Substituted quinolinones. Part 17: Some nucleophilic reactions with 4-hydroxy-1-methyl-3-[(2-oxo-2H-chromen-3-yl)carbonyl]quinolin- 2(1H)-one

Article abstract of DOI:10.1007/s12039-012-0303-8

The reactivity of 4-hydroxy-1-methyl-3-[(2-oxo-2H-chromen-3-yl)carbonyl]- quinolin-2(1H)-one (2), as a new asymmetric diheterocyclic ketone, towards different nucleophilic reagents, was examined. The reaction of the ketone 2 with hydrazine led to pyrazolinone 5, and excess of hydrazine pyrazolinopyrazole 7 was obtained. Treatment of the ketone 2 with 2,2-dimethoxyethanamine gave pyrrolocoumarin 12, while cyanoguanidine afforded pyrimidinone 15. Under PTC conditions, the ketone 2 was reacted with chloroacetonitrile, diethyl malonate, ethyl cyanoacetate, malononitrile, and cyanoacetamide to give coumarinyl furoquinoline 18, pyranoquinolines 20a, 20b, 21, and benzonaphthyridine 22, respectively. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-012-0303-8

c
J. Chem. Sci. Vol. 124, No. 5, September 2012, pp. 1033–1041. ꢀ Indian Academy of Sciences.
Substituted quinolinones. Part 17: Some nucleophilic reactions with
4-hydroxy-1-methyl-3-[(2-oxo-2H-chromen-3-yl)carbonyl]quinolin-
2(1H)-one
MOHAMED ABASSa,∗, EL-HUSSAIN A MOHAMEDa, AISHA S MAYASb and
AKRAM H IBRAHIMc
aDepartment of Chemistry, Faculty of Education, Ain Shams University, Roxy, Heliopolis 11757, Cairo, Egypt
bDepartment of Chemistry, Faculty of Education, Sana’a University, Sana’a, Yemen
cCurriculum Development Center, Ministry of Education, Ramsis 13411 Cairo, Egypt
e-mail: m.abass@chemist.com
MS received 8 November 2011; revised 4 April 2012; accepted 26 April 2012
Abstract. The reactivity of 4-hydroxy-1-methyl-3-[(2-oxo-2H-chromen-3-yl)carbonyl]-quinolin-2(1H)-one
(2), as a new asymmetric diheterocyclic ketone, towards different nucleophilic reagents, was examined. The
reaction of the ketone 2 with hydrazine led to pyrazolinone 5, and excess of hydrazine pyrazolinopyrazole
7 was obtained. Treatment of the ketone 2 with 2,2-dimethoxyethanamine gave pyrrolocoumarin 12, while
cyanoguanidine afforded pyrimidinone 15. Under PTC conditions, the ketone 2 was reacted with chloroaceto-
nitrile, diethyl malonate, ethyl cyanoacetate, malononitrile, and cyanoacetamide to give coumarinyl furoquino-
line 18, pyranoquinolines 20a, 20b, 21, and benzonaphthyridine 22, respectively.
Keywords. Quinolinone; coumarin; ketones; nucleophilic heterocyclization; PTC.
1. Introduction
new heterocyclic 3-substituted quinolinone derivatives
of expected biological activity.
The coumarin derivatives are representative of the lac-
tones which have well-known pharmaceutical applica-
tions such as antimicrobial,1–4 cytotoxic activity against
tumour cells and treatment of cancer5,6 and signi-
ficant value of anticoagulation potency drugs such as
Warfarin.7–9 In addition, coumarin derivatives consti-
tute an important class of organic fluorescent dyes
with considerable interest for widespread applica-
tion as sensitive fluorescent.10,11 On the other hand,
quinolin-2-ones reveal important medicinal applica-
tions. For example, some quinolin-2-ones showed
potential antidepressant, sedative and anti-Parkinson
activities,12 antimicrobial activity,13 antifungal activi-
ty,14 inhibitory activity against HIV-1 Reverse Tran-
scriptase,15 inhibitory activity against cyclin-dependent
kinase 5 (CDK5),16 antiparasitic and antischistosomal
activity.17–20 The above interesting biological applica-
tion of both coumarin and quinolin-2-one derivatives
invoked our attention to synthesize new heterocyclic
compounds combining quinolin-2-one and coumarin
moieties in one molecular-frame. This comes as a part
of our research program directed at the synthesis of
2. Experimental
2.1 General
Melting points were determined in open capillary tubes
on a digital Stuart SMP3 apparatus. IR spectra were
taken on a Perkin-Elmer FT-IR 1650, using samples
in KBr disks. 1H NMR spectra were recorded on Vari-
an Gemini-200 NMR-spectrometer (200 MHz), using
DMSO-d6 as solvents and TMS as internal reference.
Mass spectra were determined on a Shimadzu GC-MS-
QP 1000 EX mass spectrometer by direct inlet, operat-
ing at 70 eV. Elemental microanalyses were performed
on a Perkin Elmer CHN-2400 Analyzer at the Micro-
analytical Center, Cairo University. All reactions were
monitored by thin-layer chromatography (TLC) on
0.2 mm silica gel F-254 (Merck) plates, using UV light
(254 and 366 nm) for detection.
2.2 4-Hydroxy-1-methyl-3-[(2-oxo-2H-chromen-
3-yl)carbonyl]quinolin-2(1H)-one (2)
This compound was prepared according to the method
described in the literature.21
∗For correspondence
1033

1034
Mohamed Abass et al.
several times with diethyl ether and crystallized from
2.3 4-Hydroxy-3-[4-(2-hydroxybenzylidene)-5-oxo-
4,5-dihydro-1H-pyrazol-3-yl]-1-methylquinolin-2(1H)- DMSO to give the compound 12; yield 65%; mp 200–
one (5)
202◦C. IR (KBr), ν (cm−1): 3420, 3250, (H-bonded O–
H + N–H), 1723 (C=OCoumarin), 1639 (C=Oquinolone),
1
To a suspension of the compound 2 (0.7 g, 2 mmol), in
ethanol (20 mL), was added hydrazine hydrate (0.1 mL,
2 mmol, 100%). Then, the mixture was heated under
reflux for 3 h. The solution so formed was cooled to
room temperature to give a crystalline precipitate which
was filtered and recrystallized from DMF to give the
pyrazole 5; yield 75%; mp 245–246◦C. Literature22
m.p. 241–242◦C.
1188, 1130, 1077(C-O). H NMR (200 MHz, DMSO-
d6): δ = 3.30 (s, 3H, NCH3), 3.35 (s, 3H, OCH3), 4.60
(s, 2H, CH2OCH3), 7.23–8.15 (s, 8H, Harom.), 13.17(s,
1H, NH), 14.52 (s, 1H, OH). MS (m/z; %) = 402 (13)
(M+.), 403 (M+1; 3.3), 404 (M+2; 2.5), 359 (2.6), 330
(14.3), 104 (4.8), 75 (100), 51 (4.6). Anal. Calcd. (%)
for C23H18N2O5 (402.41): C, 68.65; H, 4.47; N, 6.96.
Found (%): C, 68.60; H, 4.50; N, 6.70.
2.4 4-Hydroxy-3-[4-(2-hydroxyphenyl)-1,4,5,
6-tetrahydropyrazolo[3,4-c]pyrazol-3-yl]-1-
methylquinolin-2(1H)-one (7)
2.6 2-(N-Cyanoimino)-4-(4-hydroxy-1-methyl-2-oxo-
1,2-dihydroquinolin-3-yl)-5-(2-hydroxybenzylidene)-
1,2-dihydropyrimidin-6(5H)-one (15)
2.4a Procedure A: To a suspension of the compound
5 (0.72 g, 2 mmol), in DMF (15 mL), hydrazine hydrate
(0.1 mL, 2 mmol) was added and heated under reflux
for 2 h. After cooling, the crystalline material that
formed was filtered and recrystallized from DMF to
give the pyrazolopyrazole 7; yield 70%; mp >300◦C.
IR (KBr), ν (cm−1): 3333–2625 (H-bonded O–H +
A mixture of compound 2 (0.7 g, 2 mmol), cyanoguani-
dine hydrochloride (0.25 g, 2 mmol) and (0.1 mL), fine
powdered potassium hydroxide (0.56 g, 10 mmol), in
ethanol (30 mL), was heated under reflux for 3 h. After-
wards, the mixture was left to cool at room temper-
ature, poured onto cold water and then acidified with
ice-cold dilute hydrochloric acid till complete precipi-
tation. The solid precipitate so obtained was filtered,
washed with water and crystallized from DMF, afford-
ing the pyrimidine 15; yield 56%; mp 220–221◦C. IR
(KBr), ν (cm−1): 3424 (H-bonded OH, NH), 2198
(C≡N), 1652 (C=Oquinolone), 1637 (C=Opyrimidone), 1570
1
N–H), 1644 (C=Oquinolone), 1611 (C=N). H NMR
(200 MHz, DMSO-d6): δ = 2.75 (s, 1H, CHpyrazoline),
3.74 (s, 3H, NCH3), 7.35–8.09 (m., 8H, H arom.), 8.40
(b, 1H, NHpyrazole), 9.20 (b, 1H, NHpyrazole), 9.40 (b,
1H, NHpyrazoline) 11.00 (s, 1H, OHphenolic), 13.8 (s, 1H,
OHquinolinone). MS (m/z; %) = 375 (10) (M+.), 376
(M+1; 2.8), 377 (M+2; 3.2), 364 (6.3), 363 (26.4), 361
(100), 228 (12.7), 200 (19.9), 188 (19.6), 187 (14.0),
176 (16.2), 175 (86.3), 147 (23.4), 134 (23.7), 104
(26.3), 77 (50.9), 63 (12.9), 51 (26.7). Anal. Calcd. (%)
for C20H17N5O3 (375.39): C, 63.99; H, 4.56; N, 18.66.
Found (%): C, 64.10; H, 4.40; N, 18.60.
1
(C=N). H NMR (200 MHz, DMSO-d6): δ = 3.53
(s, 3H, NCH3), 6.80 (s,1H, Holefin), 6.99–8.00 (m, 8H,
Harom), 10.40 (s, 1H, NH), 11.35 (s, 1H, OHphenol), 13.85
(s, 1H, OHquinolone). MS (m/z; %) = 413 (6.6) (M+.),
414 (M+1; 2.2), 399 (28.5), 371(100), 227 (10.5), 185
(30.0), 159 (32.1), 146 (8.2), 143 (13.4), 55 (50.6).
Anal. Calcd. (%) for C22H15N5O4 (413.40): C, 63.92; H,
3.66; N, 16.94. Found (%): C, 63.90; H, 3.60; N, 16.60.
2.4b Procedure B: To a suspension of the compound
2 (0.35 g, 1 mmol), in ethanol (10 mL), was added
hydrazine hydrate (0.1 mL, 2 mmol). The mixture was
heated under reflux for 4 h and the solid precipitate that
obtained was filtered, and crystallized from DMF to
give the pyrazolopyrazole 7; yield 78%.
2.7 PTC-Reaction of the ketone 2 with active
methylene compounds
To a mixture of compound 2 (0.7 g, 2 mmol), TBAB
(0.25 g, 1 mmol) and potassium carbonate (1.38 g,
10 mmol), in DMF (20 mL), was added 2 mmol of the
proper active methylene reagent viz; chloroacetonitrile
(0.15 mL), diethyl malonate (0.3 mL), ethyl cyanoace-
tate (0.22 mL), malononitrile (0.14 g), and cyanoace-
2.5 3-(4-Hydroxy-1-methyl-2-oxo-1,
2-dihydroquinolin-3-yl)-1-(methoxymethyl-
chromeno[3,4-c]pyrrol-4(2H)-one (12)
A mixture of the compound 2 (0.7 g, 1 mmol) and 2,2- tamide (0.17 g). The mixture was heated under reflux
dimethoxyethanamine (0.5 mL, 4 mmol), in toluene was for 4 h. The mixture was filtered off, while hot, and the
heated under reflux 4 h. The solvent was evaporated to filtrate was poured onto cold water and then acidified
dryness and the residue was treated with cold methanol with dilute hydrochloric acid. The solid precipitate so
(5 mL) to obtain a solid powder, which was washed obtained was filtered and crystallized from DMF.

Reactions with substituted quinolinones
1035
2.7a 5-Methyl-4-oxo-3-(2-oxo-2H-chromen-3-yl)-4, (s, 3H, CH3), 7.25 (t, 1H, 8-Hfuroquinoline), 7.38–7.45 (m,
5- dihydrofuro[3,2-c]quinoline-2-carbonitrile (18): Yield 3H, Harom), 7.65 (t, 1H, Harom, 7-Hcoumarin), 7.78–7.92
73%; mp 270–2◦C. IR (KBr), ν (cm−1): 3082, 2957, (m, 3H, Harom), 8.05 (s, 1H, 4-Hcoumarin). MS (m/z; %) =
2196 (C≡N), 1724 (C=Ocoumarin), 1642 (C=Oquinolone), 368 (M+.) (100), 369 (M = 1; 23), 370(M+2; 2), 342
1602 (C=C). 1H NMR (200 MHz, DMSO-d6): δ = 3.48 (64), 340 (72), 324 (36), 314 (22), 195 (47), 175 (35),
CHO
OH
O
O
OH
O
O
O
OH
CO2H
O
piperidine
EtOH
N
N
CH3
1
CH3
2
N2H4.H2O (Mr,1:1)
EtOH/DMF
NH2
NH2
O
OH
OH
N
O
O
O
O
HN
O
or
N
N
CH3
CH3
HO
3
4
X
H
N
O
N
HN
N
N
OH
O
O
N
O
O
HO
CH3
CH3
5
6
N2H4.H2O
EtOH/DMF
NH
OH
N
NH
NH
H
OH
N
O
CH3
7
Scheme 1. Synthesis of compound 2 and its reaction with hydrazine hydrate.

1036
Mohamed Abass et al.
174 (22), 169 (14), 160 (22), 149 (11), 90 (16), 89 (14), 1642 (C=Ocoumarin), 1629 (C=Oquinolone). 1H NMR
72 (24), 69 (41). Anal. Calcd. (%) for C22H12N2O4 (200 MHz, DMSO-d6): δ = 1.24 (t, 3H, OCH2CH3),
(368.08): C, 71.74; H, 3.28; N, 7.61. Found (%): C, 3.97 (s, 3H, NCH3), 4.23 (q, 2H, CH2CH3), 7.36–
72.10; H, 3.30; N, 7.50.
7.88 (m, 8H, Harom.), 8.16 (s, 1H, C4-Hcoumarin). MS
(m/z; %) = 443 (M+.) (6.8), 444 (M+1; 2.1), 362
(15.2), 341 (2.7), 342 (22.6), 343 (8.6), 324 (5.4), 307
(6.3), 262 (11.7), 215 (11.5), 175 (26.3), 144 (100),
104 (26.3), 71 (71.4), 55 (74.2), 57 (94.1). Anal. Calcd.
(%) for C25H17NO7 (443.42): C, 67.72; H, 3.86; N,
3.16. Found (%): C, 67.60; H, 3.80; N, 3.10.
2.7b Ethyl 6-methyl-2,5-dioxo-4-(2-oxo-2H-chromen-
3-yl)-5,6-dihydro-2H-pyrano[3,2-c]-quinoline-3-carbo-
xylate (20a): Yield 66%; mp >300◦C. IR (KBr), ν
(cm−1): 3072, 2856, 1710 (C=Oester), 1693 (C=Opyrone),
O
N
O
CH3
O
H3C
OH
CH3
O
OH2
H3C
OH
N
O
O
O
H2N
Toluene / Heat
O
N
O
O
O
CH3
2
CH3
8
OH
O
N
O
N
δ−
δ+
OH
OH
H+
N
O
O
N
O
O
O
CH3OH
CH3
CH3
9
OH
O
O
OH HN
OH HN
O
O
O
N
O
N
O
CH3
CH3
10
CH3
O
OCH3
OH
O
O
H3C
OH HN
OH HN
H2N
H+
O
O
N
O
O
O
N
CH3
CH3
12
11
H2N
CH3OH
+
O
Scheme 2. A mechanistic pathway for formation of compound 12.

Reactions with substituted quinolinones
1037
2.7c 6-Methyl-2,5-dioxo-4-(2-oxo-2H-chromen-3-yl)- (cm−1): 3396 (NH), 2925, 2201 (C≡N), 1710
5,6-dihydro-2H-pyrano[3,2-c]quinoline-3-carbonitrile
(C=Ocoumarin), 1640 (C=Oquinolone), 1601(C=N). 1H
(20b): Yield 63%; mp >300◦C. IR (KBr), ν (cm−1): NMR (200 MHz, DMSO-d6): δ = 3.70 (s, 3H, NCH3),
3076, 2203 (C≡N), 1703 (C=O coumarin), 1969 7.22–7.57 (m., 8H, Harom.), 8.10 (s, 1H, C4-Hcoumarin),
1
(C=Opyrone), 1633 (C=Oquinolone). H NMR (200 MHz, 8.75 (b, 1H, NH). MS (m/z; %) = 395 (M+.) (56.4),
DMSO-d6): δ = 3.58 (s, 3H, NCH3), 7.31 (t, J = 8 Hz, 396 (M+1; 14.3), 266 (23.2), 265 (22.4), 260 (16.3),
2H, C8-H), 7.50 (d, J = 8 Hz, 2H, C7-H), 7.66 (t, J = 233 (14.4), 232 (16.6), 168 (20.3), 141 (19.5), 115
8 Hz, 2H, C6-H), 8 (d, J = 8 Hz, C5-H), 8.56 (s, 1H, (14.3), 111 (11.2), 82 (21.5), 73 (31.7), 68 (23.8),
C4-Hcoumarin). MS (m/z; %) = 396 (M+.) (5.0), 397 60 (100), 59 (87.7), 57 (28.3). Anal. Calcd. (%) for
(M+1; 1.9), 395 (28.3), 285 (24.4), 284 (24.6), 238 C23H13N3O4 (395.38): C, 69.87; H, 3.31; N, 10.63.
(48.6), 239 (38.6), 217 (48.9), 206 (43.6), 186 (28.9), Found (%): C, 69.80; H, 3.30; N, 10.60.
169 (33.4), 159 (62.6), 142 (33.7), 119 (19.8), 117
(71.0), 115 (23.8), 90 (23.8), 60 (100), 53 (33.6). Anal.
Calcd. (%) for C23H12N2O5 (396.36): C, 69.70; H, 3.05;
N, 7.07. Found (%): C, 69.60; H, 3.10; N, 7.20.
2.7e 6-Methyl-2,5-dioxo-4-(2-oxo-2H-chromen-3-yl)-
1,2,5,6-tetrahydrobenzo[h]-1,6-naphthyridine-3-carbo-
nitrile (22): Yield 59%; mp 288–9◦C. IR (KBr), ν
(cm−1): 3424 (NH), 3061, 2938, 2198 (C≡N), 1722
(C=Ocoumarin), 1644 (C=Opyridone), 1637 (C=Oquinolone).
1H NMR (200 MHz, DMSO-d6): δ = 3.44 (s, 3H,
NCH3), 7.10–7.81 (m, 8H, Harom.), 7.99 (s, 1H, C4-
2.7d 2-Imino-6-methyl-5-oxo-4-(2-oxo-2H-chromen-
3-yl)-5,6-dihydro-2H-pyrano[3,2-c]quinoline-3-carbo-
nitrile (21): Yield 84%; mp 291–2◦C. IR (KBr), ν
O
O
NH2
N
OH
O
O
O
C
OK
OH
N
NH2
NH2
O
N
H
N
C
N
N
KOH / EtOH
N
O
CH3
CH3
2
O
O
OH
H
O
NH2
OK
N
OK
N
- H2O
C
N
N
N
C
N
N
N
O
N
O
CH3
CH3
13
O
N
OK
HO
KO
OH
NH
OK
N
N
C
- H2O
dil. HCl
N
N
N
C
N
O
N
O
N
CH3
CH3
14
15
Scheme 3. A mechanistic pathway for formation of compound 15.

1038
Mohamed Abass et al.
H
coumarin), 8.30 (s, 1H, NH). MS (m/z; %) = 395 (M+.) in 70% yield, when the pyrazolylquinolinone 5 was
(3.5), 396 (M+1; 1), 354 (3.8), 238 (21.2), 239 (12.2), subjected to react with hydrazine hydrate, in DMF.
218 (21.4), 217 (13.6), 206 (21.9), 186 (18.1), 169 The same compound was obtainable by treating the
(12.8), 159 (21.6), 142 (43.2), 119 (14.3), 117 (73.4), ketone 2 with excess of hydrazine hydrate. The struc-
115 (23.2), 90 (15.2), 61 (100), 53 (33.4). Anal. Calcd. ture of compound 7 was inferred from its analytical
(%) for C23H13N3O4 (395.38): C, 69.87; H, 3.31; N, and spectral data. IR spectrum showed broad stretch-
10.63. Found (%): C, 69.60; H, 3.20; N, 10.30.
ing band at ν˜ 3333–2625, characteristic for H-bonded
O–H and N–H, 1644 due to C=O of quinolin-2-one. 1H
NMR spectrum revealed a singlet peak at δ 2.75 due
to C5-H of pyrazolinopyrazole, a singlet peak at δ 3.74
due to N–CH3. In addition, five broad peaks, which dis-
appeared on deutration with D2O, were observed at δ
8.40, 9.20, 9.40 (NH groups), 11.00 and 13.80 (pheno-
lic OH groups). Mass spectrum confirmed the proposed
formula revealing a molecular ion peak at m/z 375
along with a base peak at 361 due (M+ – CH3) cation. In
addition, a fragment appeared at m/z 175 characteristic
for 4-hydroxy-1-methylquinolin-2-one cation.
The reaction of the ketone 2 with 2,2-dime-
thoxyethanamine was carried out in boiling toluene
in order to obtain the corresponding Schiff’s base.
1H NMR spectrum of the product showed three sin-
glet chemical shifts at δ 3.30 due to (NCH3), δ 3.35
attributed to three protons of (OCH3), and δ 4.60 due
to two protons of (CH2OMe). The aromatic eight pro-
tons were observed as multiplet at δ 7.23–8.15. The
characteristic proton at position 4 of coumarin was
absent. Two D2O-exchangeable protons were noticed at
3. Results and discussion
Some literature reports had cited important reactions
of α-pyrones with hydrazine derivatives in synthesis of
pyrazolines.23 Accordingly, the reaction of the ketone
2 with hydrazine hydrate was carried out at equimo-
lar ratio, to give pyrazolylquinolinone 5. This product
may be afforded through intermediacy of the hydrazide
3 or the hydrazone 4. Anyhow formation of the hydra-
zone intermediate 4 may lead to formation of the pyra-
zoloquinolinone 6 and/or the pyrazolylquinolinone 5
(scheme 1). Since pyrazolylquinolinone 5 was only sep-
arated from this reaction. This result led to assuming
that the formation of the pyrazolylquinolinone 5 takes
place via ring-opening ring closure (RORC) pathway.
Moreover, the spectral and analytical data of the pyra-
zolylquinolinone 5 are coincident with data of a pre-
viously prepared authentic sample, using different syn-
thetic route.22 The pyrazolopyrazole 7 was obtained,
N
OH
O
O
O
O
O
Cl
O
O
N
N
N
O
2
K2CO3/TBAB
DMF
O
CH3
CH3
16
N
N
H
O
O
O
O
OH
O
H+
O
- H2O
N
O
N
O
CH3
CH3
18
17
Scheme 4. Formation of chromenylfuro[3,2-c]quinoline derivative 18.

Reactions with substituted quinolinones
1039
δ 13.17 and 14.52 due to N–H and O–H, respectively. TBAB, in DMF. IR spectrum of the product demon-
IR spectrum exhibited stretching bands at ν˜ 3420, and strated absorption band at ν˜ 2196 characteristic for
3250 cm−1, due to N–H and O–H. The absorption bands (C≡N), in addition to ν˜ 1724 and 1642 cm−1 due to
due to the carbonyl groups of coumarin, quinolinone (C=O) of both coumarin and quinolin-2one, respec-
1
moieties appeared at ν¯ 1723, 1639 cm−1, respectively. tively. H NMR revealed peaks at δ 7.25–7.92 due to
Accordingly, the product was characterized as the eight aromatic protons, in addition to a singlet peak at
quinolinylchromeno[3,4-c]pyrrole 12. The formation of δ 8.05 distinguishing proton at position 4 of coumarin.
the product is thought to pass through these consecu- MS spectrum represented the molecular ion peak (M+.)
tive steps; condensation, de-methanolysis, intramole- at m/z 368 as the base peak (I%, 100), along with M+1
cular Michael addition, and SN2 O-methylation of the at 369 (23%), and (M+2) at 370 (2%). These results are
presumed condensation intermediate (scheme 2).
perfectly integrated with elemental microanalysis of the
Cyanoguanidine, as 1,3-nucleophile, was subjected product and suggested that the 3-coumarinylfuro[3,2-
to react with the ketone 2, in the presence of potassium c]quinoline-2-carbonitrile derivative 18 is the product
1
hydroxide. H NMR spectrum of the product showed (scheme 4).
no indication for the proton, at position-4, of coumarin
The reaction of the compound 2 with diethyl malo-
and revealed the following characteristic peaks at δ nate was carried out, in DMF, under phase transfer
3.53 (N–CH3), 6.80 (olefinic C–H, 1H), 6.99–8.00 (aro- catalysis (PTC) conditions, using potassium carbo-
matic C–H, 8H), 10.40 (N–H), 11.35 (O–H), and 13.85 nate and tetrabutylammonium bromide (TBAB). PTC
(O–H). IR spectrum confirmed the disappearance of reaction technique was selected to prevent unde-
C=O of coumarin nucleus and showed the following sired α-pyrone ring opening open which is expected
absorption bands at ν˜ 3424 (N–H), 2198 (C≡N), 1652 on use of ordinary basic media, e.g., hydrox-
1
(C=O), 1637 (C=O) cm−1. H NMR and IR spectra ides or alkoxides. Under PTC conditions, ethyl
proved opening of coumarin ring via an intramolecular 4-coumarinylpyranoquinoline-3-carboxylate 20a was
nucleophilic tetrahedral addition in intermediate 13 and obtained, in 66% yield (scheme 5). 1H NMR spectrum
closure of pyrimidinone ring, leading to sodium eno- of compound 20a confirmed the presence of signals
late 14 which upon acidification afforded the product. owing to OCH2CH3 appeared as triplet at δ 1.24 and
Hence, the 4-quinolinylpyrimidine derivative 15 was quartet at δ 4.23, in addition to a singlet peak at δ 8.16
characterized as the product of this reaction (scheme 3). due to chemical shift of C4–H of coumarin. IR spec-
The reaction of chloroacetonitrile with the ketone 2, trum fortified the supposed structure of compound 20a
was carried out under phase transfer catalytic condi- where its spectrum showed characteristic bands at ν˜
tions (PTC), in the presence of potassium carbonate and 1710, 1693, 1642 cm−1, due to C=O of carboxylate,
O
Et
O
O
R
H
O
OH
O
O
CO2Et
H+
R
O
O
N
N
CH3
O
O
2
K2CO3/TBAB
DMF
CH3
19
O
H
O
O Et
R
R
O
O
O
O
H+
O
O
N
O
N
O
CH3
CH3
EtOH
R = CO Et
R = CN2
20a,
20b,
Scheme 5. Formation of chromenylpyrano[3,2-c]quinoline derivatives 20a,b.

1040
Mohamed Abass et al.
α-pyrone, and 2-quinolone, respectively. Mass spectrum Additionally, 1H NMR spectrum gave no indication for
showed a base peak at m/z 144 corresponding to 3,4- the presence of O-ethyl protons, revealing the absence
dehydrocoumarin cation in addition to a peak at m/z of carboxylate group. These results have led to decision
175 (26.3%) characteristic for 4-hydroxy-1-methyl-2- that the product was the coumarinylpyranoquinoline-3-
quinolone cation. Under the same PTC conditions, the carbonitrile 20b (scheme 5).
compound 2 was reacted with ethyl cyanoacetate,. IR
Reaction of the compound 2 with malononitrile, at
spectrum of the product showed a clear evidence for the the molar ratio 1:1, was carried out either under the
presence of a cyano group, as observed at ν˜ 2203 cm−1. above PTC-conditions. Characterization of the product
OH
O
O
O
N
O
CH3
2
O
N
N
N
NH2
K2CO3/TBAB
DMF
K2CO3/TBAB
DMF
O
O
N
O
N
O
N
H
H2N
O
H
O
O
O
N
O
N
CH3
CH3
H+
H+
H2O
O
NH
CN
CN
O
HN
N
O
O
O
O
O
N
O
CH3
22
Scheme 6. Formation of chromenylpyrano[3,2-c]quinoline 21 and chromenylbenzonaphthyridine 22.
CH3
21

Reactions with substituted quinolinones
1041
satisfactorily supported that malononitrile underwent
nucleophilic condensation at the chain carbonyl group,
followed by an intramolecular nucleophilic addition of
enolate oxygen anion to one of the two cyano functions
(6-exo-dig ring closure), leading to 2-iminopyrano[3,2-c]
quinoline-3-carbonitrile 21, in 84% yield (scheme 6).
1H NMR spectrum showed signal peaks at δ 3.70
due to N–CH3, and at δ 8.10 which was attributed to
C4–H of coumarin. In addition, a singlet signal was
observed at δ 8.75 due to N–H, disappeared on addi-
tion of deuterium oxide. IR spectrum exhibited vibra-
tional bands at ν˜ 3396 due to N–H, 2201 due to CN,
1710 due to C=O of coumarin, and 1640 due to C=O
of quinolone. The same PTC-conditions were applied
in the reaction of the compound 2 with cyanoacetamide.
IR spectrum of the product showed stretching bands
at ν˜ 3424 due to NH, 2198 due to C≡N, 1722 due
to C=O of α-pyrone, and 1644 cm−1 due to C=O
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1
of α-pyridone. H NMR spectrum indicated the pres-
ence of an acidic proton, observed as singlet signal
at δ 8.30 exchangeable with deuterium, due to N–H
of naphthyridine. Consequently, the structure was
deduced as 4-coumarinylbenzo[h][1,6]naphthyridine-
3-carbonitrile 22 (scheme 6).
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4. Conclusion
The reaction of 4-hydroxy-1-methyl-3-[(2-oxo-2H-
chromen-2-yl)carbonyl]quinoline-2(1H)-one (2) with
some selected nucleophilic reagents gave new inter-
esting polynuclear heterocyclic compounds. PTC-
Conditions have been proved to be useful in reaction
of the ketone 2 with nucleophiles, in particular C-
nucleophiles, leading to fused polynuclear heterocycles.
19. El-Shennawy A M, Hammam O A, Abass M, and Ali E
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