Synthesis of 2-aminopentafluoro-1,4-naphthoquinone derivatives

Article abstract of DOI:10.1134/S1070428009060050

Potential biologically active derivatives of 2-aminopentafluoro-1,4- naphthoquinone modified at the amino group were synthesized in 32-96% yield by reactions of hexafluoro-1,4-naphthoquinone with nitrogencentered nucleophiles. Pleiades Publishing, Ltd., 2

Full text of DOI:10.1134/S1070428009060050

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 6, pp. 835–841. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © L.I. Goryunov, N.M. Troshkova, G.A. Nevinskii, V.D. Shteingarts, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45,
No. 6, pp. 851–856.
Synthesis of 2-Aminopentafluoro-1,4-naphthoquinone Derivatives
L. I. Goryunova, N. M. Troshkovaa, G. A. Nevinskiib, and V. D. Shteingartsa, c
a Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: shtein@nioch.nsc.ru
b Institute of Chemical Biology and Fundamental Medicine, Siberian Division, Russian Academy of Sciences,
Novosibirsk, Russia
c Novosibirsk State University, Novosibirsk, Russia
Received May 13, 2008
Abstract—Potential biologically active derivatives of 2-aminopentafluoro-1,4-naphthoquinone modified at the
amino group were synthesized in 32–96% yield by reactions of hexafluoro-1,4-naphthoquinone with nitrogen-
centered nucleophiles.
DOI: 10.1134/S1070428009060050
1,4-Naphthoquinone derivatives exhibit versatile
physiological activity. For example, naturally occur-
ring or synthetic compounds known as vitamins K1–K7
are efficient blood coagulants [1], while mono- and di-
aminonaphthoquinone derivatives display antimalarial
[2] and antitumor activity [3]. Such compounds as
2-(2-hydroxyethylsulfanyl)-3-methyl- and 2,3-bis(2-
hydroxyethylsulfanyl)-1,4-naphthoquinones were also
shown to inhibit growth of tumor cells, and the effect
of their tetrafluoro-substituted analogs Ia and Ib was
even stronger [4, 5].
halogen replacement in chloro- and fluoroanil and
2-chloro- and 2,3-dichloro-1,4-naphthoquinone upon
treatment with amines, alcohols, and other nucleo-
philes [8] have been reported. The above data illustrate
prospects in using such reactions for the synthesis of
potential biologically active polyfluorinated 1,4-naph-
thoquinone derivatives.
In the present communication we report on reac-
tions of fluorinated 1,4-naphthoquinone III with ali-
phatic and aromatic amines with a view to obtain
2-aminopentafluoro-1,4-naphthoquinone derivatives as
potential cell growth inhibitors and starting compounds
for the preparation of polyfunctionalized fluorine-con-
taining 1,4-naphthoquinones. The reactions of quinone
III with primary and secondary amines were per-
formed using 1.1–1.8 equiv of nucleophile, and their
progress was monitored by 19F NMR spectroscopy.
O
O
Me
S
S
S
OH
OH
F
F
OH
O
O
Ia
Ib
tert-Butylamine, 2-methylsulfanylethanamine, and
2-aminoethanol reacted with compound III at room
temperature to give the corresponding 2-(alkylamino)-
pentafluoro-1,4-naphthoquinones IV–VIII (Scheme 1).
In the reaction with ethylamine, 2-ethylaminopenta-
fluoro-1,4-naphthoquinone (IV) was obtained in 97%
yield in 2 h. The reaction mixture obtained from
quinone III and butylamine contained (after 3 h) ~70%
of 2-(butylamino)pentafluoro-1,4-naphthoquinone (V),
~15% of di- and triamino-substituted quinones (as-
sumingly), and ~15% of initial quinone III. The reac-
tion of III with tert-butylamine gave in 2 h ~80% of
Compounds Ia and Ib were synthesized by re-
placement of fluorine atoms in 2-methylpentafluoro-
and hexafluoro-1,4-naphthoquinones II and III by the
action of 2-sulfanylethanol or its tetrahydropyran-2-yl
ether, respectively, in methanol at room temperature
[4, 5]. It was shown previously that fluorine atom in
the quinone fragment is readily replaced by the action
of methylene bases derived from nitrogen-containing
heterocycles (compound III) [6] or sodium methoxide
[2-(heptafluoronaphthalen-1-yloxy)pentafluoro-1,4-
naphthoquinone (IIa)] [7]. Numerous examples of
835

GORYUNOV et al.
836
Scheme 1.
O
O
O
F
F
NR1R2
R1R2NH, dioxane, 20°C
–HF
F
F
F
O
III
IV–XIII
IV–IX, R1 = H; IV, R2 = Et; V, R2 = Bu; VI, R2 = t-Bu; VII, R2 = MeSCH2CH2; VIII, R2 = HOCH2CH2; IX, R2 = Ph;
X, R1 = R2 = Et; XI, R1R2N = morpholino; XII, R1 = Me, R2 = HOCH2CH2; XIII, R1 = R2 = HOCH2CH2.
2-(tert-butylamino)pentafluoro-1,4-naphthoquinone
(VI) and ~20% of quinone III. The fraction of com-
pound VI did not increase when the reaction time was
extended to 24 h, but in this case the reaction mixture
contained (in addition to initial quinone III) ~10% of
products resulting from subsequent transformations of
quinone VI. Compounds V and VI were isolated by
preparative thin-layer chromatography in 63 and 62%
yield, respectively.
Obviously, reactions of III with difunctional nucle-
ophiles, such as 2-aminoethanol, 2-methylaminoetha-
nol, and 2,2′-iminodiethanol, could follow two concur-
rent pathways leading to the formation of both amino-
and hydroxydefluorination products. To confirm the
structure of the isolated compounds, quinone III was
subjected to methanolysis which afforded 65% of
2-methoxypentafluoro-1,4-naphthoquinone (XIV)
(Scheme 2).
The reaction of quinone III with 2-methylsulfanyl-
ethanamine (2 h) gave 94% of 2-[2-(methylsulfanyl)-
ethylamino]pentafluoro-1,4-naphthoquinone (VII). In
the reaction with 2-aminoethanol, 2-(2-hydroxyethyl-
amino)pentafluoro-1,4-naphthoquinone (VIII) was
smoothly formed in 89% yield in 3 h. Quinone III
reacted with aniline at 20°C to give in 15 h 2-(phenyl-
amino)pentafluoro-1,4-naphthoquinone (IX, ~90%)
and products of its further transformations (~10%).
Compound IX was isolated in 62% yield by thin-layer
chromatography.
Scheme 2.
O
MeOH, K2CO3
dioxane, 20°C
OMe
F
F
III
O
XIV
The chemical shift of 3-F (δF 17.5 ppm) in the
19F NMR spectrum of XIV considerably differed from
those observed in the spectra of 2-amino derivatives
VIII, XII, and XIII (δF –0.01 to 6.8 ppm; see table).
Moreover, the latter values approach the chemical
shifts of 3-F for quinones IV, V, VII, and XV obtained
from primary amines. An exception is compound VI
having a relatively large tert-butylamino group
(δF 16.5 ppm). The structure of VIII was confirmed by
Likewise, quinone III readily reacted with second-
ary amines. 2-Diethylaminopentafluoro-1,4-naphtho-
quinone (X) was obtained in 96% yield by reaction of
III with 1.5 equiv of diethylamine (reaction time 2 h).
Analogous reaction with morpholine at a ratio of 1:1.5
(2 h) led to the formation of 2-morpholinopentafluoro-
1,4-naphthoquinone (XI) whose concentration in the
reaction mixture was ~70% (preparative yield 59%);
the reaction mixture also contained ~30% of products
resulting from its further transformations. 2-[2-Hy-
droxyethyl(methyl)amino]pentafluoro-1,4-naphtho-
quinone (XII) was isolated in 87% yield from the
product mixture obtained by reaction of quinone III
with 1.8 equiv of 2-methylaminoethanol (2.5 h). In the
reaction of III with 2,2′-iminodiethanol (reactant ratio
1:1.5), 2-[bis(2-hydroxyethyl)amino]pentafluoro-1,4-
naphthoquinone (XIII) was formed; after 3.5 h, its
concentration was ~70% (yield 32%); also, ~15% of
the initial quinone and some other products were pres-
ent in the reaction mixture.
1
the H NMR spectrum which contained signals from
both NH and OH protons. In the 1H NMR spectrum of
XII, the NCH3 signal was split due to coupling with
the fluorine atom in position 3 (JHF = 4.8 Hz); anal-
ogous coupling was also observed for the methoxy
protons in the spectrum of XIV (JHF = 5.0 Hz). Like-
wise, quinone XIII was assigned the structure corre-
sponding to replacement of fluorine by the nucleophil-
ic nitrogen center. We can conclude that aminoetha-
nols act as just N-centered nucleophiles in reactions
with quinone III. This conclusion is consistent with
the results of the reaction of hexafluorobenzene with
2-aminoethanol, reported in [9].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 6 2009

SYNTHESIS OF 2-AMINOPENTAFLUORO-1,4-NAPHTHOQUINONE DERIVATIVES
1H and 19NMR spectra of polyfluoro-1,4-naphthoquinone derivatives in CDCl3
837
19F NMR spectrum, δF, ppm (J, Hz)
Comp.
no.
1H NMR spectrum, δ, ppm (J, Hz)
2-F, 3-F
48.7
5-F, 8-F
25.0, 25.8
6-F, 7-F
II
2.50 d (3H, CH3, J = 3.6)
19.3, 18.1
17.7
IIa
IIb
IIc
IId
III
IV
27.6
25.0
6.70 d (1H, J = 9.7)
51.0
24.0, 25.0
25.9
18.0, 16.5
18.5
4.2
36.9
22.1
25.8
18.8
25.5
18.6
5.39 br.s (1H, NH), 3.58 m (2H, CH2), 1.29 d.t
05.3 br.s 24.2 d.d.d, 25.8 d.t
19.8 d.d.t (J = 4.1), 15.1 d.t
(3H, CH3, J = 7.2, 0.9)
J5,6, J6,7, J7,8 = 19.7–19.8; J5,7, J5,8, J6,8 = 10.1–12.1
V
5.44 br.s (1H, NH), 3.51 d.d.t (2H, CH2, J =
3.3, 7.0, 6.6), 1.60 m (2H, CH2), 1.38 m (2H,
CH2), 0.93 t (3H, CH3, J = 7.2)
05.8 br.s 24.2 d.d.d, 25.8 d.t
19.8 d.d.t (J = 4.5), 15.0 d.t
J5,6, J6,7, J7,8 = 19.4–20.1; J5,7, J5,8, J6,8 = 10.8–12.7
VI
5.74 br.s (1H, NH), 1.43 s (9H, t-Bu)
16.5 br.c 24.2 d.d.d (J = 2.0), 19.8 d.d.t (J = 4.5), 15.1 d.t
26.0 d.t
J5,6, J6,7, J7,8 = 19.4–19.8; J5,7, J5,8, J6,8 = 10.1–12.3
VII
5.80 br.s (1H, NH), 3.73 d.d.t (2H, CH2, J =
2.6, 6.4, 6.6), 2.76 t (2H, SCH2, J = 6.6),
2.13 s (3H, CH3)
06.7 br.s 24.4 d.t, 26.1 d.t
19.9 d.d.t (J 4.4), 15.4 d.t
J5,6, J6,7, J7,8 = 19.6; J5,7, J5,8, J6,8 = 9.8–12.0
VIII 5.80 br.s (1H, NH), 3.87 t (2H, CH2, J = 4.9),
06.8 br.s 24.3 d.t, 26.0 d.t
19.8 d.d.t (J = 4.2), 15.4 d.t
3.70 m (2H, CH2), 3.68 s (1H, OH)
J5,6, J6,7, J7,8 = 19.3–19.7; J5,7, J5,8, J6,8 = 10.4–12.1
IX
X
7.34–7.42 m (2H, CH), 7.20–7.27 m (1H, CH),
7.09–7.17 m (2H, CH)
28.1 br.s 24.9 d.t, 26.6 d.t
20.2 d.d.t (J = 4.5), 16.3 d.t
J5,6, J6,7, J7,8 = 19.2–20.1; J5,7, J5,8, J6,8 = 10.8–12.7
3.45 d.q (4H, CH2, J = 1.9, 7.0), 1.26 d.t (6H,
CH3, J = 0.6, 7.0)
18.7 br.s 22.7 d.d.d,
22.9 d.d.d
17.4 d.d.t (J 3.8), 15.1 d.t
J5,6, J6,7, J7,8 = 18.7–19.7; J5,7, J6,8 = 9.3–10.7
XI
3.85 t (4H, CH2, J = 4.7), 3.56 m (4H, CH2)
23.5 br.s 23.9 m (2F)
–1.38 q 20.8 d.d.d,
(J = 4.8) 23.1 d.d.d
J5,6, J6,7, J7,8 = 19.2–20.1; J5,7, J5,8, J6,8 = 4.8–13.3
18.3 m, 16.4 m
XII
4.34 d.t (1H, CH2, J = 3.7, 9.7), 4.22 br.s (1H,
OH), 3.97–4.17 m (2H, CH2), 3.32 d (3H,
CH3, J = 4.8), 3.16 d.t (1H, CH2, J = 3.7, 11.9)
13.4 d.t, 8.6 d.t
XIIIa 3.40–4.35 m
–0.01 s
19.9 d.d.d, 26.6
d.d.d
11.9 d.t, 7.3 d.t
J5,6, J6,7, J7,8 = 19.9–20.1; J5,7, J5,8, J6,8 = 4.5–13.3
25.3 d.t, 25.9 d.t 19.2 d.d.t (J = 3.9), 18.4 d.t
J5,6, J6,7, J7,8 = 19.4–19.8; J5,7, J5,8, J6,8 = 11.3–12.2
21.2 d.d.d, 23.4 d.t 17.4 d.d.t (J = 4.4), 13.6 d.t
J5,6, J6,7, J7,8 = 20.7; J5,7, J5,8, J6,8 = 8.9–11.7
20.4 d.d.d, 21.9 d.t 16.5 d.t, 11.4 d.t
J5,6, J6,7, J7,8 = 18.7–19.3; J5,7, J5,8, J6,8 = 8.3–12.8
XIV 4.30 d (3H, CH3, J = 4.9)
17.5 m
04.22 s
XVb 7.30 br.s (1H, NH), 3.70 m (2H, CH2N), 2.90 t
(2H, CH2S, J = 6.7)
XVIb 8.80 d.m, 8.60 t.t (J = 10.3, 55.2), 8.20 m
a
In acetone-d6.
In DMSO-d6.
b
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 6 2009

GORYUNOV et al.
838
1
In the H NMR spectra of quinones XII and XIII,
signals from the methylene protons (obviously, this
applies to only one CH2CH2 fragment in XIII) give
rise to a more complex pattern, as compared to qui-
none VIII, indicating nonequivalence of protons in
each methylene group. By analogy with the data for
2-[bis(2-hydroxyethyl)amino]- and 2-[2-hydroxyethyl-
(methyl)amino]-1,4-benzoquinones [10−12], the ob-
served pattern may be interpreted in terms of ring–
chain tautomerism, i.e., formation of closed structures
XIIa and XIIIa.
converted into 2-chloro-3-phenylamino-1,4-naphtho-
quinone upon irradiation of its alcoholic solution with
sunlight [13].
All newly synthesized compounds were charac-
1
terized by H and 19F NMR spectra (see table) and
high-resolution mass spectra or elemental analyses.
The 19F NMR parameters of quinones IV–XIII were
very consistent with published data for compounds II
[14], III, IIa [7], 2,5,6,7,8-pentafluoro-1,4-naphtho-
quinone (IIb) [15], 2-(heptafluoronaphthalen-1-yloxy)-
3-methoxytetrafluoro-1,4-naphthoquinone (IIc), and
2-(pentafluorobenzoyloxy)pentafluoro-1,4-naphtho-
quinone (IId) [7]. Fluorine nuclei in the quinone
fragment (2-F or 3-F) resonated as slightly broadened
singlets or multiplets, obviously due to weak spin–spin
couplings with fluorine nuclei in the benzene ring.
Signals from the latter appear in the 19F NMR spectra
as multiplets in the regions δF 24–27 ppm (5-F, 8-F)
and 15–20 ppm (6-F, 7-F).
O
HO
N
R
F
F
O
XIIa, XIIIa
XII, R = Me; XIII, R = HOCH2CH2.
Quinone III reacted with 2,2′-dithiodiethanamine
to give N,N′-bis(3,5,6,7,8-pentafluoro-1,4-dioxo-1,4-
dihydronaphthalen-2-yl)-2,2′-dithiodiethanamine (XV)
in 75% yield (Scheme 3). The H NMR spectrum of
disulfide XV contained signals from protons in the NH
We found that crystalline quinone X underwent
deethylation to give compound IV upon prolonged
storage (for several months) in a vessel made of color-
less glass. Presumably, this transformation occurs with
participation of atmospheric moisture. When quinone
X was kept for 4 weeks in dioxane containing a few
drops of water on exposure to daylight, it was com-
pletely converted into a mixture of solvolysis products,
from which we isolated 39% of quinone IV. No trans-
formation was observed in the dark. Analogous de-
ethylation was reported previously for 3-chloro-2-
[ethyl(phenyl)amino]-1,4-naphthoquinone which was
1
and CH2 groups.
The reaction of III with pyridine in moist metha-
nol is likely to begin with replacement of fluorine in
position 2 to produce pyridinium salt A. The presence
of a positively charged group in position 2 activates
the neighboring position of the quinoid ring to nucleo-
philic attack, and the 3-fluorine atom in A is rapidly
replaced by methoxy or hydroxy group (due to the
Scheme 3.
O
O
F
H
(H2NCH2CH2S)2
dioxane, 20°C
N
F
S
S
2III
F
N
H
F
O
O
XV
Scheme 4.
O
O
O
O
O
N
F
N
N
MeOH, 20°C
ROH
–HF
III
+
F
F
F
F–
F–
–RF
N
OR
O–
O
A
B
XVI
R = H, Me.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 6 2009

SYNTHESIS OF 2-AMINOPENTAFLUORO-1,4-NAPHTHOQUINONE DERIVATIVES
839
presence of water in the solvent) with formation of
quinone B. The final product is zwitterionic 1,4-dioxo-
3-pyridinio-1,4-dihydronaphthalen-2-olate (XVI, yield
90%; Scheme 4). The 19F NMR spectrum of XVI
contained signals from the fluorine atoms on C5–C8
with equal intensities, and signals from protons in the
(1.675 mmol) of potassium hydroxide, and 2 ml of
dioxane was stirred for 30 min at room temperature.
The precipitate was separated by centrifugation,
0.101 g (0.379 mmol) of quinone III was added to the
solution, and the mixture was stirred for 2 h at 20°C,
and diluted with 10 ml of water. The precipitate was
separated by centrifugation and washed with water.
Yield 0.106 g (97%); after vacuum sublimation
(150°C, 0.03 mm), yield 0.095 g (88%), dark red
crystals, mp 184–185°C. Found, %: C 49.23; H 1.85;
N 4.86. C12H6F5NO2. Calculated, %: C 49.5; H 2.08;
N 4.81.
1
pyridinium fragment were observed in its H NMR
spectrum.
Thus the results of the present study demonstrate
that reactions of quinone III with amines ensure fairly
selective replacement of one fluorine atom in the
quinoid ring by amino group (obviously, due to de-
activating effect of the entering amino group). The
resulting 2-aminopentafluoro-1,4-naphthoquinone
derivatives attract interest from the viewpoint of their
subsequent modifications at the amino group to obtain
new potential biologically active compounds.
2-Butylamino-3,5,6,7,8-pentafluoro-1,4-dihydro-
naphthalene-1,4-dione (V). A mixture of 0.200 g
(0.751 mmol) of quinone III, 0.099 g (1.354 mmol) of
butylamine, and 2 ml of dioxane was stirred for 3 h at
20°C. The mixture was diluted with 10 ml of water,
and the precipitate was separated by centrifugation,
washed with water (2×3 ml), and purified by prepara-
tive thin-layer chromatography on silica gel using
chloroform–hexane (3:1) as eluent. Yield 0.15 g
(63%), bright red crystals, mp 135–137°C. Found:
m/z 319.0618 [M]+. C14H10F5NO2. Calculated:
M 319.06316.
EXPERIMENTAL
1
The H and 19F NMR spectra were recorded on
1
Bruker WP-200SY (200.13 MHz for H and
188.28 MHz for 19F) and Bruker AV-300 spectrometers
1
(300.13 MHz for H and 282 MHz for 19F); the
chemical shifts were measured relative to CD3COCD3
(δ 2.04 ppm), CDCl3 (δ 7.24 ppm), and C6F6
(δF 0.0 ppm) as internal references. The molecular
weights were determined from the high-resolution
mass spectra which were obtained on a Finnigan MAT-
8200 instrument.
2-tert-Butylamino-3,5,6,7,8-pentafluoro-1,4-dihy-
dronaphthalene-1,4-dione (VI). An NMR ampule
was charged with 0.175 g (0.657 mmol) of quinone III
and cooled with liquid nitrogen, and 1.5 ml of dioxane
and 0.086 g (1.17 mmol) of tert-butylamine were con-
densed thereto under reduced pressure (0.03 mm). The
ampule was sealed, kept for 24 h at 20°C, and opened,
the mixture was poured into ~6 ml of water, and the
precipitate was separated by centrifugation, evacuated
for 2 h at a residual pressure of 0.03 mm at 20°C, and
purified by thin-layer chromatography on Silufol using
chloroform–hexane (3:1) as eluent. Yield 0.128 g
(62%), orange crystals, mp 186–190°C. Found:
m/z 319.06247 [M]+. C14H10F5NO2. Calculated:
M 319.06316.
1,4-Dioxane was distilled under reduced pressure
(0.1 mm) and stored over 3-Å molecular sieves. Meth-
anol was distilled under reduced pressure (0.03 mm)
and stored over 3-Å molecular sieves. Diethylamine,
aniline, morpholine, tert-butylamine, and 2,2′-iminodi-
ethanol of chemically pure grade were purified by
vacuum distillation (0.03 mm). Butylamine (99.5%,
Acros Organics), 2-methylaminoethanol (99%, Riedel-
deHaen), and 2-(methylsulfanyl)ethanamine (95%,
Maybridge) were used without additional purification.
Pyridine of chemically pure grade was distilled under
reduced pressure (0.03 mm) and stored over 3-Å mo-
lecular sieves. Hexafluoro-1,4-naphthoquinone III was
synthesized according to the procedure reported in
[16]; 2,2′-Dithiodiethanamine was prepared as de-
scribed in [17] and was isolated as the corresponding
dihydrochloride according to [18].
2,5,6,7,8-Pentafluoro-3-[2-(methylsulfanyl)-
ethylamino]-1,4-dihydronaphthalene-1,4-dione
(VII) was synthesized as described above for quinone
V from 0.100 g (0.376 mmol) of quinone III and
0.051 g (0.559 mmol) of 2-(methylsulfanyl)ethan-
amine in 1.5 ml of dioxane (20°C, 2 h). Yield 0.119 g
(94%), dark red crystals, mp 136–139°C. Found, %:
C 46.41; H 2.52; F 28.15; N 4.13. C13H8F5NO2S. Cal-
culated, %: C 46.3; H 2.39; F 28.16; N 4.15.
2-Ethylamino-3,5,6,7,8-pentafluoro-1,4-dihydro-
naphthalene-1,4-dione (IV). A mixture of 0.070 g
(0.556 mmol) of ethylamine hydrobromide, 0.094 g
2-(2-Hydroxyethylamino)-3,5,6,7,8-pentafluoro-
1,4-dihydronaphthalene-1,4-dione (VIII). A mixture
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 6 2009

GORYUNOV et al.
840
of 0.200 g (0.751 mmol) of quinone III and 0.069 g
(1.127 mmol) of 2-aminoethanol in 2 ml of dioxane
was stirred for 3 h at 20°C. The red precipitate was
separated by centrifugation and washed with water.
Yield 0.204 g (89%), dark red crystals, mp 159–160°C.
Found, %: C 47.24; H 2.08; N 4.59. C12H6F5NO3. Cal-
culated, %: C 46.92; H 1.97; N 4.56.
0.059 g (0.56 mmol) of 2,2′-iminodiethanol, and 1.5 ml
of dioxane was stirred for 3.5 h at room temperature.
The solvent was distilled off under reduced pressure
(0.03 mm), the residue was dissolved in acetone, and
the product was precipitated with hexane–diethyl ether
(4:1), separated by centrifugation, and purified by
TLC using acetone–hexane (1:1) as eluent. Yield
0.042 g (32%), yellow–brown crystals, mp 147–
150°C. Found: m/z 351.05165 [M]+. C14H10F5NO4.
Calculated: M 351.05299.
2,5,6,7,8-Pentafluoro-3-phenylamino-1,4-dihy-
dronaphthalene-1,4-dione (IX) was synthesized as
described above for compound V from 0.174 g
(0.653 mmol) of quinone III and 0.067 g (0.719 mmol)
of aniline in 1.5 ml of dioxane (20°C, 15 h). The prod-
uct was purified by TLC on Silufol using chloroform–
carbon tetrachloride (1:1) as eluent. Yield 0.136 g
(62%), red–brown crystals, mp 211–212°C. Found:
m/z 339.03150 [M]+. C16H6F5NO2. Calculated:
M 339.03186.
2-Methoxy-3,5,6,7,8-pentafluoro-1,4-dihydro-
naphthalene-1,4-dione (XIV). A reactor was charged
with 0.026 g (0.188 mmol) of potassium carbonate and
0.050 g (0.188 mmol) of quinone III, the reactor was
cooled with liquid nitrogen, 1.5 ml of dioxane was
condensed thereto under reduced pressure (0.03 mm),
and 0.018 g (0.53 mmol) of methanol was then added
under argon. The progress of the reaction was moni-
tored by 19F NMR spectroscopy. After 9 days, the mix-
ture was diluted with ~5 ml of water. The precipitate
was separated by centrifugation, washed with water
(3×3 ml), and dissolved in 1 ml of methanol on heat-
ing. After cooling, the yellow crystalline solid was
separated by centrifugation. Yield 0.034 g (65%),
mp 189–191°C. Found, %: C 47.64; H 0.76.
C11H3F5O3. Calculated, %: C 47.5; H 1.09.
2-Diethylamino-3,5,6,7,8-pentafluoro-1,4-dihy-
dronaphthalene-1,4-dione (X) was synthesized as
described above for compound V from 0.174 g
(0.653 mmol) of quinone III and 0.071 g (0.971 mmol)
of diethylamine in 1.5 ml of dioxane under argon
(20°C, 2 h). The product was precipitated with water.
Yield 0.2 g (96%), dark red crystals, mp 90–92°C.
Found: m/z 319.06220 [M]+. C14H10F5NO2. Calculated:
M 319.06316.
N,N′-Bis(3,5,6,7,8-pentafluoro-1,4-dihydro-1,4-
dioxonaphthalen-2-yl)-2,2′-dithiodiethanamine
(XV). A mixture of 0.050 g (0.188 mmol) of quinone
III, 0.021 g (0.093 mmol) of 2,2′-dithiodiethanamine
dihydrochloride, 0.019 g (0.188 mmol) of triethyl-
amine, and 1.5 ml of dioxane was stirred for 2 h at
20°C and was then left overnight. The red precipitate
was separated by centrifugation, washed with 2 ml of
dioxane and 5 ml of water, and evacuated for 2 h at
a residual pressure of 0.03 mm at 20°C. Yield 0.045 g
(75%), mp 230–235°C. Found; m/z 643.9919 [M]+.
C24H10F10N2O4S2. Calculated: M 643.9922.
2,5,6,7,8-Pentafluoro-3-morpholino-1,4-dihydro-
naphthalene-1,4-dione (XI) was synthesized as
described above for compound V from 0.175 g
(0.658 mmol) of quinone III and 0.085 g (0.975 mmol)
of morpholine in 1.5 ml of dioxane (20°C, 2 h). The
product was purified by TLC on a Sorbfil plate using
chloroform as eluent. Yield 0.112 g (52%), dark red
crystals, mp 158–161°C. Found: m/z 333.0422 [M]+.
C14H8F5NO3. Calculated: M 333.04242.
2,5,6,7,8-Pentafluoro-2-[2-hydroxyethyl(methyl)-
amino]-1,4-dihydronaphthalene-1,4-dione (XII).
2-methylaminoethanol, 0.102 g (1.353 mmol), was
added to a suspension of 0.200 g (0.751 mmol) of
compound III in 2 ml of dioxane, and the mixture was
stirred for 2.5 h at room temperature. The mixture was
diluted with ~8 ml of water, and the precipitate was
separated by centrifugation, washed with water (2×
2 ml), and evacuated for 2 h at a residual pressure of
0.03 mm (20°C). Yield 0.21 g (87%), yellow–brown
crystals, mp 146–147°C. Found: m/z 321.04168 [M]+.
C13H8F5NO3. Calculated: M 321.04242.
1,4-Dioxo-3-pyridinio-1,4-dihydronaphthalen-2-
olate (XVI). Pyridine, 0.590 g (7.459 mmol), was add-
ed under argon to a solution of 0.200 g (0.751 mmol)
of quinone III in 3 ml of methanol, and the mixture
was stirred for 1 h at room temperature. The precipitate
was separated by centrifugation and washed with
methanol (3×2 ml). Yield 0.22 g (90%), orange crys-
tals, mp 317–319°C. Found, %: C 55.59; H 1.55;
F 23.51; N 4.29. C15H5F4NO3. Calculated, %: C 55.74;
H 1.56; F 23.51; N 4.33.
2-[Bis(2-hydroxyethyl)amino]-3,5,6,7,8-penta-
fluoro-1,4-dihydronaphthalene-1,4-dione (XIII).
A mixture of 0.100 g (0.376 mmol) of quinone III,
Deethylation of quinone (X). An NMR ampule
was charged with a solution of 0.014 g (0.043 mmol)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 6 2009

SYNTHESIS OF 2-AMINOPENTAFLUORO-1,4-NAPHTHOQUINONE DERIVATIVES
841
7. Kobrina, L.S., Vlasova, L.V., and Yakobson, G.G.,
Zh. Org. Khim., 1971, vol. 7, p. 555.
8. Finley, K.T., The Chemistry of the Quinonoid Com-
pounds, Patai, S., Ed., London: Wiley, 1974, vol. 2.
9. Burdon, J., Damodaran, V.A., and Tatlow, J.C., J. Chem.
Soc., 1964, p. 763.
10. Day, J.H. and Joachim, A., J. Org. Chem., 1965, vol. 30,
p. 4107.
11. Berg, H. and Zuman, P., J. Chem. Soc., Perkin Trans. 2,
2000, p. 1459.
12. Jancke, H., Radeglia, R., Tresselt, D., and Berg, H.,
Z. Chem., 1977, vol. 17, p. 105.
13. Vladimirtsev, I.F., Postovskii, I.Ya., and Trefilova, L.F.,
Zh. Obshch. Khim., 1954, vol. 24, p. 181.
14. Shtark, A.A., Shteingarts, V.D., and Maidanyuk, A.G.,
Izv. Sibirsk. Otd. Akad. Nauk SSSR, Ser. Khim. Nauk,
1974, vol. 6, p. 117.
of naphthoquinone X in 0.5 ml of dioxane, one drop
of water was added, and the mixture was kept for
23 days, the progress of the reaction being monitored
by 19F NMR spectroscopy. The mixture was then
diluted with ~3 ml of water, and the precipitate was
separated by centrifugation and purified by TLC on
a Sorbfil plate using chloroform–hexane (1 :1) as
eluent. Yield of quinone IV 0.005 g (39%).
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