Molecules 2012, 17
4469
2
RS,4RS-Toluene-4-sulfonic acid 2-(4-fluorophenyl)-2-1,2,4-triazol-1-ylmethyl-1,3-dioxolan-4-yl-
1
methyl ester (6c). (36.5%). H-NMR (CDCl ), δ: 2.47 (s, 3H), 3.49–3.53 (m, 1H), 3.69 (dd, J = 4.4, 8.8 Hz,
3
1
H), 3.77–3.83 (m, 2H), 4.21–4.27 (m, 1H), 4.45 (s, 2H), 7.02–7.08 (m, 2H), 7.37–7.41 (m, 4H),
.77–7.81 (m, 3H), 8.10 (s, 1H).
7
2
RS,4RS-Toluene-4-sulfonic
acid
2-(4-trifluoromethylphenyl)-2-1,2,4-triazol-1-yl-methyl-1,3-di-
1
oxolan-4-yl-methyl ester (6d). (36.1%). H-NMR (CDCl ), δ: 2.48 (s, 3H), 3.55 (dd, J = 5.6, 10.6 Hz,
3
1
7
H), 3.78–3.85 (m, 3H), 4.22–4.28 (m, 1H), 4.48 (s, 2H), 7.36–7.41 (m, 2H), 7.54–7.69 (m, 4H),
.78–7.82 (m, 3H), 8.11 (s, 1H).
2
RS,4RS-Toluene-4-sulfonic acid 2-(biphenyl-4-yl)-2-1,2,4-triazol-1-yl-methyl-1,3-dioxolan-4-yl-
1
methyl ester (6e). (42.7%). H-NMR (CDCl ), δ: 2.48 (s, 3H), 3.48 (dd, J = 6.2, 10.3 Hz, 1H), 3.69
3
(
(
dd, J = 4.4, 8.8 Hz, 1H), 3.79–3.86 (m, 2H), 4.27–4.30 (m, 1H), 4.50 (d, J = 1.5 Hz, 2H), 7.37–7.41
m, 3H), 7.43–7.50 (m, 4H), 7.57–7.60 (m, 4H), 7.79 (d, J = 8.4 Hz, 2H), 7.83 (s, 1H), 8.10 (s, 1H).
2
RS,4RS-Toluene-4-sulfonic acid 2-(naphthalen-2-yl)-2-1,2,4-triazol-1-yl-methyl-1,3-dioxolan-4-yl-
1
methyl ester (6f). (26.3%). H-NMR (CDCl
3
), δ: 2.48 (s, 3H), 3.53 (dd, J = 6.2, 10.6 Hz, 1H),
3
.61–3.65 (m, 1H), 3.81–3.86 (m, 2H), 4.28–4.30 (m, 1H), 4.56 (d, J = 2.2 Hz, 2H), 7.39 (dd,
J = 8.1, 11.7 Hz, 3H), 7.49–7.56 (m, 2H), 7.79–7.95 (m, 7H), 8.13 (s, 1H).
2
RS,4RS-Toluene-4-sulfonic acid 2-(2,4-dichlorophyenyl)-2-1,2,4-triazol-1-yl-methyl-1,3-dioxolan-4-
1
yl-methyl ester (6g) (14.0%). H-NMR (CDCl
3
), δ: 2.47 (s, 3H), 3.51 (dd, J = 6.4, 10.4 Hz, 1H), 3.71
(
(
dd, J = 4.3, 9.3 Hz, 1H), 3.80–3.85 (m, 2H), 4.25–4.28 (m, 1H), 4.67–4.79 (m, 2H), 7.38–7.47
m, 4H), 7.77–7.81 (m, 4H), 8.11 (s, 1H).
2
RS,4RS-Toluene-4-sulfonic acid 2-(3,4-dichlorophyenyl)-2-1,2,4-triazol-1-yl-methyl-1,3-dioxolan-4-
1
yl-methyl ester (6h). (45.8%). H-NMR (CD
3
OD), δ: 2.46 (s, 3H), 3.64 (dd, J = 5.1, 8.8 Hz, 1H),
3
7
.76–3.81 (m, 2H), 3.95–3.98 (m, 1H), 4.22–4.24 (m, 1H), 4.79 (s, 2H), 7.23 (d, J = 8.1 Hz, 2H),
.44–7.48 (m, 3H), 7.77 (d, J = 8.4 Hz, 2H), 8.62 (s, 1H), 9.48 (s, 1H).
Preparation of 1-[2-Phenyl-4-(2-trifluoromethoxyphenoxymethyl)-1,3-dioxolan-2-yl-methyl]-1H-1,2,4-
triazole (7a). Potassium hydroxide (160 mg, 2.8 mmol) was added to a solution of tosylate 6 (485 mg,
0
.78 mmol) and 2-trifluoromethoxyphenol (133 mg, 0.72 mmol) in dry DMF (5 mL), and the reaction
mixture was heated at 50 °C overnight. After cooling to room temperature, the reaction mixture was
diluted with water (20 mL) and EtOAc (20 mL), and the organic phase was separated. The aqueous
phase was extracted with EtOAc (3 × 20 mL). All of the organic layers were combined, washed with
brine (20 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by flash
chromatography on silica gel (EtOAc/hexanes = 1:1), affording target compound 7a (58.9% yield),
1
mp: 100–103 °C. H-NMR (CD
3
OD), : 3.34–3.38 (m, 1H), 3.86–3.95 (m, 3H), 4.40–4.44 (m, 1H),
4
7
3
.51–4.60 (m, 2H), 6.87–6.89 (m, 1H), 6.95–7.00 (m, 1H), 7.21–7.28 (m, 2H), 7.40–7.44 (m, 3H),
+
.51–7.54 (m, 2H), 7.93 (s, 1H), 8.17 (s, 1H). HRMS-ESI calculated for C H N O Na [M+Na] was
1
9
19
3
3
94.0928, and 394.0891 was the experimental value.