Sep-Oct 2007
Synthesis of Phenyl Furyl Sulfides and Phenyl Furyl Ethers
1147
Isobutyl 5-(2-Carboxyphenylthio)-2-furancarboxylate (3f).
The product was pale yellow needles; IR (potassium bromide):
3200-2800 (OH), 1720 (COOCH3), 1685 (COOH) cm-1; 1H-
NMR (dimethyl-d6 sulfoxide) ꢀ: 8.06-6.60 (4H, m, Ph-H), 7.40
(1H, d, J=4 Hz, F-3), 7.14 (1H, d, J=4 Hz, F-4), 4.28-3.97 (2H,
m, CH2), 2.17-1.76 (1H, m, CH), 0.96 (6H, d, J=6 Hz, CH3 x 2);
MS m/z: 320 (M+). Anal. Calculated for C16H16O5S: C, 59.99; H,
5.03. Found: C, 60.05; H, 4.95.
nucleophilic substitution reactions readily occurred with
5-nitrofurans using electron withdrawal groups, similar to
previous reports of nucleophilic substitution with 5-
nitrofurans [10-12]. Using the disodium salt of
thiosalicylic acid (1a), we found that nucleophilic
substitution reactions readily proceeded with several 5-
nitrofurans having electron withdrawal groups.
5-(2-Carboxyphenylthio)furan-2-nitrile (3g). The product
was pale yellow prisms; IR (potassium bromide): 3000-2500
(OH), 2230 (CN), 1630 (CO) cm-1; 1H-NMR (dimethyl-d6
sulfoxide) ꢀ: 8.08-6.67 (4H, m, Ph-H), 7.78 (1H, d, J=4 Hz, F-
3), 7.27 (1H, d, J=4 Hz, F-4); MS m/z: 245 (M+). Anal.
Calculated for C12H7NO3S: C, 58.77; H, 2.88; N, 5.71. Found: C,
58.57; H, 2.72; N, 5.93.
EXPERIMENTAL
All melting points (open capillaries) were determined using a
Yamato MP-21 and are uncorrected. 1H-NMR spectra were
determined at 60 MHz using a Nippon Denshi JNM PMX60 SI
spectrometer with tetramethylsilane as an internal reference. IR
spectra were measured using a JASCO IR-810 spectrometer. MS
5-(2-Carboxyphenylthio)-2-acetylfuran (3h). The product
was pale yellow needles; IR (potassium bromide): 3100-2600
spectra were measured with
spectrometer at 70 eV.
a Nippon Denshi DX-300
1
(OH), 1780 (CO) cm-1; H-NMR (deuteriochloroform) ꢀ: 8.00-
6.60 (4H, m, Ph-H), 7.52 (1H, d, J=4 Hz, F-3), 7.15 (1H, d, J=4
Hz, F-4), 2.42 (3H, s, CH3); MS m/z: 262 (M+). Anal. Calculated
for C13H10O4S: C, 59.53; H, 3.84. Found: C, 59.50; H, 3.95.
5-(2-Methoxycarbonylphenylthio)-2-furancarbaldehyde (3j).
A solution of methyl salicylate (16.8 g, 0.1 mol) in dimethyl-
sulfoxide (DMSO) (150 ml) was added to a suspension of 60%
sodium hydride (4 g, 0.167 mol) in DMSO (50 ml) with stirring
at room temperature, and the mixture was warmed to 50-55°C.
To this mixture, a solution of 5-nitro-2-furancarbaldehyde (14.1
g, 0.1 mol) in DMSO (50 ml) was added, and stirring was
performed for 30 min. The solution was then cooled to room
temperature and poured into ice-cold water. The resulting
product was collected by filtration and purified by recrystal-
lization (Table 1). The product was pale yellow needles; IR
(potassium bromide): 1710, 1680 (CO) cm-1; 1H-NMR
(dimethyl-d6 sulfoxide) ꢀ: 9.56 (1H, s, CHO), 8.01-6.70 (4H, m,
Ph-H), 7.61 (1H, d, J=4 Hz, F-3), 7.21 (1H, d, J=4 Hz, F-4),
3.80 (3H, s, CH3); MS m/z: 262 (M+). Anal. Calculated for
C13H10O4S: C, 59.53; H, 3.84. Found: C, 59.86; H, 3.66.
General procedure for nucleophilic substitution of 5-nitro-
furans with disodium salt of thiosalicylic acid. A solution of
thiosalicylic acid (15.4 g, 0.1 mol) in N,N-dimethylformamide
(DMF) (120 ml) was added to a suspension of 60% sodium
hydride (8 g, 0.333 mol) in DMF (120 ml) with stirring at <5°C,
and the mixture was warmed to 80°C. To this mixture, a solution
of 5-nitrofurans (0.1 mol) in DMF (50 ml) was added, and
stirring was performed for 3 h at 80°C. The solution was then
cooled to room temperature and poured into ice-cold water. The
solution was acidified with 10% hydrochloric acid and the
resulting product was collected by filtration and purified by
recrystallization (Table 1).
Ethyl 5-(2-Carboxyphenylthio)-2-furancarboxylate (3b).
The product was pale yellow needles; IR (potassium bromide):
1
3200-2800 (OH), 1730 (COOCH3), 1670 (COOH) cm-1; H-NMR
(dimethyl-d6 sulfoxide) ꢀ: 8.10-6.83 (4H, m, Ph-H), 7.50 (1H, d,
J=4 Hz, F-3), 7.24 (1H, d, J=4 Hz, F-4), 4.38 (2H, q, J=7 Hz, CH2),
1.25 (3H, t, J=7 Hz, CH3); MS m/z: 292 (M+). Anal. Calculated for
C14H12O5S: C, 57.53; H, 4.14. Found: C, 57.48; H, 4.06.
5-(2-Methoxycarbonylphenoxy)furan-2-nitrile (3m). A
solution of methyl salicylate (10.6 g, 0.07 mol) in dimethyl-
sulfoxide (DMSO) (50 ml) was added to a suspension of 60%
sodium hydride (2.8 g, 0.117 mol) in DMSO (50 ml) with
stirring at room temperature, and the mixture was warmed to 60-
70°C. To this mixture, a solution of 5-nitrofuran-2-nitrile (8 g,
0.058 mol) in DMSO (50 ml) was added, and stirring was
performed for 3 h. The solution was then cooled to room
temperature and poured into ice-cold water. The resulting oil
was extracted with benzene. The benzene layer was washed with
brine and dried over anhydrous sodium sulfate. The solution was
evaporated and the residue was distilled under reduced pressure
to give 11.3 g (80.2%). The product was a colorless liquid.; IR
(neat): 2230 (CN), 1736 (CO) cm-1; 1H-NMR (dimethyl-d6
sulfoxide) ꢀ: 8.00-6.94 (4H, m, Ph-H), 6.98 (1H, d, J=4 Hz, F-
3), 5.32 (1H, d, J=4 Hz, F-4), 3.81 (3H, s, CH3); MS m/z: 243
(M+). Anal. Calculated for C13H9NO4S: C, 64.20; H, 3.73; N,
5.76. Found: C, 64.12; H, 3.61; N, 5.56.
Propyl 5-(2-Carboxyphenylthio)-2-furancarboxylate (3c).
The product was pale yellow needles; IR (potassium bromide):
3200-2800 (OH), 1730 (COOCH3), 1680 (COOH) cm-1; 1H-
NMR (dimethyl-d6 sulfoxide) ꢀ: 8.01-6.65 (4H, m, Ph-H), 7.22
(1H, d, J=4 Hz, F-3), 6.85 (1H, d, J=4 Hz, F-4), 4.25 (2H, t, J=7
Hz, OCH2), 1.36 (2H, m, CH3), 1.00 (3H, t, J=7 Hz, CH3); MS
m/z: 306 (M+)ꢀ Anal. Calculated for C15H14O5S: C, 58.81; H,
4.61. Found: C, 58.76; H, 4.75.
Isopropyl 5-(2-Carboxyphenylthio)-2-furancarboxylate
(3d). The product was colorless needles; IR (potassium
bromide): 3200-2800 (OH), 1725 (COOCH3), 1690 (COOH)
1
cm-1; H-NMR (dimethyl-d6 sulfoxide) ꢀ: 8.30-6.63 (4H, m, Ph-
H), 7.36 (1H, d, J=4 Hz, F-3), 7.12 (1H, d, J=4 Hz, F-4), 5.25-
4.93 (1H, m, CH), 1.30 (6H, d, J=6 Hz, CH3 x 2); MS m/z: 306
(M+). Anal. Calculated for C15H14O5S: C, 58.81; H, 4.61. Found:
C, 58.89; H, 4.57.
Butyl 5-(2-Carboxyphenylthio)-2-furancarboxylate (3e).
The product was pale yellow needles; IR (potassium bromide):
3200-2800 (OH), 1725 (COOCH3), 1675 (COOH) cm-1; 1H-
NMR (dimethyl-d6 sulfoxide) ꢀ: 8.06-6.60 (4H, m, Ph-H), 7.41
(1H, d, J=4 Hz, F-3), 7.15 (1H, d, J=4 Hz, F-4), 4.23 (2H, t, J=6
Hz, OCH2), 1.83-1.20 (4H, m, CH2 x 2), 0.90 (3H, t, J=6 Hz,
CH3); MS m/z: 320 (M+). Anal. Calculated for C16H16O5S: C,
59.99; H, 5.03. Found: C, 59.92; H, 5.06.
REFERENCES
[1] Yamanaka, H.; Hino, T.; Nakagawa, M.; Sakamoto, T.
Shinpen Heterokankagoubutsu kisohen (in Japanese), KODANSHA
LTD., 2004, pp 49-52.