HETEROCYCLES

Paper | Special issue | Vol. 77, No. 1, 2009, pp. 521-532
Received, 23rd July, 2008, Accepted, 27th August, 2008, Published online, 28th August, 2008.
DOI: 10.3987/COM-08-S(F)56

■ Cooper/HP20: Novel and Polymer-Supported Copper Catalyst for Huisgen Cycloaddition

Yoshiaki Kitamura, Kazum taniguchi, Tomohiro Maegawa, Yasunari Monguchi, Yukio Kitade, and Hironao Sajiki*

Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan

Abstract

A polymer-supported copper catalyst (Cu/HP20) is easily prepared in water and effectively catalyzed the Huisgen cycloaddition between azides and terminal alkynes.

introduction
Recently, heterogeneous catalysts have attracted much attention due to the increasing global momentum for the development of environmentally-friendly reactions in terms of green chemistry. Activated carbon, polymers, alumina, silica-gel, zeolites and clay are usually used as the support of a heterogeneous catalyst. Activated carbon is a useful and versatile support, although the catalyst activity of activated carbon-supported catalysts is often and subtly different depending on the production lot because it is a natural material. Therefore, various catalysts supported by synthetic polymers have been investigated.1 Copper plays a remarkable role as a catalyst in various reactions, and many homogeneous copper catalysts are well known,2 while quite a few heterogeneous catalysts are reported in the literature.3,4 For example, Girard et al. recently developed a heterogeneous catalyst that relies on chelation to potentially labile copper using a polystyryl-based benzylic amine polymer,3 and Lipshutz et al. reported an activated carbon-supported copper catalyst (Cu/C).4 In this article, we report the preparation of a polystyrene polymer supported novel copper catalyst (Diaion HP20: commercially available from Mitsubishi Chemical Corporation), Cu/HP20, and its evaluation as a catalyst for the Huisgen cycloaddition reaction between azides and terminal alkynes.

RESULTS AND DISCUSSION
Preparation of 1% Cu/HP20: We followed the preparation method of Cu/C developed by Lipshutz et al.4 A suspension of Diaion HP20 in a Cu(NO3)2 aqueous solution was sonicated for 2 h and then filtered. Subsequently, the resulting Cu/HP20 was washed with toluene and dried under vacuum to produce approximately 1% Cu/HP20 (See Experimental for the determination of the Cu content in the Cu/HP20).
To investigate the catalyst activity of the 1% Cu/HP20, the Huisgen cycloaddition reaction was carried out. It is well known that the reaction rate of the Huisgen cycloaddition was dramatically accelerated in the presence of a copper catalyst and stoichiometric amount of Et3N.4 Thus we examined the cycloaddition of benzylazide (1a) and 1.1 equiv. of 3-methyl-1-butyn-3-ol (2a) in the presence of 1.0 mol% Cu/HP20 and 1.1 equiv. of Et3N at room temperature. The cycloaddition was completed in toluene within 6 h and provided [2-(1-benzyl-1H-1,2,3-triazol-4-yl)propane-2-ol] (3a) in 98% yield as the sole product (Scheme 1).

To optimize the reaction conditions, several reaction parameters were surveyed (Table 1). The reduction of the Cu/HP20 dose caused an extended reaction time (Entry 2), and no product was obtained in the absence of Cu/HP20 (Entry 1). Among the tested solvents (Entries 4-7), hexane and H2O appeared to be of equal potential to toluene (Entries 4 and 5), while EtOAc and MeOH were found to be less efficient (Entries 6 and 7). In the absence of Et3N, the Huigen cycloaddition reaction never proceeded (Entry 8).

We explored the scope and limitations of substrates for the Huisgen cycloaddition reaction under the optimal conditions (1.0 mol% Cu/HP20 and 1.1 equiv. of Et3N in toluene at room temperature, Tables 2 and 3). As shown in Table 2, a wide range of azide derivatives smoothly reacted with 2a within 24 h except for Entry 2. In the case of 3,5-dinitrobenzylazide (1b), the reaction could be successfully achieved by applying heat (60 ˚C) (Entry 2), since the low solubility of 1b in toluene might be the cause of the difficult cycloaddition reaction at room temperature in this unusual case.

We next attempted to apply the coupling of 4-fluorobenzylazide (1c) with various terminal alkynes (Table 3). A wide range of terminal alkynes smoothly reacted with 1c within 24 h. Remarkably, the coupling with 3-methyl-1-butyn-3-ol (2a) and 2-ethynylpyridine (2e) were completed within 5 h and 3 h, respectively (Entries 1 and 5). In the case of 2a or 2-ethynylpyridine (2e), the coordination of the oxygen or nitrogen atom of the alkyne to the Cu metal facilitated the approach of Cu species to the adjacent C-C triple bond. In addition, the cycloaddition of 2a was completed within 0.5 h by applying heat (60 ˚C), while the same reaction could be completed within 5 h at room temperature (Entry 1).

The reusability of the heterogeneous catalyst could offer significant advantages by association with the cost reduction and the concept of green chemistry. Cu/HP20 could be recovered by only simple filtration and reused at least two additional reaction cycles without any loss of activity in the present Huisgen cycloaddition reaction between 4-fluorobenzylazide (1c) and 3-methyl-1-butyn-3-ol (2a) (Table 4).

CONCLUSION
In conclusion, we have developed a novel polystyrene polymer-supported catalyst (Cu/HP20) for the Huisgen cycloaddition. Aliphatic and aromatic azides underwent the Huisgen cycloaddition reaction with various terminal alkynes in good-to-excellent yields under mild reaction conditions.

EXPERIMENTAL
General Methods. All reactions were carried out under argon unless otherwise noted. Unless otherwise stated, the commercially obtained materials were used without further purification. Deionized water was purchased from Wako Pure Chemical Industries, Ltd. HP20 was gifted from the Mitsubishi Chemical Co. The azides were prepared according to the known procedure. The terminal alkynes were purchased from Tokyo Chemical Industry Co., Ltd. Et3N and the solvents were purchased from Nacalai Tasque, Inc. or Wako Pure Chemical Industries, Ltd. The 1H and 13C NMR spectra were recorded by a JEOL JNM EX-400 or JEOL JNM AL-400 spectrometer (400 MHz for 1H NMR and 100 MHz for 13C NMR). Chemical shifts (δ) are expressed in ppm and internally referenced (0.00 ppm for tetramethylsilane (TMS)-CDCl3 and 2.49 ppm for DMSO-d6 for 1H NMR and 77.0 ppm for CDCl3, 39.5 ppm for DMSO-d6 for 13C NMR). The EI mass spectra were obtained using a JEOL JMS-SX102A instrument. The elemental analyses were performed by a YANACO MT-5 instrument. The flash column chromatography was
performed using Kanto Chemical Co., Inc. silica gel 60N, spherical neutral (63-210 µm).

Preparation of 1% Cu/HP20: Diaion HP20 (10.0 g) was suspended in an aqueous solution of Cu(NO3)2·3H2O (Wako Pure Chemical Industries, Ltd., 1.91 g, 7.9 mmol) in deionized water (40 mL) at rt. The mixture was sonicated [Honda Electronics W-240R (Honda Electronics Co., Ltd., Aichi, Japan)] for 2 h and the resulting Cu/HP20 was filtered, washed with toluene (20 mL) and dried under vacuum at rt for 12 h to give approximately 1% Cu/HP20 (4.47 g). Commercially available Diaion HP20 contains around 50% water and the resulting Cu/HP20 is nearly anhydrous. Therefore, the copper contents of HP20 was calculated on the basis of the measurement of the copper absorbance of the aqueous filtrate using an atomic absorption photometer [Shimadzu AA-6500 (Shimadzu, Kyoto, Japan)].

Synthesis of substrate:
Preparation of aliphatic azides. Under an argon atmosphere, a mixture of an alkylchloride or alkylbromide (10.0 mmol), sodium azide (30.0 mmol), and DMF (10 mL) was stirred overnight at rt. The mixture was extracted with AcOEt (50 mL) and H2O (50 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel to give the corresponding azide.
Benzylazide (1a)5: Colorless oil; 1H NMR (CDCl3) δ 7.41–7.31 (m, 5H), 4.34 (s, 2H); 13C NMR (CDCl3) δ 135.3, 128.8, 128.3, 128.2, 54.8; HRMS (EI) Calcd for C7H7N3 (M+) 133.0640. Found 133.0649.
3,5-Dinitrobenzylazide (1b): Pale yellow solid; mp 50–52 °C. 1H NMR (DMSO-d6) δ 8.76 (s, 1H), 8.65 (s, 2H), 4.82 (s, 2H); 13C NMR (DMSO-d6) δ 148.1, 140.6, 128.5, 117.9, 51.6; HRMS (EI) Calcd for C7H5N5O4 (M+) 223.0342. Found 223.0348. Anal. Calcd for C7H5N5O4: C, 37.68; H, 2.26; N, 31.38. Found: C, 37.65; H, 2.41; N, 31.40.
4-Fluorobenzylazide (1c)6: Colorless oil; 1H NMR (CDCl3) δ 7.31–7.27 (m, 2H), 7.09–7.04 (m, 2H), 4.31 (s, 2H); 13C NMR (CDCl3) δ 162.6 (d, J = 247.7 Hz), 131.2 (d, J = 3.3 Hz), 130.0 (d, J = 8.2 Hz), 115.7 (d, J = 21.4 Hz), 54.0; HRMS (EI) Calcd for C7H6N3F (M+) 151.0546. Found 151.0540.
4-Methoxybenzylazide (1d)7: Colorless oil; 1H NMR (CDCl3) δ 7.25 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 4.27 (s, 2H), 3.82 (s, 3H); 13C NMR (CDCl3) δ 159.6, 129.7, 127.4, 114.2, 55.2, 54.3; HRMS (EI) Calcd for C8H9N3O (M+) 163.0746. Found 163.0750.
Phenylpropylazide (1g)8: Colorless oil; 1H NMR (CDCl3) δ 7.32–7.28 (m, 2H), 7.22–7.18 (m, 2H), 3.29 (t, J = 6.8 Hz, 2H), 2.71 (t, J = 6.8 Hz, 2H), 1.92 (quint, J = 6.8 Hz, 2H); 13C NMR (CDCl3) δ 140.8, 128.5, 128.4, 126.1, 50.6, 32.7, 30.4
4-Azido-4’-bromobutylphenone (1h)9: Yellow oil; 1H NMR (CDCl3) δ 7.83 (d, J = 7.2 Hz, 2H), 7.62 (d, J = 7.2 Hz, 2H), 3.42 (t, J = 6.4 Hz, 2H), 3.05 (t, J = 7.0 Hz, 2H), 2.07-2.00 (m, 2H); 13C NMR (CDCl3) δ 197.8, 135.4, 131.9, 129.5, 128.3, 50.7, 35.1, 25.3; HRMS (EI) Calcd for C10H10BrN3O (M+) 267.0007. Found 267.0019

Preparation of aromatic azides. To a solution of an arylamine (10.0 mmol) in 10% HCl (15 mL) was added a solution of sodium nitrite (0.690 g, 10.0 mmol) in water (3 mL) at 0–5°C with vigorous stirring. The mixture was kept below 5 °C for 30 min and then a solution of sodium azide (0.72 g, 11.0 mmol) in water (15 mL) was dropwise added while the temperature was kept below 5 °C. After being stirred for 1 h, the mixture was warmed to rt and extracted with AcOEt (50 mL) and H2O (50 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel to give the corresponding azide.
Phenylazide (1e)10: Colorless oil; 1H NMR (CDCl3) δ7.35 (t, J = 7.6 Hz, 2H), 7.14 (t, J = 7.6 Hz, 1H), 7.03 (d, J = 7.6 Hz, 2H); 13C NMR (CDCl3) δ 140.0, 129.7, 124.8, 119.0; HRMS (EI) Calcd for C6H5N3 (M+) 119.0484. Found 119.0487.
4-Benzyoylphenylazide (1f)11: Pale yellow solid; 1H NMR (CDCl3) δ 7.82 (d, J = 7.6 Hz, 2H), 7.75 (d, J = 8.0 Hz, 2H), 7.57 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3) δ 195.0, 144.3, 137.4, 133.9, 132.2, 131.9, 129.7, 128.2, 118.6; HRMS (EI) Calcd for C13H9N3O (M+) 223.0746. Found 223.0751.

Experiment for the determination of the regiochemistry. Under an argon atmosphere, a mixture of a benzylazide (650 mg, 5 mmol) and 3-methyl-1-butyn-3-ol (2a, 540 μL, 5.5 mmol) in DMF (5 mL) was stirred at 80 °C. After being stirred for 72 h, the mixture was extracted with AcOEt (50 mL) and H2O (50 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (CHCl3/MeOH, 20:1) to give 2-(1-benzyl-1H-1,2,3-triazol-4-yl)propan-2-ol (467 mg, 43%) and 2-(1-benzyl-1H-1,2,3-triazol-5-yl)- propan-2-ol (445 mg, 41%).
2-(1-benzyl-1H-1,2,3-triazol-4-yl)propan-2-ol (3a)12: Colorless solid; 1H NMR (CDCl3) δ 7.36 (s, 1H), 7.35-7.33 (m, 3H), 7.29-7.27 (m, 2H), 5.46 (s, 2H), 1.61 (s, 6H); 13C NMR (CDCl3) δ 156.0, 134.6, 129.0, 128.6, 128.0, 119.1, 68.4, 54.0, 30.3; HRMS (EI) Calcd for C12H15N3O (M+) 217.1215. Found 217.1221. 2-(1-benzyl-1H-1,2,3-triazol-5-yl)propan-2-ol13: Colorless solid; 1H NMR (CDCl3) δ 7.27-7.21 (m, 3H), 7.20-7.17 (m, 3H), 5.88 (s, 2H), 1.58 (s, 6H); 13C NMR (CDCl3) δ 143.6, 136.4,130.6, 128.7, 128.2, 128.0, 127.6, 67.6, 52.8, 30.7; HRMS (EI) Calcd for C12H15N3O (M+) 217.1215. Found 217.1221.

General procedure for Huisgen cycloaddition in a solvent system. To a test tube with a stir bar were added the azide (1.0 mmol), terminal alkyne (1.1 mmol), Et3N (152 μL, 1.1 mmol), 1% Cu/HP20 (63.5 mg, 10 μmol), and toluene (1 mL), and then the system was sealed with a septum. The air inside was replaced with argon (balloon) by three vacuum/argon cycles and the mixture was stirred at rt. After a certain period, the mixture was diluted with H2O (10 mL) and EtOAc (10 mL), and passed through a filter paper. The filtrate was separated into two layers and the aqueous layer was extracted with EtOAc (2 × 10 mL). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel to give the corresponding 1,4-triazole.
2-[1-(3,5-Dinitrobenzyl)-1H-1,2,3-triazol-4-yl]propan-2-ol (3b): Pale yellow solid; mp 117–119 °C. 1H NMR (DMSO-d6) δ 8.79 (s, 1H), 8.65 (s, 2H), 8.09 (s, 1H), 5.86 (s, 2H), 5.16 (s, 1H), 1.44 (s, 6H); 13C NMR (DMSO-d6) δ 156.4, 148.2, 140.1, 128.9, 121.2, 118.4, 67.1, 50.9, 30.7; HRMS (EI) Calcd for C12H13N5O5 (M+) 307.0917. Found 307.0910. Anal. Calcd for C12H13N5O5: C, 46.91; H, 4.26; N, 22.79. Found: C, 46.33; H, 4.04; N, 22.20.
2-[1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl]propan-2-ol (3c): Pale brown solid; mp 74–76 °C. 1H NMR (CDCl3) δ 7.36 (s, 1H), 7.27 (dd, J = 8.6 Hz, 5.4 Hz, 2H), 7.06 (t, J = 8.6 Hz, 2H), 5.46 (s, 2H), 1.61 (s, 6H); 13C NMR (CDCl3) δ 162.8 (d, J = 247.0 Hz), 156.1, 130.5, 130.0 (d, J = 8.2 Hz), 118.9, 116.0 (d, J = 21.4 Hz), 68.5, 53.3, 30.4; HRMS (EI) Calcd for C12H15N3OF (M+) 236.1199. Found 236.1205. Anal. Calcd for C12H15N3OF: C, 61.26; H, 6.00; N, 17.86. Found: C, 61.11; H, 5.90; N, 17.63.
2-[1-(4-Methoxybenzyl)-1H-1,2,3-triazol-4-yl]propan-2-ol (3d): Yellow solid; mp 86–88 °C. 1H NMR (CDCl3) δ 7.30 (s, 1H), 7.23 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 5.43 (s, 2H), 3.81 (s, 3H), 1.60 (s, 6H); 13C NMR (CDCl3) δ 159.9, 155.9, 129.7, 126.5, 118.7, 114.4, 68.4, 55.3, 53.6, 30.4; HRMS (EI) Calcd for C13H17N3O2 (M+) 247.1321. Found 247.1313. Anal. Calcd for C13H17N3O2: C, 63.14; H, 6.93; N, 16.99. Found: C, 62.81; H, 7.00; N, 16.83.
2-(1-Phenyl-1H-1,2,3-triazol-4-yl)propan-2-ol (3e): Yellow solid; mp 69–71 °C. 1H NMR (CDCl3) δ 7.95 (s, 1H), 7.72 (d, J = 7.8 Hz, 2H), 7.50 (t, J = 7.8 Hz, 2H), 7.42 (t, J = 7.8 Hz, 1H), 1.72 (s, 6H); 13C NMR (CDCl3) δ 156.5, 136.8, 129.4, 128.4, 120.2, 117.8, 68.3, 30.3; HRMS (EI) Calcd for C11H13N3O (M+) 203.1059. Found 203.1063. Anal. Calcd for C11H13N3O: C, 65.01; H, 6.45; N, 20.68. Found: C, 65.03; H, 6.47; N, 20.30.
{4-[4-(2-Hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl]phenyl}phenylmethanone (3f): Pale brown solid; mp 142–144 °C. 1H NMR (CDCl3) δ 8.03 (s, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.88 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 7.8 Hz, 2H), 7.63 (t, J = 7.8 Hz, 1H), 7.52 (t, J = 7.8 Hz, 2H), 1.73 (s, 6H); 13C NMR (CDCl3) δ 195.2, 139.7, 137.3, 137.0, 132.8, 131.7, 129.9, 128.5, 119.8, 117.4, 68.7, 30.4; HRMS (EI) Calcd for C18H17N3O2 (M+) 307.1321. Found 307.1317. Anal. Calcd for C18H17N3O2: C, 70.34; H, 5.58; N, 13.67. Found: C, 69.27; H, 5.42; N, 13.30.
2-[1-(3-Phenylpropyl)-1H-1,2,3-triazol-4-yl]propan-2-ol (3g): Yellow oil; 1H NMR (CDCl3) δ 7.45 (s, 1H), 7.28 (t, J = 8.2 Hz, 2H), 7.19 (t, J = 8.2 Hz, 1H), 7.15 (d, J = 8.2 Hz, 2H), 4.29 (t, J = 8.2 Hz, 2H), 2.64 (t, J = 8.2 Hz, 2H), 2.21 (quint, J = 8.2 Hz, 2H), 1.63 (s, 6H); 13C NMR (CDCl3) δ 155.8, 140.1, 128.5, 128.3, 126.2, 119.1, 68.3, 49.4, 32.4, 31.5, 30.4; HRMS (EI) Calcd for C14H19N3O (M+) 245.1528. Found 245.1524. Anal. Calcd for C14H19N3O: C, 68.54; H, 7.81; N, 17.13. Found: C, 68.01; H, 8.03; N, 16.91.
1-(4-Bromophenyl)-4-[4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl]butan-1-one (3h): Colorless solid; mp 126–128 °C. 1H NMR (CDCl3) δ 7.78 (d, J = 8.8 Hz, 2H), 7.60 (d, J = 8.8 Hz, 2H), 7.49 (s, 1H), 4.46 (t, J = 6.8 Hz, 2H), 3.01 (t, J = 6.8 Hz, 2H), 2.34 (t, J = 6.8 Hz, 2H), 1.63 (s, 6H); 13C NMR (CDCl3) δ 197.5, 155.8, 135.1, 132.0, 129.5, 128.6, 119.2, 100.5, 68.4, 49.2, 34.7, 30.4, 24.4; HRMS (EI) Calcd for C15H18N3O2Br (M+) 351.0582. Found 351.0575. Anal. Calcd for C15H18N3O2Br: C, 51.15; H, 5.15; N, 11.93. Found: C, 51.27; H, 5.11; N, 11.77.
3-[1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl]propan-1-ol (3i): Pale yellow solid; mp 45–47 °C. 1H NMR (CDCl3) δ 7.41 (s, 1H), 7.25 (dd, J = 8.7 Hz, 5.2 Hz, 2H), 7.02 (t, J = 8.7 Hz, 2H), 5.43 (s, 2H), 3.97 (s, 1H), 3.85 (t, J = 6.0 Hz, 1H), 2.89 (t, J = 6.0 Hz, 1H); 13C NMR (CDCl3) δ 163.2 (d, J = 248.6 Hz), 146.4, 131.1 (d, J = 3.3 Hz), 130.4 (d, J = 8.2 Hz), 122.2, 116.4 (d, J = 22.2 Hz), 61.6, 53.7, 29.3; HRMS (EI) Calcd for C11H12N3OF (M+) 221.0964. Found 221.0973. Anal. Calcd for C11H12N3OF: C, 59.72; H, 5.47; N, 18.99. Found: C, 59.13; H, 5.49; N, 18.63.
1-(4-Fluorobenzyl)-4-phenyl-1H-1,2,3-triazole (3j): Colorless solid; mp 125–127 °C. 1H NMR (CDCl3) δ 7.79 (d, J = 7.4 Hz, 2H), 7.67, 7.40 (t, J = 7.4 Hz, 2H), 7.33-7.26 (m, 3H), 7.07 (t, J = 8.4 Hz, 2H), 5.54 (s, 2H); 13C NMR (CDCl3) δ 162.6 (d, J = 246.2 Hz), 148.1, 130.5 (d, J = 3.3 Hz), 130.3, 129.8 (d, J = 8.2 Hz), 128.7, 128.1, 125.5, 119.4, 115.9 (d, J = 21.2 Hz), 53.2; HRMS (EI) Calcd for C15H12N3F (M+) 253.1015. Found 253.1009. Anal. Calcd for C15H12N3F: C, 71.13; H, 4.78; N, 16.59. Found: C, 71.15; H, 4.82; N, 16.46.
4-Cyclohexenyl-1-(4-fluorobenzyl)-1H-1,2,3-triazole (3k): Colorless solid; mp 97–99 °C. 1H NMR (CDCl3) δ 7.30 (s, 1H), 7.25 (dd, J = 8.5 Hz, 5.2 Hz, 2H), 7.05 (t, J = 8.5 Hz, 2H), 6.50 (t, J = 1.9 Hz, 1H), 5.47 (s, 2H), 2.35–2.33 (m, 2H), 2.19–2.17 (m, 2H), 1.75–1.71 (m, 2H), 1.68–1.63 (m, 2H); 13C NMR (CDCl3) δ 162.7 (d, J = 247.0 Hz), 150.0, 130.8 (d, J = 3.3 Hz), 129.7 (d, J = 8.2 Hz), 127.1, 125.2, 118.0, 116.0 (d, J = 22.2 Hz), 53.2, 26.3, 25.2, 22.4, 22.1; HRMS (EI) Calcd for C15H16N3F (M+) 257.1328. Found 257.1321. Anal. Calcd for C15H16N3F: C, 70.02; H, 6.27; N, 16.33. Found: C, 70.01; H, 6.23; N, 16.17.
2-[1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl]pyridine (3l): Pale brown solid; mp 104–106 °C. 1H NMR (CDCl3) δ 8.53 (d, J = 5.0 Hz, 1H), 8.16 (d, J = 7.8 Hz, 1H), 8.08 (s, 1H), 7.74 (dd, J = 7.8 Hz, 6.3 Hz, 1H), 7.31 (dd, J = 8.7 Hz, 5.2 Hz, 2H), 7.19 (dd, J = 6.3 Hz, 5.0 Hz, 1H), 7.04 (t, J = 8.7 Hz, 2H), 5.54 (s, 2H); 13C NMR (CDCl3) δ 162.7 (d, J = 247.0 Hz), 149.9, 149.2, 148.6, 136.7, 130.2 (d, J = 3.3 Hz), 130.0 (d, J = 8.2 Hz), 122.7, 121.7, 120.0, 115.9 (d, J = 21.4 Hz), 53.3; HRMS (EI) Calcd for C14H11N4F (M+) 254.0968. Found 254.0962. Anal. Calcd for C14H11N4F: C, 66.13; H, 4.36; N, 22.04. Found: C, 65.96; H, 4.46; N, 21.80.
1-(4-Fluorobenzyl)-4-trimethylsilyl-1H-1,2,3-triazole (3m): Pale yellow solid; mp 59–61 °C. 1H NMR (CDCl3) δ 7.18 (s, 1H), 6.98 (dd, J = 8.6 Hz, 4.8 Hz, 2H), 6.75 (t, J = 8.8 Hz, 2H), 5.24 (s, 2H), 0.01 (s, 9H); 13C NMR (CDCl3) δ 162.6 (d, J = 248.6 Hz), 147.1, 130.8 (d, J = 3.3 Hz), 129.8 (d, J = 8.1 Hz), 128.6, 115.8 (d, J = 22.2 Hz), 60.2, 52.5; HRMS (EI) Calcd for C12H16N3FSi (M+) 249.1098. Found 249.1093. Anal. Calcd for C12H16N3FSi: C, 57.80; H, 6.47; N, 16.85. Found: C, 57.75; H, 6.32; N, 16.90.

ACKNOWLEDGEMENTS
We thank Mitsubishi Chemical Corporation for a gift of Diaion HP20.

This paper is dedicated to Dr. Keiichiro Fukumoto, Professor Emeritus at Tohoku University and editor of Heterocycles for the occasion of his 75th birthday.

References

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