Oxidation of 3-furfurylcarbinols with bromine in acetone-water

Article abstract of DOI:10.1002/jccs.200800035

Oxidation of 3-furfurylcarbinols 3a-e and 7 with bromine in acetone-water solution gave the 2-substituted-3-furfurals 4a-e and 8 in good yields, respectively. Reaction of 2-alkyl-3-furfurylcarbinols 9a and 9b with bromine in acetone-water gave the bromoal

Full text of DOI:10.1002/jccs.200800035

Journal of the Chinese Chemical Society, 2008, 55, 233-238
233
Oxidation of 3-Furfurylcarbinols with Bromine in Acetone-Water
Piin-Jye Harna,d
(
), Chu-Chung Lina,c
(
) and Hsien-Jen Wua,b,* (
)
aDepartment of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan, R.O.C.
bDepartment of Food Science, Yuanpei University, Hsinchu, Taiwan, R.O.C.
cDepartment of Medicinal Chemistry, TaiGen Biotechnology Co., Ltd., Taipei, Taiwan, R.O.C.
dSinoPharm Taiwan Ltd., Tainan County, Taiwan, R.O.C.
Oxidation of 3-furfurylcarbinols 3a-e and 7 with bromine in acetone-water solution gave the 2-substi-
tuted-3-furfurals 4a-e and 8 in good yields, respectively. Reaction of 2-alkyl-3-furfurylcarbinols 9a and
9b with bromine in acetone-water gave the bromoalkyl 3-furfuryl ketones 10a and 10b as the major prod-
ucts. A reaction mechanism via the cis-trans isomerization of the 2-ene-1,4-diones 13 and 14 was pro-
posed to account for the transposition of the alkyl group of the 3-furfurylcarbinols 3, 7 and 9 to the 2-posi-
tion on the furan ring of the products 4, 8 and 10.
Keywords: 3-Furfurylcarbinols; Oxidation with bromine.
INTRODUCTION
Furan derivatives and their oxidation products are im-
the oxidation reaction of 3-furfuryl alcohols with bromine
in aqueous acetone solution.
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 deriva-
tives with bromine in absolute methanol is known as
Clauson-Kaas reaction to give the 2,5-dimethoxy-2,5-di-
hydrofuran derivatives B,9 presumably via the dibromo in-
termediates A (Scheme I). About two decades ago, a direct
transformation of C to D by modified reaction conditions
of the bromine oxidation with furan C was reported.10 Re-
action of 2-furfuryl alcohols E with bromine in methanol
followed by mild acid hydrolysis gave 6-hydroxyl-2H-
pyran-3(6H)-ones F,11 a route to monosaccharides from
furan compounds. This transformation from E to F was
also accomplished with peroxy acids12 and PCC.13 6-Hy-
droxy-2H-pyran-3(6H)-ones are useful intermediates for
the synthesis of natural products.3,11 In this paper, we report
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
RESULTS AND DISCUSSION
The required 3-furfuryl alcohols were prepared by
Paterno-Büchi photocycloaddition14 of aldehydes with
furan15 followed by ring opening of the oxetane ring with a
catalytic amount of p-toluenesulfonic acid (PTSA) in anhy-
drous ether or CCl4.16 The other way to prepare 3-furfuryl
alcohols is by nucleophilic addition of organometallic
compounds to 3-furfuryl aldehyde. Both methods were
adopted in this paper. Photocycloaddition of aldehydes
1a-d with excess furan in Quartz tubes with wavelength
300 nm light produced by Rayonet photometry for 40 h
gave the photocycloadducts 2a-d in 70-85% yields (based

234 J. Chin. Chem. Soc., Vol. 55, No. 1, 2008
Harn et al.
on consumed aldehydes). Treatment of 2a-d with a cata-
lytic amount of PTSAin dry tetrahydrofuran (THF) at room
temperature for 2 h gave the 3-furfuryl alcohols 3a-d in
65-75% yields. Reaction of 1-hexyne with n-butyllithium
in dry THF followed by addition of 3-furfural at 0 °C gave
the furfuryl alcohol 3e in 80% yield (Scheme II). Oxidation
of the 3-furfuryl alcohols 3a-e with two equivalents of bro-
mine in acetone-water (volume ratio 85:15) at 0 °C for 2 h
gave 2-substituted 3-furfural 4a-e in 65-75% yields, re-
spectively.
with two equivalents of bromine in aqueous acetone, the
3-furfural 4e was obtained in good yield (65%) even in the
presence of a carbon-carbon triple bond. The amount of the
other products 5 or 6, which might be obtained by addition
of bromine to the triple bond, was too small to be isolated.
This result may imply that the reaction rate of the oxidation
of bromine on the furan ring of 3e is much faster than that
of the addition of bromine to the triple bond.
Treatment of thiophene with n-BuLi in dry THF at
room temperature followed by addition of 3-furfural gave
3-furfuryl-2-thienyl carbinol (7) in 70% yield. Reaction of
7 with bromine in the same reaction conditions as the previ-
ous oxidations gave compound 8 in 65% yield (Scheme
III). The amount of the other products, which might be ob-
tained by reaction on the thiophene ring, was too small to
be isolated. Thus, the oxidation selectively took place on
the furan ring of 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 1685 cm-1 for the carbonyl
group. The 1H NMR spectrum of 4a showed a singlet at d
9.94 for the aldehyde proton, a doublet (J = 1.5 Hz) at d
7.31 for the C5 proton on the furan ring, a doublet (J = 1.5
Hz) at d 6.69 for the furan ring C4 proton, and a singlet at d
2.60 for the methyl protons. The 13C NMR spectrum of 4a
displayed one peak (CH) at d 184.8 for the aldehyde car-
bonyl carbon, four peaks at d 161.9 (C), 141.9 (CH), 122.5
(C) and 108.0 (CH) for the furan ring carbons, and one
peak (CH3) at d 12.6 for the methyl carbon. The mass spec-
trum of 4a showed its molecular parent peak at 110 with
25% relative intensity. In the case of the oxidation of 3e
In order to understand the feasibility of the applica-
tion of this oxidation reaction to the interexchange of the
substituents on the furan ring, the following experiments
were performed. Addition of the Grignard reagent,
CH3MgCl, to compound 4b in dry THF at 0 °C gave the ad-
ditional product 9a in 80% yield. Reaction of 4a with
n-BuLi in dry THF at 0 °C gave compound 9b in 85% yield.
Scheme II
H
R
H
O
R
OH
hv (300 nm)
PTSA
THF
+
O
R
H
O
40 h
O
1
H
O
2
3
a, R = CH3
b, R = C2H5
c, R = C3H7
d, R = Ph
H
HO
O
C4H9
n-BuLi
O
C4H9
H
THF
O
3e
O
H
Br
O
C4H9
H
Br2
O
3a-e
Br
5
acetone-H2O
0 oC
R
O
O
4
a, R = CH3
b, R = C2H5
c, R = C3H7
d, R = Ph
H
Br
C4H9
Br
O
C
C C4H9
Br
e, R =
Br
6

Oxidation of 3-Furfurylcarbinols with Bromine in Acetone-Water
J. Chin. Chem. Soc., Vol. 55, No. 1, 2008 235
Scheme V
Scheme III
O
OH
HO
OH
H
R
Br2
H
R
Br2
H
S
O
Br
acetone-H2O
Br
acetone-H2O
O
O
O
11
S
7
8
OH
O
OH
H
R
R
-H2O
R
Oxidation of 9a and 9b with two equivalents of bromine in
acetone-H2O (85:15) at 0 °C gave compounds 10a and 10b
as the major products in 50-55% yields, respectively, with a
small amount of other unidentified products (Scheme IV).
When one equivalent of bromine was used in the oxidation
of 9a and 9b, compounds 10a and 10b were obtained as the
major products with unreacted starting compounds 9a and
9b, respectively. This result may imply that the reaction
rate of the bromination of the a carbon of the carbonyl
group of 10 is faster than that of the oxidation of the furan
ring of the 3-furfuryl alcohols. The bromine atom of 10a
and 10b can be eliminated by reduction reaction, for exam-
ple, with Zn/HOAc. Thus, the substituents at C2 and C3 on
the furan ring of the 3-furfurylcarbinols can be inter-
changed by this oxidation reaction.
H
H
H
H
H
O
O
O
HO
OH
O HO
12
13
14
O
O
-H2O
H
H
R
HO
R
O
O
15
4
A similar reaction mechanism can be applied to account for
the transformation from 9a and 9b to 10a and 10b, except
that further bromination on the a-carbon of the carbonyl
group of 10 proceeded.
CONCLUSION
In summary, we have demonstrated the oxidation of
the 3-furfurylcarbinols 3a-e, 7, 9a and 9b with brimine in
acetone-water solution gave the 2-substituted-3-furfuryl
aldehydes 4a-e and ketones 8, 10a and 10b. A reaction
mechanism via the cis-trans isomerization from the Z-iso-
mer 13 of the 2-ene-1,4-dione to the E-isomer 14 was pro-
posed to account for the transformation of the alkyl group
from the 3-position on the furan ring of the reactants to the
2-position on the furan ring of the products.
Scheme IV
HO
HO
CH3MgCl
THF
n-BuLi
4b
4a
THF
O
O
9a
9b
O
R'
Br
Br2
acetone-H2O
9a, 9b
R
O
10
a, R = R' = CH3
b, R = C4H9, R' = H
EXPERIMENTAL SECTION
Infrared spectra were recorded in CHCl3 solutions or
1
A reaction mechanism was proposed for the transfor-
on neat thin films between NaCl disks. H NMR spectra
mation from the 3-furfuryl alcohols 3a-e and 7 to the 3-fur-
furals 4a-e and 8 (Scheme V). The initial step of this oxida-
tion is similar to the Clauson-Kaas reaction as shown in the
first line of Scheme I. The oxidation reaction of 3 with bro-
mine in acetone-water solution gives the 2,5-dihydroxy-
2,5-dihydrofuran 12, presumably via the dibromo interme-
diate 11. Dehydration of 12 followed by ring opening gives
the Z-isomer of 2-ene-1,4-dione 13. Cis-trans isomeriza-
tion of 13 gives the E-isomer 14. Acetal formation by the
intramolecular cyclization of 14 gives the hemiacetal 15,
which was followed by dehydration to yield the product 4.
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)
analysis, precoated TLC plates (Kieselgel 60 F254) were
used, and column chromatography was done by using

236 J. Chin. Chem. Soc., Vol. 55, No. 1, 2008
Harn et al.
Kieselgel 60 (70-230 mesh) as the stationary phase. THF
was distilled immediately prior to use from sodium benzo-
phenone ketyl under nitrogen.
2-Methyl-3-furfural (4a)
Pale yellow liquid; IR (CHCl3) 1685, 1500 cm-1; 1H
NMR (300 MHz, CDCl3) d 9.94 (s, 1H), 7.31 (d, J = 2.1 Hz,
1H), 6.69 (d, J = 2.1 Hz, 1H), 2.60 (s, 3H); 13C NMR (75
MHz, CDCl3, DEPT) d 184.81 (CH), 161.93 (C), 141.95
(CH), 122.54 (C), 108.03 (CH), 12.58 (CH3); LRMS m/z
(rel int) 110 (M+, 25), 95 (100); HRMS (EI) calcd for
C6H6O2 110.0368, found 110.0374.
Preparation of the 3-Furfuryl Alcohols 3a-e
Photoaddition of aldehydes 1a-d with excess furan in
quartz tubes with wavelength 300 nm radiation produced
by Rayonet photometry for 40 hours gave the photoadducts
2a-d in 70-85% yields (based on consumed aldehydes).
Treatment of 2a-d with a catalytic amount of PTSA in dry
THF at room temperature for 2 h gave the 3-furfuryl alco-
hols 3a-d in 65-75% yields, which are known compounds.16
To a solution of 1-hexyne (0.82 g, 10.0 mmol) in dry
THF (30 mL) was added n-butyllithium (2.5 M in n-hex-
ane, 4.0 mL) at 0 °C. The solution was stirred at room tem-
perature for one hour. To this solution was added 3-furfural
(0.96 g, 10.0 mmol) at 0 °C. The reaction mixture was
stirred at room temperature for two hours. The solvent was
evaporated, and saturated NH4Cl (30 mL) was added. After
extraction with ether (5 ´ 30 mL), the organic layer was
washed with brine, dried over MgSO4, and evaporated, and
the residue was purified by column chromatography to give
3e (1.42 g, 80%).
2-Ethyl-3-furfural (4b)
Pale yellow liquid; IR (CHCl3) 1685, 1500 cm-1; 1H
NMR (300 MHz, CDCl3) d 9.96 (s, 1H), 7.32 (d, J = 2.1 Hz,
1H), 6.69 (d, J = 2.1 Hz, 1H), 2.99 (q, J = 7.5 Hz, 2H), 1.33
(t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) d
184.63 (CH), 166.83 (C), 141.92 (CH), 121.61 (C), 107.86
(CH), 20.33 (CH2), 12.58 (CH3); LRMS m/z (rel int) 124
(M+, 20), 123 (40), 57 (100); HRMS (EI) calcd for C7H8O2
124.0524, found 124.0534.
2-n-Propyl-3-furfural (4c)
Pale yellow liquid; IR (CHCl3) 1685, 1500 cm-1; 1H
NMR (300 MHz, CDCl3) d 9.94 (s, 1H), 7.32 (d, J = 2.1 Hz,
1H), 6.69 (d, J = 2.1 Hz, 1H), 2.93 (t, J = 7.5 Hz, 2H),
1.80-1.73 (m, 2H), 0.97 (t, J = 7.5 Hz, 3H); 13C NMR (75
MHz, CDCl3, DEPT) d 184.72 (CH), 165.93 (C), 141.98
(CH), 122.51 (C), 107.68 (CH), 28.52 (CH2), 21.58 (CH2),
13.45 (CH3); LRMS m/z (rel int) 138 (M+, 24), 95 (100);
HRMS (EI) calcd for C8H10O2 138.0681, found 138.0688.
Spectral data for 3e: pale yellow liquid; IR (CHCl3)
3500-3300, 2220, 1500 cm-1; 1H NMR (300 MHz, CDCl3)
d 7.49 (s, 1H), 7.38 (d, J = 3.0 Hz, 1H), 6.49 (d, J = 3.0 Hz,
1H), 5.36 (brs, 1H), 2.40 (brs, 1H), 2.25 (t, J = 6.6 Hz, 2H),
1.38-1.57 (m, 4H), 0.92 (t, J = 7.2 Hz, 3H); 13C NMR (75
MHz, CDCl3, DEPT) d 143.40 (CH), 139.99 (CH), 127.06
(C), 109.17 (CH), 85.92 (C), 79.48 (C), 57.33 (CH), 30.53
(CH2), 21.87 (CH2), 18.29 (CH2), 13.48 (CH3); LRMS m/z
(rel int) 178 (M+, 100), 121 (50); HRMS (EI) calcd for
C11H14O2 178.0994, found 178.0986.
2-Phenyl-3-furfural (4d)
Pale yellow oil; IR (neat) 1685, 1600, 1500, 760, 700
cm-1; 1H NMR (300 MHz, CDCl3) d 10.13 (s, 1H), 7.75-
7.71 (m, 2H), 7.53-7.43 (m, 4H), 6.91 (d, J = 2.1 Hz, 1H);
13C NMR (75 MHz, CDCl3, DEPT) d 185.65 (CH), 161.53
(C), 142.70 (CH), 130.15 (CH), 128.98 (2CH), 128.86 (C),
128.02 (2CH), 122.92 (C), 109.40 (CH); LRMS m/z (rel
int) 172 (M+, 86), 171 (100), 95 (60); HRMS (EI) calcd for
C11H8O2 172.0524, found 172.0514.
General Procedure for the Oxidation of 3-Furfuryl-
carbinols 3a-e with Bromine in Acetone-Water
To a solution of 3-furfurylcarbinol 3a (0.56 g, 5.0
mmol) in acetone (17 mL) and water (3 mL) was dropwise
added bromine (0.80 g, 10.0 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
°C, and the mixture was stirred at room temperature for 20
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 column chromatog-
raphy to give 4a (0.36 g, 66%).
2-(1-Hexynyl)-3-furfural (4e)
Pale yellow oil; IR (neat) 2250, 1695 cm-1; 1H NMR
(300 MHz, CDCl3) d 9.98 (s, 1H), 7.33 (d, J = 2.1 Hz, 1H),
6.73 (d, J = 2.1 Hz, 1H), 2.53 (t, J = 6.9 Hz, 2H), 1.68-1.60
(m, 2H), 1.53-1.45 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H); 13
C
NMR (75 MHz, CDCl3, DEPT) d 184.75 (CH), 143.64
(CH), 128.54 (C), 107.42 (CH), 101.24 (C), 94.42 (C),

Oxidation of 3-Furfurylcarbinols with Bromine in Acetone-Water
J. Chin. Chem. Soc., Vol. 55, No. 1, 2008 237
68.58 (C), 29.94 (CH2), 21.87 (CH2), 19.22 (CH2), 13.39
(CH3); LRMS m/z (rel int) 176 (M+, 95), 147 (100); HRMS
(EI) calcd for C11H12O2 176.0837, found 176.0848.
layer was washed with brine, dried over MgSO4, and evap-
orated, and the residue was purified by column chromatog-
raphy to give compound 9a (0.56 g, 80%).
Preparation of 2-Thienyl-3-furfurylcarbinol (7)
2-Ethyl-3-furfuryl Methyl Carbinol (9a)
To a solution of thiophene (0.42 g, 5.0 mmol) in dry
THF (30 mL) was added n-butyllithium (2.5 M in n-hex-
ane, 2.0 mL) at 0 °C. The solution was stirred at room tem-
perature for 4 h. To this solution was added 3-furfural (0.48
g, 5.0 mmol) at 0 °C. The reaction mixture was stirred at
room temperature for one hour. Then, to this solution was
added saturated NH4Cl (20 mL). After extraction with
ether (5 ´ 30 mL), the organic layer was washed with brine,
dried over MgSO4, and evaporated, and the residue was pu-
rified by column chromatography to give 7 (0.63 g, 70%);
Pale yellow oil; IR (CHCl3) 3600-3200, 1050 cm-1;
1H NMR (300 MHz, CDCl3) d 7.23 (d, J = 2.1 Hz, 1H), 6.36
(d, J = 2.1 Hz, 1H), 4.82 (q, J = 6.6 Hz, 1H), 2.64 (q, J = 7.2
Hz, 2H), 2.19 (brs, 1H), 1.41 (d, J = 6.6 Hz, 3H), 1.20 (t, J =
7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) d 152.58
(C), 140.31 (CH), 122.54 (C), 108.21 (CH), 62.20 (CH),
23.97 (CH3), 19.51 (CH2), 13.13 (CH3); LRMS m/z (rel int)
140 (M+, 7), 125 (100); HRMS (EI) calcd for C8H12O2
140.0837, found 140.0830.
pale yellow oil; IR (CHCl3) 3600-3200, 1500 cm-1; H
2-Methyl-3-furfuryl n-Butyl Carbinol (9b)
1
1
NMR (300 MHz, CDCl3) d 7.34 (d, J = 2.1 Hz, 1H), 7.32 (s,
1H), 7.22 (d, J = 2.1 Hz, 1H), 6.92 (d, J = 1.8 Hz, 1H), 6.90
(d, J = 1.8 Hz, 1H), 6.36 (d, J = 2.1 Hz, 1H), 5.89 (d, J = 4.5
Hz, 1H), 3.10 (d, J = 4.5 Hz, 1H); 13C NMR (75 MHz,
CDCl3, DEPT) d 147.07 (C), 143.26 (CH), 139.64 (CH),
128.22 (C), 126.50 (CH), 125.13 (CH), 124.67 (CH),
109.02 (CH), 65.14 (CH); LRMS m/z (rel int) 180 (M+, 78),
85 (100).
Pale yellow oil; IR (CHCl3) 3600-3200 cm-1; H
NMR (300 MHz, CDCl3) d 7.23 (d, J = 2.1 Hz, 1H), 6.33
(d, J = 2.1 Hz, 1H), 4.57 (t, J = 6.6 Hz, 1H), 2.26 (s, 3H),
1.88 (s, 1H), 1.80-1.18 (m, 6H), 0.89 (t, J = 7.2 Hz, 3H); 13C
NMR (75 MHz, CDCl3, DEPT) d 148.04 (C), 140.40 (CH),
122.37 (C), 108.53 (CH), 66.66 (CH), 37.46 (CH2), 27.91
(CH2), 22.46 (CH2), 13.95 (CH3), 11.65 (CH3); LRMS m/z
(rel int) 168 (M+, 8), 43 (100); HRMS (EI) calcd for
C10H16O2 168.1151, found 168.1160.
Oxidation of Compound 7 with Bromine in Acetone-
Water
General Procedure for the Oxidation of Compounds
9a and 9b
The same reaction conditions for the oxidation of
compounds 3a-e with bromine were applied for the oxida-
tion of 7 with bromine to give compound 8 in 65% yield;
pale yellow oil; IR (CHCl3) 1685, 1500 cm-1; 1H NMR (300
MHz, CDCl3) d 10.21 (s, 1H), 7.69 (d, J = 4.2 Hz, 1H), 7.50
(d, J = 5.1 Hz, 1H), 7.39 (d, J = 1.5 Hz, 1H), 7.16 (dd, J =
4.2, 5.1 Hz, 1H), 6.68 (d, J = 1.5 Hz, 1H); 13C NMR (75
MHz, CDCl3, DEPT) d 184.63 (CH), 155.32 (C), 142.15
(CH), 130.82 (C), 128.60 (CH), 128.19 (CH), 127.99 (CH),
121.73 (C), 109.87 (CH); LRMS m/z (rel int) 178 (M+, 34),
177 (20), 121 (100).
The same reaction conditions for the oxidation of
compounds 3a-e were applied for the oxidation of com-
pounds 9a and 9b to give the bromoketones 10a and 10b as
the major products, respectively. When one equivalent of
bromine was used in the oxidation of 9a and 9b, com-
pounds 10a and 10b were obtained as the major products
with the unreacted compounds 9a and 9b.
2-Methyl-3-furfuryl a-Bromoethyl Ketone (10a)
Pale yellow oil; IR (neat) 1685, 1570 cm-1; 1H NMR
(300 MHz, CDCl3) d 7.28 (d, J = 2.1 Hz, 1H), 6.71 (d, J =
2.1 Hz, 1H), 4.86 (q, J = 6.6 Hz, 1H), 2.63 (s, 3H), 1.83 (t, J
= 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3, DEPT) d 189.44
(C), 161.18 (C), 140.37 (CH), 118.05 (C), 110.01 (CH),
44.51 (CH), 19.66 (CH3), 14.47 (CH3); LRMS m/z (rel int)
219 (M+, 4), 217 (M+, 4), 109 (100).
General Procedure for the Preparation of Com-
pounds 9a and 9b
To a solution of compound 4b (0.62 g, 5.0 mmol) in
dry THF (40 mL) was slowly added methylmagnesium
chloride (2.5 M in THF, 2.0 mL) at 0 °C. The reaction mix-
ture was stirred at room temperature for one hour. To this
solution was slowly added saturated NH4Cl (10 mL) at 0
°C. After extraction with ether (5 ´ 30 mL), the organic
2-n-Butyl-3-furfuryl Bromomethyl Ketone (10b)
Pale yellow oil; IR (neat) 1685, 1575 cm-1; 1H NMR

238 J. Chin. Chem. Soc., Vol. 55, No. 1, 2008
Harn et al.
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Chern, J. H.; Lin, H. C. J. Org. Chem. 1997, 62, 6367.
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.
(300 MHz, CDCl3) d 7.29 (d, J = 2.1 Hz, 1H), 6.65 (d, J =
2.1 Hz, 1H), 4.19 (s, 2H), 3.02 (t, J = 7.2 Hz, 2H), 1.68-1.63
(m, 2H), 1.40-1.32 (m, 2H), 0.92 (t, J = 7.2 Hz, 3H); 13
C
NMR (75 MHz, CDCl3, DEPT) d 186.96 (C), 165.02 (C),
140.63 (CH), 117.56 (C), 109.87 (CH), 33.27 (CH2), 29.60
(CH2), 27.85 (CH2), 22.31 (CH2), 13.72 (CH3); LRMS m/z
(rel int) 247 (M+, 15), 245 (M+, 16), 165 (100).
ACKNOWLEDGEMENT
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.
We thank the National Science Council of the Repub-
lic of China for financial support.
Received July 11, 2007.
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