Utility of the pfitzinger reaction in the synthesis of novel quinoline derivatives and related heterocycles

Article abstract of DOI:10.1002/jhet.1607

2-(2-Amino-3,5-dinitrophenyl)-2-oxoacetic acid (2) was obtained from hydrolysis of 5,7-dinitroisatin (1) in alkaline media. A novel quinoxaline derivative (3) was synthesized from the reaction of the same compound (1) with o-phenylenediamine. Reacting 2 with ethyl 3-oxo-3-phenylpropanoate yields 6,8-dinitro-2-phenylquinoline-3,4-dicarboxylic acid (4). Then, 4 was converted into new quinoline-diacylchloride, quinoline-ester, quinoline-dicarboxamide, pyridazine, and pyrroledione derivatives (5, 6a, 6b, 6c, 6d, 7a, 7b, 7c, 7d, 8, 9, 10a, 10b, 10c, 10d, 11a, 11b, 12) with SOCl₂, alcohols, amines, and hydrazines, respectively. The structures of synthesized compounds were clarified by ¹H NMR, ¹³C NMR, IR, mass and elemental analysis methods.

Full text of DOI:10.1002/jhet.1607

224
Utility of the Pfitzinger Reaction in the Synthesis of Novel Quinoline
Vol 51
Derivatives and Related Heterocycles
a
b
c
b
*
Derviş Gök, Rahmi Kasımoğulları, Mustafa Cengiz, and Samet Mert,
aDepartment of Chemistry and Chemical Processing Technologies, Kutahya Vocational School, Dumlupinar University,
43100 Kutahya, Turkey
bDepartment of Chemistry, Faculty of Arts and Sciences, Dumlupinar University, 43100 Kutahya, Turkey
cDepartment of Chemistry, Faculty of Arts and Sciences, Suleyman Demirel University, 32260 Isparta, Turkey
*
E-mail: rahmikasimoglu@hotmail.com
Received September 22, 2011
DOI 10.1002/jhet.1607
Published online 31 October 2013 in Wiley Online Library (wileyonlinelibrary.com).
O2N
O
COOH
O
O
O
O2N
COOH
O2N
O
Ph
OEt
Ac2O
O
NaOH
(aq)
O
N
Ph
N
O2N
N
9
H
NO2
H
2
Ph
NO2
N
-
R
1
4
Ph-NH-NH2
H
O
N
O2N
H2N
H2N
O
O2N
O
NH2
R
NH
N
O2N
N
N
Ph
O
O2N
N
O2N
N
O
Ph
NO2
Ph
3
10a-d
12
2-(2-Amino-3,5-dinitrophenyl)-2-oxoacetic acid (2) was obtained from hydrolysis of 5,7-dinitroisatin (1) in
alkaline media. A novel quinoxaline derivative (3) was synthesized from the reaction of the same compound (1)
with o-phenylenediamine. Reacting 2 with ethyl 3-oxo-3-phenylpropanoate yields 6,8-dinitro-2-phenylquinoline-
3,4-dicarboxylic acid (4). Then, 4 was converted into new quinoline-diacylchloride, quinoline-ester, quinoline-
dicarboxamide, pyridazine, and pyrroledione derivatives (5, 6a–d, 7a–d, 8, 9, 10a–d, 11a–b, 12) with SOCl2,
alcohols, amines, and hydrazines, respectively. The structures of synthesized compounds were clarified by
1H NMR, 13C NMR, IR, mass and elemental analysis methods.
J. Heterocyclic Chem., 51, 224 (2014).
INTRODUCTION
and pyridazine derivatives as candidate drug molecules.
Hence, we intended to contribute to the heterocyclic
chemistry by showing synthetic routes to excellent yield
percentages. To achieve that goal, first, hydrolysis reaction
was performed on 1 in alkali medium. In this reaction,
corresponding dicarboxylic acid derivative (2) was obtained
via the cleavage of isatin ring (Scheme 1).
A new quinoxaline-2-one (3) derivative was synthesized
from the reaction of 1 with o-phenylenediamine in THF at
25ꢀC (Scheme 2). The interaction of 1 with ethyl 3-oxo-3-
phenylpropanoate under the Pfitzinger reaction [25] condi-
tions forms the corresponding quinoline dicarboxylic acid
derivative (4) (Scheme 2). The carbonyl groups of 4 were
activated by treating with SOCl2 (5). In addition, the com-
pound 4 was simply converted to the new ester derivatives
(6a–d) by reacting with various alcohols in which the catalyst
was H2SO4. Novel amide derivatives were synthesized (7a–d)
by the reaction of 5 with various aryl and alkyl amines.
The interaction of 6a and 6d with hydrazine hydrate
yielded the same product (8) (Scheme 2).
Quinoxaline-2-one ring derivatives show various biologi-
cal activities [1–4]. The heterocyclic quinoline ring building
block of many natural compounds is widely used in medici-
nal chemistry. Substituted quinolines possess diverse biolog-
ical activities including antibacterial [5,6], antifungal [7,8],
antiamoebic [9,10], antileishmanial [11,12], antimalarial
[13,14], and antitumor [15,16] activities.
The synthesis and some biological activities of various
pyrroloquinoline (general structure A) and quinoline
dicarboxylic acid (general structure B) derivatives have
also been reported in the literature [17–19]. Among the
quinoline derivatives, pyrrolo[3,4-c]quinolines constitute
an interesting group of physiologically active molecules.
For instance, pyrrolo[3,4-c]quinolines were described as
potential antimalarial [20], cytotoxic agents [21], and
caspase-3 inhibitors [22–24] (Fig. 1).
In the current report, we aimed to show synthesis,
characterization of new quinoline, quinoxaline, pyrrole,
© 2013 HeteroCorporation

January 2014
Quinoline Dicarboxylic Acid
225
A new anhydride derivative (9) was synthesized from
the reaction of 4 with acetic anhydride. Imide derivatives
including the quinoline rings (10a–d) were obtained from
the reaction of 9 with various alkyl and aryl amines. The
reaction of the same compound (9) with aryl diamines
yielded symmetric imide derivatives (11a–b) (Scheme 3).
N-Aminopyrrole derivative (10e) was obtained from the
reaction of 9 with hydrazine hydrate in benzene, whereas
the reaction of 9 with phenylhydrazine gave a pyridazine
derivative (12) under the same conditions (Scheme 4).
RESULTS AND DISCUSSION
In the current study, further stage reaction of indole-2,3-
dione (isatin) was performed. Thus, novel derivatives of
quinoxaline, quinoline, pyridazinoquinoline, and pyrroloqui-
noline ring systems were systematically synthesized. The
structures of the synthesized molecules were characterized
1
by different techniques. H NMR and 13C NMR spectros-
copy were employed to elucidate the chemical structures,
whereas FTIR was applied for determining the frequencies
of functional groups such as C═O and C═N. Molecular
weight of some compounds was determined with
LC/MS analysis. Elemental analysis was useful in deter-
mining variation of the fractions of elements that form
the compounds.
Compound 2 was obtained from alkaline hydrolysis of
5,7-dinitroindole-2,3-dione (1). This compound (2) con-
verted back to 1 after reacting with SOCl2. In this reaction,
first, acyl chloride of 2 was formed. Second, amino group
of the same compound attacked the acyl carbonyl yielding
back the starting compound (1) (Scheme 1).
I
R2
COOH
O
II
4
N
O2N
COOH
3
R1
O
N
2
Ph
1
N
R3
NO2
A
B
Figure 1. Structures of pyrrolo[3,4-c]quinoline and quinoline-3,4-dicar-
boxylic acid.
On the other hand, one of the amino groups of
o-phenylenediamine attack the carbonyl group of 1 at the
C-3 position. Elimination of one mol water formed an
intermediate compound. Then, other amino group attack
the carbonyl group at the C-2 position. Finally, rearrange-
ment of the molecule led to novel indolo-[3,2-b]-quinoxaline
derivative (3) (Figure 2).
Scheme 1. The cleavage of isatin ring.
1) NaOH(aq),
2) HCl
rt / 4h
O
OH
O
O
O2N
O2N
O
The synthesis of b-dicarboxylic acid derivative (4) was
performed under the Pfitzinger reaction conditions. In this
reaction, first, 1 was hydrolyzed in alkaline media. Second,
amino group of the hydrolysis product formed a Schiff
N
NH2
H
NO2
NO2
SOCl2
1
2
Scheme 2. Synthetic route of novel quinoline-3,4-dicarboxylic acid and quinoxaline derivatives.
O
RHN
Cl
O
O
O
COOH
O
O
O
O2N
O2N
O2N
COOH
Ph
O2N
NHR
Cl
EtO
Ph
SOCl2
NH2-R
O
80 oC / 5h
1) NaOH(aq) / 40 oC / 6 h
2) HCl
N
Ph
N
Ph
N
N
H
NO2
NO2
5
4
NO2
NO 2
1
7a-d
CH3(CH2)3OH
reflux / 8 h
R
1
-O H
7a: R= H
7b: R= (CH2)2CH3
7c: R= CH(CH3)2
reflu x / 8 h
NH2
THF
rt / 48h
Bu
O
7d
: R= Ph
R1
O
O
O
O
O
NH
2
O2N
OH
Bu
O
O2N
H
N
N
Ph
O
N
Ph
NO2
6a-c
NO2
H
N
O2N
6d
O
6a: R1= CH3
6b: R1= CH2CH3
6c: R1= CH(CH3)2
N
NH
O2N
NH2
NH2NH2 H2O
toluene / reflux / 5h
O
NH2NH2 H2O
6a
NO 2
toluene / reflux / 5h
N
Ph
3
NO2
8
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D. Gök, R. Kasımoğulları, M. Cengiz, and S. Mert
Vol 51
Scheme 3. Synthesis of various pyrrolo[3,4-c]quinoline derivatives.
H2N
O
O
O2N
NH2
NH3
Benzene / rt, 3h /reflux, 2h
N
Ph
O
6a
NO2
O2N
R2
Ph
N
O
O
COOH
O
R2-NH2
O2N
COOH
O2N
O
Ac2O
Benzene
N
85 oC / 8h
N
Ph
N
Ph
10a-d
NO2
9
NO2
NO2
4
10a
10b
: R2 = CH2CH2CH3
: R2 = CH(CH3)2
10c: R2 = Ph
10d: R2 = PhF(3)
NO2
NO2
NH -R -N
H2
reflux / 24 h
O2N
2
3
O
O
11a
: R3 =
NO2
N
R3
N
N
N
11b: R3 =
O
O
Ph
Ph
11a-b
Scheme 4. Synthesis of pyrrolo[3,4-c]quinoline and pyridazino[4,5-c]quinoline derivatives.
H
N
O
NH
Ph
O2N
O
N
NO2
8
O
NH2
O
O
NH2NH2
N
O2N
O
benzene / rt / 5h
O2N
O
N
Ph
N
Ph
NO2
NO2
10e
9
H
O
N
Ph
O
N
O2N
NH2NH-Ph
benzene / reflux / 4h
N
Ph
NO2
12
base by the reaction with ketone carbonyl of ethyl benzoyl
acetate. Then, the rearranged Schiff base turned into an
enaminone derivative. And then, sodium salt of 4 formed
after the elimination of water and cyclocondensation
reaction. Finally, this salt turned into a dicarboxlic acid
(4) after the addition of HCl (Fig. 3).
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Quinoline Dicarboxylic Acid
227
N
O
H2N
H2N
O2N
O2N
NH2
O
O
+
-H2O
N
H
N
H
NO2
NO2
N
N
N
O2N
O2N
NH
NH
H
O2N
NH
O
O
N
H
OH
NH2
N
H
NO2
NO2
3
NO2
Figure 2. The reaction mechanism for quinoxaline-2-one derivative.
O
O-Na+
O
O-Na+
Ph
O
O2N
Ph
O
O
O2N
O2N
O
O
O
O
NaOH(aq)
-EtOH
O
+
+
O
N
-H2O
N
NH2
O2N
+Na-O
H
EtO
O-Na+
Ph
O
NO2
1
NO2
O-Na+
O
+Na-O
O
HO
O
O
O
O2N
H+
O2N
O2N
O-Na+
OH
Ph
NH
O
-H2O
N
N
Ph
O2N
O-Na+
Ph
NO2
NO2
4
Figure 3. The reaction mechanism for quinoline-3,4-dicarboxylic acid synthesized via Pfitzinger reaction.
Interestingly, it was observed that in the reaction of 4
with alcohols having lower molecular weight and lower
boiling point (such as methanol, ethanol, and 2-propanol)
with H2SO4 catalyst, only one of the carboxyl group
yielded an ester (6a–c) molecule. However, after the
reaction of the same compound (4) with butanol having
higher molecular weight and higher boiling point, both
carboxyl groups have given esters (6d).
In mono esterification reactions of dicarboxylic acid
(general structure B) (Fig. 1), it was considered that esterifi-
cation occurred at the carboxyl group adjacent to the C-4 of
quinoline ring. Because of the mesomeric effect of the
phenyl group of 4 substituting to the C-2 position, the C-4
position in quinoline ring became less electronegative.
Consequently, the carbonyl group next to the C-4 position
(I) also turned out to be less electronegative. Thus, this
carbonyl group (I) had higher activity for the possible nucle-
ophilic attacks compared with the other carboxyl group (II)
(Fig. 1). Because alcohol molecules are more nucleophilic,
the alcohol molecules attack the I position of 4 first.
Consequently, 6a–c compounds were formed including
an ester in I position and also a carboxylic acid in II position
(Scheme 3).
The spectroscopic data depicted that same product (6a)
was obtained by the reaction of both 5 and 9 with NH3
(see Experimental).
An anhydride derivative (9) was formed in high yield
(92%) and purity from intramolecular cyclocondensation of
4 in acetic anhydride at 85ꢀC. The structure of the product
was confirmed by spectral data. Characteristic absorption
bands were observed at 3100cmꢁ1 (aromatic CH), 1788
and 1706cmꢁ1 (anhydride C═O), and 1618–1455 cmꢁ1
1
(aromatic C═C and C═N). In H NMR spectrum of 9,
the peak at 12.05 ppm arising from the COOH group
was not observed. In 13C NMR spectrum, the peaks at
169.64 and 165.96ppm indicated the existence of two
C═O groups having different chemical environments.
The LC/MS results have confirmed the molecular
weight. LC-MSD m/z = 365.9 [M+ H]+ Anal. Calcd for,
C17H7N3O7: 365.25 g/mol.
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D. Gök, R. Kasımoğulları, M. Cengiz, and S. Mert
Vol 51
(n, cmꢁ1): 3466–3390 (NH), 3103 (Ar CH), 1656 (C═O, amide),
1617–1581 (Ar C═C and C═N), 1526 (NO2 asym.), 1302 (NO2
An N-amino imide derivative (10e) was obtained from
the reaction of 9 with hydrazine hydrate [26] rather than
the expected pyridazine dione ring (8). The spectral data of
the synthetic molecule were consistent with the assigned
sym.); 1H NMR (400 MHz, DMSO-d6)
d
(ppm): 8.93
(d, J=2.92Hz, 1H, H-40) 8.92 (br, s, 1H, NH) 8.74 (br, s, 2H,
NH2), 7.82 (d, J= 7.68 Hz, 1H, H-60) 7.57 (t, J= 7.31 Hz, 1H, H-8)
7.36 (m, 3H, H-5, H-6 and H-7); 13C NMR (100 MHz, DMSO-d6)
d (ppm): 155.09 (C-3, bicyclic ring), 154.40 (C═O), 148.93 (C-
NH2), 134.59, 133.37, 132.19, 132.00, 131.78, 131.14, 129.39,
124.84, 124.57, 124.04, 115.98; Anal. Calcd for C14H9N5O5: C,
51.38; H, 2.77; N, 21.40. Found: C, 50.42; H, 2.85; N, 21.35.
6,8-Dinitro-2-phenylquinoline-3,4-dicarboxylic acid (4).
Compound 1 (4g, 16.9mmol) was added at 25ꢀC to a stirred
solution of NaOH (2.1 g, 52.5 mmol) in water (250 mL). Ethyl
benzoylacetate (3.5mL, 20.3mmol) was added. The resulting
mixture was stirred and heated in an oil bath (40ꢀC) for 6 h. The
obtained solution was cooled to 0ꢀC and acidified with 2N HCl
till reaching pH 1. Then, the mixture was kept at 0ꢀC overnight;
the precipitate was filtered off and washed with ether (3ꢂ 15mL).
The product was crystallized from methanol and dried in vacuo
at 70ꢀC. Yield: 1.29g (20%); mp 289–291ꢀC; IR (n, cmꢁ1):
3416–2459 (COOH), 3084 (Ar CH), 1740 and 1676 (C═O, acid),
1630–1453 (Ar C═C and C═N), 1569 (NO2 asym.), 1343 (NO2
sym.); 1H NMR (400 MHz, DMSO-d6) d (ppm): 12.05 (br, s, 2H,
2COOH), 9.21 (d, J = 2.56 Hz, 1H, H-5,), 9.07 (d, J = 2.56Hz,
1H, H-7), 7.86–7.49 (m, 5H, other ArH); 13C NMR (100MHz,
DMSO-d6) d (ppm): 165.71 (2C═O), 159.40 (quinoline, C-2),
141.22, 137.67, 136.28, 136.12, 135.96, 134.08, 134.02,
129.47, 129.23, 128.11, 123.48, 118.41; LC-MSD (API-ES (ꢁ)
70eV) m/z: 383.0 [M + H]+; Anal. Calcd for C17H9N3O8: C,
53.27; H, 2.37; N, 10.96. Found: C, 52.42; H, 2.39; N, 10.99.
6,8-Dinitro-2-phenylquinoline-3,4-dicarbonyl dichloride (5). A
mixture of 4 (0.383g, 1 mmol) and SOCl2 (95%; 5 mL) was heated
in an oil bath (80ꢀC) for 5 h. The solvents were removed on a rotary
evaporator at 50ꢀC. The residue was washed with ether
(3ꢂ 15 mL). The product was crystallized from toluene and dried
in vacuo at 70ꢀC. Yield: 0.36g (85%); mp 246–248ꢀC; IR (n,
cmꢁ1): 3082 (Ar CH), 1783 and 1719 (C═O), 1615–1463
(aromatic C═C and C═N), 1550 (NO2 asym.), 1357 (NO2 sym.);
1H NMR (400MHz, DMSO-d6) d (ppm): 9.39 (d, J = 2.56Hz,
1H, H-5), 9.11 (d, J = 2.56Hz, 1H, H-7), 7.79–7.48 (m, 5H, other
ArH); 13C NMR (100 MHz, DMSO-d6) d (ppm): 165.29 (2C═O),
155.59 (quinoline, C-2), 145.00, 141.62, 138.15, 135.72, 134.87,
132.09, 131.38, 129.34, 127.36, 125.75, 124.33, 116.47; Anal.
Calcd for C17H7Cl2N3O6: C, 48.60; H, 1.68; N, 10.00. Found: C,
47.98; H, 1.85; N, 10.02.
1
structure. In the H NMR spectrum of compound 10e, two
exchangeable protons appeared as a broad singlet shifted to
4.59ppm that was in agreement with N-NH2. As expected,
from the reaction of 9 with phenylhydrazine gave a
1
pyridazine derivative (12) [27]. In the H NMR spectrum
of 12, an exchangeable proton (CO-NH-N-) shifted to
11.78 ppm confirmed the conversion of the structure to a
pyridazinedione ring.
EXPERIMENTAL
Chemical compounds used in this research were analytically
pure, and the solvents were purified using appropriate purifying
agents and distillation. All reactions were monitored by analytical
thin-layer chromatography (TLC) (E. Merck Co., Darmstadt,
Germany) on 0.25 mm precoated Kieselgel 60 F 254 plates
(Merck); compounds were visualized by Camag TLC devices UV
(254 and 366nm) Barnstead Electrothermal 9200 (Camag, Upland,
CA) capillary melting point apparatus (Electrothermal Co, Essex,
UK) and remained uncorrected. The IR data (Agilent Technologies
Inc., Santa Clara, CA) were recorded on a Bruker Vertex 70 Sample
compartment spectrometer using potassium bromide pellets. 1H
NMR and 13C NMR spectra were recorded on Varian spectrometers
(400MHz for 1H NMR and 100 MHz for 13C NMR) in DMSO-d6
using TMS as an internal standard. LC/MS spectra were
recorded on an Agilent 1100 LC-MSD mass spectrometer operating
at 55–100 eV (Agilent Technologies Inc., Santa Clara, CA, USA).
Elemental analyses were carried out on a Leco CHNS-932
instrument (LECO Corporation, Saint Joseph, MI). The starting
compound (1) was synthesized from isatin as described in reference
[28] and crystallized from xylene in bright yellow leaflets.
2-(2-Amino-3,5-dinitrophenyl)-2-oxoacetic acid (2). Compound
1 (1 g, 4.2 mmol) was added at 25ꢀC to a stirred solution of NaOH
(0.5 g, 12.5 mmol) in distilled water (80 mL). The mixture was
stirred at 25ꢀC for 4 h. The obtained solution was cooled to 0ꢀC
and acidified with 2N HCl till reaching pH 1. The resulting
mixture was kept at 5ꢀC overnight. Then, the precipitate was
filtered off and washed with water (3 ꢂ 15mL). The product was
crystallized from xylene and dried in vacuo at 70ꢀC. Yield: 0.75 g
(70%); mp 158–159ꢀC; IR (n, cmꢁ1): 3421 (NH), 3600–2600
(COOH), 3089 (Ar CH), 1748 (C═O, ketone), 1667 (C═O, acid),
1595–1433 (aromatic C═C), 1523 and 1337 (NO2 asym. and
4-(Methoxycarbonyl)-6,8-dinitro-2-phenylquinoline-3-carboxylic
acid (6a). H2SO4 (95–97%, 0.5 mL) was added to a solution of 4
(0.4 g, 1 mmol) in methanol (40 mL) at 25ꢀC, and the mixture was
stirred and heated to reflux for 8 h. The resulting mixture was kept at
25ꢀC overnight. Then, the precipitate was filtered off, washed with
ether (3 ꢂ 15 mL). The product was recrystallized from methanol
and dried in vacuo at 70ꢀC. Yield: 0.36 g (86%); mp 228–230ꢀC; IR
(n, cmꢁ1): 3550–2521 (COOH), 3109 (Ar CH), 2965 (aliphatic
CH), 1735 (C═O, ester), 1675 (C═O, acid), 1620–1451 (Ar C═N
and C═C), 1544 (NO2 asym.), 1340 (NO2 sym.); 1H NMR
(400 MHz, DMSO-d6) d (ppm): 12.21 (br, s, 1H, COOH), 9.07
(br, s, 2H, H-5 and H-7), 7.91–7.55 (m, 5H, other ArH), 3.63 (s, 3H,
OCH3); 13C NMR (100 MHz, DMSO-d6) d (ppm): 192.31 (C═O,
acid), 164.12 (C═O, ester), 159.74 (quinoline, C-2), 141.23, 138.88,
137.69, 136.06, 135.90, 135.08, 129.64, 128.53, 123.59, 118.50,
54.08 (OCH3); Anal. Calcd for C18H11N3O8: C, 54.42; H, 2.79;
N, 10.58. Found: C, 53.62; H, 2.86; N, 10.59.
1
sym.); H NMR (400 MHz, DMSO- d6) d (ppm): 9.25 (br, s, 3H,
NH2 and COOH), 9.01 (d, J= 2.56 Hz, 1H, H-4), 8.73
(d, J= 2.56 Hz, 1H, H-6); 13C NMR (100 MHz, DMSO- d6)
d (ppm): 189.60 (C═O, ketone), 164.95 (C═O, acid), 150.20
(C-NH2), 136.34, 134.34, 133.29, 129.28, 116.28; LC-MSD (API-
ES (ꢁ) 70eV) m/z: 255.0 [M + H]+; Anal. Calcd for C8H5N3O7: C,
37.66; H, 1.98; N, 16.47. Found: C, 36.51; H, 2.03; N, 16.23.
3-(2-Amino-3,5-dinitrophenyl)quinoxalin-2(1H)-one (3).
A
solution of 1 (0.7 g, 3 mmol) in THF (50mL) was added at room
temperature to a stirred solution of o-phenylenediamine (0.32 g,
3 mmol) in THF (20 mL). The mixture was stirred at 25ꢀC for
48h. The formed precipitate was filtered off, washed with ether
(3ꢂ 15mL). The product was crystallized from DMF and dried in
vacuo at 70ꢀC. Yield: 0.88 g (91%); mp over 300ꢀC; IR
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Quinoline Dicarboxylic Acid
229
4-(Ethoxycarbonyl)-6,8-dinitro-2-phenylquinoline-3-carboxylic
acid (6b). H2SO4 (95–97%, 0.5 mL) was added to a solution of 4
(0.4 g, 1 mmol) in ethanol (60 mL) at 25ꢀC, and the mixture was
stirred and heated to reflux for 8 h. The resulting mixture was kept
at 25ꢀC overnight; the precipitate was filtered off and washed with
ether (3 ꢂ 15 mL). The product was recrystallized from ethanol
and dried in vacuo at 70ꢀC. Yield: 0.36 g (84%); mp 214–216ꢀC;
IR (n, cmꢁ1): 3417–2511 (COOH), 3123 (Ar CH), 2989 (aliphatic
CH), 1728 (C═O, ester), 1690 (C═O, acid), 1621–1449 (Ar C═N
and C═C), 1550 (NO2 asym.), 1338 (NO2 sym.); 1H NMR
(400 MHz, DMSO-d6) d (ppm): 12.20 (br, s, 1H, COOH), 9.11
(d, J = 2.19 Hz, 1H, H-5), 9.07 (d, J= 2.56 Hz, 1H, H-7), 7.92–7.55
(m, 5H, other ArH), 4.17 (q, J = 7.10 Hz, 2H, OCH2), 0.89
(t, J = 7.32 Hz, 3H, CH3); 13C NMR (100 MHz, DMSO-d6)
d (ppm): 192.31 (C═O, acid), 163.53 (C═O, ester), 159.81
(quinoline, C-2), 141.17, 138.66, 137.65, 136.13, 135.12, 129.77,
129.61, 128.45, 123.51, 118.53, 63.63 (OCH2), 13.42 (CH3);
Anal. Calcd for C13H13N3O8: C, 55.48; H, 3.19; N, 10.22. Found:
C, 55.17; H, 3.21; N, 10.09.
4-(Isopropoxycarbonyl)-6,8-dinitro-2-phenylquinoline-3-
carboxylic acid (6c). H2SO4 (95–97%, 0.5 mL) was added to a
solution of 4 (0.4g, 1 mmol) in isopropanol (80 mL) at 25ꢀC, and
the mixture was stirred and heated to reflux for 8 h. The resulting
mixture was kept at 25ꢀC overnight. Then, the precipitate was
filtered off and washed with ether (3ꢂ 15mL). The product was
recrystallized from isopropanol and dried in vacuo at 70ꢀC. Yield:
0.27 g (62%); mp 232–234ꢀC; IR (n, cmꢁ1): 3415–2363 (COOH),
3123 (Ar CH), 2989 (aliphatic CH), 1721 (C═O, ester), 1692
(C═O, acid), 1621–1449 (Ar C═N and C═C), 1547 (NO2
asym.), 1341 (NO2 sym.); 1H NMR (400 MHz, DMSO-d6)
d (ppm): 12.19 (br, s, 1H, COOH), 9.11 (d, J = 2.56Hz, 1H, H-5),
9.07 (d, J = 2.56 Hz, 1H, H-7), 7.94–7.56 (m, 5H, other ArH),
5.07 (heptet, J = 6.22Hz, 1H, OCH), 0.95 (d, J = 6.22Hz, 6H,
CH3); 13C NMR (100MHz, DMSO-d6) d (ppm): 192.29 (C═O,
acid), 162.97 (C═O, ester), 159.87 (quinoline, C-2), 141.19,
138.73, 137.68, 136.22, 135.14, 129.89, 129.59, 128.32, 123.46,
118.55, 72.22 (OCH), 21.13 (CH3); LC-MSD (API-ES (+) 55eV)
m/z: 426.0 [M + H]+; Anal. Calcd for C20H15N3O8: C, 56.47;
H, 3.55; N, 9.88. Found: C, 56.31; H, 3.62; N, 9.58.
Dibutyl 6,8-dinitro-2-phenylquinoline-3,4-dicarboxylate (6d).
H2SO4 (95–97%, 0.5 mL) was added to a solution of 4 (0.4 g,
1 mmol) in n-butanol (90 mL) at 25ꢀC, and the mixture was stirred
and heated to reflux for 8 h. The resulting mixture was kept at 25ꢀC
overnight. Then, the precipitate was filtered off and washed with
ether (3 ꢂ 15 mL). The product was recrystallized from n-butanol
and dried in vacuo at 70ꢀC. Yield: 0.35 g (67%); mp 159–161ꢀC;
IR (n, cmꢁ1): 3112 (Ar CH), 2966 (aliphatic CH), 1725 (C═O,
ester), 1621–1453 (Ar C═N and C═C), 1548 (NO2 asym.), 1341
(NO2 sym.); 1H NMR (400 MHz, DMSO-d6) d (ppm): 9.09
(d, J= 2.56 Hz, 1H, H-5), 9.07 (d, J= 2.56 Hz, 1H, H-7), 7.93–7.55
(m, 5H, other ArH), 4.10 (t, J=6.22Hz, 4H, OCH2), 1.22 (pentet,
J= 6.95 Hz, 4H, 2OCH2CH2CH2), 0.95 (hextet, J=7.32Hz, 4H,
2CH2CH2CH3), 0.63 (t, J= 7.32 Hz, 6H, 2CH3); 13C NMR
(100 MHz, DMSO-d6) d (ppm): 163.73 (C═O, ester), 159.80
(quinoline, C-2), 141.17, 138.80, 137.66, 136.20, 136.10,
135.98, 135.12, 129.82, 129.57, 128.49, 123.54, 118.56, 67.40
(OCH2), 29.92 (OCH2CH2), 19.04 (CH2CH3), 14.01 (CH3); LC-
MSD (API-ES (+) 70 eV) m/z: 496.0 [M+H]+; Anal. Calcd for
C25H25N3O8: C, 60.60; H, 5.09; N, 8.48. Found: C, 59.69; H, 5.15;
N, 8.51.
0ꢀC. The obtained solution was slowly added to ammonium
hydroxide solution (0.25 mL, 3.44 mmol) at 0ꢀC, stirred, and kept
at this temperature for 1 h. The solvents were removed on a rotary
evaporator at 50ꢀC. The residue was washed with water
(3ꢂ 20 mL) and ether (3 ꢂ 15mL). The product was crystallized
from methanol and dried in vacuo at 70ꢀC. Yield: 0.3 g (94%).
Method B. Triethylamine (0.1mL, 0.7 mmol) and ammonium
hydroxide solution (0.25mL, 3.44 mmol) were added to a solution
of 9 (0.5g, 1.4 mmol) in benzene (70 mL) at room temperature,
and the resulting mixture was stirred for 3 h. The reaction mixture
was continued and heated to reflux for an additional 2 h. The formed
precipitate was filtered while it was still hot and washed with ether
(3ꢂ 15 mL). The product was crystallized from ethanol and dried in
vacuo at 70ꢀC. Yield: 0.31g (60%); mp 280–282ꢀC; IR (n, cmꢁ1):
3279 (NH), 3078 (Ar CH), 1677 (C═O, amide), 1609–1454
(aromatic C═C and C═N), 1548 (NO2 asym.), 1344 (NO2 sym.);
1H NMR (400MHz, DMSO-d6) d (ppm): 10.01 (s, 2H, CONH2)
9.82 (d, J = 2.56Hz, 1H, H-5), 9.04 (d, J = 2.56Hz, 1H, H-7),
7.60–7.33 (m, 5H, other ArH), 7.15 (s, 2H, CONH2); 13C NMR
(100 MHz, DMSO-d6) d (ppm): 167.05 (2C═O, amide), 156.44
(quinoline, C-2), 143.94, 141.33, 138.68, 138.20, 135.91, 134.84,
128.99, 128.68, 126.92, 126.12, 123.17, 117.78; LC-MSD
(API-ES (ꢁ) 70eV) m/z: 381.0 [M+ H]+; Anal. Calcd for
C17H11N5O6: C, 53.55; H, 2.91; N, 18.37. Found: C, 52.75; H,
2.98; N, 18.38.
6,8-Dinitro-2-phenyl-N3,N4-dipropylquinoline-3,4-dicarboxamide
(7b). n-Propylamine (0.4 mL, 4.8 mmol) was added to a solution of
5 (0.5 g, 1.2 mmol) in toluene (60 mL) at 25ꢀC. The mixture was
stirred and heated to reflux for 5 h. The reaction mixture was
filtered while it was still hot. The obtained solution was kept at
25ꢀC overnight. The formed precipitate was filtered off, washed
with water (3ꢂ 20mL) and ether (3ꢂ 15mL). The product was
recrystallized from toluene and dried in vacuo at 70ꢀC. Yield:
0.4 g (72%); mp 254–256ꢀC; IR (n, cmꢁ1): 3291 (NH), 3094
(Ar CH), 2968 (aliphatic CH), 1672 (C═O, amide), 1612–1451
(Ar C═N and C═C), 1551 (NO2 asym.), 1342 (NO2 sym.);
1H NMR (400MHz, DMSO-d6) d (ppm): 9.83 (d, J = 2.56Hz,
1H, H-5), 9.04 (d, J = 2.56Hz, 1H, H-7), 7.46 (br, s, 2H, 2CONH)
7.32 (m, 5H, other ArH), 3.29 (s, 4H, 2NCH2), 1.39 (m, 4H,
2CH2), 0.74 (s, 6H, 2CH3); 13C NMR (100MHz, DMSO-d6)
d (ppm): 165.24 (2C═O), 156.12 (quinoline, C-2), 142.70,
141.35, 138.07, 136.88, 136.22, 129.27, 128.98, 126.89, 126.24,
123.23, 117.53, 41.39 (NCH2), 21.89 (CH2), 12.15 (CH3); Anal.
Calcd for C23H23N5O6: C, 59.35; H, 4.98; N, 15.05. Found: C,
58.85; H, 5.02; N, 15.09.
N3,N4-diisopropyl-6,8-dinitro-2-phenylquinoline-3,4-
dicarboxamide (7c). A mixture of 5 (0.55 g, 1.3 mmol) and THF
(60 mL) was cooled to 0ꢀC. The obtained solution was slowly
added into isopropylamine (0.45 mL, 5.2mmol) at 0ꢀC, and the
resulting mixture was stirred for 30min. The reaction mixture was
continued and heated to reflux for an additional 4 h. The solvents
were removed on a rotary evaporator at 50ꢀC. The residue was
washed with water (3ꢂ 20 mL) and ether (3 ꢂ 15mL). The
product was crystallized from a chloroform–hexane mixture and
dried in vacuo at 70ꢀC. Yield: 0.37 g (61%); mp 154–156ꢀC; IR
(n, cmꢁ1): 3392 (NH), 3062 (Ar CH), 2985 (aliphatic CH), 1678
(C═O, amide), 1633–1422 (Ar C═N and C═C), 1545 (NO2
asym.), 1334 (NO2 sym.); 1H NMR (400MHz, DMSO-d6)
d (ppm): 9.54 (d, J = 2.56Hz, 1H, H-5), 8.57 (d, J = 2.56 Hz, 1H,
H-7), 7.89 (br, s, 2H, 2CONH), 7.40–6.80 (m, 5H, other ArH),
3.41 (m, 2H, 2CH), 1.11 (d, J = 5.85 Hz, 6H, 2CH3), 1.06
(d, J = 6.58Hz, 6H, 2CH3); 13C NMR (100MHz, DMSO-d6)
6,8-Dinitro-2-phenylquinoline-3,4-dicarboxamide (7a). Method A.
A mixture of 5 (0.36g, 0.86mmol) and THF (20 mL) was cooled to
Journal of Heterocyclic Chemistry
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D. Gök, R. Kasımoğulları, M. Cengiz, and S. Mert
Vol 51
d (ppm): 166.87 and 165.88 (2C═O, amide), 147.40 (quinoline,
C-2), 141.97, 141.47, 138.75, 136.13, 134.87, 128.41, 128.34,
126.99, 123.35, 118.17, 117.37, 44.20 and 43.60 (CH), 21.10 and
20.11 (CH3); Anal. Calcd for C23H23N5O6: C, 59.35; H, 4.98; N,
15.05. Found: C, 58.73; H, 4.99; N, 15.07.
100 eV) m/z: 365.9 [M + H]+; Anal. Calcd for C17H7N3O7: C,
55.90; H, 1.93; N, 11.50. Found: C, 55.30; H, 1.98; N, 11.51.
6,8-Dinitro-4-phenyl-2-propyl-2H-pyrrolo[3,4-c]quinoline-1,3-
dione (10a). Triethylamine (0.1 mL, 0.7 mmol) and n-propylamine
(0.12 mL, 1.4 mmol) were added to a solution of 9 (0.5 g,
1.4 mmol) in benzene (70mL) at 25ꢀC, and the resulting mixture
was stirred for 3 h. The reaction mixture was heated to reflux for
an additional 2 h. The formed precipitate was filtered while it was
still hot and washed with hexane (3 ꢂ 15 mL). The product was
crystallized from a hexane–chloroform mixture and dried in vacuo
at 70ꢀC. Yield: 0.37 g (66%); mp 260–262ꢀC; IR (n, cmꢁ1): 3094
(Ar CH), 2968 (aliphatic CH), 1673 and 1641 (C═O, imide),
1612–1452 (aromatic C═N and C═C), 1551 (NO2 asym.), 1342
(NO2 sym.); 1H NMR (400MHz, DMSO-d6) d (ppm): 9.84
(d, J= 2.92 Hz, 1H, H-9), 9.05 (d, J= 2.56 Hz, 1H, H-7), 7.48–7.32
(m, 5H, other ArH), 3.29 (t, J=5.85Hz, 2H, NCH2), 1.41 (m, 2H,
CH2CH3), 0.74 (t, J=7.68Hz, 3H, CH3); 13C NMR (100 MHz,
DMSO-d6) d (ppm): 165.24 (2C═O), 156.15 (quinoline, C-2),
142.71, 141.35, 138.05, 136.89, 136.23, 129.29, 128.99, 126.90,
126.23, 123.24, 117.51, 41.39 (N-CH2), 21.90 (CH2-CH3), 12.16
(CH3); LC-MSD (API-ES (+) 55 eV) m/z: 407.0 [M + H]+; Anal.
Calcd for C20H14N4O6: C, 59.12; H, 3.47; N, 13.79. Found: C,
58.62; H, 3.47; N, 13.76.
2-Isopropyl-6,8-dinitro-4-phenyl-2H-pyrrolo[3,4-c]quinoline-
1,3-dione (10b). Triethylamine (0.1mL, 0.7 mmol) and
isopropylamine (0.12 mL, 1.4 mmol) were added to a solution of 9
(0.5g, 1.4 mmol) in benzene (70 mL) at 25ꢀC. The mixture was
stirred and heated to reflux for 5 h. The reaction mixture was
filtered while it was still hot. The obtained solution was kept at
room temperature overnight. The formed precipitate was filtered
off and washed with ether (3 ꢂ 15mL). The product was
recrystallized from benzene and dried in vacuo at 70ꢀC. Yield:
0.46g (82%); mp 190–192ꢀC; IR (n, cmꢁ1): 3095 (Ar CH), 2982
(aliphatic CH), 1690 and 1645 (C═O, imide), 1613–1454
(aromatic C═N and C═C), 1550 (NO2 asym.), 1343 (NO2 sym.);
1H NMR (400 MHz, CDCl3) d (ppm): 10.14 (d, J = 2.56Hz, 1H,
H-9), 9.39 (d, J = 2.56 Hz, 1H, H-7), 7.48–7.40 (m, 5H, other
ArH), 3.70 (heptet, J = 6.96Hz, 1H, CH), 1.25 (d, J = 6.59Hz, 6H,
2CH3); 13C NMR (100 MHz, CDCl3) d (ppm): 164.28 (2C═O,
imide), 156.01 (quinoline, C-2), 142.05, 141.89, 138.20, 137.13,
134.88, 132.82, 129.80, 129.12, 128.27, 126.05, 123.81, 118.07,
46.00 (N-CH), 20.94 (CH3); Anal. Calcd for C20H14N4O6: C,
59.12; H, 3.47; N, 13.79. Found: C, 58.76; H, 3.50; N, 13.80.
6,8-Dinitro-2,4-diphenyl-2H-pyrrolo[3,4-c]quinoline-1,3-dione
(10c). Triethylamine (0.1 mL, 0.7 mmol) and aniline (0.13 mL,
1.4 mmol) were added to a solution of 9 (0.5 g, 1.4 mmol) in
benzene (70 mL) at 25ꢀC. The mixture was stirred and heated to
reflux for 5 h. The formed precipitate was filtered while it was still
hot and washed with ether (3 ꢂ 15mL). The product was
crystallized from ethanol and dried in vacuo at 70ꢀC. Yield: 0.45 g
(75%); mp 248–250ꢀC; IR (n, cmꢁ1): 3096 (aromatic CH), 1703
and 1648 (C═O, imide), 1613–1453 (aromatic C═N and C═C),
1548 (NO2 asym.), 1343 (NO2 sym.); 1H NMR (400MHz,
DMSO-d6) d (ppm): 9.90 (d, J = 2.56Hz, 1H, H-9), 9.08
(d, J = 2.56 Hz, 1H, H-7), 7.91–7.19 (m, 10H, other ArH);
13C NMR (100 MHz, DMSO-d6) d (ppm): 165.02 (C═O, imide),
156.13 (quinoline, C-2), 142.55, 141.42, 138.08, 136.58, 135.72,
135.45, 129.28, 129.13, 128.79, 127.46, 127.23, 126.39, 126.29,
123.36, 117.39; Anal. Calcd for C23H12N4O6: C, 62.73; H, 2.75;
N, 12.72. Found: C, 62.27; H, 2.78; N, 12.75.
6,8-Dinitro-N3,N4,2-triphenylquinoline-3,4-dicarboxamide
(7d). Aniline (0.6 mL, 6.4mmol) was added to a solution of 5
(0.65 g, 1.6mmol)) in toluene (70 mL) at 25ꢀC. The mixture was
stirred and heated to reflux for 5 h. The formed precipitate was
filtered while it was still hot and washed with water (3ꢂ 20 mL)
and ether (3 ꢂ 15mL). The product was crystallized from
methanol and dried in vacuo at 70ꢀC. Yield: 0.59 g (72%); mp
264–266ꢀC; IR (n, cmꢁ1): 3408 (NH), 3097 (Ar CH), 1704 and
1648 (C═O, amide), 1613–1453 (Ar C═N and C═C), 1548
1
(NO2 asym.), 1343 (NO2 sym.); H NMR (400 MHz, DMSO-d6)
d (ppm): 9.89 (d, J = 2.56Hz, 1H, H-5), 9.08 (d, J = 2.56Hz, 1H,
H-7), 7.90 (s, 1H, CONH), 7.51–7.17 (m, 16H, other ArH
and CONH); 13C NMR (100 MHz, DMSO-d6) d (ppm): 165.01
(2C═O), 156.09 (quinoline, C-2), 142.56, 141.46, 138.06,
136.59, 135.72, 135.47, 129.27, 129.13, 128.79, 127.46, 127.23,
126.40, 126.30, 123.37, 117.41; Anal. Calcd for C29H19N5O6: C,
65.29; H, 3.59; N, 13.13. Found: C, 64.79; H, 3.65; N, 13.18.
7,9-Dinitro-5-phenyl-2,3-dihydropyridazino[4,5-c]quinoline-
1,4-dione (8). Method A. Hydrazine hydrate (80%, 0.051 mL,
0.85 mmol) was added to a solution of 6a (0.34 g, 0.85 mmol) in
toluene (80 mL) at 25ꢀC. The mixture was stirred and heated to
reflux for 5 h. The formed precipitate was filtered while it was
still hot and washed with water (3 ꢂ 20 mL) and ether
(3 ꢂ 15 mL). The product was crystallized from a methanol–
THF mixture and dried in vacuo at 70ꢀC. Yield: 0.3 g (91%).
Method B. Hydrazine hydrate (80%, 0.055mL, 0.9 mmol) was
added to a solution of 6d (0.45 g, 0.9 mmol) in toluene (60mL) at
25ꢀC. Then, the mixture was stirred and heated to reflux for 5 h.
The formed precipitate was filtered while it was still hot and washed
with water (3 ꢂ 20mL) and ether (3 ꢂ 15mL). The product was
crystallized from an n-butanol–THF mixture and dried in vacuo at
70ꢀC. Yield: 0.23g (68%); mp over 300ꢀC; IR (n, cmꢁ1): 3220
(NH), 3112 (Ar CH), 1701 (C═O, amide), 1616–1434 (Ar C═N
and C═C), 1535 (NO2 asym.), 1343 (NO2 sym.); 1H NMR
(400MHz, DMSO-d6) d (ppm): 12.20 (br, s, 2H, CONH),
9.10 (d, J = 2.56 Hz, 1H, H-10), 9.08 (d, J = 2.19Hz, 1H, H-8),
7.93–7.55 (m, 5H, other ArH); 13C NMR (100MHz, DMSO-d6)
d (ppm): 159.50 and 158.29 (C═O, amide), 146.00 (quinoline,
C-2), 141.11, 138.00, 137.32, 134.86, 131.68, 129.84, 129.28,
128.72, 128.06, 126.04, 123.75, 119.04; LC-MSD (API-ES (ꢁ)
70eV) m/z = 379.0 [M + H]+; Anal. Calcd for C17H9N5O6: C,
53.83; H, 2.39; N, 18.46. Found: C, 53.28; H, 2.43; N, 18.51.
6,8-Dinitro-4-phenylfuro[3,4-c]quinoline-1,3-dione (9). A
mixture of 4 (0.383 g, 1 mmol) and acetic anhydride (95%;
60 mL) was heated in an oil bath (85ꢀC) for 8 h. The solvents
were removed on a rotary evaporator at 75ꢀC. The residue was
washed with ether (3 ꢂ 15 mL). The product was crystallized
from a methanol–THF mixture and dried in vacuo at 70ꢀC.
Yield: 0.34 g (92%); mp 271–273ꢀC; IR (n, cmꢁ1): 3100
(Ar CH), 1788 and 1706 (C═O, anhydride asym. and sym.),
1618–1455 (Ar C═N and C═C), 1550 (NO2 asym.), 1344
1
(NO2 sym.); H NMR (400 MHz, DMSO-d6) d (ppm): 9.40 (d,
J = 2.56 Hz, 1H, H-9), 9.10 (d, J = 2.56 Hz, 1H, H-7), 7.73–7.46
(m, 5H, other ArH); 13C NMR (100 MHz, DMSO-d6) d (ppm):
169.64 and 165.96 (2C═O, anhydride), 155.87 (quinoline,
C-2), 143.70, 141.80, 138.14, 135.85, 133.62, 133.16, 131.07,
129.34, 126.80, 125.71, 124.13, 116.24; LC-MSD (API-ES (+)
2-(3-Fluorophenyl)-6,8-dinitro-4-phenyl-2H-pyrrolo[3,4-c]
quinoline-1,3-dione (10d). Triethylamine (0.1 mL, 0.7 mmol)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2014
Quinoline Dicarboxylic Acid
231
and 3-fluoroaniline (0.14 mL, 1.4 mmol) were added to a solution
of 9 (0.5g, 1.4 mmol) in benzene (70mL) at 25ꢀC. The mixture
was stirred and heated to reflux for 8 h. The solvents were
removed on a rotary evaporator at 50ꢀC. The residue was washed
with ether (3ꢂ 15mL). The product was crystallized from a
benzene–hexane mixture and dried in vacuo at 70ꢀC. Yield:
0.41 g (65%); mp 275–277ꢀC; IR (n, cmꢁ1): 3093 (aromatic
CH), 1708 and 1678 (C═O, imide), 1615–1452 (aromatic C═N
and C═C), 1549 (NO2 asym.), 1342 (NO2 sym.); 1H NMR
(400MHz, DMSO-d6) d (ppm): 9.89 (d, J = 2.56 Hz, 1H, H-9),
9.08 (d, J = 2.56 Hz, 1H, H-7), 8.03–7.02 (m, 9H, other ArH);
13C NMR (100 MHz, DMSO-d6) d (ppm): 165.24 (2C═O),
156.15 (quinoline, C-2), 142.71, 141.35, 138.05, 136.89, 136.23,
129.29, 128.99, 126.90, 126.23, 123.24, 117.51; LC-MSD
(API-ES (+) 100 eV) m/z: 459.0 [M + H]+; Anal. Calcd for
C23H11FN4O6: C, 60.27; H, 2.42; N, 12.22. Found: C, 59.80;
H, 2.40; N, 12.27.
imide), 1613–1455 (aromatic C═N and C═C), 1550 (NO2 asym.),
1341 (NO2 sym.); H NMR (400 MHz, DMSO-d6) d (ppm): 9.86
1
(d, J= 2.93 Hz, 2H, H-9 and H-90), 9.02 (d, J=2.56Hz, 2H, H-7
and H-70), 7.94–7.20 (m, 18H, other ArH); 13C NMR (100 MHz,
DMSO-d6) d (ppm): 165.30 (4C═O), 157.12 (quinoline, C-4 and
C-40), 142.47, 137.69, 136.81, 135.40, 134.99, 129.10, 128.82,
127.30, 127.25, 126.11, 126.09, 125.98, 125.85, 122.79, 117.31,
114.87; Anal. Calcd for C46H22N8O12: C, 62.88; H, 2.52; N, 12.75.
Found: C, 62.88; H, 2.52; N, 12.75.
7,9-Dinitro-2,5-diphenyl-2,3-dihydropyridazino[4,5-c]quinoline-
1,4-dione (12). Phenylhydrazine (98%, 0.14 mL, 1.4 mmol) was
added to a solution of 9 (0.5 g, 1.4 mmol) in benzene (70mL) at
25ꢀC. Then, the resulting mixture was stirred for 1 h. The reaction
mixture was heated to reflux for an additional 4 h. The formed
precipitate was filtered while it was still hot and washed with
ether (3ꢂ 15 mL). The product was crystallized from isopropanol
and dried in vacuo at 70ꢀC. Yield: 0.42 g (68%); mp 203–205ꢀC;
IR (n, cmꢁ1): 3300 (NH), 3092 (Ar CH), 1689 (C═O, amide),
1609–1452 (Ar C═C and C═N), 1550 (NO2 asym.), 1343 (NO2
2-Amino-6,8-dinitro-4-phenyl-2H-pyrrolo[3,4-c]quinoline-1,3-
dione (10e). Hydrazine hydrate (80%, 0.06 mL, 1.4 mmol) was
added to a solution of 9 (0.5 g, 1.4 mmol) in benzene (70mL) at
25ꢀC. Then, the resulting mixture was stirred for 5 h. The formed
precipitate was filtered off and washed with ether (3ꢂ 15mL).
The product was crystallized from an ethanol–methanol mixture
and dried in vacuo at 70ꢀC. Yield: 0.44g (85%); mp over 300ꢀC;
IR (n, cmꢁ1): 3093 (Ar CH), 1685 and 1640 (C═O, imide),
1613–1452 (aromatic C═N and C═C), 1551 (NO2 asym.), 1341
(NO2 sym.); 1H NMR (400MHz, DMSO-d6) d (ppm): 9.83
(d, J= 2.56 Hz, 1H, H-9), 9.04 (d, J= 2.56 Hz, 1H, H-7), 7.47–7.27
(m, 5H, other ArH), 4.55 (br, s, 2H, NH2); 13C NMR (100 MHz,
DMSO-d6) d (ppm): 163.57 (2C═O, imide), 155.99 (quinoline,
C-2), 141.35, 141.16, 138.02, 136.47, 135.76, 129.07, 128.75,
127.46, 126.25, 123.25, 117.45; LC-MSD (API-ES (+) 100 eV)
m/z: 380.0 [M + H]+; Anal. Calcd for C17H9N5O6: C, 53.83; H,
2.39; N, 18.46. Found: C, 53.20; H, 2.38; N, 18.49.
sym.); 1H NMR (400 MHz, DMSO-d6)
d (ppm): 9.74
(d, J = 2.56Hz, 1H, H-10), 9.07 (d, J = 2.56Hz, 1H, H-8), 8.14
(s, 1H, NH), 7.62–6.68 (m, 10H, other ArH); 13C NMR
(100 MHz, DMSO-d6) d (ppm): 164.31 and 156.12 (C═O,
amide), 148.40 (quinoline, C-2), 141.58, 141.42, 138.00, 136.51,
135.12, 129.16, 129.07, 128.71, 127.48, 126.23, 123.37, 119.82,
117.32, 113.51; LC-MSD (API-ES (+) 70eV) m/z: 456.0
[M+ H]+; Anal. Calcd for C23H13N5O6: C, 60.66; H, 2.88; N,
15.38. Found: C, 60.23; H, 2.91; N, 15.39.
Acknowledgments. The authors would like to thank Dr. Salim Ok
for useful comments and suggestions. Also, we gratefully
acknowledge the Dumlupinar University Technology Research
Fund for the financial support of this study through project
number of 2007/6.
2,20-(1,4-Phenylene)bis(6,8-dinitro-4-phenyl-2H-pyrrolo
[3,4-cquinoline-1,3-dione) (11a).
p-Phenylenediamine (0.15 g,
1.4 mmol) was added to a solution of 9 (1.02 g, 2.8 mmol) in
xylene (100 mL) at 25ꢀC. The mixture was stirred and heated to
reflux for 24 h. The formed precipitate was filtered while it was
still hot, treated with warm ethanol, and washed with ether
(3ꢂ 15mL). The product was crystallized from an ethyl acetate–
hexane mixture and dried in vacuo at 70ꢀC. Yield: 0.65g (58%);
mp over 300ꢀC; IR (n, cmꢁ1): 3091 (aromatic CH), 1694 and
1644 (C═O, imide), 1614–1454 (aromatic C═N and C═C),
1549 (NO2 asym.), 1342 (NO2 sym.); 1H NMR (400 MHz,
DMSO-d6) d (ppm): 9.84 (d, J = 2.19 Hz, 2H, H-9 and H-90),
9.03 (d, J = 1.83 Hz, 2H, H-7 and H-70), 7.88–7.25 (m, 14H,
other ArH); 13C NMR (100 MHz, DMSO-d6) d (ppm): 165.12
(4C═O), 156.69 (quinoline, C-4 and C-40), 142.42, 141.06,
138.76, 136.61, 135.04, 133.89, 129.16, 128.83, 127.18,
127.05, 126.05, 125.72, 123.02, 117.28; Anal. Calcd for
C40H18N8O12: C, 59.86; H, 2.26; N, 13.96. Found: C, 59.45;
H, 2.28; N, 13.96.
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