Specificity of the cyclization of 1-alkyl(aryl)sulfonylamino-9,10- anthraquinones into naphtho[1,2,3-cd]indol-6(2H)-ones

Article abstract of DOI:10.1134/S1070428008100187

Cyclization of N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)methanesulfonamides to 2,6-dihydronaphtho[1,2,3-cd]indol-6-ones in DMSO-KOH involves intermediate formation of 2,3-dihydroanthra[1,9-cd]-[1λ⁶,2]thiazin-7-one 2,2-dioxides, whereas heterocy

Full text of DOI:10.1134/S1070428008100187

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 10, pp. 1508–1511. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © V.A. Beresnev, L.M. Gornostaev, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 10, pp. 1531–1533.
Dedicated to Full Member of the Russian Academy of Sciences
B.A. Trofimov on his 70th anniversary
Specificity of the Cyclization of 1-Alkyl(aryl)sulfonylamino-
9,10-anthraquinones into Naphtho[1,2,3-cd]indol-6(2H)-ones
V. A. Beresnev and L. M. Gornostaev
Astaf’ev Krasnoyarsk State Pedagogical University, ul. Lebedevoi 89, Krasnoyarsk, 660049 Russia
e-mail: gornostaev@kspu.ru
Received May 13, 2008
Abstract—Cyclization of N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)methanesulfonamides to 2,6-dihydro-
naphtho[1,2,3-cd]indol-6-ones in DMSO–KOH involves intermediate formation of 2,3-dihydroanthra[1,9-cd]-
[1λ6,2]thiazin-7-one 2,2-dioxides, whereas heterocyclization of N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)-
ethane- and -arenesulfonamides under analogous conditions occurs with participation of methylsulfonyl-
methanide.
DOI: 10.1134/S1070428008100187
We previously [1] proposed a simple procedure for
the synthesis of naphtho[1,2,3-cd]indol-6(2H)-ones II
via cyclization of N-(9,10-dioxo-9,10-dihydroanthra-
cen-1-yl)methanesulfonamides I in DMSO in the pres-
ence of potassium hydroxide. It was presumed that the
cyclization I → II involves intermediate formation of
2,3-dihydroanthra[1,9-cd][1λ6,2]thiazin-7-one 2,2-di-
oxides IIIa–IIIc (Scheme 1). The goal of the present
work was to determine the scope of that cyclization
and its mechanism. For this purpose, we examined
transformations of compounds I having different
substituents in the sulfonyl fragment under different
conditions.
tions (heating of the amine in excess butane- or
phenylmethanesulfonyl chloride) decomposition of
the reagents or products occurred. We succeeded in
isolating only N-(9,10-dioxo-9,10-dihydroanthracen-1-
yl)ethanesulfonamide (Id). Another synthetic approach
to 1-R-sulfonylamino-9,10-anthraquinones is based on
the reaction of sulfonamides with 1-halo-9,10-anthra-
quinones. However, it was successful only with arene-
sulfonamides. Therefore, we examined in detail the
behavior of previously [1] synthesized N-(9,10-dioxo-
9,10-dihydroanthracen-1-yl)methanesulfonamides Ib
and Ic, as well as of newly prepared N-((9,10-dioxo-
9,10-dihydroanthracen-1-yl)ethanesulfonamide (Id) in
DMSO in the presence of bases.
Unfortunately, we failed to obtain a wide series of
1-alkylsulfonylamino-9,10-anthraquinones because of
low nucleophilicity of aminoanthraquinones. When re-
actions of 1-amino-9,10-anthraquinones with alkane-
sulfonyl chlorides were carried out under severe condi-
We found that sulfonamides Ib and Ic in the system
DMSO–KOH were converted into sultams IIIb and
IIIc (Scheme 1) which were isolated and character-
ized by spectral and analytical data. Surprisingly, by
Scheme 1.
O
O
S
O
NHSO2Me
R
NH
NH
R
R
KOH–DMSO
O
R'
O
R'
O
R'
Ia–Ic
IIIa–IIIc
IIa–IIc
R = H (a), PhO (b), 4-MeC6H4O (c); R′ = H (a), HO (b, c).
1508

SPECIFICITY OF THE CYCLIZATION OF 1-ALKYL(ARYL)SULFONYLAMINO-...
1509
Scheme 2.
NH
O
O
NHSO2Et
O
KOH–DMSO
IIa
Me
NH
Id
O
IV
Scheme 3.
O
O
NHSO2Ar
NH
KOH–DMSO
O
Ie, If
IIa
Ar = Ph (e), 4-MeC6H4 (f).
heating ethanesulfonamide Id in DMSO in the pres-
ence of KOH at 100–110°C we obtained naphthoindole
IIa rather than expected 1-methylnaphtho[1,2,3-cd]-
indol-6(2H)-one (IV) (Scheme 2). Moreover, under
analogous conditions N-(9,10-dioxo-9,10-dihydroan-
thracen-1-yl)arenesulfonamides Ie and If were also
converted into compound IIa (Scheme 3).
other hand, the mass spectra of samples of IIb ob-
tained in 13C-DMSO and 12C-DMSO were identical
(m/z 327 [M]+).
Obviously, the cyclization of N-(9,10-dioxo-9,10-
dihydroanthracen-1-yl)methanesulfonamides Ia–Ic to
naphtho[1,2,3-cd]indol-6(2H)-ones IIa–IIc follows the
path proposed previously (I → III → II), while the
transformation of analogous ethyl- and arylsulfonyl
derivatives involves nucleophilic attack by the dimeth-
yl sulfoxide anion with subsequent cyclization of inter-
mediate methylene quinone V (Scheme 4). This mech-
anism is consistent with published data on the reac-
tions of some ketones with a s suspension of KOH in
DMSO, which leads to allyl alcohols [2]. The key
stage in the reductive methylenation of ketones is addi-
Presumably, the pyrrole ring is formed in the above
reactions with participation of DMSO molecule. This
assumption was confirmed by special experiment:
heterocyclization of sulfonamide Id was carried out
using 13C-labeled dimethyl sulfoxide. The molecular
weight of the product obtained in 13C-DMSO was
220 a.m.u. (according to the MS data) against 219 for
compound IIa isolated from unlabeled DMSO. On the
Scheme 4.
CH2 NHSO2R
NH
CH2S(O)Me
I
O
O
V
R = Et, Ar.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008

BERESNEV, GORNOSTAEV
1510
tion of methylsulfonylmethanide at the carbonyl car-
bon atom [3].
200 ml of 5% hydrochloric acid cooled to 0–5°C. The
precipitate was filtered off, dried, and thrice recrystal-
lized from toluene.
Presumably, intramolecular hydrogen bonding in
sulfonamides I favors enhanced electrophilicity of the
neighboring carbonyl group. For example, the same
factor was assumed to be responsible for the amination
of 1-hydroxy-9,10-anthraquinones with ammonia to
1-hydroxy-9-imino derivatives [4]. The proposed
heterocyclization path is likely to be possible for other
1-amino-9,10-anthraquinone derivatives.
6-Hydroxy-4-phenoxy-2,3-dihydroanthra-
[1,9-cd][1λ6,2]thiazin-7-one 2,2-dioxide (IIIb). Yield
1
0.31 g (47%), mp 295–297°C. H NMR spectrum, δ,
ppm: 13.52 s (1H, OH), 12.01 br.s (1H, NH), 8.51 m
(2H, 1-H, 7-H or 10-H), 8.34 d (1H, 10-H or 7-H),
7.91 t (1H, 9-H or 8-H), 7.80 t (1H, 8-H or 9-H), 7.55 t
(2H), 7.38 t (1H), 7.35 d (2H), 6.44 s (1H, 5-H). Mass
spectrum: m/z 391 [M]+. Found, %: C 64.37; H 3.39;
N 3.47; S 8.26. C21H13NO5S. Calculated, %: C 64.45;
H 3.25; N 3.58; S 8.18. M 391.40.
EXPERIMENTAL
1
6-Hydroxy-4-(4-methylphenoxy)-2,3-dihydroan-
The H NMR spectra were recorded on a Bruker
thra[1,9-cd][1λ6,2]thiazin-7-one 2,2-dioxide (IIIc).
DRX spectrometer (500 MHz) from solutions in
DMSO-d6 using tetramethylsilane as internal refer-
ence. The mass spectra were obtained on Finnigan
MAT-8200 and Hewlett–Packard G1800A (GC–MS)
instruments. The melting points were measured on
a Boetius hot stage. The progress of reactions and the
purity of products were monitored by TLC on Silufol
plates using toluene–acetone (10:1) as eluent. Labeled
dimethyl sulfoxide containing 99% of 13C isotope
(Isotec) was used.
1
Yield 0.30 g (45%), mp 289–291°C. H NMR spec-
trum, δ, ppm: 13.51 s (1H, OH), 12.01 br.s (1H, NH),
8.45 m (2H, 1-H, 7-H or 10-H), 8.05 d (1H, 10-H or
7-H), 7.78 t (1H, 9-H or 8-H, J = 7.2 Hz), 7.71 t (1H,
8-H or 9-H, J = 7.2 Hz), 7.25 m (2H), 7.05 m (2H),
6.49 s (1H), 2.42 s (3H, Me). Mass spectrum: m/z 405
[M]+. Found, %: C 64.71; H 3.74; N 3.49; S 7.54.
C22H15NO5S. Calculated, %: C 65.18; H 3.70; N 3.45;
S 7.90. M 405.42.
N-(9,10-Dioxo-9,10-dihydroanthracen-1-yl)-
ethanesulfonamide (Id). Ethanesulfonyl chloride,
1 ml, was added to a solution of 0.5 g (2.23 mmol) of
1-amino-9,10-anthraquinone in 5 ml of nitrobenzene.
The mixture was stirred for 28 h at 100°C and cooled
to 15°C, and the precipitate was filtered off, washed
with alcohol, and recrystallized from 1,4-dioxane.
Cyclization of 1-alkyl(aryl)sulfonylamino-9,10-
anthraquinones Id–If into naphtho[1,2,3-cd]indol-
6(2H)-one (IIa). Sulfonamide Id–If, 1.70 mmol, was
dissolved in 10 ml of DMSO, 0.5 g (8.90 mmol) of
finely powdered potassium hydroxide was added, and
the mixture was stirred for 2 h at 100–110°C, cooled to
20°C, and poured into a mixture of 200 g of crushed
ice and 10 ml of 36% hydrochloric acid. The precip-
itate was filtered off, dried, and twice recrystallized
from toluene. Yield 68% (from Id), 60–62% (from Ie
1
Yield 2.45 g (78%), mp 187–188°C. H NMR spec-
trum, δ, ppm: 11.90 s (1H, NH), 8.25–8.34 m (2H),
7.92–8.02 m (5H), 3.2 d (2H, CH2), 1.49 d (3H, CH3).
Found, %: C 61.02; H 4.12; N 4.57. C16H13NO4S. Cal-
culated, %: C 60.95; H 4.13; N 4.44.
1
and If), mp 255–257°C. H NMR spectrum, δ, ppm:
12.00 s (1H, NH), 8.45 br.s (1H), 8.32 d (1H, J =
7.8 Hz), 8.12 d (1H, J = 7.8 Hz), 7.97 d (1H, J =
7.5 Hz), 7.88 d (1H, J = 7.5 Hz), 7.70 br.t (1H, J =
7.0 Hz), 7.52 br.t (1H, J = 7.5 Hz), 7.42 br.t (1H, J =
7.0 Hz). Mass spectrum, m/z (Irel, %): 219 (100) [M]+,
190 (8.3) [M – HCN – H2]+, 163 (23.3) [M – HCN –
CO]+, 95 (10.0), 82 (13.3). Found, %: C 82.17; H 4.14;
N 6.38. C15H9NO. Calculated, %: C 82.19; H 4.14;
N 6.39. M 219.23.
4-Aryloxy-2,3-dihydroanthra[1,9-cd][1λ6,2]thia-
zin-7-one 2,2-dioxides IIIb and IIIc (general proce-
dure). Finely powdered potassium hydroxide, 0.25 g
(4.45 mmol), was added to a solution of 1.70 mmol of
sulfonamide Ib or Ic in 10 ml of DMSO, and the
mixture was stirred for 8 h at 85°C and poured into
Cyclization of N-(9,10-dioxo-9,10-dihydroan-
thracen-1-yl)ethanesulfonamide (Id) into naphtho-
[1,2,3-cd]indol-6(2H)-one (IIa) in 13C-labeled
DMSO. Sulfonamide Id, 0.02 g (6.35 μmol), was
mixed with 0.1 ml of 13C-DMSO and 0.02 g
(0.036 mmol) of KOH, and the mixture was stirred for
2 h at 100–110°C. The mixture was cooled, neutralized
with 1.5 ml of 10% hydrochloric acid, and treated with
methylene chloride (2×2 ml). The extract was sub-
jected to preparative thin-layer chromatography on
a Silufol plate (width 20 cm) using toluene–acetone
(10:1) as eluent. The product was extracted from the
sorbent into diethyl ether, and the solution was con-
centrated and analyzed by gas chromatography–mass
spectrometry. Mass spectrum, m/z (Irel, %): 220 (100)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008

SPECIFICITY OF THE CYCLIZATION OF 1-ALKYL(ARYL)SULFONYLAMINO-...
1511
[M]+, 191 (8.3) [M – HCN – H2]+, 164 (23.3) [M –
sorbent into diethyl ether, and the solvent was distilled
off. Mass spectrum: m/z 327 [M]+ (cf. [1]).
HCN – CO]+, 96 (10.0), 82 (13.3).
Cyclization of N-(4-hydroxy-9,10-dioxo-2-phen-
oxy-9,10-dihydroanthracen-1-yl)methanesulfon-
amide (Ib) into 5-hydroxy-3-phenoxynaphtho-
[1,2,3-cd]indol-6(2H)-one (IIb) in 13C-labeled
DMSO. A mixture of 0.04 g (0.1 mmol) of sulfon-
amide Ib, 0.2 ml of 13C-DMSO, and 0.04 g
(0.072 mmol) of KOH was stirred for 2 h at 100–
110°C. The mixture was cooled, neutralized with
1.5 ml of 10% hydrochloric acid, and extracted with
methylene chloride (2 × 2 ml). The extract was
subjected to preparative thin-layer chromatography on
a Silufol plate (width 20 cm) using toluene–acetone
(10:1) as eluent. The product was extracted from the
The authors thank B.A. Trofimov for helpful
advices.
REFERENCES
1. Gornostaev, L.M. and Beresnev, V.A., Russ. J. Org.
Chem., 2006, vol. 42, p. 615.
2. Trofimov, B.A., Mikhaleva, A.I., Petrova, O.V., and
Sigalov, M.V., Zh. Org. Khim., 1985, vol. 21, p. 2613.
3. Trofimov, B.A., Mikhaleva, A.I., Petrova, O.V., and
Sigalov, M.V., Zh. Org. Khim., 1988, vol. 24, p. 2095.
4. Müller, A., Körmendy, K., and Ruff, F., Acta Chim. Acad.
Sci. Hung., 1968, vol. 58, p. 453.
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