New procedure for synthesis alkyl esters of 5-acetyl-2-furan-carboxylic acid alkyl ester

Article abstract of DOI:10.1134/S1070427209020335

The possibility to synthesize alkyl esters of 5-acetyl-2-furan-carboxylic acid by the reaction of 5-acetyl-2-furan with CCl₄ and aliphatic alcohols under the action of iron-containing catalysts was studied.

Full text of DOI:10.1134/S1070427209020335

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2009, Vol. 82, No. 2, pp. 340−342. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © R.I. Khusnutdinov, A.R. Baiguzina, R.R. Mukminov, U.M. Dzhemilev, 2009, published in Zhurnal Prikladnoi Khimii, 2009, Vol.
82, No. 2, pp. 346−348.
BRIEF
COMMUNICATIONS
New Procedure for Synthesis Alkyl Esters
of 5-Acetyl-2-Furan-Carboxylic Acid Alkyl Ester
R. I. Khusnutdinov, A. R. Baiguzina, R. R. Mukminov, and U. M. Dzhemilev
St. Petersburg State Polytechnical University, St. Petersburg, Russia
Received January 13, 2009
Abstract—The possibility to synthesize alkyl esters of 5-acetyl-2-furan-carboxylic acid by the reaction of 5-
acetyl-2-furan with CCl4 and aliphatic alcohols under the action of iron-containing catalysts was studied.
DOI: 10.1134/S1070427209020335
furfulyl alcohol as an example was unsuccessful and has
led to obtaining methyl ester of levulinic acid [6].
Furan derivatives find wide application as starting
compounds in the synthesis of pharmaceuticals. Thus,
2-furan-carboxylic acid and its esters possess anti-
tumor activity [1], and methyl ester of 5-acetyl-2-furan-
carboxylate (I) is used as a starting compound in the
synthesis of pharmaceuticals applied to treatment and
prophylaxis of mammals’ peptide cankers [2].
It has been shown that methyl 5-acetyl-2-furan-
carboxylate (I) is the main product of the reaction between
2-acetylfuran and the system CCl4−CH3OH−catalyst.As
the catalysts we have tested compounds and complexes of
Ni, Cu, Mn, Pd, V, and Fe, which have the common ability
to labilize the C-Cl bond in the CCl4 molecule [7, 8].
The majority of known procedures for the preparation
of methyl 5-acetyl-2-furan-carboxylate (I) are based on
a catalytic acylation of 2-furan-carboxylic acid esters by
acetic anhydride. When H2SO4 is used as the acylation
catalyst the yield of I is only 0.5% [3], whereas in the
presence of fourfould SnCl4 excess it reaches 96% [2].
Among the compounds and complexes, which have
shown catalytic activity, iron derivatives form the
following series: Fe(acac)3 (95%) > Fe(C5H5)2 (90%)
> FeBr2 (87%). The reaction proceeds at 120ºC and is
completed within 9 h by the full conversion of initial
2-acetyl-2-furan:
With the aim to develop a new procedure for the
synthesis of methyl 5-acetyl-2-furan-carboxylate (I),
we studied the possibility of introducing the CO2CH3
group in a molecule of 2-acetylfuran (more accessible
than the methyl 2-furancarboxylates [4]) by means of
a new procedure successfully tested on thiophene and its
derivatives [5]. The essence of the procedure consists in the
interaction of thiophenes with the system CCl4−CH3OH−
catalyst: under the action of the catalyst thiophene is
alkylated by CCl4 to form 2-trichloromethylthiophene,
which then undergoes alcoholysis to form methyl 2-
thiophenecarboxylateic acid. Starting the study of the
reaction of 2-acetyl-2-furan with the system CCl4−
CH3OH−catalyst, it was necessary to take into account
the pronounced tendency of the furan cycle to opening, as
the attempt to realize the above-mentioned reaction using
CH3CO
[Catalyst]
+ CCl4 + CH3OH
CO2CH3,
(1)
CH3CO
120 C, 9 h
HCl, CHCl3
I
[Catalyst]: Fe(C5H5)2, Fe(acac)3, FeBr2.
The structure of compound I was confirmed by
the methods of one-dimensional [1Н, 13С, and APT
(Attached proton treatment) NMR spectroscopy] and
two-dimensional NMR spectroscopy [HMBC (Hetero
Multiple-bond Correlation)]. The 2,5-position of the
340

NEW PROCEDURE FOR SYNTHESIZING ALKYL ESTERS
341
substituents is unambiguously determined by the down-
field values of chemical shifts (δ С2 = 145.80 and δ С5 =
154.26 ppm), the latter signal correlating in the HMBC
experiment with protons of the acetyl group which
resonate at 2.57 ppm.
[90 MHz (1Н), 22.5 MHz (13С)] spectrometers in CDCl3,
chemical shifts δ (ppm) were measured relative to TMS.
GS-MS data were obtained on a Finnigan MAT-112S
chromatography-mass spectrometer (electron impact
70 eV). The chromatographic analysis was carried out on
a Chrom-5 instrument [a 1.2 m × 33 mm column, silicon
SE-30 (5%) as the istationary, on a Chromaton N-AW-
HMDS, a temperature mode from 50 up to 250ºC with
the heating rate of 8 deg min−1 and helium as a gas-carrier
(47 ml min−1)].
We can assume that, similarly to the case of thiophene,
the probable reaction scheme includes the successive
alkylation of 2-acetyl-2-furan by carbon tetrachloride
with the formation of 5 trichloromethyl-2-acetyl-2-furan,
which undergoes alcoholysis with the conversion to the
corresponding 5-acetyl-2-furancarboxylic acid ester:
As the initial reagents we used commercially
available 2-acetyl-2-furan, methanol, ethanol, propanol,
isopropanol, and carbon tetrachloride, which were
preminarily distilled. Iron acetylacetonate, ferrocene,
and iron bromide (“Acros” made) were recrystallized and
dried in a vacuum desiccator before using.
[Fe]
CH3CO
+ CCl4
CH3CO
+ CCl3
+ CH3OH
General procedure of obtaining esters of 5-acetyl-2-
furancarboxylic acid. In a stainless-steel microreactor
(V = 17 ml) or in a glass ampula (V = 20 ml) 0.1 mmol
of Fe(acac)3, 10 mmol of 2-acetyl-2-furan, 80 mmol of
an aliphatic alcohol, and 20 mmol of CCl4 were charged
under argon; the reactor was hermetically closed (the
ampula was sealed) and heated up at 120ºC within 6−9 h
with permanent stirring.After the reaction termination the
reactor (ampule) was cooled to room temperature, opened,
and the reaction mixture was filtered through a silica gel
layer (eluent−hexane). After distilling off a solvent the
residuel was recrystallized or distilled in a vacuum.
CH3CO
CO2CH3,
This assumption is supported by the fact that when
methanol is replaced by ethyl, propyl, and isopropyl
alcohols, ethyl (II), propyl (III), and isopropyl (IV)
esters, respectively, of 5-acetyl-2-furan-carboxylic acid
are formed with fairly high yields. Furthermore HCl and
esters of the alcohols taken in the reaction were detected
in the reaction mass. A reactively low yield of ethyl 5-
acetyl-2-furancarboxylate (II) is attributable to the fact
that the side reaction of the formation of diethyl ester
readily proceeds:
Methyl 5-acetyl-2-furancarboxylate (I). Mp
100.5−101ºC (according to the published data [9] 101−
102ºC). Yield 95%. 1H NMR spectrum, δ, ppm: 2.57 (s,
3H, СН3СO), 3.95 (s, 3H, ОСН3), 7.15-7.25 (m, 2H,
furan, =CH−СH=). 13С NMR, δ, ppm: 26.30 (COCH3),
52.37 (ОСН3), 116.54 (С4), 118.75 (С3), 145.80 (С2),
154.26 (С5), 158.62 (COOCH3), 187.46 (COCH3). Mass
spectrum, m/e (Irel, %): 168 [M]+ (42), 43 (30), 59 (10),
69 (12), 79 (5), 95 (21), 125 (4), 137 (20), 153 (100), 154
(10), 169 (18). Found (%): C 57.28, Н 5.06, O 37.66.
Calculated (%): C 57.14, Н 4.80, O 38.06.
CH3CO
+ CCl4 + ROH
[Catalyst]
CO2R
CH3CO
[Cat.] - Fe(C5H5)2, Fe(acac)3, FeBr2; R = Me (I), Et (II),
n-Pr (III), i-Pr (IV).
Ethyl 5-acetyl-2-furancarboxylate (II). Mp 71−72ºC
(according to the published data [9] 71−71.5ºC). Yield 45
%. 1H NMR spectrum, δ, ppm: 1.38 (t, 3JHH =7.2 Hz, 3H,
CH3CH2), 2.55 (s, 3H, COСН3), 4.39 (q, 3JHH = 7.2 Hz,
2H, CH3CH2), 7.15−7.25 (m, 2H, furan, =CH-СH=). 13С
NMR, δ, ppm: 14.21 (CH3CH2), 26.30 (COСН3), 61.63
(ОСН2), 116.59 (С4), 118.54 (С3), 146.53 (С2), 154.14
(С5), 158.14 (COOEt), 187.51 (COCH3). Found (%):
C 60.01, Н 5.86, O 34.13. С9Н10О4. Calculated (%):
C 59.33, Н 5.53, O 35.13.
We have found experimentally that the optimal ratio
of the catalyst and reagents is Fe(acac)3 : [2-acetyl-2-
furan] : [CCl4] : [ROH] =1 : 100 : 200 : 800.
EXPERIMENTAL
The 1Н and 13С NMR spectra were recorded on Bruker
Avance-400 (400.13 and 100.62 MHz) and JEOLFX90Q
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 82 No. 2 2009

342
KHUSNUTDINOV et al.
Propyl 5-acetyl-2-furancarboxylate (II). Mp 90ºC/2
This work was supported by Ministry of Education and
Science of the Russian Federation (grant NSh 7470.2006)
and the Program OKhNM no. 8 of the Russian Academy
of Sciences.
1
mm Hg. Yield 60%. H NMR spectrum, δ, ppm: 0.93
3
(t, 3H, JHH = 8.2 Hz, СН3CH2CH2), 1.4−2.0 (m, 2H,
СН3CH2CH2), 2.47 (s, 3H, COСН3), 4.22 (t, 3JHH = 7.4
Hz, 2H, СН3CH2CH2), 7.05-7.4 (m, 2H, furan, =CH−
СH=). 13С NMR, δ, ppm: 9.76 (СН3CH2CH2), 21.48
(СН3CH2CH2), 25.68 (COСН3), 66.55 (ОСН2), 116.43
(С4), 118.16 (С3), 146.19 (С2), 153.78 (С5), 157.75 (Pr-
n-COO), 187.51 (COCH3). Found (%): C 60.52, Н 5.87,
O 33.61. С10Н12О4. Calculated (%): C 61.21, Н 6.17, O
32.62.
REFERENCES
1. Ziganshina, E.Kh., Kazantseva, V.M., Pisareva, V.S., and
Korshunov, S.P., Izv. Vyssh. Uchebn. Zaved., Khim. Khim.
Tekhnol., 1988, vol. 31, no. 11, pp. 40−42.
2. US Patent 4814341, 514/370; 548/193.
3. Lolya, D.O., Venter, K.K., and Giller, S.A., Izv. Akad. Nauk
LatvSSR, Ser. Khim., 1976, no. 4, pp. 431−435.
4. Ponomarev, A.A., Sintezy i reactsii furanovykh veshchestv
(Syntheses and Reactions of Furan Substances), Saratov:
Saratov. universitet, 1960.
Isoropyl 5-acetyl-2-furancarboxylate (II). Mp
96ºC/4 mm Hg. Yield 60%. 1H NMR spectrum, δ, ppm:
1.27 [d, JHH =7.1 Hz, 6Н, (СH3)2СH], 2.37 (s, 3H,
СН3CO), 4.95−5.5 (m, 1H, [СH3)2СH], 7.05−7.5 (m,
2H, furan, СН). 13С NMR, δ, ppm: 21.57 [СH3)2СH],
25.68 (COСН3), 69.35 (ОСН2), 116.53 (С4), 118.19
(С3), 146.32 (С2), 153.84 (С5), 157.30 (i-COOPr),
186.57 (COCH3). Found (%): C 62.40, Н 6.32, O 31.28.
С10Н12О4. Calculated (%): C 61.21, Н 6.17, O 32.62.
3
5. Husnutdinov, R.I., Shchadneva, N.A., Baiguzina, A.R., et
al., Neftekhim., 2008, vol. 48, no. 4, pp. 1−8.
6. Husnutdinov, R.I., Baiguzina, A.R., Smirnov, A.A., et al.,
Zh. Prikl. Khim., 2007, vol. 80, no. 10, pp. 1658−1661.
7. Husnutdinov, R.I., Shchadneva, N.A., Baiguzina, A.R., et
al., Neftekhim., 2004, vol. 44, no. 5, pp. 329−335.
8. Husnutdinov, R.I., Shchadneva, N.A., Burangulova, R.Yu.,
et al., Zh. Org. Khim., 2006, vol. 42, no. 11, pp. 1629−
1635.
CONCLUSION
The reactions of 2-acetyl-2-furan with CCl4 and
aliphatic alcohols in the presence of iron complexes
result in the formation of 5-acetyl-2-furancarboxylate
with 45−95% yields.
9. Ercoli, R., Mantica, E., Chozotto, G., and Santambrogio, E.,
J. Org. Chem., 1967, vol. 32, pp. 2917−2918.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 82 No. 2 2009