Quinone imines with a fused azine ring: I. Synthesis and hydrochlorination of 5-(p-tolylsulfonylimino)quinolin-8-one

Article abstract of DOI:10.1023/B:RUJO.0000034916.63587.a4

5-(p-Tolylsulfonylimino)quinolin-8-one was synthesized, and its reaction with hydrogen chloride was studied. The reaction leads to formation of 7-chloro-8-hydroxy-5-(p-tolylsulfonylamino)quinoline hydrochloride.

Full text of DOI:10.1023/B:RUJO.0000034916.63587.a4

Russian Journal of Organic Chemistry, Vol. 40, No. 1, 2004, pp. 93-96. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 1, 2004,
pp. 102-105.
Original Russian Text Copyright Ó 2004 by Belov, Nichvoloda.
Quinone Imines with a Fused Azine Ring: I. Synthesis
and Hydrochlorination of 5-(p-Tolylsulfonylimino)quinolin-8-one
A. V. Belov and V. M. Nichvoloda
Ukrainian State University of Chemical Technology, pr. Gagarina 8, Dnepropetrovsk, 49005 Ukraine
Received April 4, 2003
Abstract—5-(p-Tolylsulfonylimino)quinolin-8-one was synthesized, and its reaction with hydrogen chloride
was studied. The reaction leads to formation of 7-chloro-8-hydroxy-5-(p-tolylsulfonylamino)quinoline
hydrochloride.
Quinoline-5,8-diones attract attention due to their
versatile biological activity. Their analogs with
an endocyclic nitrogen atoms are structural fragments of
most marine alkaloids [1]. Studies in the field of synthesis
and transformations of quinoline-5,8-dione imines are very
interesting from the viewpoint of controlling the reactiv-
ity of the quinoid ring through variation of substituent at
the imino nitrogen atom, as well as of the position and
electron-acceptor properties of the nitrogen atom in the
fused pyridine ring. Up to now, only fragmentary data have
been published on N-substituted 5-iminoquinolin-8-ones:
We have synthesized 5-(p-tolylsulfonylimino)quinolin-
8-one (III) as the first representative of N-arylsulfonyl
quinone imines of the quinoline series and examined its
reaction with hydrogen chloride with a view to elucidate
the effect of arylsulfonylimino group in the 5-position
on the reactivity of these compounds. By nitrosation of
8-hydroxyquinoline (IV) we obtained 8-hydroxy-5-
nitrosoquinoline hydrochloride (V) (Scheme 2). Compound
V was reduced to 5-amino-8-hydroxyquinoline
dihydrochloride (VI) by reaction with tin(II) chloride di-
hydrate in concentrated hydrochloric acid. This proce-
dure allowed us to avoid isolation of the ditin salt of amine
VI and its subsequent decomposition with hydrogen
sulfide. Treatment of dihydrochloride VI with p-toluenesul-
fonyl chloride in an alcohol–pyridine mixture afforded
5
-(hydroxyphenylimino)quinolin-8-ones [2, 3], N-aryl
quinone iminesoftheindoanilineseries[4–6], andN-hydroxy
derivatives were reported [7]. N-Arylsulfonyl quinone imi-
nes of the quinoline series were not studied at all.
8-hydroxy-5-(p-tolylsulfonylamino)quinoline which was
Quinoline-5,8-dione (I) is known to react with hy-
converted into the corresponding hydrochloride VII for
convenience in handling and storing. The most difficult
stage in the synthesis of quinone imine III was oxidation
of VII. The use of conventional reagents, such as lead
tetraacetate in acetic acid, potassium hexacyano-
ferrate(III), or sodium hypochlorite in alkaline medium,
was inefficient because of the low selectivity for forma-
tion of target quinone imine III. We succeeded in obtain-
drogen chloride according to the 1,4-addition pattern
(
6
Scheme 1), resulting in formation of the corresponding
-chloro derivative [8]. This reaction path is favored by
the following factors: (1) the presence of an electron-
acceptor endocyclic nitrogen atom increases the positive
8
charge on the neighboring carbonyl carbon atom (C =O);
(2) intermediate II formed by protonation of the carbonyl
group is stabilized via intramolecular H-bonding.
Scheme 1.
1070-4280/04/4001-0093Ó2004 MAIK “Nauka/ Interperiodica”

94
BELOV, NICHVOLODA
Scheme 2.
ing compound III in 90% yield by oxidation of VII with
diacetoxyiodo)benzene in glacial acetic acid after pre-
liminary treatment of the substrate with sodium acetate.
was formed in the reaction of quinone imine III with
hydrochloric acid. The structure of compounds III, VII,
and VIII was confirmed by the data of IR and H NMR
(
1
spectroscopy.
The reaction of quinone imine III with hydrogen
chloride was expected to give both 1,4-addition products
Our results led us to conclude that replacement of
the oxygen atom in the C =O carbonyl group of quino-
5
(due to the presence of an arylsulfonylimino group [9])
and 6,3-adduct (due to the presence of electron-acceptor
endocyclic nitrogen atom). The site of chlorine addition
to the quinoid ring of III was proved by independent syn-
thesis of 7-chloro-8-hydroxy-5-(p-tolylsulfonylamino)-
quinoline which was isolated and identified as hydrochlo-
ride VIII. For this purpose, 8-hydroxyquinoline (IV) was
converted into 8-hydroxy-5-nitroquinoline (IX). Compound
IX was treated with sodium hypochlorite in alkaline me-
dium to obtain 7-chloro-8-hydroxy-5-nitroquinoline (X) [8],
and the latter was readily reduced with tin(II) chloride
dihydrate in concentrated hydrochloric acid. The reduc-
tion product, 5-amino-7-chloro-8-hydroxyquinoline
dihydrochloride (XI) was brought into reaction with
p-toluenesulfonyl chloride in an alcohol–pyridine mixture,
followed by treatment with hydrochloric acid. As a re-
sult, hydrochloride VIII was obtained. The same product
line-5,8-dione by arylsulfonylimino group reduces the
effect of the nitrogen atom in the pyridine ring on the
reactivity of the quinoid system. Therefore, the reaction
with hydrogen chloride follows the 1,4-addition pattern
with formation of the corresponding 7-chloro derivative.
EXPERIMENTAL
The IR spectra of compounds III, VII, and VIII
were recorded on a Specord 75IR spectrometer in KBr.
1
The H NMR spectra were obtained on a Varian VXR-
300 instrument from solutions in DMSO-d using TMS
6
as internal reference. It should be noted that hydrochlo-
rides VII and VIII with dimethyl sulfoxide give rise to
exchange reaction leading to formation of dimethyl-
sulfoxonium chloride and the corresponding free quino-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 1 2004

9
5
QUINONE IMINES WITH A FUSED AZINE RING: I.
line bases; protons of the pyridine ring in the latter appear
in the H NMR spectrum as an ABC spin system. The
purity of compounds III and VI–XI was checked by TLC
on aluminum oxide (III, VI, IX–XI) or silica gel (VII,
5
-(p-Tolylsulfonylimino)quinolin-8-one (III).
1
(
Diacetoxyiodo)benzene, 1.84 g (5.7 mmol), was added
with stirring to a suspension of 2 g (5.7 mmol) of hydro-
chloride VII and 0.47 g (5.7 mmol) of anhydrous sodium
acetate in 8 ml of acetic acid. After 1 h, the precipitate
was filtered off, washed with hexane, and dried. Yield
VIII) using BuOH–AcOH–H O,4 : 5 : 1 (IV–XI),or EtOAc
2
(
III) as eluent. Spots were visualized by treatment with
gaseous ammonia (IX, X), by UV light (VII, VIII), or by
the indophenol reaction [10] with a-naphthol (III). Satis-
factory elemental analyses for nitrogen and sulfur were
obtained.
1
.6 g (90%). The crude product was dissolved in dry chlo-
roform, charcoal was added, the solution was filtered,
and the filtrate was partially distilled off under reduced
pressure without heating. The yellow finely crystalline
precipitate was filtered off, dried, and stored at –10 to
–5°C. The purified product begins to decompose at 177–
178°C. IR spectrum, n, cm : 1312, 1147 (SO ); 1692
(C=O); 1676 (C=N). H NMR spectrum, d, ppm: 2.450 s
8-Hydroxy-5-nitrosoquinoline hydrochloride (V)
was synthesized by nitrosation of 11.6gof8-hydroxyquino-
line (IV) in hydrochloric acid according to the procedure
described in [8]. Yield 15.7 g (95%). The product was
brought into further synthesis without additional purifica-
tion.
–
1
2
1
(3H, CH ), 7.525 d (2H, Harom, J = 9 Hz), 7.975 d (2H,
Harom, J = 9 Hz), 7.170 d (1H, 7-H, J = 11.5 Hz), 8.295 d
3
(
9
1H, 6-H, J = 11.5 Hz), 7.790 d.d (1H, 3-H, J = 4.5, J =
.0 Hz), 8.415 d.d (1H, 4-H, J = 3.0, J = 9.0 Hz), 9.015
1 2
1 2
5
-Amino-8-hydroxyquinoline dihydrochloride
(
(
VI). A suspension of freshly prepared hydrochloride V
obtained from 0.08 mol of compound IV), in 100 ml of
d.d (1H, 2-H, J =3.0, J =4.5Hz). Found, %:N8.92;S 10.19.
C H N O S. Calculated, %: N 8.97; S 10.26.
1
2
concentrated hydrochloric acid was added with stirring
at –1 to 10°C to a solution of 56.41 g (0.25 mol) of tin(II)
chloride dihydrate in 25 ml of concentrated hydrochloric
acid. The mixture was stirred for 1 h, and the precipitate
was filtered off and recrystallized from dilute hydrochlo-
ric acid. Yield 13.7 g (73%, calculated on quinoline IV).
Brown crystals, mp 245–246 °C (decomp.); published
data [3]: mp 243°C.
16 12 2 3
8-Hydroxy-5-nitroquinoline (IX) was synthesized
by nitrosation of 8-hydroxyquinoline (IV), followed by
oxidation of nitroso derivative V with nitric acid accord-
ing to the procedure described in [11]. From 23.2 g of
compound IV we obtained 18.6 g (61%) of the product
as a greenish–yellow powder with mp 179–181°C
(decomp.); published data [8, 11, 12]: mp 177–181°C.
8
-Hydroxy-5-(p-tolylsulfonylamino)quinoline
7
-Chloro-8-hydroxy-5-nitroquinoline (X) was
hydrochloride (VII). Pyridine, 6.5 ml, and
p-toluenesulfonyl chloride, 4 g (0.021 mol), were added
with stirring at room temperature to a solution of 4.6 g
0.02 mol) of amine VI in 25 ml of ethanol. The mixture
was stirred for 2 h, left to stand for 24 h, and poured into
50 ml of an ice–water mixture. The precipitate was fil-
tered off, washed with distilled water, and added to 50 ml
of 15% hydrochloric acid, and the mixture was heated to
the boiling point and cooled to 0°C. The precipitate of
crude product VII was filtered off, washed with concen-
trated hydrochloric acid, and dried. Yield 50%. The prod-
uct was recrystallized from 15–18% hydrochloric acid or
glacial acetic acid. Yellow finely crystalline substance,
synthesized by treatment of nitroso compound IX with
sodium hypochlorite in alkaline medium according to the
procedure reported in [8]. From 10 g of compound IX
we obtained 8.5 g (71%) of product X as a bright orange
powder with mp 238–240°C (decomp.), 239–240.5°C [8].
(
1
5-Amino-7-chloro-8-hydroxyquinoline dihydro-
chloride (XI). A solution of 34.2 g (0.15 mol) of tin(II)
chloride dihydrate in 40 ml of concentrated hydrochloric
acid was heated to 70°C, and 8.5 g (0.38 mol) of quino-
line X was added with stirring. The mixture was stirred
for 2.5 h at 90°C and cooled, the precipitate of
dihydrochloride XI ditin salt was filtered off and dissolved
in 450 ml of hot water, a stream of hydrogen sulfide was
passed through the solution, the precipitate of tin(II)
sulfide was filtered off, the filtrate was evaporated to
a volume of 45–50 ml and cooled, and the precipitate of
amine dihydrochloride XI was filtered off and dried.Yield
6.7 g (66%). The product was purified by recrystalliza-
tion from dilute hydrochloric acid. Decomposition point
267.5–269.5°C. Found, %: N 10.41. C H ClN O·2HCl.
–
1
mp 252–256°C (decomp.). IR spectrum, n, cm : 1358,
1
1
160 (SO ). H NMR spectrum, d, ppm: 2.352 s (3H,
2
CH ), 7.323 d (2H, Harom, J = 8.4 Hz), 7.516 d (2H, Harom
,
3
J = 8.4 Hz), 7.111 d (1H, 7-H, J = 8.1 Hz), 7.379 d (1H,
-H, J = 8.1 Hz), 7.961 d.d (1H, 3-H, J = 5.4, J = 8.6 Hz),
.960 d.d (1H, 4-H, J = 3.8, J = 8.6 Hz), 9.060 d.d (1H,
-H, J = 3.8, J = 5.4 Hz), 10.360 s (1H, NH), 11.890 s
1H, OH). Found, %: N 7.91; S 9.10. C H N O S · HCl.
Calculated, %: N 7.98; S 9.14.
6
8
2
1 2
1
2
1
2
(
16
14
2
3
9
7
2
Calculated, %: N 10.47.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 1 2004

96
BELOV, NICHVOLODA
7
-Chloro-8-hydroxy-5-(p-tolylsulfonylamino)-
8.532 d.d (1H, 4-H, J = 3.3, J = 7.7 Hz), 8.958 d.d (1H,
1 2
quinoline hydrochloride (VIII). (a) p-Toluenesulfonyl
2-H, J = 3.3, J = 4.5 Hz), 10.402 s (1H, NH), 11.989 s
1 2
chloride, 2.8 g (0.015 mol), was added to a solution of 4 g
(1H, OH). Found, %: N 7.20; S 8.28. C H ClN O S ·
16 13 2 3
(0.015 mol) of compound XI in a mixture of 7 ml of pyri-
HCl. Calculated, %: N 7.27; S 8.32.
dine and 30 ml of ethanol. The mixture was stirred for 2 h
at room temperature, left to stand for 24 h, and poured
onto 200 g of crushed ice. The precipitate was filtered
off, washed with water, and transferred (while wet) into
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45–50 ml of 10% hydrochloric acid. The mixture was
stirred for 30 min, and the precipitate of compound VIII
was filtered off and dried. Yield 4.6 g (80%, calculated
on XI). The product was purified by recrystallization from
dilute hydrochloric acid. Yellowish–light green crystals,
mp 224–225°C.
3
4
5
6
7
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(4.3 mmol) of hydrochloride VII, was dispersed in 9 ml
of acetic acid, 4 ml of concentrated hydrochloric acid
was added with stirring, and the mixture was stirred for
10 min and poured into 30 ml of water containing ice.
The precipitate was filtered off, washed on a filter with
water, and dried. Yield of the crude product 0.75 g (46%,
calculated on VII). The crude product was purified by
double recrystallization from glacial acetic acid. Green-
ish–grey needles, mp 224.5–225°C. The product showed
no depression of the melting point on mixing with a sample
prepared from amine XI as described in a. IR spectrum,
8
9
1
1
–1
1
n, cm : 1317, 1155 (SO ), 3241 (NH), 3295 (OH). H
2
NMR spectrum, d, ppm: 2.343 s (3H, CH ), 7.095 s (1H,
3
6-H), 7.321 d (2H, Harom, J = 8.2 Hz), 7.540 d (2H, Harom
,
12. Voronin, V.G., Petrova, I.D., Leksin, A.N., and Shemeryan-
J = 8.2 Hz), 7.677 d.d (1H, 3-H, J = 4.5, J = 7.7 Hz),
kin, B.V., Khim.-Farm. Zh., 1976, no. 3, p. 82.
1
2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 1 2004