in the vinyl bridged pyrrolopyridazine series has been characterized by its X-ray crystal structure analysis.

Full text of DOI:10.1016/j.tet.2005.08.038

Tetrahedron 61 (2005) 10227–10234
New pyrrolopyridazine derivatives as blue organic luminophors
K. M. K. Swamy,a Min Sun Park,a Su Jung Han,b Sook Kyung Kim,a Ju Hee Kim,a
Chongmok Lee,b Hyunjin Bang,a Youngmee Kim,b Sung-Jin Kima,b and Juyoung Yoona,b,
*
aDivision of Nano Sciences, Ewha Womans University, 11-1 Daehyon-Dong, Sodaemun-Ku, Seoul 120-750, Korea
bDepartment of Chemistry, Ewha Womans University, 11-1 Daehyon-Dong, Sodaemun-Ku, Seoul 120-750, Korea
Received 14 May 2005; revised 10 August 2005; accepted 11 August 2005
Available online 2 September 2005
Abstract—New pyrrolopyridazine derivatives were synthesized as potential blue organic luminophors. Three different classes of
pyrrolopyridazine derivatives were made, for example, aryl groups directly connected to the core PPY (pyrrolo[1,2-b]pyridazine-5,6,7-
tricarboxylic acid trimethyl ester) moiety, aryl groups connected to the PPY via a vinylene linker and aryl groups connected to the PPY via an
acetylene linker. Their optical and electrochemical properties were productively compared. One of the derivatives 2 showed a relative
quantum yield as high as 0.9. Compound 8 in the vinyl bridged pyrrolopyridazine series has been characterized by its X-ray crystal structure
analysis.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
compounds. To study the relationship between optical
properties and the effect of conjugation and substitution, we
systematically designed and synthesized a series of
luminophors containing a core pyrrolo[1,2-b]pyridazine-
5,6,7-tricarboxylic acid trimethyl ester moiety. Three
different classes of pyrrolopyridazine derivatives were
synthesized, for example, aryl groups directly connected
to the core PPY (pyrrolo[1,2-b]pyridazine-5,6,7-tri-
carboxylic acid trimethyl ester) moiety, aryl groups
connected to the PPY via a vinylene linker and aryl groups
connected to the PPY via an acetylene linker. Their
comparative optical and electrochemical properties were
investigated to study the effect of extended conjugation.
Compound 8 in the vinyl bridged pyrrolopyridazine series
has been characterized by its X-ray crystal structure
analysis.
Since the discovery of a thin-film organic electrolumines-
cent device by the team at Kodak,1a organic light emitting
diodes (OLED) have become the most promising new
optoelectronic devices for practical industrial applications.
Electroluminescent thin films of organic molecules have
been extensively investigated because of their low operating
voltage, tunable red-green-blue output colors, high bright-
ness, mechanical flexibility and ease of fabrication.1b
Although polymeric as well as small organic molecules
are well established electroluminescent materials used in
fabricating the thin film devices, smaller organic units were
realized to be advantageous with facile emission color
control and the easy fabrication of multilayer devices.2
Investigations on synthesizing new blue luminous materials
for applications in electroluminescent (EL) display have
attracted great attention recently, but there are very few
single component deep blue- and pure red-emitting dyes.2
2. Results and discussion
2.1. Synthesis
Recently, Wudl et al. reported pyrrolopyridazine derivatives
as a new class of blue organic luminophors. They
demonstrated the possibility of tuning colors and energy
levels by modifying the structures of these luminophors.3
Herein, we report the synthesis of new pyrrolopyridazine
derivatives, along with the optical properties of these new
For the synthesis of various pyrrolopyridazine derivatives,
3-iodopyridazine (26) was synthesized from 3,6-dichloro-
pyridazine in four steps following the procedures reported
elsewhere. The treatment of 3,6-dichloropyridazine with
sodium iodide gave 3,6-diiodopyridazine, which was then
reacted with hydrazine to give 6-iodo-3-pyridazinyl-
hydrazine. This hydrazine was reacted with mercuric
oxide to give 3-iodopyridazine.4,5
Keywords: Pyrrolopyridazine; Fluorescence; Luminophor; Blue lumino-
phor; Sonogashira coupling; Blue shift; Red shift.
Corresponding author. Tel.: C82 2 3277 2400; fax: C82 2 3277 2384;
e-mail: jyoon@ewha.ac.kr
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.08.038

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K. M. K. Swamy et al. / Tetrahedron 61 (2005) 10227–10234
The 3-arylpyridazine derivatives (14–16) were synthesized
as shown in Scheme 1 by modifying the literature
procedures.6 Synthesis of aryl pyridazines via Suzuki
cross-coupling is a single step and more convenient than
the reported method for the preparation of compound (15).7
On the other hand, 3-(2-arylvinyl)pyridazine derivatives
were also obtained in one step by the treatment of aromatic
aldehydes with 3-methylpyridazine using the reported
methodology (Scheme 2).8a
Scheme 3. 3-Arylethynylpyridazines (24–25) from Sonogashira reaction.
ethynylaryl) and dimethyl acetylenedicarboxylate (DMAD)
in methanol at a low temperature as depicted in Scheme 4,
by modifying the reported procedure.3b
Scheme 1. Synthesis of 3-arylpyridazines (14–16) via Suzuki cross-
coupling.
Scheme 4. Synthesis of luminophors (1–13).
2.2. X-ray crystal structure
A single crystal of compound 8 was grown from a CH2Cl2/
MeOH solution and was characterized using X-ray
Scheme 2. Synthesis of 3-(2-aryl-vinyl)pyridazines (17–23).
Figure 1. Luminophors synthesized (1–13).
The structural data of the compounds 18 and 19 were in a
good agreement with the earlier reports.8b,c Sonogashira
coupling9 between 3-iodopyridazine and terminal alkynes in
the presence of (PPh3)2PdCl2 and CuI in basic condition
yielded 3-arylethynylpyridazines (Scheme 3).
The luminescent pyrrolopyridazine derivatives (1–13) were
prepared (Fig. 1) in one step via 1,3-dipolar cycloaddition
reaction between 3-substituted pyridazines (aryl/vinylaryl/
Figure 2. X-ray structure of 8 (in (b) and (c), blue: N and red: O).

K. M. K. Swamy et al. / Tetrahedron 61 (2005) 10227–10234
10229
crystallography. Figure 2 shows the p stacking of
compound 8 in a head to tail mode. The molecules stack
along the b axis and the average distance between the p
planes was 3.66 A (Fig. 2b). Hydrogen bonds between the
oxygens and methyl group in the ester moieties were
observed and the distances between these oxygens and
these compounds resulted from the stronger electronic
perturbation in the ground and excited states due to the
extended conjugation provided by the vinylene linkage. On
the other hand, the compounds 12 (44%) and 13 (52%)
bearing acetylene linkage displayed better fluorescent
quantum yield compared to those of compounds bearing
vinylene linkage. The introduction of a fluorine atom on the
aryl ring increased the fluorescent quantum yields in both
cases (compound 2 vs 1 or 3; compound 7 vs 5 or 6;
compound 13 vs 12) (Table 1). Compounds with vinylene
and acetylene spacers induced red shifts in their fluor-
escence lmax by 5 and 18 nm, respectively. It is likely that
extended conjugation enhances the intersystem crossing
(ISC) rates thereby resulting in quenched emission for
compounds 3–13. The theory also gains significance in view
that compounds 2, 7 and 13 have relative higher quantum
yield values when compared with the others in the
corresponding series.
˚
˚
carbons are in the range of 3.40–4.49 A (Fig. 2c).
2.3. Optical properties
The absorption and fluorescence spectra of compounds 2–13
were recorded in DMSO, methanol, methylene chloride, and
hexane solutions at room temperature. The relative quantum
yields were determined using 9,10-diphenylanthracene in
degassed hexane (FZ0.96). The optical data for compound
1 was taken from the literature.3
As expected and illustrated in the cyclic voltametry data,
significant red shifts were observed in UV as well as
fluorescence for the compounds 6 and 7 being extended
conjugation. Figure 3 exhibits that the second absorption
bands of 7 (315 nm) and 6 (331 nm) are red-shifted
compared with those of 2 (280 nm) and 3 (300 nm). These
red shifts of compounds 6 and 7 were probably due to
ground state stabilization arising from extended conjugation
via vinylene linkage. The first absorption bands were
assigned at around 350 nm for compound 1, 2 and 3.
However, for compounds 5, 6 and 7, the absorption
maximum around 320–340 nm was used as the excitation
wavelength since the first absorption bands were overlapped
with the second absorption bands. On the other hand, the
compounds 12 and 13 bearing acetylene linkage displayed
red shifts in their UV as well as fluorescence spectra (Figs 3
& 4) compared to those of 1 and 2.
2.4. Electrochemical studies
Table 2 summarizes the cyclic voltametric data in CH3CN
containing 0.1 M tetrabutylammonium hexafluoro-
phosphate with the scan rate of 0.1 V/s. The potential
values of the first redox wave in the scan of both the positive
and negative direction are included in Table 2 along with
some multiple redox waves, which are known to be related
to the HOMO and LUMO energy levels. Overall, as the
interpretation of the electrochemical properties is similar to
that reported by Wudl et al.3a their assignments can be
applied to these compounds.
Compounds 1–3 show the oxidation potential at 1.89, 1.90,
and 1.76 V, respectively, and the reduction potential at
K1.59, K1.58, and K1.63 V, respectively, which indicates
that the substituent group on the 2-phenyl group connected
to PPY (pyrrolo[1,2-b]pyridazine-5,6,7-tricarboxylic acid
trimethyl ester) affects the HOMO level slightly and the
LUMO level trivially. Compounds 5–7 also showed a
similar tendency. Compounds 1 and 4 exhibited almost the
same oxidation and reduction potential, which implies that
both the HOMO and LUMO level are not changed when the
2-phenyl or 2-naphthyl moiety are connected to PPY.
A relative large difference in the oxidation potential was
found by a comparison of the (2, 7), (3, 6), and (4, 8)
couples, respectively. In compounds 2, 3, and 4, the
aromatic moieties were linked directly to position 2 of
PPY while the same aromatic moieties were linked to
position 2 of PPY via a vinylene linkage in compounds 7, 6,
and 8, respectively. Interestingly, compounds 7, 6, and 8 had
lower oxidation potential than the corresponding com-
pounds 2, 3, and 4 by 0.45, 0.37, and 0.24 V, respectively,
while their reduction potentials remained similar within
0.08 V compared with their corresponding compounds. This
indicates that such elongated conjugation at the position 2 in
PPY mainly affects the HOMO as shown in compounds 1–3
and 5–7 (Table 2). It is likely that a vinylene linkage at
position 2 affects the HOMO level but affects the LUMO
level to a much lesser extent, however, no further effort to
explain this phenomenon is made in this study. Figure 5
shows the cyclic voltammograms of compounds 6 and 3,
where an improvement in the reversibility in the reduction
Figure 3. The UV absorption spectra of compounds 2, 3, 6 and 7 in
dichloromethane.
Compound 2 displayed a relatively higher quantum yield
values when compared to the compounds bearing extended
conjugation moiety. As shown in Table 1, there was a
dramatic difference in quantum yield between compounds 2
(90%) and 7 (27%). The compounds bearing aryl groups via
a vinylene linkage (5–11) show relatively low fluorescent
quantum yields. It is likely that the significant differences in

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K. M. K. Swamy et al. / Tetrahedron 61 (2005) 10227–10234
Table 1. lmax (nm) of absorption spectra, lmax (nm) of fluorescence spectra, and relative efficiency (%) of compound 1–13
Compd
Absorption (lmax/nm)
Fluorescence [(lmax/nm) (quantum efficiency (%))]
DMSO
MeOH
CH2Cl2
Hexane
DMSO
MeOH
CH2Cl2
Hexane
1
2
3
4
5
6
7
8
348a
352
348
348
321
331
315
329
343
337
394
356
359
346a
347
348
348
316
335
312
323
341
335
350a
348
349
340
330
328
313
328
335
332
373
358
358
351a
446 (81)a
449 (90)
445 (51)
450 (39)
450 (9)
463 (5)
454 (27)
460 (9)
453 (8)
441 (6)
510 (5)
467 (44)
467 (52)
443 (73)a
444 (85)
439 (43)
445 (22)
452 (8)
444 (68)a
443 (79)
441 (41)
444 (31)
447 (7)
438 (9)
448 (23)
448 (8)
450 (12)
453 (8)
505 (13)
456 (41)
453 (50)
442 (75)a
b
b
b
b
b
b
305
b
443 (27)
b
466 (8)
b
b
b
b
b
b
b
b
451 (25)
451 (12)
453 (11)
455 (10)
9
10
11
12
13
389
b
389
b
490 (8)
b
472 (28)
b
b
b
b
b
a Taken from Ref. 3a.
b Insoluble.
Table 2. Cyclic voltammetric data for 1–8, 11, and anthracenea
Compd
1
2
3
4
5
6
7
8
11
Anthracene
1.28/.c
b
Eox
Ered
1.89/.c
K1.59/
K1.67
1.90/.c
K1.58/
K1.66
1.76/.c
K1.63/
K1.71
1.90/.c
K1.57/
K1.64
1.69/.c
K1.54/
K1.61
1.39/.c
K1.55/
K1.63
1.46/.c
K1.54/
K1.61
1.66/.c
1.29/.c
K1.48/.d K1.45/.d K1.92/
K1.99
b
a CVs were recorded at room temperature in CH3CN/0.1 M TBAPF6.
b Eox and Ered are represented as Epa/Epc (V vs SCE), respectively.
c It is hard to measure the value because of lack of reversibility.
d It is hard to determine the exact value due to multiple redox waves.
0/K1 couple at EZK1.59 V of compound 6 compared with
that of 3 are easily observed at a scan rate (n) of 0.1 V/s
(Fig. 5a and b). A 5-fold increase in the scan rate leads to an
enhancement in the reversibility in the reduction process of
compound 3 (Fig. 5c). Judging from the ipc/ipa ratio
depending on n, the half-life of the anion radical of
compound 3 was approximately 1 s.10 Such kinetic
stabilization phenomena of the radical anion of compound
7 and 8 in the CVs depending on n were also observed by
comparing them with compounds 2 and 4, respectively. The
estimated half-life of the anion radical of compounds 2 and
4 was O1 s and a few seconds, respectively. The above
redox potential measurement data were parallel with the
optical measurement data, that is, the UV lmax of
compounds 7 and 6 is longer than that of compounds 2
and 3 by 35 and 31 nm, respectively.
Compound 11 had the lowest oxidation potential among
compounds 5, 8, and 11. The origin of this could be
understood partially by observing the cyclic voltam-
mograms of compound 11 and anthracene (An) in Figure 6.
Anthracene itself shows an oxidation potential of EZ1.28 V
and a reduction potential of K1.95 V (Fig. 6b). The
oxidation potential is retained in compound 11 (Fig. 6a).
However, the reduction potential is in the similar range with
the other species shown in Table 2. This suggests that the
tuning of the HOMO level is possible via the covalent
bonding of the substituent that has the lower oxidation
potential. But it is also possible to lose some extent of the
electrochemical reversibility as shown in Figure 6.
3. Conclusion
Twelve new luminescent pyrrolopyridazine pyrrolo[1,2-b]
pyridazine-5,6,7-tricarboxylic acid trimethyl esters were
synthesized from less expensive reagents and under mild
reaction conditions. In this systematic investigation, three
different classes of target molecules were synthesized, for
example, aryl groups directly connected to the core PPY
(pyrrolo[1,2-b]pyridazine-5,6,7-tricarboxylic acid trimethyl
ester) moiety, aryl groups connected to the PPY via a
vinylene linker and aryl groups connected to the PPY via an
acetylene linker. Their optical and electrochemical proper-
ties were studied in detail and compared. One of these
compounds was characterized by X-ray structure analysis.
In particular, it was observed that, compounds bearing
fluorine substituent were showing relatively higher quantum
Figure 4. Fluorescence spectra of compounds 2, 3, 5, 6, 7, 10, 11 and 13 in
dichloromethane.

K. M. K. Swamy et al. / Tetrahedron 61 (2005) 10227–10234
10231
Figure 5. Cyclic voltammograms of 1 mM 6 (a) and 3 (b, c) at a glassy
carbon disk electrode with negative scan direction; in CH3CN containing
0.1 M TBAPF6; vZ0.1 V/s (a, b) or 0.5 V/s (c). The scale bar represents 20
(a, b) and 50 mA (c), respectively.
Figure 6. Cyclic voltammograms of 1 mM 11 (a) and anthracene (b) at a
glassy carbon disk electrode with negative scan direction; in CH3CN
containing 0.1 M TBAPF6; vZ0.1 V/s. The scale bar represents 10 (a) and
20 mA (b), respectively.
recorded using Bruker 250 MHz spectrometer with TMS as
the internal standard. Fluorescence measurements were
made on a RF-5301 PC Spectrofluorophotometer with
excitation at 367 nm; both emission and excitation slit
widths were 5 nm. Mass spectra were obtained using JMS-
700 Mstation spectrometers.
yield values in comparison with the other substituents in that
series. The possibility of tuning the colors and energy levels
of these luminophors was studied by extending the
p-system at the position 2 of the core PPY through a
proper modification such as vinylene or acetylene linkage.
We also demonstrated that pyrrolopyridazine systems
bearing an aryl groups with a suitable electron donor/
withdrawing groups can result in push–pull effects on the
overall photochemical properties of the luminophors.
3-Phenylpyridazine was purchased from Spec, Rijswijk,
The Netherlands. Compound 1 was prepared following the
published procedure.3 Preparation of recently reported
compound 15 involves four steps.7 But in our case we
could able to get the same in one step via Suzuki coupling.
The vinyl derivatives such as 18 and 19 were confirmed with
reported results.8
4. Experimental
4.1. General methods
Unless otherwise noted, materials were obtained from
commercial suppliers and were used without further
purification. Flash chromatography was carried out on silica
gel 60 (230–400 mesh ASTM; Merck). Thin-layer
chromatography (TLC) was carried out using Merck 60
F254 plates with a thickness of 0.25 mm. Preparative TLC
was performed using Merck 60 F254 plates with a thickness
of 1 mm.
4.2. General procedure for the preparation of 2-aryl-
pyrrolo[1,2-b]pyridazine-5,6,7-tricarboxylic acid tri-
methyl ester (1–4) and 2-(2-arylvinyl)pyrrolo[1,2-b]-
pyridazine-5,6,7-tricarboxylic acid trimethyl ester
(5–11)
Dimethyl acetylenedicarboxylate (DMAD) (1 mmol) was
added dropwise to a stirring solution of 3-arylpyridazine/
3-(2-arylvinyl)pyridazine (0.5 mmol) in anhydrous
methanol (2 mL) at 0 8C. Stirring was continued at 0 8C
for 1.5 h and then at ambient temperature 5 h. Solvents were
Melting points were measured using a Bu¨chi 530 melting
point apparatus, and are uncorrected. 1H NMR spectra were

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K. M. K. Swamy et al. / Tetrahedron 61 (2005) 10227–10234
evaporated under reduced pressure and added 2 mL of
methanol. Solid separated slowly on standing the solution at
room temperature for 2–4 h. It was filtered, washed with
small amount of methanol and dried in vacuo. The crude
product was crystallized in dichloromethane/methanol.
Yields were ranging from 20 to 30%.
4.2.6. 2-[2-(4-Fluorophenyl)vinyl]pyrrolo[1,2-b]pyrida-
zine-5,6,7-tricarboxylic acid trimethyl ester (7). Mp
189–190 8C; H NMR (CDCl3) d 8.58 (d, 1H, JZ9.5 Hz),
7.61–7.02 (m, 8H), 4.01 (s, 3H), 3.95 (s, 3H), 3.87 (s, 3H);
13C NMR (CDCl3) d 165.7, 165.4, 162.8, 159.70, 157.4,
152.4, 135.1, 131.8, 131.4, 130.9, 127.8, 124.3, 117.3,
116.2, 115.9, 114.8, 103.0, 53.0, 52.0, 51.8; MS (FAB)
m/zZ413.3 (MCH)C. Anal. Calcd for C21H17FN2O6: C,
61.16; H, 4.16; N, 6.79. Found: C, 61.01; H, 4.26; N,
6.64.
1
4.2.1. 2-(4-Fluorophenyl)pyrrolo[1,2-b]pyridazine-5,6,7-
tricarboxylic acid trimethyl ester (2). Mp 194–195 8C; 1H
NMR (CDCl3) d 8.66 (d, 1H, JZ9.5 Hz), 8.12 (dd, 2H),
7.58 (d, 1H, JZ9.5 Hz), 7.19 (m, 2H), 4.03 (s, 3H), 3.98 (s,
3H), 3.94 (s, 3H); 13C NMR (CDCl3) d 166.4, 165.6, 162.8,
162.4, 158.7, 152.2, 131.0, 130.9, 130.6, 129.3, 129.1,
128.8, 128.5, 117.4, 116.5, 116.1, 102.8, 53.1, 52.2, 51.9;
HRMS (FAB) m/zZ387.0982 (MCH)C, calcd for
C19H16FN2O6Z387.0992.
4.2.7. 2-(2-Naphthalen-2-yl-vinyl)pyrrolo[1,2-b]pyrida-
zine-5,6,7-tricarboxylic acid trimethyl ester (8). Mp
191–192 8C; 1H NMR (CDCl3) d 8.53 (d, 1H, JZ
10.0 Hz), 7.95 (s, 1H), 7.85–7.77 (m, 4H), 7.68 (d, 1H,
JZ17.5 Hz), 7.52–7.43 (m, 3H), 7.38 (d, 1H, JZ17.5 Hz),
4.02 (s, 3H), 3.97 (s, 3H), 3.91 (s, 3H); 13C NMR (CDCl3) d
165.7, 162.7, 158.7, 152.5, 136.4, 133.8, 133.4, 133.0,
130.8, 128.7, 128.3, 127.8, 127.6, 126.8, 126.6, 124.6,
123.4, 117.3, 116.0, 102.9, 53.0, 52.2, 51.9; MS (FAB)
m/zZ445.3 (MCH)C. Anal. Calcd for C25H20N2O6: C,
67.56; H, 4.54; N, 6.30. Found: C, 67.68; H, 4.46; N,
6.32.
4.2.2. 2-(4-Methoxyphenyl)pyrrolo[1,2-b]pyridazine-5,6,
7-tricarboxylic acid trimethyl ester (3). Mp 157–158 8C;
1H NMR (CDCl3) d 8.57 (d, 1H, JZ9.6 Hz), 8.02 (d, 2H,
JZ8.8 Hz), 7.55 (d, 1H, JZ9.6 Hz), 7.01 (d, 2H, JZ
2.7 Hz), 4.02 (s, 3H), 3.97 (s, 3H), 3.92 (s, 3H), 3.88 (s, 3H);
13C NMR (CDCl3) d 165.8, 162.8, 161.7, 158.8, 152.7,
130.6, 128.6, 128.1, 127.2, 117.3, 116.2, 114.6, 102.6, 55.4,
53.0, 52.1, 51.9; HRMS (FAB) m/zZ399.1199 (MCH)C,
calcd for C20H19N2O7Z399.1192. Anal. Calcd for
C20H18N2O7: C, 60.30; H, 4.55; N, 7.03. Found: C, 60.03;
H, 4.36; N, 7.26.
4.2.8. 2-(2-Naphthalen-1-yl-vinyl)pyrrolo[1,2-b]pyrida-
zine-5,6,7-tricarboxylic acid trimethyl ester (9). Mp
1
192–193 8C; H NMR (CDCl3) d 8.57 (d, 1H, JZ9.5 Hz),
8.35 (d, 1H, JZ16.2 Hz), 8.22 (d, 1H, JZ8.0 Hz), 7.85–
7.89 (m, 3H), 7.52–7.59 (m, 4H), 7.32 (d, 1H, JZ16.2 Hz),
4.03 (s, 3H), 3.97 (s, 3H), 3.93 (s, 3H); 13C NMR (CDCl3) d
165.7, 162.8, 158.8, 152.6, 133.7, 133.3, 132.9, 131.3,
130.9, 129.7, 128.8, 128.7, 127.7, 127.1, 126.7, 126.1,
125.7, 124.6, 123.3, 117.4, 116.2, 102.9, 53.0, 52.2, 51.9;
MS (FAB) m/zZ445.3 (MCH)C. Anal. Calcd for
C25H20N2O6: C, 67.56; H, 4.54; N, 6.30. Found: C, 67.45;
H, 4.54; N, 6.26.
4.2.3. 2-Naphthalen-2-yl-pyrrolo[1,2-b]pyridazine-5,6,7-
tricarboxylic acid trimethyl ester (4). Mp 180–182 8C; 1H
NMR (CDCl3) d 8.58 (d, 1H, JZ9.5 Hz), 8.41 (s, 1H), 8.25
(dd, 1H, J1Z8.6 Hz and J2Z1.5 Hz), 7.94 (d, 2H, JZ
8.3 Hz), 7.86 (m, 1H), 7.70 (d, 1H, JZ9.5 Hz), 7.53 (m,
2H), 4.04 (s, 3H), 3.98 (s, 3H), 3.92 (s, 3H); 13C NMR
(CDCl3) d 165.7, 162.8, 158.7, 152.8, 134.3, 133.1, 132.0,
130.7, 129.1, 128.8, 128.7, 128.4, 128.1, 127.8, 127.5,
127.2, 126.7, 123.9, 117.4, 116.5, 102.7, 53.0, 52.2, 51.9;
HRMS (FAB) m/zZ419.1243 (MCH)C, calcd for
C23H19N2O6Z419.1243.
4.2.9. 2-(2-Biphenyl-4-yl-vinyl)pyrrolo[1,2-b]pyridazine-
5,6,7-tricarboxylic acid trimethyl ester (10). Mp 236–
237 8C; 1H NMR (CDCl3) d 8.56 (d, 1H, JZ9.5 Hz), 7.59–
7.71 (m, 6H), 7.52 (d, 1H, JZ6.4 Hz), 7.34–7.49 (m, 4H),
7.26 (d, 1H), 4.01 (s, 3H), 3.97 (s, 3H), 3.92 (s, 3H); 13C
NMR (CDCl3) d 165.7, 162.8, 158.7, 152.6, 142.2, 140.3,
135.9, 134.5, 130.9, 128.9, 128.6, 127.9, 127.7, 127.6,
127.5, 127.0, 124.4, 117.3, 116.0, 102.9, 53.0, 52.2, 51.9;
MS (FAB) m/zZ471.3 (MCH)C. Anal. Calcd for
C27H22N2O6: C, 68.93; H, 4.71; N, 5.95. Found: C, 68.85;
H, 4.78; N, 5.92.
4.2.4. 2-(2-p-Tolylvinyl)pyrrolo[1,2-b]pyridazine-5,6,7-
tricarboxylic acid trimethyl ester (5). Mp 240–241 8C;
1H NMR (CDCl3) d 8.53 (d, 1H, JZ9.6 Hz), 7.43–7.68 (m,
4H), 7.12–7.26 (m, 3H), 4.01 (s, 3H), 3.96 (s, 3H), 3.91 (s,
3H); 13C NMR (CDCl3) d 165.7, 162.8, 158.8, 152.8, 139.7,
136.4, 132.8, 130.9, 129.7, 128.5, 127.6, 127.4, 123.5,
117.3, 116.0, 102.9, 53.0, 52.2, 51.9, 21.4; MS (FAB)
m/zZ409.3 (MCH)C. Anal. Calcd for C22H20N2O6: C,
64.70; H, 4.94; N, 6.86. Found: C, 64.87; H, 4.97; N,
6.74.
4.2.10. 2-(2-Anthracen-9-yl-vinyl)pyrrolo[1,2-b]pyrida-
zine-5,6,7-tricarboxylic acid trimethyl ester (11). Mp
209–210 8C; H NMR (CDCl3) d 8.65 (d, 1H, JZ9.5 Hz),
4.2.5. 2-[2-(4-Methoxyphenyl)vinyl]pyrrolo[1,2-b]pyri-
dazine-5,6,7-tricarboxylic acid trimethyl ester (6). Mp
216–217 8C; H NMR (CDCl3) d 8.52 (d, 1H, JZ9.6 Hz),
1
1
8.44 (d, 1H, JZ16.7 Hz), 8.43 (s, 1H), 8.31 (m, 2H), 8.03
(m, 2H), 7.62 (d, 1H, JZ9.6 Hz), 7.50 (m, 4H), 7.16 (d, 1H,
JZ16.7 Hz), 4.03 (s, 3H), 3.94 (s, 3H), 3.92 (s, 3H); 13C
NMR (CDCl3) d 178.7, 177.0, 173.8, 165.7, 162.8, 158.8,
152.1, 151.5, 133.4, 132.8, 131.4, 131.0, 130.4, 129.5,
128.9, 128.8, 128.0, 127.9, 126.5, 126.2, 125.7, 125.4,
125.3, 53.1, 52.2, 51.9; HRMS (FAB) m/zZ495.1531 (MC
H)C, calcd for C29H23N2O6Z495.1556.
7.55 (d, 2H, JZ8.8 Hz), 7.48 (d, 1H, JZ9.6 Hz), 7.43 (d,
1H, JZ2.7 Hz), 7.13 (d, 1H, JZ16.5 Hz), 6.94 (d, 2H, JZ
8.8 Hz), 4.01 (s, 3H), 3.96 (s, 3H), 3.91 (s, 3H), 3.86 (s, 3H);
13C NMR (CDCl3) d 165.8, 162.8, 160.7, 158.8, 152.9,
136.0, 130.9, 128.9, 128.4, 128.3, 127.5, 122.2, 117.2,
116.0, 114.4, 102.8, 55.4, 53.0, 52.2, 51.9; MS (FAB) m/zZ
425.3 (MCH)C. Anal. Calcd for C22H20N2O7: C, 62.26; H,
4.75; N, 6.60. Found: C, 62.41; H, 4.79; N, 6.59.

K. M. K. Swamy et al. / Tetrahedron 61 (2005) 10227–10234
10233
4.3. General procedure for the preparation of 2-aryl-
ethynyl-pyrrolo[1,2-b]pyridazine-5,6,7-tricarboxylic
acid trimethyl ester (12–13)
4.4.2. 3-(4-Methoxyphenyl)pyridazine (15). Mp 107–
108 8C; H NMR (CDCl3) d 9.10 (dd, 1H, J1Z4.8 Hz and
1
J2Z1.6 Hz), 8.03–8.08 (m, 2H), 7.80 (dd, 1H, J1Z8.7 Hz
and J2Z1.6 Hz), 7.47 (dd, 1H, J1Z8.7 Hz and J2Z4.9 Hz),
7.02–7.08 (m, 2H), 3.89 (s, 3H); 13C NMR (CDCl3) d 161.7,
159.4, 149.9, 129.16, 129.0, 128.8, 127.1, 123.6, 114.8,
114.3, 55.8; HRMS (EI) m/zZ186.0789 (M)C, calcd for
C11H10N2OZ186.0793. Anal. Calcd for C11H10N2O: C,
70.95; H, 5.41; N, 15.0. Found: C, 70.71; H, 5.49; N, 15.18.
Dimethyl acetylenedicarboxylate (DMAD) (1 mmol) was
added dropwise to a stirring solution of 3-arylethynyl-
pyridazine (0.5 mmol) in anhydrous methanol (6 mL) at
0 8C. Stirring was continued at 0 8C for 1.5 h and then at
ambient temperature 24 h. Solvents were evaporated under
vacuum and the residue, which contains tarry impurities was
eluted on silica gel column using hexaneCethyl acetate 7:3.
It was again crystallized in methanol with trace amount of
dichloromethane. Yields were ranging from 15 to 20%.
4.4.3. 3-Naphthalen-2-yl-pyridazine (16). Mp 173–
1
174 8C; H NMR (CDCl3) d 9.20 (dd, 1H, J1Z4.8 Hz and
J2Z1.6 Hz), 8.58 (d, 1H, JZ102 Hz), 8.24 (dd, 1H, J1Z
8.6 Hz and J2Z1.8 Hz), 8.05–7.99 (m, 4H), 7.62–7.55 (m,
3H); 13C NMR (CDCl3) d 159.4, 150.0, 134.1, 133.6, 133.4,
128.9, 128.8, 127.8, 127.2, 127.0, 126.8, 126.6, 124.2,
124.1; MS (FAB) m/zZ206.2 (MCH)C.
4.3.1. 2-Phenylethynylpyrrolo[1,2-b]pyridazine-5,6,7-
tricarboxylic acid trimethyl ester (12). Mp 188–189 8C;
1H NMR (CDCl3) d 8.60 (d, 1H, JZ9.4 Hz), 7.66–7.62 (m,
2H), 7.45–7.36 (m, 3H), 7.30 (d, 1H, JZ10.00 Hz), 4.02 (s,
3H), 3.97 (s, 3H), 3.92 (s, 3H); 13C NMR (CDCl3) d 165.4,
162.5, 158.5, 140.8, 132.3, 130.4, 129.9, 129.0, 128.5,
127.7, 121.2, 117.6, 103.2, 93.9, 84.9, 53.0, 52.4, 52.0;
HRMS (FAB) m/zZ393.1098 (MCH)C, calcd for
C21H17N2O6Z393.1087. Anal. Calcd for C21H16N2O6: C,
64.28; H, 4.11; N, 7.14. Found: C, 64.26; H, 4.14; N, 7.40.
4.5. General procedure for the preparation of 3-(2-aryl-
vinyl)pyridazine derivatives (17–23)
These compounds were prepared according to a modified
literature method.8a Aromatic aldehyde (10 mmol) was
slowly added over a period of 5 h to a mixture of the
3-methylpyridazine (10 mmol) and tetrabutylammonium
hydrogen sulfate (1 mmol) in a hot aqueous solution
(50 mL) of sodium hydroxide (5 M) under stirring. The
reflux was maintained for 3 h. After cooling overnight the
separated solid was filtered, washed with small amount of
cold water and dried. The crude product was purified by
eluting on silica gel column using ethyl acetate/hexane 1:1.
Yields were ranging from 40 to 60%.
4.3.2. 2-(4-Fluorophenylethynyl)pyrrolo[1,2-b]pyrida-
zine-5,6,7-tricarboxylic acid trimethyl ester (13). Mp
1
167–168 8C; H NMR (CDCl3) d 8.61 (d, 1H, JZ10 Hz),
7.67–7.59 (m, 2H), 7.29 (d, 1H, JZ10 Hz), 7.14–7.08 (m,
2H), 4.02 (s, 3H), 3.97 (s, 3H), 3.92 (s, 3H); 13C NMR
(CDCl3) d 165.1, 162.5, 161.4, 158.5, 140.7, 134.4, 134.3,
130.4, 129.1, 127.8, 121.1, 117.6, 117.3, 117.2, 116.2,
115.8, 103.3, 92.8, 84.7, 53.1, 52.4, 52.0; HRMS (FAB)
m/zZ411.1007 (MCH)C, calcd for C21H16FN2O6Z
411.0992. Anal. Calcd for C21H15FN2O6: C, 61.47; H,
3.68; N, 6.83. Found: C, 61.62; H, 3.64; N, 7.00.
4.5.1. 3-(2-p-Tolyl-vinyl)pyridazine (17). Mp 121–122 8C;
1H NMR (CDCl3) d 9.03 (dd, 1H, J1Z4.8 Hz and J2Z
1.6 Hz), 7.72–7.58 (m, 2H), 7.51 (s, 1H), 7.48 (s, 1H), 7.44
(dd, 1H, J1Z8.6 Hz, J2Z4.9 Hz), 7.31 (d, 1H, JZ10.7 Hz),
7.19 (s, 1H), 7.14 (s, 1H), 2.38 (s, 3H); 13C NMR (CDCl3) d
158.4, 149.5, 139.3, 135.1, 134.8, 133.2, 129.6, 129.2,
127.7, 127.3, 127.0, 126.3, 124.7, 123.9, 123.8, 21.4; MS
(FAB) m/zZ197.3 (MCH)C.
4.4. General procedure for the preparation 3-aryl-
pyridazines via Suzuki cross-coupling (14–16)
These compounds were prepared according to a modified
literature method.6 A mixture of 3-iodopyridazine
(2.42 mmol), arylboronic acid (3.64 mmol), Pd(PPh3)4
(0.075 mmol), toluene (20 mL) and Na2CO3 (2.6 mL,
2 M) was flushed with N2 for 5 min under stirring. The
reaction mixture was heated at 120 8C for 18–24 h under a
N2 atmosphere. After cooling to room temperature the
solvents were evaporated to dryness under reduced pressure.
EtOAc (80 mL) was added and the suspension was placed in
an ultrasonic bath for 5 min. The mixture was filtered,
washed the residue thoroughly with EtOAc (w40 mL) and
the filtrate evaporated under reduced pressure to dryness.
The residue was purified by flash column chromatography
on silica gel using EtOAc.
4.5.2. 3-(2-Biphenyl-4-yl-vinyl)pyridazine (20). Mp 186–
1
187 8C; H NMR (CDCl3) d 9.05 (dd, 1H, J1Z4.8 Hz and
J2Z1.5 Hz), 7.74 (d, 1H, JZ16.5 Hz), 7.61–7.66 (m, 7H),
7.36–7.49 (m, 4H), 7.13 (d, 1H, JZ16.5 Hz); 13C NMR
(CDCl3) d 158.3, 149.6, 141.8, 140.4, 134.9, 134.7, 128.9,
127.8, 127.6, 127.5, 127.3, 127.0, 126.4, 125.1, 123.9; MS
(FAB) m/zZ259.3 (MCH)C.
4.5.3. 3-(2-Naphthalen-2-yl-vinyl)-pyridazine (21). Mp
1
166–167 8C; H NMR (CDCl3) d 9.05 (dd, 1H, J1Z4.9 Hz
and J2Z1.6 Hz), 7.95 (s, 1H), 7.79–7.88 (m, 5H), 7.66 (d,
1H, JZ8.4 Hz), 7.42–7.51 (m, 4H); 13C NMR (CDCl3) d
158.3, 149.7, 135.2, 133.7, 133.5, 133.4, 128.6, 128.5,
128.3, 127.8, 126.7, 126.6, 126.5, 125.5, 124.0, 123.4; MS
(FAB) m/zZ233.3 (MCH)C. Anal. Calcd for C16H12N2: C,
82.73; H, 5.21; N, 12.06. Found: C, 82.59; H, 5.25; N, 11.87.
4.4.1. 3-(4-Fluorophenyl)pyridazine (14). Mp 122–
1
123 8C; H NMR (CDCl3) d 9.15 (dd, 1H, J1Z4.9 Hz and
J2Z1.6 Hz), 8.03–8.11 (m, 2H), 7.83 (dd, 1H, J1Z8.7 Hz
and J2Z1.6 Hz), 7.54 (dd, 1H, J1Z8.6 Hz and J2Z4.8 Hz),
7.16–7.27 (m, 2H); 13C NMR (CDCl3) d 166.4, 162.5,
158.7, 150.2, 132.8, 129.4, 129.2, 127.0, 123.8, 116.5,
116.2; HRMS (EI) m/zZ174.0588 (M)C, calcd for
C10H7FN2Z174.0593.
4.5.4. 3-(2-Naphthalen-1-yl-vinyl)-pyridazine (22). Mp
82–83 8C; 1H NMR (CDCl3) d 9.05 (dd, 1H, J1Z4.9 Hz and
J2Z1.6 Hz), 8.54 (d, 1H, JZ16.5 Hz), 8.29 (d, 1H, JZ
7.6 Hz), 7.82–7.86 (m, 3H), 7.68 (dd, 1H, J1Z8.6 Hz and

10234
K. M. K. Swamy et al. / Tetrahedron 61 (2005) 10227–10234
J2Z1.6 Hz), 7.43–7.56 (m, 4H), 7.40 (d, 1H, JZ16.5 Hz);
13C NMR (CDCl3) d 158.2, 149.7, 133.7, 133.5, 132.2,
131.4, 129.4, 128.7, 127.7, 126.5, 126.4, 126.1, 125.6,
124.4, 124.3, 123.6; MS (FAB) m/zZ233.3 (MCH)C.
Anal. Calcd for C16H12N2: C, 82.73; H, 5.21; N, 12.06.
Found: C, 82.56; H, 5.27; N, 11.99.
calibrated versus the ferrocene/ferrocenium (FcjFcC) redox
couple. The potential values shown in this text were then
corrected to the saturated calomel electrode (SCE) on the
basis of FcjFcC redox potential as 0.44 V versus SCE,3a,10–12
unless otherwise specified. The potential scan rate was
varied from 0.1 to 1 V/s to check the reversibility of redox
waves. Epa (anodic peak potential) and Epc (cathodic peak
potential) were shown for redox waves.
4.5.5. 3-(2-Anthracen-9-yl-vinyl)-pyridazine (23). Mp
1
172–173 8C; H NMR (CDCl3) d 9.15 (dd, 1H, J1Z4.9 Hz
and J2Z1.6 Hz), 8.66 (d, 1H, JZ16.5 Hz), 8.45 (s, 1H),
8.36 (m, 2H), 8.03 (m, 2H), 7.72 (dd, 1H, J1Z8.6 Hz and
J2Z1.6 Hz), 7.45–7.53 (m, 5H), 7.21 (d, 1H, JZ16.5 Hz);
13C NMR (CDCl3) d 157.8, 150.0, 133.6, 132.2, 131.4,
131.1, 129.6, 128.8, 127.5, 126.6, 125.9, 125.5, 125.3,
124.4; MS (FAB) m/zZ283.3 (MCH)C. Anal. Calcd for
C20H14N2: C, 85.08; H, 5.00; N, 9.92. Found: C, 84.88; H,
5.01; N, 9.73.
Acknowledgements
This work was supported by the Korea Research Foundation
Grant funded by the Korean Government (MOEHRD)
(KRF-R14-2003-014-01001-0) and by the SRC program of
the Korea Science and Engineering Foundation (KOSEF)
through the Center for Intelligent Nano-Bio Materials at
Ewha Womans University (R11-2005-008-02001-0)
K.M.K.S. is thankful to KOFST for Brain Pool Fellowship.
4.6. General procedure for the preparation of 3-(2-
arylethynyl)pyridazines via Sonogashira coupling
(24–25)
These compounds were prepared according to a modified
literature method.9 The suspension of iodopyridazine
(2.91 mmol), Pd(PPh3)2Cl2 (0.06 mmol) and copper(I)
iodide (0.30 mmol), in dry THF (12 mL) and dry
triethylamine (12 mL) was stirred at room temperature
under argon atmosphere for 15 min. To this suspension the
terminal alkyne (3.50 mmol), dissolved in dry THF (5 mL)
was added. The reaction mixture was stirred for 5 h at
55–60 8C. The solvents were removed in vacuo, and the
residue was dissolved in chloroform (50 mL) and filtered
out the solids. The chloroform solution was washed with
water (4!10 mL each), dried over Na2SO4 and evaporated
the solvents in vacuo. The residue was purified on silica
column using hexaneCethyl acetate 3:7 solvent mixture.
Yields were ranging from 60 to 70%.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2005.08.038
References and notes
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1
4.6.1. 3-Phenylethynylpyridazine (24). Mp 72–73 8C; H
NMR (CDCl3) d 9.14 (d, 1H, JZ3.93 Hz), 7.71–7.61 (m,
3H), 7.42–7.38 (m, 4H); 13C NMR (CDCl3) d 149.3, 148.4,
132.6, 132.2, 129.5, 129.6, 128.5, 125.7, 121.5, 93.9, 85.7;
HRMS (EI) m/zZ180.0692 (M)C, calcd for C12H8N2Z
180.0687. Anal. Calcd for C12H8N2: C, 79.98; H, 4.47; N,
15.55. Found: C, 79.88; H, 4.38; N, 15.60.
4. Coad, P.; Coad, R. A.; Clough, S.; Hyepock, J.; Salisbury, R.;
Wilkins, C. J. Org. Chem. 1963, 28, 218.
¨ ¨
5. Haider, N.; Kaferbock, J. Heterocycles 2000, 53, 2527.
`
6. Maes, B. U. W.; Lemiere, G. L. F.; Dommisse, R.; Augustyns,
K.; Haemers, A. Tetrahedron 2000, 56, 1777.
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Y. S. Mater. Sci. Eng. C 2004, 24, 349.
4.6.2. 3-(4-Fluorophenylethynyl)pyridazine (25). Mp
1
129–130 8C; H NMR (CDCl3) d 9.18 (s, 1H), 7.66–7.52
(m, 4H), 7.19–7.06 (m, 2H); 13C NMR (CDCl3) d 165.3,
161.3, 149.3, 134.3, 134.2, 129.5, 125.7, 117.6, 117.5,
116.1, 115.8, 92.8, 85.5; HRMS (EI) m/zZ198.0611 (M)C,
calcd for C12H7FN2Z198.0593.
8. (a) Eynde, J. J. V.; Pascal, L.; Haverbeke, Y. V.; Dubois, P.
Synth. Commun. 2001, 31, 3167. (b) Heinisch, G.; Mayrhofer,
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4.7. Cyclic voltammetry (CV) measurement
All the electrochemical measurements were carried out in
acetonitrile solutions containing 1 mM electroactive com-
pound and 0.1 M tetrabutylammonium hexafluorophosphate
(TBAPF6), respectively, at room temperature using a BAS
100B electrochemical analyzer. A glassy carbon disk
(diameter 3 mm) and platinum wire were used as working
and counter electrodes. The reference electrode used was
AgjAgNO3 (0.1 M), and all the potential values were
11. Clerac, R.; Cotton, F. A.; Dunbar, K. R.; Lu, T.; Murillo, C. A.;
Wang, X. J. Am. Chem. Soc. 2000, 122, 2272.
12. The potential values of compound 1 reported here are
somewhat different from those in Ref. 1, but the potential
values of anthracene are the same as those in Bard, A. J.;
Faulkner, L. R. Electrochemical Methods: Fundamentals and
Applications, 2nd ed.; Wiley: New York, 2001; p 81.