F.-li Yu et al. / Tetrahedron 66 (2010) 9145e9150
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4.1.1. 1-Hydroxymethyl-1,2,4-triazole (1). 1H-1,2,4-triazole (98%,
0.1 mol, 7.04 g), 96% paraformaldehyde (0.1 mol, 3.13 g), and cata-
lytic amount of triethylamine were put into a 100 mL three-neck
flask with a magnetic stirrer, a thermometer, and a reflux con-
denser. The resulted mixture was stirred and heated to melt. The
reaction was kept for 0.5 h at the molten temperature. After that,
the mixture was cooled to room temperature. Acetone was added
to recrystallize. The product was desiccated under infrared lamp to
give compound 1 (9.12 g, 92.1%) as a white solid: mp 68e69 ꢁC; 1H
phase was washed with water and then dried over MgSO4. The
solvents were removed by atmospheric distillation and the residue
was purified by fractional distillation, recrystallization or flash
chromatography on silica gel to afford corresponding Stetter
product.
4.2.1. 4-Oxo-4-(2-furyl)-butyric acid ethyl ester (5). The residue was
recrystallized from acetone to afford compound 5 as a white nee-
dle-shaped crystal: mp 52e53 ꢁC; 1H NMR (CDCl3, 500 MHz)
d 1.24
NMR (CDCl3, 500 MHz)
d
5.73 (s, 2H), 7.48 (s, 1H), 8.13 (s, 1H), 8.65
71.2, 145.2, 157.4.
(t, J¼7.0 Hz, 3H), 2.73 (t, J¼6.8 Hz, 2H), 3.16 (t, J¼7.0 Hz, 2H), 4.15 (q,
(s, 1H); 13C NMR (CDCl3, 125 MHz)
d
J¼7.0 Hz, 2H), 6.55 (t, J¼7.1 Hz, 1H), 7.24 (d, J¼6.9 Hz, 1H), 7.60 (d,
J¼6.9 Hz,1H); 13C NMR (CDCl3,125 MHz)
d 14.19, 27.90, 33.07, 60.72,
4.1.2. Bromine-substituted poly(ethylene glycol) monomethyl ether
(2). Poly(ethylene glycol) monomethyl ether (10 mmol, n¼11, 16,
42) and 20 mL CCl4 were put into a 100 mL four-neck flask
equipped with a thermometer, a reflux condenser, and a dropping
funnel. Under the stirring, fresh distilled PBr3 (15 mmol, 4.05 g) in
30 mL CCl4 was slowly added dropwise to the poly(ethylene
glycol) monomethyl ether solution. During the dropwise process,
the temperature of the reaction solutions was kept at 30e40 ꢁC.
After finishing the addition, the temperature was elevated to
65e70 ꢁC and the reaction solution was stirred for 5 h. After
completion of the reaction, the product was separated from the
reaction mixture with a separatory funnel. The upper light yellow
liquid was washed twice with CCl4 to afford compound 2 (n¼11,
16, 42) as a pale yellow oil that was used without further
purification.
112.26, 117.07, 146.38, 152.43, 172.70, 187.39; MS m/z (relative in-
tensity, %) 197 (0.85, Mþþ1), 196 (8.62, Mþ), 151 (15.08), 95 (100),
67 (9.87), 55 (11.67).
4.2.2. 4-Oxo-heptanoic acid ethyl ester (6). The residue was vacuum
distilled to afford compound 6 as a colorless oil: 88e90 ꢁC/
13 mmHg; 1H NMR (CDCl3, 500 MHz)
d
0.82 (t, J¼7.2 Hz, 3H), 1.14 (t,
J¼7.1 Hz, 3H), 1.50 (m, 2H), 2.32 (t, J¼7.1 Hz, 2H), 2.46 (t, J¼7.0 Hz,
2H), 2.61 (t, J¼7.0 Hz, 2H), 4.01 (q, J¼7.1 Hz, 2H); 13C NMR (CDCl3,
125 MHz)
d 13.62, 14.08, 17.20, 28.86, 36.98, 44.61, 60.52, 172.82,
209.09; MS m/z (relative intensity, %) 145 (0.55, Mþþ1), 144 (7.87,
Mþ), 127 (19.23), 101 (45.78), 71 (58.87), 43 (100).
4.2.3. 2,4-Diphenyl-1-(2-furyl)-1,4-butanedione (11). The residue
was chromatographed on silica gel using 9:1 hexane/EtOAc to af-
ford compound 11 as a pale yellow solid: mp 120e122 ꢁC; 1H NMR
4.1.3. Polyether-substituted triazole (3). 1-Hydroxymethyl-1,2,4-
triazole 1 (5 mmol, 0.495 g) was first dissolved in 20 mL toluene.
Then, 5 mmol of bromine-substituted poly(ethylene glycol) mon-
omethyl ether 2 (n¼11, 16, 42), and Et3N (5 mmol, 0.505 g) were
added. The resulted mixture was stirred and heated under reflux
for 6 h. After completion of the reaction, the mixture was cooled to
room temperature. Et3N salt was separated from the solution by
filtration, and the solvent was removed under atmospheric distil-
lation to afford compound 3 (n¼11, 16, 42) as a yellow oil. Yield:
(CDCl3, 500 MHz)
10.0 Hz, 1H), 5.12 (dd, J¼10.0, 4.0 Hz, 1H), 6.53 (m, 1H), 7.24e7.57
(m, 10H), 7.97(m, 2H); 13C NMR (CDCl3, 125 MHz)
42.74, 48.67,
112.28, 118.18, 127.45e129.00, 133.26, 136.36, 138.24, 146.50, 152.16,
187.70, 197.82; MS m/z (relative intensity, %) 305 (7.46, Mþþ1), 304
(7.87, Mþ), 199 (68.13), 105 (100), 95 (87.91), 77 (87.04).
d
3.32 (dd, J¼18.0, 4.0 Hz, 1H), 4.17 (dd, J¼18.0,
d
4.2.4. 1,2,4-Triphenyl-1,4-butanedione (12). The residue was chro-
matographed on silica gel using 15:1 hexanes/EtOAc to afford com-
pound 12 as a white needle-shaped crystal: mp 124e126 ꢁC; 1H NMR
75%e80%. Compound 3 (n¼16): 1H NMR (D2O, 500 MHz)
d 3.12 (s,
3H), 3.30e3.80 (m, 64H), 5.56 (s, 2H), 8.25 (s, 1H), 8.86 (s, 1H); 13C
(CDCl3, 500 MHz)
10.0 Hz, 1H), 5.34 (dd, J¼10.0, 3.5 Hz,1H), 6.53 (m, 1H), 7.22e7.59 (m,
11H), 7.97(m, 4H); 13C NMR (CDCl3, 125 MHz)
43.85, 48.69,
d
3.32 (dd, J¼21.0, 3.5 Hz, 1H), 4.23 (dd, J¼21.0,
NMR (D2O, 125 MHz)
d
30.5, 67.1e73.2, 145.0, 158.1.
d
4.1.4. Thermoregulated
triazolium ionic liquids
catalyst
127.33e129.17, 132.85, 133.21, 136.45, 138.63, 198.04, 198.89; MS m/z
(4). Polyether-substituted triazole 3 (n¼11, 16, 42) (10 mmol),
bromoethane (10 mmol, 1.09 g), and 30 mL dried acetonitrile were
mixed in a 100 mL round-bottomed flask with a reflux condenser
(potassium hydroxide drying tube) and heated under reflux for
24 h. After cooling, the acetonitrile was removed under atmo-
spheric distillation. The residue was washed twice with heptane to
afford the product 4 (n¼11, 16, 42) as a yellow and viscous liquid.
Yield: 80%e83%. Compound 4 (n¼16): 1H NMR (D2O, 500 MHz)
(relative intensity, %) 314 (3.16, Mþ), 209 (9.33),105 (100), 77 (58.65).
4.2.5. 4-Oxo-4-(2-furyl)-butyronitrile (13). The residue was chro-
matographed on silica gel using 15:1 hexanes/EtOAc to afford
compound 13 as a pale yellow needle-shaped crystal: mp 76e78 ꢁC;
1H NMR (CDCl3, 500 MHz)
d
2.73 (t, J¼7.5 Hz, 2H), 3.23 (t, J¼7.5 Hz,
2H), 6.56 (t, J¼6.8 Hz, 1H), 7.61 (d, J¼6.5 Hz, 1H), 7.76 (d, J¼6.5 Hz,
1H); 13C NMR (CDCl3, 125 MHz)
11.29, 33.78, 112.61, 117.70, 118.88,
d
d
1.30 (t, J¼7.2 Hz, 3H), 3.08 (s, 3H), 3.20e3.84 (m, 64H), 4.52 (q,
146.89, 151.71, 184.48; MS m/z (relative intensity, %) 150 (2.10,
J¼7.2 Hz, 2H), 5.68 (s, 2H), 8.01 (s, 1H), 8.83 (s, 1H); 13C NMR (D2O,
Mþþ1), 149 (15.23, Mþ), 95 (100), 67 (8.06).
125 MHz)
d 15.8, 32.2, 55.4, 69.2e77.8, 147.6, 160.3.
4.2. General procedure for Stetter reaction
Freshly distilled aldehyde (50 mmol) and
Acknowledgements
a
,
b-unsaturated ester,
This work was supported by the National Natural Science
Foundation of China (No. 21006055).
ketone or nitrile (50 mmol), a certain amount of thermoregulated
triazolium ionic liquids catalyst 4, and the same amount of Et3N,
and the selected solvents were mixed together in a 100 mL round-
bottomed flask with a reflux condenser. Under the stirring, the
temperature raised to determinate temperature and kept for de-
terminate time. After that, the reaction mixture was cooled to room
temperature. By simple decantation, the upper organic phase
containing products was separated from the ionic liquids catalyst,
which was at the bottom of the flask. Subsequently, the organic
Supplementary data
Supplementary data associated with this article can be found in
clude MOL files and InChIKeys of the most important compounds
described in this article.