Cyclization of 2-chloro-3-(1,4-oxocyclohexa-2,5-dienylideneamino)-1,4- dihydronaphthalene-1,4-diones into 6-chloro-10,12a-dihydroxy-7H,12aH-benzo[c] phenoxazin-5-ones

Article abstract of DOI:10.1134/S1070428013050012

2-Chloro-3-(4-oxocyclohexa-2,5-dienylideneamino)-1,4-dihydronaphthalene-1, 4-diones maintained in the conc. sulfuric acid undergo cyclization affording in a high yield 6-chloro-10,12a-dihydroqEe Cyrillic sign-7H,12aH-benzo[c] phenoxazin-5-ones whose structure is proved by XRD analysis.

Full text of DOI:10.1134/S1070428013050012

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 5, pp. 746−749. © Pleiades Publishing, Ltd., 2013.
Original English Text © L.M. Gornostaev, A.E. Devyashina, Yu.V. Gatilov, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 5, pp. 763−766.
Cyclization of 2-Chloro-3-(1,4-oxocyclohexa-2,5-
dienylideneamino)-1,4-dihydronaphthalene-1,4-diones into
6-Chloro-10,12а-dihydroxy-7Н,12аН-benzo[с]phenoxazin-5-ones
L. M. Gornostaeva, A. E. Devyashinaa, and Yu. V. Gatilovb
aAstaf’ev Krasnoyarsk State Pedagogical University, Krasnoyarsk, 660049 Russia
e-mail: gornostaev@kspu.ru
bVorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia
Received July 10, 2012
Abstract—2-Chloro-3-(4-oxocyclohexa-2,5-dienylideneamino)-1,4-dihydronaphthalene-1,4-diones maintained
in the conc. sulfuric acid undergo cyclization affording in a high yield 6-chloro-10,12а-dihydroqси-7Н,12аН-
benzo[с]phenoxazin-5-ones whose structure is proved by XRD analysis.
DOI: 10.1134/S1070428013050012
In [1] an approach was described to a synthesis of
2-chloro-3-(1,4-oxocyclohexa-2,5-dienylideneamino)
[1,4]-naphthoquinones Ia, Ib. quinoneimines Ia, Ib in
sulfuric acid of various concentrations: in the acid of
5–80% concentration these compounds remained intact,
and at a short keeping in the acid of 92–95% concentration
at 0–5°С they converted into 6-chloro-10,12а-dihydroxy-
7Н,12аН-benzo[с]phenoxazine-5-oneы IIа, IIb in high
yields (Scheme 1). The latter substances were identified
by 1Н NMR and mass spectra and by XRD analysis.
Similar phenoxazinones [6-chloro-12а-hydroxy-5Н-
benzo[с]phenoxazin-5-one (IV)] were obtained in [2]
by the reaction of 2,3-dichloro-1,4-naphthoquinone (III)
with ortho-aminophenols.
HO
IIa, 27%
III +
H2N
OH
In the 1Н NMR spectrum of compound IIa the proton
signsld of the hemiketal hydroxy group (7.99 ppm) and
of the proton linked to the nitrogen atom (10.35 ppm)
appeared close to the region of the corresponding signals
in the spectrum of compound IV (8.06, 10.54 ppm) [2].
We presume that the reaction mechanism includes the
preliminary hydration of initial quinoneimines Iа, Ib at
the carbonyl group giving diol А followed by its cycliza-
tion into phenoxazinones IIа, IIb.
Scheme 1.
R2
R2
O
O
OH
HO
OH
O
O
N
N
O
H2SO4
0_5oC
HO
R1
R2
O
Cl
Cl
N
H
R1
R1
O
Cl
IIа, IIb
A
Iа, Ib
R1 = R2 = H (a); R1 = OH, R2 = CH3 (b).
746

CYCLIZATION OF 2-CHLORO-3-(1,4-OXOCYCLOHEXA-2,5-...
747
The mass spectrum of phenoxazinone IIa lacks the
molecular ion, but contains intensive ions of m/z 299
(54.75%) and 297 (100%) that apparently have formed
by dehydration of molecular ions (M+ 315 and 317). The
fragment ions of m/z 269 (31.63%) and 271 (10.21%)
evidently form by decarbonylation of the preceding ions.
At the same time the high resolution mass spectrum con-
tains a peak of the protonated molecular ion [M + Н]+ of
the mass 316.0371 corresponding to the composition of
the obtained product.
Electron absorption spectra of compounds IIа, IIb
also resemble that of phenoxazinone IV: λmax (logε) in
ethanol is 261 (4.51), 411 (4.17) (IIа); 255 (4.39), 390
(4.28) (IV).
The structure of the molecule of 6-chloro-10,12а-dihydroxy-
7Н,12аН-benzo-[c]phenoxazin-5-one (IIа) by XRD data.
We also obtained by the reaction of 2,3-dichloro-1,4-
naphthoquinone (III) with 4-aminobenzene-1,3-diol
phenoxazinone IIa identical by its parameters to that
obtained from quinoneimine Ia, but the yield was small.
The structure of phenoxazinone IIa was proved by
XRD analysis (see the figure).
and interplanar distance 3.5 Å.
Compounds IIа, IIb exist in solution (according to
1Н NMR data) and in solid state in the hemiketal form.
Compound IIа reacts with alcohols in this form, but at
the acetylation with acetic anhydride in pyridine the
phenoxazine ring suffers opening with the formation of
2-(2,4-diacetoxyphenylamino)-3-chloro-1,4-naphthoqui-
none (V) (Scheme 2).
n the 1Н NMR spectrum of ketal VI the methyl group
protons appear as two doublets at 0.49 and 0.67 ppm
with a ratio of integral intensities close to unity. This is
apparently due to the existence of compound VI as two
diastereomers since the carbon atom in the position 12а
is asymmetrical.
The Cambrodge Crystallographic Database [3] has
no compounds with this tetraheterocyclic scaffold. Oxa-
zine ring is present in an envelop conformation with the
deviation of atom C12 from the plane by 0.595 Å. The
conformation of the dienone ring is nearly a flattened
boat with the deviation from the plane of atoms С6 and
С6a by 0.373 and 0.414 Å respectively. The molecules in
the crystal are bound by the hydrogen bonds О2–Н⋯О1
[Н⋯О 1.89(4) A, О–Н⋯О 164(4)°], and О3–Н⋯О2
[1.89(4) Å, 169(4)°] into bands along the (a–c) axis. A
We believe that the presence in the molecules of
compounds IIа, IIb of versatile functional groups opens
opportunities to their further modification.
π-stacking interaction π(С1–4С4аС12а)-π(С7аC8–11С11а
ists between the bands with intercenter distance 3.815(2)
) ex-
Scheme 2.
OAc
O
O
H
N
OAc
(CH3CO)2O
Cl
OH
V
O
HO
H
H3C C CH3
H
C
O
N
H
H3C
CH3
O
O
Cl
HO
OH
IIа
O
N
H
Cl
VI
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

GORNOSTAEV et al.
748
EXPERIMENTAL
Found, %: C 60.40; H 3.46; Cl 11.40; N 4.14. [M + Н]+
316.0371. C16H10СlNO4. Calculated, %: C 60.85; H 3.16;
Cl 11.25; N 4.43. M + Н 316.0371. Crystallographic data:
triclinic crystal system P-1, a 7.5379(6), b 8.6464(8),
c 11.3916(11) Å, α 72.417(3), β 76.542(3), γ 66.240(3)°,
V 642.5(1) Å3, Z 2, dcalc 1.632 g/cm3, μ 0.317 cm–1. The
intensities of 8325 reflections were measured in the range
2θ < 51°, 2338 among them independent (Rint 0.0414).
Refinement parameters: wR2 0.1110, S 1.040 (for all
reflections), R1 0.0399 [1671 I ≥ 2σ(I)].
1Н NMR spectra were registered on a spectrometer
Bruker DRX (500 MHz), solvent DMSO-d6, internal
referenc TMS. The monitoring of the reaction progress
and checking the purity of obtained compounds was
performed by TLC in toluene on Silufol UV-254 plates.
The melting points were measured on a Boёtius heating
microblock. Mass spectra were obtained on an instru-
ment Finnigan MAT-8200 (direct admission, EI, 70 eV),
high resolution mass spectra were recorded on a GC-MS
instrument Bruker micrOTOF equipped with electrospray
ionization and quadrupole mass analyzer using sample
solutions in acetonitrile Electron absorption spectra were
taken on a spectrophotometer Evolution 300 in ethanol
at the layer thickness 1 cm and the sample concentra-
tion 1·10–4 mol l–1. In the study were used commercially
available 2,3-dichloro-1,4-naphthoquinone (Acros) and
4-aminobenzene-1,3-diol hydrochloride (Aldrich).
Authentic synthesis of compound IIa. To 0.45 g
(2 mmol) of 2,3-dichloro-1,4-naphthoquinone (III) in
15mlofdioxanefirst0.24g(1.5mmol)of4-aminobenzene-
1,3-diol hydrochloride, then 0.2 g (1.4 mmol) of potas-
sium carbonate dissolved in 10 ml of water was added,
and the mixture was stirred at 25°C for 20 min. The brown
precipitate was filtered off and chromatographed on silica
gel. Yield 0.12 g (27%).
6-Chloro-4,10,12а-trihydroxy-9-methyl-7Н,12аН-
benzo[c]phenoxazin-5-one (IIb). To 20 ml of 92–95%
sulfuric acid cooled to 0–5°С was added gradually
within 15 min 0.3 g (0.9 mmol) of 2-chloro-3-(3-methyl-
4-oxocyclohexa-2,5-dienylideneamino)-8-hydroxy-1,4-
dihydronaphthalene-1,4-dione (Ib), and the reaction
mixture was stirred for 15 min, poured on ice, the brown
precipitate was filtered off and subjected to column
chromatography on silica gel eluting with a mixture hex-
ane−ethyl acetate, 1 : 1. Yield 0.13 g (43%), mp 297°С.
1Н NMR spectrum, δ, ppm: 2.10 s (3Н, СН3), 6.62 s (1H,
Н11), 6.99 d (1Н, Н1, J 8.2 Hz), 7.20 s (1Н, Н8), 7.44 d
(1Н, Н3, J 7.8 Hz), 7.57 t (1Н, Н2, J 7.8 Hz), 7.96 s (1Н,
ОН12а), 9.50 s (1Н, ОН10), 10.65 s (1Н, NН), 13.15 s
(1Н, OН4). Mass spectrum, m/z (Irel, %): 345 (1.60)
[M]+, 43(100), 36 (85.19), 29 (69.57). Found, %: C 59.29;
H 4.12; Cl 10.11; N 4.02. C17H12СlNO5. Calculated, %:
C 59.04; H 3.47; Cl 10.27; N 4.05.
XRD experiment was carried out on a diffractom-
eter Bruker Kappa APEX II [graphite monochromator
,
λ(MoKα) 0.71073 Å, ω,φ-scanning, 200 K]. The correc-
tion for extinction was performed using SADABS pro-
gram. The structure was solved by the direct method and
refined in the anisotropic approximation for nonhydrogen
atoms. The positions of hydrogen atoms of the OH and
NH groups were determined from the difference synthe-
sis ant were refined in the isotropic approximation. The
other hydrogen atoms were refined in the rider model.
All calculations were carried out applying SHELX-97
software. The data obtained are deposited in Cambrodge
Crystallographic Datab Center (CCDC № 888778).
6-Chloro-10,12а-dihydroxy-7Н,12аН-benzo[c]-
phenoxazin-5-one (IIа). To 20 ml of 92–95% sulfuric
acid cooled to 0–5°С was added gradually within 15 min
2 g (7 mmol) of 2-chloro-3-(1,4-oxocyclohexa-2,5-
dienylideneamino)-1,4-dihydronaphthalene-1,4-dione
(Iа), and the reaction mixture was stirred for 10 min,
poured on ice, the brown precipitate was filtered off and
recrystallized from a mixture DMF–Н2О, 1 : 2. Yield
1.85 g (92%), mp >300°С. EAS, λmax, nm (logε): 261
(4.51), 411 (4.17). 1Н NMR spectrum, δ, ppm: 6.50 d.d
(1H, Н9, J 8.6, 2.5 Hz), 6.60 d (1Н, Н11, J 2.5 Hz), 7.30 d
(1Н, Н8, J 8.6 Hz), 7.60 t (1Н, Н2(3), J 7.5 Hz), 7.73 t (1Н,
Н3(2), J 7.5 Hz), 7.97 d (1Н, Н1, J 6.6 Hz), 7.99 s (1Н,
ОH12а), 8.00 d (1Н, Н4, J 6.6 Hz), 9.45 s (1Н, OН10),
10.35 s (1Н, NН). Mass spectrum, m/z (Irel, %): 299
(54.75), 297 (100), 271 (10.21), 269 (31.63), 63 (30.63).
2-(2,4-Diacetoxyphenylamino)-3-chloro-1,4-naph-
thoquinone (V). To a solution of 0.58 g (1.4 mmol) of
compound IIa in 10 ml of pyridine was added 4 ml of
acetic anhydride, and the reaction mixture was stirred at
25°С for 10 min, poured on ice, the yellow-orange pre-
cipitate was filtered off and recrystallized from toluene.
1
Yield 0.45 g (78%), mp 163°С. Н NMR spectrum, δ,
ppm: 2.00 s (3H, СН3), 2.25 s (3H, СН3), 7.04 d (1Н,
Н5',J 7.0 Hz), 7.07 s (1Н, Н3'), 7.32 d (1Н, Н6', J 7.0 Hz),
7.82 t (1Н, Н7(6), J 8.0 Hz), 7.87 t (1Н, Н6(7), J 8.0 Hz),
8.02 d (1Н, H8(5), J 8.0 Hz), 8.04 br.d (1Н, Н5(8), J 8.0 Hz),
8.90 s (1Н, NН). Mass spectrum, m/z (Irel, %): 399
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

CYCLIZATION OF 2-CHLORO-3-(1,4-OXOCYCLOHEXA-2,5-...
749
(13.01) [M]+, 357 (27.03), 315 (52.55), 280 (56.76), 279
(100), 43 (45.25). Found, %: C 59.62; H 3.51; N 3.52.
C20H14СlNO6. Calculated, %: C 60.07; H 3.50; N 3.50.
(100), 62 (21.92), 32 (47.05). Found, %: C 63.66; H 5.79;
Cl 8.59; N 3.20. C19H16СlNO4. Calculated, %: C 63.77;
H 4.47; Cl 9.93; N 3.91.
6-Chloro-10-hydroxy-12а-isopropoxy-7Н,12аН-
benzo[c]phenoxazine-5-one (VI). In 10 ml of 2-propanol
was dissolved 0.22 г (0.7 mmol) of compound IIa, and
the mixture was stirred at 83–85°С for 40 min. Then
7 ml of water was added dropwise, the reaction mixture
was cooled, the yellow-brown precipitate was filtered off
and subjected to column chromatography on silica gel
eluting with chloroform. Yield 0.19 g (76%), mp 128°С.
1Н NMR spectrum, δ, ppm: 0.49 d (3Н, СН3, J 6.1 Hz),
0.67 d (3Н, СН3, J 6.1 Hz), 4.04 m (1Н, СН), 6.54 d.d
(1H, Н9, J 8.6 Hz), 6.69 d (1Н, Н11, J 2.5 Hz), 7.32 d.
(1Н, Н8, J 8.6 Hz), 7.67 t (1Н, Н2(3), J 7.5 Hz), 7.75 t
(1Н, Н3(2), J 7.5 Hz), 8.03 d (1Н, Н1, J 7.5 Hz), 8.13 d
(1Н, Н4, J 7.5 Hz), 9.55 s (1Н, NН), 10.50 s (1Н, OН).
Mass spectrum, m/z (Irel, %): 299 (7.61), 297 (34.83), 63
ACKNOWLEDGMENTS
The study was carried out under the financial support
of theAstaf’ev Krasnoyarsk State Pedagogical University
(grant no. 01-12-1/NP).
REFERENCES
1. Devyashina, A.E., Gornostaev, L.M. and Gatilov, Yu.V.,
Zh. Org. Khim., 2012, vol. 48, p. 245.
2. Agarwal, N.L. and Shafer, W., J. Org. Chem., 1980, vol. 45,
p. 2155.
3. Allen, F.H., Acta Cryst., 2002, vol. B58, p. 380 (Version,
5.33).
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