Synthesis of 3-phenoxyphenyl-containing 1,3-diketones

Full text of DOI:10.1134/S1070363214110371

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 11, pp. 2264–2266. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © Yu.V. Popov, T.K. Korchagina, V.S. Lobasenko, S.A. Pavel’ev, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 11,
pp. 1906–1908.
LETTERS
TO THE EDITOR
Synthesis of 3-Phenoxyphenyl-Containing 1,3-Diketones
Yu. V. Popov, T. K. Korchagina, V. S. Lobasenko, and S. A. Pavel’ev
Volgograd State Technical University, ul. Lenina 28, Volgograd, 400005 Russia
e-mail: viktori_2008@bk.ru
Received June 16, 2014
Keywords: alkyl-3-phenoxybenzoate, 1,3-diketone, 3-phenoxyphenyl group, 5-methyl-3-(3-phenoxyphenyl)isoxazole
DOI: 10.1134/S1070363214110371
Diphenyl oxide derivatives containing various func-
tional groups have been used as drugs showing a wide
range of physiological activity.
diketones synthesis. Esters of 3-phenoxybenzoic acid
and ketones containing α-hydrogen atom were used as
starting compounds.
A promising direction in the chemistry of diphenyl
oxide compounds is synthesis of dicarbonyl com-
pounds, namely, 1,3-diketones. This class of diphenyl
oxide derivatives has been scarcely studied so far.
Aromatic β-diketones have attracted increased atten-
tion because of the valuable pharmacological proper-
ties. For instance, some of them are active blood
anticoagulants and are used to treat thrombosis and
myocardial infarction. They also possess pronounced
antiviral activity against herpes simplex virus types 1
and 2 as well as DNA and RNA viruses [1, 2].
Synthesis of alkyl 3-phenoxybenzoates VI and VII
was performed via two pathways starting from 3-
phenoxybenzaldehyde I. In the first scheme, 3-phen-
oxybenzaldehyde I reacted sequentially with hydroxyl-
amine and acetic anhydride to give 3-phenoxy-
benzonitrile III [3], its interaction with alcohols in the
presence of catalytic amounts of concentrated sulfuric
acid at heating leading to formation of the
corresponding alkyl 3-phenoxybenzoates VI and VII
[4] with yields of 52–55% (Scheme 1).
The second approach involved acylation of alcohols
with a corresponding acid chloride. Acid chloride V
was prepared by reacting 3-phenoxybenzoic acid IV
In this work we developed a convenient and
efficient method of 3-phenoxyphenyl-containing 1,3-
Scheme 1.
NOH
O
O
C
H
O
C N
O
C
.
(CH3CO)2O
HCl,
NH2OH
H
_2CH3COOH
C2H5OH, NaOH
I
II
III
_MnO2
_K2O
ROH,
KMnO4
_NH4HSO
H2SO4,
H2O
O
C
O
C
O
C
O
O
O
PCl5
OH
Cl ROH
_HCl
OR
_POCl3
_HCl
IV
V
VI, VII
R = CH3 (VI), C2H5 (VII).
2264

2265
SYNTHESIS OF 3-PHENOXYPHENYL-CONTAINING 1,3-DIKETONES
Scheme 2.
Na
O
C
O
C
_
O
O
O
O
NaH
R2
C
C
C
R2
+
OR1
H2
_RONa,
_2H2
H3C
VI, VII
O
C
O
C
O
R2
CH3COOH
C
H2
_CH3COONa
VIII_X
R1 = CH3 (VI), C2H5 (VII); R2 = CH3 (VIII), C2H5 (IX), C6H5 (X).
Scheme 3.
O
O
C
O
N
O
O
C
C
C
NaOH
CH3
C
CH3
CH
+ NH2OH HCl
H2
_2H2O, HCl
VIII
ХI
with phosphorus(V) chloride. The method enabled to
improve the yield of 3-alkyl phenoxybenzoates VI and
VII to reach 94% (Scheme 2).
poured into 50 mL of distilled water. The organic layer
was separated, diluted with 20–30 mL of diethyl ether,
washed with saturated aqueous sodium bicarbonate
solution until carbon dioxide evolution ceased, then
washed with water until neutral reaction, and dried
with anhydrous sodium sulfate. After removal of the
solvent, the residue was distilled under vacuum. Yield
6.6 g (55%), bp 195–197°C (4 mmHg), nD20 1.5578. IR
spectrum, ν, cm–1: 1745, 1696 (C=O), 2975–3545 (C–H),
Synthesis of 3-phenoxyphenyl-substituted 1,3-di-
ketones VIII–X was performed via the Claisen reac-
tion between alkyl 3-phenoxybenzoates and ketones
(acetone, butan-2-one, or acetophenone) at the molar
ratio of 2.0:1 in anhydrous cyclohexane in the presence
of catalytic amounts of sodium hydride under reflux
during 2.5–3 h. Yields of 3-phenoxyphenyl derived
1,3-diketones were as high as 50–74% (Scheme 3).
1
1294 (С–С, CH2). Н NMR spectrum, δ, ppm: 1.80–
2.25 m (3Н, СН3), 4.2 m (2Н, СН2), 6.0 s (Н, =СН),
6.94–7.76 m (9Н, С6Н5ОС6Н4).
1,3-Diketones comprising diphenyloxide moiety
could undergo the cyclocondensation reaction. In par-
ticular, 1-(3-phenoxyphenyl)butane-1,3-dione reacted
with hydroxylamine to form 5-methyl-3-(3-phenoxy-
phenyl)isoxazole XI with yield of 62%.
Methyl 3-phenoxybenzoate (VI) was prepared
similarly. Yield 74%, bp 187–189°C (4 mmHg). IR
1
spectrum, ν, cm–1: 1750 (С=О), 1250 (С–О). Н NMR
spectrum, δ, ppm: 1.7 s (3Н, СН3), 6.32–7.46 m (9Н,
С6Н5ОС6Н4).
Structures of the prepared compounds were
established from IR and NMR spectroscopy data.
1-(3-Phenoxyphenyl)butane-1,3-dione (VIII). A
suspension of 0.2 g (7.07 mmol) of sodium hydride in
50 mL of anhydrous cyclohexane was added upon
stirring and cooling to a solution of 3 g (12.3 mmol) of
ethyl 3-phenoxybenzoate VII in 10 mL of cyclo-
hexane. Then a mixture of 0.3567 g (6.15 mmol) of an-
hydrous acetone and 10 mL of anhydrous cyclohexane
Ethyl 3-phenoxybenzoate (VII). A mixture of
10 g (50.0 mmol) of 3-phenoxybenzonitrile, 9.8 g
(212.0 mmol) of anhydrous ethanol, and 11.7 g
(119.5 mmol) of conc. sulfuric acid was refluxed
during 8 h. The reaction mixture was cooled and
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2266
POPOV et al.
was slowly added. The reaction started spontaneously
at room temperature and was accompanied by
hydrogen evolution and slight heating of the reaction
mixture. When the gas evolution ceased (2.5 h), the
mixture was cooled to room temperature and incubated
overnight. The reaction mixture was acidified with
10% acetic acid and diluted with 50 mL of icy water.
The precipitate was filtered off, washed with cyclo-
hexane and dried. The organic layer was separated, and
the aqueous layer was extracted with diethyl ether
(2Ч50 mL). The combined organic extracts were
washed with 200 mL of distilled water until neutral
reaction, dried over anhydrous sodium sulfate, and
evaporated. The resulting crystals were filtered off,
washed with cyclohexane, dried in air, and recrystal-
lized from methanol. Yield 1.16 g (74%), mp 125–
130°C. IR spectrum, ν, cm–1: 2740–2890 (OH), 2900–
3300 (C–H), 1780, 1696 (C=O), 1546 (C=C), 1294
40% aqueous sodium hydroxide solution was added to
a solution of 3 g (11.8 mmol) of 1-(3-phenoxyphenyl)-
butane-1,3-dione VIII in 30 mL of ethanol. The
mixture was refluxed during 8 h. After cooling to room
temperature, the resulting crystals were filtered off and
recrystallized from ethanol. Yield 1.84 g (62%), mp
245°C. Н NMR spectrum, δ, ppm: 2.24 s (3Н, СН3),
6.02 s (=СН), 6.82–7.45 m (9Н, С6Н5ОС6Н4). Mass
spectrum, m/z (Irel): 251 (100), 252 (17.8), 253 (2).
1
IR spectra were recorded with a SPECORD-M-82
(Perkin-Elmer) spectrometer at 400–5000 cm–1. The
spectra of liquid samples were registered in thin film,
and the solid samples were examined in the form of
1
suspension in paraffin oil. H NMR spectra of the
solutions in CDCl3 were registered with a Varian
Mercury 300BB instrument relative to HMDS. Mass
spectra were obtained using a Variant MAT-11
spectrometer with ionizing voltage of 70 eV.
1
(CH3). Н NMR spectrum, δ, ppm: 0.80–2.25 m (3Н,
СН3), 16.0 s (Н, ОН), 4.2 m (2Н,СН2), 6.03 s (Н,
=СН), 6.94–7.76 m (9Н, С6Н5ОС6Н4).
ACKNOWLEDGMENTS
1-(3-Phenoxyphenyl)pentane-1,3-dione (IX) was
prepared similarly. Yield 1.34 g (69%), mp 142–145°C.
IR spectrum, ν, cm–1: 2758–2890 (OH), 2920–3300
(C–H), 1786, 1654 (C=O), 1546 (C=C). 1Н NMR spec-
trum, δ, ppm: 1.047–1.3 m (3Н, СН3), 8.780 s (Н, ОН),
2.98 m (Н, =СН), 4.2 s (2Н, СН2), 6.94–7.76 m (9Н,
С6Н5ОС6Н4).
This work was financially supported by Ministry of
Education and Science of the Russian Federation in the
frame of the basic part of the governmental task
no. 2014/16 (project no. 28-79).
REFERENCES
1. Diana, G.D., Carabateas, Ph.M., and Johnson, R.E.,
J. Med. Chem., 1977, vol. 20, no. 6, p. 757. DOI:
10.1021/jm00216a004.
1-(3-Phenoxyphenyl)-3-phenylpropane-1,3-dione
(X) was prepared similarly. Yield 1.15 g (52%), mp
152–157°C. IR spectrum, ν, cm–1: 2740–2896 (OH),
2900–3300 (C–H), 1786, 1654 (C=O), 1546 (C=C). 1Н
NMR spectrum, δ, ppm: 7.978 s (Н, ОН), 3.81 s (2Н,
СН2), 6.07 s (Н, =СН), 6.92–7.73 m (14Н,
С6Н5ОС6Н4, С6Н5).
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jm00207a010.
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Volgograd, 2008,.
5-Methyl-3-(3-phenoxyphenyl)isoxazole (XI). A
solution of 1.6 g (23.6 mmol) of hydroxylammonium
hydrochloride in 4 mL of water containing a drop of
4. Furniss, B.S., Hannaford, A.J., Smith, P.W.G., and
Tatchell, A.R., Vogel’s Text-Book of Practical Organic
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