Synthesis of (E)- and (Z)-5-(bromomethylene)furan-2(5H)-one by bromodecarboxylation of (E)-2-(5-oxofuran-2(5H)-ylidene)acetic acid

Article abstract of DOI:10.1080/00397910500522108

(E)- and (Z)-5-(bromomethylene)furan-2(5H)-one have been prepared starting from the commercially available adduct between furan and maleic anhydride. A bromodecarboxylation reaction is a key step in the synthesis. The reaction gives the (E)- or (Z)-5-(bromomethylene)furan-2(5H)-one as the major product, dependent on the method used in the bromodecarboxylation. Copyright Taylor & Francis Group, LLC.

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Synthesis of (E)‐ and
(Z)‐5‐(Bromomethylene)furan‐2(5H)‐one
by Bromodecarboxylation of
(E)‐2‐(5‐Oxofuran‐2(5H)‐ylidene)acetic Acid
Tore Benneche a , Jessica Lönn b & Anne Aamdal Scheie b
a Department of Chemistry, University of Oslo, Norway
b Department of Oral Biology, Faculty of Dentistry, University of Oslo,
Norway
Version of record first published: 16 Aug 2006.
To cite this article: Tore Benneche, Jessica Lönn & Anne Aamdal Scheie (2006): Synthesis of (E)‐ and
(Z)‐5‐(Bromomethylene)furan‐2(5H)‐one by Bromodecarboxylation of (E)‐2‐(5‐Oxofuran‐2(5H)‐ylidene)acetic
Acid, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 36:10, 1401-1404
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Synthetic Communicationsw, 36: 1401–1404, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500522108
Synthesis of (E)- and
(Z)-5-(Bromomethylene)furan-2(5H)-one
by Bromodecarboxylation of
(E)-2-(5-Oxofuran-2(5H)-ylidene)acetic
Acid
Tore Benneche
Department of Chemistry, University of Oslo, Norway
¨
Jessica Lonn and Anne Aamdal Scheie
Department of Oral Biology, Faculty of Dentistry, University of Oslo,
Norway
Abstract: (E)- and (Z)-5-(bromomethylene)furan-2(5H)-one have been prepared
starting from the commercially available adduct between furan and maleic
anhydride. A bromodecarboxylation reaction is a key step in the synthesis. The
reaction gives the (E)- or (Z)-5-(bromomethylene)furan-2(5H)-one as the major
product, dependent on the method used in the bromodecarboxylation.
Keywords: Alkenes, g-alkylidene butenolides, bromodecarboxylation, carboxylic
acids, halogenations
A number of 5-(bromomethylene)furan-2(5H)-ones have interesting biologi-
cal activity.[1] It has been reported that (Z)-5-(bromomethylene)furan-
2(5H)-one (5) (Scheme 1) is capable of interfering with N-acyl homoserine
lactone-mediated quorum sensing in Pseudomonas aeruginosa.[2]
Received in Poland October 6, 2005
Address correspondence to Tore Benneche, Department of Chemistry, University of
Oslo, P.O. Box 1033 Blindern, 0315 Oslo, Norway. Fax: þ47 22 85 55 07; E-mail:
tore.benneche@kjemi.uio.no
1401

¨
T. Benneche, J. Lonn, and A. A. Scheie
1402
Scheme 1. Method A: 1, Br2, TFA, CH2Cl2, rt, 3 d; 2, NEt3, DMF, MW, 1 min.
Method B: Brþ(coll)2PF62, CH2Cl2, rt, 2 h.
We needed both (E)- and (Z)-5-(bromomethylene)furan-2(5H)-one, (4)
and (5) respectively, for biological testing.
(Z)-5-(Bromomethylene)furan-2(5H)-one (5) has previously been
prepared from levulinic acid.[3] The preparation of the (E)-isomer 4 has, to
our knowledge, not been reported.
The a,b-unsaturated ester 2 can be prepared in good yield from the commer-
cially available anhydride 1 in a Wittig reaction,[4] and the ester 2 can be cleaved
to the acid 3 in quantitative yield with trifluoroacetic acid in dichloromethane.
A number of methods have been used in the bromodecarboxylation of
a,b-unsaturated acids having a b-aryl substituent.[5] Without such a substitu-
ent the methods are much more limited.[6] Bromination of the acid 3 with
excess bromine in a mixture of trifluoroacetic acid and deuterated chloroform
1
gave, according to H NMR, the corresponding 2,3-dibromoalkanoic acid as
the major product. When this crude product was heated in a microwave
oven (200 W) for 1 min in dimethylformamide and in the presence of triethy-
lamine,[6b] the (Z)-furanone 5 was isolated in 46% yield together with 7% of
the (E)-isomer 4 (method A, Scheme 1). On the other hand, if the acid 3 was
reacted with bis(2,4,6-trimethylpyridine)bromine(I) hexafluorophosphate[6a]
in dichloromethane at room temperature (method B, Scheme 1), the (E)-
1
furanone 4 was the only isomer observed (TLC and H NMR). However,
the yield in this reaction was low (22%).
Exposure of the (E)-isomer to UV light led to isomerization of the
thermodynamically more stable (Z)-isomer. A thermal isomerization of
(E)-5-(iodomethylene)furan-2(5H)-one to the (Z)-isomer has been observed.[7]
EXPERIMENTAL
1H NMR and the 13C NMR spectra were recorded on Bruker Avance
DPX instruments. Mass spectra, under electron-impact conditions, were

(E) and (Z)-5-(Bromomethylene)furan-2(5H)-one
1403
recorded at 70 eV ionizing energy on a Fision ProSpec instrument.
Microwave irradiation was carried out with a CEM MDS-81D microwave
oven.
Preparation of (E)-5-(Bromomethylene)furan-2(5H)-one (4)
and (Z)-5-(Bromomethylene)furan-2(5H)-one (5)[3]
Method A
(E)-t-Butyl 2-(5-oxofuran-2(5H)-ylidene) acetate (2[4]; 196 mg, 1.0 mmol)
was dissolved in a mixture of CH2Cl2 (1 mL) and TFA (1 mL). The reaction
mixture was stirred at room temperature for 2 h, evaporated, and redissolved
in a mixture of CDCl3 (2 mL) and TFA (0.1 mL). Bromine (2 mL, 2 M in
1
CCl4) was added, and the mixture was stirred at room temperature until H
NMR showed that all starting material had been consumed (3 d). The
solvents were evaporated off, and the residue was dissolved in DMF (2 mL).
Triethylamine (0.15 mL, 1.08 mmol) was added, and the mixture was heated
in a microwave oven (200 W) for 1 min. Water was added and the product
was extracted into Et2O, washed with brine (3 ꢀ 10 mL), dried (MgSO4),
and evaporated. The products were separated by flash chromatography
(silica, hexane–EtOAc 3 : 2). Rf ¼ 0.55; (E)-5-(bromomethylene)furan-
1
2(5H)-one (4). Yield: 12 mg (7%); mp ¼ 33–358C; H NMR (200 MHz,
0
CDCl3): d ¼ 6.42 (dd, J3,1 ¼ 1.8 Hz, J3,4 ¼ 5.6 Hz, 3-H), 6.55 (dd,
J1 ,4 ¼ 0.7 Hz, J1 ,3 ¼ 1.8 Hz, 10-H), 7.80 (dd, J4,1 ¼ 0.7 Hz, J4,3 5.6 Hz,
4-H). 13C NMR (125 MHz, CDCl3): d ¼ 94.66, 122.81, 140.43, 152.12,
168.81. MS: m/z ¼ 176 (M þ 2, 100), 174 (M, 100), 148 (47), 146
(48), 122 (30) 120 (32), 95 (52). Rf ¼ 0.31; (Z)-5-(bromomethylene)furan-
2(5H)-one (5).[3] Yield 80 mg (46%); 1H NMR (200 MHz, CDCl3):
d ¼ 6.09 (s, 10-H), 6.30 (d, J3,4 ¼ 3.5 Hz, 3-H), 7.37 (d, J4,3 ¼ 3.5 Hz, 4-H).
MS: m/z ¼ 176 (M þ 2, 100), 174 (M, 100), 148 (33), 146 (35), 122 (28)
120 (30), 95 (34).
0
0
0
Method B
Bis(2,4,6-trimethylpyridine)bromine(I) hexafluorophosphate[6a] (700 mg,
1.50 mmol) was added at 08C to a solution of (E)-(5-oxofuran-2(5H)-ylide-
ne)acetic acid (3[4]; 197 mg, 1.40 mmol) in CH2Cl2 (5 mL). The mixture was
stirred at 08C for 15 min and at room temperature for 2 h before Et2O was
added. The Et2O was washed with 1 M HCl, saturated NaHCO3, and brine
before it was dried (MgSO4) and evaporated. The crude product was
purified by flash chromatography (silica, hexane–EtOAc 4 : 1). Rf ¼ 0.33;
(E)-5-(bromomethylene)furan-2(5H)-one (4). Yield: 54 mg (22%).

¨
T. Benneche, J. Lonn, and A. A. Scheie
1404
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