Convenient synthesis of 5-alkylfuran-2(5H)-ones

Article abstract of DOI:10.1080/00397911.2010.516461

A convenient synthesis of 5-alkylfuran-2(5H)-ones are described starting from 3-nitropropanoate and aldehydes, promoted by neutral alumina, in 35-60% overall yields, via a condensation-lactonization-elimination pathway. Copyright

Full text of DOI:10.1080/00397911.2010.516461

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Convenient Synthesis of 5-
Alkylfuran-2(5H)-ones
a
b
a
Jie Ma , Si Hong Wang & Yan Bing Yin
a
College of Chemistry and Chemical Engineering, Qiqihaer
University, Qiqihaer, Heilongjiang, China
b
Analysis and Test Center, Yanbian University, Yanji, Jilin, China
Published online: 11 Jul 2011.
To cite this article: Jie Ma , Si Hong Wang & Yan Bing Yin (2011) Convenient Synthesis of 5-
Alkylfuran-2(5H)-ones, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 41:20, 3026-3031, DOI: 10.1080/00397911.2010.516461
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Synthetic Communications , 41: 3026–3031, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.516461
CONVENIENT SYNTHESIS OF
-ALKYLFURAN-2(5H)-ONES
5
1
Jie Ma, Si Hong Wang, and Yan Bing Yin
2
1
1
College of Chemistry and Chemical Engineering, Qiqihaer University,
Qiqihaer, Heilongjiang, China
2
Analysis and Test Center, Yanbian University, Yanji, Jilin, China
GRAPHICAL ABSTRACT
Abstract A convenient synthesis of 5-alkylfuran-2(5H)-ones are described starting from
3-nitropropanoate and aldehydes, promoted by neutral alumina, in 35–60% overall yields,
via a condensation–lactonization–elimination pathway.
Keywords 5-Alkylfuran-2(5H)-ones; condensation; elimination; lactonization; neutral
alumina
INTRODUCTION
Compounds containing the furan-2(5H)-one scaffold are important synthetic
[
targets because of their presence in many natural products, which are widely used
1]
[
2]
as antibiotics, anticancer drugs, bactericides, insecticides, fungicides, and so on.
The presence of the a,b-unsaturated carbonyl moiety bestows high reactivity of
furan-2(5H)-ones towards various reagents. Therefore, furan-2(5H)-ones serve
as useful building blocks in organic synthesis. Numerous synthetic methods have
[
3]
[4]
been developed. However, some of these methods have modest yields, harsh reac-
tion conditions, or tedious procedures. As part of our growing interest in using
furan-2(5H)-ones as heterocyclic building blocks in organic synthesis, we describe
herein a convenient and efficient synthetic route for the preparation of furan-2
(
5H)-ones. The whole route is via three steps: condensation of 3-nitropropanoate
[5]
with aldehydes promoted by neutral alumina, lactonization by treatment with tri-
fluoroacetic acid (CF COOH), and then elimination of nitrous acid (HNO )
3
2
(Scheme 1).
Received December 7, 2009.
Address correspondence to Jie Ma, College of Chemistry and Chemical Engineering, Qiqihaer
University, Qiqihaer, Heilongjiang 161006, China. E-mail: majie227@126.com
3
026

CONVENIENT SYNTHESIS OF 5-ALKYLFURAN-2(5H)-ONES
3027
Scheme 1. Synthesis of 5-alkylfuran-2(5H)-ones.
RESULTS AND DISCUSSION
It is feasible that methyl 3-nitropropanoate acts as starting material just
because of the simultaneous behavior of the nitro group as an electron-withdrawing
group and a good leaving group. Moreover, pKa values of the methyl group in
[6]
[7]
nitromethane and ethyl acetate are 17.2 and 30.5, respectively, so the a-carbon
atom activated by the nitro group is much easier to form into a carbanion in the
presence of alumina. Alumina has long been used as a heterogeneous catalyst and
reagent in organic synthesis. Our procedure works on neutral alumina, which has
been widely used for the very mild preparation of polyfunctional and labile
[
8]
2
-nitroalkanols.
A series of substituted 5-alkylfuran-2(5H)-ones 1a–1g were synthesized in good
yields. The results are shown in Table 1.
Promoted by neutral alumina, intermediates 3 were obtained in quantitative
[9]
yields via the Henry reaction. In the presence of trifluoroacetic acid, the desired nitro
[
lactones 2 were formed in quantitative yields. Then 2 was treated with triethylamine
10]
1
to produce the corresponding 1. All products were confirmed on the basis of H NMR,
1
3
C NMR, mass (MS), and Fourier transform–infrared (FT-IR) spectra. Thus, the
whole process is via a Henry reaction–lactonization–elimination pathway (Scheme 2).
To investigate the generality of this method, several attempts were made to
condense methyl 3-nitropropanoate with benzaldehyde and trimethylacetaldehyde.
However, it was difficult to avoid dehydration of the nitroalcohols into nitroalkenes
[11]
when benzaldehyde was employed. The corresponding nitroalcohols could not be
obtained when trimethylacetaldehyde was used instead of benzaldehyde. The results
may be attributed to the steric hindrance around the carbonyl carbon and the revers-
[9b]
ible nature of the Henry reaction.
In summary, the present procedure provides a convenient method for the
synthesis of 5-alkylfuran-2(5H)-ones via the Henry reaction–lactonization–elimin-
ation pathway. The advantages offered by this method are available starting
Table 1. Total yields of 5-alkylfuran-2(5H)-ones promoted by neutral alumina
Compounds
1a
1b
1c
1d
1e
1f
1g
R
Yields (%)
Methyl
54.3
Ethyl
49.2
i-Propyl
42.0
Propyl
45.6
Butyl
40.3
Pentyl
38.7
Hexyl
35.1

3028
J. MA, S. H. WANG, AND Y. B. YIN
Scheme 2. The proposed mechanism of 5-alkylfuran-2(5H)-ones.
material, simple operation, insensitivity to air and moisture, good yields of products,
and cost-effectiveness.
EXPERIMENTAL
[
12] 1
Methyl 3-nitropropanoate was prepared according to the literature.
1
H
3
NMR and C NMR spectra were recorded on a Bruker AV 300 spectrometer. Elec-
trospray ionization ESI (MS)–spectra (70 eV) were measured on an Abqstar pulsar
mass spectrometer. Only molecular ions [M ] were given. IR spectra were obtained
on a PE-1730 spectrometer.
þ
General Procedure for the Synthesis of 3
Cooled with an ice-water bath, the mixture of methyl 3-nitropropanoate
7.5 mmol) and an aldehyde (10 mmol) was added to a 100-mL, three-necked flask
(
equipped with a mechanical stirrer and charged with neutral alumina (10 g). Then
the mixture was vigorously stirred for 5 min. After standing for 24 h, the mixture
was washed with ethyl acetate and evaporated at reduced pressure to produce crude 3.
General Procedure for the Synthesis of 2
Trifluoroacetic acid (0.1 mL) was added to a solution of 3 in dry dichloro-
methane (10 mL), and the resulting mixture was refluxed for 6 h. Then the mixture
was cooled, washed with water, dried over anhydrous sodium sulfate, and evapo-
rated to obtain crude products as diasteromeric mixture 2.
General Procedure for the Synthesis of 1
Triethylamine (0.1 mL) was added to a solution of 2 in dry dichloromethane
10 mL) and stirred at reflux until elimination was complete. Then the mixture was
(
cooled, washed with water, dried over anhydrous sodium sulfate, and evaporated
to yield 1. The crude product was purified by a silica-gel column chromatography
with petroleum ether and ethyl acetate as eluent to give the desired 1. The spectro-
scopic data of compounds 1a–1 g have been reported in Ref. 13.

CONVENIENT SYNTHESIS OF 5-ALKYLFURAN-2(5H)-ONES
3029
Data for Selected Compounds
1
Compound 3a. Yellow viscous oil. H NMR (300 MHz, CDCl ): d 1.25 and
3
1
.35 (pair doublets, J ¼ 6.0 Hz, 3H each, -CH ), 3.16 and 3.24 (pair doublets,
3
J ¼ 3.0 Hz, 2H each, -CH COO-), 3.63 and 3.69 (pair singlets, 3H each, -COOCH ),
2
3
4
.05–4.11 and 4.17–4.20 (pair multiplets, 1H each, -CHOH), 4.90–4.95 and 5.04–5.32
1
3
(
3
2
pair multiplets, 1H each, -CHNO2). C NMR (75 MHz, CDCl ): d 20.2, 20.5, 31.4,
3
ꢀ
1
1.6, 52.3, 52.4, 67.6, 67.9, 87.6, 87.8, 170.3, 170.8. IR (cm , film): 3217, 2976, 2899,
ꢀ
þ
883, 1715, 1560, 1395, 1340. HR-MS (ESI ) calcd. for C H NO :176.0637 [M
6
1]; found: 176.0573 [M ꢀ 1].
11
5
þ
ꢀ
1
Compound 3b. Yellow viscous oil. H NMR (300 MHz, CDCl ): d 0.87 and
3
0
multiplets, 2H each, -CH -), 3.17–3.20 and 3.22–3.24 (pair multiplets, 2H each,
.96 (pair multiplets, J ¼ 6.0 Hz, 3H each, -CH ), 1.43–1.45 and 1.45–1.48 (pair
3
2
-CH COO-), 3.62 and 3.68 (pair singlets, 3H each, -COOCH ), 3.95–3.98 and
2 3
4
.03–4.21 (pair multiplets, 1H each, -CHOH), 4.82–4.92 and 4.95–5.02 (pair multi-
3
1
plets, 1H each, -CHNO2). C NMR (75 MHz, CDCl ): d 9.7, 9.8, 26.1, 26.7, 31.3,
3
3
1.9, 52.3, 52.4, 73.1, 73.5, 86.5, 86.8, 170.2, 170.8.
1
Compound 3c. Yellow viscous oil. H NMR (300 MHz, CDCl ): d 1.03 and
3
1
each, -CH-), 3.23–3.25 and 3.27–3.30 (pair multiplets, 2H each, -CH ), 3.72 and
.05 (pair doublets, J ¼ 7.2 Hz, 3H each, -CH ), 1.72 and 1.68 (pair multiplets, 1H
3
2
3
1
.74 (pair singlets, 3H each,COOCH ), 3.89–3.92 and 3.96–4.00 (pair multiplets,
3
H each, -CHOH), 4.99–5.02 and 5.03–5.07 (pair multiplets, 1H each, -CHNO2).
C NMR (75 MHz, CDCl ): d 17.2, 17.5, 31.6, 31.9, 34.5, 34.9, 52.4, 52.5, 70.2,
1
3
3
7
0.3, 84.9, 85.3, 169.8, 170.7.
1
Compound 2a. Yellow viscous oil. H NMR (300 MHz, CDCl ): d 1.42 and
3
1
.55 (pair doublets, J ¼ 6.3 Hz, 3H each, CH ), 3.24 and 3.30 (pair doublets,
3
J ¼ 3.0 Hz, 2H each, -CH CO-), 4.88–4.90 and 4.90–4.95 (pair multiplets, 1H each,
2
1
3
O NCH-), 4.95–5.01 and 5.30–5.32 (pair multiplets, 1H each, -CHOCO).
2
C
NMR (75 MHz, CDCl ): d 13.8, 14.9, 31.7, 32.4, 76.6, 78.9, 85.0, 85.1, 171.6,
3
ꢀ ꢀ1
1
-
72.4; IR (cm , film): 2976, 2899, 2883, 1706, 1560, 1171 cm . HR-MS (ESI )
1
þ
þ
calcd. for C H NO : 144.0375 [M ꢀ 1]; found 144.0309 [M ꢀ 1].
5
7
4
1
Compound 2b. Yellow viscous oil. H NMR (300 MHz, CDCl ): d 1.08 and
3
1
.16 (pair triplets, J ¼ 6.3 Hz, 3H each, -CH ), 1.69–1.74 and 1.83–1.88 (pair multi-
3
plets, 2H each, -CH -), 3.29 and 3.36 (pair doublets, J ¼ 3.0 Hz, 2H each, -CH CO-),
2
2
4
.60–4.62 and 4.78–4.79 (pair multiplets, J ¼ 6.3 Hz, 1H each, O NCH-), 4.98–5.00
2
1
3
and 5.31–5.32 (pair multiplets, J ¼ 6.3 Hz, 1H each, -CHOCO-). C NMR
(75 MHz, CDCl ): d 9.0, 10.11, 23.2, 27.6, 32.0, 32.5, 81.9, 83.6, 83.7, 84.0, 171.4,
3
1
71.8.
1
Compound 2c. Yellow viscous oil. H NMR (300 MHz, CDCl ): d 1.07 and
3
1
.16 (pair doublets, J ¼ 6.9 Hz, 6H each, 2CH ), 2.02–2.03 and 2.03–2.04 (pair multi-
3
plets, 1H each, -CH-), 3.24 and 3.30 (pair doublets, J ¼ 3.3 Hz, 2H each, -CH CO-),
2
4
.67–4.69 and 4.77–4.90 (pair multiplets, 1H each, O NCH-), 5.03–5.06 and
2

3030
J. MA, S. H. WANG, AND Y. B. YIN
1
3
5
1
.35–5.37 (pair multiplets, 1H each, -CHOCO-). C NMR (75 MHz, CDCl ): d 17.1,
3
7.5, 29.2, 30.9, 33.0, 32.5, 82.2, 82.4, 86.8, 87.2, 171.5, 171.7.
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