Synthesis of fluorine-containing poly(phenylamino)-1,4-naphthoquinones

Full text of DOI:10.1134/S1070428010100271

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 10, pp. 1585–1587. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © N.M. Troshkova, L.I. Goryunov, V.D. Shteingarts, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 10,
pp. 1578–1580.
SHORT
COMMUNICATIONS
Synthesis of Fluorine-Containing Poly(phenylamino)-
1,4-naphthoquinones
N. M. Troshkovaa, L. I. Goryunova, and V. D. Shteingartsa, b
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 Novosibirsk State University, Novosibirsk, Russia
Received January 12, 2010
DOI: 10.1134/S1070428010100271
2-X-Substituted pentafluoro-1,4-naphthoquinones
(X = BuNH, Et2N, MeO) are readily converted into the
corresponding di- and polysubstituted quinones via nu-
cleophilic replacement of fluorine by the action of ali-
phatic amines R1R2NH (R1R2N = BuNH, EtNH, Et2N)
[1]. When X = BuNH or Et2N, nucleophilic attack is
directed at the aromatic ring to give products of re-
placement of one to three fluorine atoms in that ring.
On the other hand, 2-methoxypentafluoro-1,4-naphtho-
quinone reacts with butylamine to give products of
fluorine replacement in both aromatic and quinone
rings. Thus the regioselectivity of these reactions de-
pends on the nature of substituent in position 2 of the
substrate. The solvent nature is also important: the
ratio of β- and α-substituted products changes toward
the latter as the solvent polarity decreases; obviously,
the reason is stabilization of transition state for α-sub-
stitution via intramolecular hydrogen bonding [1]. In
the present work we made an attempt to elucidate
whether analogous relations are inherent to reactions
of polyfluorinated 1,4-naphthoquinones with aromatic
amines. For this purpose, we examined nucleophilic
substitution of fluorine in 2-phenylaminopentafluoro-
1,4-naphthoquinone (I) which is the primary product
of the reaction of perfluoro-1,4-naphthoquinone with
aniline [1]. As solvents we selected dioxane, toluene,
and dimethyl sulfoxide (DMSO).
(II), and ~7, 50, and 60% of 3,6,7-trifluoro-2,5,8-tris-
(phenylamino)-1,4-naphthoquinone (III). After 30 h,
the fraction of quinone III attained 90%, and it was
isolated in 81% yield. The fact that quinone II which is
an obvious precursor of III does not accumulate in the
reaction mixture during the process (its fraction does
not exceed 10%) indicates that the former is more
reactive toward aniline than quinone I. The reason is
the lack of effective conjugation in molecule II be-
tween the nitrogen atom in the 8-phenylamino group
(which is forced out from the benzene ring plane) and
reaction center (C5–F). Analogous explanation was
proposed for change of meta orientation in the de-
fluorination of pentafluoroaniline to para in going to
N-phenylpentafluoroaniline [2].
Unlike previously reported [1] reaction of 2-X-pen-
tafluoro-1,4-naphthoquinones (X = BuNH, Et2N) with
alkylamines in dioxane, nucleophilic substitution of
fluorine atom in quinone I occurs mainly at the α-posi-
tion of the benzene fragment. Therefore, stabilization
of transition state in the substitution reaction with
aniline (which is a stronger NH acid than alkylamines)
may be contributed to an appreciable extent by coor-
dination of hydrogen atom of the amino group to
oxygen.
Quinone II was obtained in a poor yield when the
reaction was carried out in toluene. The major product
in DMSO was 3,5,7,8-tetrafluoro-2,6-bis(phenyl-
amino)-1,4-naphthoquinone (IV). Presumably, in this
case stabilization of transition state for α-substitution
via intramolecular hydrogen bonding is weak due to
higher polarity of DMSO as compared to dioxane (cf.
The reaction of quinone I with aniline at a molar
ratio of 1:3 in dioxane at 100°C afforded in 3, 9, and
18 h mixtures containing, respectively, ~70, 25, and
17% of unreacted quinone I, ~10, 9, and 7% of 3,5,6,7-
tetrafluoro-2,8-bis(phenylamino)-1,4-naphthoquinone
1585

TROSHKOVA et al.
1586
O
O
PhNH
O
PhNH
F
O
PhNH2
dioxane, 100°C, 30 h
toluene, 20°C, 20 days
NHPh
F
NHPh
F
NHPh
F
PhNH2, dioxane
F
F
O
PhNH
O
I
II, 13%
III, 81%
PhNH
O
O
NHPh
NHPh
PhNH2, DMSO, 100°C, 8 h
F
PhNH
V, 31%
O
NHPh
F
PhNH2, DMSO, 20°C, 24 h
I
F
PhNH
O
IV, 67%
the data reported in [1] for double defluorination of
quinone I).
II also contained three signals with equal intensities at
δF 15.5, 17.4, and 32.5 ppm. The first of these (6-F)
appeared as a triplet of multiplets with ЈFF ≈ 18 Hz due
to similarity of two coupling constants ЈF, o-F, while the
second (d.d) and third signals (d.d.m due to neighbor-
hood of amino group [1]) were characterized each by
The reaction of quinone III with aniline in DMSO
resulted in replacement of the fluorine atom in the
quinone ring with formation of 6,7-difluoro-2,3,5,8-
tetrakis(phenylamino)-1,4-naphthoquinone (V, yield
31%, conversion 55%). In contrast, the reaction of
2,5,8-tris(butylamino)-3,6,7-trifluoro-1,4-naphtho-
quinone (IIIa) with butylamine gave 2,5,6,8-tetrakis-
(butylamino)-3,7-difluoro-1,4-naphthoquinone as
a result of fluorine replacement in the aromatic ring
[1]. Presumably, the observed change of the relative
reactivity of the benzene and quinoid fragments is
related to sharp weakening of electron-donating effect
of the RNH substituent in going from quinone IIIa
(R = Bu) to II (R = Ph), though replacement of
fluorine at the quinoid double C=C bond is likely to be
more sensitive to the neighboring substituent as com-
pared to the replacement in the benzene ring.
one coupling with ЈF, o-F = 19.4 and 17.3 Hz and ЈF, m-F
≈
9 Hz and were assigned to 5-F and 7-F, respectively.
Signals with equal intensities at δF 23.4, 25.7, and
36.5 ppm in the 19F NMR spectrum of quinone IV
belong to 8-F, 7-F, and 5-F, respectively, taking into
account doublet splittings with ЈF, o-F ≈ 18, ЈF,p-F
≈
10.5 Hz and ЈF, m-F ≈ 12, ЈF, p-F ≈ 10.5 Hz for the first
and third signals and with ЈF, o-F ≈ ЈF, m-F ≈ 16 Hz for the
second signal. Two signals with equal intensities at
δF 30.2 and 34.7 ppm in the spectrum of III were
assigned to 7-F and 6-F, for their δF values are close to
the chemical shifts calculated using PhNH increments
(ΔδF values corresponding to replacement of 8-F in
quinone I by PhNH group). Symmetric quinone V
showed only one signal in the 19F NMR spectrum. In
The structure of newly synthesized compounds
II–V was determined on the basis of their 19F and
1H NMR and high-resolution mass spectra. Signals in
the 19F NMR spectra were assigned by analogy with
the corresponding fluorinated butylamino-1,4-naphtho-
quinones [1]. Quinones II–IV displayed in the
19F NMR spectra multiplets in the region δF 27.2–
28.3 ppm, which were assigned to the 3-F atom; the
3-F signal in the spectrum of initial quinone I is
located at δF 28.1 ppm [3]. The 19F NMR spectrum of
1
the H NMR spectra of quinones II, III, and V NH
protons in the α-positions resonated in the region
δ 10.5–11.5 ppm, whereas signals from β-NH protons
in quinones II–V, as well as in the quinoid fragment
of I [3], appeared in a stronger field, at δ 7.0–7.5 ppm,
as in the spectra of structurally similar fluorinated
butylamino-1,4-naphthoquinones [1]. Signals from
protons in the phenyl rings were located as a rule in the
region δ 7.0–7.5 ppm. An exception was compound V.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010

SYNTHESIS OF FLUORINE-CONTAINING POLY(PHENYLAMINO)-...
1587
Aromatic protons in the PhNH group in the quinoid
fragment of V resonated in the region δ 6.3–7.0 ppm
(as in aniline [4]), obviously due to rupture of conjuga-
tion between the nitrogen atom and quinoid ring as
a result of steric interactions.
10.5 Hz), 25.7 t (1F, 7-F, J5,7 ≈ J7,8 ≈ 16 Hz), 23.4 d.d
(1F, 8-F, J7, 8 = 17.9, J5, 8 ≈ 10.5 Hz). Found:
m/z 412.0825 [M]+. C22H12F4N2O2. Calculated:
M 412.0829.
6,7-Difluoro-2,3,5,8-tetrakis(phenylamino)-1,4-
naphthoquinone (V). A mixture of 0.021 g
(0.04 mmol) of quinone III, 0.008 g (0.09 mmol) of
aniline, and 0.7 ml of DMSO was heated for 8 h at
100°C. Water, ~3 ml, was added, and the precipitate
was separated by centrifugation, washed with water
(3×3 ml), and dried under reduced pressure (0.03 mm).
Compound V was isolated by thin-layer chromatog-
raphy using chloroform–hexane (3:1) as eluent. Yield
0.0074 g (31%; 56% with account taken of the recov-
ery of quinone III, 0.0095 g, 45%), blue crystals,
3,5,6,7-Tetrafluoro-2,8-bis(phenylamino)-1,4-
naphthoquinone (II). A mixture of 0.051 g
(0.19 mmol) of hexafluoro-1,4-naphthoquinone,
0.019 g (0.21 mmol) of aniline, and 1.5 ml of toluene
was stirred for 4 h at room temperature. Aniline,
0.035 g (0.38 mmol), was added to the resulting solu-
tion of quinone I [3], and the mixture was stirred for
20 days at room temperature. The precipitate was sepa-
rated by centrifugation, and quinone II was isolated
therefrom by thin-layer chromatography (chloroform–
hexane, 3:1). Yield 0.010 g (13%), dark violet crystals,
1
mp 76–79°C. H NMR spectrum (CDCl3), δ, ppm:
1
mp 228–232°C. H NMR spectrum (acetone-d6), δ,
6.30–6.39 m (4H, o-H in 2,3-NHPh), 6.73 t.t (2H, p-H
in 2,3-NHPh, J = 1.0, 7.4 Hz), 6.84–6.95 m (4H, m-H
in 2,3-NHPh), 7.05–7.16 m (6H, o-H in 5,8-NHPh, NH
or p-H), 7.26–7.37 m (6H, m-H in 5,8-NHPh, NH or
p-H), 11.17 br.s (2H, NH in 5,8-NHPh). 19F NMR
spectrum, δF, ppm: 31.3 s (2F, 6-F, 7-F). Found:
m/z 558.1858 [M]+. C34H24F2N4O2. Calculated:
M 558.1862.
ppm: 7.12–7.44 m (11H, Harom, NH), 10.51 br.s (1H,
NH). 19F NMR spectrum, δF, ppm: 28.3 m (1F, 3-F),
17.4 d.d (1F, 5-F, J5,6 = 19.4, J5,7 ≈ 9 Hz), 15.5 t.m
(1F, 6-F, J5,6 ≈ J6,7 ≈ 18 Hz), 32.5 d.d.m (1F, 7-F,
J6,7 = 17.3, J5,7 ≈ 9 Hz). Found: m/z 412.0823 [M]+.
C22H12F4N2O2. Calculated: M 412.0829.
3,6,7-Trifluoro-2,5,8-tris(phenylamino)-1,4-
naphthoquinone (III). Aniline, 0.051 g (0.56 mmol),
was added to a solution of quinone I, prepared as
described above in 1.5 ml of dioxane, and the mixture
was heated for 30 h at 100°C. The mixture was diluted
with ~5 ml of water, and the precipitate was separated
by centrifugation, washed with water (2×3 ml), dried
in air, and recrystallized from ethanol. Yield 0.074 g
1
The H and 19F NMR spectra were recorded on
a Bruker AV-300 spectrometer operating at 300.13 and
282.36 MHz, respectively, using the residual solvent
signal (CDCl3, δ 7.24 ppm; acetone-d6, δ 2.07 ppm) or
C6F6 (δF 0.0 ppm) as internal reference. The mass spec-
tra were obtained on a Thermo Fisher Scientific DFS
high-resolution mass spectrometer. Reagents and sol-
vents were purified as described previously [1, 3].
Preparative thin-layer chromatography was performed
using Sorbfil plates.
1
(81%), dark blue crystals, mp 163–165°C. H NMR
spectrum (CDCl3), δ, ppm: 7.02–7.21 m (9H, Harom),
7.25–7.39 m (7H, Harom, NH), 11.24 br.s (1H, NH),
11.45 br.s (1H, NH). 19F NMR spectrum, δF, ppm:
27.2 m (1F, 3-F), 34.7 d (1F, 6-F, J6,7 = 14.2 Hz),
30.2 d (1F, 7-F, J7,6 = 14.2 Hz). Found: m/z 485.1339
[M]+. C28H18F3N3O2. Calculated: M 485.1346.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 09-03-00248)
3,5,7,8-Tetrafluoro-2,6-bis(phenylamino)-1,4-
naphthoquinone (IV). Aniline, 0.017 g (0.19 mmol),
was added to a solution of quinone I in 1.5 ml of
DMSO, prepared as described above for the solution in
toluene, and the mixture was stirred for 24 h at room
temperature. The precipitate was separated by centrif-
ugation, washed with water (2×4 ml) and chloroform
(3×2 ml), and dried under reduced pressure (0.03 mm).
Yield 0.052 g (67%), dark brown crystals, mp 310–
REFERENCES
1. Troshkova, N.M., Goryunov, L.I., Gatilov, Yu.V., Nevin-
sky, G.A., and Shteingarts, V.D., J. Fluorine Chem., 2010,
vol. 131, p. 70.
2. Burdon, J., Castaner, J., and Tatlow, J.C., J. Chem. Soc.,
1964, p. 5017.
3. Goryunov, L.I., Troshkova, N.M., Nevinskii, G.A., and
Shteingarts, V.D., Russ. J. Org. Chem., 2009, vol. 45,
p. 835.
1
313°C. H NMR spectrum (acetone-d6), δ, ppm: 7.08–
7.44 m (12H, Harom, NH). 19F NMR spectrum, δF, ppm:
4. The Sadtler Standard Spectra. NMR Spectra. Philadel-
phia: Sadtler Research Laboratories, 1966–1983, 191M.
28.3 m (1F, 3-F), 36.5 d.d (1F, 5-F, J5,7 ≈ 12, J5,8
≈
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010