Preparation and oxidative-chlorination splitting of nitro derivatives of 1,4-dithiino[2,3-c:5,6-c′]diquinoline as a source of 4-substituted 5-and 8-nitro-3-quinolinesulfonic acid derivatives

Article abstract of DOI:10.1080/10426507.2012.680085

Treatment of 1,4-dithiino[2,3-c:5,6-c]diquinoline (a thioquinanthrene) (1a) with an excess of nitrating mixture (0 C, 14days) led to a mixture of mono-and dinitrothioquinanthrene 7-oxides 2b-e and 2f-h. This mixture was: (i) reduced to a mixture of mono-and dinitrothioquinanthrenes 1b-e, or (ii) oxidatively chlorinated with a gaseous chlorine/80% acetic acid/hydrochloric acid system to a mixture of 4-chloro-3-chlorosulfonylquinoline 3a and its 5-and 8-nitroderivatives 3b and 3d. Sulfochlorides 3a-d were independently synthesized from 3,4-diquinolinyl sulfides 4 and converted to the respective 4-dimethylamino-3-quinoline-N,N-dimethylsulfonamides 9a-d. Taylor and Francis Group, LLC.

Full text of DOI:10.1080/10426507.2012.680085

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Phosphorus, Sulfur, and Silicon and the
Related Elements
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Preparation and Oxidative-Chlorination
Splitting of Nitro Derivatives OF 1,4-
Dithiino[2,3-C:5,6-C′]Diquinoline as a
Source of 4-Substituted 5- and 8-Nitro-3-
Quinolinesulfonic Acid Derivatives
Elwira Chrobak a , Andrzej Maślankiewicz a , Magdalena Chyćko a
,
Leszek Skrzypek a , Małgorzata Szmielew a , Maria J. Maślankiewicz
b , Joachim Kusz c & Maciej Zubko c
a Department of Organic Chemistry, Medical University of Silesia,
Sosnowiec, Poland
b Institute of Chemistry, University of Silesia, Katowice, Poland
c Institute of Physics, University of Silesia, Katowice, Poland
Accepted author version posted online: 13 Apr 2012. Version of
record first published: 20 Jul 2012
To cite this article: Elwira Chrobak, Andrzej Maślankiewicz, Magdalena Chyćko, Leszek Skrzypek,
Małgorzata Szmielew, Maria J. Maślankiewicz, Joachim Kusz & Maciej Zubko (2012): Preparation and
Oxidative-Chlorination Splitting of Nitro Derivatives OF 1,4-Dithiino[2,3-C:5,6-C′]Diquinoline as a
Source of 4-Substituted 5- and 8-Nitro-3-Quinolinesulfonic Acid Derivatives, Phosphorus, Sulfur, and
Silicon and the Related Elements, 187:10, 1208-1225
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Phosphorus, Sulfur, and Silicon, 187:1208–1225, 2012
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.680085
PREPARATION AND OXIDATIVE-CHLORINATION
SPLITTING OF NITRO DERIVATIVES OF
1,4-DITHIINO[2,3-C:5,6-Cꢁ]DIQUINOLINE AS A SOURCE
OF 4-SUBSTITUTED 5- AND
8-NITRO-3-QUINOLINESULFONIC ACID DERIVATIVES
Elwira Chrobak,1 Andrzej Mas´lankiewicz,1 Magdalena
Chyc´ko,1 Leszek Skrzypek,1 Małgorzata Szmielew,1
Maria J. Mas´lankiewicz,2 Joachim Kusz,3 and Maciej Zubko3
1Department of Organic Chemistry, Medical University of Silesia,
Sosnowiec, Poland
2Institute of Chemistry, University of Silesia, Katowice, Poland
3Institute of Physics, University of Silesia, Katowice, Poland
GRAPHICAL ABSTRACT
S
N
N
S
N
Cl
NO2
5
8
S
SO2Cl
N
NO2
N
S
O
N
NO2
Abstract Treatment of 1,4-dithiino[2,3-c:5,6-cꢀ]diquinoline (a thioquinanthrene) (1a) with
an excess of nitrating mixture (0 ◦C, 14 days) led to a mixture of mono- and dinitrothio-
quinanthrene 7-oxides 2b–e and 2f–h. This mixture was: (i) reduced to a mixture of mono-
and dinitrothioquinanthrenes 1b–e, or (ii) oxidatively chlorinated with a gaseous chlorine/80%
acetic acid/hydrochloric acid system to a mixture of 4-chloro-3-chlorosulfonylquinoline 3a and
its 5- and 8-nitroderivatives 3b and 3d. Sulfochlorides 3a–d were independently synthesized
from 3,4ꢀ-diquinolinyl sulfides 4 and converted to the respective 4-dimethylamino-3-quinoline-
N,N-dimethylsulfonamides 9a–d.
Keywords 1,4-Dithiins; quinolines nitration; quinolinyl sulfoxides; oxidative chlorination;
quinolinesulfonyl chlorides
Received 5 February 2012; accepted 24 March 2012.
This work was supported by the Medical University of Silesia, Poland, Grant No KNW-1-073/P/1/0.
# Part CXXX in the series of Azinyl Sulfides
Address correspondence to Andrzej Mas´lankiewicz, Department of Organic Chemistry, Medical University
of Silesia, Jagiellon´ska 4, 41-200 Sosnowiec, Poland. E-mail: maslankiewicz@sum.edu.pl
1208

TREATMENT OF THIOQUINANTHRENE WITH EXCESS MIXTURE
1209
INTRODUCTION
Nitroquinolines may be of interest for two reasons. First, directly, because introduc-
tion of a nitro substituent into the quinoline molecule induces a significant increase in
the biological activity of quinolines as antibacterial1 or antitumor2 agents. Second, indi-
rectly, since nitro derivatives of quinoline may be used for preparation of other substituted
quinolines, both with3 nitro and without the nitro group.4
The aim of this paper is to extend previous findings on double 3,4-functionalization
of quinoline via thioquinanthrene (1a), i.e., 1,4-dithiino[2,3-c:5,6-cꢀ]diquinoline (see
Scheme 1) as a source of new 5- or 8-nitro 3,4-disubstituted quinolines. Oxidative chlorina-
tion of thioquinanthrene (1a) resulted directly in 4-chloro-3-chlorosulfonylquinoline (3a)
(with 80% yield),5 which could be applied for the preparation of numerous 4-substituted
3-thioquinolines of types A and B.5,7 (see Scheme 1, ref., 6)
Y
NR1R2
SO2NR3R4
or
Cl
S
SO2Z
SO2Cl
ref.,5,7
S8
Cl2
N
ref.,5
ref.,6
N
N
S
N
R5
N
N
Y=O, S,
Z=OH, NR2, alkyl
R5=H,alkyl
1a
3a
A
B
thioquinanthrene
Scheme 1
An attempt to obtain nitro derivatives of 1a by way of reaction with nitrating mixture
led almost quantitatively to thioquinanthrene 7-oxide 2a.8 (Scheme 2) However, treatment
of sulfoxide 2a with an excess of nitrating mixture for a longer reaction time transformed
2a into a mixture of nitrothioquinanthrene 7-oxides 2b, 2c, 2d, and 2e9 and even into a
mixture of mononitrothioquinanthrene 7-oxides 2b, 2c, 2d, and 2e and dinitrothioquinan-
threne 7-oxides 2f–h, as presented in this paper. The mixture of 2b–e and 2f–h was directly
subjected to oxidative chlorination with the gaseous chlorine/80% acetic acid/hydrochloric
acid system, which resulted in a mixture of 4-chloro-3-chlorosulfonylquinoline (3a), and its
5-, 8-, and small amounts of 6-nitro derivatives (3b), (3d), and (3c). 3-Quinolinesulfonyl
chlorides 3a–d were characterized in the form of 4-dimethylamino-3-quinoline- N,N-
dimethylsulfonamides 9a–d.
RESULTS AND DISCUSSION
Reaction of Thioquinanthrene (1a) with Nitrating Mixture
As reported previously,8 the reaction of thioquinanthrene (1a) with nitrating mixture
proceeded stepwise (3.6 molar eqv. of HNO3, 0–5 ◦C, 1 h) to form thioquinanthrene 7-oxide
(2a), which were then (7.2 molar eqv. of HNO3, 0–5 ◦C, 3 days) nitrated at the 5- and 8-
quinolinyl positions to form a mixture of 1-, 4-, 8-, and 11-nitrothioquinanthrene 7-oxides
2b (5%), 2c (12%), 2d (32%), and 2e (11%) and non-nitrated 2a (40%).9 (Scheme 2) As the
total content of nitrothioquinanthrene 7-oxides 2b, 2c, 2d, and 2e was too low, this mixture
was treated with larger excess of nitrating mixture (32 molar eqv. of HNO3) for longer time
(up to 14 days at 0 ◦C) to yield a mixture containing mononitrothioquinanthrene 7-oxides
2b, 2c, 2d, and 2e and dinitrothioquinanthrene 7-oxides 2f, g, h (where x = 8 or 11, y = 1,
4, or 2). Attempts to accelerate the reaction by performing it at a slightly higher temperature

1210
E. CHROBAK ET AL.
S
N
a)
S
S
N
7
S
N
ref.8
N
O
1a
2a
ref.9
b)
1
y-NO2
S
S
4
N
N
7
S
7
S
N
N
11
x-O2N
O
O
8
2b, y=1, (5 %)
2c, y=4, (12 %)
2d, x=8, (32 %)
2e, x=11, (11 %)
c)
2
1
y-NO2
S
4
N
7
N
11
S
x-O2N
O
8
2f,g,h
OTqNO2 mixture
(2b-e + 2f-h + 10)
d)
NO2 Cl
.
5
SO2Cl
SO2Cl
1
1
y-NO2
S
N
y-NO2
Cl2
e)
S
N
4
S
N
4
3b
N
7
N
7
S
Cl
N
7
S
S
11
N
11
8
O2
x-O2N
NO2
8
1d, x=8,y=1
1e, x=11,y=1
1b, y=1
1c, y=4
10
8
N
lack of the peri effect
3a
ref.,9
b)
b)
1
O2N
2
(O)m 1
1
S
y-NO2
N
y-NO2
S
S
4
4
N
N
14
7
N
7
7
S
N
N
11
11
O2
S
(O)n
S
x-O2N
H
8
O
8
10a
8
2g (x=11,y=1, m=0, n=1)
and 2h (x=11,y=1, m=1, n=0) from 1e
2f (x=8,y=1, m=0, n=1) from 1d
2b (y=1) and 2d (y=8) from 1b
2c (y=4) and 2e (y=11) from 1c
Reagents and conditions: for a), b), and c) - nitrating mixture. a) HNO3 (3.6 molar. eqv.), 0-5 oC, 1h. b) HNO3
(7.2 molar. eqv.), 0-5 oC, 3 days; or 1 day for 1b,c,d,e. c) HNO3 (32 molar. eqv.), 0-5 oC, 14 days. d) KI/ HCl
aq, rt, 0.5 h. e) Cl2, 80 % AcOH, HCl, 17 oC, 15 min.
Scheme 2

TREATMENT OF THIOQUINANTHRENE WITH EXCESS MIXTURE
1211
(20–40 ◦C) led to a 35% decrease in the formation of nitrothioquinanthrene 7-oxides 2b–2e
and 2f–h accompanied by substantial amounts of aqueous alkali-soluble products.
The mixture of 2b–2e and 2f–h, and 7,7-dioxide 10 (see below—Scheme 2) was
termed the OtqNO2 mixture. Elemental analysis data of the OtqNO2 mixture (C 53.50%,
H 2.10%; N 12.25%; S 15.82%) compared to values for mononitrothioquinanthrene 7-
oxides (e.g., 2b) (C18H9N3S2O3, C 56.98%, H 2.39%; N 11.08%; S 16.90%) and those
for dinitrothioquinanthrene 7-oxides 2f (C18H8N4O5S2, C 50.94%, H 1.90%; N 13.20%; S
15.11%) suggest that the OtqNO2 mixture consists of ca. 42% of mononitrothioquinanthrene
7-oxides and ca. 58% of dinitrothioquinanthrene 7-oxides. Furthermore, this supposition is
supported by chlorination results presented below (Schemes 4, 5). As deduced from TLC
analysis, the OtqNO2 mixture consists of ca. 12 compounds. TLC separation (see experi-
mental) gave only the nonhomogeneous fractions, containing, as deduced from MS data,
two or three species with molecular ions of magnitude of 424 or 379 indicating dinitroth-
ioquinanthrene 7-oxide (M+ = 424) and mononitrothioquinanthrene 7-oxide (M+ = 379).
Species with M+ = 395, corresponding to nitrothioquinanthrene S,S-dioxides, were also
observed. These fractions showed positive confirmatory tests for the sulfinyl group (reac-
tion with H+/NaI system, ref.10) and for the nitro group (reduction to arylhydroxylamines
and reaction with Ag+ ion).11 IR spectra (KBr pellet) showed strong sulfinyl group bands
at νSO∼1050–1089 cm−1 and bands of the nitro group at ca. 1360 cm−1 and 1530 cm−1
,
all in agreement with literature data.11,12
For further evaluation of the OtqNO2 mixture, it was subjected to determination of
its sulfoxide content using reaction of sulfoxides with iodide anion in a trifluoroacetic
anhydride/acetone medium followed by titration of iodine with thiosulfate.10 The above
method was confirmed on pure thioquinanthrene 7-oxide (2a) with an accuracy of 99.8
0.2%. Determination of sulfoxide content for the OtqNO2 mixture with this analytic system
gave only 85–87% of the expected sulfoxide content.
The analytical data presented above prompted us to preparative reduction of the
OtqNO2 mixture with KI/conc. HClaq. system. The reaction led to a five-component mix-
ture of nitrothioquinanthrenes (1b, 1c, 1d, and 1e) and nitrothioquinanthrene S,S-dioxide
10 (Scheme 2), which were then chromatographically isolated in the pure state. Proper-
ties of 1- and 4-nitrothioquinanthrenes (1b, 1c) were reported previously.9 Structure of
1,8-dinitrothioquinanthrene (1d) and 1,11-dinitrothioquinanthrene (1e) was deduced from
oxidative chlorination products. (Scheme 4) Splitting of dinitrothioquinanthrene 1d by ox-
idative chlorination resulted in 4-chloro-5-nitroquinolinesulfonyl chloride (3b) as a sole
product, which indicates that nitro groups in compound 1d are located at the 5-quinolinyl
positions, i.e. positions 1 and 8 according to the numbering of thioquinanthrene (1a).
The same treatment of compound 1e led to a mixture of 4-chloro-5-nitro and 4-chloro-
8-nitroquinolinesulfonyl chlorides (3b and 3d), the nitro groups in compound 1e must,
therefore, be located in positions 1 (i.e., 5-quinolinyl) and 11 (i.e., 8-quinolinyl). As sul-
fones are not reduced by H+/KI system (ref.,10), 8-nitrothioquinanthrene 7,7-dioxide (10)
remains unchanged during treatment of the OtqNO2 mixture with KI/conc. HClaq sys-
tem. Structure of compound 10 was deduced from oxidative chlorination leading to 3b
1
and 3a, moreover H NMR spectrum of compound 10 exhibited lack of a proton being
peri-influenced by the sulfonyl group.
To reconstruct the composition of the OtqNO2 mixture, each of nitrothioquinanthrenes
(1b, 1c, 1d, and 1e) was subjected to oxidation with the nitrating mixture (Scheme 2). As
reported previously,9 reaction of mononitrothioquinanthrenes 1b, 1c gave sulfoxides 2b
and 2d for 1b or 2c and 2e for 1c. In the case of newly prepared dinitrothioquinanthrene

1212
E. CHROBAK ET AL.
sulfoxides 2f, 2g, and 2h strong bands in the sulfoxide region12 at νSO ∼ 1059–1085 cm−1
1
were observed. H NMR assignment of compounds 1e and 2g was deduced from HSQC
and HMBC experiments (see the experimental part) while that of sulfoxide 2h from COSY
spectra. Crucial data for the structure assignment of sulfoxides 2g and 2h and the position
of the newly-introduced sulfinyl group come from spectroscopic effects due to deshielding
of the peri and ortho protons by the sulfinyl group (Scheme 3).
0.19
0.25
O2N
(O)n
O2N
S
0.15
0.14
0.12
0.22
0.17
0.56
S
S
N
N
N
N
O2N
N
O2N
0.21
N
S
S
S
0.55
(O)n 0.47
O
H
0.21
H
0.05
1.12
0.16
0.03
ortho effect
∆δH ~0.5 ppm
peri effect
∆δH ~0.8 ppm
(2h) n=1, vs (1e) n=0
(2g) n=1, vs (1e) n=0
Selected substituted chemical shifts values ∆δH= δsulfoxide - δsulfide for 1,11-dinitrothioquinanthrene 7-oxide
(2g) n=1, vs 1,11-dinitrothioquinanthrene (1e) n=0, (CDCl3 solutions) and 4,8-dinitrothioquinanthrene 7-
oxide (2h) n=1, as related to 1,11-dinitrothioquinanthrene (1e) n=0 (DMSO-d6 solutions).
Scheme 3
The NMR spectral conclusions concerning the structure of compounds (2f,g,h) were
supported by X-ray analysis of 1,11-dinitrothioquinanthrene 7-oxide (2g), X-ray data of
compound 2g provided evidence for the presence of 1- and 11-nitro groups, and equatorial
7-S-oxide substituent at the parent thioquinanthrene moiety.
Figure 1, ORTEP drawing of 1,11-dinitro-1,4-dithiino[2,3-c:5,6-cꢀ]diquinoline 7-
oxide (i.e., 1,11-dinitrothioquinanthrene 7-oxide) (2g) with the atom labeling scheme.
Displacement ellipsoids are drawn at the 70% probability level.
Figure 1 X-Ray Structure of 2g shown at 70% probability.

TREATMENT OF THIOQUINANTHRENE WITH EXCESS MIXTURE
1213
Oxidative Chlorination of the OtqNO2 Mixture
For a better understanding of the complex composition of the OtqNO2 mixture, it
was directly subjected to oxidative chlorination in order to split the biquinoline systems
of thioquinanthrene S-oxides 2a–h and 10 into the monoquinoline units of 4-chloro-3-
quinolinesulfonyl chlorides 3a–d.
To extend previous findings on oxidative chlorination of thioquinanthrene (1a)5 to the
same treatment of the OtqNO2 mixture, thioquinanthrene 7-oxide (2a) and, subsequently,
8-nitrothioquinanthrene 7-oxide (2d) were subjected to the reaction (Scheme 4). This
proved that the 1,4-dithiino-S-oxide unit of thioquinanthrene 7-oxides 2a and 2d undergoes
chlorination in the same manner as the 1,4-dithiin ring of thioquinanthrene (1a) with the
nucleophilic cleavage of the γ -quinolinyl-sulfur bonds by chloride anions and oxidative
chlorination of β-quinolinyl ones.
Cl
S
SO2Cl
Cl2
N
2
7
N
80 % AcOH
HCl aq.
S
(O)n
N
3a
mode of the
oxidative-chlorination
splitting
1a, n=0
2a, n=1
NO2 Cl
5
S
SO2Cl
Cl2
N
+
3a
7
S
N
80 % AcOH
HCl aq.
N
8
3b
O
2d
NO2
1
Cl
NO2 Cl
y-NO2
S
SO2Cl
4
SO2Cl
N
Cl2
7
S
+
N
11
80 % AcOH
HCl aq.
N
N
x-O2N
3d
3b
NO2
8
1d, x=8,y=1
1e, x=11,y=1
2 molar eqvs. of 3b from 1d
3b + 3d from 1e
Cl
5
SO2Cl
6
OTqNO2 mixture
(2b-e + 2f-h + 10)
Cl2
x-O2N
+
3a
80 % AcOH
HCl aq.
N
8
3b-d
Scheme 4
However, chlorination of compounds with a 1,4-dithiino-S- oxide unit, i.e., 2a and 2d
required the presence of conc. hydrochloric acid. The mixture obtained from the oxidative
chlorination of 2d contained both expected products: 4-chloro-3-chlorosulfonylquinoline
(3a) (Rf = 0.51, system II) and 4-chloro-3-chlorosulfonyl-5-nitroquinoline (3b) (Rf = 0.42,
system II) (prepared as a reference compound, Scheme 6) in the ratio of 1:1 (deduced
1
from H NMR spectrum) with total yield of 80%. The mixture of 3a and 3b could be

1214
E. CHROBAK ET AL.
separated to individual sulfonyl chlorides by column chromatography with yields of 65%
for 3a and 60% for 3b as compared to the 90% yield of bis-dimethylamination of the
starting mixture of 3a and 3b to 4-dimethylamino-3-quinoline-N,N-dimethylsulfonamides
(9a and 9b).
Oxidative chlorination of the OtqNO2 mixture led to a mixture of four 4-chloro-3-
chlorosulfonylquinolines 3a–d in the ratio of 3a:3b:3c:3d = 0.57:0.96:0.05:1 as concluded
from 1H NMR spectrum, based on intensities of α-quinolinyl proton singlets. TLC analysis
(system II) revealed spots of 3a (Rf = 0.51), 3b (Rf = 0.42), and 3d (Rf = 0.36). Attempts to
separate sulfonyl chlorides 3a–d by column chromatography led to 3a (58%) and a mixture
of 3b and 3d with a yield of only 54%. Bis-dimethylamination of the mixture of 3a–d
(Scheme 5) gave a mixture of 4-dimethylamino-3-quinoline-N,N-dimethylsulfonamides in
the ratio 9a:9b:9c:9d = 0.60:1:0.05:1, with a total yield of ca. 75%.
Cl
NMe2
S
SO2Cl
N
SO2NMe2
OtqNO2 mixture
X
N
X
S
1a
(7.85 g)
N
N
aminoquinolinesulfonamides 9a-d (8.83 g)
ratio 9a:9b:3c:9d=0.60:1:0.05:1
9a, X=H, 1.70 g, 6.3 mmol, 16 % *
9b, X=5-NO2, 3.40 g, 10.8 mmol, 27 % *
9d, X=8-NO2, 3.55 g, 11.3 mmol, 28 % *
quinolinesulfonyl chlorides 3a-d
(9.6 g)
ratio 3a:3b:3c:3d=0.57:0.96:0.05:1
thioquinanthrene (1a)
6.4 g, 20 mmol,
(40 mmolar eqv. of
quinoline unit)
*Yields of 9a, 9b, 9d were calculated with respect
to the amounts of compounds isolated from column
chromatography.
Scheme 5
Formation yields of 3a, 3b, and 3d from thioquinanthrene (1a) were evaluated as
presented in Scheme 5. This confirms that the OtqNO2 mixture contains more than 3.5
nitroquinoline units per one non-nitrated quinoline unit.
Synthesis of 5-, 6-, and 8-nitro-4-chloro-3-quinolinesulfonyl chlorides
3b,c,d from 4-substituted 3ꢁ-methylsulfinyl-3,4ꢁ-diquinolinyl sulfides 4
Reference samples of 3-quinolinesulfonyl chlorides 3b,c,d (required for analytical
purposes during the chlorination study of nitrothioquinanthrene 7-oxides 2b–h mentioned
above) were prepared by independent routes. (see Scheme 6) They consisted of two stages:
synthesis of 3-benzylsulfanyl-4-chloro-5-, 6-, and 8-nitroquinolines 7a,b,c and their oxida-
tive chlorination to quinolinesulfonyl chlorides 3b,c,d.
Following previous findings, 4-substituted 5-, 6-, and 8-nitro-3-thioquinoline
units 6A,B and 7A,B could be obtained by aryloxy-de-sulfidation of 4-substituted
3ꢀ-methylsulfinyl-3,4ꢀ-diquinolinyl sulfides 4 with potassium aryloxides.13,14 4-Aryloxy-3-
methylsulfinylquinoline 5 as a neutral product was separated by extraction from alkaline
solution and the remaining aqueous-DMSO solution of 3-quinolinethiolates 6A,B or 7A,B
and 8A was benzylated to the respective 3-benzylsulfanylquinolines 6, 7, and 8.
In this way, a mixture of 3-benzylsulfanyl-4-methoxy-6- and 8-nitroquinolines
(6a,b) was prepared from the mixture of 6- and 8-nitro-4-methoxy-3ꢀ-methylsulfinyl-
3,4ꢀ-diquinolinyl sulfides (4a,b) and potassium phenoxide but reaction of potassium
2,6-dimethylphenoxide with a mixture of 5- and 8-nitro-4-chloro- 3ꢀ-methylsulfinyl-3,

TREATMENT OF THIOQUINANTHRENE WITH EXCESS MIXTURE
1215
Y
4'
4
S
N
x-O2N
N
S(O)Me
4a + 4b, Y=OMe, x=6 or 8
4c + 4d, Y=Cl, x=5 or 8
a) ArO
Y
N
Y
N
OAr
5
5
SCH2Ph
S
S(O)Me
6
6
PhCH2Cl
b)
x-O2N
x-O2N
N
8
8
5a, Ar=Ph
5b, Ar=2,6diMePh
6A, Y=OMe, x=6
6B, Y=OMe,x=8
7A, Y=Cl, x=5
6a, Y=OMe, x=6
6b, Y=OMe, x=8
7a, Y=Cl, x=5
7B, Y=Cl, x=8
7c, Y=Cl, x=8
8A, Y=2,6diMePh
8, Y=2,6diMePhO, x=8
OCH3
SCH2Ph
Cl
5
5
SCH2Ph
6
6
c)
x-O2N
x-O2N
N
N
8
8
6a, Y=OMe, x=6
6b, Y=OMe, x=8
7b, Y=Cl, x=6
7c, Y=Cl, x=8
Cl
N(Me)2
5
5
SO2Cl
(Me)2NH
6
SO2N(Me)2
Cl2
7a,b,c
6
x-O2N
x-O2N
80 % AcOH
N
N
8
8
3b-d
9b-d
Reagents and conditions: a) DMSO, rt, 20 min. b) OH , 40-50 oC, 30 min. c) POCl3 , Et3NH Cl ,
boiling temp., 0.5 h.
Scheme 6
4ꢀ-diquinolinyl sulfides (4c,d) afforded a mixture of 5- and 8-nitro-4-chloro- 3-benzyl-
sulfanylquinolines 7a,c and 4-(2,6-dimethylphenoxy)-8-nitro-3-benzylsulfanylquinoline
(8). The mixture of 6a and 6b could be easily separated by chromatography into indi-
vidual components, and the resulting 4-methoxyquinolines 6a and 6b were chlorinated
with phosphorus oxychloride to the 4-chloroquinolines 7b or 7c, respectively. Chromato-
graphic separation of the mixture of 7a,c and 8 resulted in pure 3-benzylsulfanyl-4-chloro-
5-nitroquinoline 7a and a fraction with 8-nitroquinolines 7c and 8, which was rechro-
matographed to yield 7d and 8. 5-, 6-, and 8-nitro-4-chloro-3-benzylsulfanylquinolines
(7a,b,c) were finally chlorinated under the “wet-chlorination procedure” to 5-, 6-, or 8-
nitro-4-chloro-3-quinolinesulfonyl chlorides (3b,c,d).

1216
E. CHROBAK ET AL.
CONCLUSIONS
Treatment of thioquinanthrene (1a) with an excess of nitrating mixture (0 ◦C, 14 days)
led to a mixture of mono- and dinitrothioquinanthrene 7-oxides 2b–e and 2f–h, and 7,7-
dioxide 10, all with nitro groups in the 5-quinolinyl and 8-quinolinyl positions. Nitrothio-
quinanthrene S-oxides 2b–h were reduced to mono- and dinitrothioquinanthrenes 1b–e.
The above results open the way to extend previous findings on the two-step synthe-
sis of 4-chloro-3-quinolinesulfonyl chloride (3a) from quinoline5 to a three-step prepara-
tion of 5- and 8-nitro-4-chloro-3-quinolinesulfonyl chlorides (3b and 3d) from quinoline.
(Scheme 7)
2
1
Cl
y-NO2
5
8
S
SO2Cl
4
S
N
ref.,6
N
7
S
x-O2N
N
11
N
N
N
S
x-O2N
O
8
3b, x=5; 3d, x=8
and 3a (without NO2 group)
1a
2b-h
Scheme 7
This process comprises: (i) sulfurization of quinoline to thioquinanthrene (1a), (ii)
treatment of 1a with a large excess of nitrating mixture, leading to mono- and dinitrothio-
quinanthrene 7-oxides 2b–e and 2f–h, and (iii) oxidative-chlorination splitting of 2b–h to a
mixture of 4-chloro-3-quinolinesulfonyl chlorides (3a,b,d). Furthermore, this process is of
preparative value as direct nitration of 4-chloro-3-quinolinesulfonyl chloride (nitrating mix-
ture, 0–50 ◦C, 1–24 h) appeared to be completely uneffective. The oxidative chlorination
of dithiins 1 and dithiin S-oxides 2 provides very useful data both for the structure assign-
ment of 1,4-dithiino[2, 3-c; 5, 6-cꢀ]diquinoline derivatives 1 and 2, and for the preparative
conditions to convert dithiin S-oxides 2 into 3-quinolinesulfonyl chlorides 3.
EXPERIMENTAL
1
Melting points were taken in open capillary tubes and are uncorrected. H NMR
spectra were recorded on a Bruker AVANCE 400 spectrometer operating at 400.22 MHz,
in CDCl3 or in DMSO-d6 solutions with (Me)4Si (δ 0.0 ppm) as internal standard. Two-
dimensional 1H-13C HSQC and HMBC experiments were performed using standard Bruker
software HSQCGP and HMBCGP, respectively, and the following parameters: the spectral
1
widths in F2 and F1 were ca 5 kHz for H and 16.7 kHz for 13C, the relaxation delay
was 1.5 s, the refocusing in the HSQC experiment was 1.7 ms and the delay for long-
range evolutions was 50 ms in 1H/13C HMBC. 2D spectra were acquired as 2048 × 1024
hypercomplex files, with 1–4 transients. IR spectra were recorded with a Magma—IR 500
(Nicolet) spectrometer in potassium bromide pellets. EI MS spectra were determined on a
Finnigan Mat 95 spectrometer at 70 eV and at a temperature of 80–100 ◦C.
TLC analyses were performed employing Merck’s silicagel 60 F254 plates and a
solution of CHCl3-EtOH (19:1, v/v) as an eluent (system I) or hexane-dried acetone (2:1,
v/v) (system II), or Merck’s aluminium oxide 60 F254 neutral (type E) plates using mixture
of CHCl3-EtOH (19:1, or 10:1, v/v) as eluent (system III).

TREATMENT OF THIOQUINANTHRENE WITH EXCESS MIXTURE
1217
Mixtures of 4-methoxy-6- and 8-nitro-3ꢀ-methylsulfinyl-3,4ꢀ-diquinolinyl sulfides
4b)15 or 4-chloro-5- and 8-nitro-3ꢀ-methylsulfinyl-3,4ꢀ-diquinolinyl sul-
(4a
+
fides (4c + 4d)16 were prepared as described previously. The crude mixture (4a +
4b) or (4b +4d) (1 g) was purified by dissolution in hot chloroform (10 mL), hot filtration
of the insoluble material and evaporation of the solvent. In this form, the above mixture
exhibited mainly the presence of nitro isomers (4a + 4b) or (4c +4d), and was used for
reactions with potassium aryloxide.
Potassium aryloxides were prepared by dissolving equimolar amounts of phenol
or 2,6-dimethylphenol and potassium methoxide (Merck product) in anhydrous methanol
(1.5 mL per 1 mMol of phenol). Then, a clear mixture was evaporated to dryness from
water bath. Potassium aryloxide was immediately used for reaction with sulfides 4.
Reaction of 4-Substituted 3ꢁ-Methylsulfinyl-3,4ꢁ-Diquinolinyl Sulfides 4
with Potassium Aryloxide (Scheme 6)
A mixture of 3,4ꢀ-diquinolinyl sulfides (4a,4b) or (4c,4d) (total amount, 1 mM) was
added at rt to DMSO (8 mL) and then potassium phenoxide (0.4 g, 3 mM) [for the reaction
with (4a,4b)] or potassium 2,6-dimethylphenoxide (0.48 g, 3 mM) [for the reaction with
(4c,4d)] was introduced in one portion on stirring. The mixture was stirred for 20 min at rt
and then poured into 5% aqueous sodium hydroxide (15 mL).
4-Aryloxy-3-methylsulfinylquinoline (5) was filtered off. The residual part of 5 was
extracted with chloroform (3 × 5 mL). The solid and the extracts were combined, and the
solution was dried with sodium sulfate. The solve◦nt was then distilled off to give crude
5. Properties of 5a (Ar = C6H5, mp = 111–113 C, recrystallized from ethanol) or 5b
(Ar = 2,6-diMeC6H3, an oil), were identical (1H NMR data and TLC) to those of samples
prepared previously.13,14
Alkaline aqueous-DMSO solution of 3-quinolinethiolates 6A or 7A + 8A was alky-
lated on stirring (30 min) at 40–50 ◦C with 0.18 mL (1.5 mM) of benzyl chloride. The pre-
cipitates containing the mixtures of 3-benzylsulfanylquinolines (6a + 6b) or (7a + 7c + 8)
(for details see Scheme 6) were filtered off and air-dried to give the first crop of the products.
The filtrates were extracted with chloroform (2 × 5 mL). The extracts were treated in a typ-
ical manner to give the second crop (∼20 mg) of the mixture of 3-benzylsulfanylquinolines
mentioned above. Both crops were combined and subjected to chromatographic separation
(SiO2, CHCl3:EtOH, 30:1, v/v). The mixture of 4-methoxyquinolines (6a + 6b) could be
separated into individual components to give 6a (160 mg, 74%) (lower Rf value) and 6b
(76 mg, 70%) (higher Rf value)—yields were calculated to the content of 6- and 8-nitro
isomers in the starting mixture of 4a and 4b (in the ratio 2:1).
Chromatographic separation (SiO2, chloroform:ethanol, 50:1, v/v) of the mixture
of 4-chloroquinolines (7a, 7c) and 4-(2,6-dimethylphenoxy)quinoline 8 gave a fraction
(117 mg) with higher Rf value (8-nitro isomers 7c and 8, in the ratio 1:0.12) and a fraction
of 5-nitro isomer 7a (150 mg, 76%) with lower Rf value. The fraction of 8-nitro isomers 7c
and 8 was triturated with 1 mL of the mixture of hexane-dried acetone (2:1, v/v) and pure
4-chloroquinoline 7c (60 mg) was filtered off, the filtrate was evaporated to dryness and
rechromatographed (Al2O3, methylene chloride) to afford pure 7c (40 mg) and 8 (16 mg).
For analytical purposes compound 8 (from 3 runs) was recrystallized from ether. Total
yields of 7c (76%) and of 8 (9.5%) were calculated to the content of 5- and 8-nitro isomers
in the starting mixture of 4c and 4d (in the ratio 3:2).

1218
E. CHROBAK ET AL.
3-Benzylsulfanyl-4-Methoxy-6-Nitroquinoline (6a)
◦
1
74% yield. mp 95–96 C (ethanol). H NMR (CDCl3), δ: 4.17 (s, 2H, CH2), 4.21
(s, 3H, OCH3), 7.19–7.25 (m, 5H, C6H5), 8.13 (d, 3J = 9.2 Hz, 1H, H-8), 8.43 (dd, 3J =
4
4
9.2 Hz, J = 2.5 Hz, 1H, H-7), 8.83 (s, 1H, H-2), 9.04 (d, J = 2.5 Hz, 1H, H-5). Anal.
Calcd for C17H14N2O3S (326.07): C 62.56, H 4.32; N 8.58; S 9.82. Found C 62.29; H 4.25;
N 8.28; S 9.75.
3-Benzylsulfanyl-4-Methoxy-8-Nitroquinoline (6b)
70% yield. mp 70–72 ◦C (ethanol). 1H NMR (CDCl3), δ: 4.11 (s, 3H, OCH3), 4.25
(s, 2H, CH2), 7.21–7.45 (m, 5H, C6H5), 7.59 (dd, 3J = 8.5 Hz, 4J = 7.5 Hz, 1H, H-6), 7.99
3
4
3
4
(dd, J = 7.5 Hz, J = 1.4 Hz, 1H, H-7), 8.30 (dd, J = 8.5 Hz, J = 1.4 Hz, 1H, H-5),
8.89 (s, 1H, H-2). Anal. Calcd for C17H14N2O3S (326.07): C 62.56, H 4.32; N 8.58; S 9.82.
Found C 62.31; H 4.27; N 8.38; S 9.65.
3-Benzylsulfanyl-4-Chloro-5-Nitroquinoline (7a)
◦
1
76% yield. mp 162–164 C (ethanol). H NMR (CDCl3), δ: 4.35 (s, 2H, CH2),
3
3
7.26–7.39 (m, 5H, Hphenyl), 7.69 (m, 1H, J = 8.3 Hz, J = 7.5 Hz, H-7), 7.75 (dd, 1H,
3J = 7.5 Hz, 4J = 1.3 Hz, H-6), 8.22 (dd, 1H, 3J = 8.3 Hz, 4J = 1.3 Hz, H-8), 8.80 (s, 1H,
H-2). Anal. Calcd for C16H11N2O2SCl (330.02): C 58.09; H 3.35; N 8.47; S 9.69. Found C
57.91; H 3.30; N 8.38; S 9.55.
3-Benzylsulfanyl-4-Chloro-8-Nitroquinoline (7c)
◦
1
76% yield. mp 169–171 C (ethanol). H NMR (CDCl3), δ: 4.35 (s, 2H, CH2),
7.26–7.39 (m, 5H, C6H5), 7.69 (dd, 3J = 8.6 Hz, 3J = 7.5 Hz, 1H, H-6), 7.99 (d, 3J = 7.5 Hz,
H-7), 8.40 (d, 3J = 8.6 Hz, 1H, H-5), 8.87 (s, 1H, H-2). Anal. Calcd for C16H11N2O2SCl
(330.02): C 58.09; H 3.35; N 8.47; S 9.69. Found C 57.84; H 3.27; N 8.32; S 9.48.
3-Benzylsulfanyl-8-Nitro-4-(2,6-Dimethylphenoxy)Quinoline (8)
9.5% yield. mp 99–101 ◦C (ether). 1H NMR (CDCl3), δ: 2.06 (s, 6H, 2 × CH3), 3.89
(s, 2H, CH2), 7.08–7.13 (m, 5H, Harom.), 7.22–7.26 (m, 3H, Harom.), 7.56 (dd, 3J = 8.5 Hz,
3J = 7.5 Hz, 1H, H-6), 7.99 (dd, 3J = 7.5 Hz, 4J = 1.2 Hz, H-7), 8.40 (dd, 3J = 8.5 Hz,
4J = 1.2 Hz, 1H, H-5), 8.80 (s, 1H, H-2). Anal. Calcd for C24H20N2O3S (416.12): C 69.12;
H 4.84; N 6.73; S 7.70. Found C 68.93; H 4.77; N 6.48; S 7.45.
Synthesis of 3-Benzylsulfanyl-4-Chloro-6- and 8-Nitroquinolines 7b,c
from 3-Benzylsulfanyl-4-Methoxy-6- and 8-Nitroquinolines 6a,b. Mixture of 4-
methoxyquinoline 6a or 6b (0.21 g, ca. 0.64 mM), phosphorus oxychloride (1.5 mL) and
triethylamine hydrochloride (0.14 g) was stirred on boiling for 30 min. It was cooled down
to rt and poured into mixture of ice and water (5 g) and then neutralized on cold with
conc. ammonia. The solid was filtered off, washed with water and dried on air. It was
recrystallized from ethanol to give 0.2 g (94%) of product 7b or 7c. Properties of 7c (Rf
value, and mp) were the same as for the sample prepared from the mixture of 4c and 4d
(see above).

TREATMENT OF THIOQUINANTHRENE WITH EXCESS MIXTURE
1219
3-Benzylsulfanyl-4-Chloro-6-Nitroquinoline (7b). 94% yield. mp 179–181 ◦C
(ethanol). 1H NMR (CDCl3), δ: 4.35 (s, 2H, CH2), 7.24–7.39 (m, 5H, C6H5), 8.19 (d, 3J =
3
4
9.2 Hz, 1H, H-8), 8.45 (dd, J = 9.2 Hz, J = 2.4 Hz, 1H, H-7), 8.87 (s, 1H, H-2), 9.13
(d, 1H, 4J = 2.4 Hz, H-5). Anal. Calcd for C16H11ClN2O2S (330.02): C 58.09, H 3.35; N
8.47; S 9.69. Found: C 57.89, H 3.30; N 8.33; S 9.40.
Reaction of Thioquinanthrene (1a) with an Excess of Nitrating Mixture
Leading to the OtqNO2 Mixture. Thioquinanthrene (1a) (6.4 g, ∼20 mM) was dis-
◦
solved upon stirring in conc. sulfuric acid (64 mL) at 0 C and the solution was cooled
down to −5 ◦C. Then, a nitrating mixture [prepared from fuming nitric acid (16 mL) and
conc. sulfuric acid (16 mL)] was added dropwise at −5–0 ◦C and kept at 0–5 ◦C for 7 days.
The same amount of nitrating mixture was added again and the mixture was kept in refrig-
erator (4 ◦C) for the next 7 days. The mixture was poured on crushed ice (800 g) and then
neutralized at 0 ◦C with conc. aqueous ammonia up to pH 6. The precipitate was filtered
off, washed with warm water and dried on air to give mixture of nitrothioquinanthrene
S-oxides (termed the OtqNO2 mixture) (7.85 g) as a yellow solid. Elemental analysis of the
OtqNO2 mixture gave: C 53.50%, H 2.10%; N 12.25%; S 15.82%.
Two-dimentional TLC analysis (SiO2, CH2Cl2:methanol, 23:1, v/v) revealed 11 spots
with the following Rf values: 0.82, 0.78, 0.75, 0.69, 0.65, 0.63, 0.57, 0.55, 0.53, 0.44 (traces),
0.10. To evaluate the composition of the OtqNO2 mixture, analysis of reference samples of
nitrothioquinanthrene S-oxides 2a-h and 10 was performed under the same conditions. It
revealed spots of 2g (Rf = 0.78), 10 (Rf = 0.75), 2f (Rf = 0.69), 2h (Rf = 0.65), 2b (Rf =
0.63), 2c (Rf = 0.57), 2d (Rf = 0.55), 2e (Rf = 0.53), 2a (Rf = 0.44).
Preparative TLC separation (SiO2, 0.5 mm, CH2Cl2:ethanol, 20:1, v/v) yielded fol-
lowing fractions: (1) Rf = 0.66–0.71; (2) Rf = 0.63–0.64;.3. Rf = 0.53–0.58; 4. Rf =
0.47–0.52; 5. Rf = 0.41–0.45; 6. Rf = 0.36–0.40. They were subjected to MS analysis
and as deduced from evaporation curves all fractions were nonhomogeneous and contained
two or three compounds. For fractions No. 3, 4, 5, and 6 species with molecular ions
of magnitude of 424 or 379 indicating dinitrothioquinanthrene 7-oxide (M+ = 424) and
mononitrothioquinanthrene 7-oxide (M+ = 379) were detected, but for fractions No. 1 and
2 species with M+ = 395, corresponding to nitrothioquinanthrene S,S-dioxides, were also
observed.
Reductions of Thioquinanthrene S-Oxides.
• Determination of sulfoxide content with NaI/(CF3CO)2O/acetone system according to
the method reported10
Thioquinanthrene 7-oxide (2a), or 8-nitrothioquinanthrene 7-oxide (2d) or the
OtqNO2 mixture (87–100 mg, ca. 250 µM) was suspended in a mixture of acetic acid
(2.5 mL) and acetic anhydride (0.2 mL), and 0.5 M solution of NaI in acetone (2 mL)
was added, followed by 1 M solution of trifluoroacetic anhydride in acetone (1 mL). The
mixture was stirred for 2 min and diluted with aqueous solution of KI (40 mL) and titrated
with 0.02 M aqueous Na2S2O3.
Results (from three runs):
2a, 87 mg, volume of 0.02 M aqueous Na2S2O3 = 12.5 mL 0.1
2d, 90 mg, volume of 0.02 M aqueous Na2S2O3 = 12.5 mL 0.1
OtqNO2 mixture, 100 mg, of 0.02 M aqueous Na2S2O3 = 10.5 mL 0.2
• Preparative reduction of the OtqNO2 mixture with KI/conc. HClaq. system

1220
E. CHROBAK ET AL.
OtqNO2 mixture (2.3 g) was added portionwise on stirring at rt to conc. HClaq.
(25 mL) up to complete dissolution of the solid. Then, solution of KI (2.25 g, 13.5 mM) in
water (5 mL) was added. The mixture was stirred at rt for 30 min and diluted on cooling
with water (30 mL). The mixture was partially neutralized at rt with 20% aqueous NaOH
(30 mL) to pH < 6. 0.1 M Solution of Na2SO3 (30 mL) was added portionwise up to
complete consumption of iodine and the mixture was stirred for 15 min. The precipitate
was filtered off, washed with 20% aqueous Na2CO3 (2 × 10 mL) and water (3 × 10 mL)
and dried on air to give 2.2 g of yellow solid. TLC analysis (system II) reveals five spots
with Rf = 0.44 for 1e, Rf = 0.32 for 1c, Rf = 0.30 for 1d, Rf = 0.28 for 10, and Rf = 0.24
for 1b.
Column chromatography: The solid (4.2 g) was dissolved in warm CH2Cl2—acetone
(30:1, v/v) solution and the solution was cooled down to rt and placed in a chromato-
graphic column packed with 500 g of SiO2 (70–230 mesh). The mixture was eluted with
CH2Cl2—acetone (30:1, v/v) solution to give fraction I with compound 1e (Rf = 0.44),
fraction II with spots Rf = 0.32 for 1c, Rf = 0.30 for 1d, and Rf = 0.28 for 10, and fraction
III with compound 1b (Rf = 0.24). Fraction II was evaporated to dryness and twice rechro-
matographed on Al2O3 and mixture of CH2Cl2—acetone (30:2, v/v) as an eluent to give
compounds 1c (Rf = 0.32), 1d (Rf = 0.30), and 10 (Rf = 0.28).
1
Properties (mp’s and H NMR spectra in DMSO-d6) of 1-nitro- and 4-nitro-1,4-
dithiino[2,3-c:5,6-cꢀ]diquinoline 7-oxides 1b and 1c were identical with the reported data.9
1,8-Dinitrothioquinanthrene (1d). mp 292–293 ◦C (DMF). EI MS (70 eV), m/z
1
(%): (M+ = 408, 100%). IR (KBr pellet) ν: 1351 cm−1 and 1523 cm−1 (NO2). H NMR
(CDCl3), δ: 7.80 (dd, 3J = 8.5 Hz, 3J = 7.6 Hz, 2H, H-3, and H-10), 8.06 (dd, 3J = 7.6 Hz,
4J = 1.3 Hz, 2H, H-2, and H-9), 8.36 (dd, 3J = 8.4 Hz, 4J = 1.3 Hz, 2H, H-4, and H-11),
8.98 (s, 2H, H-6, and H-13). Anal. Calcd for C18H8N4O4S2 (408.0): C 52.94; H 1.97; N
13.73. Found: C 52.78; H 1.85; N 13.55.
◦
1,11-Dinitrothioquinanthrene (1e). mp 284–285 C (DMF). EI MS (70 eV),
m/z (%): (M+ = 408), 100%). IR (KBr pellet) ν: 1342 cm−1 and 1526 cm−1 (NO2). H
1
NMR (CDCl3), δ: 7.78 (dd, 3J = 8.4 Hz, 3J = 7.6 Hz, 1H, H-3), 7.81 (dd, 3J = 8.4 Hz, 3J =
7.6 Hz, 1H, H-9), 8.06 (d, 3J = 7.6 Hz, 2H, H-2, and H-10), 8.37 (dd, 3J = 8.4 Hz, 4J =
1.2 Hz, 1H, H-4), 8.60 (dd, 3J = 8.4 Hz, 4J = 1.2 Hz, 1H, H-8), 8.94 (s, 1H, H-13), 9.06
(s, 1H, H-6). 2D 1H-13C NMR data from HSQC and HMBC experiments are collected in
Supplemental Materials. Anal. Calcd for C18H8N4O4S2 (408.0): C 52.94; H 1.97; N 13.73.
Found: C 52.80; H 1.88; N 13.59.
Oxidation of Nitrothioquinanthrenes 1b–e to Nitrothioquinanthrene 7-
Oxides 2b–h. Nitrothioquinanthrene 1b–e (1 mM) was dissolved upon stirring in 96%
◦
sulfuric acid (5 mL) at 0 C. The nitrating mixture (fuming nitric acid, d = 1.50 g/mL,
0.32◦mL, ca. 7.2 mM of HNO3 and conc. ◦H2SO4, 0.32 mL) was then added dropwise at
◦
0–5 C, the mixture was maintained at 0 C for 1.5 h, and left at 0–5 C for 1 day for
1b,c,e and for 2.5 h for dinitrothioquinantrene 1d. It was then cautiously poured onto ice
◦
(40 g), and neutralized at 0 C with 25% aqueous ammonia. The solid was filtered off,
washed twice with cold water, and air-dried to give yellow products containing a mixture
of nitrothioquinanthrene S-oxides 2. Mixtures of sulfoxides 2b and 2d as well as 2c and 2e
were separated as described previously.9 Mixture of 2g and 2h was heated to boiling with
DMF and then decanted off on hot from insoluble 2h. The supernatant liquid was evaporated
under vacuum. The residue was then twice chromatographed (SiO2, acetone-CH2Cl2, 1:30,
v/v) to give 2g and a second crop of 2h.

TREATMENT OF THIOQUINANTHRENE WITH EXCESS MIXTURE
1221
Results: Substrate → products (yields):
1b → 2b (27%) + 2d (54%), in agreement with literature data.9
1c → 2c (49%) + 2e (34%), in agreement with literature data.9
1e → 2g (14%) + 2h (76%)
1d → 2f (82%)
The yields of sulfoxides 2b,d,c,e,g,h were deduced from 1H NMR spectra of crude
products.
Properties (mp’s and 1H NMR spectra in DMSO-d6)of 1-nitro-, 4-nitro-, 8-nitro-, and
11-nitro-1,4-dithiino[2,3-c:5,6-cꢀ]diquinoline 7-oxides 2b, c, d, e were identical with the
reported data.9
1,8-Dinitro-1,4-Dithiino[2,3-c:5,6-cꢁ]Diquinoline 7-Oxide (2f). 82% yield.
◦
mp 245–246 C (DMF). EI MS (70 eV), m/z (%):(M+ = 424, 12%). IR (KBr pellet)
ν: 1068 cm−1 (SO), 1328 cm−1 and 1526 cm−1 (NO2). 1H NMR (CDCl3), δ: 7.88–7.95 (m,
2H, H-3, and H-10), 8.23 (dd, 3J = 7.6 Hz, 4J = 1.2 Hz, 1H, H-2), 8.37 (d, 3J = 8.0 Hz,
1H, H-9), 8.50 (dd, 3J = 8.0 Hz, 4J = 0.8 Hz, 1H, H-4), 8.53 (dd, 3J = 8.0 Hz, 4J = 0.8 Hz,
1H, H-11), 9.32 (s, 1H, H-13) 9.50 (s, 1H, H-6). Anal. Calcd for C18H8N4O5S2 (424.4): C
50.94; H 1.90 N 13.20. Found: C 50.74; H 1.79, N 12.95.
1,11-Dinitro-1,4-Dithiino[2,3-c:5,6-cꢁ]Diquinoline 7-Oxide (2g). 14% yield.
◦
mp 275–276 C (DMF). EI MS (70 eV), m/z (%):(M+ = 424, 3%). IR (KBr pellet) ν:
1085 cm−1 (SO), 1347 cm−1 and 1528 cm−1 (NO2). 1H NMR (CDCl3), δ: 7.84 (dd, 3J =
8.7 Hz, 3J = 7.5 Hz, 1H, H-9), 7.93 (dd, 3J = 7.6 Hz, 3J = 8.5 Hz, 1H, H-3), 8.11 (dd, 3J =
7.5 Hz, 4J = 1.0 Hz, 1H, H-10), 8.25 (dd, 3J = 7.6 Hz, 4J = 1.0 Hz, 1H, H-2), 8.51 (dd,
3J = 8.5 Hz, 4J = 1.0 Hz, 1H, H-4), 9.11 (s, 1H, H-13), 9.53 (s, 1H, H-6), 9.72 (dd, 3J =
8.7 Hz, 4J = 1.0 Hz, 1H, H-8). Anal. Calcd for C18H8N4O5S2 (424.4): C 50.94; H 1.90 N
13.20. Found: C 50.76; H 1.79, N 12.95.
4,8-Dinitro-1,4-Dithiino[2,3-c:5,6-cꢁ]Diquinoline 7-Oxide (2h). 74% yield.
mp 295–296 ◦C (DMSO). EI MS (70 eV), m/z (%):(M+ = 424), 15%). IR ν: 1059 (SO),
1
1347 and 1525 cm−1 (NO2). H NMR (DMSO-d6), δ: 8.07–8.12 (m, 2H, H-3, and H-9),
3
3
4
8.54 (dd, J = 7.6 Hz,4J = 1.1 Hz, 1H, H-10), 8.56 (dd, J = 7.8 Hz, J = 1.0 Hz, 1H,
H-2), 8.60 (dd, 3J = 8.4 Hz, 4J = 1.0 Hz, 1H, H-4), 8.83 (dd, 3J = 8.5 Hz, 4J = 1.1 Hz,
1H, H-8), 9.51 (s, 1H, H-13), 9.72 (s, 1H, H-6). Anal. Calcd for C18H8N4O5S2 (424.4): C
50.94; H 1.90 N 13.20. Found: C 50.72; H 1.75 N, 12.94.
Oxidative Chlorination o-1,4-Dithiino[2,3-c:5,6-cꢁ]Diquinoline 7-Oxides
2a, 2d and the OtqNO2 Mixture and of 3-Benzylsulfanyl-4-Chloro-5-, 6-, and
8-nitroquinolines 7b,c,d.
• Chlorination of 1,4-dithiino[2,3-c:5,6-cꢀ]diquinoline 7-oxide (2a) (general procedure):
Gaseous chlorine was passed through a well-stirred mixture of thioquinanthrene-
7-oxide 2a (6.68 g, 20 mM), chloroform (65 mL), conc. hydrochloric acid (6 mL) and
80% acetic acid (70 mL) cooled to 5 ◦C at such a rate that temperature was maintained at
15–17 ◦C. After 15 min. no more heat seemed to be produced. The passage of chlorine was
discontinued after 15 min. The mixture was poured into water (400 mL). The chloroform
layer was separated, washed twice with water and dried over anhydrous sodium sulfate.
Chloroform was evaporated to leave a semi-solid residue. The residue was boiled with
carbon tetrachloride (70 mL), hot solution was decanted from insoluble material and evap-
orated to dryness to give 4-chloro-3-quinolinesulfonyl chloride (3a) (8.22 g, 80%) with mp
125–7 ◦C, lit.,5 mp 129–130 ◦C (Rf = 0.51, system II).

1222
E. CHROBAK ET AL.
• Chlorination of 8-nitro-1,4-dithiino[2,3-c:5,6-cꢀ]diquinoline 7-oxide (2d) and 8-nitro-
1,4-dithiino[2,3-c:5,6-cꢀ]diquinoline 7,7-dioxide (10)
2d or 10 (1 mM) was treated as for 2a to give 460 mg of the solid containing the mix-
ture of 4-chloro-3-quinolinesulfonyl chloride (3a) and 4-chloro-5-nitro-3-quinolinesulfonyl
chloride (3b) in the ratio of 1:1 as deduced from 1H NMR spectrum based on the intensity
of singlets of α-quinolinyl protons δ = 9.44 ppm for 3a and δ = 9.53 ppm for 3b. TLC
analysis (system II) reveals two spots with Rf = 0.51 for 3a and Rf = 0.42 for 3b.
The mixture of 3a and 3b could be separated to individual sulfonyl chlorides by
column chromatography (SiO2, hexane-dried acetone 2:1, v/v) to afford 3a (170 mg, 65%)
and 3b (184 mg, 60%), both with mp of the samples of 3a and 3b described below.
• Chlorination of mono- and dinitro-1,4-dithiino[2,3-c:5,6-cꢀ]diquinoline 7-oxides 2b-h
and 10 mixture, i.e. OtqNO2 mixture
Gaseous chlorine was passed through a well stirred mixture of mono and dinitro-
1,4-dithiino[2,3-c:5,6-cꢀ]diquinoline 7-oxides 2b–h and 10 (i.e., OtqNO2 mixture) (7.85 g),
chloroform (65 mL), conc. hydrochloric acid (6 mL) and 80% acetic acid (70 mL) cooled
at 5 ◦C at such a rate that temperature was maintained between 15–17 ◦C. After 15 min. no
more heat seemed to be produced. The passage of chlorine was discontinued after 15 min.
The mixture was poured into water (400 mL). The chloroform layer was separated, washed
twice with water and dried over anhydrous sodium sulfate. Chloroform was evaporated
to leave semi-solid residue (9.5–9.6 g). It was subjected to chromatographic analysis and
separation, and characterized by amination with dimethylamine—see the next procedure.
TLC analysis (system II) reveals three spots with Rf = 0.51 for 3a, Rf = 0.42 for 3b
and Rf = 0.36 for 3d. 1H NMR spectrum based on the intensity of singlets of α-quinolinyl
protons δ = 9.44 ppm for 3a, δ = 9.53 ppm for 3b, δ = 9.60 ppm for 3c and δ = 9.54 ppm
for 3d proves that the ratio of 3a:3b:3c:3d equals 0.57:0.96:0.05:1.
The mixture of 3a, 3b, and 3d (1g) was separated by column chromatography (SiO2,
hexane-dried acetone 2:1, v/v) to afford 3a (125 mg, 65%) and a mixture of 3b and 3d
(467 mg, 60%). Rechromatography of the mixture 3b and 3d gave individual samples of
3b (145 mg) and 3d (130 mg).
• Chlorination of 3-benzylsulfanyl-4-chloro-5-, 6 and 8-nitroquinolines 7a,b,c to 4-chloro-
5-, 6 and 8-nitro-3-chlorosulfonylquinolines 3b,c,d
It was performed as for 2a with two changes: (i) no hydrochloric acid was added,
(ii) to remove benzyl esters (acetate and chloride), the semi-solid residue was triturated
with cold ether, and crude sulfonyl chloride 3b–d was recrystallized from ether or carbon
tetrachloride.
4-Chloro-5-Nitro-3-Chlorosulfonylquinoline (3b). 68% yield. mp 126–128 ◦C
(CCl4). 1H NMR (CDCl3), δ: 7.96 (dd, 1H, 3J = 7.5 Hz, 4J = 1.2 Hz, H-6), 8.04 (dd, 1H,
3J = 7.5 Hz, 3J = 8.5 Hz, H-7), 8.44 (dd, 1H, 3J = 8.5 Hz, 4J = 1.2 Hz, H-8), 9.53 (s, 1H,
H-2). Anal. Calcd for C9H4Cl2N2O4S (305.93): C 35.20; H 1.31; N 9.12; S 10.44. Found:
C 34.98; H 1.34; N 9.01; S 10.22.
4-Chloro-6-Nitro-3-Chlorosulfonylquinoline (3c). 82% yield. mp 168–172 ◦C
(ether). 1H NMR (CDCl3), δ: 8.43 (d, 3J = 9.2 Hz, 1H, H-8), 8.75 (dd, 3J = 9.2 Hz, 4J =
4
2.4 Hz, 1H, H-7), 9.42 (d, J = 2.4 Hz, 1H, H-5), 9.60 (s, 1H, H-2). Anal. Calcd for
C9H4Cl2N2O4S (305.93): C 35.20; H 1.31; N 9.12; S 10.44. Found: C 35.01; H 1.25; N
8.98; S 10.21.

TREATMENT OF THIOQUINANTHRENE WITH EXCESS MIXTURE
1223
4-Chloro-8-Nitro-3-Chlorosulfonylquinoline (3d). 80% yield. mp 134–136 ◦C
(ether). 1H NMR (CDCl3), δ: 7.95 (dd, 3J = 7.5 Hz, 3J = 8.6 Hz, 1H, H-6), 8.29 (dd, 3J =
7.5 Hz, 4J = 1.2 Hz, 1H, H-7), 8.75 (dd, 3J = 8.6 Hz, 4J = 1.2 Hz, 1H, H-5), 9.54 (s, 1H,
H-2). Anal. Calcd for C9H4Cl2N2O4S (305.93): C 35.20; H 1.31; N 9.12; S 10.44. Found:
C 34.96; H 1.23; N 8.97; S 10.27.
Synthesis of 4-Dimethylamino-5-, 6- and 8-nitro-3-Quinoline-N,N-
Dimethylsulfonamides 9b,c,d.
• From individual 4-chloro-5-(or 6- or 8-)nitro-3-chlorosulfonylquinolines (3b,c,d)
A mixture of, 4-chloro-5- (or 6- or 8-)nitro-3-chlorosulfonylquinoline 3b or 3c or
3d (306 mg, 1 mM), 40% aqueous dimethylamine (1 mL, ca. 8 mM), benzene (3 mL)
and water (2 mL) was refluxed for 2 h. It was then cooled to rt and diluted with benzene
(4 mL). The organic layer was separated and concentrated to dryness. The residue was
recrystallized from EtOH to give 90% of sulfonamide 9.
• From chlorination products of OtqNO2 mixture
A mixture of 4-chloro-3-chlorosulfonylquinoline 3a and 4-chloro-5- (6- and 8-nitro-
3-chlorosulfonyl quinolines (3b,c,d) (9.6 g) (from chlorination of OtqNO2 mixture), 40%
aqueous dimethylamine (30 mL, ca. 0.24 M), benzene (100 mL) and water (70 mL) was
refluxed for 2 h. It was then cooled to rt and diluted with benzene (40 mL). The organic layer
was separated and concentrated to dryness. The semisolid residue (ca. 8.8 g) was subjected
to TLC analysis (SiO2, CH2Cl2-ethanol, 35:1, v/v) which reveals three main spots: Rf =
0.32 of sulfonamide 9a; Rf = 0.42 of sulfonamide 9b and Rf = 0.59 of sulfonamide 9d. 1H
NMR spectrum showed the ratio 9a:9b:9c:9d = 0.60:1:0.05:1, based on the intensities of
singlets of α-quinolinyl protons.
Chromatographic separation (SiO2, CH2Cl2-ethanol 35:1, v/v) gave 9d (3.55 g), 9b
(3.41 g) and 9a (1.7 g).
4-Dimethylamino-3-Quinoline-N,N-Dimethylsulfonamide (9a). mp 50–
◦
◦
1
52 C, ref.,5 mp 45–48 C. H NMR spectrum in CDCl3 was identical with the reported
data.5
4-Dimethylamino-5-Nitro-3-Quinoline-N,N-Dimethylsulfonamide (9b).
1
90% yield (from 3b). mp 135–137 ◦C (ethanol). H NMR (CDCl3), δ: 2.92 [s, 6H,
3
4
SO2N(CH3)2], 3.03 [s, 6H, C-N(CH3)2], 7.72–7.75 (dd, 1H, J = 7.6 Hz, J = 1.2 Hz,
H-6), 7.81–7.85 (dd, 1H, 3J = 7.6 Hz, 3J = 8.4 Hz, H-7), 8.22–8.25 (dd, 1H, 3J = 8.4 Hz,
4J = 1.2 Hz, H-8), 9.03 (s, 1H, H-2). Anal. Calcd for C13H16N4O4S (324.09): C 48.14, H
4.97; N 17.27; S 9.42. Found C 48.18; H 4.95; N 17.17; S 9.21.
4-Dimethylamino-6-Nitro-3-Quinoline-N,N-Dimethylsulfonamide (9c).
1
90% yield (from 3c). mp 154–156 ◦C (ethanol). H NMR (CDCl3), δ: 3.00 [s, 6H,
3
3
SO2N(CH3)2], 3.37 [s, 6H, C-N(CH3)2], 8.17 (d, J = 9.2 Hz, 1H, H-8), 8.49 (dd, J =
4
9.2 Hz, J = 2.4 Hz, 1H, H-7), 9.01 (s, 1H, H-2), 9.09 (d, J = 2.4 Hz, 1H, H-5). Anal.
Calcd for C13H16N4O4S (324.09): C 48.14, H 4.97; N 17.27; S 9.42. Found C 47.96; H
4.95; N 16.90; S 9.27.
4-Dimethylamino-8-Nitro-3-Quinoline-N,N-Dimethylsulfonamide (9d).
1
90% yield (from 3d). mp 160–161 ◦C (ethanol). H NMR (CDCl3), δ: 3.02 [s, 6H,
3
3
SO2N(CH3)2], 3.30 [s, 6H, C-N(CH3)2], 7.61 (dd, 1H, J = 8.4 Hz, J = 7.6 Hz, H-6),
3
4
3
4
8.03 (dd, 1H, J = 7.6 Hz, J = 1.2 Hz, H-7), 8.32 (dd, 1H, J = 8.4 Hz, J = 1.2 Hz,
H-5), 8.97 (s, 1H, H-2). Anal. Calcd for C13H16N4O4S (324.09): C 48.14, H 4.97; N 17.27;
S 9.42. Found C 47.86; H 4.90; N 16.95; S 9.30.

1224
E. CHROBAK ET AL.
Table 1 Crystal structure and data refinement parameters
Compound
2g
Empirical formula
Formula weight
C18H8N4O5S2
424.40
Crystal system/space group
a/Å
b/Å
Monoclinic/P21/c
15.2324(1)
7.5651(1)
14.4198(1)
90.00
c/Å
α/◦
β/◦
99.981(1)
90.00
1636.51(3)
4
1.723
0.371
γ /◦
V/Å3
Z
Dcalc (g/cm3)
µ (mm−1
)
Crystal size (mm)
Color/shape
Temp (K)
0.18 × 0.34 × 0.42
white/polyhedral
100(1)
Theta range for collection
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness of fit on F2
Final R indices [I > 2σ(I)]
R indices (all data)
2.95–25.06
16,285
2893
2893/271/0
1.083
0.0285
0.0305
Largest difference peak/hole
0.952/−0.272
X-Ray Structure Analysis
Crystals of 1,11-dinitro-1,4-dithiino[2,3-c:5,6-cꢀ]diquinoline 7-oxide (2g) were
grown by slow evaporation from DMSO solution at rt. The diffraction data were collected
with a four—circle Xcalibur diffractometer with Sapphire3 CCD detector using graphite
monochromated Mo Kα radiation (Table 1). The intensity data were collected and processed
using Oxford Diffraction CrysAlisPro Software.17 The crystal structures were solved by
direct methods with the program SHELXS-9718 and refined by full-matrix least-squares
method on F2 with SHELXL-97.18 The aromatic hydrogen atoms were treated as “riding”
ꢀ
on their parent carbon atoms with d(C H) = 0.95 Å and assigned isotropic atomic
displacement parameters equal to 1.2 times the value of the equivalent atomic displacement
parameters of the parent carbon atom [Uiso(H) = 1.2Ueq(C)]. Hydrogen atoms involved
in hydrogen bonding were refined freely with isotropic atomic displacement parameters.
Crystallographic data for compound 2g have been deposited with Cambridge Crys-
tallographic Data Centre (CCDC deposition number 849692). Copies of the data can be
obtained upon request from CCDC, 12 Union Road, Cambridge CB2 1EZ, UK). Selected
bond lengths and angles (Tables S1 and S2) are found in the supplemental materials.
REFERENCES
1. (a) Peletier, C.; Prognon, P.; Bourlioux, P. Antimicrob. Agents Chemother. 1995, 39, 707-713;
(b) Murugasu-Osei, B.; Dick,T. Int. J. Antimicrob. Agents 2001, 18, 579-582.

TREATMENT OF THIOQUINANTHRENE WITH EXCESS MIXTURE
1225
2. (a) Denny, W. A. Eur. J. Med. Chem. 2001, 36, 577-595; (b) Siim, B. G.; Atwell, G. J.; Anderson,
R. F.; Wardman, P.; Pullen, S. M.; Wilson, W. R.; Denny, W. A. J. Med. Chem. 1997, 40,
1381-1390.
3. Makosza, M.; Kinowski, A.; Danikiewicz, W.; Mudryk, B. Liebigs Ann. Chem. 1986, 69-77.
ꢀ
4. Hasegawa, M.; Takabatake, T.; Miyazawa, T. Yakugaku Zasshi 2001, 121, 379-393.
5. Mas´lankiewicz, A.; Skrzypek, L. Heterocycles 1994, 38, 1317-1320.
6. Mas´lankiewicz, A. Polish J. Chem. 1985, 59, 511-520.
7. (a) Skrzypek, L.; Mas´lankiewicz, A. Heterocycles 1997, 75, 2015-2021; (b) Skrzypek, L. Het-
erocycles 1999, 51, 2111-2118; (c) Skrzypek, L.; Mas´lankiewicz, A. Heterocycles 2008, 75,
2769-2778; (d) Skrzypek, L.; Mas´lankiewicz, A.; Suwin´ska, K. Heterocycles 2011, 83, 777-787.
8. Mas´lankiewicz, M. J. Polish J. Chem. 1993, 67, 245-250.
9. Mas´lankiewicz, M. J.; Głowiak, T. Heterocycles 2003, 60, 1387-1400.
10. Ciesielski, W.; Jedrzejewski, W.; Kudzin, Z. H.; Skowron´ski, R.; Drabowicz, J. Talanta 1988,
ꢀ
35, 969-972.
11. Furniss, B. S.; Hannaford, A. J.; Rogers, V.; Smith, P. W. G.; Tachell, A. R. Vogel’s Textbook of
Practical Organic Chemistry, 4th ed.; Longman: London and New York, 1978, p.1082.
12. (a) Hull, C. M.; Bargar, T. W. J. Org. Chem. 1974, 40, 3152-3154; (b) Mas´lankiewicz, M. J.
Polish J. Chem. 1999, 73, 1477-1487; (c) Chrobak, E.; Mas´lankiewicz, A. Heterocycles 2004,
63, 2329-2340; (d) Mas´lankiewicz, M. J.; Rudnik, M.; Mas´lankiewicz, A. Phosphorus, Sulfur,
Silicon Relat. Elem. 2002, 177, 2481-2490.
13. Kosiecka, M.; Mas´lankiewicz, A.; Mas´lankiewicz, M. J. Heterocycles 2005, 65, 1577-1588.
14. Kosiecka, M.; Mas´lankiewicz, A. (in preparation).
15. Mas´lankiewicz, M. J.; Mas´lankiewicz, A. J. Heterocycl. Chem. 1996, 33, 1153-1158.
16. Mas´lankiewicz, M. J. J. Heterocycl. Chem. 2000, 37, 697-702.
17. Oxford Diffraction (2006) CrysAlis CCD and CrysAlis RED. Versions 1.171.32.29. Oxford
Diffraction Ltd: Wrocław, Poland.
18. Sheldrick, G. M. Acta Crystallogr. 2008, A 64, 112.