Synthesis of 3-Phenoxybenzoylacetonitrile

Full text of DOI:10.1134/S1070363208110340

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 11, pp. 2164–2165. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © Yu.V. Popov, T.K. Korchagina, M.V. Smirnova, V.S. Kamaletdinova, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78,
No. 11, pp. 1928–1929.
LETTERS
TO THE EDITOR
Synthesis of 3-Phenoxybenzoylacetonitrile
Yu. V. Popov, T. K. Korchagina, M. V. Smirnova, and V. S. Kamaletdinova
Volgograd State Technical University,
pr. Lenina 28, Volgograd, 400131 Russia
е-mail: vgdci@mail.ru
Received May 15, 2008
DOI: 10.1134/S1070363208110340
O
C
The introduction of 3-phenoxyphenyl fragment into
a pharmacophore molecule is promising for the
synthesis of the new biologically active substances
opening a way to further synthetic modifications.
Nitriles with molecules containing in the side chain
other functional groups aside from cyano group are of
great interest in the diphenyloxide derivatives series.
O
CH(CN)COOC2H5
II
O
NaOH, −CO2
O
CH2
C
C
N
Effective synthetic way to 3-phenoxybenzoyl-
acetonitrile was developed on the basis of 3-
phenoxybenzoyl chloride and ethyl cyanoacetate.
III
It is a common knowledge now that diphenyloxide
functional derivatives exhibit pharmacological activity
of various kinds [1–4].
The second stage consists in the alkaline hydrolysis
of ethyl 3-phenoxybenzoylcyanoacetate II followed by
thermal decarboxylation.
We obtained 3-phenoxybenzoylacetonitrile III by a
two-stage synthesis. In the first stage ethyl 3-phenoxy-
benzoylcyanoacetate II was formed as a result of ethyl
cyanoacetate acylation with 3-phenoxybenzoyl chlo-
ride I.
The alkaline hydrolysis of the ester obtained and 3-
phenoxybenzoylacetonitrile precipitation with carbon
dioxide furnished 3-phenoxybenzoylacetonitrile III in
an yield about 50%.
O
O
C
Better results were achieved using the other way of
3-phenoxybenzoylacetonitrile III isolation from ethyl
3-phenoxybenzoylcyanoacetate II. This procedure
consisted in 3-phenoxybenzoylcyanoacetic acid IV
isolation followed by its decarboxylation at heating
above the melting point.
Cl
+ CH2(CN)COOC2H5
O
I
O
CH(CN)COOC2H5
C
NaOH
The structure and composition of the nitrile pre-
pared were proved with IR and 1H NMR spectroscopy.
−HCl
3-Phenoxybenzoylacetonitrile. To a solution of
9.35 g (0.16 mol) of 3-phenoxybenzoyl chloride in
40 ml of anhydrous acetone was added 5 g (0.176 mol)
of ethyl cyanoacetate. To the mixture obtained was
added dropwise 40% solution of sodium hydroxide to
pH = 8–9 at vigorous stirring and external cooling with
II
The acylation was carried out in the presence of
sodium hydroxide in acetone for 2 h at a temperature
not exheeding 20°С. Yield of ethyl 3-phenoxyben-
zoylcyanoacetate II was up to 94–95%.
2164

SYNTHESIS OF 3-PHENOXYBENZOYLACETONITRILE
2165
O
C
O
NaOH
O
CH(CN)COOH
O
CH(CN)COOC2H5
C
−C2H5OH
IV
II
O
O
150−152oC
−CO2
O
CH2
C
O
CH(CN)COOH
C
C
N
III
IV
ice-salt mixture. The reaction mixture was stirred at
20°С for 2 h. Then 300 ml of ice water was added.
Ethyl 3-phenoxybenzoylcyanoacetate was isolated by
acidification with 10% hydrochloric acid. Yield 94–
95%, mp 140–142°С, finely dispersed powder.
1960 (C=O), 2248 (C≡N). 1Н NMR spectrum, δ, ppm:
4.402 s (2Н, СН2), 6.65-7.4 m (9Н, С6Н5ОС6Н4).
IR spectra were recorded on a Specord M-82
1
spectrophotometer (mineral oil, NaCl or KBr). Н
NMR spectra were registered on a Varian Mercury
300BB instrument in DMSO-d6, internal reference
HMDS.
Further to ethyl 3-phenoxybenzoylcyanoacetate
was added 150 ml of 10% aqueous sodium hydroxide
solution. The reaction mixture was refluxed at stirring
for 1–2 h to complete dissolution of the ester in alkali.
On cooling, the reaction mixture was acidified with
100 ml of 5 N НСl. 3-Phenoxybenzoylcyanoacetic acid
precipitated was filtered off and washed with distilled
water. mp 150–152°С.
REFERENCES
1. Chicherina, G.V., Candidate Sci. (Chem.) Dissertation,
Volgograd, 1998.
2. Yermakova, T.A., Candidate Sci. (Chem.) Dissertation.,
Volgograd, 2002, p. 155.
The acid prepared was heated above melting point
to form 3-phenoxybenzoylacetonitrile. Yield 90%, mp
140–143°С. IR spectrum, ν, сm–1: 1600–700 (Ar),
3. Khimicheskaya entsyklopediya (Chemical Encyclo-
pedia), Knunyants, I.L., Ed., Мoscow: Bol’shaya Ros-
siyskaya Entsyklopediya, 1992, p. 639.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 11 2008