2-Polyfluoroalkylchromones 5. Nitration and chlorination of 2-trifluoromethylchromones

Article abstract of DOI:10.1023/A:1009544630187

Electrophilic nitration of 2-trifluoromethylchromone and its 6-and 7-methoxy derivatives affords 6-, 5-, and 8-nitro derivatives, respectively, while 5,7-dimethyl-2-trifluoromethylchromone yields a 6,8-dinitro derivative. Radical chlorination results in 3-chloro derivatives.

Full text of DOI:10.1023/A:1009544630187

2
074
Russian Chemical Bulletin, International Edition, Vol. 49, No. 12, December, 2000
2-Polyfluoroalkylchromones
.* Nitration and chlorination of 2-trifluoromethylchromones
5
V. Ya. Sosnovskikh« and B. I. Usachev
A. M. Gor´ky Ural State University,
1 prosp. Lenina, 620083 Ekaterinburg, Russian Federation.
5
Fax: +7 (343 2) 61 5978. E-mail: vyacheslav.sosnovskikh@usu.ru
Electrophilic nitration of 2-trifluoromethylchromone and its 6- and 7-methoxy derivatives
affords 6-, 5-, and 8-nitro derivatives, respectively, while 5,7-dimethyl-2-trifluoromethyl-
chromone yields a 6,8-dinitro derivative. Radical chlorination results in 3-chloro derivatives.
Key words: 2-trifluoromethylchromones, electrophilic nitration, radical chlorination.
Chromones are an important class of oxygen-con-
Scheme 1
taining heterocyclic compounds. Unlike the properties
2
of 2-alkylchromones, numerous representatives of which
O
O
occur in nature and are well studied, those of 2-poly-
fluoroalkylchromones have been little studied.
O N
2
i
Recently, we have described the reactions of 2-poly-
fluoroalkylchromones with ammonia, primary amines,3
ethylenediamine, trimethylenediamine, and diethylene-
O
O
CF3
O
O
CF3
4
1
2
triamine5 which revealed significant differences in the
reactivities of 2-alkyl- and 2-polyfluoroalkylchromones
with respect to N-nucleophiles. In the present work, we
report for the first time the behavior of 2-trifluoro-
methylchromones in the reactions of electrophilic nitra-
tion and radical chlorination, which are best studied for
their nonfluorinated analogs.
NO2
MeO
MeO
i
O
O
CF3
O
O
CF3
3
Nitrochromones are accessible intermediates in the
2
synthesis of biologically active aminochromones. It is
well known6 that chromone, 2- and 3-alkyl-, 2-alkoxy-
carbonyl-, and 2,3-dialkylchromones with non-substi-
tuted benzene rings are easily nitrated at position 6 at
i
0
—20 °C; dinitration of the benzene ring is not ob-
MeO
O
CF3
MeO
O
CF3
7
served. We found that 2-trifluoromethylchromone (1),
despite the presence of the electron-withdrawing CF3
group, is also easily nitrated at ambient temperature to
give 6-nitro-2-trifluoromethylchromone (2) in 67% yield
NO2
4
Me
O
O
Me
O
(
Scheme 1). Nitration in 20% oleum with 95% HNO at
3
O N
2
1
10 °C did not result in a dinitro derivative (TLC). The
i
maximum yield of chromone 2 (96%) was attained when
the nitration was carried out at 75 °C for 1 h.
Me
CF3
Me
O
CF3
Previously, it was shown that the nitration of 6- and
NO2
7
-methoxychromones with a nitrating mixture at 0 °C
5
8
i. HNO3, H2SO4.
gives 5- and 8-nitro derivatives, respectively, while
-methoxy-2-methylchromone transforms into 7-meth-
7
oxy-8-nitro-2-methylchromone at 0 °C and into 6,8-di-
nitro-7-methoxy-2-methylchromone at 30 °C. We found
that 6- and 7-methoxy-2-trifluoromethylchromones10 af-
dinitro derivatives (TLC) even under more drastic con-
ditions (75 °C). The relatively low yields of chromones 3
and 4 (41 and 34%, respectively) are probably due to the
destabilization effect of the electron-donor MeO group
on the chromone system, which causes undesirable de-
struction. It is of note that, under the same condi-
9
ford only mononitrated products 3 and 4, with no
*
For Part 4, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2109—2111, December, 2000.
066-5285/00/4912-2074 $25.00 © 2000 Plenum Publishing Corporation
1

Nitration and chlorination of 2-CF -chromones
Russ.Chem.Bull., Int.Ed., Vol. 49, No. 12, December, 2000 2075
3
tions, 5,7-dimethyl-2-trifluoromethylchromone10,11 gives
dinitro derivative 5 in virtually quantitative yield.
The structures of chromones 2—5 were unambigu-
Experimental
IR spectra were recorded on an IKS-29 instrument (Nujol
mulls). 1H NMR spectra were recorded on a Bruker WM-250
1
ously determined by H NMR spectroscopy (see Experi-
mental). Thus the 1H NMR spectrum of chromone 2
shows a doublet with Jm = 2.7 Hz at δ 9.06 for the most
deshielded HC(5) proton (owing to an anisotropic effect
of the carbonyl and nitro groups). The proton at the
C(7) atom affected only by the nitro group manifests
itself as a doublet of doublets with Jo = 9.1 Hz and
Jm = 2.7 Hz at δ 8.60, while the HC(8) proton, as a
doublet with Jo = 9.1 Hz at δ 7.75. A singlet for the
vinylic proton in chromone 2 appears at δ 6.82, i.e., is
shifted downfield by 0.1 ppm compared to that for non-
substituted chromone 1 (see Ref. 7).
spectrometer in CDCl3 with Me Si as the internal standard.
The starting 2-trifluoromethylchromones were prepared as de-
scribed in Refs. 7, 10, and 11.
4
6-Nitro-2-trifluoromethylchromone (2). A mixture of conc.
H SO (0.5 mL) and 70% HNO3 (0.5 mL, 7.8 mmol) was
2
4
added to a solution of chromone 1 (0.50 g, 2.33 mmol) in
2
7
.0 mL of conc. H SO . The reaction mixture was heated at
2 4
5 °C for 1 h, cooled, and poured with stirring onto crushed ice.
The precipitate that formed was filtered off, washed with water,
dried, and recrystallized from ethanol. Yield 0.58 g (96%), m.p.
155—156 °C. Found (%): C, 46.50; H, 1.64; N, 5.34.
C10H4F3NO4. Calculated (%): C, 46.35; H, 1.56; N, 5.41.
–
1
IR, ν/cm : 1675 (C=O); 1625, 1580 (C=C, arom.); 1535
NO ). 1H NMR, δ: 6.82 (s, 1 H, =CH); 7.75 (d, 1 H, H(8),
Halogenation of chromones at the C(3) atom is
usually a more difficult problem than halogenation in
the benzene ring.2 Examples of both electrophilic and
radical chlorination of the chromone system in position
(
2
Jo = 9.1 Hz); 8.60 (dd, 1 H, H(7), Jo = 9.1 Hz, Jm = 2.7 Hz);
9
.06 (d, 1 H, H(5), Jm = 2.7 Hz).
The same nitrating mixture was used for the preparation of
3
3
are documented. Treatment of a solution of chromone-
-carbaldehyde and chromone-3-carboxylic acid in
compounds 3—5 and 8.
6-Methoxy-5-nitro-2-trifluoromethylchromone (3) was ob-
tained by the nitration of 6-methoxy-2-trifluoromethylchromone
at 45 °C for 30 min. Yield 41%, m.p. 191—192 °C (ethanol).
Found (%): C, 45.78; H, 2.17; N, 4.83. C11H F NO . Calcu-
AcOH with NaOCl at ∼ 20 °C gave12 3-chlorochromone
in 86 and 41% yields, respectively. When refluxed in
SO Cl2 in the presence of benzoyl peroxide for 10 h,
ethyl chromone-2-carboxylate afforded a mixture of three
products in nearly equal amounts; one of them is ethyl
3
6
–
3
5
2
1
lated (%): C, 45.69; H, 2.09; N, 4.84. IR, ν/cm : 1680 (C=O);
1
6
1
630 (C=C); 1560 (NO ). 1H NMR, δ: 4.00 (s, 3 H, MeO);
.69 (s, 1 H, =CH); 7.55 (d, 1 H, H(7), Jo = 9.5 Hz); 7.72 (d,
H, H(8), Jo = 9.5 Hz).
2
-chlorochromone-2-carboxylate.13
The reaction of 2-trifluoromethylchromone (1) with
7
-Methoxy-8-nitro-2-trifluoromethylchromone (4) was ob-
chlorine in the light in CCl4 at 60 °C for 1 h yields an
unstable compound, which is likely to be a product of
radical addition of Cl2 to the double bond (6) (cf.
Ref. 13). The latter was treated with ammonium hydrox-
ide at ∼ 20 °C to give 3-chloro-2-trifluoromethylchromone
tained by the nitration of 7-methoxy-2-trifluoromethylchromone
at 65 °C for 30 min. Yield 34%, m.p. 193—194 °C (ethanol).
Found (%): C, 45.69; H, 1.83; N, 4.91. C11H F NO . Calcu-
6
–
3
5
1
lated (%): C, 45.69; H, 2.09; N, 4.84. IR, ν/cm : 1680 (C=O);
1
6
1
620 (C=C); 1550 (NO ). 1H NMR, δ: 4.09 (s, 3 H, MeO);
.73 (s, 1 H, =CH); 7.22 (d, 1 H, H(6), Jo = 9.2 Hz); 8.29 (d,
H, H(5), Jo = 9.2 Hz).
2
(
7). Chlorination of chromone 2 for 8 h under similar
conditions results in 3-chloro-6-nitro-2-trifluoromethyl-
chromone (8), which was alternatively obtained by the
nitration of chromone 7 (Scheme 2).
5
,7-Dimethyl-6,8-dinitro-2-trifluoromethylchromone (5) was
obtained by the nitration of 5,7-dimethyl-2-trifluoromethyl-
chromone as described for compound 2. Yield 95%, m.p.
1
71—172 °C (ethanol). Found (%): C, 43.59; H, 2.27;
N, 8.55. C12H F N O . Calculated (%): C, 43.39; H, 2.12;
7
3
2
–1
6
Scheme 2
N, 8.43. IR, ν/cm : 1690 (C=O); 1620 (C=C); 1550 (NO ).
2
1
H NMR, δ: 2.39 (s, 3 H, Me(7)); 2.79 (s, 3 H, Me(5)); 6.76
O
O
O
O
(
s, 1 H, =CH).
Cl
Cl
Cl
3-Chloro-2-trifluoromethylchromone (7). A flow of Cl2 was
Cl2
NH3
passed at ∼ 60 °C through a solution of chromone 1 (4.0 g,
18.7 mmol) in 50 mL of CCl4 with irradiation with a 60-W
lamp. After 1 h, the solution was concentrated, and the liquid
residue was dissolved in 20 mL of ethanol and mixed with
1
hν
CF3
CF3
7
6
2
00 mL of 1% aqueous solution of NH . The precipitate that
3
HNO3
formed was filtered off, washed with water, dried, and recrys-
tallized from ethanol. Yield 2.2 (47%), m.p. 137 °C.
Found (%): C, 48.58; H, 1.72. C H ClF O . Calculated (%):
H SO
2
4
g
O
1
0
4
3
2
O N
Cl
C, 48.32; H, 1.62. IR, ν/cm–1: 1665 (C=O); 1630, 1615, 1580
C=C, arom.). 1H NMR, δ: 7.53 (td, 1 H, H(6), J = 7.9 Hz,
2
Cl2
hν
(
2
o
Jm = 1.4 Hz); 7.58 (dd, 1 H, H(8), Jo = 7.9 Hz, Jm = 1.4 Hz);
.81 (td, 1 H, H(7), Jo = 7.9 Hz, Jm = 1.8 Hz); 8.27 (dd, 1 H,
H(5), Jo = 7.9 Hz, Jm = 1.8 Hz).
-Chloro-6-nitro-2-trifluoromethylchromone (8). A. Chro-
O
CF3
7
8
3
Hence, unlike the reactions with N-nucleophiles, the
mone 7 was nitrated at 45 °C for 40 min. The yield of
compound 8 was 37%, m.p. 142—143 °C (ethanol). Found (%):
C, 40.98; H, 1.06; N, 4.68. C10H ClF NO . Calculated (%):
reactions of 2-trifluoromethylchromones with electro-
philic and radical reagents do not differ from those
involving 2-alkyl- and 2-alkoxycarbonylchromones.
3
3
4
–
1
C, 40.91; H, 1.03; N, 4.77. IR, ν/cm : 1680 (C=O); 1630,

2
076
Russ.Chem.Bull., Int.Ed., Vol. 49, No. 12, December, 2000
Sosnovskikh and Usachev
1
580 (C=C, arom.); 1540 (NO ). 1H NMR, δ: 7.78 (d, 1 H,
4. V. Ya. Sosnovskikh and V. A. Kutsenko, Izv. Akad. Nauk,
Ser. Khim., 1999, 817 [Russ. Chem. Bull., 1999, 48, 812
(Engl. Transl.)].
2
H(8), Jo = 9.1 Hz); 8.64 (dd, 1 H, H(7), Jo = 9.1 Hz,
Jm = 2.8 Hz); 9.12 (d, 1 H, H(5), Jm = 2.8 Hz).
B. A solution of chromone 2 (0.43 g, 1.7 mmol) in 5 mL of
5. V. Ya. Sosnovskikh, Yu. G. Yatluk, and V. A. Kutsenko,
Izv. Akad. Nauk, Ser. Khim., 1999, 1825 [Russ. Chem. Bull.,
1999, 48, 1800 (Engl. Transl.)].
CCl was saturated with Cl2 at ∼ 20 °C. Then, the reaction vessel
4
was hermetically sealed and irradiated with the light of a
6
0-W lamp at 60 °C for 8 h. The solution was concentrated, and
the residue was dissolved in 15 mL of EtOH and refluxed for
min. After cooling, the precipitate that formed was filtered
6. G. P. Ellis and I. L. Thomas, J. Chem. Soc., Perkin Trans. 1,
1973, 2781.
7. V. Ya. Sosnovskikh and I. S. Ovsyannikov, Zh. Org. Khim.,
1993, 29, 89 [Russ. J. Org. Chem., 1993, 29, 74 (Engl.
Transl.)].
5
off, washed with ethanol, dried, and recrystallized from ethanol.
The yield of compound 8 was 0.15 g (31%), m.p. 142—143 °C
(
ethanol).
8. P. P. Joshi, T. R. Ingle, and B. V. Bhide, J. Indian Chem.
Soc., 1959, 36, 59.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 99-03-
2960).
9
. A. M. Mehta, G. V. Jadhav, and R. C. Shah, Proc. Indian
Acad. Sci., 1949, 29A, 314.
3
10. W. B. Whalley, J. Chem. Soc., 1951, 3235.
1
1
1
1. V. Ya. Sosnovskikh, Izv. Akad. Nauk, Ser. Khim., 1998, 362
Russ. Chem. Bull., 1998, 47, 354 (Engl. Transl.)].
2. A. Nohara, K. Ukawa, and Y. Sanno, Tetrahedron, 1974,
0, 3563.
3. G. P. Ellis and I. L. Thomas, J. Chem. Soc., Perkin Trans. 1,
974, 2570.
[
References
3
1
2
. V. Ya. Sosnovskikh and B. I. Usachev, Mendeleev Commun.,
000, No. 6.
. G. P. Ellis, Chromenes, Chromanones, and Chromones, in
The Chemistry of Heterocyclic Compounds, Ed. G. P. Ellis,
Wiley, New York, 1977, 31.
2
1
3
. V. Ya. Sosnovskikh, V. A. Kutsenko, and D. S. Yachevskii,
Mendeleev Commun., 1999, 204.
Received June 8, 2000;
in revised form September 13, 2000