Chemistry of substituted quinolinones. Part VI. Synthesis and nucleophilic reactions of 4-chloro-8-methylquinolin-2(1H)-one and its thione analogue

Article abstract of DOI:10.3390/51201224

The synthesis of 4-chloro-8-methylquinolin-2(1H)-one and its thione analogue is described. Some nucleophilic substitution reactions of the 4-chloro group were carried out to get new 4-substituted 2-quinolinones and quinolinethiones, such as 4-sulfanyl, hydrazino, azido and amino derivatives, which are of important synthetic use. The structure of the new compounds was established by their elemental analysis, IR and (1)H-NMR spectra. Also the mass fragmentation pattern of some products is discussed.

Full text of DOI:10.3390/51201224

Molecules 2000, 5, 1224–1239
molecules
ISSN 1420-3049
http://www.mdpi.org
Chemistry of Substituted Quinolinones. Part VI.† Synthesis and
H
Nucleophilic Reactions of 4-Chloro-8-methylquinolin-2(1 )-one
and its Thione Analogue
Mostafa M. Ismail, Mohamed Abass* and Mohamed M. Hassan
Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, 11711 Cairo, Egypt.
Tel: + 202 7104060, Fax: + 202 2581243.
* Author to whom correspondence should be addressed; E-mail: mohamedabass@hotmail.com
† For part V see reference [1].
Received: 12 October 2000; in revised form: 2 November 2000 / Accepted: 9 November 2000 /
Published:18 December 2000
Abstract: The synthesis of 4-chloro-8-methylquinolin-2(1H)-one and its thione analogue is
described. Some nucleophilic substitution reactions of the 4-chloro group were carried out to
get new 4-substituted 2-quinolinones and quinolinethiones, such as 4-sulfanyl, hydrazino,
azido and amino derivatives, which are of important synthetic use. The structure of the new
1
compounds was established by their elemental analysis, IR and H-NMR spectra. Also the
mass fragmentation pattern of some products is discussed.
Keywords: quinolinone, quinolinethione, nucleophilic substitution, thiol-thione
tautomerism, mass fragmentation.
Introduction
In connection with our previous studies on nucleophilic reactions with chloroquinolines [1-3], we
have synthesized 4-chloro-8-methylquinolin-2(1H)-one and its thio-analogue to investigate their
reactivity towards certain nucleophilic substitution reactions at position-4. Thiation, hydrazination,
azidation and amination reactions led to formation of a series of 4-substituted quinolin-2-ones (or 2-
© 2000 MDPI. All rights reserved.

Molecules 2000, 5
1225
thiones). Since the thiation of quinolinones with Lawesson reagent or phosphorous pentasulfide is
often poor in yield and leads to 2- and/or 4-thiated products [4], this work explores a facile and simple
thiation using the known reaction of thiourea with haloheteroarenes [5,6].
Results and Discussion
Chlorination of 4-hydroxy-8-methylquinolin-2(1H)-one (1) [7] with a mixture of phosphoryl
chloride and phosphorus pentachloride afforded 2,4-dichloro-8-methylquinoline (2) [1]. Acid
hydrolysis of dichloroquinoline 2, using dilute dichloroacetic acid, furnished 4-chloro-8-
methylquinolin-2(1H)-one (3). Heating of compound 3 with phosphorus pentasulfide gave its thio-
isomer 4-chloro-8-methylquinoline-2(1H)-thione (4), in a relatively low yield. The same compound 4
was prepared in fair yield when dichloroquinoline 2 was reacted with a 1:1 molar ratio of thiourea in
1
boiling ethanol. The H-NMR spectrum of compound 4 in DMSO revealed the existence of a
thiolactam-thiolactim equilibrium. Thus, the acidic proton (deuterium exchangeable) is fractionally
present at two chemical shifts. We found that the thiolactam tautomer is predominant (thione : thiol
ratio 3 : 2). This behaviour is similar to the known behaviour of most thiolactams and lactams, in
particular 2-quinolinones [8].
X
X
N
H
S
N
SH
CH3
CH3
X = Cl, SH, SR,SAr, N H3, N , N=P(C6H5)3, NH2
2
3
Thiolactam-thiolactim Tautomerism of 4-Substituted Quinoline-2(1H)-thiones
The mass fragmentation pattern showed the stability of the molecular ion (m/e 209.5), which
appeared as the base peak (cf. Chart 1). Increasing of the molar ratio of thiourea and using boiling
DMF as the solvent led to formation of 8-methyl-4-sulfanylquinoline-2(1H)-thione (5). Application of
these conditions to the reaction of thiourea with compound 4 also gave compound 5. Tthe mass
fragmentation pattern of compound 5 also showed the molecular ion (m/e 207) as the base peak (cf.
Chart 2). The direct thiation of hydroxyquinolinone 1 with phosphorus pentasulfide was tested and the
yield again is found to be much poorer. Building on the reaction yield and product purity we can
conclude that direct thiation of quinolinones 1 and 3 using phosphorus pentasulfide is disfavored, when
it is compared with the described thiation of chloroquinolines (Scheme 1).

Molecules 2000, 5
1226
OH
Cl
N
Cl
H+ / H2O
POCl3
PCl5
N
H
O
Cl
N
H
O
CH3
CH3
CH3
(1)
(3)
(2)
P4S10
H2NCSNH2
P4S10
1:2
1:1
Cl
SH
DMF
EtOH
H2NCSNH2
DMF
N
H
S
N
H
(5)
S
CH3
CH3
(4)
Scheme 1.
4-Chloroquinolinone 3 was used as a precursor for obtaining some new 4-substituted quinolinones.
Thus, thiation of compound 3 with thiourea was carried out under fusion conditions to give 8-methyl-
4-sulfanylquinolin-2(1H)-one (6). It was found that compound 6 is selectively S-alkylated, using alkyl
iodides; namely ethyl iodide and butyl iodide, in the presence of a base catalyst, leading to 4-alkylthio-
8-methylquinolinones 7a and 7b, respectively. Alternatively, compounds 7a and 7b were also obtained
when chloroquinolinone 3 was treated with the appropriate alkanethiol in the presence of sodium
ethoxide. Similarly, 8-methyl-4-phenylthioquinolin-2(1H)-one (7c) was prepared from compound 3
and thiophenol. Hydrazination of each of 4-chloroquinolinone 3, 4-ethylthioquinolinone 7a and/or 4-
tosyloxyquinolinone 9 resulted in the same product, which was characterized as 4-hydrazino-8-
methylquinolin-2(1H)-one (8). The tosylate 9 was prepared from reaction of 4-hydroxyquinolinone 1
with toluene-4-sulfonyl chloride in pyridine. Although the yield of hydrazinoquinolinone 8 is
apparently the lowest (53 %), we can say that use of tosylate 9, as a reagent for preparing
hydrazinoquinolinone 8, is much more favorable as a synthetic approach. This is obvious if we
compare this obtained yield with the overall yield starting from preparation of dichloroquinoline 2
(overall yield = 36.8 %) (Scheme 2). In a similar fashion both chloroquinolinone 3 and tosylate 9 were
subjected to azidation reaction with sodium azide in DMF, furnishing 4-azido-8-methylquinolin-2(1H)-
one (10). The compound 10 was also obtained in a much higher yield and purity, by action of nitrous
acid on the hydrazinoquinolinone 8. Staudinger reaction [9] was employed to reduce the azide 8 to its
corresponding amine. The advantage of this method goes back to its controlled conversion of azide
function to phosphazene, which subsequently could be hydrolyzed smoothly to the desired amine.
Other reduction methods like catalytic hydrogenation are more expensive and could lead to several by-

Molecules 2000, 5
1227
products especially when other sensitive functions are present in the substrate [10]. Thus, treatment of
the azide 10 with triphenylphosphine afforded the phosphazene 11, which upon hydrolysis, using dilute
hydrochloric acid, gave 4-amino-8-methylquinolin-2(1H)-one (12) [1] (Scheme 2).
Cl
Cl
H
-Cl.
+ H.
+H.
N
SH
- H2S
N
H
S
N
S
CH
3
H
CH
3
CH
3
M
m/e 209.5 (100%)
M+1 m/e 210.5 (15.6%)
M+2 m/e 211.5 (37.3%)
m/e 175 (19.45%)
- CS
- C2H2
Cl
Cl
S
H
H
NH
N
H
N
H C
3
CH
CH
3
3
m/e 165.5 (2.92%)
- Cl.
m/e 149 (4.49%)
m/e 176.5 (11.49%)
- Cl.
- CS
H
+ H.
NH
H
N
H
N
- C2H2
CH
3
CH
CH
3
3
m/e 130 (7.37%)
m/e 141 (10.77%)
m/e 105 (5.34%)
Chart 1. Mass Fragmentation Pattern of Compound 4

Molecules 2000, 5
1228
SH
N
SH
S
-H.
- H2S
H
SH
N
H
S
CH
3
N
S
CH
3
H
CH
3
M
m/e 207 (100 %)
M+1 m/e 208 (11.5 %)
M+2 m/e 209 (8.3 %)
m/e 206 (22.85 %)
- CS
H
S
- CS
S
H
N
H
N
H
CH
CH
3
3
H
N
m/e 174 (11.49 %)
H
m/e 130 (27.65 %)
CH
3
+ H.
+ H.
or
- C2H2
- C2H2
H
S
S
N
NH
H
NH
CH
3
H C
3
CH
3
m/e 149 (7.32%)
m/e 162 (33.47 %)
m/e 105 (10.07 %)
Chart 2. Mass Fragmentation Pattern of Compound 5
4-Chloroquinoline-2-thione 4 was subjected to alkylation reactions, using dimethyl sulfate and/or
ethyl iodide, resulting in 2-alkylthio-4-chloro-8-methylquinolines 13a and 13b. Interestingly compound
13a (R = C2H5) was hydrazinated at both the 2- and 4- sites to give 2,4-dihydrazino-8-methylquinoline
(14). Hydrazination of dichloroquinoline 2 revealed the inactivity of position-2 towards this
nucleophilic displacement. This shows that the presence of ethylthio group instead of chloro group at
position-2 enabled the hydrazinolysis reaction i.e. the leaving group plays an important role in such
substitution reactions at position-2. The structure of dihydrazinoquinoline 14 was established by its
reaction with nitrous acid which led to 5-azido-8-methyltetrazolo[1,5-a]quinoline (15) [1] (Scheme 3).

Molecules 2000, 5
1229
SR
SH
OH
RX /Base
N
H
O
N
H
O
N
H
O
CH3
CH3
CH3
(6)
( )
1
(7a-c)
TsCl
pyridine
H2NCSNH2
N2H4.H2O
DMF
RSH
EtONa
Cl
NHNH2
OTs
N2H4.H2O
EtOH
N2H4.H2O
DMF
N
H
O
N
H
O
N
H
O
CH3
CH3
CH3
(3)
(8)
(9)
NaNO2 / HCl
0-5 oC
NaN3
DMF
NaN3
DMF
N3
N
O
H
CH3
(10)
7
R
TPP
C2H5
n-C4H9
C6H5
a
b
c
benzene
C6H5
C6H5
P
N
NH2
C6H5
(i) HCl / H2O
(ii) NaOH
N
H
O
N
O
H
CH3
CH3
(
11
)
(
)
12
Scheme 2.

Molecules 2000, 5
1230
Cl
SR
Cl
RSH
RX
EtONa
base
N
H
S
N
H
S
N
SR
CH3
CH3
CH3
(
)
16a-c
(13a,b)
(4)
N2H4.H2O
N2H4.H2O
EtOH
N2H4.H2O
NaN3
DMF
NHNH2
N3
NHNH2
NaNO2 / HCl
0-5 oC
N
H
S
N
S
N
NHNH2
H
CH3
CH3
CH3
(17)
(14)
(18)
16
R
R
13
a
b
c
C2H5
n-C4H9
C6H5
TPP
NaNO2 / HCl
0-5 oC
a
b
CH3
C2H5
benzene
C6H5
C6H5
C6H5
P
N3
N
NH2
(i) HCl / H2O
(ii) NaOH
N
N
S
N
N
H
S
H
N
CH3
N
CH3
CH3
(15)
(19)
(20)
Scheme 3.
Reaction of 4-chloroquinolinethione 4 with certain thiols, viz. ethanethiol, butanethiol and
thiophenol, gave the corresponding 4-alkyl(or phenyl)thio-8-methylquinolin-2(1H)-thiones 16a-c.
Hydrazination of the chloroquinolinethione 4 or the sulfide 16a (R = C2H5) led to the same product; 4-
hydrazino-8-methylquinoline-2(1H)-thione (17). The structure of compound 17 was elucidated via the
mass fragmentation pattern (Chart 3). Reaction of compound 4 with sodium azide furnished 4-azido-8-
methylquinolin-2(1H)-thione (18), which was also prepared by reacting the hydrazinoquinolinethione
with nitrous acid. 4-Amino-8-methylquinolin-2(1H)-thione (20) was prepared in a similar manner to
obtain aminoquinolinone 12. Thus, the azide 18 was reacted with triphenylphosphine in boiling

Molecules 2000, 5
1231
benzene to give the phosphazene 19 which was subjected to acid hydrolysis furnishing the desired 4-
aminoquinoline-2-thione 20 (Scheme 3).
NH
NH
2
N
HN
NH
.
-H2
-NH2
H
S
N
H
S
N
H
S
N
H
CH
3
CH
3
CH
3
m/e 203 (100 %)
M
m/e 205 (19.44 %)
M+1 m/e 206 (12.39 %)
M+2 m/e 207 ( 4.2 %)
m/e 189 (23.67 %)
- N2H2
-N2
- CS
NH
H
H
H
N
H
H
- CS
CH
3
H
N
N
S
H
m/e 145 (23.1 %)
H
CH
CH
3
3
m/e 175 (19.07 %)
- C2H2
m/e 131 (40.13 %)
- C2H2
S
- CS
NH
NH
H C
3
CH
3
m/e 149 (20.5 %)
m/e 105 (15.72 %)
Chart 3. Mass Fragmentation Pattern of Compound 17

Molecules 2000, 5
1232
Experimental
General
Melting points were determined on a Gallenkamp apparatus and are uncorrected. IR spectra were
1
recorded on a Perkin-Elmer FT-IR 1650 spectrophotometer using KBr disks. H-NMR spectra were
measured in CDCl3 or DMSO-d6 on Jeol FX-90 (90 MHz) and Jeol EX-270 (270 MHz) spectrometers,
using TMS as an internal standard. Mass spectra were obtained on a HP MS-5988 (Electron energy 70
eV). Elemental analyses were performed at Cairo University Microanalytical Centre. Compounds 1 and
2 were prepared as previously described in the literature (References [7] and [1], respectively).
4-Chloro-8-methylquinolin-2(1H)-one (3)
A solution of dichloroquinoline 2 (2.12 g, 10 mmol) in dilute dichloroacetic acid (50 mL, 90 %) was
heated under reflux for 1h. The clear solution was then poured onto ice-cold water and the precipitate
that formed was collected by filtration and crystallized.
4-Chloro-8-methylquinoline-2(1H)-thione (4)
Method A
A mixture of dichloroquinoline 2 (2.12 g, 10 mmol) and thiourea (0.76 g, 10 mmol), in absolute
ethanol (30 mL), was refluxed on a boiling water-bath for 4h. The reaction mixture was then left to
cool and poured onto 2M sodium hydroxide solution (50 mL), then filtered off and acidified using 2M
hydrochloric acid (50 mL). The yellow deposits thus formed were collected by filtration, washed with
water and crystallized.
Method B
To a solution of chloroquinolinone 3 (1.94 g, 10 mmol) in o-xylene (100 mL), phosphorus
pentasulfide (4.44 g, 10 mmol) was added and the mixture was heated under reflux for 24 h. The
solvent was removed by evaporation and the residue extracted several times with chloroform (4 x 25
mL). The extracts were washed with water and dried over anhydrous calcium chloride. The solvent
was removed in vacuo and the residue was crystallized to give quinolinethione 4 (identified by its m.p.,
mixed m.p. and spectral data).
8-Methyl-4-sulfanylquinoline-2(1H)-thione (5)
Method A
A mixture of dichloroquinoline 2 (2.12 g, 10 mmol) and thiourea (2.28 g, 30 mmol), in DMF (30
mL), was heated under reflux for 4h. Afterwards the reaction mixture was poured onto cold water and

Molecules 2000, 5
1233
the solid so obtained was dissolved in 0.5 M sodium hydroxide solution (100 mL) and filtered off to
remove insoluble materials. The alkaline solution was precipitated using 1 M hydrochloric acid (60
mL) to give yellow precipitates, which were collected by filtration and crystallized.
Method B
To a solution of hydroxyquinolinone 1 (1.75 g, 10 mmol) in o-xylene (100 mL), phosphorus
pentasulfide (8.88 g, 20 mmol) was added and the reaction was processed as described for compound
4, Method A.
Method C
Using the same method B that used for obtaining compound 4, compound 5 was obtained from
equimolar amounts (10 mmol) of chloroquinolinethione 4 and thiourea in boiling DMF (30 mL).
8-Methyl-4-sulfanylquinolin-2(1H)-one (6)
A mixture of 4-chloroquinolinone 3 (1.94 g, 10 mmol) and thiourea (1.52 g, 20 mmol) was heated
in an oil-bath at 170–190 °C for 1h. The reaction mixture was cooled and treated with aqueous solution
of sodium hydroxide (50 mL, 0.5 M) and the solution so obtained was filtered from insoluble
materials. The clear filtrate was acidified by hydrochloric acid (50 mL, 0.5 M). The yellow precipitate
that separated was filtered off and crystallized.
4-Alkyl (or aryl)thio-8-methylquinolin-2(1H)-ones 7a-7c
Method A
A mixture of chloroquinolinone 3 (1.94 g, 10 mmol) and the appropriate thiol: ethanethiol,
butanethiol or thiophenol (15 mmol) was treated with sodium ethoxide (1.7 g, 25 mmol), in absolute
ethanol (50 mL). The reaction mixture was heated under reflux on a boiling water-bath for 4h, then
cooled and poured onto ice-cold water. The solid so formed was filtered off and crystallized to give
compounds 7a-7c, respectively.
Method B
A solution of potassium hydroxide (1.12 g, 20 mmol) in ethanol (50 mL) was added to a mixture of
sulfanylquinolinone 6 (1.91 g, 10 mmol) and ethyl iodide or butyl iodide (15 mmol). The mixture was
heated under reflux on a boiling water-bath. The precipitate that formed was filtered off and
crystallized to give compounds 7a and 7b, respectively (identified by m.p., mixed m.p. and spectral
data).

Molecules 2000, 5
1234
4-Hydrazino-8-methylquinolin-2(1H)-one (8)
Method A
A mixture of chloroquinolinone 3 (1.94 g, 10 mmol) and hydrazine hydrate (5 mL, 0.1 mol), in
absolute ethanol (30 mL), was heated under reflux for 4h. Then the mixture was left to cool and the
crystals so obtained were filtered off and recrystallized.
Method B
A mixture of 4-ethylthioquinolinone 7a (1.1 g, 5 mmol), hydrazine hydrate (2 mL, 40 mmol) and
DMF (25 mL) was heated under reflux for 6h. The reaction mixture was left to cool, poured onto
crushed ice to give white deposits, which were filtered off and crystallized.
Method C
Using the same above method B, compound 8 was obtained from 4-tosyloxyquinolone 9 (1.65 g, 5
mmol) and hydrazine hydrate (2 mL, 40 mmol) in DMF (25 mL).
8-Methyl-4-tosyloxyquinolin-2(1H)-one (9)
To a suspension of compound 1 (1.75 g, 10 mmol), in pyridine (50 mL), tosyl chloride (1.91 g, 10
mmol) was added portion-wise with continuous stirring. Then the mixture was heated under reflux on a
boiling water-bath for 2h. The precipitate thus formed during the course of reaction was filtered off,
washed thoroughly with acidified cold water, dried and crystallized.
4-Azido-8-methylquinolin-2(1H)-one (10)
Method A
To a solution of chloroquinolinone 3 (1.94 g, 10 mmol), in DMF (20 mL), sodium azide (1g, 15
mmol) was added and the mixture was heated under reflux for 2h. The reaction mixture was poured
onto ice-cold water and the precipitate that formed was filtered off and crystallized.
Method B
Using the above method A compound 10 was also obtained from 4-tosyloxyquinolinone 9 (1.65 g, 5
mmol) and sodium azide (0.65, 10 mmol) in DMF (20 mL).
Method C
To a solution of hydrazinoquinolinone 8 (1.89 g, 10 mol), in 2 M hydrochloric acid (10 mL),
sodium nitrite solution (10 mL, 11 mmol) was added drop-wise with continuous stirring, in a crushed

Molecules 2000, 5
1235
ice bath. The precipitate that formed was collected by filtration, washed and crystallized.
8-Methyl-4-(triphenylphosphoranylideneamino)quinolin-2(1H)-one (11)
A mixture of 4-azidoquinolone 10 (2.0 g, 10 mmol) and triphenylphosphine (2.88 g, 11 mmol), in
benzene (50 mL) was heated under reflux on a boiling water-bath for 3h. Afterwards, the solvent was
removed in vacuum and the residue was washed with diethyl ether (2 x 25 ml) and crystallized.
4-Amino-8-methylquinolin-2(1H)-one (12)
A suspension of phosphazene 11 (4.34 g, 10 mmol), in hydrochloric acid (50 mL) was heated under
reflux for 4h. The solution was then left to cool and filtered from insoluble triphenylphosphine oxide.
The acidic solution was neutralized using aqueous 2M sodium hydroxide solution (50 mL). The solid
precipitates thus formed were filtered off and crystallized from DMF to give compound 12, m.p.: > 300
oC (Lit. [1] m.p.: > 300 oC).
4-Chloro-2-methylthio-8-methylquinoline (13a)
To a solution of quinolinethione 4 (2.1 g, 10 mmol), in ethanolic potassium hydroxide (20 mL, 2
M), dimethyl sulfate (1.43 mL, 15 mmol) was added drop-wise with continuous stirring. Then the
mixture was aerated over-night and the precipitate so formed was collected by filtration and
crystallized.
4-Chloro-2-ethylthio-8-methylquinoline (13b)
A mixture of 4-chloroquinoline-2-thione 4 (2.1 g, 10 mmol) and ethyl iodide (1.21 mL, 15 mmol),
in absolute ethanol (30 mL), was heated under reflux for 3h. Then, the mixture was left to cool and the
precipitate that obtained was collected by filtration and crystallized.
2,4-Dihydrazino-8-methylquinoline (14)
A mixture of compound 13b (2.38 g, 10 mmol) and hydrazine hydrate (2 mL, 40 mmol) was heated
under reflux for 8h. Then the mixture was poured onto ice-cold water to give a precipitate, which was
collected by filtration washed well with cold water and crystallized.
5-Azido-9-methyltetrazolo[1,5-a] quinoline (15)
To an icy solution of dihydrazinoquinoline 14 (1 g, 5 mmol) in hydrochloric acid (10 mol, 2 M),
sodium nitrite solution (10 mL, 10 mmol) was added drop-wise over a period of 15 min in a crushed
ice-bath. After stirring for additional 30 min, the reaction mixture was left at room temperature for a
night. The precipitation so formed was collected by filtration and crystallized from THF to give

Molecules 2000, 5
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azidotetrazoloquinoline 15, m.p.: 208-9 oC (Lit. [1] m.p.: 208 °C).
4-Alkyl(or phenyl)thio-8-methylquinoline-2(1H)-thiones 16a-c
Compound 4 (2.1 g, 10 mmol) was dissolved in absolute ethanol containing sodium ethoxide (20
mmol) and treated with a proper thiol: ethanethiol, butanethiol, or thiophenol (20 mol) and the mixture
was heated under reflux for 4h. Afterwards, the mixture was cooled, poured onto cold water and
precipitated using hydrochloric acid (30 mL, 1 M). The solid so formed was filtered off and
crystallized to give the sulfides 16a-c, respectively.
4-Hydrazino-8-methylquinoline-2(1H)-thione (17)
Method A
To a solution of compound 4 (2.1 g, 10 mmol) in ethanol (30 mL) hydrazine hydrate (0.5 mL, 10
mmol) was added. The mixture was then heated under reflux for 4h, poured onto ice-cold water. The
product so deposited was filtered off and crystallized.
Method B
To 10 mmol of either sulfides 16a (2.35 g) or 16b (2.63 g), hydrazine hydrate (1 mL, 2 mmol) was
added and heated under reflux for 3h. On dilution of the cooled reaction mixture, a precipitate was
obtained which was collected by filtration and crystallized.
4-Azido-8-methylquinoline-2(1H)-thione (18)
Method A
Using the same method A that used for obtaining compound 10, chloroquinolinethione 4 (2.1 g, 10
mmol) was treated with sodium azide (0.65 g, 10 mmol) in boiling DMF (30 mL).
Method B
Using the same method B for obtaining compound 10, compound 18 was obtained from
hydrazinoquinolinethione 17 (2.05 g, 10 mmol) treated with hydrochloric acid (20 mL, 1 M) and
sodium nitrite (10 mL, 10 mmol) at 0-5°C.
8-Methyl-4-(triphenylphosphoranylideneamino)quinoline-2(1H)-thione (19)
A similar procedure to that used for preparation of compound 11 was followed to obtain
phosphazene 19 starting with azidoquinolinethione 18 (2.16 g, 10 mmol) and triphenylphosphine (2.62
g, 10 mmol) in dry benzene (50 mL).

Molecules 2000, 5
1237
4-Amino-8-methylquinolin-2(1H)-thione (20)
A similar method to that used for hydrolysis of compound 11 was followed. Compound 19 (4.5 g,
10 mmol) was suspended in 2 M hydrochloric acid (25 mL) and heated for 4h to give compound 20.
Table 1. Analytical data of the new compounds.
Compd.
Mol. Formula
Mol. Weight
C10H8NClO
193.5
C10H8NClS
209.5
C10H9NS2
207
C10H9NOS
191
C12H13NOS
219
C14H17NOS
247
C16H13NOS
267
C10H11N3O
189
C17H15NSO4
329
C10H8N4O
200
C20H23N2OP
434
C11H10NClS
223.5
C12H12NClS
237.5
Analyses (Calcd./Found)
C % N %
M.P. (°C)
Solvent
250-2
Dioxane
154-5
EtOH
246-8
EtOH
> 300
DMF
216-7
AcOH
212-3
EtOH
280-2
EtOH
> 300
DMF
Yield (%)
No.
3
H %
4.13
4.10
3.80
3.50
4.35
4.20
4.71
4.70
5.94
5.80
6.92
6.60
4.87
4.80
5.82
5.80
4.56
4.50
4.00
4.00
5.29
5.30
4.47
4.30
5.05
4.80
6.40
6.20
5.53
5.50
6.46
6.30
4.59
4.40
5.37
5.40
3.70
3.60
5.11
5.00
5.26
5.10
91
62.02
62.10
57.28
57.10
57.97
57.70
62.83
62.50
65.75
65.60
68.02
67.90
71.91
71.80
63.49
63.60
62.01
62.00
60.00
60.10
77.42
77.30
59.06
58.80
60.63
60.30
59.11
58.80
61.28
61.00
63.88
63.60
67.84
67.60
58.54
58.30
55.56
55.40
74.67
74.30
63.16
63.10
7.24
7.20
6.68
6.70
6.76
6.50
7.33
7.00
6.39
6.10
5.67
5.60
5.24
5.20
22.22
22.30
4.25
4.20
28.00
27.80
6.45
6.40
6.26
6.00
5.89
5.60
34.48
34.30
5.96
5.80
5.32
5.20
4.95
4.80
20.49
20.60
25.93
25.70
6.22
6.10
14.74
14.50
4
5
82a, 10b
58a, 8b
45c
51
6
7a
7b
7c
8
58a, 79b
63a, 56b
67a
88a, 75b
53c
9
70
222-224
MeOH
224
DMF
290
10
11
13a
13b
14
16a
16b
16c
17
18
19
20
60a, 80b
40c
55
EtOH
75-7
65
78
MeOH
144-6
EtOH
280-282
EtOH
187-8
Dioxane
106-7
DMF
223-5
AcOH
> 300
EtOH
172-4
DMF
60
C10H13N5
203
C12H13NS2
235
C14H17NS2
263
C16H13NS2
283
C10H11N3S
205
C10H8N4S
216
C28H23N2PS
450
C10H10N2S
190
66
72
85
70a, 74b
60a, 75b
70
208-10
CHCl3
164-5
EtOH
56
a, b and c yields by Methods A, B and C, respectively.

Molecules 2000, 5
1238
Table 2. IR and 1H-NMR spectra of the new compounds.
-1
1
Cpd.
ν
δ
H-NMR, (ppm)
IR, (cm )
3
3190 (N-H), 1670 (C=O), 760 (C-Cl)
2.45 (s, 3H, CH3), 5.95 (s, 1H, C3-H), 7.10-7.90 (m, 3H, Harom), 10.30
(bs, 1H, N-H)
4
3175 (N-H), 2600 (br S-H), 1275,
1205 (NHC=S), 762 (C-Cl)
3245 (N-H), 2620-2550 (br S-H),
1290, 1145 (NHC=S)
3165 (N-H), 2510 (br S-H), 1660
(C=O)
1.95 (b, 0.4H, SH), 2.40 (s, 3H, CH3), 6.80 (s, 1H, C3-H), 6.95-7.80
(m, 3H, Harom), 10.15 (b, 0.6H, N-H)
1.65 (b, 0.4H, C2-SH), 1.90 (bs, 1H, C4-SH), 2.30 (s, 3H, CH3), 6.40
(s, 1H, C3-H), 7.05-8.15 (m, 3H, Harom), 10.20 (b, 0.6H, N-H)
1.55 (bs, 1H, C4-SH), 2.35 (s, 3H, CH3), 6.60 (s, 1H, C3-H), 7.00-
7.90 (m, 3H, Harom), 10.45 (b, 1H, N-H)
5
6
7a
7b
3170 (N-H), 1655 (C=O)
1.28 (t, 3H, SCH2CH3), 2.40 (s, 3H, C8-CH3), 3.45 (q, 2H, SCH2CH3),
6.80 (s, 1H, C3-H), 7.15-8.08 (s, 3H, Harom), 10.45 (bs, 1H, N-H)
1.25 (t, 3H, S(CH2)3CH3), 1.35-1.45 (m, 4H, SCH2(CH2)2CH3), 2.45
(s, 3H, C8-CH3), 3.05 (t, 2H, SCH2(CH2)2CH3), 6.90 (s, 1H, C3-H),
7.15-8.05 (m, 3H, Harom), 10.40 (bs, 1H, N-H)
3172 (N-H), 2965-2930 aliph C-H),
1660 (C=O)
7c
8
3140 (N-H), 1643 (C=O)
2.40 (s, 3H, CH3), 6.85 (s,1H,C3-H), 7.10-8.05 (m, 8H, Harom), 10.40
(bs, 1H, N-H)
3430, 3310-3278 (NH2), 3161 (N-H), 2.35 (s, 3H, CH3), 4.30 (bs, 2H, NH2), 5.90 (s, 1H, C3-H), 7.10-7.90
1645 (C=O)
(m, 3H, Harom), 8.20 (bs, 1H, N-Hhydrazino), 10.30 (bs, 1H, N-Hquinolone)
9
3172 (N-H), 3050 (arom C-H),
2956 (aliph C-H), 1648 (C=O), 1383,
1173 (S=O)
10
11
3180 (N-H), 2120 (N3), 1660 (C=O)
2.55 (s, 3H, CH3), 6.80 (s, 1H, C3-H), 7.10-7.85 (m, 3H, Harom), 10.55
(bs, 1H, NH)
2.35 (s, 3H, CH3), 5.95 (s, 1H, C3-H), 7.10-8.00 (m, 18H, Harom),
10.30 (bs, 1H, N-H)
3160 (N-H), 1645 (C=O), 1440
(P=N)
13a
3066 (arom C-H), 2945-2901 (aliph
C-H), 1610 (C=N), 762 (C-Cl), 660
(C-S)
2.60 (s, 3H, C8-CH3), 3.00 (s, 3H, S-CH3), 6.95 (s, 1H, C3-H), 7.25-
8.05 (m, 3H, Harom
)
13b
14
3065 (arom C-H), 2970 (aliph C-H),
1620 (C=N), 750 (C-Cl), 660 (C-S)
3450-3320 (NH2), 3190,3180 (NH)
,1610 (def. N-H, C=N)
1.30 (t, 3H, SCH2CH3), 2.65 (s, 3H, C8-CH3), 3.30 (q, 2H, SCH2CH3),
7.05 (s, 1H, C3-H), 7.25-8.00 (m, 3H, Harom
)
16a
16b
3160 (N-H), 1605 (def. N-H), 1282,
1150 (C=S)
3140 (N-H), 2960-2900 (aliph C-H),
1612 (def N-H), 1270, 1143
(NHC=S), 695 (C-S)
1.26 (t, 3H, SCH2CH3), 2.40 (s, 3H, C8-CH3), 3.18 (q, 2H, SCH2CH3),
6.75 (s, 1H, C3-H), 7.24-8.03 (m, 3H, Harom), 10.20 (b, 1H, N-H)
1.28 (t, 3H, SCH2(CH2)2CH3), 1.35-1.50 (m, 4H, SCH2(CH2)2CH3),
2.15 (s, 3H, C8-CH3), 3.20 (t, 2H, SCH2(CH2)2CH3), 6.85 (s, 1H, C3-
H), 7.15-8.05 (m, 3H, Harom), 10.65 (bs, 1H, N-H)
16c
17
3200 (N-H), 3060 (arom C-H), 1605
(def N-H), 1280, 1147 (NHC=S), 670 (s,1H,N-H)
(C-S)
2.40 (s, 3H, CH3), 6.80 (s, 1H, C3H), 7.20-8.03 (m, 8H, Harom), 10.45
3430, 3365 (NH2), 3170 (N-H), 2600
1.95 (b, 0.3H, SH), 2.55 (s, 3H, CH3), 6.20 (bs, 2H, NH2), 6.45 (s, 1H,
(br S-H), 1620 (def N-H), 1250, 1145 C3-H),7.00-8.03 (m, 3H, Harom), 8.15 (s,1H, N-Hhydrazino), 10.20 (b,
(NHC=S)
0.7H, CSN-H)
18
19
20
3200 (N-H), 2120 (N3), 1600 (def N-
H, str C=C), 1250, 1135 (NHC=S)
3165 (N-H), 1610 (def N-H), 1425
(P=N), 1255, 1150, 1040 (NHC=S)
3430, 3320 (NH2), 3170 (N-H), 2520
(S-H), 1605 (def N-H, C=C), 1270,
1125 (NHC=S)
1.95 (s, 0.3H, S-H), 2.55 (s, 3H, CH3), 6.65 (s,1H, C3-H), 7.05-8.15
(m, 3H, Harom), 10.45 (bs, 0.7H, CSN-H)
1.85 (s, 3H, CH3), 6.25 (s, 1H, C3-H), 6.95-8.05 (m, 18H, Harom),
10.40 (s, 1H, N-H)
1.95 (s, 3H, CH3), 5.85 (s, 1H, C3-H), 6.40 (bs, 2H, NH2), 7.15-7.95
(m, 3H, Harom), 10.40 (s, 1H, N-H)

Molecules 2000, 5
1239
References and Notes
1. Ismail, M. M.; Abass, M.; Hassan, M. M. Phosph. Sulfur Silicon 2000, accepted for publication;
International Electronic Conference on Synthetic Organic Chemistry (ECSOC-4), 2000:
http://www.reprints.net/ecsoc-4/a0088/a0088.htm.
2. Mohamed, E. A.; Ismail, M. M.; Gabr, Y.; Abass, M. J. Serb. Chem. Soc. 1993, 58, 737.
3. Ismail, M. M.; Abass, M. Acta Chim. Slov. 2000, 47, 327.
4. Sarac-Arneri, R.; Mintas, M.; Pustec, N.; Mannschreck, A. Monatsh. Chem. 1994, 125, 457.
5. Urquhart, G. G.; Gates, T. W.; Connor, R. Org. Synth. 1955, 3, 363.
6. Bourguignon, J.; Lemarchand, M.; Queguiner, G. J. Heterocycl. Chem. 1980, 17, 257.
7. Abass, M.; Ismail, M. M. Chem. Papers 2000, 51, 186.
8. Mirek, J.; Sygula, A. Z. Naturforsch 1982, 37a, 1276.
9. Staudinger, H.; Meyer, J. Helv. Chim. Acta 1919, 2, 635.
10. Rylander, P. N. Hydrogenation Methods, Academic Press: London, 1985, p. 170.
Samples Availability: Available from the authors.
© 2000 by MDPI (http://www.mdpi.org)