Substituted quinolinones. 18. 3-Acetyl-4-methylthioquinolin-2(1H)-one as useful synthon intermediate for synthesis of some new quinolinones

Article abstract of DOI:10.1007/s11164-012-0678-7

3-Acetyl-4-methylthioquinolin-2(1H)-one (3) has been prepared and its reactivity towards treatment with different reagents, dilute sulfuric acid, aqueous sodium hydroxide, and hydrogen peroxide, is described. The reactions of compound 3 with benzylamine,

Full text of DOI:10.1007/s11164-012-0678-7

Res Chem Intermed
DOI 10.1007/s11164-012-0678-7
Substituted quinolinones. 18. 3-Acetyl-4-
methylthioquinolin-2(1H)-one as useful synthon
intermediate for synthesis of some new quinolinones
•
Mohamed M. Hassan Elham S. Othman
Mohamed Abass
•
Received: 26 April 2012 / Accepted: 4 June 2012
Ó Springer Science+Business Media B.V. 2012
Abstract 3-Acetyl-4-methylthioquinolin-2(1H)-one (3) has been prepared and its
reactivity towards treatment with different reagents, dilute sulfuric acid, aqueous
sodium hydroxide, and hydrogen peroxide, is described. The reactions of compound 3
with benzylamine, benzaldehyde, DMF-DMA, Vilsmeier-Haack reagent, 2-chloro-3-
formyl-pyridopyrimidone and malononitrile have been carried out under convenient
conditions. Compound 3 underwent heterocyclization reactions with some binucle-
ophiles, hydrazine, hydroxylamine, urea, thiourea, semicarbazide, and thiosemicar-
bazide, furnishing some known five, six, and seven heterocyclic annellated quinolines.
All the new compounds have been characterized using different spectral and analytical
tools.
Keywords Quinolinone ꢀ Phase transfer catalysis ꢀ Vilsmeier reaction ꢀ
Nucleophilic condensation ꢀ Annellation
Introduction
Among fused six-membered heterocyclic azines, quinoline is of great importance in
biological applications and, in particular, 2-quinolinone derivatives are naturally
important members of this category. As previously reported, many 2-quinolinone
derivatives, having miscellaneous substituent groups at positions 3 and/or 4,
displayed potent biological activities [1, 2]. 2-Quinolinones and their analogues
M. M. Hassan ꢀ E. S. Othman ꢀ M. Abass (&)
Faculty of Education, Department of Chemistry,
Ain Shams University, Roxy Cairo 11757, Arab Republic of Egypt
e-mail: m.abass@chemist.com
M. M. Hassan
Basic Science Unit, College of Engineering, Majmaah University,
Majmaah 11952, Kingdom of Saudi Arabia
123

M. M. Hassan et al.
exhibit a wide spectrum of valuable biological activities, such as antiparasitic
activity [2–6], antimicrobial effect [7–10], antioxidant agents [11, 12], anti-hepatitis
C and B viruses activity [13, 14], anticancer and antitumor activity [15, 16],
androgen receptor modulators [17], gonadotropin-releasing hormone receptors [18],
CB2 receptor inverse agonists [19], potent CDK5 inhibitors [20], inhibitors of
steroid 5a reductases types [21], potential Rho-kinase inhibitors [22], and
antiproliferative and antiplatelet activities [23]. The present work is an extension
to our previous work which dealt with substituted quinolinones and its analogues
with promising biological activities [1, 2, 24, 25]. Consequently, in this work, the
key compound; 3-acetyl-4-methylthioquinolin-2(1H)-one was selected, containing
both 4-methylthio as a good leaving group and 3-acetyl functional group which is
susceptible to different condensation reactions, including those leading to annel-
lation with the quinoline nucleus.
Results and discussion
The key compound; 3-acetyl-4-(methylthio)quinolin-2(1H)-one (3) was obtained
via two-step methodology starting from acetoacetanilide (1). Modified phase
transfer catalyzed (PTC) addition of acetoacetanilide to carbon disulfide, using
potassium carbonate and tetrabutylammonium bromide (TBAB) and in situ
methylation, using dimethyl sulfate, led to the ketene dithioacetal 2 [26], in 96 %
yield. Thermal cyclization of the compound 2, in boiling o-dichlorobenzene,
according to the described method of Pak et al. [27], afforded the quinolone 3, in
fair yield (Scheme 1). The reactivity of the quinolone 3 towards different reagents
was studied leading to miscellaneous 3,4-disubstituted quinolin-2(1H)-one deriv-
atives. Thus, boiling of compound 3 in dilute sulfuric acid (50 %) caused
deacetylation along with replacement of the methylthio function with a hydroxyl
function giving rise to 4-hydroxyquinolin-2(1H)-one (4) [28]. The alkaline
hydrolysis of the quinolone 3, using aqueous sodium hydroxide, afforded the
known 3-acetyl-4-hydroxyquinolin-2(1H)-one (5) [29], in 78 % yield. Obviously,
this takes place via nucleophilic replacement of the 4-methylthio function. During
trials to carry out condensation of the acetyl function of the quinolone 3 with some
amines, it was found that treatment of the quinolone 3 with benzylamine, in the
presence of a catalytic amount of benzylamine hydrochloride, led to an unexpected
nucleophilic replacement of 4-methylthio function with a benzylamino one,
affording 3-acetyl-4-benzylaminoquinolin-2(1H)-one (6). It was found that these
results are correlated with those reported in the literature [27]. The convenient
oxidation of the quinolone 3 with hydrogen peroxide, in glacial acetic acid,
1
furnished the sulfoxide derivative 7. H NMR spectrum (CDCl3) of the product 7
revealed two singlet chemical shifts at d 2.78 and 3.01 due to protons of (MeSO)
and (MeCO) functions, while its IR spectrum showed two absorption vibrations due
to stretching of the C=O bond at mmax 1,668 and 1,632 cm-1, corresponding to
acetyl and 2-quinolone carbonyls (Scheme 1).
Knoevenagel condensation of the quinolone 3 with benzaldehyde, to obtain the
enone 8, was carried out in the presence of piperidine. Mass spectrum and elemental
123

Substituted quinolinones. 18. 3-Acetyl-4-methylthioquinolin-2(1H)-one
OH
CH3
O
H2SO4 (50%)
100 oC / 4 h
O
N
H
N
H
O
1
i. CS2/K2CO3/TBAB/r.t./2.5 h
ii. Me2SO4/r.t./ 4.5 h
4
CH3
S
H3C
OH
O
S
O
O
S
NaOH (15%)
CH3
CH3
CH3
H
N
o-DCB
CH3
100 oC / 4 h
180oC/4 h
N
H
O
N
H
O
O
5
2
3
H3C
O
S
O
O
NH
O
O
BzNH2/BzNH3+Cl-
H2O2 (30%)/AcOH
r.t./24 h
CH3
CH3
o-DCB/180oC/6 h
N
H
N
H
7
6
Scheme 1 Preparation and some reactions of the compound 3
analysis of the product 8 confirmed the resulting condensate product. 1H NMR and
IR spectra showed that this product is present in a chain-ring tautomerism and
1
predominately assumes a cyclic structure (Scheme 2). H NMR spectrum (CDCl3)
of this product did not reveal any indication of either Z- or E-enone side chains.
Instead, the spectrum showed three chemical shifts for three protons; two of them
appeared as an AB system at d 3.06 and 3.21 and the third proton appeared as a
multiplet signal at d 5.76. At the same time, the IR spectrum showed only one strong
band due to stretching vibration of the C=O bond which belongs to a 4-pyranone
moiety. This can be attributed to the existence of a chain-ring tautomerism in which
the 2-hydroxy function undergoes an intramolecular addition at the b-position of the
enone chain. The reaction of the compound 8 with hydroxylamine hydrochloride, in
boiling DMF, furnished the isoxazoline 9 (Scheme 2). Obtaining isoxazoline 9
indicated that compound 8 is present in equilibrium between the enone chain and
the 4-pyranone ring tautomers. This hypothetical conclusion arose from the
transformation of compound 8 to the isoxazoline 9 which is obtainable, as known,
from chalcon derivatives (enones), while 4-pyranone can lead to the corresponding
4-oximopyrane. Even though there is no doubt about the presence of chain-ring
tautomerism in compound 8, we feel that this behavior may need more study to
rationalize the relative amounts of both tautomers in different solvents and at
different temperatures.
123

M. M. Hassan et al.
H3C
H3C
CHO
S
O
O
S
O
O
Piperidine/EtOH
3
+
Δ / 6 h
N
H
N
H
8
H3C
O
S
N
DMF
+
8
NH2OH.HCl
Δ / 4 h
N
H
O
9
Scheme 2 Reaction of compound 3 with benzaldehyde and cyclization of the product 8 with
hydroxylamine
An interesting study of the reaction between the quinolone 3 and dimethylform-
amide dimethylacetal (DMF-DMA) was carried out. Thus, this reaction when
carried out at the molar ratio (1:1), in boiling benzene, afforded only one product.
1
The product was characterized as the expected b-enaminone 10 (Scheme 3). H
NMR spectrum of the product represented two distinctive chemical shifts at d 6.42
and 8.24, both appeared as doublets (J = 13.2 Hz), corresponding to E-enaminone
olefinic protons (CO–CH=CH–NMe2). When the same reaction was carried out at a
higher molar amount of DMF-DMA, in boiling benzene, there is not any change in
either the type of the product or even in the reaction yield. But a remarkable change
was observed with molar ratio (1:3) when we replaced boiling benzene as the
reaction solvent with boiling o-xylene. Under these conditions, a mixture of
the b-enaminone 10 and the acrylaldehyde 11 was obtained (Scheme 3). The
acrylaldehyde 11 was separated as a crystalline product after reflux of the reaction
mixture for 4 h, while it was found that the concentration of the reaction filtrate
furnished the b-enaminone 10 (cf. ‘‘Experimental’’ section). Spectral data of the
compound 11 confirmed the presence of a carbaldehyde function as indicated by the
chemical shift at d 10.06 and the absorption stretching vibration at mmax 1,719 cm-1
.
Also, 1H NMR spectrum ((CD3)2SO) of the compound 11 gave important
information about the geometry of the b-(dimethylamino)-acrylaldehyde moiety
where the olefinic proton appeared as a singlet at d 8.99 which is characteristic for
E-form. We expect that the acrylaldehyde 11 was formed by firstly formation of the
b-enaminone 10, which in turn is electrophilically formylated with excess DMF-
DMA. During attempts to recrystallize the acrylaldehyde 11 from glacial acetic
acid, a dramatic change in the melting point of the recrystallized material (before,
[300 °C, and after, 187–190 °C) was observed. However, recrystallization from
dioxane maintained the melting point of this material, before and after, at[300 °C.
The acrylaldehyde 11 was subjected to boiling in glacial acetic acid, and the lower-
melting point product 12 was obtained in high yield (84 %). Characterization of the
product 12 showed that we have a new compound, in which an intramolecular
123

Substituted quinolinones. 18. 3-Acetyl-4-methylthioquinolin-2(1H)-one
nucleophilic replacement of the dimethylamino group took place effecting c-pyrone
ring closure. 1H NMR spectrum ((CD3)2SO) showed four types of protons; the first
type is the SCH3 protons which appeared as singlet signal at d 2.72, the second type
is the aromatic four protons at d 7.33–8.09, the third type is the a-proton of c-pyrone
which appeared as singlet signal at d 8.56, and the fourth type is the aldehydic
proton which appeared as singlet signal at d 10.04. A confirmatory synthesis of the
compound 12 was achieved via Vilsmeier–Haack formylation of the quinolone 3,
dimethylformamide, and using phosphoryl chloride (Scheme 3). The 3-acetyl-2-
hydroxyquinoline form of the quinolone 3 performed the same behavior of
o-hydroxyacetophenone towards the Vilsmeier reagent [30].
The reaction of the quinolone 3 with 2-chloro-4-oxo-4H-pyrido[1,2-a]pyrimi-
dine-3-carbaldehyde (13) [31], in the presence of piperidine, is expected to give one
product or a mixture of the condensate enone 14 and/or the diheterocycle ether 15
(Scheme 4). Characterization of the resultant indicated that only one product was
obtained, in which both acetyl and formyl groups are present, as indicated by IR and
1H and 13C NMR spectra of the separated product. The product includes chlorine
and does not contain any deuterium exchangeable protons (cf. ‘‘Experimental’’
section). In addition to this structural evidence, mass spectrum confirmed that the
obtained product is the diheterocycle ether 15, not the condensate enone 14. The
molecular ion peak was observed at m/z 405 along with a base peak at m/z 218 due
3
DMFDMA
Mr 1:1
Mr 1:3
Benzene
o-Xylene
80 oC/ 4 h
145 oC/ 4 h
H3C
S
H3C
O
O
S
O
O
CH3
N
CH3
CH3
CHO
+
N
H
N
10
N
H
CH3
11
10
glacial AcOH
100 oC / 2 h
H3C
S
O
CHO
DMF / POCl3
80 oC / 2 h
3
N
O
12
Scheme 3 Reaction of the compound 3 with DMF-DMA and the Vilsmeier reagent
123

M. M. Hassan et al.
to the 3-acetyl-4-(methylthio)quinolinium ion (C12H12NOS?). This fragment ion
cannot be expected in the mass fragmentation pattern of the hypothetical compound
14 because its acetyl function is no longer present.
Treatment of the quinolone 3 with malononitrile, in the presence of piperidine,
afforded the pyranoquinoline 16, in 79 % yield (Scheme 5). IR and 1H NMR spectra
proved that the product assumed the a-iminopyran structure and the known Dimorth
rearrangement of a-iminopyran to a-pyridone is not observed in the present case.
Thus, IR spectrum did not show any indication for a-pyridone carbonyl; at the same
time, absorption bands appeared at mmax 3,275 and 3,138 cm-1 due to (=N–H)
stretching vibration. In addition there was a sharp band at mmax 2,208 cm-1, due to
1
(C:N) vibration. H NMR spectrum (CDCl3) revealed a deuterium exchangeable
proton at d 10.02 due to imino (NH) which is expected to be a downfield chemical
shift if it belongs to 1H-pyridone. Moreover, 13C NMR spectrum fortified this
conclusion about structure since no C=O characteristic peak was observed.
Aiming to prepare the pyrazolo[40,30:5,6]pyrano[2,3-b]quinoline 17 as a new
linear tetraheterocyclic compound, the pyranoquinoline 16 was reacted with
hydrazine hydrate, in boiling DMF. IR spectrum showed that the product contains a
carbonitrile functional group which appeared at mmax 2,209 cm-1. In addition, an
amino group was observed, revealing its characteristic sym and asym vibrational
bands at mmax 3,430 and 3,341 cm-1 besides the vibrations due to (=N–H) at mmax
1
3,271 and 3,134 cm-1. H NMR spectrum (CDCl3) is in good accordance showing
both amino and imino protons as deuterium replaceable signals at d 8.68 and 9.96.
Elemental analysis indicated the presence of sulfur and the correspondence of the
H3C
S
O
O
O
CHO
Cl
CH3
N
+
N
H
N
13
3
Piperidine
EtOH
Δ /4 h
H3C
CH3
O
S
O
O
O
CHO
N
O
O
S
N
H3C
N
N
N
H
Cl
N
14
15
Scheme 4 Reaction of the compound 3 with 2-chloro-3-formylpyridopyrimidone 13
123

Substituted quinolinones. 18. 3-Acetyl-4-methylthioquinolin-2(1H)-one
H3C
S
CH3
N
N
N
3
Piperidine
EtOH / Δ / 4 h
N
H
O
N
H3C
S
CH3
O
N
N
NH
16
NH2NH2.H2O
DMF / Δ / 6 h
H3C
H3C
S
N
CH3
S
N
CH3
O
N
NH
NH
N
NH
N
NH2
17
18
Scheme 5 Reaction of the compound 3 with malononitrile and treatment of the product 16 with
hydrazine hydrate
structure formula to a molecule lacking oxygen. These results suggested that the
obtained compound is 1-amino-2-iminobenzo[b] [1,8]naphthyridine 18 (Scheme 5).
Heterocyclization reactions with the key compound 3, especially annellation at
the face [c] of quinoline nucleus, attracted our attention as a result of the presence of
two vicinal functional groups: acetyl and methylthio groups, which are susceptible
to nucleophilic reactions. Hence, the reaction of the quinolone 3 with some selected
1,2-, 1,3-, and 1,4-binucleophiles led to several interesting triheterocyclic fused
systems. The reaction of the quinolone 3 with hydrazine hydrate afforded the
pyrazoloquinolinone 19a [32, 33], while with hydroxylamine hydrochloride
afforded isoxazoloquinolinone 19b [32]. Also, the reaction of the quinolone 3 with
urea and thiourea led to the formation of pyrimioquinolinones 20a and 20b,
respectively. Similarly, cyclo-condensation of the quinolone 3 with semicarbazide
hydrochloride and thiosemicarbazide furnished the corresponding [1,2,4] triazepi-
noquinolinones 21a and 21b (Scheme 6).
123

M. M. Hassan et al.
N
X
NH2NH2.H2O
CH3
or NH2OH.HCl
DMF / Δ / 6 h
N
O
H
19a, X = NH
19b, X = O
X
HN
N
NH2CONH2
or NH2CSNH2
H3C
S
O
O
CH3
CH3
DMF / Δ / 6 h
N
H
O
N
H
20a, X = O
20b, X = S
3
X
H
N
HN
NH2NHCONH2
N
or NH2NHCSNH2
CH3
DMF / Δ / 6 h
N
H
O
21a, X = O
21b, X = S
Scheme 6 Reaction of the compound 3 with some binucleophiles
A literature survey showed that the last six products (19a,b, 20a,b, and
21a,b) had been reported by Sankaran et al. [32], who had prepared these
compounds starting from 3-acetyl-4-hydroxyquinolin-2(1H)-one (5). Only the
melting points of both the isoxazoloquinolinone 19b and 2-thioxopyrimidoquinoli-
none 20b are compatible with those described in the literature, but the remaining
four newly obtained compounds showed different melting points, mostly higher
than those reported, by about 66 9 °C. For this reason, full spectral character-
izations are described here. The spectral characterizations of these four compounds
showed the correctness of the suggested structures and mostly are in good
accordance with the reported spectra [32].
Conclusion
Efficient and convenient methodologies have been described to prepare 3-acetyl-4-
methylthioquinolin-2(1H)-one as a useful synthon intermediate and different
annellated 2-quinolinone derivatives using this compound. Compared to the
previously reported methodologies, the present synthesis offers some advantages
including economical procedure, milder conditions, and easy work-up procedure.
Hence, it is a useful addition to the existing synthetic methods.
123

Substituted quinolinones. 18. 3-Acetyl-4-methylthioquinolin-2(1H)-one
Experimental
General
Melting points were determined in open capillary tubes on a digital Stuart SMP3
apparatus. IR spectra were taken on Bruker or Perkin-Elmer-1650 FT-IR
1
spectrophotometers, using samples in KBr disks. H NMR spectra were recorded
on Gemini-200 NMR (200 MHz) or Geminin-300BB (300 MHz) spectrometers,
using (CD3)2SO or CDCl3 as solvents and TMS as internal reference. 13C NMR
spectra were recorded at 50 or 75 MHz. Mass spectra were determined on a
Shimadzu QP-2010 Plus mass spectrometer, Ionization mode: EI (70 eV).
Elemental microanalyses were performed on a Perkin Elmer CHN-2400 Analyzer
at the Microanalytical 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. Acetoacetanilide (1) is commercially
available and was purified by recrystallization twice from ethanol.
2-(Bis(methylthio)methylene)-3-oxo-N-phenylbutanamide (2)
To a solution of acetoacetanilide 1 (0.1 mol; 18.08 g), in DMF (100 mL),
anhydrous potassium carbonate (0.3 mol; 42 g) and tetrabutylammonium bromide
(3.22 g; 0.01 mol) were added. The mixture was stirred for 30 min at room
temperature then carbon disulfide (0.1 mol; 6 mL) was added in one portion and the
stirring was continued for an additional 2 h. Afterwards, dimethyl sulfate (0.22 mol;
21 mL) was added portion-wise over a period of 30 min and stirring was continued
for 4 h, at the ambient temperature. The dark red solution that was obtained was
poured onto crushed ice and the precipitate so formed was filtered and washed
thoroughly using cold methanol until the obtaining of free red-colored washing
filtrate. The solid product was crystallized from ethanol to afford the pure product 2.
White crystal, yield 26.97 g (96 %); mp 159-161 °C (lit. [26] 161–163 °C).
3-Acetyl-4-(methylthio)quinolin-2(1H)-one (3)
A solution of the ketene dithioacetal 2 (0.1 mol; 28.1), in o-dichlorobenzene
(100 mL), was heated under reflux until evolution of methanethiol ceased for ca.
4 h. The reaction solution was left to cool at room temperature overnight and the
crystalline product was filtered and washed several times with diethyl ether
(200 mL). The product was recrystallized from o-xylene to give the quinolone 3.
Pale yellow crystal, yield 18.60 g (80 %); mp 237–239 °C (lit. [26] 230–232 °C, lit.
[27] 226–231 °C). IR (KBr, cm-1) : mmax 3,277, 3,224, 3,138 (N–H), 3,065, 2,986,
1,662–1,648 (C=O), 1,615 (C=N, N–H), 1,566, 1,533, 1,465, 1,429, 1,344, 1,275,
996, 947, 753, 693. 1H NMR ((CD3)2SO, 200 MHz): d 2.53 (s, 3H, SCH3), 2.66 (s,
3H, COCH3), 7.39 (t, J = 7.2 Hz, 1H, C6-H), 7.71 (d, J = 7.6 Hz, 1H, C8-H), 7.78
(t, J = 7.4 Hz, 1H, C7-H), 8.11 (t, J = 7.2 Hz, 1H, C5-H), 10.88 (s, 1H, N–H).
123

M. M. Hassan et al.
4-Hydroxyquinolin-2(1H)-one (4)
A suspension of the quinolone 3 (0.01 mol; 2.33 g), in dilute sulfuric acid (30 mL;
50 %), was heated under reflux for 4 h. Then, the mixture was left to cool and
diluted with ice-cold water (100 mL). The solid precipitate so obtained was filtered,
washed with plenty of water, and crystallized from ethanol to afford the
hydroxyquinolone 4. White crystal, yield 1.05 g (65 %); mp [300 °C (lit. [28]
338–340 °C). IR (KBr, cm-1): mmax 3,095–2,555 (H-bonded OH), 1,672 (C=O),
1,634 (C=O), 1,615 (C=N, N–H), 1,609, 1,595, 1,515, 1,505, 1,471, 1,421, 1,361,
1,333, 1,236, 764, 755. 1H NMR ((CD3)2SO, 300 MHz): d 5.81 (s, 1H, C3-H), 7.14
(t, J = 7.8 Hz, 1H, C6-H), 7.29 (d, J = 8.2 Hz, 1H, C8-H), 7.48 (t, J = 7.8 Hz, 1H,
C7-H), 7.80 (t, J = 8.2 Hz, 1H, C5-H), 11.00 (s, 1H, N–H). 13CNMR ((CD3)2SO,
75 MHz): d 98.3, 115.0, 120.9, 122.6, 130.7, 139.2, 162.4, 163.6. MS (EI): m/z ( %)
161 (100), 162 (10.4), 163 (1.2), 120 (35.4), 119 (67.7), 105 (11.8), 92 (34.4), 77
(8.9), 64 (10.8).
3-Acetyl-4-hydroxyquinolin-2(1H)-one (5)
A solution of the quinolone 3 (0.01 mol; 2.33 g), in sodium hydroxide solution
(50 mL; 15 %), was heated under reflux for 4 h. Then, the mixture was left to cool
and filtered off and the clear filtrate was acidified using dilute hydrochloric acid
(1 M) until complete precipitation. The solid precipitate so obtained was filtered,
washed with plenty of water, and crystallized from glacial acetic acid to afford the
hydroxyquinolone 5. White crystal, yield 1.58 g (78 %); mp 258–260 °C (lit. [29]
261–263 °C, lit. [34] 254–257).
3-Acetyl-4-(benzylamino)quinolin-2(1H)-one (6)
A mixture of the quinolinone 3 (0.01 mol; 2.33 g), freshly distilled benzylamine
(0.01 mol; 1.1 mL), and benzylamine hydrochloride (0.001 mol; 0.15 g), in
1,2-dichlorobenzene (25 mL) was heated under reflux for 6 h. Then, the solvent
was evaporated in vacuo and the residue was washed with ethanol several times
(3 9 20 mL), and crystallized from DMF. Light brown crystal, yield 1.84 g (63 %);
mp 221–223 °C. IR (KBr, cm-1): mmax 3,254, 3,189 (NH), 3,095 (CHarom), 2,955,
2,865, 2,765 (CHaliph), 2,638, 2,555 (H-Bond OH), 1,672 (C=Oacetyl), 1,634
(C=Oquinolinone), 1,615, 1,595, 1,465, 1,429, 1,361, 1,349, 1,333, 1,242, 1,236, 1,104,
1
868, 775, 755. H NMR ((CD3)2SO, 300 MHz): d 2.68 (s, 3H, CH3), 4.61 (d,
J = 5.8 Hz, 2H, NCH2),7.20 (t, J = 8.0 Hz, 1H, Harom), 7.27 (d, J = 7.2 Hz, 1H,
H
H
arom), 7.38–7.52 (m, 6H, Harom), 7.79 (br s, 1H, NH), 8.14 (d, J = 8.0 Hz, 1H,
arom), 11.82 (br, s, 1H, NH). 13CNMR ((CD3)2SO, 75 MHz): d 30.7, 46.6, 102.8,
115.9, 120.8, 124.3, 126.9, 127.0, 128.5, 128.6, 132.2, 134.6, 136.4, 162.3, 168.7,
196.4. MS (EI): m/z (%) 292 (36), 293 (8), 274 (29), 201 (36), 172 (45), 106 (73,
C6H5CH2NH?), 91 (100, C6H5CH2?). Analysis Calculated for C18H16N2O2
(292.33): C, 73.95; H, 5.52; N, 9.58 %. Found: C, 74.10; H, 5.40; N, 9.30 %.
123

Substituted quinolinones. 18. 3-Acetyl-4-methylthioquinolin-2(1H)-one
3-Acetyl-4-methylsulfoxyquinolin-2(1H)-one (7)
To a solution of the quinolone 3 (0.005 mol, 1.165 g), in glacial acetic acid
(50 mL), was added hydrogen peroxide (0.013 mol, 30 %, 1.3 mL). The reaction
mixture was stirred at room temperature for 24 h. The reaction mixture was diluted
with ice-water (50 mL). The solid so precipitated was filtered, water several times,
dried, and crystallized from ethanol. White crystal, yield 1.6 g (78 %); mp
234–235 °C. IR (KBr, cm-1): mmax 3,176, 3,092, 2,995, 2,915, 2,887, 1,668
(C=Oacetyl), 1,632 (C=Oquinolone), 1,608, 1,555, 1,437, 1,407, 1,311, 1,301, 1,245,
1,212, 1,108, 1,050 (S=O), 966, 934, 898, 775. 1H NMR (CDCl3, 300 MHz): d 2.78
(s, 3H, SOCH3), 3.01 (s, 3H, COCH3), 7.34–7.52 (m, 2H, Harom), 7.76 (t,
J = 7.2 Hz, 1H), 8.18 (d, J = 7.8 Hz, 1H, C5-H), 11.35 (brs, 1H, N–H). 13CNMR
(CDCl3, 75 MHz): d 29.3, 42.5, 112.3, 117.6, 126.5, 126.2, 126.9, 132.6, 138.1,
140.9, 166.4, 197.4. MS (EI): m/z (%) 249 (26.1), 250 (3.4), 232 (46.8), 218 (58.3),
191 (80.7), 158 (23.5), 130 (27.7), 114 (67.0), 89 (100), 77 (22.4). Analysis
Calculated for C12H11NO3S (249.29): C, 57.82; H, 4.45; N, 5.62 %. Found: C,
58.10; H, 4.40; N, 5.70 %.
5-(Methylthio)-2-phenyl-2H-pyrano[2,3-b]quinolin-4(3H)-one (8)
A mixture of the quinolone 3 (0.01 mol, 2.33 g), benzaldehyde (0.01 mol, 1 mL),
and piperidine (0.2 mL) was heated in a dry quick-fit pear-shaped flask in a boiling
water bath for 5 h. Afterwards the reaction mixture was diluted with absolute
ethanol (10 mL) and the tube was fitted to a reflux condenser and heated for an
additional 1 h. Then, the reaction mixture was left to cool overnight and the
crystalline product so obtained was filtered and recrystallized from DMF/H2O (1:1)
to afford the product 8. White crystal, yield 2.73 g (85 %); mp 198–200 °C. IR
(KBr, cm-1): mmax 3,048, 2,916, 1,672 (C=O pyrone), 1,610, 1,552, 1,488, 1,417,
1,001, 761. 1H NMR (CDCl3, 300 MHz): d 2.82 (s, 3H, SCH3), 3.06 (dd, J = 13.2,
1H, C3-HAHB), 3.21 (dd, J = 12.9, 1H, C3-HAHB), 5.76 (m, 1H, C2-H), 7.46–7.54
(m, 6H, Harom), 7.82 (t, J = 7.8, 1H, C7-H), 8.18 (d, J = 8.0, 1H, C9-H), 8.29 (d,
J = 8.2, 1H, C6-H). MS (EI): m/z (%) 321 (100), 322 (23.1), 323 (7.7), 306 (15.8),
288 (43.6), 275 (10.5), 274 (46.5), 230 (42.3), 218 (19.1), 217 (83), 204 (20.1), 189
(65), 171 (20.4), 170 (10.3), 161 (26.2), 145 (13.2), 143 (13.7), 130 (9.8), 115
(53.9), 114 (50.9), 104 (43.4), 103 (50.6), 102 (21), 88 (13.9), 78 (37.8), 77 (46.7),
76 (20), 63 (14.4). Analysis Calculated for C19H15NO2S (321.39): C, 71.00; H, 4.70;
N, 4.36 %. Found: C, 70.80; H, 4.60; N, 4.50 %.
4-(Methylthio)-3-(5-phenyl-4,5-dihydroisoxazol-3-yl)quinolin-2(1H)-one (9)
To a solution of the compound 8 (0.005 mol, 1.6 g), in DMF (25 mL),
hydroxylamine hydrochloride (0.005 mol, 0.35 g) was added and the reaction
mixture was heated under reflux for 4 h. Then, the reaction mixture was poured onto
crushed ice and the obtained solid deposit was filtered and crystallized from DMF to
give the isoxazoline 9. Beige crystal, yield 1.31 g (78 %); mp 202–204 °C. IR (KBr,
cm-1): mmax 3,182 (NH), 3,075, 2,995, 2,914, 2,884, 2,835, 1,643 (C=O), 1,618
123

M. M. Hassan et al.
1
(C=N), 1,605, 1,579, 1,554, 1,435, 1,310, 776. H NMR ((CD3)2SO, 300 MHz): d
2.67 (s, 3H, SCH3), 3.24–3.43 (m, 2H, 4-C H2 isoxazoline), 5.17 (dd, J = 10.2, 6.2,
1H, 5-CH isoxazoline), 7.24–7.43 (m, 6H, Harom), 7.54 (d, J = 8.1, 1H, C8-Hquinoline),
7.73 (t, J = 7.6, 1H, C7-Hquinoline), 8.14 (d, J = 8.1, 1H, C5-Hquinoline). MS (EI):
m/z (%) 336 (2.1), 337 (0.5), 338 (0.2), 321 (12.3), 320 (24.48), 319 (100), 303
(11.7), 290 (13.7), 115 (11.4), 114 (11.7), 104 (14.5), 103 (20.8), 102 (12.8), 91
(14.3), 78 (13.9), 77 (29.9), 76 (11.2). Analysis Calculated for C19H16N2O2S
(336.41): C, 67.84; H, 4.79; N, 8.33 %. Found: C, 67.5; H, 4.60; N, 8.50 %.
(E)-3-(3-(Dimethylamino)acryloyl)-4-(methylthio)quinolin-2(1H)-one (10)
To a suspension of the quinolone 3 (0.005 mol, 1.165 g), in dry benzene (30 mL),
DMF-DMA (0.0052 mol, 0.7 mL) was added. The reaction mixture was boiled
under reflux for 4 h, then left to cool. The crystalline product was collected by
filtration, washed with diethyl ether (30 mL), and recrystallized from benzene to
afford the enaminone 10. Beige crystal, yield 0.82 g (57 %); mp 265–267 °C. IR
(KBr, cm-1): mmax 3,271–3,182 (NH), 3,058, 2,922, 2,855, 1,653 (C=Oenone), 1,628
1
(C=Oquinolone), 1,610 (C=C), 1,567, 1,536, 1,420, 1,345, 1,274, 987, 801. H NMR
(CDCl3, 300 MHz): d 2.83 (s, 3H, SCH3), 2.90 (s, 3H, NCH3), 3.02 (s, 3H, NCH3),
6.42 (d, J = 13.2, 1H, NCH = CHCO), 7.32 (t, J = 7.8, 1H, C6-H), 7.43 (t, J = 8.1,
1H, C8-H), 7.67 (t, J = 8.1, 1H, C7-H), 7.91 (d, J = 8.7, 1H, C5-H), 8.24 (d,
J = 13.2, 1H, NCH=CHCO), 11.19 (s, 1H, NH). MS (EI): m/z (%) 288 (2.6), 257
(11.5), 254 (27.1), 239 (12.4), 195 (45.6), 180 (41.1), 153 (54.9), 152 (11.4), 139
(6.2), 138 (98.8), 137 (8.2), 136 (10.2), 135 (100), 110 (19.2), 95 (12.2), 93 (41.6), 77
(61.5), 66 (12.2), 65 (9.6), 51 (22.8). Analysis Calculated for C15H16N2O2S (288.36):
C, 62.48; H, 5.59; N, 9.71 %. Found: C, 62.20; H, 5.70; N, 9.50 %.
(E)-3-(Dimethylamino)-2-(4-(methylthio)-2-oxo-1,2-dihydroquinoline-3-
carbonyl)acrylaldehyde (11)
To a solution of the quinolone 3 (0.005 mol, 1.165 g), in dry o-xylene (50 mL),
DMF-DMA (0.015 mol, 2.0 mL) was added. The reaction mixture was boiled under
reflux for 4 h, then left to cool. The crystalline product was collected by filtration.
The filtered solid material was washed with diethyl ether (30 mL), and recrystallized
from dioxane to afford the acrylaldehyde 11. Brown crystal, yield 0.49 g (31 %); mp
[300 °C. IR (KBr, cm-1): mmax 3,230 (NH), 3,082, 3,046, 2,937, 2,839, 1,719
(CH=O), 1,657 (C=Oenone), 1,623 (C=Oquinolone), 1,587, 1,542, 1,457, 1,318, 1,193,
1,127, 1,101, 1,070, 980, 765. 1H NMR ((CD3)2SO, 300 MHz): d 2.68 (s, 3H, SCH3),
3.38 (s, 6H, N(CH3)2), 7.42 (m, 1H, C6-H), 7.76–7.83 (m, 2H, C8-H, C7-H), 8.13 (m,
1H, C5-H), 8.99 (s, 1H, C=CH-N), 10.06 (s, 1H, O=CH), 11.23 (b, 1H, NH). MS
(EI): m/z (%) 316 (7.9), 317 (2.8), 318 (0.8), 315 (35.8), 272 (23.0), 271 (100), 257
(9.5), 229 (9.2), 228 (31.0), 226 (14.4), 225 (15.4), 224 (9.1), 223 (16.8), 210 (12.7),
182 (10.5), 111 (12.1), 76 (7.9), 58 (24.5). Analysis Calculated for C16H16N2O3S
(316.37): C, 60.74; H, 5.10; N, 8.85 %. Found: C, 60.40; H, 5.20; N, 9.10 %.
The o-xylene filtrate was collected and concentrated in vacuum to one-third of its
initial volume (*15 mL) and left to cool overnight to give a beige crystalline
123

Substituted quinolinones. 18. 3-Acetyl-4-methylthioquinolin-2(1H)-one
product which is characterized and found identical in every respect with the
enaminone 10, yield 0.33 g (23 %); mp 265–266 °C (mixed mp with no depression).
5-(Methylthio)-4-oxo-4H-pyrano[2,3-b]quinoline-3-carbaldehyde (12)
Procedure (A)
A solution of the acrylaldehyde 11 (0.001 mol, 0.32 g), in glacial acetic acid (10 mL),
was boiled under reflux for 2 h. After cooling overnight at room temperature a yellow
crystalline material was obtained which was collected by filtration and recrystallized
from ligroin (110–140 °C) to afford the aldehyde 12. Pale yellow crystal, yield 0.23 g
(84 %); mp 187–190 °C. IR (KBr, cm-1): mmax 3,028, 2,980, 2,929, 1,718 (CH=O),
1
1,643 (C=Oc-pyrone), 1,596, 1,564, 1,541, 1,414, 1,240, 831, 804, 733. H NMR
((CD3)2SO, 300 MHz): d 2.72 (s, 3H, SCH3), 7.33 (t, J = 7.5 Hz, 1H, C7-H), 7.57 (d,
J = 8.7 Hz, 1H, C9-H), 7.83 (t, J = 7.8 Hz, 1H, C8-H), 8.09 (d, J = 8.1 Hz, 1H, C6-
H), 8.56 (s, 1H, C2-H), 10.04 (s, 1H, O=CH). MS (EI): m/z (%) 271 (52.5), 272 (7.8),
273 (3.2), 243 (78.2), 216 (7), 215 (47), 192 (11), 191 (100), 163 (27), 116 (42), 115
(17), 92 (43), 91 (74), 75 (21). Analysis Calculated for C14H9NO3S (271.29): C,
61.98; H, 3.34; N, 5.16 %. Found: C, 62.10; H, 3.40; N, 4.90 %.
Procedure (B)
To a stirred cold DMF (20 mL), phosphoryl chloride (0.02 mol, 1.9 mL) was added
dropwise, in an ice-bath. After complete addition, stirring was continued for 30 min
at 0–5 °C. To this mixture, a solution of quinolone 3 (0.005 mol, 1.165 g), in DMF
(10 mL), was added with continuous stirring. The reaction mixture was allowed to
attain room temperature and afterwards heated under reflux at 80 °C for 2 h. The
reaction mixture was allowed to cool and poured onto crushed ice. The solid product
was filtered, washed with water, and crystallized to give the product 12. Pale yellow
crystal, yield 0.76 g (56 %); mp 188–190 °C (mixed mp with no depression).
2-(3-Acetyl-4-(methylthio)quinolin-2-yloxy)-4-oxo-4H-pyrido[1,2-
a]pyrimidine-3-carbaldehyde (15)
A mixture of the quinolone 3 (0.005 mol, 1.165 g), 2-chloro-4-oxo-4H-pyrido[1,2-
a]pyrimidine-3-carbaldehyde (13) [31] (0.005 mol, 1.043 g), and piperidine
(0.2 mL), in ethanol (50 mL), was heated under reflux for 4 h. The reaction
mixture was left to cool at room temperature overnight and the crystalline product
so formed was collected by filtration and recrystallized from ethanol to afford the
ether 15. Orange crystal, yield 1.68 g (83 %); mp 227–229 °C. IR (KBr, cm-1):
mmax 3,072, 2,925, 1,728 (C=Oformyl), 1,650 (C=Opyrimidone), 1,621 (C=Oquinolone),
1,566, 1,529, 1,474, 1,430, 1,366, 1,271, 1,146, 1,110 (C–O–C), 993, 879, 758, 685.
1H NMR ((CD3)2SO, 300 MHz): d 2.51 (s, 3H, COCH3), 2.64 (s, 3H, SCH3), 7.38
(m, 3H, Harom), 7.69–7.76 (m, 2H, Harom), 8.105 (d, J = 8.1, 1H, C5-Hquinoline), 8.22
(t, J = 8.4, 1H, C8-Hpyridopyrimidine), 8.95 (d, J = 8.0, 1H, C6-Hpyridopyrimidine),
10.04 (s, 1H, O = CH). 13CNMR ((CD3)2SO, 75 MHz): d 23.6 (SCH3), 31.6
123

M. M. Hassan et al.
(COCH3), 90.0, 97.7, 98.1, 105.6, 107.8, 110.4, 115.5, 116.9, 119.3, 125.2, 129.9,
141.5, 146.6, 150.1, 155.2, 164.4, 169.8, 184.2, 186.3. MS (EI): m/z (%) 405 (0.61),
233 (8.1), 218 (100), 200 (14.9), 190 (8.9), 172 (29.3), 162 (6.4), 145 (10.7), 130
(8.6), 117 (14.5), 116 (11.1), 103 (9.7), 89 (21.1), 78 (9.9), 77 (19.7), 76 (18.8), 69
(8.5), 63 (12.9). Analysis Calculated for C21H15N3O4S (405.43): C, 62.21; H, 3.73;
N, 10.36 %. Found: C, 62.10; H, 350; N, 10.40 %.
2-Imino-4-methyl-5-(methylthio)-2H-pyrano[2,3-b]quinoline-3-carbonitrile (16)
A mixture of the quinolone 3 (0.005 mol, 1.165 g), malononitrile (0.005 mol,
0.34 g), and piperidine (0.2 mL), in ethanol (50 mL), was heated under reflux for
4 h. The reaction mixture was left to cool at room temperature overnight and the
crystalline product so formed was collected by filtration and recrystallized from
methanol/H2O (1:1) to afford the pyranoquinoline 16. Sandy yellow crystal, yield
1.11 g (79 %); mp 218–220 °C. IR (KBr, cm-1): mmax 3,275, 3,138 (N–H), 3,065,
2,687, 2,931, 2,208 (C:N), 1,616 (C=N), 1,569, 1,533, 1,468, 1,430, 1,345, 1,277,
1
997, 758. H NMR (CDCl3, 300 MHz): d 2.83 (s, 3H, 4-CH3), 2.9 (s, 3H, SCH3),
7.44 (t, J = 7.8 Hz, 1H, C7-H), 7.69 (t, J = 7.8 Hz, 1H, C8-H), 7.91 (d,
J = 7.8 Hz, 1H, C9-H), 8.28 (d, J = 8.1, 1H, C6-H), 10.02 (s, exchangeable with
D, 1H, NH). 13CNMR (CDCl3, 75 MHz): d 17.9, 23.8, 98.9, 114.8, 116.6, 121.7,
123.4, 126.0, 127.8, 129.2, 114.8, 149.0, 156.4, 159.9, 164.6. MS (EI): m/z (%) 281
(100), 282 (20.7), 283 (6.6), 280 (39.9), 279 (30.9), 275 (15.0), 264 (15.7), 253
(12.3), 250 (15.2), 248 (27.6), 236 (14.8), 235 (23.4), 234 (15.0), 222 (29.5), 208
(12.7), 179 (16.9), 152 (12.2), 140 (13.8), 84 (12.1), 80 (18.9), 77 (14.0), 76 (16.3),
64 (24.4). Analysis Calculated for C15H11N3OS (281.33): C, 64.04; H, 3.94; N,
14.94 %. Found: C, 63.80; H, 3.80; N, 14.60 %.
1-Amino-2-imino-4-methyl-5-(methylthio)-1,2-dihydro-
benzo[b][1,8]naphthyridine-3-carbonitrile (18)
To a solution of the pyranoquinoline 16 (0.003 mol, 0.85 g), in DMF (10 mL),
hydrazine hydrate (0.004 mol, 0.2 mL) was added and the reaction mixture was
heated under reflux for 6 h. Then, the reaction mixture was left to cool at room
temperature and diluted with cold water to give a solid deposit which was filtered
and crystallized from DMSO to afford the diamine 18. Pale Beige crystal, yield
0.75 g (85 %); mp 282–284 °C. IR (KBr, cm-1): mmax 3,430, 3,341 (NH2), 3,271,
3,134 (N–H), 3,018, 2,929, 2,209 (C:N), 1,622 (C=N), 1,578, 1,527, 1,473, 1,433,
1,374, 1,292, 1,254, 761. 1H NMR (CDCl3, 300 MHz): d 2.48 (s, 3H, 4-CH3), 2.60
(s, 3H, SCH3), 7.43 (t, J = 7.8 Hz, 1H, C7-H), 7.68 (t, J = 6.8 Hz, 1H, C8-H), 7.90
(d, J = 6.4 Hz, 1H, C9-H), 8.26 (d, J = 8.0, 1H, C6-H), 8.68 (s, exchangeable with
D, 2H, N-NH2), 9.96 (s, exchangeable with D, 1H, C=NH). MS (EI): m/z (%) 295
(0.73), 296 (0.11), 290 (8.1), 289 (7.8), 282 (7.3), 281 (24.8), 264 (9.0), 250 (7.8),
248 (7.2), 230 (18.9), 229 (100), 222 (6.7), 214 (6.3), 184 (8.0), 183 (35.4), 154
(11.5), 152 (10.7), 140 (7.9), 127 (15.3), 126 (8.7), 116 (9.0), 114 (14.8), 80 (13.7),
77 (16.0). Analysis Calculated for C15H13N5S (295.36): C, 61.00; H, 4.44; N,
23.71 %. Found: C, 60.70; H, 4.30; N, 23.50 %.
123

Substituted quinolinones. 18. 3-Acetyl-4-methylthioquinolin-2(1H)-one
General procedure for heterocyclization reactions of the quinolone 3 with some
binucleophiles
To a solution of the quinolone 3 (0.005 mol, 1.165 g), in DMF (30 mL), the proper
binucleophile (0.005 mol): hydrazine hydrate (0.3 mL), hydroxylamine hydrochlo-
ride (0.35 g), urea (0.31 g), thiourea (0.39 g), semicarbazide hydrochloride
(0.57 g), thiosemicarbazide (0.47 g), was added and the reaction mixture was
heated under reflux for 6 h. After cooling to room temperature the solid deposit that
obtained was filtered and crystallized from the appropriate solvent to give the
compounds 19a, 19b, 20a, 20b, 21a, and 21b, respectively.
3-Methyl-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (19a)
This compound was obtained from hydrazine hydrate. Pale yellow crystal (EtOH),
yield 0.89 g (89 %); mp[300 °C (lit. [32] 238 °C, lit. [33] not reported). IR (KBr,
cm-1): mmax 3,174, 3,146 (N–H), 3,062, 2,964, 1,624 (C=O), 1,585, 1,534, 1,473,
1
1,419, 1,343, 1,244, 1,122, 752. H NMR ((CD3)2SO, 300 MHz): d 2.50 (s, 3H,
3-CH3), 7.01 (t, 1H, C8-H), 7.32 (d, 1H, C6-H), 7.47 (t, 1H, C7-H), 7.86 (b, 1H, N1-
H), 7.99 (d, J = 6.2 Hz, 1H, C9-H), 11.85 (b, 1H, N5-H). MS (EI): m/z (%) 199
(72.5), 200 (10.3), 201 (1.2), 198 (19.8), 170 (34.1), 142 (15.3), 130 (8.2), 117
(15.3), 116 (15.1), 115 (42.3), 114 (15.8), 104 (21.5), 103 (14.9), 102 (27.5), 90
(24.7), 89 (25.4), 78 (18.3), 77 (54.9), 76 (96.6), 75 (64.7), 74 (69.4), 67 (28.5), 66
(82.0), 65 (92.9), 64 (65.6), 63 (74.2), 62 (34.4), 53 (35.5), 52 (76.8), 51 (73.3), 50
(100). Analysis Calculated for C11H9N3O (199.21): C, 66.32; H, 4.55; N, 21.09 %.
Found: C, 66.20; H, 4.50; N, 21.10 %.
3-Methylisoxazolo[4,5-c]quinolin-4(5H)-one (19b)
This compound was obtained from hydroxylamine hydrochloride. Pale white crystal
(EtOH), yield 0.84 g (84 %); mp 244–245 °C (lit. [32] 246 °C).
4-Methylpyrimido[5,4-c]quinoline-2,5(1H,6H)-dione (20a)
This compound was obtained from urea. Yellow crystal (AcOH), yield 0.93 g
(82 %); mp [300 °C (lit. [32] 225 °C). IR (KBr, cm-1): mmax 3,187, 3,118 (N–H),
3,017, 2,927, 2,883, 1,668 (C=Opyrimidone), 1,645 (C=Oquinolone), 1,608 (C=N), 1,554,
1
1,490, 1,340, 1,250, 1,160, 975, 881, 752. H NMR ((CD3)2SO, 300 MHz): d.71
(s, 3H, 4-CH3), 7.19 (t, J = 8.4 Hz, 1H, C9-H), 7.26 (d, J = 8.1 Hz, 1H, C7-H), 7.64
(t, J = 8.1 Hz, 1H, C8-H), 7.95 (d, J = 8.2 Hz, 1H, C10-H), 8.56 (s, 1H, N1-H),
11.53 (b, 1H, N6-H). 13CNMR ((CD3)2SO, 75 MHz): d 30.6, 105.8, 113.4, 115.5,
115.8, 122.0, 124.7, 135.1, 140.7, 161.2, 174.8, 205.9. MS (EI): m/z (%) 227 (100),
228 (9.2), 197 (4.9), 183 (8.3), 181 (17.4), 153 (7.8), 138 (9.2), 137 (7.4), 136 (6.7),
125 (18.3), 110 (12.5), 95 (9.0), 79 (4.5), 77 (4.4). Analysis Calculated for
C12H9N3O2 (227.22): C, 63.43; H, 3.99; N, 18.49 %. Found: C, 63.30; H, 4.10; N,
18.20 %.
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M. M. Hassan et al.
4-Methyl-2-thioxo-1,2-dihydropyrimido[5,4-c]quinolin-5(6H)-one (20b)
This compound was obtained from thiourea. Pale yellow crystal (DMF/EtOH, 1:1),
yield 1.04 g (86 %); mp 238–239 °C (lit. [32] 235 °C).
5-Methyl-1H-[1,2,4]triazepino[6,5-c]quinoline-2,6(3H,7H)-dione (21a)
This compound was obtained from semicarbazide hydrochloride. Yellowish orange
crystal (EtOH), yield 0.94 g (78 %); mp [300 °C (lit. [32] 243 °C). IR (KBr,
cm-1): mmax 3,248, 3,148 (N–H), 2,925, 2,848, 1,681 (C=Otriazepinone), 1,656
(C=Oquinolone), 1,619 (C=N), 1,590, 1,526, 1,466, 1,413, 1,323, 1,167, 1,109, 958,
1
744. H NMR (CDCl3, 300 MHz): d 2.46 (s, 3H, 5-CH3), 7.27 (t, J = 8.1 Hz, 1H,
C10-H), 7.61–7.71 (m, 2H, C8-H and C9-H), 8.10 (d, J = 8.1 Hz, 1H, C11-H),
10.20 (bs, 1H, 3-NH), 10.51 (bs, 1H, 1-NH), 11.41 (bs, 1H, 7-NH). MS (EI):
m/z (%) 242 (56.8), 243 (18.9), 241 (55.4), 229 (60.8), 227 (58.1), 226 (39.2), 221
(62.2), 220 (44.6), 206 (60.8), 193 (44.6), 191 (20.3), 175 (78.4), 164 (100), 158
(56.8), 157 (55.4), 137 (55.4), 136 (75.7), 130 (47.3), 127 (44.6), 102 (81.1), 100
(45.9), 88 (64.9), 85 (48.6), 77 (45.9), 71 (66.2), 63 (71.6), 51 (71.6), 50 (79.7).
Analysis Calculated for C12H10N4O2 (242.23): C, 59.50; H, 4.16; N, 23.13 %.
Found: C, 59.30; H, 4.20; N, 22.90 %.
5-Methyl-2-thioxo-2,3-dihydro-1H-[1, 2, 4]triazepino[6,5-c]quinolin-6(7H)-one
(21b)
This compound was obtained from thiosemicarbazide. Yellowish Beige crystal
(EtOH), yield 1.07 g (83 %); mp 286–287 °C (lit. [32] 240 °C). IR (KBr, cm-1):
mmax 3,181, 3,117 (N–H), 3,056, 2,962, 2,904, 1,658 (C=Oquinolone), 1,602
(C=Ntriazepinone), 1,568, 1,487, 1,383, 1,326, 1,260, 1,226 (N–C=S), 1,112, 1,082,
783. 1H NMR ((CD3)2SO, 300 MHz): d 2.46 (s, 3H, 5-CH3), 7.18-7.28 (m, 2H, 1H,
C10-H and C8-H), 7.64 (t, J = 7.8 Hz, C9-H), 7.97 (d, J = 7.8 Hz, 1H, C11-H),
9.58 (bs, 2H, 1-NH and 3-NH), 11.51 (bs, 1H, 7-NH). MS (EI): m/z (%) 258 (21.3),
259 (4.1), 257 (100), 256 (10.3), 229 (23.1), 200 (46.6), 185 (18.7), 172 (7.2), 144
(15.4), 134 (10.3), 132 (8.9), 104 (8.9), 78 (10.5), 77 (27.5), 76 (8.5), 63 (12.6), 51
(20.4). Analysis Calculated for C12H10N4OS (258.30): C, 55.80; H, 3.90; N,
21.69 %. Found: C, 55.60; H, 3.80; N, 21.80 %.
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