Pyrrolopyridazine derivatives as blue organic luminophores: synthesis and properties. Part 2

Article abstract of DOI:10.1016/j.tet.2009.10.110

Two environmentally friendly methods, one in liquid and other in solid phase, for preparation of highly fluorescent pyrrolopyridazine (PP) derivatives under microwave (MW) irradiation is presented. The first synthesis in solid phase of fluorescent PP derivatives using activated alkynes under MW and conventional heating is also reported. Under MW irradiation the yields are higher, the amount of used solvent in liquid phase is at least five-fold less while solid phase does not use solvents, so these reactions may be considered as environmentally friendly. Eight new blue fluorescent 2-aryl-pyrrolopyridazine derivatives were synthesised. A certain influence of the PP substituents concerning absorption and fluorescent properties was observed. Introduction of a π-conjugated system in the second position of PP moiety increase the fluorescent properties. In the absorption spectra were observed a gradual decrease of wavelengths simultaneously with an increasing of molar extinction coefficient, due to increased number of ester groups from pyrrolic ring.

Full text of DOI:10.1016/j.tet.2009.10.110

Tetrahedron 66 (2010) 278–282
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Pyrrolopyridazine derivatives as blue organic luminophores: synthesis
and properties. Part 2q
*
Gheorghita Zbancioc, Ionel I. Mangalagiu
Al. I. Cuza University, Faculty of Chemistry, Organic Chemistry Department, Bd. Carol I no. 11, Iasi 700506, Romania
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 June 2009
Received in revised form 12 October 2009
Accepted 29 October 2009
Available online 4 November 2009
Two environmentally friendly methods, one in liquid and other in solid phase, for preparation of highly
fluorescent pyrrolopyridazine (PP) derivatives under microwave (MW) irradiation is presented. The first
synthesis in solid phase of fluorescent PP derivatives using activated alkynes under MW and conven-
tional heating is also reported. Under MW irradiation the yields are higher, the amount of used solvent in
liquid phase is at least five-fold less while solid phase does not use solvents, so these reactions may be
considered as environmentally friendly. Eight new blue fluorescent 2-aryl-pyrrolopyridazine derivatives
were synthesised. A certain influence of the PP substituents concerning absorption and fluorescent
properties was observed. Introduction of a
p-conjugated system in the second position of PP moiety
increase the fluorescent properties. In the absorption spectra were observed a gradual decrease of
wavelengths simultaneously with an increasing of molar extinction coefficient, due to increased number
of ester groups from pyrrolic ring.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
environmentally friendly method for preparation of these de-
rivatives using MW technologies (in liquid and solid phase).
Synthesis of highly fluorescent derivatives with extended
-conjugation has opened new research horizons because of their
p
2. Results and discussion
applications as sensors and biosensors, electroluminescent mate-
rials, lasers and other optoelectronic devices.1–4a–d Recent studies
show that pyrrolopyridazine (PP) derivatives represent such
a class, being a ‘pure’ blue-emitting moiety.4c,d,11 During the last
years MW irradiation has became an increasingly valuable tool in
organic chemistry, since it offers a versatile and facile pathway in
a large variety of syntheses.5–14 Solid phase reactions have the great
advantage of using no organic solvents (‘solvent-free’), such
reactions being more environmentally friendly and generate less
side products. The application of MW irradiation under solvent-free
conditions enables organic reactions to occur expeditiously at
ambient pressure, providing unique chemical processes with
special attributes such as higher yields, shorter reaction time,
milder conditions and the associated ease of manipulation.5–7,12–14
In a preliminary communication,11 we synthesized a series of
pyrrolopyridazine derivatives with fluorescent properties. The aim
of this work was to synthesise new fluorescent PPs, to study the
relationship between optical properties and structure (the effect
The pyrrolopyridazine moiety I was proved to be responsible
for blue fluorescent properties.4c,d,11 A rational design shows us
that a suitable and accessible modification could be made in
order to increase the fluorescent properties, would be in-
troduction of a phenyl ring in the 2- position, which would allow
expansion of the
p system conjugation, as we have shown in
structure II. In equal measure we were interested to study the
influence of this modification and of the substituents at the 5-, 6-
and 7- positions concerning the synthesis, absorption and
emission spectra.
X
X
2
1
3
of substituents and conjugation), and to develop
a new
N
N
N
N
4
7
5
6
q
See Ref. 11.
I
II
* Corresponding author. Tel.: þ40 232 201343; fax: þ40 232 201313.
E-mail address: ionelm@uaic.ro (I.I. Mangalagiu).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.110

G. Zbancioc, I.I. Mangalagiu / Tetrahedron 66 (2010) 278–282
279
The strategies adopted for construction of fluorescent PP
derivatives II are depicted in Scheme 1. The reaction pathway
involves two steps: initially N-alkylations of the pyridazines
followed by a [3þ2] dipolar cycloaddition of pyridazinium ylides 2
to the corresponding dipolarophiles. Pyridazinium ylides 2 were
generated in situ from the corresponding cycloimmonium salts 1,
using the Kro¨hnke salt method15 (alkaline medium, Et3N in liquid
phase and KF–Al2O3 in solid phase). As dipolarophiles we used
activated alkynes, methyl propiolate and dimethyl acetylenedi-
carboxylate. Fully aromatised PP cycloadducts 3a–d and 4a–d were
obtained, via a spontaneously oxidative (by air) dehydrogenation of
intermediates 30 and 40.
As indicated in Table 1, under MW heating the reaction times
decreased dramatically from hours to minutes (5 min. in liquid
phase, 15 min. in solid phase) and the yields are higher. In solid
phase, on solid support KF–Al2O3, the results are even more
spectacular: while under MW heating the cycloadducts were
obtained in good yields (around 50%), under conventional heating
(oil bath) we obtained decomposition products only. We also
observed that under MW irradiation the consumed energy
decreased considerably, the amount of used solvent in liquid phase
is at least five-fold less (see Experimental) while solid phase does
not use solvents, so these reactions may be considered as envi-
ronmentally friendly.
X
X
X
X
TEA
BrCH COOR
2
N
N
R= Me, Et
N
N
N
N
Br
CH COOR
N
N
CH COOR
2
2
X= Cl, Br
1
CH COOR
COOMe
MeOOC
COOMe
X
X
4'
3'
4'
C H X '
3'
2'
6
4 4
C H X '
6
4 4
N
2'
N
N
1'
2
1'
2
COOR
N
+
+
1
-2H
N
N
1
-2H
N
COOR
3
3
4
4
N
7
COOR
COOR
MeOOC
MeOOC
3'
7
COOMe
5
6
5
6
4'
MeOOC
MeOOC
COOMe
3. a. X= Cl; R=Me
b. X= Cl; R= Et
c. X= Br; R= Me
d. X= Br; R= Et
4. a. X= Cl; R=Me
b. X= Cl; R= Et
c. X= Br; R= Me
d. X= Br; R= Et
Scheme 1. Synthesis of fluorescent PP, under microwaves and conventional heating.
Under conventional heating this strategy has some major
disadvantages: long reaction time (around 2 h), high energy
consumption, low yields and the need for large amounts of
solvents. This is why we decided to synthesise the desired
fluorescent adducts by microwave irradiation, both in liquid and
solid phase. The MW-assisted reactions were carried out using
a monomode reactor, using a constant irradiation power and
varying the temperature (the so-called ‘power control’). The best
results were obtained when 25% of the full power of the magnetron
(800 W) was used. Table 1 lists the optimized conditions we
employed, under MW irradiation as well as under conventional
heating.
The structure of the synthesized compounds was proved by
elemental (C, H, N) and spectroscopic analysis (IR, 1H NMR, 13C
NMR, 2D-COSY, 2D-HETCOR (HMQC), long range 2D-HETCOR
(HMBC). Thus, in the 1H NMR spectra of PP adducts, the most
important signals are those of the H-4, H-3 and H-6 atoms (for 3)
and H-4, H-3 (for 4). The lack of signals between z4 and 7 ppm, is
solid evidence for the aromatized structure. The H-4 protons
appear at high chemical shifts (z8.5 ppm), as a doublet, H-3
protons appear at z7.5 ppm and in compound 3, the H-6 protons
appear also at high chemical shifts (z7.75 ppm) because of the
neighbouring of the two carbonyl-ester groups (from 5 and 7
position). 13C NMR spectroscopy also confirmed the proposed
Table 1
Synthesis of PP cycloadducts 3a–d and 4a–d under MW and conventional heating conditions, in liquid and solid phase
Compd.
Microwaves
Conventional heating
Liquid phase
Liquid phase
Solid phase
Solid phase
Reaction time (min)
Yield, %
Reaction time (min)
Yield, %
Reaction time (min)
Yield, %
Reaction time (min)
Yield, %
3a
3b
3c
3d
4a
4b
4c
4d
5
5
5
5
5
5
5
5
50
52
53
50
49
52
51
53
15
15
15
15
15
15
15
15
51
49
52
50
45
49
48
49
120
120
120
120
120
120
120
120
41
44
43
35
40
46
41
43
15–240
15–240
15–240
15–240
15–240
15–240
15–240
15–240
d
d
d
d
d
d
d
d

280
G. Zbancioc, I.I. Mangalagiu / Tetrahedron 66 (2010) 278–282
structure, the corresponding carbons appearing at chemical shifts
in accordance with the proposed structure.
The absorption maxima and the corresponding molar extinction
coefficients for compounds 3a–d and 4a–d are listed in Table 2.
As Table 2 and Figures 1 and 2 show, the position of the ab-
sorption bands and the values of the molar extinction coefficients,
evidence the influence of the substituents at the pyrrolic ring.
Apparently, the absorption spectral profile of compounds 3 and 4
are essentially the same: the absorption peak maxima occur around
360, 340, 280, 265 and 225 nm. However, the absorption spectra
change significantly from adducts 3 (with two ester groups) to 4
(with three ester groups), a hypsochromic shift and molar extinc-
tion coefficient increase being observed. Thus, while the fourth (IV)
and the fifth (V) absorption band remain roughly the same, the
absorption bands I to III are significantly blue shifted in 4. The
gradual decrease in absorption wavelengths and molar extinction
coefficient increasing, due to increased number of ester groups, is
also reported by some other authors in related cases.4a–d
The fluorescence spectra were recorded with a Turner Bio-
Systems fluorimeter using FluoOpticalKitID PN:9300-043 SN:F20
00000BB5A4C2D SIG:UV with lex¼365 nm and lem¼410–460 nm.
Intensity of fluorescence for compounds 3 and 4 are listed in Table
3. As can be noticed from Table 3, PP are very intense blue emitters
[intensity of fluorescence for these compounds are much higher
compared with the solvent (with about 120–190 fold higher)],
which proved that introduction of a benzene ring in the 2- position
from PP moiety I, has a beneficial effect concerning fluorescent
properties.
In the next stage of our work, we studied the absorption and
emission spectra of the obtained PP cycloadducts. The absorption
of compounds 3 and 4 (acetonitrile, recorded in the spectral range
190–600 nm), exhibit clear differences in their experimental
UV–VIS spectra as can be seen in Figures 1 and 2.
It could be also noticed from Table 3 that compounds with
a para-chlorophenyl- substituent in the 2- position of PP moiety
and those, which possess a carbethoxy group, in it 7- position have
a much higher fluorescence.
Figure 1. The absorption spectra of the compound 3a–d (c¼ 5ꢀ10ꢁ5) in acetonitrile.
3. Conclusions
Two environmentally friendly methods, one in liquid and other
in solid phase, for the preparation of highly fluorescent PP
derivatives under microwave irradiation are presented. The first
synthesis in solid phase of fluorescent PP derivatives using
activated alkynes under microwave and conventional heating is
also reported. Under MW irradiation the yields are higher, the
amount of used solvent in liquid phase is at least five-fold less while
solid phase do not use solvents, so these reactions may be
considered as environmentally friendly. Eight new blue fluorescent
2-aryl-PP derivatives were synthesised. A certain influence of the
PP substituents concerning absorption and fluorescent properties
were observed. Compounds with a para-chlorophenyl- substituent
in the 2- position of PP moiety and those one, which possess
a carboethoxy groups, in the 7- position have a much higher fluo-
rescence. In the absorption spectra were observed a gradual
decrease of wavelengths simultaneously with an increasing of
molar extinction coefficient, due to increased number of ester
groups from the pyrrolic ring.
Figure 2. The absorption spectra of the compound 4a–d (c¼ 5ꢀ10ꢁ5 M) in acetonitrile.
Table 2
Absorption (lmax) and molar extinction coefficients (3), for PP derivatives in acetonitrile
Compound/number of
absorption maxima
lmax (nm) [
3
(L molꢁ1 cmꢁ1)ꢀ103]
I
II
III
IV
V
3a
3b
3c
3d
4a
4b
4c
4d
356.00 [2.65]
357.00 [2.93]
355.00 [2.93]
356.00 [3.00]
344.00 [3.50]
350.00 [3.18]
350.00 [3.18]
350.00 [3.31]
347.00 [2.33]
277.00 [30.33]
280.00 [32.95]
284.00 [30.23]
284.00 [31.68]
276.00 [31.15]
276.00 [32.38]
282.00 [30.21]
276.00 [34.46]
264.00 [25.02]
263.00 [26.00]
265.00 [24.15]
264.00 [24.73]
264.00 [26.75]
264.00 [26.75]
265.00 [25.68]
264.00 [29.01]
225.00 [11.30]
226.00 [11.90]
228.00 [11.91]
227.00 [11.75]
226.00 [7.45]
226.00 [11.51]
227.00 [6.00]
228.00 [12.33]
337.00 [2.58]
341.00 [2.80]
340.00 [2.73]
340.00 [3.46]
335.00 [2.95]
335.00 [3.01]
334.00 [3.06]

G. Zbancioc, I.I. Mangalagiu / Tetrahedron 66 (2010) 278–282
281
Table 3
Intensity of fluorescence for 3 and 4 PP derivatives in acetonitrile
Compd.
3a
3b
3c
3d
4a
4b
4c
4d
Solvent
40.86
Intensity of fluorescence
6276.11
6554.21
7510.05
8264.76
5016.82
5269.64
6018.34
6304.55
4. Experimental section
4.1. General procedures
H4); 13C NMR (TMS, CDCl3,
51.69 (CH3 from 7, COOMe), 105.02 (C5), 114.87 (C3), 119.71 (C7),
d, ppm): 51.51 (CH3 from 5, COOMe),
0
0
122.79 (C6), 128.12 (C4), 128.30 (C2 ), 129.34 (C3 ), 131.84 (C4a),
0
0
133.63 (C1 ), 136.65 (C4 ), 151.09 (C2), 159.53 (7-CO), 163.90 (5-CO).
Anal. calcd for C17H13ClN2O4 (344.75): C 59.23, H 3.80, N 8.13;
found: C 59.20, H 3.73, N 8.05.
All the reagents and solvents used were of the best grade
available and were used without further purification. 1H and 13C
NMR spectra were recorded on
spectrometer, downfield from an internal standard, SiMe4 in CDCl3.
Chemical shifts are given in ppm ( -scale), coupling constants (J) in
a Bruker Avance 400 DRX
4.3.2. 7-Ethyl, 5-methyl 2-(4-chlorophenyl)pyrrolo[1,2-b] pyridazine-
5,7-dicarboxylate (3b). White solid, mp 167–168 ꢂC. IR (KBr, cmꢁ1):
3122 (C–H arom.), 2952 (C–H aliph.), 1708, 1672 (C]O est.), 1550,
1521, 1479, 1469 (C]C, C]N), 1242, 1209 (C–O–C), 825 (C–Cl). 1H
d
Hertz. IR spectra were recorded with a Shimadzu Prestige 8400s
FTIR spectrophotometer in KBr. UV–VIS spectra were recorded with
a Schimadzu UV-1800 spectrometer in acetonitrile. The fluores-
cence values were recorded with a Turner BioSystems fluorimeter.
For the microwave (MW) irradiation a monomode reactor (STAR-2,
CHEM corporation, USA, (800 W) was used. Melting points
were determined using an electrothermal apparatus and are
uncorrected. Flash chromatography was performed with Aldrich
230–400 mesh silica gel (eluent: CH2Cl2:CH3OH¼99:1). TLC was
carried out with Merck silica gel 60-F-254 plates.
NMR (TMS, CDCl3,
d
, ppm): 1.45(t, J¼7.2, 3H: CH3–CH2), 3.93 (s, 3H:
CH3 from 5 position), 4.45 (q, J¼7.2, 2H: CH2–CH3), 7.51–7.47 (m,
0
overlapped peaks, 3H: 2H3 , 1H3), 8.00 (s, 1H: H6), 8.04 (dd, J¼8.8,
J¼2.0, 2H: H2 ), 8.64 (d, J¼9.6, 1H: H4); 13C NMR (CDCl3,
d, ppm, J,
0
Hz): 14.43 (CH3–CH2), 51.48 (CH3 from 5, COOMe), 60.60 (CH2),
104.92 (C5), 114.72 (C3), 120.06 (C7), 122.74 (C6), 128.08 (C4), 128.27
0
0
0
0
(C2 ), 129.30 (C3 ), 131.77 (C4a), 133.67 (C1 ), 136.60 (C4 ), 150.98 (C2),
159.16 (7-CO), 163.93 (5-CO). Anal. calcd for C18H15ClN2O4 (358.78):
C 60.26, H 4.21, N 7.81; found: C 60.23, H 4.12, N 7.71.
4.2. General procedure for [3D2] dipolar cycloaddition in the
liquid phase
4.3.3. Dimethyl 2-(4-bromophenyl)pyrrolo[1,2-b]pyridazine-5,7-di-
carboxylate (3c). Yellow solid, mp 220–221 ꢂC. IR (KBr, cmꢁ1): 3124
(C–H arom.), 2947 (C–H aliph.), 1726, 1695 (C]O est.), 1560, 1463,
1434, 1404 (C]C, C]N), 1245, 1193 (C–O–C), 810 (C–Br). 1H NMR
3-(4-Halophenyl)-pyridazinium bromide (5 mmol) and dipo-
larophile (5.5 mmol) were suspended in 50 mL of anhydrous tolu-
ene (under conventional heating) and 10 mL of anhydrous toluene
(under microwave heating). Then, triethylamine (5.5 mmol) was
added. Under conventional conditions, the solution was refluxed
(oil bath) for 2 h. Under microwave heating, the solution was
exposed to microwaves for 5 min. Using MW irradiation, the best
results were obtained using a constant irradiation power (25% from
the full power of the magnetron, 800 W) and varying the temper-
ature (the so-called ‘power control’). The resulting mixture was
filtered hot to remove triethylamine hydrobromide and the clear
solution was evaporated. The crude product was purified by chro-
matography on silica gel with dichloromethane/methanol (99/1) as
eluent.
(CDCl3,
d, ppm, J, Hz): 3.94 (s, 3H: CH3 from 5 position), 3.97 (s, 3H:
CH3 from 7 position), 7.52 (d, J¼9.6, 1H: H3), 7.65 (dd, J¼8.4, J¼2.0,
0
0
2H: H3 ), 7.98 (dd, J¼8.4, J¼2.0, 2H: H2 ), 8.00 (s, 1H: H6), 8.65 (d,
J¼9.6, 1H: H4); 13C NMR (TMS, CDCl3,
d, ppm): 51.54 (CH3 from 5,
COOMe), 51.72 (CH3 from 7, COOMe), 105.06 (C5), 114.83 (C3), 119.73
0
0
(C7), 122.82 (C6), 125.05 (C4 ), 128.16 (C4), 128.55 (C2 ), 131.87 (C4a),
0
0
132.33 (C3 ), 134.12 (C1 ), 151.18 (C2), 159.55 (7-CO), 163.92 (5-CO).
Anal. calcd for C17H13BrN2O4 (389.20): C 52.46, H 3.37, N 7.20;
found: C 52.37, H 3.29, N 7.10.
4.3.4. 7-Ethyl, 5-methyl 2-(4-bromophenyl)pyrrolo[1,2-b] pyr-
idazine-5,7-dicarboxylate (3d). Yellowsolid, mp 163–164 ꢂC. IR (KBr,
cmꢁ1): 3070 (C–H arom.), 2948 (C–H aliph.), 1706, 1674 (C]O est.),
1552, 1517, 1473 (C]C, C]N), 1242, 1203 (C–O–C), 821 (C–Br). 1H
4.3. General procedure for [3D2] dipolar cycloaddition in the
solid phase
NMR (DMSO,
d
, ppm, J, Hz): 1.40(t, J¼6.8, 3H: CH3–CH2), 3.88 (s, 3H:
CH3 from 5 position), 4.38 (q, J¼6.8, 2H: CH2–CH3), 7.77 (dd, J¼8.4,
0
3-(4-Halophenyl)-pyridazinium bromide (2 mmol), dipolar-
ophile (2.1 mmol) and 15 g of mineral support (KF–Al2O3) were
ground in an agate mortar until a fine homogeneous mixture was
obtained. The mixture was heated under conventional conditions
(oil bath) or exposed to microwaves. The mixture was exposed to
microwaves for 15 min. using 20% power of the magnetron. The
activated solid was cooled, then washed four times: three times
with 10 mL of dichloromethane and once with 10 mL of acetone.
The acetone and dichloromethane were then evaporated and the
product was purified by chromatography on silica gel with
dichloromethane/methanol (99/1) as eluent.
J¼2.0, 2H: H3 ), 7.81 (s,1H: H6), 7.91 (d, J¼9.6,1H: H3), 8.09 (dd, J¼8.4,
J¼2.0, 2H: H2 ), 8.58 (d, J¼9.6, 1H: H4); 13C NMR (TMS, DMSO,
d,
0
ppm): 13.90 (CH3–CH2), 51.05 (CH3 from 5, COOMe), 59.93 (CH2),
0
104.00 (C5), 115.42 (C3), 119.29 (C7), 121.48 (C6), 123.96 (C4 ), 127.51
0
0
0
(C4), 128.50 (C2 ), 130.98 (C4a), 131.74 (C3 ), 133.56 (C1 ), 150.27 (C2),
157.85 (7-CO),162.65 (5-CO). Anal. calcd for C18H15BrN2O4 (403.23):
C 53.62, H 3.75, N 6.95; found: C 53.57, H 3.69, N 6.83.
4.3.5. Trimethyl 2-(4-chlorophenyl)pyrrolo[1,2-b]pyridazine-5,6,7-
tricarboxylate (4a). White solid, mp 185–186 ꢂC. IR (KBr, cmꢁ1):
3109 (C–H arom.), 2954 (C–H aliph.), 1743, 1716, 1685 (C]O est.),
1550, 1523, 1488, 1442 (C]C, C]N), 1255, 1209, 1178 (C–O–C), 817
4.3.1. Dimethyl 2-(4-chlorophenyl)pyrrolo[1,2-b]pyridazine-5,7-di-
carboxylate (3a). White solid, mp 225–226 ꢂC. IR (KBr, cmꢁ1): 3112
(C–H arom.), 2950 (C–H aliph.), 1728, 1697 (C]O est.), 1552, 1465,
1406 (C]C, C]N), 1245, 1199 (C–O–C), 810 (C–Cl). 1H NMR (CDCl3,
(C–Cl). 1H NMR (CDCl3,
d, ppm, J, Hz): 3.92 (s, 3H: CH3 from 5
position), 3.96 (s, 3H: CH3 from 7 position), 4.02 (s, 3H: CH3 from 6
0
position), 7.49 (dd, J¼8.4, J¼2.0, 2H: H3 ), 7.57 (d, J¼9.6,1H: H3), 8.02
(dd, J¼8.4, J¼2.0, 2H: H2 ), 8.64 (d, J¼9.6, 1H: H4); 13C NMR (TMS,
0
d, ppm, J, Hz): 3.93 (s, 3H: CH3 from 5 position), 3.97 (s, 3H: CH3
CDCl3, d, ppm): 51.97 (CH3 from 5, COOMe), 52.21 (CH3 from 7,
0
from 7 position), 7.52–7.47 (m, overlapped peaks, 3H: 2H3 , 1H3),
COOMe), 53.05 (CH3 from 6, COOMe),102.85 (C5), 115.99 (C3),117.45
0
0 0
(C6), 128.39 (C2 ), 128.53 (C4), 128.93 (C7), 129.44 (C3 ), 130.63 (C4a),
7.99 (s, 1H: H6), 8.04 (dd, J¼8.8, J¼2.0, 2H: H2 ), 8.64 (d, J¼9.2, 1H:

282
G. Zbancioc, I.I. Mangalagiu / Tetrahedron 66 (2010) 278–282
0
0
133.25 (C1 ), 137.00 (C4 ), 151.99 (C2), 158.64 (7-CO), 162.72 (5-CO),
165.59 (6-CO). Anal. calcd for C19H15ClN2O6 (402.79): C 56.66, H
3.75, N 6.95; found: C 56.62, H 3.69, N 6.89.
(C]O est.), 1552, 1519, 1479, 1440 (C]C, C]N), 1230, 1180, 1141 (C–
O–C), 817 (C–Br). 1H NMR (CDCl3,
CH3–CH2), 3.92 (s, 3H: CH3 from 5 position), 4.01 (s, 3H: CH3 from 6
d
, ppm, J, Hz): 1.42(t, J¼7.2, 3H:
position), 4.43 (q, J¼7.2, 2H: CH2–CH3), 7.55 (d, J¼9.6, 1H: H3), 7.64
0
0
4.3.6. 7-Ethyl, 5,6-dimethyl 2-(4-chlorophenyl)pyrrolo[1,2-b] pyr-
idazine-5,6,7-tricarboxylate (4b). White solid, mp 142–143 ꢂC. IR
(KBr, cmꢁ1): 3066 (C–H arom.), 2954 (C–H aliph.), 1739, 1699 (C]O
est.), 1552, 1483, 1442 (C]C, C]N), 1232, 1188, 1133 (C–O–C), 819
(dd, J¼8.4, J¼2.0, 2H: H3 ), 7.95 (dd, J¼8.4, J¼2.0, 2H: H2 ), 8.63 (d,
J¼9.6, 1H: H4); 13C NMR (TMS, CDCl3,
d, ppm): 14.18 (CH3–CH2),
51.95 (CH3 from 5, COOMe), 52.92 (CH3 from 6, COOMe), 61.17
0
(CH2), 102.81 (C5), 115.79 (C3), 125.35 (C4 ), 126.78 (C6), 128.53 (C4),
(C–Cl). 1H NMR (CDCl3,
d
, ppm, J, Hz): 1.42(t, J¼7.2, 3H: CH3–CH2),
128.60 (C2 ), 128.89 (C7), 130.59 (C4a), 132.38 (C3 ), 133.77 (C1 ),
151.97 (C2), 158.17 (7-CO), 162.75 (5-CO), 165.58 (6-CO). Anal. calcd
for C20H17BrN2O6 (461.26): C 52.08, H 3.71, N 6.07; found: C 52.04, H
3.64, N 5.99.
0
0
0
3.92 (s, 3H: CH3 from 5 position), 4.01 (s, 3H: CH3 from 6 position),
0
4.43 (q, J¼7.2, 2H: CH2–CH3), 7.49 (dd, J¼8.4, J¼2.0, 2H: H3 ), 7.56 (d,
0
J¼9.6,1H: H3), 8.02 (dd, J¼8.4, J¼2.0, 2H: H2 ), 8.63 (d, J¼9.6,1H: H4);
13C NMR (TMS, CDCl3,
d, ppm): 14.15 (CH3–CH2), 51.92 (CH3 from 5,
COOMe), 52.90 (CH3 from 6, COOMe), 61.14 (CH2),102.74 (C5),115.83
0
0
(C3), 117.61 (C6), 128.34 (C2 ), 128.48 (C4), 128.84 (C7), 129.38 (C3 ),
References and notes
0
0
130.55 (C4a), 133.27 (C1 ), 136.93 (C4 ), 151.87 (C2), 158.14 (7-CO),
162.73 (5-CO), 165.57 (6-CO). Anal. calcd for C20H17ClN2O6 (416.81):
C 57.63, H 4.11, N 6.72; found: C 57.60, H 4.03, N 6.67.
1. Valeur, B. Molecular Fluorescence; Wiley-VCH: Weinheim, 2002.
2. Lee, S.; Nakamura, T.; Tutsui, T. Org. Lett. 2001, 3, 2005–2007.
3. McQuade, D. T.; Pullen, A. E.; Swager, T. M. Chem. Rev. 2000, 100, 2537–2574.
4. (a) Vasilescu, M.; Bandula, R.; Cramariuc, O.; Hukka, T.; Lemmetyinen, H.;
Rantala, T.; Dumitrascu, F. J. Photochem. Photobiol., A 2008, 194, 308–317; (b)
Swamy, K. M. K.; Park, M. S.; Han, S. J.; Kim, S. K.; Kim, J. H.; Lee, C.; Bang, H.;
Kim, Y.; Kima, S. J.; Yoona, J. Tetrahedron 2005, 61, 10227–10234; (c) Mitsumori,
T.; Craig, I. M.; Martini, I. B.; Schwartz, B. J.; Wudl, F. Macromolecules 2005, 38,
4698–4704; (d) Mitsumori, T.; Bendikov, M.; Sedo, J.; Wudl, F. Chem. Mater.
2003, 15, 3759–3768.
5. Loupy, A. Microwaves in Organic Synthesis; Wiley-VCH: Weinheim, Germany,
2006.
6. Kappe, C. O.; Stadler, A. Microwaves in Organic and Medicinal Chemistry; Wiley-
VCH: Weinheim, Germany, 2005.
7. Tierney, J. T.; Lindstro¨m, P. Microwave-assisted Organic Synthesis; Blackwell:
Oxford, UK, 2005.
8. Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250–6284.
9. Bogdal, D. Molecules 1999, 4, 333–337.
4.3.7. Trimethyl 2-(4-bromophenyl)pyrrolo[1,2-b]pyridazine-5,6,7-
tricarboxylate (4c). White solid, mp 177–178 ꢂC. IR (KBr, cmꢁ1):
3087 (C–H arom.), 2954 (C–H aliph.), 1743, 1716, 1685 (C]O est.),
1591, 1548, 1488, 1442 (C]C, C]N), 1253, 1209, 1178 (C–O–C), 815
(C–Br). 1H NMR (CDCl3,
d, ppm, J, Hz): 3.92 (s, 3H: CH3 from 5
position), 3.97 (s, 3H: CH3 from 7 position), 4.02 (s, 3H: CH3 from 6
0
position), 7.54 (d, J¼9.6,1H: H3), 7.66 (dd, J¼8.4, J¼2.0, 2H: H3 ), 7.95
(dd, J¼8.4, J¼2.0, 2H: H2 ), 8.65 (d, J¼9.6, 1H: H4); 13C NMR (TMS,
0
CDCl3, d, ppm): 51.98 (CH3 from 5, COOMe), 52.22 (CH3 from 7,
COOMe), 53.05 (CH3 from 6, COOMe), 102.88 (C5), 115.93 (C3),
125.40 (C6), 128.58 (C4), 128.62 (C2 ), 128.95 (C7), 130.66 (C4a),
0
0
0
10. Lidstro
¨m, P.; Tierney, J.; Wathey, B.; Westman, J. Tetrahedron 2001, 57,
132.42 (C3 ), 133.74 (C1 ), 152.09 (C2), 158.65 (7-CO), 162.73 (5-CO),
165.58 (6-CO). Anal. calcd for C19H15BrN2O6 (447.24): C 51.03, H
3.38, N 6.26; found: C 50.98, H 3.32, N 6.17.
9225–9283.
11. Zbancioc, G. N.; Mangalagiu, I. I. Synlett 2006, 804–806.
12. Dima, St.; Zbancioc, G. N.; Mangalagiu, I. I. J. Serb. Chim. Soc. 2006, 71, 103–110.
13. Zbancioc, Ghe.; Caprosu, M.; Moldoveanu, C.; Mangalagiu, I. I. Rev. Roum. Chim.
2005, 50, 353–358.
14. Zbancioc, Ghe.; Caprosu, M.; Moldoveanu, C.; Mangalagiu, I. I. ARKIVOC 2005, 5,
174–187.
4.3.8. 7-Ethyl, 5,6-dimethyl 2-(4-bromophenyl)pyrrolo[1,2-b] pyr-
idazine-5,6,7-tricarboxylate (4d). White solid, mp 151–152 ꢂC.
IR (KBr, cmꢁ1): 3103 (C–H arom.), 2952 (C–H aliph.), 1737, 1697
15. Kro¨hnke, F. Ber. Dtsch. Chem. Ges. 1935, 68, 1177.