Synthesis of 2-substituted benzoxazoles and benzimidazoles from 3-phenoxyphenyl-containing acrylonitriles

Full text of DOI:10.1134/S1070363214110383

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 11, pp. 2267–2269. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © Yu.V. Popov, T.K. Korchagina, V.S. Lobasenko, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 11, pp. 1909–
1911.
LETTERS
TO THE EDITOR
Synthesis of 2-Substituted Benzoxazoles and Benzimidazoles
from 3-Phenoxyphenyl-Containing Acrylonitriles
Yu. V. Popov, T. K. Korchagina, and V. S. Lobasenko
Volgograd State Technical University, ul. Lenina 28, Volgograd, 400005 Russia
e-mail: viktori_2008@bk.ru
Received June 16, 2014
Keywords: acrylonitrile, benzoxazole, benzimidazole, 3-phenoxyphenyl group
DOI: 10.1134/S1070363214110383
Diphenyl oxide derivatives are promising active
compounds that exhibit a number of pharmacological
properties. In particular, Nimesulide [4-(4-nitro-2-
phenylacetonitrile:aldehyde = 1 : 1.2 mol/mol). Yields
of nitriles II and III were of 84–90% (Scheme 1).
When selecting the optimal reaction temperature,
we took into account that at T > 30°C a competitive
Cannizzaro reaction and disproportionation of the
starting aldehyde could occur. On top of that, at 20–
30°C the formed 3-phenoxyphenyl acrylonitriles readily
crystallized and precipitated, thus greatly facilitating
the product isolation.
phenoxyphenyl)methanesulfonamide]
provides
antiinflammatory,
analgesic,
antipyretic, and
antiplatelet effects [1].
Some 2-aryl-substituted benzoxazoles have been
used as herbicides [2] and drugs [3]. Some benzimi-
dazole derivatives have shown fungicidal activity [4].
Interaction of the synthesized 3-phenoxyphenyl-
derived acrylonitriles II and III with o-phenylene-
diamine hydrochloride or o-aminophenol hydrochlo-
ride resulted in formation of 2-(3-phenoxyphenyl)benz-
oxazoles and benzimidazoles IV–VII (Scheme 2).
It was of interest to prepare previously never
described 2-substituted benzimidazoles and benzoxa-
zoles based on 3-phenoxyphenyl derived acrylonitriles.
The starting 1-phenyl-2-(3-phenoxyphenyl)acrylo-
nitrile II and 1,2-bis-(3-phenoxyphenyl)acrylonitrile
III were prepared via reaction of 3-phenoxyphenyl-
acetonitrile I [5] with the corresponding aldehydes.
The reactions were carried out at room temperature
in sealed tubes.
The structure and composition of the obtained 2-(3-
phenoxyphenyl)benzimidazoles and benzoxazoles IV–
VII were confirmed by IR and H NMR spectroscopy
as well as gas chromatography–mass spectrometry.
The synthesis was carried out via stirring the rea-
ctants in ethanol in the presence of sodium hydroxide
at room temperature (20–25°C) during 1 h (3-phenoxy-
1
Scheme 1.
C
C
N
CH
O
CH2
O
C
N
O
H
NaOH
_H2O
R
+ R
C
II, III
O
(II),
R =
(III).
2267

2268
POPOV et al.
Scheme 2.
N
C
C
N
C
.
CH
NH2 HCl
O
X
O
C
R1
CH
R1
+
R2
II, III
IV–VII
O
R2 = NH ,
R1 =
R1 =
(IV),
(V);
X = NH,
2
O
R2 = OH
(VII).
(VI)
, X = O,
,
1
1,2-Bis(3-phenoxyphenyl)acrylonitrile (III). 5 mL
of a 40% alcoholic solution of sodium hydroxide was
added dropwise upon stirring to a mixture of 17.46 g
(0.09 mol) of freshly distilled 3-phenoxybenzaldehyde,
19.7 g (0.09 mol) of 3-phenoxyphenylacetonitrile, and
10 mL of 95% ethanol The reaction was exothermic.
After cooling, the precipitate was filtered off and
sequentially washed with distilled water and 95%
ethanol. Alcoholic filtrates were combined, evapo-
rated, and the residue was recrystallized from 95%
ethanol. Yield 84% (32.6 g), mp 98–100°С. IR spec-
cm–1: 1632 (С=N), 1650 (C=C), 3405(NH). Н NMR
spectrum, δ, ppm: 6.83–7.75 m (18Н, С6Н5ОС6Н4,
С6Н5, С6Н4), 6.65 s (1Н,CH).
2-[1,2-Bis(3-phenoxyphenyl)vinyl]benzimidazole
(V) was prepared similarly. Yield 35% (3.4 g), mp
256–258°С. IR spectrum, ν, cm–1: 1625 (С=N), 1670
(C=C), 3400 (NH). Н NMR spectrum, δ, ppm: 6.70–
7.53 m (22Н, 2С6Н5ОС6Н4, С6Н4), 6.61 s (1Н, CH).
1
2-[1-Phenyl-2-(3-phenoxyphenyl)vinyl]benz-
oxazole (VI). A mixture of 3.5 g (0.024 mol) of o-
aminophenol hydrochloride and 6 g (0.02 mol) of 1-
phenyl-2-(3-phenoxyphenyl)acrylonitrile was heated at
220–250°C in a sealed glass tube during 10 h. Then,
the reaction mixture was triturated with diethyl ether
and washed with 4 mol/L solution of NaOH. The
resulting precipitate was filtered off, washed with
warm water and diethyl ether, and dried. Yield 36%
(3 g), mp 165–168°С. 1H NMR spectrum, δ, ppm: 7.17–
7.74 m (18Н, C6H5OC 6H4, C6H5, C6H4), 6.96 s (1Н,
Ar-СН), 5.62–5.67 d (1Н, CHCN). Mass spectrum,
m/z (Irel, %): 389 (24) [М]+, 388 (100), 207 (48), 77 (19).
1
trum, ν, cm–1: 2254 (С≡N), 1620 (C=C). Н NMR
spectrum, δ, ppm: 6.77–7.37 m (9Н, С6Н5ОС6Н4), 6.40
s (Н, CH). Mass spectrum, m/z (Irel, %): 389 (100), 77
(15), 51 (16). C27H19O2N. M 389.
1-Phenyl-2-(3-phenoxyphenyl)acrylonitrile (II)
was prepared similarly. Yield 90% (29 g), mp 87–89°С.
1
IR spectrum, ν, cm–1: 2246 (С≡N), 1607 (C=C). Н
NMR spectrum, δ, ppm: 6.70–7.21
m
(14Н,
С6Н5ОС6Н4, С6Н5), 6.51 s (Н, CH). Mass spectrum,
m/z (Irel, %): 297 (100) [М+], 77 (25), 51 (14). C21H15ON.
M 297.
2-[1,2-Bis(3-phenoxyphenyl)vinyl]benzoxazole
2-[1-Phenyl-2-(3-phenoxyphenyl)vinyl]benzimi-
dazole (IV). A mixture of 3.47 g (0.024 mol) of o-
phenylenediamine hydrochloride and 6 g (0.02 mol) of
1-phenyl-2-(3-phenoxyphenyl)acrylonitrile was heated
at 220–250°C in a sealed glass tube during 10 h. Then
the reaction mixture was triturated and heated (90–95°C)
with 5% hydrochloric acid during 1 h. The mixture
was filtered, and aqueous ammonia was added to the
filtrate. The solution color changed from blue to purple,
and precipitation occurred. The precipitate was filtered
off, dried, and recrystallized from anhydrous ethanol.
Yield 52% (4.0 g), mp 234–235°С. IR spectrum, ν,
(VII) was prepared similarly. Yield 25% (2.4 g), mp
1
180–182°С. H NMR spectrum, δ, ppm: 7.14–7.74 m
(22Н, С6Н5ОС6Н4, С6H4), 6.99 s (1Н, Ar-CH). Mass
spectrum, m/z (Irel, %): 481 (14) [М]+, 480 (100), 352
(51), 281 (17), 207 (28), 77 (29), 51 (18).
IR spectra were recorded using a Specord M 82
1
spectrometer (KBr, paraffin oil). H NMR spectra of
the solutions in DMSO-d6 were recorded with a Varian
Mercury 300 instrument (300 MHz). Gas
chromatography–mass spectra were obtained with a
Varian MAT-11 spectrometer at 70 eV (EI).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 11 2014

SYNTHESIS OF 2-SUBSTITUTED BENZOXAZOLES AND BENZIMIDAZOLES
2269
Med. Chem. Lett., 2013, vоl. 23, no. 24, p. 6721. DOI:
10.1016/j.bmcl.2013.10.035.
ACKNOWLEDGMENTS
2. Suzuki, J., Japan Patent 058213, 2008.
3. Schunk, S., Germany Patent 142402, 2010.
4. Pilyugin, V.S. and Kuznetsova, S.L., Russ. J. Gen.
Chem., 2008, vol. 78, no. 3, p. 446. DOI: 10.1134/
S1070363208030195.
This work was financially supported by the
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
5. Popov, Yu.V., Korchagina, T.K., and Lobasenko, V.S.,
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 11 2014