Synthesis of 5-acetyl derivatives of alkyl 2-furoates and 3-(2-furyl)acrylates

Article abstract of DOI:10.1134/S1070363215020127

Methyl 5-acetyl-2-furoate has been prepared via oxidation of 5-(1-hydroxyethyl)-2-furoate with the Jones reagent. In turn, the starting compound has been synthesized via sequential chloroethylation of ethyl 2-furoate, substitution of chlorine with acetoxy group, and methanolysis of the acetate in presence of sodium methylate. The vinylog 2-furoate has been obtained as the major product via acetylation of ethyl 3-(2-furyl)-acrylate with acetic anhydride in the presence of magnesium perchlorate.

Full text of DOI:10.1134/S1070363215020127

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 2, pp. 424–427. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © K.V. Kuticheva, L.M. Pevzner, M.L. Petrov, 2015, published in Zhurnal Obshchei Khimii, 2015, Vol. 85, No. 2, pp. 251–254.
To the 80th Anniversary of B.I. Ionin
Synthesis of 5-Acetyl Derivatives of Alkyl 2-Furoates
and 3-(2-Furyl)acrylates
K. V. Kuticheva, L. M. Pevzner, and M. L. Petrov
St. Petersburg State Technological Institute (Technical University),
Moskovskii pr. 26, St. Petersburg, 190031 Russia
e-mail: pevzner_lm@list.ru
Received October 23, 2014
Abstract—Methyl 5-acetyl-2-furoate has been prepared via oxidation of 5-(1-hydroxyethyl)-2-furoate with the
Jones reagent. In turn, the starting compound has been synthesized via sequential chloroethylation of ethyl 2-
furoate, substitution of chlorine with acetoxy group, and methanolysis of the acetate in presence of sodium
methylate. The vinylog 2-furoate has been obtained as the major product via acetylation of ethyl 3-(2-furyl)-
acrylate with acetic anhydride in the presence of magnesium perchlorate.
Keywords: acetylfuran, chloroethylation, oxidation, acetylation, magnesium perchlorate
DOI: 10.1134/S1070363215020127
Acetylfurans are valuable starting materials for
preparation of various heterocyclic compounds [1–3].
Most acetylfurans known to date have been prepared
by acetylation of furan derivatives; however, in the
case of alkyl 2-furoates, 5-acetoacetyl-2-furoates (II)
are the major products [4] (Scheme 1).
various acylating agents. Therefore, we synthesized
compound I via oxidation of the corresponding
secondary alcohol III. In turn, the latter was obtained
from ethyl 2-furoate via the following transformations
sequence (Scheme 2).
Chloroethylation of ethyl 2-furoate was carried out
according to the procedure described elsewhere [5],
but we used paraldehyde instead of acetaldehyde for
It was impossible to find the conditions to prepare
acetylfuran I in reasonable yield via the reaction with
Scheme 1.
COOEt
COOEt
COOEt
CH CO
O
3
O
O
O
O
I
II
Scheme 2.
(
CH CHO)3
CH COONa
3
3
H C
H C
3
3
COOEt
COOEt
COOEt
O
O
HCl + ZnCl
2
O
O
Cl
O
H C CO
3
[
O]
MeOH
H C
H C
3
3
COOMe
COOMe
MeONa
O
OH
O
III
IV
4
24

SYNTHESIS OF 5-ACETYL DERIVATIVES OF ALKYL 2-FUROATES
425
Scheme 3.
CH MgI
3
CHO
O
O
O
OH
O
OCOCH3
VI
POCl , (CH ) NCHO
3
3 2
Ph P=CHCOOMe
3
OHC
O
MeOOC
COOMe
O
OCOCH3
OCOCH3
MeOH
H C
3
O
OH
V
convenience. The reaction mixture temperature was
maintained at 25–30°C in the course of the exothermic
reaction. Under such conditions, yield of the target
product was up to 41%. Substitution of chlorine with
acetoxy group was carried out via treatment with
sodium acetate in acetic acid. The reaction selectively
followed the above-mentioned pathway. No elimina-
tion of hydrogen chloride was observed. Methanolysis
of the acetate in the presence of catalytic amount of
sodium methylate occurred at room temperature
involving the both ester groups to give methyl 5-(1-
hydroxyethyl)furan-2-carboxylate III. According to
the spectral data, the target product was pure, and no
further purification was required.
formed in this reaction. In view of this, we proposed to
use oxidation of alcohol V to synthesize alkyl 3-(2-
furyl)acrylates. Possible pathway of the process is
presented in Scheme 3.
However, in contrast to the case of the esters of
furfuryl alcohol, formylation of acetate VI under the
Vilsmeier reaction conditions was slower than
polymerization of the substrate, even in the excess of
DMF. Thus, we failed to prepare the target aldehyde.
We further studied acetylation of alkyl 3-(2-furyl)-
acrylate with magnesium perchlorate as catalyst. The
catalyst has been successively used for acetylation of
phenol ethers and naphthalene derivatives [7], but has
revealed no advantage as compared to phosphoric acid
in acetylation of furan [8]. In the case of alkyl 3-(2-
furyl)acrylates, the presence of acidic agents in the
reaction mixture might cause polymerization of the
unsaturated compounds. Hence, neutral magnesium
perchlorate seemed better suitable in that case than the
inorganic or Lewis acids. The acetylation was carried
out upon boiling; the substrate : anhydride : catalyst
molar ratio was of 1 : 1.5 : 0.05. Reaction progress was
monitored by TLC. It was found that substitution
proceeded exclusively at position 5 of the furan ring.
In contrast to the data reported in [5], furfuryli-
deneacetone was not formed.
Oxidation of the secondary alcohol III in aqueous
acetone was carried out with a diluted mixture of
chromic and sulfuric acids at 10–20°C. However, even
under such mild conditions oxidation was not selec-
tive, and significant part of the oxidant was consumed
in side processes. When the stoichiometric amount of
the oxidant was taken, a mixture of the parent alcohol
III and methyl 5-acetylfuran-2-carboxylate IV in the
1
: 1 ratio was obtained. Repeated treatment of that
mixture with the oxidant in the 1.3 : 1 molar ratio with
respect to the residual alcohol III, other conditions
being the same, yielded the target acetylfuran IV as
1
green crystals. According to H NMR spectroscopy
data, the so obtained product was pure.
COOEt
O
Acetylation of alkyl 3-(2-furyl)acrylates has not
been described so far. It has been reported that
furylacrylic acid can be acetylated with acetic an-
hydride under catalysis with phosphoric acid. Besides
(
Ac) O
2
Mg(ClO4)2
COOEt
O
3-(5-acetylfur-2-yl)acrylic acid, furfurylidenacetone is
O
VII
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 2 2015

4
26
KUTICHEVA et al.
To conclude, alkyl 5-acetyl-2-furoates could be
added to a solution of sodium methylate prepared from
0.35 g of sodium and 120 mL of methanol. The
reaction mixture was incubated at room temperature
during 24 h and neutralized with 0.9 mL of acetic acid;
the solvent was then removed. The residue was
dissolved in 70 mL of dichloromethane, washed with
10 mL of water, and dried over sodium sulfate. After
the solvent removal, the residue was kept in vacuum
(1 mmHg) during 1 h at room temperature to give
obtained via oxidation of 2-furylethanol III, while its
vinylog VII was formed as the major product of
acetylation of 3-(2-furyl)acrylate with magnesium
perchlorate as catalyst.
EXPERIMENTAL
Melting points were measured with a Boetius
1
13
apparatus. H and C NMR spectra were recorded
with a Bruker DPX-400 spectrometer [400.13 MHz
14.9 g (90%) of the target product III as light-yellow
1
oil. Н NMR spectrum (CDCl ), δ, ppm: 1.52 d (3Н,
3
1
13
(
H) and 100.16 MHz ( C)] in deuterochloroform.
СН -hydroxyethyl, J 6.8 Hz), 3.84 s (3Н, СН О),
3
HH
3
4
Reaction progress was monitored with TLC on Silufol
UV-254 plates, developing by UV irradiation or in
iodine vapor.
4.89 q (1Н, СНОН, JHH 6.8 Hz), 6.33 d (1Н, Н -furan,
JHH 3.6 Hz), 7.09 d (1Н, Н -furan, J 3.6 Hz).
3
13
С
HH
NMR spectrum, (CDCl ), δ , ppm: 21.32 (СН -
3
С
3
hydroxy-ethyl), 51.86 (СН О), 63.56 (СНОН), 107.09
3
All solvents were purified and dried following the
standard procedures.
4
3
2
(
С -furan), 118.90 (С -furan), 143.33 (С -furan),
5
1
59.34 (С -furan), 162.43 (С=О).
Ethyl 5-(1-chloroethyl)furan-2-carboxylate. 3.9 g
of zinc chloride was added to a solution of 16.0 mL of
paraldehyde and 16.9 g of ethyl 2-furoate in 36 mL of
chloroform. Hydrogen chloride was passed through the
mixture during 5 h at 25–30°C under vigorous stirring.
Then, 50 mL of chloroform was added; the reaction
mixture was washed with water (2 × 30 mL) and dried
over calcium chloride. Solvent was removed under
reduced pressure, and the residue was distilled in
Methyl 5-acetylfuran-2-carboxylate (IV).
A
solution of 5.7 g of chromium trioxide in a mixture of
0.7 mL of water and 4.4 mL of concentrated sulfuric
acid was added dropwise under vigorous stirring at 10–
0°C to a solution of 14.9 g of methyl 5-(1-
4
2
hydroxyethyl)-2-furoate in 100 mL of acetone. The
reaction mixture was incubated during 1 h at room
temperature. Acetone was then removed on a rotary
evaporator. The formed precipitate was filtered off,
washed with several portions of water until neutral-
lization, and dried in air. 10.5 g of a mixture of com-
pound III and methyl 5-acetylfuran-2-carboxylate in
vacuum to give 10.0 g (41%) of the target product with
1
bp 91°C (1 mmHg). Н NMR spectrum (CDCl ), δ,
3
ppm: 1.33 t (3Н, СН -ethyl, J 7.0 Hz), 1.18 d (3Н,
3
HH
СН -chloroethyl, J 7.2 Hz), 4.32 q (2Н, СН О, J
3
HH
2
HH
1
the 1 : 1 ratio (according to the H NMR spectroscopy
7
.0 Hz), 5.09 q (1Н, СНСl, J 7.2 Hz), 6.41 d (1Н,
HH
4
3
data) was obtained. It was dissolved in 50 mL of
acetone and cooled to 10°C; a solution of 2.7 g of
chromium oxide and 2.4 mL of concentrated sulfuric
acid in 19 mL of water was added dropwise to the
mixture upon stirring at 20–26°C. The reaction
mixture was incubated during 3 h at room temperature,
and acetone was distilled off on a rotary evaporator.
The formed precipitate was washed with water until
neutralization and dried in air at room temperature.
Н -furan, J 3.6 Hz), 7.07 d (1Н, Н -furan, J 3.6 Hz).
HH
HH
Ethyl 5-(1-acetoxyethyl)furan-2-carboxylate. 15 g
of anhydrous sodium acetate was added to a solution
of 25.4 g of ethyl 5-chloroethyl-2-furoate in 125 mL of
glacial acetic acid. The reaction mixture was refluxed
during 9 h under vigorous stirring, poured in 300 mL
of water, and extracted with toluene (3 × 50 mL). The
extract was dried over calcium chloride, toluene was
removed under reduced pressure, and the residue was
1
Yield 6.9 g (47%), mp 88°C, light-green crystals. Н
distilled in vacuum. Yield 20.3 g, colorless oil, bp
NMR spectrum (CDCl ), δ, ppm: 2.57 s (3Н, СН СО),
3
3
1
1
20–121°C (1 mmHg). Н NMR spectrum (CDCl ), δ,
3
3.94 s (3Н, СН О), 7.20 d (1Н, J 3.6 Hz), 7.30 d
3
HH
13
3
4
ppm: 1.36 t (3Н, СН -ethyl, J 7.2 Hz), 1.61 d (3Н,
3
HH
(1Н, JHH 3.6 Hz) (Н ,Н -furan). С NMR spectrum
(CDCl ), δ , ppm: 26.31 (СН СО), 52.39 (СН О),
СН -ethanol, J 6.8 Hz), 2.07 s (3Н, СН -acetate),
3
HH
3
3
С
3
3
3
,4
2
4
6
.35 q (2Н, СН О, J 7.2 Hz), 5.94 q (1Н, СНО, J
2 HH HH
116.63 + 118.78 (С -furan), 146.21 (С -furan),
154.21 (С -furan), 158.55 (С=О-ester), 187.49 (С=О-
4
3
5
.8 Hz), 6.41 d (Н -furan, J 3.6 Hz) 7.10 d (Н -
HH
furan, JHH 3.6 Hz).
ketone).
Methyl 5-(1-hydroxyethyl)furan-2-carboxylate
III). 20.3 g of ethyl 5-(1-acetoxyethyl)-2-furoate was
Ethyl 3-(5-acetylfur-3-yl)acrylate (VI). A mixture
of 9.5 g of 3-(2-furyl)acrylate, 8.1 mL of acetic
(
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 2 2015

SYNTHESIS OF 5-ACETYL DERIVATIVES OF ALKYL 2-FUROATES
427
anhydride, and 0.6 g of anhydrous magnesium perchlo-
rate was heated under vigorous stirring during 1.5 h at
27–128°C. The reaction progress was monitored via
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ACKNOWLEDGMENTS
The work was in scope of the governmental
contract; financial support of Ministry of Education
and Science of Russian Federation is acknowledged.
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