Amination of thioxanthene-1,4,9-trione and its chloro derivatives

Article abstract of DOI:10.1134/S1070428011100186

Thioxanthene-1,4,9-trione and its 2(3)-chloro and 2,3-dichloro derivatives reacted with amines to give the corresponding 2-amino-substituted products. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S1070428011100186

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 10, pp. 1551–1555. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.A. Loskutov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 10, pp. 1523–1526.
Amination of Thioxanthene-1,4,9-trione
and Its Chloro Derivatives
V. A. Loskutov
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: val@nioch.nss.ru
Received December 3, 2010
Abstract—Thioxanthene-1,4,9-trione and its 2(3)-chloro and 2,3-dichloro derivatives reacted with amines to
give the corresponding 2-amino-substituted products.
DOI: 10.1134/S1070428011100186
Quinones are known to react with amines according
to nucleophilic 1,4-addition pattern with intermediate
formation of aminohydroquinones which undergo
oxidation with the initial quinone (or other oxidant) to
give aminoquinones [1–3]. The site of nucleophile ad-
dition to benzo-, naphtho-, and anthraquinones is
obvious, whereas formation of different regioisomers
is possible in reactions with unsymmetrical quinones,
e.g., those in which the quinoid ring is fused to a het-
eroring or a substituted benzene ring. In these cases,
the quinone carbonyl groups are nonequivalent, and
each of them may be involved in nucleophile addition
at the conjugated bond system. In this respect, nitro-
gen-containing heterocyclic quinones were studied
most thoroughly; the direction of their reactions with
amines is determined by the solvent nature, substitu-
tion pattern in the substrate, and catalysis by metal
salts. A classical example illustrating the above stated
is given by 5,8-quinolinequinone and its monochloro
derivatives [4]. Unsubstituted 5,8-quinolinequinone
reacts with aniline to produce addition products at
positions 6 and 7 at a ratio of ~1:1 (in ethanol) or
6.5:1 (in acetic acid), whereas 6-phenylamino deriva-
tive is formed exclusively in the presence of CeCl3·
7H2O as catalyst (in ethanol). 6-Chloro-5,8-quinoline-
quinone in the absence of catalyst reacts mainly ac-
cording to the addition pattern to form 7-phenylamino
derivative, while replacement of the 6-chlorine atom
becomes the only process under catalytic conditions.
7-Chloro-5,8-quinolinequinone is converted into
7-chloro-6-phenylamino derivative as the only product
both in the absence and in the presence of catalyst.
Analogous studies were performed for other nitrogen-
containing quinones, such as indole-4,7-quinone [5],
isoquinoline-5,8-quinone [6], and phenanthridine-7,10-
quinone [7], as well as for 5-substituted 1,4-naphtho-
quinones [8].
There are no published data on the regioselectivity
of amination of sulfur-containing heterocyclic qui-
nones. Known quinones of the thioxanthene series are
thioxanthene-1,4,9-trione (I), which is available via
oxidation of 1,4-dihydroxythioxanthen-9-one (II) with
potassium bromate [9], ammonium cerium(IV) nitrate
[10], or moist iodous acid [11], and its 2,3-dichloro
derivative III obtained by oxidative chlorination of
thioxanthenone II with molecular chlorine [12] or
Scheme 1.
O
O
O
O
O
OH
NR1R2
HNR1R2
+
S
S
S
O
O
OH
I
IVa–IVd
II
R1 = H, R2 = Ph (a); R1 = H, R2 = 4-BuC6H4 (b); R1 = H, R2 = cyclohexyl (c); R1R2N = piperidino (d).
1551

LOSKUTOV
1552
Scheme 2.
O
S
OH
OH
O
S
O
O
Cl
Cl
Ce(NH4)2(NO3)6
PhNH2
IVa
Va
VI
O
S
OH
OH
O
S
O
O
O
S
O
O
NHPh
Cl
Ce(NH4)2(NO3)6
PhNH2
Cl
Cl
Vb
VII
VIII
O
S
O
O
Cl
PhNH2
VIII
Cl
III
X = Cl, Y = H (a); X = H, Y = Cl (b).
thionyl chloride [13]. In the present work reactions of
quinones I and III with amines were examined with
a view to elucidate regioselectivity of the process.
By analogy with light-sensitive amino-substituted
1,4-naphthoquinones [14], the resulting aminothioxan-
thenones could be promising as nonsilver photographic
materials.
the process. As shown previously [13], hydrochlorina-
tion of quinone I gives a mixture of 2- and 3-chloro-
1,4-dihydroxythioxanthen-9-ones, the 3-chloro isomer
prevailing.
The site of addition of amino group to the quinoid
ring of thioxanthenetrione I was determined by inde-
pendent synthesis. Oxidation of 2- and 3-chloro-1,4-
dihydroxythioxanthenones Va and Vb with ammonium
cerium(IV) nitrate gave isomeric monochloro-substi-
tuted quinones VI and VII which were then brought
into reaction with aniline in DMSO. The reaction with
2-chlorothioxanthenetrione VI gave 2-phenylamino
derivative IVa in high yield (70%); the product was
identical to that isolated in the reaction of quinone I
with aniline. Unlike compound VI, its 3-chloro isomer
VII reacted with aniline according to the 1,4-addition
pattern with participation of the C4=O group to
produce a mixture of 3-chloro-2-phenylaminothioxan-
thene-1,4,9-trione (VIII) and reduction product of
quinone VII, 3-chloro-1,4-dihydroxythioxanthen-9-
one (Scheme 2).
Quinone I reacted with primary aromatic amines
(aniline and 4-butylaniline), as well as with primary
and secondary cyclic aliphatic amines (cyclohexyl-
amine and piperidine), in organic solvents (methylene
chloride, toluene, DMSO) at room temperature to give
the corresponding 2-substituted thioxanthene-1,4,9-tri-
ones IVa–IVd (Scheme 1). In all cases, apart from
amino derivatives IV, the reaction mixtures contained
hydroquinone II resulting from reduction of initial
quinone I. Compound II was detected by TLC and
isolated in 33% yield in the reaction with piperidine.
The formation of hydroquinone II indicates participa-
tion of quinone I in the oxidation of primary product of
amine addition to quinone I, 2-amino-1,4-dihydroxy-
thioxanthen-9-one. This is the reason for fairly poor
yields (20–30%) of quinones IVb–IVd. Another
reason is that the reaction was accompanied by tarring.
Aniline derivative IVa was isolated in a higher yield
(45%) when the reaction was carried out in toluene.
Compound IVa is poorly soluble in that solvent, and it
crystallized on the walls of the reaction flask during
Like 2-chlorothioxanthenone VI, 2,3-dichloro deriv-
ative III is characterized by enhanced reactivity of the
chlorine atom in position 2 toward amines, and the
reaction of III with aniline and piperidine resulted in
the formation of the corresponding 2-amino-substi-
tuted 3-chlorothioxanthen-1,4,9-triones in high yield.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011

AMINATION OF THIOXANTHENE-1,4,9-TRIONE AND ITS CHLORO DERIVATIVES
1553
The structure of the newly synthesized compounds
was confirmed by analytical and spectral data. The
1H NMR spectra of amino derivatives IV characteris-
tically contained a signal at δ ~6 ppm due to 2-H.
Analogous signal in the spectra of monochloro-substi-
tuted quinones VI and VII, as well as of unsubstituted
quinone I, is displaced downfield to the aromatic
region (cf. [10]). A specific property of amino- and
chloro-substituted thioxanthene-1,4,9-triones is their
ability to readily undergo reduction to the correspond-
ing hydroquinones in protic medium (e.g., in ethanol).
As a result, the [M + 2]+ ion peaks in the mass spectra
of these compounds are characterized by increased
intensity, which is consistent with published data [15].
7.50 t (5H, Ph); 7.73 t and 7.83 t (2H, 6-H, 7-H),
8.06 d (1H, 5-H), 8.36 d (1H, 8-H), 9.79 s (NH). Mass
spectrum, m/z (Irel, %): 336 (4), 335 (20), 334 (23), 333
(100). Found: m/z 333.04963 [M]+. C19H11NO3S. Cal-
culated: M 333.04596.
b. A mixture of 0.14 g (0.5 mmol) of 2-chlorothio-
xanthene-1,4,9-trione (VI) and 0.07 ml (0.75 mmol) of
aniline in 7 ml of DMSO was kept for 20 h at 20–
25°C, and the precipitate was filtered off. Yield 0.12 g
1
(70%), mp 296–299°C. The H NMR spectrum of the
product was identical to that of a sample prepared as
described in a.
2-(4-Butylphenylamino)thioxanthene-1,4,9-tri-
one (IVb). A mixture of 0.1 g (0.4 mmol) of quinone I
and 0.6 ml (4 mmol) of 4-butylaniline in 20 ml of
methylene chloride was kept for 24 h at ~20°C. The
mixture was washed with 5% hydrochloric acid and
water and subjected to column chromatography on
silica gel using chloroform as eluent. Compound IVb
was isolated from the red–violet fraction. Yield 0.036 g
(22%), mp 207–211°C (from chloroform–hexane).
IR spectrum, ν, cm–1: 3232 (NH), 1687 (C=O), 1613
(C=C). 1H NMR spectrum (DMSO-d6), δ, ppm: 0.90 t,
1.31 m, 1.56 m, 2.60 t (9H, Bu); 6.00 s (1H, 3-H),
7.29 s (4H, C6H4), 7.71 t and 7.81 t (2H, 6-H, 7-H),
8.04 d (1H, 5-H), 8.34 d (1H, 8-H), 9.75 br.s (1H, NH).
Found: m/z 389.1084 [M]+. C23H19NO3S. Calculated:
M 389.1080.
Thus unsubstituted thioxanthene-1,4,9-trione (I)
and its 3-chloro derivative VII take up amine mole-
cules at 1,4-conjugation system with predominant con-
tribution of the C4=O group as compared to C1=O,
which may be attributed to reduced electron-acceptor
power of the latter due to conjugation with the sulfur
atom. Reactions of 2-chloro- and 2,3-dichlorothioxan-
thene-1,4,9-triones VI and III with amines resulted in
replacement of the 2-chlorine atom.
EXPERIMENTAL
The IR spectra were recorded in KBr on a Bruker
1
Vector 22 spectrometer. The H NMR spectra were
measured on a Bruker AV-400 spectrometer at
400 MHz; the chemical shifts were determined relative
to the residual proton signal of the deuterated solvent.
The mass spectra were obtained on DFS and Finnigan
MAT-8200 instruments; the molecular weights and
elemental compositions were determined from the
high-resolution mass spectra. The progress of reactions
and the purity of products were monitored by TLC
on Silufol UV-254 plates using methylene chloride–
acetone (10:1) as eluent. Silica gel manufactured by
Imid Ltd. (50–160 μm) was used for column chroma-
tography.
2-Cyclohexylaminothioxanthene-1,4,9-trione
(IVc). A mixture of 0.12 g (0.5 mmol) of quinone I and
0.06 ml (0.5 mmol) of cyclohexylamine in 30 ml of
methylene chloride was kept for 5 min at ~20°C and
evaporated, and the residue was subjected to column
chromatography on silica gel using chloroform as
eluent. Aminoquinone IVc was isolated from the red–
violet fraction. Yield 0.04 g (24%), mp 258–261°C
(from CH2Cl2–hexane). IR spectrum, ν, cm–1: 3262
1
(NH), 1686 (C=O), 1594 (C=C). H NMR spectrum
(CDCl3), δ, ppm: 1.36 m, 1.66 m, 1.80 m, 2.00 m,
3.29 m (11H, C6H11); 5.76 s (1H, 3-H), 6.31 d (1H,
NH, J = 7.5 Hz); 7.69 t.d, 7.65 t.d, 7.68 m (3H, 5-H,
6-H, 7-H); 8.51 d.d (1H, 8-H, J = 8.0, 2.0 Hz). Mass
spectrum, m/z (Irel, %): 342 (7), 341 (34), 340 (22), 339
(100). Found: m/z 339.0923 [M]+. C19H17NO3S. Cal-
culated: M 339.0924.
Initial compounds I–III, Va, and Vb were synthe-
sized as described in [10, 12, 13].
2-Phenylaminothioxanthene-1,4,9-trione (IVa).
a. A mixture of 0.08 g (0.3 mmol) of quinone I and
0.3 g (3.2 mmol) of aniline in 100 ml of toluene was
kept for 24 h at 20–25°C. The precipitate was filtered
off and washed with benzene. Yield of chromato-
graphically pure product 0.05 g (45%), mp 301–304°C
(from toluene). IR spectrum, ν, cm–1: 3237 (NH); 1685
2-Piperidinothioxanthene-1,4,9-trione (IVd).
A mixture of 0.12 g (0.5 mmol) of quinone I and
0.025 ml (0.25 mmol) of piperidine in 30 ml of meth-
ylene chloride was kept for 5 min at ~20°C and evap-
orated, and the residue was subjected to column chro-
1
(C=O); 1623, 1612 (C=C). H NMR spectrum
(DMSO-d6), δ, ppm: 6.05 s (1H, 3-H); 7.29 t, 7.37 d,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011

LOSKUTOV
1554
matography on silica gel using chloroform as eluent.
Red–violet and yellow fractions were collected. The
former contained 0.05 g (31%) of aminoquinone IVd,
mp 167–169°C (from CH2Cl2–hexane). IR spectrum, ν,
and 0.1 ml (1 mmol) of piperidine in 13 ml of DMSO
was kept for 1 h at ~20°C, 20 ml of water was added,
and the precipitate was filtered off. Yield 0.13 g (76%).
The product was purified by column chromatography
on silica gel using chloroform as eluent, mp 167–
168°C. IR spectrum, ν, cm–1: 2934, 2856 (C–H); 1689
1
cm–1: 1682 (C=O); 1624, 1611 (C=C). H NMR spec-
trum (CDCl3), δ, ppm: 1.74 s (6H, CH2), 3.56 s (4H,
CH2), 5.89 s (1H, 3-H), 7.62 m (3H, 5-H, 6-H, 7-H),
8.51 d (1H, 8-H). Mass spectrum, m/z (Irel, %): 329 (3),
328 (11), 327 (48), 326 (43), 325 (100). Found, %:
C 65.90; H 4.79; N 4.39; S 9.79. m/z 325.07101 [M]+.
C18H15NO3S. Calculated, %: C 66.46; H 4.61; N 4.30;
S 9.85. M 325.07726.
1
(C=O), 1619 (C=C). H NMR spectrum (CDCl3), δ,
ppm: 1.80 m (6H, CH2), 3.67 m (4H, CH2), 7.55–
7.67 m (3H, 5-H, 6-H, 7-H), 8.47 d (1H, 8-H). Mass
spectrum, m/z (Irel, %): 364 (8), 363 (35), 362 (34), 361
(100), 360 (50), 359 (26) [M]+. Found, %: C 59.59;
H 3.89; Cl 10.32; N 4.08; S 8.99. C18H14ClNO3S. Cal-
culated, %: C 60.08; H 3.89; Cl 9.87; N 3.89; S 8.90.
The yellow fraction contained 0.04 g (33%) of
dihydroxythioxanthenone II which was identified by
comparison with an authentic sample [10] by the IR
spectrum and TLC data.
2-Chlorothioxanthene-1,4,9-trione (VI). A solu-
tion of 2.5 g (4.5 mmol) of ammonium cerium(IV)
nitrate in 5 ml of water was added under stirring at
room temperature to a solution of 0.6 g (2.2 mmol) of
2-chlorothioxanthenone Va [13] in 30 ml of DMSO,
the mixture was stirred for 30 min and poured into ice
water, and the precipitate was filtered off. Yield nearly
quantitative, mp 202–206°C (decomp.). IR spectrum,
Reaction of 3-chlorothioxanthene-1,4,9-trione
(VII) with aniline. A mixture of 0.12 g (0.4 mmol) of
compound VII and 0.05 ml (0.5 mmol) of aniline in
4.5 ml of DMSO was kept for 20 h at ~20°C. The
mixture was diluted with ice water, and the precipitate
(0.13 g) was filtered off and subjected to column
chromatography on silica gel using methylene chloride
as eluent to isolate 0.03 g (25%) of 3-chloro-1,4-dihy-
droxythioxanthen-9-one, mp 240–243°C. The product
1
ν, cm–1: 1679 (C=O), 1658 (C=C). H NMR spectrum
(DMSO-d6), δ, ppm: 7.60 s (1H, 3-H), 7.68 t.d and
7.81 t.d (2H, 6-H, 7-H), 8.03 d.d (1H, 5-H), 8.28 d.d
(1H, 8-H). Mass spectrum, m/z (Irel, %): 280 (8), 279
(7), 278 (39), 277 (16), 276 (100). Found, %: C 57.00;
H 2.08; Cl 13.12; S 11.32. m/z 275.9653 [M]+.
C13H5ClO3S. Calculated, %: C 56.42; H 1.81; Cl 12.84;
S 11.57. M 275.9642.
1
was identified by the TLC and H NMR data in com-
parison with an authentic sample [13].
Elution with methylene chloride–acetone (10:1)
gave 0.06 g (37%) of 3-chloro-2-phenylaminothioxan-
thene-1,4,9-trione (VIII), mp 297–301°C (from tolu-
ene). IR spectrum, ν, cm–1: 3262 (NH), 1686 (C=O),
3-Chlorothioxanthene-1,4,9-trione (VII) was syn-
thesized in a similar way from 3-chlorothioxanthenone
Vb [13]. Yield nearly quantitative, mp 242–246°C
(decomp.). IR spectrum, ν, cm–1: 1682 (C=O), 1657
1
1594 (C=C). H NMR spectrum (DMSO-d6), δ, ppm:
7.17 m and 7.34 t (5H, Ph), 7.71 t and 7.83 t (2H, 6-H,
7-H), 8.07 d (1H, 5-H), 8.33 d (1H, 8-H), 9.87 br.s
(1H, NH). Found, %: C 61.94; H 2.85; Cl 9.90;
N 3.94; S 8.99. m/z 367.0075 [M]+. C19H10ClNO3S.
Calculated, %: C 62.04; H 2.72; Cl 9.66; N 3.81;
S 8.71. M 367.0064.
1
(C=C). H NMR spectrum (DMSO-d6), δ, ppm: 7.37 s
(1H, 2-H), 7.73 t and 7.86 t (2H, 6-H, 7-H), 8.09 d
(1H, 5-H), 8.32 d (1H, 8-H). Found: m/z 275.9643
[M]+. C13H5ClO3S. Calculated: M 275.9642.
This study was performed under financial support
by the Siberian Division of the Russian Academy of
Sciences (integration projects nos. 55, 71).
Reaction of 2,3-dichlorothioxanthene-9-one (III)
with aniline. A mixture of 0.08 g (0.4 mmol) of qui-
none III [10] and 0.1 ml (1 mmol) of aniline in 8 ml of
DMSO was kept for 2 h at ~20°C, 20 ml of water was
added, and the precipitate was filtered off. Yield of
compound VIII 0.07 g (78%). The product was puri-
fied by column chromatography on silica gel using
chloroform as eluent, mp 300–301°C. Its IR spectrum
was identical to that of a sample of VIII isolated as
described above.
REFERENCES
1. Finley, K.T., The Chemistry of the Quinonoid Com-
pounds, Patai, S., Ed., London: Interscience, 1974, vol. 2,
p. 877; Laird, T., Comprehensive Organic Chemistry,
Barton, D. and Ollis, W.D., Eds., Oxford: Pergamon,
1979, vol. 1. Translated under the title Obshchaya orga-
nicheskaya khimiya, Moscow: Khimiya, 1982, vol. 2,
p. 830; Methoden der organischen Chemie (Houben–
Weyl), Müller, E., Bayer, O., Meerwein, H., and
3-Chloro-2-piperidinothioxanthene-1,4,9-trione.
A mixture of 0.15 g (0.5 mmol) of quinone III [10]
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011

AMINATION OF THIOXANTHENE-1,4,9-TRIONE AND ITS CHLORO DERIVATIVES
1555
Ziegler, K., Eds., Stuttgart: Georg Thieme, 1979, 4th ed.,
vol. 7 (3a), p. 660.
2. Gorelik, M.V., Khimiya antrakhinonov i ikh proizvodnykh
(Chemistry of Anthraquinones and Their Derivatives),
Moscow: Khimiya, 1983.
8. Kolesnikov, V.T., Belitskaya, L.D., and Litvin, B.L.,
Zh. Org. Khim., 1982, vol. 18, p. 90; Bukhtoyaro-
va, A.D., Rybalova, T.V., and Ektova, L.V., Russ. J. Org.
Chem., 2010, vol. 46, p. 855.
9. König, H.-B., FRG Patent no. 955510, 1957; Chem.
Abstr., 1959, vol. 53, p. 6258.
3. Kutyrev, A.A. and Moskva, V.V., Usp. Khim., 1991,
10. Loskutov, V.A. and Beregovaya, I.V., Russ. J. Org.
Chem., 2009, vol. 45, p. 1405.
11. Loskutov, V.A., Gatilov, Y.V., and Shteingarts, V.D.,
vol. 60, p. 134.
4. Pratt, Y.T., J. Org. Chem., 1962, vol. 27, p. 3905; Klimo-
vich, O.S., Kolesnikov, V.T., and Sazhnikov, V.A.,
Zh. Prikl. Khim., 1976, vol. 49, p. 1823.
Tetrahedron Lett., 2010, vol. 51, p. 6396.
12. Loskutov, V.A., Gatilov, Yu.V., and Mamatyuk, V.I.,
Russ. J. Org. Chem., 2008, vol. 44, p. 626.
13. Loskutov, V.A., Mamatyuk, V.I., and Beregovaya, I.V.,
Russ. J. Org. Chem., 2010, vol. 46, p. 241.
14. Shishkina, R.P. and Berezhnaya, V.N., Usp. Khim.,
5. Barret, R. and Roue, N., Tetrahedron Lett., 1999, vol. 40,
p. 3889; Jackson, Y.A., Billimoria, A.D., Sadanan-
dan, E.V., and Cava, M.P., J. Org. Chem., 1995, vol. 60,
p. 3543; Edstrom, E.D. and Jones, Z., Tetrahedron Lett.,
1995, vol. 36, p. 7039.
6. Valderrama, J.A., Ibacache, J.A., Rodriguez, J.A., and
Theoduloz, C.G., Bioorg. Med. Chem., 2009, vol. 17,
p. 2894.
1994, vol. 63, p. 145.
15. Vul’fson, N.S., Zaikin, V.G., and Mikaya, A.I., Mass-
spektrometriya organicheskikh soedinenii (Mass Spec-
trometry of Organic Compounds), Moscow: Khimiya,
1986.
7. Valderrama, J.A. and Ibacache, J.A., Tetrahedron Lett.,
2009, vol. 50, p. 4361.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011