3-formylpyrroles from 3-furfurylamines by bromine oxidation reaction

Article abstract of DOI:10.1002/jccs.201000195

Oxidation of 3-furfurylamines 3a-e with bromine in acetone-water solution gave N-substituted 3-formylpyrroles 4a-e in good yields. A reaction mechanism via the Clauson-Kaas reaction followed by the cis-trans isomerization of the 2-ene-1,4-diones 13 and 14

Full text of DOI:10.1002/jccs.201000195

Journal of the Chinese Chemical Society, 2010, 57, 1321-1326
1321
3-Formylpyrroles from 3-Furfurylamines by Bromine Oxidation Reaction
Piin-Jye Harna,b
(
), Chu-Chung Lina,c
(
) and Hsien-Jen Wua,d,* (
)
aDepartment of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan, R.O.C.
bSinoPharm Taiwan Ltd., Tainan County, Taiwan, R.O.C.
cDepartment of Medicinal Chemistry, TaiGen Biotechnology Co., Ltd., Taipei, Taiwan, R.O.C.
dDepartment of Environmental Engineering and Health, Yuanpei University, Hsinchu, Taiwan, R.O.C.
Oxidation of 3-furfurylamines 3a-e with bromine in acetone-water solution gave N-substituted
3-formylpyrroles 4a-e in good yields. A reaction mechanism via the Clauson-Kaas reaction followed by
the cis-trans isomerization of the 2-ene-1,4-diones 13 and 14 was proposed to account for the formation of
the pyrroles 4a-e.
Keywords: 3-Furfurylamines; 3-Formylpyrroles; Oxidation with bromine.
INTRODUCTION
Furan derivatives and their oxidation products are im-
amines with bromine to give 3-formyl pyrroles in an one-
step conversion,15 a new route to pyrroles from furans via
oxidative rearrangement.
portant intermediates in organic synthesis.1,2 The oxidation
of a furan ring has oftentimes been used to express the la-
tent functionality present within this heterocyclic frame-
work.3 Oxidation of 2-trimethylsilylfurans with peracetic
acid gave D3-butenolides.4 This transformation was applied
for the synthesis of natural products.5 Oxidation of 2,5-di-
alkylfurans with peroxy acids afforded the Z-isomers of 2-
ene-1,4-diones,6 whereas the E-isomers were obtained with
pyridinium chlorochromate (PCC) as the oxidation re-
agent.7 Treatment of 2-alkylthiofurans with PCC initially
gave the Z-isomers of S-alkyl 4-oxo-2-alkenoates, which
were converted to the E-isomers when longer reaction times
proceeded.8 The oxidation reaction of furan derivatives
with bromine in absolute methanol is known as Clauson-
Kaas reaction to give the 2,5-dimethoxy-2,5-dihydrofuran
derivatives B,9 presumably via the dibromo intermediates
A (Scheme I). About two decades ago, a direct transforma-
tion of C to D by modified reaction conditions of the bro-
mine oxidation with furan C was reported.10 Reaction of
2-furfuryl alcohols E with bromine in methanol followed
by mild acid hydrolysis gave 6-hydroxyl-2H-pyran-3(6H)-
ones F,3,11 a route to monosaccharides from furan com-
pounds. This transformation from E to F was also accom-
plished with peroxy acids12 and PCC.13 6-Hydroxy-2H-py-
ran-3(6H)-ones are useful intermediates for the synthesis
of natural products.3,11 Recently, we reported the oxidation
reaction of 3-furfuryl alcohols G with bromine in aqueous
acetone solution to give 2-substituted-3-furfurals H.14 In
this paper, we report the oxidation reaction of 3-furfuryl
Scheme I
Br2
R
R
R'
Br
R'
R
R'
O
MeOH
O
O
Br
MeO
OMe
B
A
O
Br2
acetone-H2O
Me
OR
Me
Me
OR
Me
O
O
C
D
O
R'
Br2
H+
H2O
R'
R
O
MeOH
HO
O
R
OH
F
E
R
O
Br2
acetone-H2O
OH
H
R
O
O
G
H
RESULTS AND DISCUSSION
Reaction of 3-furfuryl alcohol 1 with phosphorus
tribromide in dry tetrahydrofuran (THF) at 0 oC for one
hour gave 3-furfuryl bromide 2 in 75% yield. Treatment of
3-furfuryl bromide 2 with benzylamine, p-methylbenzyl-
amine, p-chlorobenzylamine, 1-phenylethylamine, and t-
butylamine in dry THF at room temperature for 20 h gave
the corresponding 3-furfurylamines 3a-e in 60-75% yields.
Oxidation of the 3-furfurylamines 3a-e with 1.2 equiva-
lents of bromine in acetone-water (volume ratio 85:15) at 0

1322 J. Chin. Chem. Soc., Vol. 57, No. 6, 2010
Harn et al.
oC for 2 h gave N-alkyl-3-formylpyrroles 4a-e in 50-65%
yields, respectively (Scheme II). Reaction of 4a with so-
dium borohydride in methanol gave compound 5 in 80%
yield.
The SN2 substitution reaction of 3-furfuryl bromide with
aniline proceeded very slowly at room temperature. Treat-
ment of aniline with n-BuLi in dry THF at room tempera-
ture followed by addition of furfuryl bromide 2 gave the
SN2 substitution product 6 in 75% yield. Reaction of com-
pound 6 with 1.5 equivalents of bromine in acetone-water
(85:15) at 0 oC gave compound 7 as the major product and
compound 8 as the minor product (Scheme III). No detect-
able amount of N-phenyl-3-formylpyrrole 9 was obtained.
Thus, electrophilic substitution reaction of bromine on the
benzene ring of aniline moiety of 6 is much faster than the
Scheme II
Scheme III
NH2
NHPh
n-BuLi
2
THF
O
6
Br
Br
Br2
N
H
N
H
6
+
acetone-H2O
Br
O
O
8
7
The structure of compounds 4a-e was identified by
their spectral data. The infrared (IR) spectra of 4a-e re-
vealed strong absorptions at 1670 cm-1 for the formyl car-
bonyl group. The 1H NMR spectrum of 4b showed a singlet
at d 9.72 for the aldehyde proton, a triplet (J = 1.8 Hz) at d
7.29 for the C2 proton on the pyrrole ring, two doublets (J =
7.6 Hz) at d 7.16 and d 7.06 for the benzene ring protons,
two doublets of doublet (J = 2.4, 1.8 Hz) at d 6.69 and d
6.64 for the C4 and C5 protons on the pyrrole ring, a singlet
at d 5.04 for the methylene protons and a singlet at d 2.35
for the methyl protons. The 13C NMR spectrum of 4b dis-
played one peak (CH) at d 185.4 for the aldehyde carbonyl
carbon, four peaks at d 138.2 (C), 132.9 (CH), 129.6
(2CH), and 127.4 (2CH) for the benzene ring carbons, four
peaks at d 129.1 (CH), 126.7 (C), 123.6 (CH), and 108.5
(CH) for the pyrrole ring carbons, one peak (CH2) at d 53.7
for the methylene carbon, and one peak (CH3) at d 21.1 for
the methyl carbon. The mass spectrum of 4b showed its
molecular parent peak at d 199. In the case of the oxidation
of 3e, the 3-formylpyrrole 4e was obtained in a good yield
(65%) even in the presence of a tert-butyl group on the ni-
trogen atom. In other words, the formation of the pyrrole
ring was not affected by the steric effect of the tert-butyl
group on the nitrogen atom.
H
O
N
9
oxidation of bromine on the furan ring.
A reaction mechanism was proposed for the transfor-
mation from the 3-furfurylamines 3a-e to the 3-formylpyr-
roles 4a-e (Scheme IV). The initial step of this oxidation is
similar to the Clauson-Kaas reaction as shown in the first
line of Scheme I. The oxidation reaction of 3 with bromine
in acetone-water solution gives the 2,5-dihydroxy-2,5-di-
hydrofuran 11, presumably via the dibromo intermediate
10. Dehydration of 11 followed by ring opening gives the
Z-iosmer of 2-ene-1,4-dione 12. Cis-trans isomerization of
12 gives the E-isomer 13. Intramolecular nucleophilic ad-
Scheme IV
NHR
NHR
-H2O
NHR
Br2
H
H
H
H
O
O
O
Br
Br
acetone-H2O
HO
OH
3
10
11
O
O
O
NHR
H
H
H
H
-H2O
In order to understand the feasibility of the formation
of N-phenyl-3-formylpyrroles from the oxidation of 3-fur-
furyl anilines, the following experiments were performed.
H
H
H
HO
O
O
N
R
N
R
O HN
R
12
13
14
4

3-Formylpyrrole from 3-Furfurylamine
J. Chin. Chem. Soc., Vol. 57, No. 6, 2010 1323
dition of the amino group of 13 on the aldehyde group gives
the intermediate 14 which was followed by dehydration to
yield the pyrroles 4.
3-Furfuryl benzylamine (3a)
Pale yellow liquid; IR (CHCl3) 3320, 1600, 1500,
750, 700 cm-1; 1H NMR (300 MHz, CDCl3) d 7.38-7.20 (m,
7H), 6.37 (s, 1H), 3.78 (s, 2H), 3.63 (s, 2H), 1.54 (brs, 1H);
13C NMR (75 MHz, CDCl3, DEPT) d 142.94 (CH), 140.02
(C), 139.70 (CH), 128.25 (2CH), 128.02 (2CH), 126.82
(CH), 123.85 (C), 110.30 (CH), 52.99 (CH2), 43.41 (CH2);
LRMS m/z (rel int) 187 (M+, 10), 106 (100); HRMS (EI)
calcd for C12H13ON 187.0997, found 187.0988.
CONCLUSION
In summary, we have demonstrated the reaction of the
3-furfurylamines 3a-e with bromine in acetone-water solu-
tion gave the N-sustituted-3-formylpyrroles 4a-e, a new
entry from furans to pyrroles by oxidative rearrangement.
In the case of the oxidation of 3-furfurylaniline 6 with bro-
mine under the same reaction conditions, electrophilic sub-
stitution reaction of bromine on the benzene ring of aniline
moiety was found to proceed much faster than the oxida-
tion of bromine on the furan ring. A reaction mechanism
via the Clause-Kaas reaction followed by the cis-trans iso-
merization from the Z-iosmer 12 of the 2-ene-1,4-dione to
the E-isomer 13 was proposed to account for the formation
of the pyrroles 4.
3-Furfuryl p-methylbenzylamine (3b)
Pale yellow liquid; IR (CHCl3) 3320, 1600, 1500, 830
cm-1; 1H NMR (300 MHz, CDCl3) d 7.37 (d, J = 1.5 Hz,
1H), 7.34 (s, 1H), 7.21 (d, J = 9.0 Hz, 2H), 7.12 (d, J = 9.0
Hz, 2H), 6.39 (d, J = 1.5 Hz, 1H), 3.75 (s, 2H), 3.63 (s, 2H),
2.33 (s, 3H), 1.63 (brs, 1H); 13C NMR (75 MHz, CDCl3,
DEPT) d 142.97 (CH), 139.73 (CH), 136.96 (C), 136.44
(C), 128.98 (2CH), 128.02 (2CH), 123.88 (C), 110.36
(CH), 52.76 (CH2), 43.38 (CH2), 20.97 (CH3); LRMS m/z
(rel int) 201 (M+, 40), 105 (100); HRMS (EI) calcd for
C13H15ON 201.1154, found 201.1146.
EXPERIMENTAL SECTION
Infrared spectra were recorded in CHCl3 solutions or
1
3-Furfuryl p-chlorobenzylamine (3c)
on neat thin firms between NaCl disks. H NMR spectra
Pale yellow liquid; IR (CHCl3) 3320, 1600, 1500, 835
cm-1; 1H NMR (300 MHz, CDCl3) d 7.38 (s, 1H), 7.35 (d, J
= 1.5 Hz, 1H), 7.32-7.24 (m, 4H), 6.39 (d, J = 1.5 Hz, 1H),
3.76 (s, 2H), 3.64 (s, 2H), 1.57 (brs, 1H); 13C NMR (75
MHz, CDCl3, DEPT) d 143.14 (CH), 139.82 (CH), 138.60
(C), 132.59 (C), 129.45 (2CH), 128.46 (2CH), 123.76 (C),
110.33 (CH), 52.29 (CH2), 43.44 (CH2); LRMS m/z (rel
int) 223 (M+, 22), 221 (M+, 65), 125 (100).
were determined at 300 MHz, and 13C NMR spectra were
determined at 75 MHz on Fourier transform spectrometers.
Chemical shifts are reported in ppm relative to TMS in the
solvents specified. The multiplicities of 13C signals were
determined by DEPT techniques. High-resolution mass
values were obtained with a high-resolution mass spec-
trometer at the Department of Chemistry, National Tsing
Hua University. For thin-layer chromatography (TLC) anal-
ysis, precoated TLC plates (Kieselgel 60 F254) were used,
and column chromatography was done by using Kieselgel
60 (70-230 mesh) as the stationary phase. THF was dis-
tilled immediately prior to use from sodium benzophenone
ketyl under nitrogen.
3-Furfuryl-1-phenylethylamine (3d)
Pale yellow liquid; IR (CHCl3) 3320, 1600, 1500,
760, 700 cm-1; 1H NMR (300 MHz, CDCl3) d 7.40-7.20 (m,
7H), 6.34 (s, 1H), 3.80 (q, J = 6.6 Hz, 1H), 3.47 (s, 2H),
1.58 (brs, 1H), 1.26 (d, J = 6.6 Hz, 3H); 13C NMR (75 MHz,
CDCl3, DEPT) d 145.33 (C), 142.97 (CH), 139.64 (CH),
128.43 (2CH), 126.91 (2CH), 126.59 (CH), 124.06 (C),
110.36 (CH), 57.39 (CH), 41.98 (CH2), 24.29 (CH3);
LRMS m/z (rel int) 201 (M+, 45), 105 (100); HRMS (EI)
calcd for C12H15ON 201.1154, found 201.1163.
General Procedure for the Preparation of Com-
pounds 3a-e
To a solution of benzylamine (1.98 g, 18.5 mmol) in
THF (50 mL) was slowly added 3-furfuryl bromide (1.19 g,
7.39 mmol) at 25 oC. The reaction mixture was stirred at
room temperature for 20 h. To this reaction mixture was
added saturated NaHCO3 (20 mL) at 0 oC, and the mixture
was stirred at room temperature for 20 min. After extrac-
tion with ether (5 ´ 30 mL), the organic layer was washed
with brine, dried over MgSO4, and evaporated, and the resi-
due was purified by flash column chromatography to give
3a (0.95 g, 70%).
3-Furfuryl tert-butylamine (3e)
Pale yellow liquid; IR (CHCl3), 3320, 1500 cm-1; 1H
NMR (300 MHz, CDCl3) d 7.36 (s, 2H), 6.39 (s, 1H), 3.60
(s, 2H), 1.21 (brs, 1H), 1.16 (s, 9H); 13C NMR (75 MHz,
CDCl3, DEPT) d 142.91 (CH), 139.41 (CH), 124.81 (C),
110.42 (CH), 50.49 (C), 37.55 (CH2), 28.90 (3CH3);
LRMS m/z (rel int) 153 (M+, 100), 138 (77); HRMS (EI)
calcd for C9H15ON 153.1154, found 153.1166.

1324 J. Chin. Chem. Soc., Vol. 57, No. 6, 2010
Harn et al.
General Procedure for the Oxidation of 3-Furfuryl-
amines 3a-e with Bromine in Acetone-Water
Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) d 185.21
(CH), 141.33 (C), 128.72 (2CH), 127.90 (CH), 127.49
(CH), 126.18 (C), 125.80 (2CH), 122.31 (CH), 108.03
(CH), 58.70 (CH), 21.58 (CH3); LRMS m/z (rel int) 199
(M+, 100); HRMS (EI) calcd for C13H13NO 199.0997,
found 199.0988.
To a solution of 3-furfurylamine 3a (0.79 g, 4.2
mmol) in acetone (34 mL) and water (6 mL) was dropwise
o
added bromine (0.80 g, 5.0 mmol) at 0 C. The reaction
mixture was stirred at room temperature for 2 h. This solu-
tion was neutralized with saturated NaHCO3 (20 mL) at 0
oC, and the mixture was stirred at room temperature for 30
min. After extraction with ether (5 ´ 30 mL), the organic
layer was washed with brine, dried over MgSO4, and evap-
orated, and the residue was purified by flash column chro-
matography to give 4a (0.50 g, 64%).
N-(tert-Butyl)-3-formylpyrrole (4e)
Pale yellow liquid; IR (CHCl3), 1670 cm-1; 1H NMR
(300 MHz, CDCl3) d 9.73 (s, 1H), 7.47 (dd, J = 1.8, 1.5 Hz,
1H), 6.87 (dd, J = 2.4, 1.5 Hz, 1H), 6.63 (dd, J = 2.4, 1.8
Hz, 1H), 1.56 (s, 9H); 13C NMR (75 MHz, CDCl3, DEPT) d
185.45 (CH), 126.15 (CH), 125.75 (C), 120.41 (CH),
107.91 (CH), 55.96 (C), 30.32 (3CH3); LRMS m/z (rel int)
151 (M+, 100), 136 (30); HRMS (EI) calcd for C9H13NO
151.0997, found 151.0985.
N-Benzyl-3-formylpyrrole (4a)
Pale yellow liquid; IR (CHCl3), 1665, 1150, 750, 700
cm-1; 1H NMR (300 MHz, CDCl3) d 9.69 (s, 1H), 7.35-7.24
(m, 4H), 7.15-7.10 (m, 2H), 6.67 (dd, J = 2.4, 1.8 Hz, 1H),
6.61 (dd, J = 2.4, 1.8 Hz, 1H), 5.03 (s, 2H); 13C NMR (75
MHz, CDCl3, DEPT) d 184.98 (CH), 135.94 (C), 129.16
(CH), 138.66 (2CH), 127.96 (CH), 127.09 (2CH), 126.47
(C), 123.53 (CH), 108.09 (CH), 53.52 (CH2); LRMS m/z
(rel int) 185 (M+, 5), 91 (100); HRMS (EI) calcd for
C12H11NO 185.0841, found 185.0831.
Reduction of Compound 4a with NaBH4
To a solution of compound 4a (0.15 g, 0.81 mmol) in
methanol (25 mL) was added sodium borohydride (0.080 g,
2.1 mmol) at 0 oC. The reaction mixture was stirred at room
temperature for 2 h. To this reaction mixture was added sat-
urated NH4Cl (10 mL). The solvents were evaporated. Af-
ter extraction with ether (5 ´ 30 mL), the organic layer was
washed with brine, dried over MgSO4, and evaporated, and
the residue was purified by flash column chromatography
to give 5 (0.12 g, 80%).
N-(p-Methylbenzyl)-3-formylpyrrole (4b)
Pale yellow liquid; IR (CHCl3), 1670, 1155, 820 cm-1;
1H NMR (300 MHz, CDCl3) d 9.72 (s, 1H), 7.29 (t, J = 1.8
Hz, 1H), 7.17 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 7.8 Hz, 2H),
6.69 (dd, J = 2.4, 1.8 Hz, 1H), 6.64 (dd, J = 2.4, 1.8 Hz,
1H), 5.04 (s, 2H), 2.35 (s, 3H); 13C NMR (75 MHz, CDCl3,
DEPT) d 185.36 (CH), 138.22 (C), 132.97 (C), 129.65
(2CH), 129.10 (CH), 127.44 (2CH), 126.71 (C), 123.62
(CH), 108.53 (CH), 53.72 (CH2), 21.09 (CH3); LRMS m/z
(rel int) 199 (M+, 100); 105 (60); HRMS (EI) calcd for
C13H13NO 199.0997, found 199.0989.
N-Benzyl-3-hydroxymethylpyrrole (5)
Pale yellow oil; IR (CHCl3) 3500-3200, 750, 700
1
cm-1; H NMR (300 MHz, CDCl3) d 7.34-7.24 (m, 3H),
7.14-7.10 (m, 2H), 6.66 (dd, J = 2.4, 1.5 Hz, 1H), 6.63 (t, J
= 1.5 Hz, 1H), 6.19 (dd, J = 2.4, 1.5 Hz, 1H), 5.00 (s, 2H),
4.52 (s, 2H), 1.70 (brs, 2H); 13C NMR (75 MHz, CDCl3,
DEPT) d 137.75 (C), 128.66 (2CH), 127.67 (CH), 127.06
(2CH), 124.26 (C), 121.64 (CH), 119.66 (CH), 108.15
(CH), 58.67 (CH2), 53.31 (CH2); LRMS m/z (rel int) 187
(M+, 60), 91 (100).
N-(p-Chlorobenzyl)-3-formylpyrrole (4c)
Pale yellow liquid; IR (CHCl3), 1670, 820 cm-1; 1H
NMR (300 MHz, CDCl3) d 9.74 (s, 1H), 7.34 (d, J = 8.7 Hz,
2H), 7.29 (t, J = 1.8 Hz, 1H), 7.09 (d, J = 8.7 Hz, 2H), 6.69-
6.65 (m, 2H), 5.07 (s, 2H); 13C NMR (75 MHz, CDCl3,
DEPT) d 185.21 (CH), 134.57 (C), 134.17 (C), 129.10
(2CH), 128.95 (CH), 128.60 (2CH), 126.85 (C), 123.56
(CH), 108.73 (CH), 53.14 (CH2); LRMS m/z (rel int) 221
(M+, 31), 219 (M+, 100).
Preparation of Compound 6
To a solution of aniline (0.60 g, 6.6 mmol) in dry THF
(40 mL) was dropwise added n-BuLi (2.78 mL, 6.96 mmol)
at 0 oC. The reaction mixture was stirred at room tempera-
ture for 2 h. To this solution was added compound 2 (0.80
g, 4.97 mmol) at 0oC. The reaction mixture was then stirred
at room temperature for 3 h. To this solution was added sat-
urated NH4Cl (10 mL) at room temperature. After extrac-
tion with ether (5 ´ 30 mL), the organic layer was washed
with brine, dried over MgSO4, and evaporated, and the resi-
due was purified by flash column chromatography to give 6
(0.65 g, 75%); pale yellow liquid; IR (CHCl3) 3420, 1600,
N-(1-Phenylethyl)-3-formylpyrrole (4d)
Pale yellow liquid; IR (CHCl3), 1670, 755, 700 cm-1;
1H NMR (300 MHz, CDCl3) d 7.39-7.28 (m, 4H), 7.14-
7.12 (m, 2H), 6.73 (dd, J = 2.4, 1.8 Hz, 1H), 6.64 (dd, J =
2.4, 1.8 Hz, 1H), 5.29 (q, J = 6.6 Hz, 1H), 1.83 (d, J = 6.6

3-Formylpyrrole from 3-Furfurylamine
J. Chin. Chem. Soc., Vol. 57, No. 6, 2010 1325
1500, 750, 700 cm-1; 1H NMR (300 MHz, CDCl3) d 7.36 (d,
J = 1.5 Hz, 2H), 7.18-7.14 (m, 2H), 6.74-6.61 (m, 3H), 6.38
(d, J = 1.5 Hz, 1H), 4.31 (s, 2H), 3.79 (brs, 1H); 13C NMR
(75 MHz, CDCl3, DEPT) d 147.95 (C), 143.20 (CH),
139.88 (CH), 129.18 (2CH), 123.30 (C), 117.68 (CH),
112.87 (2CH), 110.10 (CH), 39.24 (CH2); LRMS m/z (rel
int) 173 (M+, 100), 81 (75).
2. (a) Schreiber, S. L.; Hoveyda, A. H.; Wu, H. J. J. Am. Chem.
Soc. 1983, 105, 660. (b) Schreiber, S. L.; Satake, K. J. Am.
Chem. Soc. 1983, 105, 6723. (c) Schreiber, S. L.; Hoveyda,
A. H. J. Am. Chem. Soc. 1984, 106, 7200. (d) Martin, S. F.;
Gluchowski, C.; Campbell, C. L.; Chapman, R. C. J. Org.
Chem. 1984, 49, 2512. (e) Grootaert, W. M.; De Clercq, P. J.
Tetrahedron Lett. 1986, 27, 1731. (f) van Royen, L. A.;
Mijngheer, R.; De Clercq, P. J. Tetrahedron Lett. 1983, 24,
3145. (g) Klein, L. L. J. Am. Chem. Soc. 1985, 107, 2573. (h)
Dauben, W. G.; Kessel, C. R.; Takemura, K. H. J. Am. Chem.
Soc. 1980, 102, 6893. (i) Murai, A.; Takahashi, K.; Taketsuru,
H.; Masamune, T. Chem. Commun. 1981, 221. (j) Jung, M.
E.; Street, L. J. J. Am. Chem. Soc. 1984, 106, 8327. (k)
Warm, A.; Vogel, P. J. Org. Chem. 1986, 51, 5348. (l) Har-
wood, L. M.; Jones, G.; Pickard, J.; Thomas, R. M.; Watkin,
D. Chem. Commun. 1990, 605. (m) Marshall, J. A.; Du Bay,
W. J. J. Org. Chem. 1993, 58, 3602. (n) Hayakawa, K.; Yodo,
M.; Ohsuki, S.; Kanematsu, K. J. Am. Chem. Soc. 1984, 106,
6735. (o) Hayakawa, K.; Nagashima, S.; Kanematsu, K. J.
Org. Chem. 1988, 53, 860. (p) Wu, H. J.; Yen, C. H.; Chuang,
C. T. J. Org. Chem. 1998, 63, 5064. (g) Wu, H. J.; Lin, C. C.
J. Org. Chem. 1995, 60, 7558. (r) Wu, H. J.; Wu, C. Y. J. Org.
Chem. 1999, 64, 1576. (s) Wu, H. J.; Tsai, S. H.; Chern, J. H.;
Lin, H. C. J. Org. Chem. 1997, 62, 6367. (t) Wu, C. Y.; Lin,
H. C.; Wang, Z. Y.; Wu, H. J. J. Org. Chem. 2001, 66, 4610.
(u) Wu, H. J.; Chern, J. H.; Wu, C. Y. Tetrahedron 1997, 53,
2401. (v) Wu, H. J.; Wu, C. Y. Tetrahedron Lett. 1997, 38.
2493. (w) Chuang, C. T.; Yen, C. H.; Wu, H. J. J. Chin.
Chem. Soc. 1998, 45, 789. (x) Chen, I. C.; Wu, H. J. J. Chin.
Chem. Soc. 2000, 47, 263. (y) Lin, C. C.; Chen, L. H.; Wu, H.
J. J. Chin. Chem. Soc. 1991, 38, 613. (z) Liu, W. H.; Wu, H. J.
J. Chin. Chem. Soc. 1988, 35, 241.
Reaction of Compound 6 with Bromine in Acetone-
Water
The same reaction conditions for the oxidation of
compounds 3a-e were applied for the reaction of com-
pound 6 with bromine to give compound 7 as the major
product (45%) and compound 8 as the minor product
(30%). No detectable amount of N-phenyl-3-formylpyrrole
9 was obtained.
3-Furfuryl p-bromoaniline (7)
Pale yellow oil; IR (CHCl3), 3400, 1600, 1500, 820
1
cm-1; H NMR (300 MHz, CDCl3) d 7.39-7.37 (m, 2H),
7.24 (d, J = 10 Hz, 2H), 6.50 (d, J = 10 Hz, 2H), 6.38 (s,
1H), 4.11 (s, 2H), 3.86 (brs, 1H); 13C NMR (75 MHz,
CDCl3, DEPT) d 146.90 (C), 143.37 (CH), 139.94 (CH),
131.86 (2CH), 122.89 (C), 114.47 (2CH), 109.98 (CH),
109.25 (C), 39.27 (CH2); LRMS m/z (rel int) 253 (M+,
100), 251 (M+, 95).
3-Furfuryl 2,4-dibromoaniline (8)
Pale yellow oil; IR (CHCl3) 3400, 1600, 1500, 880,
1
800 cm-1; H NMR (300 MHz, CDCl3) d 7.53 (s, 1H),
7.40-7.38 (m, 2H), 7.26-7.22 (m, 1H), 6.52 (d, J = 9.0 Hz,
1H), 6.39 (s, 1H), 4.53 (brs, 1H), 4.17 (s, 2H); 13C NMR
(75 MHz, CDCl3, DEPT) d 143.78 (C), 143.55 (CH),
139.96 (CH), 134.22 (CH), 131.14 (CH), 122.34 (C),
112.46 (CH), 109.90 (C), 109.84 (CH), 108.38 (C), 39.24
(CH2); LRMS m/z (rel int) 333 (M+, 58), 331 (M+, 100),
329 (M+, 60).
3. (a) Martin, S. F.; Guinn, D. E. J. Org. Chem. 1987, 52, 5588.
(b) Martin, S. F.; Zinke, P. W. J. Am. Chem. Soc. 1989, 111,
2311. (c) Martin, S. F.; Pacofsky, G. J.; Gist, R. P.; Lee, W. C.
J. Am. Chem. Soc. 1989, 111, 7634.
4. Kuwajima, I.; Urabe, H. Tetrahedron Lett. 1981, 22, 5191.
5. (a) Schultz, A. G.; Motyka, L. A. J. Am. Chem. Soc. 1982,
104, 5800. (b) Yu, P.; Yang, Y.; Zhang, Z. Y.; Mak, T. C. W.;
Wong, H. N. C. J. Org. Chem. 1997, 62, 6359.
ACKNOWLEDGEMENT
We thank the National Science Council of the Repub-
lic of China, Taiwan for financial support.
6. (a) Williams, P. D.; LeGoff, E. J. Org. Chem. 1981, 46, 4143.
(b) Wu, H. J.; Lin, C. C. J. Org. Chem. 1996, 61, 3820. (c)
Wu, H. J.; Chao, C. S.; Lin, C. C. J. Org. Chem. 1998, 63,
7687. (d) Lin, H. C.; Wu, H. J. Tetrahedron 2000, 56, 341. (e)
Lin, C. C.; Wu, H. J. Tetrahedron Lett. 1995, 36, 9353. (f)
Lin, C. C.; Wu, H. J. J. Chin. Chem. Soc. 1995, 42, 815. (g)
Lin, C. C.; Wu, H. J. Synthesis 1996, 715. (h) Tsai, S. H.; Wu,
H. J.; Chung, W. S. J. Chin. Chem. Soc. 1996, 43, 445. (i)
Wu, H. J.; Tasi, S. H.; Chern, J. H.; Lin, H. C. J. Org. Chem.
1997, 62, 6367. (j) Chern, J. H.; Wu, H. J. Tetrahedron 1998,
53, 5967. (k) Lin, H. C.; Wu, H. J. Tetrahedron 2000, 56,
Received July 27, 2010.
REFERENCES
1. (a) Katritzky, A. R.; Rees, C. W. Comprehensive Hetero-
cyclic Chemistry Vol. 4; Pergamon Press Ltd.: Oxford, Eng-
land, 1984. (b) Joule, J. A.; Smith, G. F. Heterocyclic Chem-
istry; Van Nostrand Rheinhold: London, 1972; p 242. (c)
Lipshutz, B. H. Chem. Rev. 1986, 86, 795.

1326 J. Chin. Chem. Soc., Vol. 57, No. 6, 2010
Harn et al.
341. (l) Wu, H. J.; Chern, J. H.; Wang, S. L.; Liao, F. L. J.
Chin. Chem. Soc. 1998, 45, 139. (m) Wu, H. J.; Chern, J. H.
Tetrahedron 1997, 53, 17653. (n) Wu, H. J.; Chern, J. H. J.
Chem. Soc., Chem. Commun. 1997, 547. (o) Lin, H. C.; Wu,
C. Y.; Wu, H. J. J. Chin. Chem. Soc. 1997, 44, 609. (p) Lin, R.
L.; Wu, C. Y.; Chern, J. H.; Wu, H. J. J. Chin. Chem. Soc.
1996, 43, 289.
Commun. 1996, 375. (g) Tsai, S. H.; Wu, H. J.; Chung, W. S.
J. Chin. Chem. Soc. 1996, 43, 481.
9. Nedenskov, P.; Elming, N.; Nielsen, J. T.; Clauson-Kaas, N.
Acta Chem. Scand. 1995, 9, 17.
10. Jurczak, J.; Pikul, S. Tetrahedron Lett. 1985, 26, 3039.
11. Achmatowicz, Jr., O.; Bukowski, P.; Szechner, B.;
Zwierzchowska, Z.; Zamojski, A. Tetrahedron 1971, 27,
1973.
7. Piancatelli, G.; Scettri, A.; D’Auria, M. Tetrahedron 1980,
36, 661.
12. Lefebvre, Y. Tetrahedron Lett. 1972, 133.
13. Piancatelli, G.; Scettri, A.; D’Auria, M. Tetrahedron Lett.
1977, 2199.
8. (a) Antonioletti, R.; D’Auria, M.; DeMico, A.; Piancatelli,
G.; Scettri, A. Synthesis 1984, 280. (b) Wu, H. J.; Pan, K.
Chem. Commun. 1987, 898, (c) Wu, H. J.; Huang, F. J.; Lin,
C. C. Chem. Commun. 1991, 770. (d) Huang, F. J.; Lin, C. C.;
Wu, H. J. J. Chin. Chem. Soc. 1996, 43, 177. (e) Wu, H. J.;
Tsai, S.H.; Chung, W. S. Tetrahedron Lett. 1996, 37, 8209.
(f) Wu, H. J.; Tsai, S. H.; Chung, W. S. J. Chem. Soc., Chem.
14. Harn, P. J.; Lin, C. C.; Wu, H. J. J. Chin. Chem. Soc. 2008,
55, 233.
15. Harn, P. J. Master Thesis, National Chiao Tung University,
1995.