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J Chem Crystallogr (2012) 42:323–329
Scheme 1 The structures
of some furanones
R
O
Ar
X
HN
O
X
Ar
O
Ar
Ar
OH
O
O
O
O
X= Cl, Br
5-alkoxy-4-aminofuran-2 (5H)-one
X= NHR(Ar), OR
4,5-diaryl-3-hydroxyfuran- 2(5H)-one
3-arylfuran-2 (5H)-one
Experimental Section
chromatography on silica gel, eluting with EtOAc/petro-
leum ether.
Reagents and Techniques
3-(3,4-Dimethoxyphenyl)-4-hydroxyfuran-2(5H)-one (1)
2-(3,4-Dimethoxyphenyl)acetic acid was purchased from
Aldrich (USA) and the other chemicals were purchased
from Sinopharm Chemical Reagent Co., Ltd (China).
Separation of the compounds by column chromatography
was carried out with silica gel 60 (200–300 mesh ASTM,
E. Merck). The quantity of silica gel used was 30–70
times the weight charged on the column. Then, the eluates
were monitored using TLC. Melting points (uncorrected)
were determined on a XT4 MP apparatus (Taike Corp.,
Beijing, China). ESI mass spectra were obtained on a
Mariner System 5304 mass spectrometer, and 1H NMR
spectra were recorded on a Bruker AV-300 spectrometer
at 25 °C with TMS and solvent signals allotted as internal
standards. Chemical shifts were reported in ppm (d).
Elemental analyses were performed on a CHN-O-Rapid
instrument and were within 0.4% of the theoretical
values.
Colorless crystal, 53%, mp 210–212 °C, 1H NMR (DMSO-
d6): 3.88 (s, 3H); 3.89 (s, 3H); 4.77 (s, 2H); 6.75 (dd,
J = 8.5 Hz, J = 2.0 Hz, 1H); 6.77 (d, J = 2.1 Hz, 1H);
6.93 (d, J = 8.1 Hz, 1H); EIMS m/z 236 (M?). Anal. Calcd
for C12H12O5: C, 61.01; H, 5.12; Found: C, 61.47; H, 5.10.
4-(2-Bromoethoxy)-3-(3,4-dimethoxyphenyl)furan-2(5H)-
one (2)
Light yellow crystal, 47%, mp 140–142 °C, 1H NMR
(CDCl3): 2.68 (t, J = 5.5 Hz, 2H); 3.88 (s, 3H); 3.90 (s,
3H); 4.20 (t, J = 5.5 Hz, 2H); 4.79 (s, 2H); 6.91 (d,
J = 8.4 Hz, 1H); 7.50 (dd, J = 8.4 Hz, J = 2.0 Hz, 1H);
7.56 (d, J = 1.8 Hz, 1H); EIMS m/z 342 (M?). Anal. Calcd
for C14H15BrO5: C, 49.00; H, 4.41; Br, 23.28; Found: C,
49.13; H, 4.41; Br, 23.24.
General Procedure for Preparation of Compounds 1–9
4-(2-(Cyclohexylamino)ethoxy)-3-(3,4-
dimethoxyphenyl)furan-2(5H)-one (3)
Compounds 1 and 2 were obtained according to the pro-
cedure previously described [11, 12], which were further
treated as follows to produce compounds 3–9 (Scheme 2;
Table 2). A mixture of compound 2 (0.5 mmol) and tri-
ethylamine (225 lL, 1.5 mmol) was dissolved in 15 mL of
dry DMF and heated to 50 °C. The solution was received
3–4 interval injections of an appropriate amine (0.6 mmol)
within 2 h. The mixture was then stirred for 6–10 h. After
30 mL of water was added, the resulted mixture was
extracted thrice with EtOAc. The combined organic layer
washed with brine and dried over MgSO4. Removement of
the solvent under reduced pressure gave a brown oil, which
was purified by column chromatography on silica gel,
eluting with CHCl3/CH3OH (saturated with ammonia, from
37/1 to 80/1) to give compounds 3–5. As for the synthesis
of compounds 6–9, a mixture of compound 1 (0.5 mmol),
an appropriately substituted aniline (0.6 mmol) and p-tol-
uene sulphonic acid (3.4 mg, 0.02 mmol) was heated to
90 °C for 10 min. Five mL toluene was then added and
refluxed for 3–7 h. After toluene was removed under
reduced pressure, the residue was purified by column
Colorless crystal, 68%, mp 137–139 °C, 1H NMR
(CDCl3): 0.80–1.02 (m, 3H); 1.23–1.42 (m, 3H); 1.60–1.74
(m, 4H); 1.93 (bs, 1H); 3.23 (t, J = 6.4 Hz, 2H); 3.32–3.43
(m, 1H); 3.54 (t, J = 6.3 Hz, 2H); 3.85 (s, 3H); 3.89 (s,
3H); 4.88 (s, 2H); 6.80 (d, J = 1.8 Hz, 1H); 6.81 (dd,
J = 8.0 Hz, J = 1.8 Hz, 1H); 6.86 (d, J = 8.3 Hz, 1H);
EIMS m/z 361 (M?). Anal. Calcd for C20H27NO5: C,
66.46; H, 7.53; N, 3.88; Found: C, 66.51; H, 7.51; N, 3.87.
3-(3,4-Dimethoxyphenyl)-4-(2-(piperidin-1-
yl)ethoxy)furan-2(5H)-one (4)
Colorless crystal, 89%, mp 116–117 °C, 1H NMR
(CDCl3): 1.38–1.49 (m, 2H); 1.51–1.67 (m, 4H); 2.46 (t,
J = 5.0 Hz, 4H); 2.73 (t, J = 5.5 Hz, 2H); 3.90 (s, 3H);
3.91 (s, 3H); 4.22 (t, J = 5.5 Hz, 2H); 4.87 (s, 2H); 6.89 (d,
J = 8.4 Hz, 1H); 7.50 (dd, J = 8.4 Hz, J = 2.0 Hz, 1H);
7.54 (d, J = 1.8 Hz, 1H); EIMS m/z 347 (M?). Anal. Calcd
for C19H25NO5: C, 65.69; H, 7.25; N, 4.03; Found: C,
65.60; H, 7.27; N, 4.04.
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