7
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R. Romeo et al. / Bioorg. Med. Chem. 21 (2013) 7929–7937
1
32.1, 145.7, 148.1. Anal. Calcd for C17
H
17
N
3
O
3
S: C, 59.46; H, 4.99;
over MgSO
475 mg (95%) of 14a as white solid, mp = 94–97 °C. H NMR
500 MHz, CDCl ) d: 5.17 (1H, dd, J = 8.9, 1.9 Hz), 5.71 (1H, dd,
J = 15.9, 1.9 Hz), 7.33–7.45 (4H, m), 7.85 (2H, dd, J = 8.3, 1.2 Hz),
4
, filtered and concentrated at reduced pressure to yield
1
N, 12.24. Found: C, 59.31; H, 4.94; N, 12.13.
(
3
5
.3.2. 2-(4-(Trimethylsilyl)-1H-1,2,3-triazol-1-yl)ethyl-4-
1
3
methylbenzenesulfonate (13b)
8.01 (1H, s). C NMR (126 MHz, CDCl3) d: 104.8, 116.3, 126.0,
128.6, 129.0, 130.1, 130.4, 148.0. Anal. Calcd for C10 : C,
Compound 13b was prepared by the general tosylation proce-
9 3
H N
dure in 91% yield as colorless oil. 1H NMR (300 MHz, CDCl
) d:
.30 (9H, s), 2.42 (3H, s), 4.37 (2H, t, J = 5.1 Hz), 4.65 (2H, t,
J = 5.1 Hz), 7.29 (2H, d, J = 8.3 Hz), 7.56 (1H, s), 7.64 (2H, d,
J = 8.3 Hz). Anal. Calcd for C14 SSi: C, 49.53; H, 6.23; N,
2.38. Found: C, 49.44; H, 6.17; N, 12.37.
70.16; H, 5.30; N, 24.54. Found: C, 70.02; H, 5.25; N, 24.53.
3
0
5.4.2. 1-Vinyl-1H-1,2,3-triazole (14b)
H
21
N
3
O
3
Compound 14b was prepared by the general elimination proce-
1
dure in 88% yield as white oil. The basic conditions lead to depro-
1
tection by TMS. H NMR (500 MHz, CDCl
3
) d: 5.03 (1H, d,
5
.3.3. 2-(4-Propyl-1H-1,2,3-triazol-1-yl)ethyl-4-methyl
J = 9.0 Hz), 5.60 (1H, d, J = 15.9 Hz), 7.24 (1H, dd, J = 15.9 e 8.9),
1
3
benzenesulfonate (13c)
7.58 (1H, s), 7.80 (1H, s). C NMR (126 MHz, CDCl
120.5, 130.1, 133.9. Anal. Calcd for C : C, 50.52; H, 5.30; N,
44.18. Found: C, 50.48; H, 5.29; N, 44.13.
3
) d: 104.9,
Compound 13c was prepared by the general tosylation proce-
4 5 3
H N
dure in 87% yield as orange oil. 1H NMR (300 MHz, CDCl
) d: 0.95
3H, t, J = 7.4 Hz), 1.48–1.81 (2H, m), 2.43 (3H, s), 2.66 (2H, t,
J = 7.5 Hz), 4.35 (2H, t, J = 4.9 Hz), 4.58 (2H, t, J = 4.9 Hz), 7.28–
.33 (3H, m), 7.66 (2H, d, J = 8.3 Hz). Anal. Calcd for C14 S:
C, 54.35; H, 6.19; N, 13.58. Found: C, 54.21; H, 6.14; N, 13.57.
3
(
5.4.3. 4-Propyl-1-vinyl-1H-1,2,3-triazole (14c)
7
H
19
N
3
O
3
Compound 14c was prepared by the general elimination proce-
1
dure in 90% yield as colorless oil. H NMR (500 MHz, CDCl
3
) d: 0.84
(
3H, t, J = 7.4 Hz), 1.52–1.64 (2H, m), 2.58 (2H, t, J = 7.6 Hz), 4.97
(1H, dd, J = 9.0, 1.8 Hz), 5.50 (1H, dd, J = 16.0, 1.8 Hz), 7.20 (1H,
5
.3.4. 2-(4-(4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl)ethyl-4-
1
3
methylbenzenesulfonate (13d)
dd, J = 16.0, 9.0 Hz), 7.52 (1H, s). C NMR (126 MHz, CDCl
13.5, 22.4, 27.4, 103.8, 117.6, 130.2, 148.3. Anal. Calcd for
: C, 61.29; H, 8.08; N, 30.63. Found: C, 61.24; H, 8.01; N,
3
) d:
Compound 13d was prepared by the general tosylation proce-
1
dure in 85% yield as white powder, mp = 135–137 °C. H NMR
7 11 3
C H N
(
500 MHz, CDCl
J = 4.8 Hz), 4.67 (2H, t, J = 4.8 Hz), 6.97 (2H, d, J = 8.8 Hz), 7.22
2H, d, J = 8.3 Hz), 7.63 (2H, d, J = 8.3 Hz), 7.65 (1H, s), 7.70 (2H,
3
) d: 2.32 (3H, s), 3.85 (3H, s), 4.44 (2H, t,
30.57.
(
5.4.4. 4-(4-Methoxyphenyl)-1-vinyl-1H-1,2,3-triazole (14d)
Compound 14d was prepared by the general elimination proce-
dure in 91% yield as white solid, mp = 100–103 °C. H NMR
1
3
d, J = 8.8 Hz). C NMR (126 MHz, CDCl
1
1
3
) d: 21.7, 49.2, 55.5, 68.1,
14.4, 119.9, 123.1, 127.1, 127.8, 130.2, 132.0, 145.6, 147.9,
59.8. Anal. Calcd for C18 S: C, 57.89; H, 5.13; N, 11.25.
1
19
H N
3
O
4
3
(500 MHz, CDCl ) d: 3.84 (3H, s), 5.16 (1H, dd, J = 8.9, 2.0 Hz),
Found: C, 57.81; H, 5.10; N, 11.26.
5.67 (1H, dd, J = 16.0, 2.0 Hz), 6.96 (2H, d, J = 8.9 Hz), 7.38 (1H,
dd, J = 16.0, 9.0 Hz), 7.78 (2H, d, J = 8.9 Hz), 7.92 (1H, s). 13C NMR
5
.3.5. 2-(4-(4-Pentylphenyl)-1H-1,2,3-triazol-1-yl)ethyl-4-
(126 MHz, CDCl
148.0, 160.0. Anal. Calcd for C11
20.88. Found: C, 65.53; H, 5.48; N, 20.85.
3
) d: 55.5, 104.5, 114.4, 115.3, 122.8, 127.3, 130.5,
methylbenzenesulfonate (13e)
11 3
H N O: C, 65.66; H, 5.51; N,
Compound 13e was prepared by the general tosylation proce-
1
dure in 75% yield as white powder, mp = 108–110 °C. H NMR
(
1
500 MHz, CDCl
.61–1.67 (2H, m), 2.29 (3H, s), 2.63 (2H, t, J = 7.4 Hz), 4.51 (2H,
t, J = 4.9 Hz), 4.65 (2H, t, J = 4.9 Hz), 7.20 (2H, d, J = 8.0 Hz), 7.24
3
) d: 0.90 (3H, t, J = 6.5 Hz), 1.29–1.37 (4H, m),
5.4.5. 4-(4-Pentylphenyl)-1-vinyl-1H-1,2,3-triazole (14e)
Compound 14e was prepared by the general elimination proce-
dure in 93% yield as white solid, mp = 78–81 °C. H NMR (500 MHz,
1
(
2H, d, J = 8.0 Hz), 7.62 (2H, d, J = 8.0 Hz), 7.67 (2H, d, J = 8.0 Hz),
3
CDCl ) d: 0.90 (3H, t, J = 7.0 Hz), 1.24–1.41 (4H, m), 1.54–1.69 (2H,
1
3
7
3
1
.70 (1H, s). C NMR (126 MHz, CDCl
1.6, 35.8, 49.2, 68.1, 120.4, 125.7, 127.6, 127.8, 129.0, 130.1,
32.0, 143.4, 145.6, 148.0. Anal. Calcd for C22 S: C, 63.90;
3
) d: 14.1, 21.6, 22.7, 31.2,
m), 2.63 (2H, t, J = 7.4 Hz), 5.17 (1H, dd, J = 8.9, 1.9 Hz), 5.69 (1H,
dd, J = 16.0, 1.9 Hz), 7.25 (2H, d, J = 8.1 Hz), 7.38 (1H, dd, J = 16.0,
1
3
27
H N
3
O
3
9.0 Hz), 7.76 (2H, d, J = 8.1 Hz), 7.97 (1H, s). C NMR (126 MHz,
CDCl ) d: 14.2, 22.7, 31.2, 31.6, 35.9, 104.6, 115.8, 126.0, 127.5,
29.1, 130.5, 143.7, 148.3. Anal. Calcd for C15 : C, 74.65; H,
7.94; N, 17.41. Found: C, 74.57; H, 7.89; N, 17.40.
H, 6.58; N, 10.16. Found: C, 63.82; H, 6.55; N, 10.15.
3
1
19 3
H N
5
.3.6. 2-(4-(4-Fluorophenyl)-1H-1,2,3-triazol-1-yl)ethyl-4-
methylbenzenesulfonate (13f)
Compound 13f was prepared by the general tosylation proce-
dure in 86% yield as white powder, mp = 140–141 °C. H NMR
5.4.6. 4-(4-Fluorophenyl)-1-vinyl-1H-1,2,3-triazole (14f)
Compound 14f was prepared by the general elimination proce-
dure in 90% yield as white solid, mp = 123–126 °C. H NMR
1
1
(
500 MHz, CDCl
3
) d: 2.34 (3H, s), 4.45 (2H, td, J = 5.3, 1.5 Hz),
.64–4.70 (2H, m), 7.13 (2H, t, J = 8.7 Hz), 7.23 (2H, d, J = 7.9 Hz),
.65 (2H, d, J = 7.9 Hz), 7.72 (1H, s), 7.75 (2H, dd, J = 8.9, 5.3 Hz).
4
7
3
(500 MHz, CDCl ) d: 5.21 (1H, d, J = 8.9 Hz), 5.71 (1H, dd, J = 15.9,
1.9 Hz), 7.14 (2H, t, J = 8.7 Hz), 7.39 (1H, dd, J = 15.9, 8.9 Hz),
1
3
13
C
NMR (126 MHz, CDCl
J = 21.8 Hz), 120.5, 126.6 (d, J = 2.7 Hz), 127.6 (d, J = 8.0 Hz),
127.8, 130.2, 132.1, 145.7, 147.2, 162.87 (d, J = 247.4 Hz). Anal.
Calcd for C17 S: C, 56.50; H, 4.46; N, 11.63. Found: C,
6.42; H, 4.39; N, 11.60.
3
)
d: 21.7, 49.3, 68.1, 116.1 (d,
3
7.82–7.85 (2H, m), 7.97 (1H, s). C NMR (126 MHz, CDCl ) d:
104.9, 116.0 (d, J = 8.9 Hz), 116.1, 126.4 (d, J = 2.9 Hz), 127.8 (d,
J = 8.3 Hz), 130.4, 147.2, 163.0 (d, J = 248.1 Hz). Anal. Calcd for
1
H16FN
3
O
3
C H
10 8
3
FN : C, 63.49; H, 4.26; N, 22.21. Found: C, 65.53; H, 5.48; N,
5
5
5
20.85.
.4. General elimination procedure
5.5. General 1,3-dipolar cycloaddition procedure
.4.1. 4-Phenyl-1-vinyl-1H-1,2,3-triazole (14a)
A solution of 14a (475 mg, 2.77 mmol) and nitrone 15 (1.04 g,
To a solution of 13a (1.0 g, 2.91 mmol) in tert-BuOH (20 mL),
3
3.3 mmol) in CHCl (5 mL) was put in a sealed tube and irradiated
tert-BuOK (0.49 g, 4.36 mmol) was added and the resulting mixture
was stirred at 40 °C for 12 h. The mixture was diluted with water
and extracted with DCM (3 ꢁ 10 mL). The organic layer was dried
under microwave conditions at 150 W, 80 °C, for 2 h. The removal
of the solvent in vacuo afforded a crude material which, after
flash chromatography purification by using as eluent a mixture