Synthesis of some novel binuclear heterocyclic compounds from 6-ethyl-3-nitropyrano [3,2-c]-quinoline-4,5(6H)-dione

Article abstract of DOI:10.3987/COM-12-12639

6-Ethyl-3-nitropyrano[3,2-c]quinoline-4,5(6H)-dione (4) was synthesized and its reactivity towards some 1,2-, 1,3-, and 1,4-binucleophiles was investigated. Ring transformation via opening of the γ-pyrone ring and heterocyclizations through out these reac

Full text of DOI:10.3987/COM-12-12639

HETEROCYCLES, Vol. 87, No. 2, 2013
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HETEROCYCLES, Vol. 87, No. 2, 2013, pp. 369 - 380. © 2013 The Japan Institute of Heterocyclic Chemistry
Received, 26th November, 2012, Accepted, 6th December, 2012, Published online, 20th December, 2012
DOI: 10.3987/COM-12-12639
SYNTHESIS OF SOME NOVEL BINUCLEAR HETEROCYCLIC
COMPOUNDS FROM 6-ETHYL-3-NITROPYRANO [3,2-c]-
QUINOLINE-4,5(6H)-DIONE
Hany M. Hassanin* and Dalia Abdel-Kader
Department of Chemistry, Faculty of Education, Ain Shams University, Roxy,
Heliopolis 11757, Cairo, Egypt
E-mail: hanyhassnin@yahoo.com
Abstract
–
6-Ethyl-3-nitropyrano[3,2-c]quinoline-4,5(6H)-dione (4) was
synthesized and its reactivity towards some 1,2-, 1,3-, and 1,4-binucleophiles was
investigated. Ring transformation via opening of the !-pyrone ring and
heterocyclizations through out these reactions led to certain interesting five, six,
and seven-membered heterocyclic substituents, viz. pyrazolyl, pyridyl, pyrimidyl,
diazepinyl, and thiazepinyl at position-3 of quinolin-2-one moiety.
INTRODUCTION
3-Substituted !-pyrones are used as valuable synthetic intermediates in the preparation of
pharmacologically relevant products and new heterocyclic systems.1-7 Introduction of a nitro group into
the 3-position of !-pyrone system enhances the reactivity of the pyrone ring towards binucleophilic
reagents and provides a broad synthetic potential of nitrogen containing heterocycles.8 However,
3-nitro-!-pyrones have not received much attention despite their potential interest as building blocks in
synthesis of heterocyclic compounds bearing a nitro group. The chemistry of nucleophilic reactions,
involving ring-opening/ring-closing (RORC) of nitropyrano[3,2-c]quinoline-4,5-dione, attracted our
attention due to the expected higher reactivity of the pyrone ring in presence of nitro group and to the
paucity of their literature reports.8,9 On the other hand, the combination of a pyrazole, pyridine,
pyrimidine, and/or diazepine nucleii with the quinoline moiety in one molecular framework is reported to
confer interesting biological activity.10-14 Herein we report the synthesis of the novel
6-ethyl-3-nitropyrano[3,2-c]quinoline-4,5(6H)-dione (4) and study of its chemical behavior towards
different binucleophiles to obtain a new series nitroheterocyclyl quinolinone derivatives with the
possibility of possessing certain activity.

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RESULTS AND DISCUSSION
Heating N-ethylaniline with two equivalents of diethyl malonate gave 4-hydroxypyrano[3,2-c]-
quinoline-2,5(6H)-dione (1).15,16 Nitration of compound 1 by using conc. nitric acid, in acetic acid, in the
presence of sodium nitrite as catalyst, gave nitropyrano[3,2-c]quinoline-2,5-dione 217 (Scheme 1).
Alkaline hydrolysis of compound 2 using aqueous sodium hydroxide solution yielded the
3-(nitroacetyl)-4-hydroxyquinolinone 3.18 Thermal cyclocondensation of the compound 3 with triethyl
orthoformate was carried out to get the desired 3-nitropyrano[3,2-c]quinoline-4,5-dione 4 (Scheme 1).
The IR spectrum of compound 4 confirmed the absence of the hydroxy group. The 1H NMR spectrum of
compound 4 showed a new characteristic singlet signal at 8.97 ppm assigned to characteristic C2-H of
!-pyranone. Moreover, the mass spectrum revealed the molecular ion peak [M+] at m/z 286 as the base
peak.
O
O
OH
N
O
O
NO2
OH
O
N
O
N
NO2
i) NaOH(2N)
ii) HCl
HNO3 /AcOH
NaNO2
OH
O
O
3
2
CH(OEt)3
OEt
1
NO2
NO2
O
OH
O
78%
O
O
N
O
N
4
Scheme 1
The structural features of the 3-nitro-!-pyranone 4 show that this molecule possesses two
electron-deficient centers (electrophilic sites) at C-2 and C-4, which is activated by strong electron
withdrawing nitro- group. The electrophilic sites at position 2 and 4 were utilized for aromatic ring
formation by Michael-type addition followed by intramolecular cyclocondensation. Reaction of !-pyrones
with hydrazine derivatives was previously reported,19,20 thus compound 4 was subjected to react with
1
hydrazine hydrate, under reflux in DMF, to afford 3-nitropyrazolylquinolinone 5 (Scheme 2). The H
NMR spectrum of compound 5, in a DMSO-d6 solution, showed two sets of signals due to the possibility
of annular prototropy of the pyrazole ring. It is well known that annular tautomerism in NH azoles is a
very fast process in the NMR time scale.21 However, in our case, four signals exhibiting broadening at
higher frequency values were observed, indicating that pyrazole 5 exists as a mixture of tautomers 5a and

HETEROCYCLES, Vol. 87, No. 2, 2013
371
5b (65:35). The structural assignments were based on the signals due to the NH and OH protons at 11.22
ppm for NH, 12.94 ppm for OH (tautomer 5a) and 11.01 ppm for NH, 12.64 ppm for OH (tautomer 5b).
This case is very similar to those of some reported pyrazols prepared from !-pyranone.21,22 The structure
5a is the more abundant tautomer (65%) since its intramolecular O–H……N=C hydrogen bond is
stronger than the intramolecular N–H……O–C hydrogen bond in tautomer 5b, hence gains more stability.
Reaction of compound 4 with methylhydrazine, in DMF, afforded 3-(1-methyl-4-nitropyrazolyl)
quinolinone 6. The 1H-NMR spectrum of compound 6 revealed that the isomer 6a was obtained excluding
the presence of the other possible isomer 6b in which the OH chemical shift appears at 12.59 ppm
indicating existence of OH……N intramolecular H -bonding which is not possible in isomer 6b (Scheme
2). The N-methyl protons were observed at 3.81 ppm in its NMR spectrum, while its methyl carbon atom
appeared at 20.5 ppm. Treatment of compound 4 with phenylhydrazine afforded the pyrazole 7 (Scheme
2). Mass spectrum of compound 7 showed a peak at 376 assigned to molecular ion peak. While, its
1H-NMR spectrum showed ten aromatic protons, in addition to a characteristic exchangeable singlet
signal at 13.68 ppm due to the OH proton. This result confirms absence of intramolecular H-bonding in
the product which is in agreement with the structure of isomer 7a. However, this contrast between
behavior of methylhydrazine and phenylhydrazine towards the pyranoquinolinedione 4 can be understood
by assuming that the most reactive nucleophilic site attacks the most reactive electrophilic site in the
reactant molecule.
NO2
O
O
N
O
4
H2N-NH2
NH2NHMe
70%
NH2NHPh
DMF
DMF
DMF
63%
67%
Me
N
H
H
H
Ph
N
O
N
O
O
N
O
N
N
OH
NO2
NO2
N
NO2
O
N
N
6a
5a
7a
Ph
N
Me
H
H
N
O
N
N
O
O
N
N
O
H
H
N
O
N
N
O
NO2
NO2
NO2
6b
7b
5b
Scheme 2

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HETEROCYCLES, Vol. 87, No. 2, 2013
Reaction of !-pyrones with guanidine derivatives was previously reported.23 Thus, the compound 4 was
allowed to react with some 1,3-binucleophilic reagents in order to prepare 4-hydroxyquinolinones bearing
pyrimidine moiety. Treatment of compound 4 with guanidine hydrochloride, in boiling DMF, caused
!-pyrone ring-opening followed by ring-closing (RORC) with loss of H2O, to give the
pyrimidylquinolinone 8 (Scheme 3). The 1H NMR spectrum of the compound 8 showed two broad signals
due to three exchangeable protons characteristic for NH2 and OH at 6.84 and 12.51 ppm. Also, the
structure of compound 8 was supported by its mass spectrum which exhibited the molecular ion peak at
m/z 327. Reaction of compound 4 with cyanoguanidine afforded the cyanoamino-pyrimidine derivative 9
(Scheme 3). The IR spectrum of the compound 9 showed the presence of absorption bands at 3120 and
1
2230 cm-1, characteristic for the NH and C"N groups, respectively. Furthermore, the H NMR spectrum
of compound 9 showed two deuterium-exchangeable singlet signals assignable to the NH and the OH
protons at ! 8.97, 12.59. The reaction of the compound 4 with thiourea, in DMF, afforded the
thioxo-pyrimidine derivative 10 (Scheme 3). The elemental analysis of the product revealed correction of
the proposed formulae, in addition to, 1H NMR spectrum of the product 10 showed two
deuterium-exchangeable singlet signals at ! 11.99 and 12.63 assignable to NH and OH protons. The
reaction of the compound 4 with acetamidine, in DMF, afforded the methylpyrimidine derivative 11
(Scheme 3). 1H NMR spectrum of compound 11 showed a methyl signal as singlet at # 2.88. This methyl
was observed at # 20.5 in the 13C NMR spectrum.
NO2
O
O
N
O
4
NH2
NH
NH2
CN
Me
Me
S
HN
H2N
DMF
71%
DMF
69%
DMF
71%
DMF
66%
H2N
H
H2N
NH
N
H2N
NH2
NH
NH
CN
HN
S
N
N
O
N
H
H
H
N
N
O
N
O
N
O
O
O
NO2
O
NO2
NO2
NO2
O
N
N
N
8
9
11
10
Scheme 3
In continuation to this study, the reactivity of the compound 4 towards 1,4-binucleophiles, such as
o-phenylendiamine and o-aminothiophenol was investigated. The reaction was carried out in boiling
DMF giving rise to the corresponding benzodiazepines 12, 13. The anticipated structure of the
1,5-benzodiazepine 12 and 1,5-benzothiazepine 13 was established on basis of elemental microanalysis,

HETEROCYCLES, Vol. 87, No. 2, 2013
373
and spectral data. 1H NMR spectra of both products 12 and 13 revealed that the integral count of protons
in the aromatic region is corresponding to nine protons of two benzo groups in addition to 2-CH of
diazepine.
NO2
O
O
N
O
4
NH2
SH
NH2
NH2
DMF
74%
DMF
67%
OH
N
N
OH
N
O
NH
S
NO2
NO2
O
N
12
13
Scheme 4
Reaction of the !-pyrones with carbon nucleophiles was previously studied.24 Thus, treatment of the
compound 4 with malononitrile, in DMF containing anhydrous potassium carbonate, gave
3-pyridinylquinolinone derivative 14 (Scheme 5). The same compound 14 was obtained from reaction of
the compound 4 with cyanoacetamide under the same conditions (Scheme 5). The IR spectrum of
compound 14 showed absorption bands at 3446, 3230 and 2245 cm-1 assigned to OH, NH and C"N
groups, respectively. 1H NMR spectrum of the compound 14 revealed two broad signals at 10.51 ppm and
12.93 ppm for the NH and OH protons exchangeable with D2O.
NH
N
O
NO2
CH2(CN)2
CN
CN
O
N
OH O
OH
N
O
NO2
NO2
O
DMF-K2CO3
O
O
N
O
4
O
CN
OH HN
NH2
rearrangement
72%
CN
NO2
N
O
DMF-K2CO3
75%
14
Scheme 5

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HETEROCYCLES, Vol. 87, No. 2, 2013
Reaction of the compound 4 with cyanoacetohydrazide as a 1,4-C,N-dinucleophile was carried out, in
refluxing DMF containing catalytic amount of triethyl amine. Compound 15 was obtained, while the
1
other possible product N-aminopyridine derivative 16 was not observed (Scheme 6). The H NMR
spectrum of compound 15 revealed three different broad signals exchangeable with D2O at 10.89, 11.01
and 12.94 ppm corresponding to one NH and two OH protons. There is no indication for presence of NH2
group characteristic chemical shift signal. These observations fortify the suggested structure of compound
15.
O
NH2NH
O
:
NO2
O
CN
HO
O
N
H2NNHCOCH2CN
NO2
O
DMF/TEA
N
O
64%
4
-H2O
//
O
H
H2N
OH
CN
CN
N
N
OH
N
O
OH
N
NO2
NO2
N
O
16
15
Scheme 6
EXPERIMENTAL
Melting points were determined on a digital Stuart SMP3 apparatus. Infrared spectra were measured on
1
Perkin-Elmer 293 spectrophotometer (cm-1), using KBr disks. H NMR spectra were measured on
Gemini-200 spectrometer (200 MHz), Mercury-300BB (300MHz), and/or Jeol Eca-500 MHz using
DMSO-d6 as a solvent and TMS (") as the internal standard. 13C NMR spectra were measured on
Mercury-300BB (75 MHz), using DMSO-d6 as a solvent and TMS (") as the internal standard. Mass
spectra were obtained using GC-2010 Shimadzu Gas chromatography instrument mass spectrometer (70
eV). Elemental microanalyses were performed on a Perkin–Elmer CHN-2400 analyzer.
6-Ethyl-3-nitropyrano[3,2-c]quinoline-4,5(6H)-dione (4)
A mixture of compound 3 (2.76 g, 10 mmol) and triethyl orthoformate (4 mL, 25 mmol), was heated
under fusion condition for 4 h. The solid deposited during heating was filtered, air dried and crystallized
o
from AcOH to give compound 4 as yellow crystals, mp > 300 C, yield (2.23 g, 78%). IR (KBr, cm-1):
3072 (CHarom), 2977, 2928, 2866 (CHaliph), 1674 (C=Opyrone), 1633 (C=Oquinolone), 1591 (C=C), 1568, 1377
(NO2). 1H NMR (DMSO-d6, "): 1.22 (t, 3H, J = 6.9 Hz, CH2CH3), 4.35 (q, 2H, J = 6.9 Hz, CH2CH3), 7.45
(t, 1H, J = 7.2 Hz, H-9), 7.78 (d, 1H, J = 8.4 Hz, H-7), 7.92 (t, 1H, J = 7.2 Hz, H-8), 8.14 (d, 1H, J = 8.1

HETEROCYCLES, Vol. 87, No. 2, 2013
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13
Hz, H-10), 8.97 (s, 1H, H-2). C NMR (125 MHz, DMSO-d6, "): 11.8 (CH3), 37.4 (CH2), 111.9, 115.9,
123.4, 124.5, 132.1, 132.3, 135.8, 140.3, 140.9, 161.1, 162.0, 174.6. M/z (relative intensity): 287 [M+ +1;
17], 286 [M+; 100], 285 [M+-1; 48], 258 (42), 225 (12), 214 (24), 200 (10), 184 (29), 169 (17), 156 (67),
154 (10), 146 (67), 141 (18), 140 (11), 132 (37), 129 (12), 128 (36), 127 (20), 118 (14), 115 (12), 114
(22), 113 (11), 105 (12), 104 (20), 102 (13), 101 (31), 91 (13), 90 (13), 89 (10), 77 (55), 76 (23). Anal.
Calcd for C14H10N2O5 (286.25): C, 58.75; H, 3.52; N, 9.79. Found C, 58.31; H, 3.49; N, 9.61%.
General procedure for formation of the 3-pyrazolylquinolines 5-7
A mixture of !-pyrone 4 (2.86 g, 10 mmol) and some hydrazines namely; hydrazine hydrate (0.6 mL, 12
mmol), methylhydrazine (0.64 mL, 12 mmol), phenylhydrazine (1.2 mL, 12 mmol), in DMF (50 mL),
was heated under reflux for 4 h. After partial evaporation of the solvent the product was isolated by
filtration, washed with EtOH, dried and crystallized from the proper solvent to give the compounds 5, 6
and 7 respectively.
1-Ethyl-4-hydroxy-3-(4-nitro-1H-pyrazol-3-yl)quinolin-2(1H)-one (5)
Crystallized from DMF to give compound 5 as pale yellow crystals, mp > 300 oC, yield (2.01 g, 67%). IR
(KBr, cm-1): 3447-3150 (OH, NH), 3055 (CHarom), 2981 (CHaliph), 1655 (C=Oquinolone), 1601 (C=N), 1591
(C=C), 1558, 1376 (NO2). 1H NMR (300 MHz, DMSO-d6, "): (5a, OH…….N, 65%) 1.28 (t, 3H, J = 6.4
Hz, CH2CH3), 4.38 (q, 2H, J = 6.4 Hz, CH2CH3), 7.37 (t, 1H, J = 7.4 Hz, H-6), 7.61 (d, 1H, J = 8.2 Hz,
H-8), 7.71 (t, 1H, J = 7.4 Hz, H-7), 7.96 (s, 1H, Hpyrazole), 8.12 (d, 1H, J = 8.0 Hz, H-5), 11.22 (s, 1H, NH
exchangeable with D2O), 12.94 (s, 1H, OH exchangeable with D2O); (5b, NH…….O, 35%) 1.20 (t, 3H, J
= 6.9 Hz, CH2CH3), 4.18 (q, 2H, J = 6.9 Hz, CH2CH3), 7.19 (t, 1H, J = 7.2 Hz, H-6), 7.50 (d, 1H, J = 8.0
Hz, H-8), 7.59 (t, 1H, J = 7.2 Hz, H-7), 7.84 (s, 1H, Hpyrazole), 8.06 (d, 1H, J = 7.9 Hz, H-5), 11.01 (s, 1H,
NH exchangeable with D2O), 12.64 (s, 1H, OH exchangeable with D2O). M/z (relative intensity): 301 [M+
+1; 5], 300 [M+; 17], 299 [M+-1; 57], 280 (12), 279 (92), 270 (20), 242 (19), 228 (22), 189 (36), 188 (38),
146 (100), 132 (60), 130 (74), 120 (39), 104 (30), 90 (27). Anal. Calcd for C14H12N4O4 (300.28): C, 56.00;
H, 4.03; N, 18.66. Found C, 55.91; H, 4.01; N, 18.31%.
1-Ethyl-4-hydroxy-3-(1-methyl-4-nitro-1H-pyrazol-3-yl)quinolin-2(1H)-one (6)
o
Crystallized from AcOH to give 6 as colorless crystals, mp 286-287 C, yield (2.19 g, 70%). IR (KBr,
cm-1): 3443 (OH), 3075 (CHarom), 2979, 2930, 2867 (CHaliph), 1630 (C=Oquinolone), 1603 (C=N), 1595 (C=C),
1
1551, 1378 (NO2). H NMR (300 MHz, DMSO-d6, "): 1.22 (t, 3H, J = 6.6 Hz, CH2CH3), 3.81 (s, 3H,
NCH3), 4.35 (q, 2H, J = 6.6 Hz, CH2CH3), 7.30 (t, 1H, J = 7.2 Hz, H-6), 7.63-7.67 (m, 2H, J = 8.0 Hz,
H-8 and H-7), 7.99 (s, 1H, Hpyrazole), 8.01 (d, 1H, J = 7.8 Hz, H-5), 12.59 (s, 1H, OH exchangeable with
D2O). 13C NMR (125 MHz, DMSO-d6, "): 12.8 (CH3), 20.5 (NCH3), 37.5 (CH2), 98.8, 108.3, 112.8, 114.9,
116.6, 122.5, 123.4, 131.3, 136.6, 138.2, 159.4, 164.6. Anal. Calcd for C15H14N4O4 (314.30): C, 57.32; H,
4.46; N, 17.83%. Found C, 57.31; H, 4.42; N, 17.81%.

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1-Ethyl-4-hydroxy-3-(4-nitro-1-phenyl-1H-pyrazol-5-yl)quinolin-2(1H)-one (7)
o
Crystallized from AcOH to give 7 as yellow crystals, mp > 300 C, yield (2.36 g, 63%). IR (KBr, cm-1):
1
3447 (OH), 3078 (CHarom), 2979, 2930 (CHaliph), 1630 (C=Oquinolone), 1603 (C=C), 1551, 1378 (NO2). H
NMR (DMSO, "): 1.18 (t, 3H, J = 6.0 Hz, CH2CH3), 4.28 (q, 2H, J = 7.2 Hz, CH2CH3), 7.19 (t, 1H, J =
6.4 Hz, Ar-H), 7.30 (d, 1H, J = 6.8 Hz, Ar-H), 7.46 (d, 1H, J = 6.0 Hz, Ar-H), 7.60 – 7.79 (m, 5H, Ar-H),
8.03 (s, 1H, Hpyrazole), 8.23 (d, 1H, J = 6.9 Hz, H-5), 13.68 (s, 1H, OH exchangeable with D2O). M/z
(relative intensity): 377 [M+ +1; 27], 376 [M+; 45], 359 (47), 357 (57), 342 (54), 333 (55), 326 (52), 310
(60), 305 (51), 288 (57), 279 (56), 269 (90), 258 (46), 241 (75), 227 (58), 209 (50), 189 (100), 174 (86),
132 (94), 105 (83), 77 (67). Anal. Calcd for C20H16N4O4 (376.37): C, 63.83; H, 4.26; N, 14.89%. Found C,
63.31; H, 4.24; N, 14.87%.
General procedure for formation of the 3-pyrimidylquinolines 8-11
A mixture of !-pyrone 4 (2.86 g, 10 mmol) and 1,3-binuchleophiles namely; guanidine hydrochloride
(0.96 g, 10 mmol), cyanoguanidine (0.84 g, 10 mmol), thiourea (0.76 g, 10 mmol), acetamidine
hydrochloride (0.95 g, 10 mmol), in DMF (50 mL), was heated under reflux for 4 h. The solid deposited
after cooling was filtered and crystallized from the proper solvent to give the compounds 8, 9, 10 and 11,
respectively.
1-Ethyl-3-(2-amino-5-nitropyrimidin-4-yl)-4-hydroxyquinolin-2(1H)-one (8)
Crystallized from DMF to give 8 as colorless crystals, mp > 300 oC, yield (2.32 g, 71%). IR (KBr, cm-1):
3420 (OH), 3316, 3234 (NH2), 3070 (CHarom), 2977, 2934 (CHaliph), 1634 (C=Oquinolone), 1610 (C=N), 1591
(C=C), 1568, 1376 (NO2). 1H NMR (300 MHz, DMSO-d6, "): 1.26 (t, 3H, J = 6.6 Hz, CH2CH3), 4.38 (q,
2H, J = 6.6 Hz, CH2CH3), 6.84 (bs, 2H, NH2 exchangeable with D2O), 7.33 (t, 1H, J = 7.2 Hz, H-6),
7.66-7.70 (m, 2H, H-8 and H-7), 7.96 (s, 1H, Hpyrimidine), 8.08 (d, 1H, J = 8.4 Hz, H-5), 12.51 (s, 1H, OH
exchangeable with D2O). m/z (relative intensity): 328 [M+ +1; 5], 327 [M+; 8], 311 (5), 256 (7), 228 (7),
213 (15), 204 (6), 194 (7), 185 (13), 169 (8), 149 (32), 137 (9), 129 (19), 121 (10), 115 (12), 109 (13), 98
(34), 81 (79), 73 (66), 69 (100). Anal. Calcd for C15H13N5O4 (327.30): C, 55.05; H, 4.00; N, 21.40%.
Found C, 55.02; H, 3.97; N, 21.36%.
4-(1-Ethyl-1,2-dihydro-4-hydroxy-2-oxoquinolin-3-yl)-5-nitropyrimidin-2-ylcyanamide (9)
o
Crystallized from DMF to give 9 as colorless crystals, mp > 300 C, yield (2.32 g, 66%). IR (KBr,
cm-1): 3416 (OH), 3120 (NH), 3055 (CHarom), 2984, 2881 (CHaliph), 2230 (CN), 1646 (C=O), 1615 (C=N),
1595 (C=C), 1558, 1365 (NO2). 1H NMR (DMSO, "): 1.20 (t, 3H, J = 7.0 Hz, CH2CH3), 4.33 (q, 2H, J =
7.2 Hz, CH2CH3), 7.33 (t, 1H, J = 6.4 Hz, H6), 7.58 - 7.71 (m, 2H, H8 and H7), 7.99 (s, 1H, Hpyrimidine),
8.11 (d, 1H, J = 6.9 Hz, H-5), 8.97 (bs, 1H, NH exchangeable with D2O), 12.59 (s, 1H, OH exchangeable
with D2O). M/z (relative intensity): 352 [M+; 40], 351 [M+ -1; 52], 331 (56), 313 (46), 304 (50), 285 (68),
267 (58), 251 (53), 235 (50), 192 (52), 188 (92), 167 (63), 161 (86), 146 (74), 130 (100), 125 (58), 104

HETEROCYCLES, Vol. 87, No. 2, 2013
377
(68), 90 (92), 82 (58), 71 (56). Anal. Calcd for C16H12N6O4 (352.31): C, 54.55; H, 3.43; N, 23.85%. Found
C, 54.73; H, 3.41; N, 23.43%.
1-Ethyl-3-(1,2-dihydro-5-nitro-2-thioxopyrimidin-4-yl)-4-hydroxyquinolin-2(1H)-one (10)
o
Crystallized from AcOH to give 10 as yellow crystals, mp > 300 C, yield (2.44 g, 71%). IR (KBr,
cm-1): 3393 (OH), 3197 (NH), 3068 (CHarom), 2922, 2870 (CHaliph), 1647 (C=O), 1615 (C=N), 1558, 1370
(NO2). 1H NMR (DMSO-d6, "): 1.22 (t, 3H, J = 6.9 Hz, CH2CH3), 4.38 (q, 2H, J = 6.9 Hz, CH2CH3), 7.37
(t, 1H, J = 7.6 Hz, H-6), 7.65–7.76 (m, 2H, H-7 and H-8), 7.99 (s, 1H, Hpyrimidine), 8.05 (d, 1H, J = 8.4 Hz,
H-5), 11.99 (s, 1H, NH exchangeable with D2O), 12.63 (s, 1H, OH exchangeable with D2O). M/z (relative
intensity): 344 [M+; 72], 343 [M+ -1; 77], 323 (95), 320 (75), 293 (91), 252 (81), 245 (79), 236 (76), 218
(75), 182 (85), 156 (79), 128 (75), 119 (65), 101 (72), 62 (72), 52 (100). Anal. Calcd for C15H12N4O4S
(344.35): C, 52.32; H, 3.51; N, 16.27; S, 9.31%. Found C, 52.13; H, 3.49; N, 16.23; S, 9.21%.
1-Ethyl-4-hydroxy-3-(2-methyl-5-nitropyrimidin-4-yl)quinolin-2(1H)-one (11)
Crystallized from DMF to give 11 as colorless crystals, mp 283 - 285 °C, yield (2.24 g, 69%). IR (KBr,
cm-1): 3426 (OH), 3068 (CHarom), 2975, 2922 (CHaliph), 1644 (C=O), 1619 (C=N), 1581 (C=C), 1548, 1392
(NO2). 1H NMR (DMSO-d6, "): 1.26 (t, 3H, J = 6.9 Hz, CH2CH3), 2.88 (s, 3H, CH3), 4.33 (q, 2H, J = 6.9
Hz, CH2CH3), 7.47 (t, 1H, J = 7.4 Hz, H-6), 7.58–7.77 (m, 2H, H-7 and H-8), 7.95 (s, 1H, Hpyrimidine), 8.08
(d, 1H, J = 8.2 Hz, H-5), 12.68 (s, 1H, OH exchangeable with D2O). 13C NMR (125 MHz, DMSO-d6, "):
12.8 (CH3), 20.5 (CH3 pyrimidine), 37.5 (CH2), 99.4, 106.8, 108.4, 114.9, 116.7, 122.4, 123.4, 129.2, 131.3,
136.7, 146.5, 159.5, 164.8. Anal. Calcd for C16H14N4O4 (326.31): C, 58.89; H, 4.32; N, 17.17%. Found C,
58.83; H, 4.31; N, 17.13%.
General procedure for formation of the 3-benzodiazepinylquinolines 12 and 13
A mixture of compound 4 (2.86 g, 10 mmol) and 1,4-binuchleophiles namely; O-phenylendiamine (1.1 g,
10 mmol), O-aminothiophenol (1.1 mL, 10 mmol), in DMF (50 mL), was heated under reflux for 4 h. The
solid deposited after cooling was filtered and crystallized from the proper solvent to give compounds 12
and 13, respectively.
1-Ethyl-4-hydroxy-3-(3-nitro-1H-benzo[b][1,4]diazepin-4-yl)quinolin-2(1H)-one (12)
Crystallized from AcOH to give 12 as yellow crystals, mp > 300 °C, yield (2.78 g, 74%). IR (KBr,
cm-1): 3477 (OH), 3227 (NH), 3055 (CHarom), 2976, 2931 (CHaliph), 1630 (C=O), 1592 (C=C), 1548,
1320 (NO2). 1H NMR (DMSO-d6, "): 1.24 (t, 3H, J = 6.9 Hz, CH2CH3), 4.31 (q, 2H, J = 6.9 Hz, CH2CH3),
6.49 - 8.12 (m, 8H, Ar-H), 8.05 (d, 1H, J = 8.4 Hz, H-5), 10.90 (s, 1H, NH exchangeable with D2O),
13
13.43 (s, 1H, OH exchangeable with D2O). C NMR (75 MHz, DMSO-d6, "): 16.1 (CH3), 38.6 (CH2),
98.5, 110.8, 113.7, 117.7, 118.2, 119.4, 119.6, 122.3, 124.2, 124.9, 128.4, 134.6, 135.4, 144.7, 153.7,
155.4, 158.5, 164.1. M/z (relative intensity): 376 [M+; 15], 375 [M+ -1; 8], 306 (20), 305 [M+- O2N-C"CH,
100], 304 (40), 326 (23), 310 (19), 290 (30), 277 (84), 250 (32), 230 (23), 223 (32), 197 (30), 188 (60),

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172 (44), 161 (58), 146 (43) , 132 (79), 118 (48), 90 (38), 77 (79). Anal. Calcd for C20H16N4O4 (376.37): C,
63.83; H, 4.28; N, 14.89%. Found C, 63.80; H, 4.19; N, 14.53.
1-Ethyl-4-hydroxy-3-(3-nitrobenzo[b][1,4]thiazepin-4-yl)quinolin-2(1H)-one (13)
Crystallized from AcOH to give 13 as white crystals, yield (2.63 g, 67%), mp 213 °C. IR (KBr, cm-1):
3416 (OH), 3068 (CHarom), 2922, 2870 (CHaliph), 1646 (C=O), 1615 (C=N), 1595 (C=C), 1558, 1378
(NO2). 1H NMR (DMSO-d6, "): 1.26 (t, 3H, J = 6.9 Hz, CH2CH3), 4.31 (q, 2H, J = 6.9 Hz, CH2CH3), 7.19
(t, 1H, J = 7.5 Hz, Ar-H), 7.31–7.35 (m, 2H, Ar-H), 7.49 (d, 1H, J = 8.2 Hz, Ar-H), 7.65 (t, 1H, J = 7.6
Hz, Ar-H), 7.76 -7.79 (m, 2H, Ar-H), 7.97 (s, 1H, Hthiazepine), 8.21 (d, 1H, J = 7.9 Hz, H-5), 13.68 (s, 1H,
OH exchangeable with D2O). M/z (relative intensity): 393 [M+; 13], 322 [M+- O2N-C"CH, 100], 321 (60),
294 (65), 286 (38), 279 (32), 268 (46), 242 (15), 237 (17), 221 (19), 146 (24), 132 (34), 120 (32), 119
(27), 108 (25), 91 (23), 73 (98). Anal. Calcd for C20H15N3O4S(393.42): C, 61.06; H, 3.84; N, 10.68; S,
8.15%. Found C, 61.03; H, 3.78; N, 10.43; S, 8.11%.
1-Ethyl-4-hydroxy-3-(5-nitro-2-oxo-3-cyanopyridin-6-yl)quinolin-2(1H)-one (14)
Method A. A mixture of !-pyrone 4 (2.86 g, 10 mmol) and malononitrile (0.66 g, 10 mmol), in DMF (50
mL) containing small amount of anhydrous potassium carbonate, was heated under reflux for 4 h. The
solid deposited after cooling was filtered and crystallized from i-PrOH to give compound 14, as pale
brown crystals, mp > 300 °C. yield (2.53 g, 72%). Method B. A mixture of !-pyrone 4 (2.86 g, 10 mmol)
and cyanoacetamide (0.84 g, 10 mmol), in DMF (50 mL) containing small amount of anhydrous
potassium carbonate, was heated under reflux for 4h. The solid deposited after cooling was filtered and
crystallized from i-PrOH to give compound 14, as pale brown crystals, mp > 300 °C. yield (2.64 g, 75%).
IR (KBr, cm-1): 3446 (OH), 3230 (NH), 3084 (CHarom), 2977, 2929 (CHaliph), 2245 (CN), 1675 (C= Opyridine),
1
1632 (C= Oquinolone), 1599 (C=C), 1574, 1384 (NO2). H NMR (300 MHz, DMSO-d6, "): 1.16 (t, 3H, J =
6.4 Hz, CH2CH3), 4.30 (q, 2H, J = 6.4 Hz, CH2CH3), 7.25 (t, 1H, J = 7.2 Hz, H-6), 7.41-7.58 (m, 2H, H-8
and H-7), 7.72 (s, 1H, Hpyridine), 8.11 (d, 1H, J = 8.0 Hz, H-5), 10.51 (s, 1H, NH exchangeable with D2O),
13
12.93 (s, 1H, OH exchangeable with D2O). C NMR (125 MHz, DMSO-d6, "): 12.9 (CH3), 35.5 (CH2),
89.8, 112.9, 114.2, 119.5, 120.8, 121.6, 123.4, 125.8, 129.6, 132.3, 133.5, 139.1, 150.2, 162.2 (C=O),
174.8 (C=O). M/z (relative intensity): 352 [M+; 40], 351 [M+ -1; 52], 331 (57), 313 (45), 297 (41), 271
(55), 260 (43), 235 (50), 210 (48), 202 (18), 188 (92), 186 (49), 169 (5), 158 (17), 146 (74), 131 (100),
104 (68), 91 (51), 82 (58), 77 (81). Anal. Calcd for C17H12N4O5 (352.31): C, 57.96; H, 3.43; N, 15.90%.
Found C, 57.83; H, 3.36; N, 15.73%.
7-(1-Ethyl-4-hydroxy-2-oxo-1,2-dihydro-quinolin-3-yl)-3-hydroxy-6-nitro-2H-[1,2]diazepine-4-
carbonitrile (15)
A mixture of compound 4 (2.86 g, 10 mmol) and cyanoacetohydrazide (1 g, 10 mmol), in DMF (50 mL)
containing few drops of triethylamine, was refluxed for 4 h. After cooling the solid obtained was filtered

HETEROCYCLES, Vol. 87, No. 2, 2013
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and crystallized from DMF to give 15 as yellow crystals, mp > 300 ºC, yield (2.34 g, 64 %). IR (KBr,
-1
cm ): 3440-3243 (bs, NH and 2OH), 3089 (CHarom), 2978, 2933 (CHaliph), 2234 (C"N), 1645 (C= Oquinolone),
1605 (C=C), 1561, 1378 (NO2). 1H NMR (DMSO-d6, "): 1.26 (t, 3H, J = 6.9 Hz, CH2CH3), 4.38 (q, 2H, J
= 6.9 Hz, CH2CH3), 7.34 (t, 1H, J = 7.6 Hz, H-6), 7.59–7.71 (m, 2H, H-7 and H-8), 7.92 (s, 1H, Hdiazepine),
8.12 (d, 1H, J = 8.4 Hz, H-5), 10.89 (s, 1H, NH exchangeable with D2O), 11.01 (s, 1H, OH exchangeable
13
with D2O), 12.94 (s, 1H, OH exchangeable with D2O). C NMR (75 MHz, DMSO-d6, "): 12.5 (CH3),
37.4 (CH2), 98.7, 111.9, 113.8, 115.9, 123.4, 124.5, 132.1, 132.3, 135.8, 140.3, 140.9, 144.7, 153,4, 159.5,
164.6. M/z (relative intensity): 367 [M+; 25], 366 [M+-1; 20], 349 (24), 326 (27), 319 (24), 303 (26), 278
(26), 265 (25), 252 (22), 230 (21), 222 (24), 213 (22), 189 (26), 175 (21), 168 (25), 160 (24), 148 (31),
129 (29), 121 (31), 115 (26), 102 (26), 95 (31), 86 (100), 77 (36), 64 (45). Anal. Calcd for C17H13N5O5
(367.32): C, 55.59; H, 3.57; N, 19.07%. Found C, 55.63; H, 3.69; N, 19.03%.
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