Synthesis of pyridazinedione derivatives starting from anhydrides of 2,3-pyridine-and 2,3-quinolinedicarboxylic acids

Article abstract of DOI:10.1134/S1070428010050210

A method was developed of preparation of heterocyclic compounds with pyridopyridazinoiso-quinalinedione and isoquinopyridazinoquinalinedione structures formed regioselectively by intramolecular cyclization of phosphorus ylides containing pyridopyridazinedione and pyridazinoquinolinedione fragments. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S1070428010050210

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 5, pp. 716−721. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © I.M. Sakhautdinov, O.R. Tukhvatullin, A.A. Fatykhov, F.Z. Galin, 2010, published in Zhurnal Organicheskoi Khimii,
2010, Vol. 46, No. 5, pp. 723−727.
Synthesis of Pyridazinedione Derivatives Starting
from Anhydrides of 2,3-Pyridine-
and 2,3-Quinolinedicarboxylic Acids
I. M. Sakhautdinova, O. R. Tukhvatullina, A. A. Fatykhova, and F. Z. Galina,b
aInstitute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences,
Ufa, 450054, Russia; ε-mail: ims@anrb.ru
bBashkir State University, Ufa, Russa
Received June 2, 2009
Abstract—A method was developed of preparation of heterocyclic compounds with pyridopyridazinoiso-
quinalinedione and isoquinopyridazinoquinalinedione structures formed regioselectively by intramolecular
cyclization of phosphorus ylides containing pyridopyridazinedione and pyridazinoquinolinedione fragments.
DOI: 10.1134/S1070428010050210
Pyridazine derivatives are extremely rare in the natural
objects [1, 2]. Some among them exhibit high biological
action, for instance, Galavit is an immuno-modulator of
the new generation and is successfully used in the
treatment of acute infectious and chronic inflam-matory
diseases [3–5]. The extension of the application field of
pyridazinedione derivatives for the synthesis of new
heterocyclic compounds is very promising.
It was shown formerly [6–9] thet keto-stabilized
phosphonium ylides prepared from the N-protected α- and
β-amino acids underwent the intramolecular cyclization.
We performed through phosphorus ylides the preparation
of products I, II with a pyridazinedione fragment starting
from 2,3-pyridine- and 2,3-quinolinedicarboxylic acids
anhydrides.
The synthesis of compound with the pyridopyridazino-
Scheme 1.
Bn
N
O
O
O
O
N
Y
X
Br
X
o-BrCH2N6D4COCl
NH2NHBn
NH
N
O
Et3N, CH2Cl2
O
Y
N
Bn
O
O
VIIa, VIIb, 86%
IV
IIIa, IIIb
O
Bn
Y
O
O
Y
O
N
O
Ph
P
Ph
N
Br
Ph
NaH
THF
X
N
Ph
X
N
P
PPh3
PhH
N
O
N
O
N
Ph
Ph
Bn
Bn
IXa, IXb, 75%
XIa, XIb, 81%
I
X = N, Y = CH (a); Y = N, X = CH (b); a : b = 2 : 1.
716

SYNTHESIS OF PYRIDAZINEDIONE DERIVATIVES
717
isoquinolidinedione structure I was carried out using the atoms of the oxo groups in the 13C NMR spectra. For
mixture of benzyl-substituted 2,3-dihydropyrido[2,3-d]- instance, the intense signals of the carbamide carbon
pyridazine-5,8-diones (IIIa, IIIb) obtained by direct atoms were observed at δ 167.83 (IIIa) and 168.97 ppm
melting of benzylhydrazine with 2,3-pyridinedicarboxylic
acid anhydride (IV) (Scheme 1).
(Va), whereas the less intense signals of more electron-
deficient carbamide carbon atoms in the β-position to the
nitrogen atom of the pyridine ring (IIIb) and quinoline
fragment (Vb) appeared upfield at δ 164.38 (IIIb) and
164.35 ppm (Vb) [10]. According to the 13C NMR data
the major isomers were compounds IIIa and Va; the
precise isomers ratio was determined from the
comparison of the integral intensities of the signals in the
1H NMR spectra.
The synthesis of compounds with the isoquino-
pyridazinoquinolinedione structure II was based on the
analogously obtained from benzylhydrazine and 2,3-
quinolinedicarboxylic acid anhydride (VI) benzyl-
substituted 2,3-dihydropyridazino[4,5-b]-quinoline-1,4-
diones (Va, Vb) (Scheme 2).
The structure of compounds IIIa, IIIb and Va, Vb
1
The acylation of the mixtures of benzyl-substituted
2,3-dihydropyrido[2,3-d]pyridazine-5,8-diones (IIIa, IIIb)
and 2,3-dihydropyridazino[4,5-b]quinoline-1,4-diones (Va,
Vb) with o-bromomethylbenzoyl chloride resulted in
benzyl bromides VIIa, VIIb and VIIIa, VIIIb in
an overall yield 86 and 83% respectively. These products
react with PPh3 in dry benzene to give phosphonium salts
IXa, IXb and Xa, Xb. The deprotonation of the latter
with NaH in THF under an argon atmosphere afforded
phosphorus ylides XIa, XIb and XIIa, XIIb in an overall
was confirmed by spectral methods. In the H NMR
spectra the informative signals are the singlets of the
methylene group of the benzyl fragment in the region δ
5.23 (IIIa), 5.21 (IIIb), 5.29 (Va), 5.21 ppm (Vb), and
also the signals of the NH group protons in the region δ
9.02 (IIIa), 8.68 (IIIb), 9.28 (Va), 8.83 ppm (Vb). It
was established from the integral intensity of the signals
1
belonging to the isomers in the H NMR spectra that
their ratio was 1:2. The structure of the prevailing isomer
was revealec from the characteristic signals of the carbon
Scheme 2.
Bn
N
O
O
O
O
O
N
Y
Br
N
NH2NHBn
o-BrCH2C6H4COCl
NH
N
O
Et3N, CH2Cl2
O
Y
X
Bn
N
O
Va, Vb
VI
VIIIa, VIIIb, 83%
Bn
O
N
O
Y
Bn
N
O
Ph
Ph
P
N
O
N
Br
Ph
NaH
THF
PPh3
PhH
P
X
Ph
X
Ph
Ph
O
O
Y
XIIa, XIIb, 93%
Xa, Xb, 68%
O
N
Bn
Bn
O
X
Y
N
O
O
N
N
N
O
XIIIa, XIIIb, 37%
X = N, Y = CH (a); Y = N, X = CH (b); a : b = 2 : 1.
II
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010

SAKHAUTDINOV et al.
718
EXPERIMENTAL
yield 81 and 93% respectively.
The structures of all compounds obtained were
confirmed by their spectra. In the H NMR spectra the
IR spectra were recorded on a spectrophotometer
Specord M-80 (from thin films or mulls in mineral oil).
NMR spectra were registered on a spectrometer Bruker
AM-300 at operating frequencies 300.13 MHz (1H), 75.25
MHz (13C), internal reference TMS. The reaction
progress was monitored by TLC on Sorbfil PTLC-AF-A
plates, spots were visualized with UV irradiation, iodine
vapor, spraying the plates with ninhydrine or anisaldehyde
followed by heating at 100–120°C. The reaction products
were isolated by column chromatography on silica gel
(eluent petroleum ether–ethyl acetate, 4:1). We did not
isolate compounds IIIa, IIIb, Va, Vb, VIIa, VIIb, VIIIa,
VIIIb, IXa, IXb, Xa, Xb, XIa, XIb, XIIa, XIIb, XIIIa,
XIIIb in an individual state and used them in subsequent
reactions as isomer mixtures.
1
most informative signal is the two-proton singlet of the
CH2Br group in the region δ 4.79 (VIIa, VIIb) and
5.28 ppm (VIIIa, VIIIb); in the 13C NMR spectrum the
corresponding carbon atom gives rise to the signal at δ
31.33 (VIIa, VIIb) and 30.78 ppm (VIIIa, VIIIb). At
1
the same time in the H NMR spectra of compounds
XIa, XIb and XIIa, XIIb the characteristic doublet
signals of ylide groups were observed in the region δ
4.33, 4.37 and 5.09, 5.21 ppm respectively.
The heating of phosphorus ylides XIa, XIb and XIIa,
XIIb in boiling dioxane led to the formation of polycyclic
compounds I and II in the yield not exceeding 9%.
However the use of ionic liquid, 1-butyl-3-methylimid-
azolium tetrafluoroborate [bmim][BF4] increased the yield
of the target products to 42% with respect to compounds
XIb and XIIb. The boiling of compounds XIIa, XIIb in
1,4-dioxane in the presence of a catalytic amount of
benzoic acid resulted in the formation of methylbenzoyl-
pyridazinoquinolinediones XIIIa, XIIIb in an overall yield
37%.
Dihydropyridopyridazinediones IIIa, IIIb and
dihydropyridazinoquinolinediones Va, Vb. A mixture
of 4.6 mmol of anhydride and 4.6 mmol of
benzylhydrazine was heated for 15 min at the temperature
of the oil bath of 155–160°C. On cooling the solid reaction
product was reprecipitated from methanol. The separated
precipitate was filtered off and washed with ether.
The structures of compounds I and II were proved
by NMR spectra. For instance, in the 13C NMR spectra
of compounds I and II appeared the signals of carbon
atoms at multiple bond in the region δ 105.86, 132.74 (I)
7-Benzyl-6,7-dihydropyrido[2,3-d]pyridazine-
5,8-dione (IIIa), 6-benzyl-6,7-dihydropyrido[2,3-
d]pyridazine-5,8-dione (IIIb). Overall yield 79%, mp
1
95–101°C. H NMR spectrum, δ, ppm, (IIIa): 5.23 s
1
and 105.89, 132.75 ppm (II); in the H NMR spectra
(2H, CH2), 7.18–7.65 m (5H, C6H5), 7.51–9.08 m (3H,
C6H3N), 9.02 s (1H, NH); (IIIb): 5.21 s (2H, CH2), 7.18–
7.65 m (5H, C6H5), 7.51–9.08 m (3H, C6H3N), 8.68 s
(1H, NH). 13C NMR spectra, δ, ppm, (IIIa): 55.06 (CH2),
128.97, 130.01, 130.27 (CHarom), 130.53 (Carom), 130.62
(CHarom), 134.03 (Carom), 138.56 (CHarom), 149.97 (N=C),
150.95 (N=C.), 158.43(C=O), 167.83(C=O); (IIIb): 54.8
(CH2), 128.48, 128.97, 130.27, 130.62 (CHarom), 130.85
(Carom), 134.46 (Carom), 136.42 (CHarom), 151.18 (N=C),
152.25 (N=C), 156.16 (C=O), 164.38 (C=O).
informative signals were those of the protons of the
formed double bonds in the region δ 6.62 ppm. The
formation of regioisomers I and II in the course of the
intramolecular cyclization at the more electron-deficient
carbon atom was proved by the NOE experiment. For
instance, in compound I the irrariation of the singlet signal
of the hydrogen at the double bond (δH 6.62 ppm) did
not produce a considerable Overhauser effect on the
pyridine proton. Analogous behavior was also observed
in compound II.
3-Benzyl-2,3-dihydropyridazino[4,5-b]quinoline-
1,4-dione (Va), 2-benzyl-2,3-dihydropyridazino[4,5-
b]quinoline-1,4-dione (Vb). Overall yield 87%, mp 173–
178°C. 1H NMR spectra, δ, ppm, (Va): 5.29 s (2H, CH2),
7.23–7.36 m (5H, C6H5), 7.46–8.38 m (5H, C9H5N), 9.28
s (1H, NH); (Vb): 5.21 s (2H, CH2), 7.23–7.36 m (5H,
C6H5), 7.46–8.38 m (5H, C9H5N), 8.83 s (1H, NH). 13C
NMR spectra, δ, ppm, (Va): 56.16 (CH2), 126.23 (Carom),
129.32, 129.76, 130.1, 130.33, 130.41, 130.56 (CHarom),
133.51 (Carom), 137.93 (CHarom), 139.29 (Carom), 140.21
Hence we synthesized compounds of pyrido-
pyridazinoisoquinolinedione (I) and isoquinopyridazino-
quinolinedione (II) structures from phosphorus ylides
prepared starting from 2,3-pyridine- and 2,3-quinolinedi-
carboxylic acid anhydrides. It was established that
employing the ionic liquid [bmim][BF4] at the intra-
molecular cyclization of phosphorus ylides by Wittig
reaction significantly increased the yield of the target
products.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010

SYNTHESIS OF PYRIDAZINEDIONE DERIVATIVES
719
(CHarom), 154.57 (N=C), 157.08 (N=C), 160.09 (C=O),
168.97 (C=O); (Vb): 56.3 (CH2), 127.73 (Carom), 129.32,
129.76, 129.96, 130.33, 130.41, 130.68, 135.82 (CHarom),
136.4 (Carom), 137.03 (Carom), 142.84 (CHarom), 153.56
(N=C), 156.47 (N=C), 160.03 (C=O), 164.35 (C=O).
7.75 m (4H, C6H4), 7.22–7.57 m (5H, C6H5), 7.56–
8.58 m (4H, C6H4), 8.67 s (1H, C6HN); (VIIIb): 5.28 s
(2H, CH2), 5.42 s (2H, CH2), 7.21–7.75 m (4H, C6H4),
7.22–7.57 m (5H, C6H5), 7.56–8.58 m (4H, C6H4), 9.31
s (1H, C6HN). 13C NMR spectra, δ, ppm, (VIIIa): 31.08
(CH2Br), 54.87 (CH2), 126.34 (Carom), 127.89, 128.27,
128.53, 128.61, 128.84, 128.91, 129.03, 129.19, 129.37,
129.57 (all CHarom), 130.32 (Carom), 132.15 (CHarom),
132.26 (CHarom), 133.10, 133.61, 134.25, 136.24, 140.86
(Carom), 143.84 (C=O Ht), 150.62 (C=O, Ht), 163.83
(C=O, Bz); (VIIIb): 30.78 (CH2Br), 54.55 (CH2), 125.70
(Carom), 127.55 (Carom), 127.89 (CHarom), 128.27, 128.53,
128.61, 128.84, 128.91, 129.03, 129.19, 129.37, 131.04
(CHarom), 132.04 (Carom), 132.15 (CHarom), 132.26
(CHarom), 133.61, 133.93, 138.15, 140.25 (Carom), 143.04
(C=O, Ht), 150.45 (C=O, Ht), 158.08 (C=O, Bz). Found,
%: C 62.43; H 3.66; Br 15.94; N 8.38. C26H18BrN3O3.
Calculated, %: C 62.41; H 3.63; Br 15.97; N 8.40.
Benzyl bromides VIIa, VIIb, VIIIa, VIIIb. To
a dispersion of 1.65 mmol of o-bromomethylbenzoic acid
in 15 ml of dry benzene was added 4.95 mmol of thionyl
chloride, and the mixture was heated at reflux to the end
of gas liberation (~6 h). On evaporation of the solution
the acid chloride was brought into further reaction without
additional purification. The solution of the acid chloride
in 5 ml of dichloromethane was at cooling and stirring
slowly added dropwise over 39 min to a dispersion of
1.65 mmol of compound IIIa, IIIb or Va, Vb and 1.65
mmol of Et3N in 20 ml of dichloromethane, the mixture
was stirred for 1 h more at room temperature and left
standing for 24 h. The formed solution was washed with
1N HCl, the organic layer was dried with MgSO4. The
solvent was distilled off, the oily residue was subjected
to column chromatography on silica gel (eluent
chloroform–acetone, 9:1).
Phosphonium salts IXa, IXb, Xa, Xb. To a solution
of 1.2 mmol of an appropriate benzyl bromide in 10 ml
of dry benzene was added in one portion at stirring
1.32 mmol of triphenylphosphine dissolved in 5 ml of
benzene. The reaction mixture was stirred for 2 h nad
then it was heated at refluxfor 6 h. The precipitate formed
in the course of the reaction was filtered off, washed
with benzene and left to dry in air.
7-Benzyl-6-[2-(bromomethyl)benzoyl]-6,7-di-
hydropyrido[2,3-d]pyridazine-5,8-dione (VIIa),
6-benzyl-7-[2-(bromomethyl)benzoyl]-6,7-dihydro-
pyrido[2,3-d]pyridazine-5,8-dione (VIIb). Overall
yield 86%. 1H NMR spectra, δ, ppm, (VIIa): 4.79 s (2H,
CH2), 4.90 s (2H, CH2), 7.18–7.74 m (9H, C6H4, C6H5),
8.06–9.05 m (3H, C6H3N); (VIIb): 4.79 s (2H, CH2),
5.09 s (2H, CH2), 7.18–7.74 m (9H, C6H4, C6H5), 8.06–
9.05 m (3H, C6H3N). 13C NMR spectra, δ, ppm, (VIIa):
31.33 (CH2Br), 54.49 (CH2), 125.59 (CHarom), 127.75
(Carom), 128.70, 128.86, 128.93, 129.63, 130.68, 131.82,
132.03 (CHarom), 134.36, 135.93, 140.35 (Carom), 145.51
(CHarom), 146.41 (CHarom), 155.24 (Carom), 159.17 (C=O),
160.10 (C=O), 171.05 (C=O); (VIIb): 31.33 (CH2Br),
54.52 (CH2), 125.59 (CHarom), 125.64 (Carom), 126.68,
128.70, 128.86, 128.93, 130.68, 131.82, 132.03 (CHarom),
135.76, 135.93, 139.41 (Carom), 139.92 (CHarom), 146.41
(CHarom), 150.16 (Carom), 155.22 (C=O), 160.02 (C=O),
170.79 (C=O). Found, %: C 58.67; H 3.61; Br 17.71;
N 9.35. C22H16BrN3O3. Calculated, %: C 58.68; H 3.58;
Br 17.75; N 9.33
2-[(7-Benzyl-5,8-dioxo-7,8-dihydropyrido-
[2,3-d]pyridazin-6(5H)-yl)carbonyl]benzyltriphenyl-
phosphonium bromide (IXa) and 2-[(6-benzyl-5,8-
dioxo-5,8-dihydropyrido[2,3-d]pyridazin6(5H)-
yl)carbonyl]benzyltriphenylphosphonium bromide
(IXb). Overall yield 75%, mp 140–142°C. Found, %:
C 67.37; H 4.46; Br 11.28; N 5.98. C40H31BrN3O3P.
Calculated, %: C 67.42; H 4.38; Br 11.21; N 5.90.
2-[(3-Benzyl-1,4-dioxo-3,4-dihydropyrid-
azino[4,5-b]quinoline-2(1H)-yl)carbonyl]benzyl-
(triphenyl)phosphonium bromide (Xa) and 2-[(2-
benzyl-1,4-dioxo-3,4-dihydropyridazino[4,5-
b]quinolin-3(2H)-yl)carbonyl]benzyl(tri-
phenyl)phosphonium bromide (Xb). Overall yield
68%, mp 185–186°C. Found, %: C 69.28; H 4.38; Br 10.45;
N 5.53. C44H33BrN3O3P. Calculated, %: C 69.30; H 4.36;
Br 10.48; N 5.51.
3-Benzyl-2-[2-(bromomethyl)benzoyl]-2,3-
dihydropyridazino[4,5-b]quinoline-1,4-dione
(VIIIa), 2-benzyl-3-[2-(bromomethyl)benzoyl]-2,3-
dihydropyridazino[4,5-b]quinoline-1,4-dione
(VIIIb). Overall yield 83%. H NMR spectra, δ, ppm,
(VIIIa): 5.28 s (2H, CH2), 5.49 s (2H, CH2), 7.21–
Phosphorus ylides XIa,XIb, XIIa, XIIb. To
a dispersion of 1 mmol of phosphonium salt IXa, IXb,
Xa, Xb in 20 ml of THF was added at stirring 3 mmol of
NaH. The reaction mixture was stirred over 1 h, the
separated precipitate was filtered off, the solvent was
distilled off to leave dark-red oily residue.
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010

SAKHAUTDINOV et al.
720
7-Benzyl-6-{2-[(triphenylphosphoranilidene)-
3-Benzyl-2-(2-methylbenzoyl)-2,3-dihydro-
pyridazino[4,5-b]quinoline-1,4-dione (XIIIa), 2-
benzyl-3-(2-methylbenzoyl)-2,3-dihydro-
pyridazino[4,5-b]-quinoline-1,4-dione (XIIIb).
Overall yield 37 (a), mp 153–160°C. 1H NMR spectra,
δ, ppm, (XIIIa): 2.72 s (3H, CH3), 5.48 s (2H, CH2),
7.24–7.74 m (4H, C6H4), 7.31–7.49 m (5H, C6H5), 7.86–
8.54 m (4H, C6H4), 8.52 s (1H, C6HN); (XIIIb): 2.73 s
(3H, CH3), 5.43 s (2H, CH2), 7.24–7.74 m (4H, C6H4),
7.31–7.49 m (5H, C6H5), 7.86–8.54 m (4H, C6H4), 9.31 s
(1H, C6HN). 13C NMR spectra, δ, ppm, (XIIIa): 21.98
(CH3), 54.82 (CH2), 126.22 (Carom), 127.78, 128.33,
128.45, 128.49, 128.74 (CHarom), 129.11 (Carom), 129.41
(Carom), 131.16, 131.67, 131.83, 131.94, 132.08, 132.28
(CHarom), 132.80, 133.84, 142.57, 144.09 (Carom), 150.54
(C=O, Ht), 158.11(C=O, Ht), 164.40 (C=O, Bz); (XIIIb):
21.54 (CH3), 54.50 (CH2), 125.90 (Carom), 126.36 (Carom),
127.78 (CHarom), 128.33 (CHarom), 128.45 (CHarom),
128.49 (CHarom), 128.74 (CHarom), 128.88 (Carom), 131.16
(CHarom), 131.67 (CHarom), 131.83 (CHarom), 131.94
(CHarom), 132.08 (CHarom), 132.28 (CHarom), 133.01
(Carom), 133.18 (Carom), 136.33 (Carom), 143.27 (Carom),
150.23 (C=Oquinoline.), 158.03 (C=Oquinoline.), 164.26
(C=O). Found, %: C 74.13; H 4.57; N 9.95. C26H19N3O3.
Calculated, %: C 74.10; H 4.54; N 9.97.
methyl]benzoyl}-6,7-dihydropyrido[2,3-d]-
pyridazine-5,8-dione (XIa), 6-benzyl-7-{2-[(tri-
phenylphosphoranilidene)methyl]benzoyl}-6,7-
dihydropyrido[2,3-d]pyridazine-5,8-dione (XIb).
1
Overall yield 81%. H NMR spectra, δ, ppm, (XIa):
4.33 s (1H, CH), 5.49 s (2H, CH2), 6.90–7.94 m (24H,
4C6H5, C6H4), 8.07–8.34 m (3H, C6H3N); (XIb): 4.37 s
(1H, CH), 5.45 s (2H, CH2), 6.90–7.94 m (24H, 4C6H5,
C6H4), 8.07–8.34 m (3H, C6H3N).
3-Benzyl-2-{2-[(triphenylphosphoranilid-
ene)methyl]benzoyl}-2,3-dihydropyridazino[4,5-b]-
quinoline-1,4-dione (XIIa), 2-benzyl-3-{2-[(tri-
phenylphosphoranilidene)methyl]benzoyl}-2,3-
dihydropyridazino[4,5-b]quinoline-1,4-dione (XIIb).
1
Overall yield 93%. H NMR spectra, δ, ppm, (XIIa):
5.09 s (1H, CH), 5.38 s (2H, CH2), 6.93–7.75 m (4H,
C6H4), 7.14–7.33 m (5H, C6H5), 7.29–7.64 m (15H,
3C6H5), 7.74–8.49 m (4H, C6H4), 8.97 s (1H, C6HN);
(XIIb): 5.21 s (1H, CH), 5.33 s (2H, CH2), 6.93–7.75 m
(4H, C6H4), 7.14–7.33 m (5H, C6H5), 7.29–7.64 m (15H,
3C6H5), 7.74–8.49 m (4H, C6H4), 9.23 s (1H, C6HN).
Thermolysis of phosphorus ylides XIa,XIb, XIIa,
XIIb. a. To a dispersion of 0.5 mmol of phosphorus ylide
in 10 ml of anhydrous dioxane was added a catalytic
quantity of benzoic acid, and the mixture was refluxed
for 24 h. The solvent was distilled off, the thermolysis
products I and XIIIa, XIIIb were subjected to chromato-
graphy on silica gel (eluent ethyl acetate–petroleum ether,
1:4).
7-Benzyl-5H-isoquino[2',3':2,3]pyridazino-[4,5-
b]quinoline-5,8(7H)-dione (II). Orange oily substance.
Yield 42% (b) with respect to compound XIIb. 1H NMR
spectrum, δ, ppm: 4.32–4.43 m (2H, CH2), 6.62 s (1H,
CH), 7.32–7.63 m (4H, C6H4), 7.16–7.42 m (5H, C6H5),
7.31–7.62 m (4H, C6H4), 8.38 s (1H, C6HN). 13C NMR
spectrum, δ, ppm: 61.50 (CH2), 105.89 (CH=), 120.33
(Carom), 120.93 (Carom), 125.09, 125.73, 125.79, 125.96,
127.52, 128.17, 129.59, 129.69, 129.77, 130.52, 131.74
(CHarom), 132.74 (Carom), 134.80 (CHarom), 134.95, 136.76,
137.48, 138.20, 141.42 (Carom), 155.57 (C=O, Ht), 162.58
(C=O, Bz). Found, %: C 77.38; H 4.27; N 10.43.
C26H17N3O2. Calculated, %: C 77.41; H 4.25; N 10.42.
b. To a dispersion of 0.3 mmol of phosphorus ylide in
10 ml of dry dioxane was added 1 ml of 1-butyl-3-
methylimidazolium tetrafluoroborate [bmim][BF4], and
the reaction mixture was boiled for 24 h. The solvent
was distilled off, the thermolysis products I and II were
isolated by column chromatography on silica gel (eluent
ethyl acetate–petroleum ether, 1:4).
6-Benzyl-6H-pyrido[3',2':4,5]pyridazino[1,6-
b]isoquinoline-5,8-dione (I). Orange oily substance.
The study was carried out under a financial support
of the Council for grants of the President of the Russian
Federation (Program for support of the leading scientific
schools, NSh-1725.2008.3) and of the Presidium of the
Russian Academy of Sciences (Program of basic
research no. 18).
1
Yield 9 (a), 36% (b) with respect to compound XIb. H
NMR spectrum, δ, ppm: 4.22–4.37 m (2H, CH2), 6.62 s
(H, CH), 7.16–7.55 m (9H, C6H5, C6H4), 7.68–8.35 m
(3H, C6H3N). 13C NMR spectrum, δ, ppm: 60.76 (CH2),
105.86 (CH=), 120.31(Carom), 125.79, 125.94, 127.11,
128.19, 129.15, 129.56, 129.75, 130.94, 131.75 (CHarom),
132.74(Carom), 134.78 (CHarom), 136.73, 137.46, 139.83,
146.06 (Carom), 155.56 (C=O), 162.53 (C=O). Found, %:
C 74.82; H 4.24; N 11.93. C22H15N3O2. Calculated, %:
C 74.78; H 4.28; N 11.89.
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