Efficient procedure for the preparation of 2-bromofuran and its application in the synthesis of 2-arylfurans

Article abstract of DOI:10.1080/00397910903219534

A simple, straightforward, and scalable procedure for the preparation of 2-bromofuran using N-bromosuccinimide (NBS) in dimethylformamide (DMF) is reported. The described preparation is conducted on a 20 to 50g scale and does not require extractive workup procedures or chromatographic purifications. To illustrate the synthetic applications of 2-bromofuran, palladium-catalyzed Suzuki coupling reactions of the prepared 2-bromofuran with various aryl boronic acids were investigated, and moderate to good yields of 2-arylfurans were obtained. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903219534

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Efficient Procedure for the Preparation
of 2-Bromofuran and Its Application in
the Synthesis of 2-Arylfurans
Mohammed-Abdul Raheem a , Jaipal R. Nagireddy a , Robin Durham a
& William Tam a
a Guelph-Waterloo Centre for Graduate Work in Chemistry and
Biochemistry, Department of Chemistry, University of Guelph,
Guelph, Ontario, Canada
Version of record first published: 17 Jun 2010.
To cite this article: Mohammed-Abdul Raheem , Jaipal R. Nagireddy , Robin Durham & William Tam
(2010): Efficient Procedure for the Preparation of 2-Bromofuran and Its Application in the Synthesis
of 2-Arylfurans, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 40:14, 2138-2146
To link to this article: http://dx.doi.org/10.1080/00397910903219534
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Synthetic Communications1, 40: 2138–2146, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903219534
EFFICIENT PROCEDURE FOR THE PREPARATION OF
2-BROMOFURAN AND ITS APPLICATION IN THE
SYNTHESIS OF 2-ARYLFURANS
Mohammed-Abdul Raheem, Jaipal R. Nagireddy,
Robin Durham, and William Tam
Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry,
Department of Chemistry, University of Guelph, Guelph, Ontario, Canada
A simple, straightforward, and scalable procedure for the preparation of 2-bromofuran using
N-bromosuccinimide (NBS) in dimethylformamide (DMF) is reported. The described prep-
aration is conducted on a 20 to 50 g scale and does not require extractive workup procedures
or chromatographic purifications. To illustrate the synthetic applications of 2-bromofuran,
palladium-catalyzed Suzuki coupling reactions of the prepared 2-bromofuran with various
aryl boronic acids were investigated, and moderate to good yields of 2-arylfurans were
obtained.
Keywords: Bromination; 2-bromofuran; N-bromosuccinimide; steam distillation; Suzuki coupling
INTRODUCTION
We have recently investigated different modes of transition metal–catalyzed
reactions of oxabenzonorbornadiene 1 and found that, depending on the reaction
conditions, several products (2–7) could be obtained (Scheme 1). For example, when
7-oxabenzonorbornadiene 1 is treated with an alkyne in the presence of the ruthenium
catalyst, CpꢀRu(COD)Cl, a [2 þ 2] cycloaddition is observed and cyclobutene
cycloadduct 2 is formed.[1] When oxabenzonorbornadiene 1 is treated with the
secondary propargylic alcohol 8 in the presence of the neutral Ru catalyst, CpꢀRu
(COD)Cl, in MeOH or using a cationic Ru catalyst (e.g., [CpRu(CH3CN)3]PF6),
isochromene 3 is formed.[2] On the other hand, if the same reaction between oxaben-
zonorbornadiene 1 and the secondary propargylic alcohol 8 is carried out with
CpꢀRu(COD)Cl in tetrahydrofuran (THF), cyclopropane 4 is produced.[3] More
recently, we have observed that in the absence of an alkyne, CpꢀRu(COD)Cl
catalyzes the isomerization of oxabenzonorbornadiene 1 to the corresponding
naphthalene oxide 5 or naphthol 6.[4] We have also reported that asymmetric cationic
rhodium(I)-catalyzed cyclodimerization of oxabenzonorbornadiene 1 to produce
dimers 7 in excellent enantioselectivity (up to 99% ee).[5]
Received May 6, 2009.
Address correspondence to William Tam, Guelph-Waterloo Centre for Graduate Work in
Chemistry and Biochemistry, Department of Chemistry, University of Guelph, Guelph, Ontario, N1G
2W1, Canada. E-mail: wtam@uoguelph.ca
2138

SYNTHESIS AND APPLICATIONS OF 2-BROMOFURAN
2139
Scheme 1. Transition metal–catalyzed reactions of oxabenzonorbornadiene 1.
Because oxabenzonorbornadiene
1
is symmetrical, no regiochemical
information could be gain from these studies. To explore the regioselectivity of these
reactions, we plan to synthesize C1-substituted oxabenzonorbornadiene 11 by the
Diels–Alder reaction of benzyne 9 and 2-substituted furans 10 (Scheme 2). Although
some 2-substituted furans are commercially available (such as R ¼ Me, tBu, COOMe
etc.), 2-substituted furans with R ¼ Br and aryl groups are not commercially avail-
able. During the course of our efforts to prepare a series of 2-aryl furans 10 (R ¼ Ar),
we required large quantities of 2-bromofuran 12. Several methods have been
described in literature for bromination of furan to 2-bromofuran.[6] Bromination of
furan using hexabromocyclopentadiene,[6b] dioxane dibromide,[6d] and microwave-
assisted bromination using 2,4,4,6-tetrabromo-2,5-cyclohexadienone[6g] are unsuit-
able for the preparation of 2-bromofuran 12 in large quantities. The two methods
developed by Brandsma are much more effective and provided 2-bromofuran 12 in
70–80% yield: (i) the metallation of furan with EtLi, followed by the reaction with
Br2, in ether at –80 ꢁC[6d] and (ii) the bromination of furan with Br2 in dimethylforma-
mide (DMF).[6e] However, we and others[6g] found that these methods are difficult to
work with and the isolation of the product is troublesome. In this article, we describe
Scheme 2. Synthesis of C1-substituted oxabenzonorbornadiene 11.

2140
M.-A. RAHEEM ET AL.
a new and practical procedure for the bromination of furan, which offers
simplified workup and isolation techniques for large-scale preparation (20–50 g) of
2-bromofuran using safe, inexpensive, and readily available reagents. The described
preparation does not require extractive workup procedures or chromatographic
purifications.
RESULTS AND DISCUSSION
We initially followed Keegstra et al.’s procedure for the synthesis
2-bromofuran 12 involving treatment of furan with Br2 in DMF.[6e] We encountered
difficulties similar to those mentioned by Gupta et al. in isolation of bromofuran.[6g]
We modified the isolation step by effecting direct steam distillation of the reaction
mixture to isolate bromofuran in moderate yields (50–55%). The residual reaction
mass contained a green, dense, tarry solid. This is not surprising in view of the
unusual sensitivity of furan toward mineral acids. It was also found that the addition
of Br2 to DMF is highly exothermic, and it is very difficult to control the reaction
temperature in the large-scale reaction (20–30 g). Furthermore, elemental bromine
itself is not easy to handle because of its highly corrosive nature. Therefore, we modi-
fied the procedure of bromination using readily available and easy to handle
N-bromosuccinimide (NBS) (Scheme 3). Interestingly, we found that addition of
NBS to DMF is not exothermic. Bromination of furan was done by controlled
addition of NBS–DMF solution at room temperature followed by stirring the reac-
tion mixture at room temperature overnight. Direct steam distillation of the reaction
mixture resulted in isolation of 2-bromofuran 12 in 65–75% yields.
To illustrate the synthetic applications of 2-bromofuran 12, palladium-
catalyzed Suzuki coupling reactions with various aryl boronic acids were carried
out, and the results are shown in Table 1. In the presence of 2 mol% of PdCl2(PPh3)2
and 2.5 equivalents of K2CO3 in DMF=H2O (3:1), the Suzuki coupling reaction
between 2-bromofuran 12 and phenylboronic acid 13a (Ar ¼ Ph) occurred smoothly
at 80 ꢁC, providing 2-phenylfuran 14a in 62% isolated yield after column chromato-
graphy (entry 1). Suzuki coupling reactions of 2-bromofuran 12 worked well with
boronic acids containing both electron-donating groups attached to the Ar ring
(Ar ¼ CH3, entries 2–4; Ar ¼ OCH3, entries 5–7; Ar ¼ Et, entry 11) as well as with
electron-withdrawing groups attached to the Ar ring (Ar ¼ Cl, entries 8–10; Ar ¼ Ac,
entry 12). The position of the substitutent on the Ar ring (ortho, meta, or para)
showed little effect on the yields of the Suzuki coupling reactions (compare entries
2 to 4, entries 5–7, and entries 8–10). In general, all the palladium-catalyzed Suzuki
coupling reactions of 2-bromofuran 12 occurred smoothly, giving moderate to good
Scheme 3. Synthesis of 2-bromofuran using NBS in DMF.

SYNTHESIS AND APPLICATIONS OF 2-BROMOFURAN
2141
Table 1. Synthesis of 2-aryl boronic acids by palladium-catalyzed Suzuki cross-coupling reactions
between 2-bromofuran 12 and aryl boronic acids
Entry
Boronic acid 13
Ar
Furan 14
Yield (%)a
1
2
13a
13b
13c
13d
13e
13f
13g
13h
13i
C6H5
14a
14b
14c
14d
14e
14f
14g
14h
14i
62
56
80
78
57
72
63
65
67
70
56
59
77
85
4-CH3-C6H4
3-CH3-C6H4
2-CH3-C6H4
4-CH3O-C6H4
3-CH3O-C6H4
2-CH3O-C6H4
4-Cl-C6H4
3
4
5
6
7
8
9
3-Cl-C6H4
2-Cl-C6H4
4-Et-C6H4
10
11
12
13
14
13j
14j
13k
13l
14k
14l
4-C(O)CH3-C6H4
4-Biphenyl
1-Naphthyl
13m
13n
14m
14n
aIsolated yield after column chromatography.
yields of the 2-arylfurans. These 2-arylfurans synthesized (14a–n) are useful
precursors for the synthesis of C1-substituted oxabenzonorbornadiene 11
(Scheme 2), which will be useful in the investigation of various regiochemical issues
in various metal-catalyzed reactions (Scheme 1).
CONCLUSION
In conclusion, we have investigated a new, simple, straightforward, and
scalable procedure for the preparation of 2-bromofuran using NBS in DMF. The
described preparation was conducted on a 20 to 50 g scale and does not require
extractive workup procedures or chromatographic purifications. We have also illu-
strated the synthetic applications of the prepared 2-bromofuran by the palladium-
catalyzed Suzuki coupling reactions with various aryl boronic acids, and moderate
to good yields of 2-arylfurans were obtained. The use of 2-bromofuran and
2-arylfurans for the synthesis of C1-substituted oxabenzonorbornadiene 11 are in
progress in our laboratories.
EXPERIMENTAL
General Considerations
All reactions are done in septum-sealed, flame-dried flasks under a nitrogen
atmosphere. All commercial reagents were used as received from their respective
suppliers. Reagent-grade furan and NBS purchased from Aldrich were used without

2142
M.-A. RAHEEM ET AL.
1
additional purification. H NMR and 13C NMR spectra were recorded at 300=400
and 75=100 MHz, respectively. Chemical shifts are reported in parts per million (d)
using internal solvent signals as references, and coupling constants are reported in
hertz (Hz).
Preparation of Bromofuran
A solution of NBS (20 g, 0.112 mol) in DMF (60 mL) was added via addition
funnel to a solution of furan (15.3 g, 0.225 mol) in DMF (40 mL) in a 500-mL,
three-necked, round-bottomed flask over a period of 40–60 min, keeping internal
temperature between 25 and 35 ꢁC under constant stirring. Addition of NBS solution
to reaction mixture was found to be exothermic. During addition, the reaction
mixture went from brown solution to dark green. After the addition was complete,
the reaction mixture was stirred at ambient temperature for an additional 2–4 h. The
resulting clear brown solution was heated gradually to 100–110 ꢁC to distill out some
of the unreacted furan. After maintaining 100–110 ꢁC temperature for 0.5–1 h, the
reaction mixture was exposed to a constant jet of steam generated by heating dis-
tilled water to 100–120 ꢁC in a separate two-necked, round-bottomed flask. Distillate
consisting of water and bromofuran was collected in a receiver. The initial few drops
contained mostly residual unreacted furan and were therefore collected separately.
Distillation continued until no organic product was present in the distillate. The
distillate was transferred to a separatory funnel along with water (20–30 mL). The
suspension was shaken well to force traces of DMF to the aqueous layer. After layer
separation, the bromofuran 12 settled down as a colorless lower layer, which was
collected and stored in a dry bottle containing anhydrous K2CO3 (11.5 g, 70%).
2-Bromofuran, 12
Colorless liquid, yield ¼ 70% (11.5 g); IR (CH2Cl2): 3140, 2930, 1679, 1472,
1
1386, 1161, 1052 cmꢂ1; H NMR (CDCl3, 300 MHz): d 6.28 (dd, J ¼ 3.3, 2.3 Hz,
1H), 6.35 (dd, J ¼ 4.9, 3.6 Hz, 1H), 7.40 (dd, J ¼ 2.1, 1.1 Hz, 1H); 13C NMR (CDCl3,
75 MHz): 111.5, 114.0, 124.0, 141.3; HRMS (EI) calcd. for C4H4BrO (Mþ):
146.9446; found: 146.9452.
General Procedure for Suzuki Coupling with Bromofuran
Under a nitrogen atmosphere, arylboronic acid (1.0 mmol) was suspended in a
DMF–water (3 mL=1 mL) mixture, followed by the addition of bromofuran
(1.7 mmol), PdCl2(PPh3)2 (0.02 mmol), and K2CO3 (2.5 equiv.). The mixture was
heated to 75–85 ꢁC for 16–20 h. After reaction completion, the mixture was cooled
to room temperature, followed by quenching by addition of 15–20 mL water. The
obtained suspension was extracted with ether (10 mL ꢃ 3), and then the combined
organic layers were washed with water, dried over anhydrous sodium sulfate, and
concentrated using rotary evaporation. The crude product was purified by column
chromatography (EtOAc–hexanes mixtures) to give the product.

SYNTHESIS AND APPLICATIONS OF 2-BROMOFURAN
2143
Data
2-Phenylfuran, 14a. Colorless oil. Yield ¼ 62% (90.0 mg); Rf ¼ 0.38
(hexanes); IR (CH2Cl2); 3054, 1608, 1507, 1477, 1265, 1023 cmꢂ1; 1H NMR (CDCl3,
300 MHz): d 6.45–6.57 (m, 1H), 6.66 (d, J ¼ 3.4 Hz, 1H), 7.26 (t, J ¼ 7.2 Hz, 1H), 7.39
(t, J ¼ 7.8 Hz, 2H), 7.47–7.48 (m, 1H), 7.69 (d, J ¼ 7.8 Hz, 2H); 13C (APT) NMR
(CDCl3, 75 MHz): 104.9 (CH), 111.6 (CH), 123.8 (CH), 127.3 (CH), 128.6 (CH),
130.9 (qC), 142.0 (CH), 154.0 (qC). HRMS (EI) calcd. for C10H8O (Mþ):
144.0575; found: 144.0579.
2-(4-Methylphenyl)furan, 14b. Colorless oil. Yield ¼ 56% (83.3 mg);
Rf ¼ 0.65 (EtOAc=hexanes ¼ 30:70); IR (CH2Cl2); 3290, 1620, 1509, 1455, 1380,
1
1260, 1100, 1052 cmꢂ1; H NMR (CDCl3, 400 MHz): d 2.24 (s, 3H), 6.33 (m, 1H),
6.47 (d, J ¼ 3.2 Hz, 1H), 7.07 (d, J ¼ 8.0 Hz, 2H), 7.32 (br s, 1H), 7.46 (d, J ¼ 8.0 Hz,
2H); 13C (APT) NMR (CDCl3, 100 MHz): 21.0 (CH3), 104.0 (CH), 111.4 (CH), 123.6
(CH), 128.1 (qC), 129.2 (CH), 136.9 (qC), 141.5 (CH), 154.0 (qC). HRMS (EI) calcd.
for C11H10O (Mþ): 158.0732; found: 158.0735.
2-(3-Methylphenyl)furan, 14c. Colorless oil. Yield ¼ 80% (119.6 mg);
Rf ¼ 0.63 (EtOAc=hexanes ¼ 30:70); IR (CH2Cl2); 3288, 1622, 1521, 1447, 1382,
1
1260, 1105, 1059 cmꢂ1; H NMR (CDCl3, 400 MHz): d 2.54 (s, 3H), 6.61 (m, 1H),
6.79 (m, 1H), 7.23 (d, J ¼ 7.5 Hz, 1H), 7.43 (td, J ¼ 7.7, 1.5 Hz, 1H), 7.60 (br s,
1H), 7.54–7.76 (m, 2H); 13C (APT) NMR (CDCl3, 100 MHz): 21.4 (CH3), 104.7
(CH), 111.5 (CH), 120.9 (CH), 124.3 (CH), 128.0 (CH), 128.5 (CH), 130.7 (qC),
138.1 (qC), 141.8 (CH), 154.0 (qC). HRMS (EI) calcd. for C11H10O (Mþ):
158.0732; found: 158.0737.
2-(2-Methylphenyl)furan, 14d. Colorless oil. Yield ¼ 78% (114.4 mg);
Rf ¼ 0.67 (EtOAc=hexanes ¼ 30:70); IR (CH2Cl2); 3034, 1617, 1510, 1479, 1266,
1
1043 cmꢂ1; H NMR (CDCl3, 400 MHz): d 2.37 (s, 3H), 6.36 (dd, J ¼ 3.4, 1.8 Hz,
1H), 6.43 (d, J ¼ 3.4 Hz, 1H), 7.06–7.15 (m, 3H), 7.37 (d, J ¼ 1.6 Hz, 1H), 7.59 (d,
J ¼ 7.7 Hz, 1H); 13C (APT) NMR (CDCl3, 100 MHz): 21.8 (CH3), 108.4 (CH),
111.2 (CH), 125.9 (CH), 127.1 (CH), 127.4 (CH), 130.2 (qC), 131.0 (CH), 134.5
(qC), 141.6 (CH), 153.5 (qC). HRMS (EI) calcd. for C11H10O (Mþ): 158.0732;
found: 158.0736.
2-(4-Methoxyphenyl)furan, 14e. White solid. Yield ¼ 57% (100.0 mg);
Rf ¼ 0.26 (EtOAc=hexanes ¼ 5:95); IR (CH2Cl2): 2959, 2937, 1617, 1218, 1047 cmꢂ1
;
1H NMR (CDCl3, 300 MHz): d 3.82 (s, 3H), 6.43 (dd, J ¼ 3.4, 1.7 Hz, 1H), 6.51 (d,
J ¼ 2.8 Hz, 1H), 6.91 (d, J ¼ 8.8 Hz, 2H), 7.41 (d, J ¼ 1.3 Hz, 1H), 7.61–7.56 (m,
2H); 13C (APT) NMR (CDCl3, 75 MHz): 55.2 (CH3), 103.3 (CH), 111.5 (CH),
114.1 (CH), 124.0 (qC), 125.2 (CH) 141.3 (CH), 154.0 (qC), 159.0 (qC). HRMS
(EI) calcd. for C11H10O2 (Mþ): 174.0681; found: 174.0686.
2-(3-Methoxyphenyl)furan, 14f. Brown oil. Yield ¼ 72% (126.0 mg);
Rf ¼ 0.45 (EtOAc=hexanes ¼ 5:95); IR (CH2Cl2): 2938, 1605, 1504, 1290, 1226,
1
1038 cmꢂ1; H NMR (CDCl3, 300 MHz): d 3.77 (s, 3H), 6.38 (dd, J ¼ 3.4, 1.8 Hz,
1H), 6.56 (d, J ¼ 3.4 Hz, 1H), 6.71–6.75 (m, 1H), 7.13–7.21 (m, 3H), 7.37 (d,
J ¼ 1.7 Hz, 1H); 13C (APT) NMR (CDCl3, 75 MHz): d 55.3 (CH3), 105.3 (CH),
109.2 (CH), 111.7 (CH), 113.2 (CH), 116.4 (CH), 129.8 (CH), 132.2 (qC), 142.1

2144
M.-A. RAHEEM ET AL.
(CH), 153.8 (qC), 159.9 (qC). HRMS (EI) calcd. for C11H10O2 (Mþ): 174.0681;
found: 174.0679.
2-(2-Methoxyphenyl)furan, 14g. Brown oil. Yield ¼ 63% (110.0 mg);
Rf ¼ 0.42 (EtOAc=hexanes ¼ 10:90); IR (CH2Cl2): 3002, 2940, 2837, 1602, 1464,
1083cmꢂ1; 1H NMR (CDCl3, 300 MHz): d 3.93 (s, 3H), 6.48–6.50 (m, 1H), 6.93–7.04
(m, 3H), 7.20–7.27 (m, 1H), 7.46 (d, J ¼ 0.7 Hz, 1H), 7.85 (dd, J ¼ 7.7, 1.3 Hz, 1H);
13C (APT) NMR (CDCl3, 75MHz): d 55.4 (CH3), 109.8 (CH), 111.0 (CH), 111.6
(CH), 119.9 (qC), 120.7 (CH), 126.0 (CH), 128.0 (CH), 141.1 (CH), 150.3 (qC), 155.3
(qC). HRMS (EI) calcd. for C11H10O2 (Mþ): 174.0681; found: 174.0685.
2-(4-Chlorophenyl)furan, 14h. White solid. Yield ¼ 65% (116.0 mg);
Rf ¼ 0.29 (hexanes); IR (CH2Cl2): 3054, 2987, 1487, 1422, 1265, 1093, 1020 cmꢂ1
;
1H NMR (CDCl3, 300 MHz): d 6.42–6.49 (m, 1H, CH), 6.62 (d, J ¼ 2.9 Hz, 1H),
7.33 (d, J ¼ 8.5 Hz, 2H), 7.45 (s, 1H), 7.58 (d, J ¼ 8.5 Hz, 2H); 13C (APT) NMR
(CDCl3, 75 MHz): d 105.4 (CH), 111.8 (CH), 125.0 (CH), 128.9 (CH), 129.4 (qC),
133.0 (qC), 142.3 (CH), 153.0 (qC). HRMS (EI) calcd. for C10H7ClO (Mþ):
178.0185; found: 178.0188.
2-(3-Chlorophenyl)furan, 14i. Colorless oil. Yield ¼ 67% (119.0 mg);
1
Rf ¼ 0.29 (hexanes); IR (CH2Cl2): 3371, 1603, 1582, 1282, 1013 cmꢂ1; H NMR
(CDCl3, 300 MHz): d 6.44 (dd, J ¼ 3.42, 1.83 Hz, 1H), 6.63 (d, J ¼ 3.4 Hz, 1H),
7.15–7.38 (m, 2H), 7.46 (d, J ¼ 1.71 Hz, 1H), 7.49–7.52 (m, 1H), 7.64 (t, J ¼ 1.77 Hz,
1H); 13C (APT) NMR (CDCl3, 75 MHz): d 106.0 (CH), 111.7 (CH), 121.8 (CH),
123.8 (CH), 127.2 (CH), 130.0 (CH), 132.5 (qC), 134.7 (qC), 142.5 (CH), 152.5
(qC). HRMS (EI) calcd. for C10H7ClO (Mþ): 178.0185; found: 178.0182.
2-(2-Chlorophenyl)furan, 14j. Colorless oil. Yield ¼ 70% (70.0 mg);
1
Rf ¼ 0.29 (hexanes); IR (CH2Cl2): 3065, 1599, 1499, 1470, 1031 cmꢂ1; H NMR
(CDCl3, 300 MHz): d 6.53 (dd, J ¼ 3.5, 1.8 Hz, 1H), 7.14 (dd, J ¼ 3.5, 0.6 Hz, 1H),
7.19 (dd, J ¼ 7.4, 1.7 Hz, 1 H), 7.31 (td, J ¼ 3.9, 1.4 Hz, 1H), 7.44 (dd, J ¼ 7.9,
1.2 Hz, 1H), 7.51 (dd, J ¼ 1.8, 0.6 Hz, 1H), 7.87 (dd, J ¼ 7.9, 1.7 Hz, 1H); 13C
(APT) NMR (CDCl3, 75 MHz): d 110.9 (CH), 111.7 (CH), 126.9 (CH), 127.9
(CH), 128.0 (CH), 129.3 (CH), 130.1 (qC), 130.7 (qC), 142.1 (CH), 150.2 (qC).
HRMS (EI) calcd. for C10H7ClO (Mþ): 178.0185; found: 178.0181.
2-(4-Ethylphenyl)furan, 14k. Brown oil. Yield ¼ 56% (96.0 mg); Rf ¼ 0.5
(EtOAc=hexanes ¼ 5:95); IR (CH2Cl2): 3023, 2965, 2931, 1516, 1457, 1157,
1007 cmꢂ1; 1H NMR (CDCl3, 300 MHz): d 1.24 (t, J ¼ 7.6 Hz, 3H), 2.65(q, J ¼ 7.6 Hz,
2H), 6.44 (dd, J ¼ 3.3, 1.8 Hz, 1H), 6.58 (d, J ¼ 3.3 Hz, 1H), 7.21 (d, J ¼ 8.2 Hz, 2H);
7.43 (d, J ¼ 1.6 Hz, 1H), 7.59 (d, J ¼ 8.2 Hz, 2H); 13C (APT) NMR (CDCl3, 75 MHz):
d 15.5 (CH3), 28.6 (CH2), 104.2 (CH), 111.5 (CH), 123.8 (CH), 128.1 (CH), 128.5
(qC), 141.6 (CH), 143.5 (qC), 154.2 (qC); HRMS (EI) calcd. for C12H12O (Mþ):
172.0888; found: 172.0886.
2-(4-Acetylphenyl)furan, 14l. White solid. Yield ¼ 59% (110.0 mg); Rf ¼ 0.24
(EtOAc=hexanes ¼ 20:80); IR (CH2Cl2): 1668, 1475, 1416, 1079, 1020 cmꢂ1; 1H NMR
(CDCl3, 300 MHz): d 2.59 (s, 3H), 6.46–6.54 (m, 1H), 6.78 (d, J ¼ 3.3 Hz, 1H), 7.51
(s, 1H), 7.72 (d, J ¼ 8.4 Hz, 2H), 7.95 (d, J ¼ 8.4 Hz, 2H); 13C (APT) NMR (CDCl3,
75 MHz): d 26.5 (CH3), 107.5 (CH), 112.1 (CH), 123.5 (CH), 128.9 (CH), 134.9 (qC),

SYNTHESIS AND APPLICATIONS OF 2-BROMOFURAN
2145
135.5 (qC), 143.3 (CH), 152.8 (qC), 197.3 (CO); HRMS (EI) calcd. for C12H10O2
(Mþ): 186.0681; found: 186.0687.
2-(4-Biphenyl)furan, 14m. White solid. Yield ¼ 77% (170.0 mg); Rf ¼ 0.33
(EtOAc=hexanes ¼ 5:95); IR (CH2Cl2): 3054, 2987, 1600, 1478, 1265, 1158 cmꢂ1
;
1H NMR (CDCl3, 300 MHz): d 6.42–6.40 (m, 1H), 6.69 (d, J ¼ 3.3 Hz, 1H),
7.32–7.37 (m, 1H), 7.33–7.50 (m, 3H), 7.62 (d, J ¼ 8.4 Hz, 4H), 7.75 (d, J ¼ 8.4 Hz,
2H); 13C (APT) NMR (CDCl3, 75 MHz): d 105.1 (CH), 111.7 (CH), 124.2 (CH),
126.9 (CH), 127.3 (CH), 128.8 (CH), 129.9 (qC), 140.0 (qC), 140.6 (qC), 142.1
(CH), 153.8 (qC). RMS (EI) calcd. for C16H12O (Mþ): 220.0888; found: 220.0885.
2-(1-Naphthyl)furan, 14n. Colorless oil. Yield ¼ 85% (165.0 mg); Rf ¼ 0.45
(EtOAc=hexanes ¼ 10:90); IR (CH2Cl2): 3054, 2987, 1512, 1422, 1265, 1015 cmꢂ1
;
1H NMR (CDCl3, 300 MHz): 6.58 (dd, J ¼ 3.3, 1.9 Hz, 1H), 6.71 (d, J ¼ 3.3 Hz,
1H), 7.40–7.56 (m, 3H), 7.61 (d, J ¼ 1.7 Hz, 1H), 7.71 (dd, J ¼ 7.2, 1.0 Hz, 1H),
7.80–7.89 (m, 2H), 8.37–8.41 (m, 1H); 13C (APT) NMR (CDCl3, 75 MHz): d 109.2
(CH), 111.3 (CH), 125.3 (CH), 125.6 (CH), 125.9 (CH), 126.2 (CH), 126.5 (CH),
128.5 (CH), 128.6 (CH), 128.7 (qC), 130.4 (qC), 134.0 (qC), 142.4 (CH), 153.4
(qC). HRMS (EI) calcd. for C14H10O (Mþ): 194.0732; found: 194.0726.
ACKNOWLEDGMENTS
This work was supported by Merck Frosst Centre for Therapeutic Research,
Natural Sciences and Engineering Research Council of Canada (NSERC), and
Boehringer Ingelheim (Canada) Ltd.
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