Dace Rasina,a Aurora Lombi,a Stefano Santoro,a Francesco Ferlin,a and Luigi Vaccaro*a

a Laboratory of Green Synthetic Organic Chemistry, CEMIN – Dipartimento di Chimica, Biologia e Biotecnologie, Università di Perugia Via Elce di Sotto, 8, 06123 Perugia, Italy E-mail: luigi.vaccaro @unipg.it; Web: www.dcbb.unipg.it/greensoc

SUPPORTING INFORMATION

Table of Contents General Information ESI 2 General procedure for the synthesis of 1,5-disubstituted 1,2,3-triazoles and E-Factors calculations ESI 2 - ESI 3 Spectral Data ESI 4 - ESI 7 Copies of NMR Spectra ESI 8 - ESI 43

ESI - 1

Electronic Supplementary Material (ESI) for Green Chemistry.This journal is © The Royal Society of Chemistry 2016

General Information Unless otherwise stated, all solvents and reagents were used as obtained from commercial sources without further purification. GC analyses were performed by using a Hewlett-Packard HP 5890A equipped with a capillary column DB-35MS (30 m, 0.53 mm), a FID detector and hydrogen as gas carrier. GC-EIMS analyses were carried out by using a Hewlett-Packard HP 6890N Network GC system/5975 Mass Selective Detector equipped with an electron impact ionizer at 70 eV. NMR spectra were recorded on a Bruker DRX-ADVANCE 400 MHz (1H at 400 MHz and 13C at 100.6 MHz) in CDCl3 or DMSO-D6 using TMS as the internal standard. All azides and non-commercially available alkynes were prepared according to methods reported in the General procedure for the synthesis of 1,5-disubstituted 1,2,3-triazoles Imidazole (14 mg, 20 mol%), sodium ascorbate (20 mg, 10 mol%) and copper(II) sulfate pentahydrate (5 mg, 2 mol%) were dissolved in 5 mL of furfuryl alcohol (20 wt%) water mixture, in a screw-capped vial equipped with a magnetic stirrer. Alkyne (1 mmol) and azide (1 mmol) were added and the resulting heterogeneous mixture was stirred vigorously at 30 ºC, until GC analysis indicated complete consumption of the reactants. Isolation procedure A: Product was collected by filtration, washed with 10 mL of distilled water and dried in vacuum to afford of pure product. Isolation procedure B: Solvent was decanted and 5 mL of ice-cold water was added to oily residue to precipitate the product that was collected by filtration, washed with 10 mL of distilled water and dried in vacuum to afford pure product. Isolation procedure C: Solvent was decanted and 10 mL of water and 10 mL of EtOAc was added. Organic phase was separated, washed with brine, dried over Na2SO4 and evaporated. The crude mixture was purified by column chromatography to afford pure product.

Calculation of E-factor

Our protocol for the preparation of 3c (Scheme 2): (0.027 mol, yield 91%)= [(4.06(azide 1a) + 2.79(alkyne 2a) + 0.367(imidazole) + 0.535(Na-asc) + 0.135(CuSO4) + 27(FA/H2O) + 20(H2O for washing)) – (6.20(isolated product 3c) + 21.87(recovered solvent)]/ 6.20(isolated product 3c) = 4.3.

Typically CuAAC reactions are performed in water and some organic co-solvent. We calculated E-factor for three representative orotocols using classical reaction conditions and work-up procedures using tBuOH/H2O solvent system done by Sharpless and Fokin, for DCM/H2O solvent system and solvent free conditions.

Reference Procedure E-factor

Vsevolod V. Rostovtsev, Luke G. Green, Valery V. Fokin K. Barry Sharpless ACIE 2002, 41, No. 14, 2596

General procedure (entry 11, Table 1): 17-ethynylestradiol (888 mg, 3 mmol) and (S)-3-azidopropane-1,2-diol (352 mg, 3 mmol) were suspended in a 1:1 mixture of water and tert-butyl alcohol (12 mL). Sodium ascorbate (0.3 mmol, 300 _L of freshly prepared 1_ solution in water) was added, followed by copper(II) sulfate pentahydrate (7.5 mg, 0.03 mmol, in 100 _L of water). The heterogeneous mixture was stirred vigorously overnight, at which point it cleared and TLC analysis indicated complete consumption of the reactants. The reaction mixture was diluted with water (50 mL), cooled in ice, and the white precipitate was collected by filtration. After washing the precipitate with cold water (2x25 mL), it was dried under

96-195 (avg 150)

(11 substrates)

ESI - 2

vacuum to afford 1.17g (94%) of pure product as an off-white powder.

Bo-Young Lee, So Ra Park, Heung Bae Jeon* and Kwan Soo Kim, Tetrahedron Letters 47 (2006) 5105

Typical procedure reported: To a solution of phenylacetylene (100 mg, 0.75 mmol) and benzyl azide (9, 80 mg, 0.83 mmol) in CH2Cl2 (0.7 mL) and H2O (0.7 mL) were added CuSO4*5H2O (9.3 mg, 0.04 mmol) and sodium ascorbate (22 mg, 0.11 mmol). The resulting solution was stirred for 7 h at room temperature. The reaction mixture was diluted with CH2Cl2 (5 mL) and H2O (5 mL). The organic layer was separated, dried over MgSO4, and concentrated. The residue was purified by flash column chromatography (hexane/EtOAc, 2:1) to give the corresponding 1,2,3-triazole (170 mg, 97%) as a white solid.

20-67 (avg 53)

(12 substrates)

solvents used in column

chromatography have not been

included because sufficient details

were not reported

Laura Rinaldi, Katia Martina, Francesca Baricco, Laura Rotolo and Giancarlo Cravotto Molecules 2015, 20, 2837

The milling jar (50 mL; stainless steel) were equipped with 1500 milling balls (d = 2 mm, stainless steel) and 48 medium balls (d = 5 mm, stainless steel). Afterwards the alkyne (1 mmol), the azide (1 mmol) and Cu powder (1 mmol, 63 mg) were added in the given order. Milling was accomplished at 650 rpm for 5 min. After cooling of the milling jar to room temperature, the crude products were filtered on Büchner funnel with a sintered glass disc using diethyl acetate (3 × 10 mL). The solvent was evaporated in vacuum, the crude products were dried and analyzed by GC-MS, 1H-, 13C-NMR spectroscopy and MALDI-TOF mass spectrometry after dissolution in an appropriate solvent.

71-155 (avg 115)

(12 substrates)

ESI - 3

Spectral Data 1-Benzyl-4-phenyl-1H-1,2,3-triazole 3a. Isolated by procedure A, yield 159 mg

(68 %), white powder with m. p.: 126-127 °C. 1H NMR (400 MHz, DMSO-D6) δ: 5.64 (s, 2H). 7.27-7.45 (m, 8H), 7.85 (d, J = 7.5 Hz, 2H), 8.62 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 53.5, 122.0, 125.6, 128.3 (2 overlapping signals), 128.6, 129.2, 129.3, 131.1, 136.5, 147.2. IR (CHCl3, cm-1): 3013, 1467, 1356, 1226, 1209, 1074, 1048, 755, 695. GC-

EIMS (m/z, %): 89 (35), 91 (63), 116 (89), 180 (21), 206 (100), 207 (20), 235 (26).

1-Benzyl-4-butyl-1H-1,2,3-triazole 3b. Isolated by procedure B, yield 171 mg (79 %), white powder with m. p.: 62-63 °C. 1H NMR (400 MHz, DMSO-D6) δ: 0.86 (t, J = 7.3 Hz, 3H), 1.19-1.38 (m, 2H), 1.45-1.62 (m, 2H), 2.58 (t, J = 7.5 Hz, 2H), 5.51 (s, 2H), 7.20-7.42 (m, 5H), 7.86 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 14.1, 22.1, 25.1, 31.5, 53.1, 122.4, 128.2, 128.4, 129.2, 136.8, 147.7. IR (CHCl3, cm-1): 3011, 2961, 2874, 1551,

1497, 1353, 1124, 1047, 798, 697. GC-EIMS (m/z, %): 65 (11), 91 (100), 92 (10), 173 (15), 215 (1). 1-(4-Methoxyphenyl)-4-phenyl-1H-1,2,3-triazole 3c. Isolated by procedure A, yield

6.02 g (91 %), light yellow powder with m.p. 160-161 °C. 1H NMR (400 MHz, DMSO-D6) δ: 3.81 (s, 3H), 7.14 (d, J = 8.7 Hz, 2H), 7.35 (t, J = 7.2 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 7.84 (d, J = 8.7 Hz, 2H), 7.93 (d, J = 7.5 Hz, 2H), 9.15 (s, 1H). 13C NMR (100 MHz, DMSO-D6) δ: 56.0, 115.3, 120.0, 122.1,

125.8, 128.6, 129.4, 130.5, 130.9, 147.6, 159.8. IR (CHCl3, cm-1): 3017, 2848, 1613, 1519, 1257, 1042, 834. GC-EIMS (m/z, %): 116 (17), 152 (23), 180 (60), 181 (27), 208 (93), 223 (100), 251 (2). 4-Phenyl-1-p-tolyl-1H-1,2,3-triazole 3d. Prepared by procedure A, yield 205 mg

(87 %), light yellow powder with m.p. 166-168 °C. 1H NMR (400 MHz, DMSO-D6) δ: 2.38 (s, 3H), 7.30-7.56 (m, 5H), 7.81 (d, J = 7.8 Hz, 2H), 7.93 (d, J = 7.3 Hz, 2H), 9.22 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 21.0, 119.9, 120.3, 125.8, 128.6, 129.4, 130.7, 130.8, 134.9, 138.8, 147.7. IR (CHCl3, cm-1): 3154,

3013, 1609, 1520, 1227, 1042, 993, 797. GC-EIMS (m/z, %): 89 (16), 116 (14), 165 (23), 206 (65), 207 (100), 235 (2). 4-Butyl-1-p-tolyl-1H-1,2,3-triazole 3e. Isolated by procedure B, yield 739 mg (81 %),

light yellow powder with m.p. 53-55 °C. 1H NMR (400 MHz, DMSO-D6) δ: 0.90 (t, J = 7.3 Hz, 3H), 1.34-1.36 (m, 2H), 1.61-.64 (m, 2H), 2.35 (s, 3H), 2.76-2.67 (m, 2H), 7.35 (d, J = 7.4 Hz, 2H), 7.74 (d, J = 7.4 Hz, 2H), 8.50 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 14.1, 21.0, 22.2, 25.1, 31.4, 120.0,

120.3, 130.6, 135.1, 138.2, 148.5. IR (CHCl3, cm-1): 3013, 2961, 2932, 2862, 1519, 1467, 1224, 1207, 1044, 990, 798. GC-EIMS (m/z, %): 65 (11), 91 (32), 144 (100), 145 (13), 186 (11), 215 (1).

ESI - 4

4-Butyl-1-dodecyl-1H-1,2,3-triazole 3f. Isolated by procedure A, yield 237 mg (81 %), white powder with m.p. 51-52 °C. 1H NMR (400 MHz, DMSO-D6) δ: 0.77-0.92 (m, 6H), 1.11-1.36 (m, 20H), 1.46-1.62 (m, 2H), 1.68-1.81 (m, 2H), 2.57 (t, J = 7.5 Hz, 2H), 4.24 (t, J = 6.9 Hz, 2H), 7.78 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 14.1, 14.4, 22.1, 22.5, 25.1, 26.2, 28.8, 29.1, 29.29, 29.32, 29.4 (2 overlapping signals), 30.1,

31.6, 31.7, 49.5, 122.0, 147.2. IR (CHCl3, cm-1): 2916, 2853, 1550, 1461, 1373, 1228, 1202, 1041, 756, 673. GC-EIMS (m/z, %): 82 (25), 96 (32), 110 (54), 111 (32), 124 (40), 126 (26), 138 (37), 152 (100), 166 (70), 180 (37), 194 (28), 222 (50), 236 (39), 250 (51), 251 (26), 293 (26). 1-(4-Methoxyphenyl)-4-(thiophen-3-yl)-1H-1,2,3-triazole 3g. Isolated by procedure

A, yield 223 mg (87 %), pale yellow powder with m.p. 161-163 °C. 1H NMR (400 MHz, CDCl3) δ: 3.87 (s, 3H), 7.02 (d, J = 8.4 Hz, 2H), 7.41 (s, 1H), 7.52 (d, J = 3.8 Hz, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.76 (s, 1H), 8.02 (s, 1H). 13C NMR (100.6 MHz, CDCl3) δ: 55.6, 114.8, 117.7, 121.4, 122.2, 125.8, 126.5, 130.4, 131.6, 144.4, 159.9. IR (CHCl3, cm-1): 3019,

1520, 1257, 1227, 1206, 1043, 719, 672. GC-EIMS (m/z, %): 96 (16), 122 (18), 186 (47), 187 (33), 214 (85), 229 (100), 257 (3). 1-Phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanone 3h. Isolated by procedure A,

yield 251 mg (95 %), yellow powder with m.p. 172-175 °C. 1H NMR (400 MHz, DMSO-D6) δ: 6.26 (s, 2H), 7.34 (t, J = 7.2 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 7.60 (t, J = 7.5 Hz, 2H), 7.73 (t, J = 7.2 Hz, 1H), 7.89 (d, J = 7.5 Hz, 2H), 8.10 (d, J = 7.5 Hz, 2H), 8.53 (s, 1H). 1H NMR (100.6 MHz, DMSO-D6) δ: 56.5, 123.5, 125.6, 128.3, 128.7,

129.4, 129.5, 131.2, 134.6, 134.7, 146.8, 192.6. IR (CHCl3, cm-1): 3013, 1707, 1598, 1468, 1227, 796, 752, 664. GC-EIMS (m/z, %): 77 (94), 91 (34), 102 (44), 103 (83), 105 (100), 119 (42), 130 (99), 206 (63), 207 (35), 234 (31), 263 (39). Ethyl 2-(4-phenyl-1H-1,2,3-triazol-1-yl)acetate 3i. Isolated by procedure A, yield

185 mg (80 %), white powder with m.p. 99-101 °C. 1H NMR (400 MHz, DMSO-D6) δ: 1.22 (t, J = 7.1 Hz, 3H), 4.19 (q, J = 7.0 Hz, 2H), 5.44 (s, 2H), 7.33 (t, J = 7.3 Hz, 1H), 7.44 (t, J = 7.5 Hz, 2H), 7.85 (d, J = 7.5 Hz, 2H), 8.55 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 14.4. 51.0, 62.0, 123.2, 125.6, 128.4, 129.4, 131.0,

146.9, 167.7. IR (CHCl3, cm-1): 3151, 3027, 3013, 1755, 1467, 1232, 1198, 1022, 777. GC-EIMS (m/z, %): 77 (36), 89 (27), 91 (35), 102 (72), 103 (74), 105 (27), 116 (100), 118 (49), 130 (70), 131 (68), 160 (27), 203 (25), 231 (50). Methyl 1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxylate 3j. Isolated by

procedure A, yield 197 mg (91 %), white powder with m.p. 138-140 °C. 1H NMR (400 MHz, DMSO-D6) δ: 3.80 (s, 3H), 3.86 (s, 3H), 7.10 (d, J = 8.9 Hz, 2H), 7.84 (d, J = 8.8 Hz, 2H), 9.34 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 52.3. 56.0, 115.3, 122.6, 127.4, 129.8, 139.8, 160.13, 161.06. IR (CHCl3, cm-1): 3159, 3022, 2955, 2841, 1724, 1612, 1553,

ESI - 5

1520, 1439, 1351, 1254, 1218, 1149, 1037, 832, 756 GC-EIMS (m/z, %): 76 (15), 131 (18), 132 (19), 134 (15), 146 (100), 147 (20), 158 (17), 162 (21), 173 (36), 174 (90), 176 (16), 190 (67), 233 (40). 1-(4-Methoxyphenyl)-4-(phenoxymethyl)-1H-1,2,3-triazole 3k. Isolated by procedure

A, yield 255 mg (91 %), pale yellow powder with m.p. 117-119 °C. 1H NMR (400 MHz, DMSO-D6) δ: 3.82 (s, 3H), 5.21 (s, 2H), 6.94-6.97 (m, 1H), 7.07 (d, J = 7.7 Hz, 2H), 7.13 (d, J = 8.2 Hz, 2H), 7.29-7.33 (m, 2H), 7.81 (d, J = 8.2 Hz, 2H), 8.85 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 56.0,

61.4, 115.1, 115.3, 121.4, 122.3, 123.3, 130.0, 130.4, 144.1, 158.5, 159.8. IR (CHCl3, cm-1): 3013, 2840, 1599, 1519, 1496, 1265, 1257, 1210, 1040, 834, 672. GC-EIMS (m/z, %): 77 (13), 117 (18), 145 (25), 160 (100), 161 (11), 281 (8). 4-((2-Iodophenoxy)methyl)-1-p-tolyl-1H-1,2,3-triazole 3l. Isolated by procedure A,

yield 365 mg (93 %), light yellow powder with m.p. 97-99 °C. 1H NMR (400 MHz, DMSO-D6) δ: 2.37 (s, 3H), 5.29 (s, 2H), 6.76-6.79 (m, 1H), 7.26-7.28 (m, 1H), 7.38-7.40 (m, 3H), 7.77-7.79 (m, 3H), 8.90 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 21.0, 62.6, 87.2, 113.7, 120.5,

123.3, 123.6, 130.2, 130.7, 134.7, 138.9, 139.6, 143.9, 157.1. IR (CHCl3, cm-1): 3013, 1582, 1520, 1220, 1209, 1046, 797, 755, 671. GC-EIMS (m/z, %): 91 (30), 143 (29), 144 (100), 236 (36), 264 (32). 1-Benzyl-4-((2-bromophenoxy)methyl)-1H-1,2,3-triazole 3m. Isolated by procedure

B, yield 296 mg (86 %), white powder with m.p. 78-80 °C. 1H NMR (400 MHz, DMSO-D6) δ: 5.23 (s, 2H), 5.62 (s, 2H), 6.88-6.92 (m, 1H), 7.30-7.37 (m, 7H), 7.55-7.57 (m, 1H), 8.30 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 53.3, 62.6, 111.6, 114.8, 122.8, 125.3, 128.4, 128.6, 129.2, 129.4, 133.5, 136.5,

143.1, 154.7. IR (CHCl3, cm-1): 3153, 3013, 1586, 1479, 1463, 1247, 1127, 1051, 1009, 795, 671. GC-EIMS (m/z, %): 91 (100), 144 (65), 145 (16), 172 (20), 173 (12), 264 (51), 344 (1), 345 (1). 4-((2-Chlorophenoxy)methyl)-1-(4-methoxyphenyl)-1H-1,2,3-triazole 3n. Isolated by

procedure A, yield 265 mg (84 %), white powder with m.p. 108-110 °C. 1H NMR (400 MHz, DMSO-D6) δ: 3.81 (s, 3H), 5.30 (s, 2H), 6.97 (t, J = 7.5 Hz, 1H), 7.12 (d, J = 8.9 Hz, 2H), 7.31 (t, J = 7.3 Hz, 1H), 7.38-7.42 (m, 2H), 7.80 (d, J = 8.9 Hz, 2H), 8.84 (s, 1H). 13C NMR

(100.6 MHz, DMSO-D6) δ: 56.0, 62.4, 114.9, 115.3, 122.0, 122.3, 122.4, 123.5, 128.7, 130.4, 130.5, 143.6, 153.8, 159.8. IR (CHCl3, cm-1): 3158, 3018, 2840, 1612, 1591, 1519, 1485, 1254, 1220, 1064, 1043, 834, 671. GC-EIMS (m/z, %): 117 (12), 145 (20), 160 (100), 161 (11), 315 (3). 1-(4-Methoxyphenyl)-4-(trimethylsilyl)-1H-1,2,3-triazole 3o. Isolated by procedure

C, yield 169 mg (68 %), white powder with m.p. 67-70 °C. 1H NMR (400 MHz, DMSO-D6) δ: 0.29 (s, 9H), 3.80 (s, 3H), 7.10 (d, J = 8.8 Hz, 2H), 7.78 (d, J = 8.8 Hz, 2H), 8.71 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: -0.6, 56.0, 115.2, 122.3,

ESI - 6

129.1, 130.5, 146.3, 159.5. IR (CHCl3, cm-1): 3013, 2962, 2839, 1613, 1519, 1302, 1252, 1227, 1171, 1109, 1043, 987, 845, 665. GC-EIMS (m/z, %): 176 (12), 204 (100), 205 (18), 219 (13), 247 (1). 1-(4-Methoxyphenyl)-1H-1,2,3-triazole 3p. After full conversion of 1-azido-4-

methoxybenzene to 1-(4-methoxyphenyl)-4-(trimethylsilyl)-1H-1,2,3-triazole 3o, tetrabutylammonium fluoride hydrate (630 mg, 2 mmol) was added and reaction stirred at 30 oC for 21 h. Product isolated by procedure C, yield 118 mg (67 %), bright yellow powder with m.p. 79-81 °C. 1H NMR (400 MHz, DMSO-D6) δ:

3.81 (s, 3H), 7.12 (d, J = 8.5 Hz, 2H), 7.79 (d, J = 8.5 Hz, 2H), 7.91 (s, 1H), 8.69 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 56.0. 115.3, 122.3, 123.6, 130.6, 134.6, 159.7. IR (CHCl3, cm-1): 3165, 3009, 2833, 1607, 1518, 1461, 1249, 1041, 984, 823. GC-EIMS (m/z, %): 77 (22), 92 (11), 104 (23), 132 (100), 133 (10), 147 (36), 175 (29). Bis(1-benzyl-1H-1,2,3-triazol-4-yl)methanol 3q. Isolated by procedure A, yield

282 mg (82 %), white powder with m.p. 180-182 °C. 1H NMR (400 MHz, DMSO-D6) δ: 5.56 (s, 4H), 5.90 (d, J = 3.8 Hz, 1H), 6.01 (d, J = 3.8 Hz, 1H), 7.32-7.36 (m, 10H), 8.04 (s, 2H). 13C NMR (100.6 MHz, DMSO-D6) δ: 53.1, 61.7, 123.2, 128.5, 128.6, 129.2, 136.6, 150.4.

1-Hexyl-4-phenyl-1H-1,2,3-triazole 3r. Imidazole (14 mg, 20 mol%), sodium ascorbate (20 mg, 10 mol%) and copper(II) sulfate pentahydrate (5 mg, 2 mol%) were dissolved in 5 mL of furfuryl alcohol (20 wt%) water mixture. Phenylacetylene (0.110 mL, 1 mmol) and 1-bromohexane (0.140 mL, 1 mmol) were suspended in the catalyst solution. After addition of sodium azide (130 mg, 2 mmol) the heterogeneous mixture

was stirred vigorously at 60 oC for 48 h. After cooling to room temperature solvent was decanted and 10 mL of ice-cold water was added to the oily residue to precipitate product. This was collected by filtration, washed with 10 mL distilled water, 10 mL hexane and dried in vacuum to afford 121 mg (53 %), light brown powder with m.p. 72-76 °C. 1H NMR (400 MHz, DMSO-D6) δ: 0.60-1.01 (m, 3H), 1.07-1.43 (m, 6H), 1.66- 1.96 (m, 2H), 4.36 (t, J = 6.5 Hz, 2H), 7.30 (t, J = 7.1 Hz, 1H), 7.42 (t, J = 7.3 Hz, 2H), 7.83 (d, J = 7.5 Hz, 2H), 8.55 (s, 1H). 13C NMR (100.6 MHz, DMSO-D6) δ: 14.3, 22.3, 26.0, 30.0, 31.0, 50.0, 121.6, 125.5, 128.2, 129.3, 131.4, 146.7. IR (CHCl3, cm-1): 3009, 2926, 2853, 1612, 1467, 1228, 1077, 745, 673. GC-EIMS (m/z, %): 89 (22), 102 (26), 103 (22), 104 (24), 116 (30), 117 (100), 130 (25), 144 (28), 145 (27), 172 (29), 200 (40), 229 (44).

OH

NN

N N

NN

Bn Bn3q

ESI - 7

9 8 7 6 5 4 3 2 1 0 ppm

5.63

9

7.30

47.

323

7.33

57.

353

7.36

97.

398

7.41

77.

436

7.83

97.

858

8.62

1

2.02

5

8.13

0

2.04

3

1.00

0

1−Benzyl−4−phenyl−1H−1,2,3−triazole (3a)

ESI - 8

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

53.4

98

121.

996

125.

627

128.

331

128.

600

129.

240

129.

324

131.

140

136.

450

147.

146

1−Benzyl−4−phenyl−1H−1,2,3−triazole (3a)

ESI - 9

9 8 7 6 5 4 3 2 1 0 ppm

0.84

30.

861

0.87

91.

242

1.26

01.

278

1.29

71.

315

1.33

31.

500

1.52

01.

538

1.55

71.

575

2.55

82.

577

2.59

6

5.51

1

7.25

17.

269

7.29

57.

313

7.32

97.

348

7.36

47.

861

3.17

8

2.16

12.

130

2.12

7

2.08

5

5.12

4

1.00

0

1−Benzyl−4−butyl−1H−1,2,3−triazole (3b)

ESI - 10

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.1

05

22.1

0625

.099

31.5

28

53.0

81

122.

360

128.

226

128.

443

129.

150

136.

761

147.

710

1−Benzyl−4−butyl−1H−1,2,3−triazole (3b)

ESI - 11

9 8 7 6 5 4 3 2 1 0 ppm3.

812

7.12

77.

148

7.33

27.

350

7.36

87.

450

7.46

97.

487

7.82

77.

848

7.92

37.

942

9.14

9

3.09

7

2.06

51.

064

2.05

32.

080

2.02

5

1.00

0

1−(4−Methoxyphenyl)−4−phenyl−1H−1,2,3−triazole (3c)

ESI - 12

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

55.9

92

115.

336

120.

003

122.

097

125.

764

128.

557

129.

386

130.

535

130.

872

147.

585

159.

752

1−(4−Methoxyphenyl)−4−phenyl−1H−1,2,3−triazole (3c)

ESI - 13

9 8 7 6 5 4 3 2 1 0 ppm

2.37

6

7.34

57.

362

7.38

17.

400

7.42

07.

460

7.47

97.

496

7.80

47.

824

7.91

97.

938

9.22

2

3.05

2

5.28

8

2.14

52.

043

1.00

0

4−Phenyl−1−p−tolyl−1H−1,2,3−triazole (3d)

ESI - 14

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

21.0

34

119.

931

120.

329

125.

775

128.

633

129.

423

130.

708

134.

866

138.

789

147.

665

4−Phenyl−1−p−tolyl−1H−1,2,3−triazole (3d)

ESI - 15

9 8 7 6 5 4 3 2 1 0 ppm

0.88

10.

898

0.91

41.

339

1.35

61.

610

1.62

71.

643

2.34

72.

656

2.67

4

7.34

27.

360

7.73

17.

750

8.49

9

3.15

0

2.08

52.

084

3.12

2

2.06

8

2.07

6

2.06

2

1.00

0

4−Butyl−1−p−tolyl−1H−1,2,3−triazole (3e)

ESI - 16

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.1

3820

.969

22.1

6425

.145

31.4

13

120.

033

120.

310

130.

587

135.

056

138.

244

148.

454

4−Butyl−1−p−tolyl−1H−1,2,3−triazole (3e)

ESI - 17

9 8 7 6 5 4 3 2 1 0 ppm

0.82

40.

843

0.86

30.

881

1.19

81.

261

1.28

01.

299

1.31

71.

503

1.52

21.

540

1.55

81.

577

1.73

21.

747

1.76

42.

550

2.56

82.

587

4.22

74.

245

4.26

2

7.78

4

6.51

3

22.1

02

2.20

52.

145

2.11

2

2.08

0

1.00

0

4−Butyl−1−dodecyl−1H−1,2,3−triazole (3f)

ESI - 18

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.3

6722

.079

22.5

3025

.127

26.2

4028

.768

29.1

4229

.287

29.3

2529

.438

30.1

0931

.591

31.7

3549

.537

121.

987

147.

237

4−Butyl−1−dodecyl−1H−1,2,3−triazole (3f)

ESI - 19

9 8 7 6 5 4 3 2 1 0 ppm

3.86

8

7.01

47.

035

7.41

17.

511

7.52

17.

653

7.67

57.

756

8.01

9

3.12

9

2.06

51.

023

1.05

32.

060

1.03

31.

000

1−(4−Methoxyphenyl)−4−(thiophen−3−yl)−1H−1,2,3−triazole (3g)

ESI - 20

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm55

.647

114.

773

117.

677

121.

382

122.

157

125.

833

126.

452

130.

439

131.

567

144.

390

159.

809

1−(4−Methoxyphenyl)−4−(thiophen−3−yl)−1H−1,2,3−triazole (3g)

ESI - 21

9 8 7 6 5 4 3 2 1 0 ppm

6.26

37.

320

7.33

87.

356

7.43

87.

457

7.47

67.

583

7.60

27.

621

7.70

97.

728

7.74

57.

880

7.89

98.

091

8.11

08.

532

1.91

2

1.08

92.

108

2.05

71.

061

2.09

32.

044

1.00

0

1−Phenyl−2−(4−phenyl−1H−1,2,3−triazol−1−yl)ethanone (3h)

ESI - 22

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

56.4

63

123.

518

125.

641

128.

328

128.

678

129.

404

129.

448

131.

221

134.

574

134.

726

146.

816

192.

625

1−Phenyl−2−(4−phenyl−1H−1,2,3−triazol−1−yl)ethanone (3h)

ESI - 23

9 8 7 6 5 4 3 2 1 0 ppm

1.20

01.

218

1.23

5

4.16

24.

180

4.19

84.

215

5.43

8

7.31

27.

330

7.34

87.

425

7.44

47.

463

7.84

07.

859

8.55

0

3.14

6

2.06

5

2.05

8

1.06

62.

052

2.05

0

1.00

0

Ethyl 2−(4−phenyl−1H−1,2,3−triazol−1−yl)acetate (3i)

ESI - 24

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.4

11

51.0

07

62.0

17

123.

186

125.

625

128.

409

129.

398

130.

995

146.

847

167.

660

Ethyl 2−(4−phenyl−1H−1,2,3−triazol−1−yl)acetate (3i)

ESI - 25

9 8 7 6 5 4 3 2 1 0 ppm3.

803

3.86

1

7.09

17.

113

7.83

17.

853

9.33

5

3.11

03.

062

2.06

5

2.06

6

1.00

0

Methyl 1−(4−methoxyphenyl)−1H−1,2,3−triazole−4−carboxylate (3j)

ESI - 26

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

52.3

0756

.010

115.

281

122.

551

127.

415

129.

822

139.

772

160.

131

161.

064

Methyl 1−(4−methoxyphenyl)−1H−1,2,3−triazole−4−carboxylate (3j)

ESI - 27

9 8 7 6 5 4 3 2 1 0 ppm3.

820

5.20

5

6.94

06.

957

6.97

47.

058

7.07

77.

121

7.14

17.

292

7.31

07.

328

7.79

97.

820

8.84

5

3.06

0

2.01

9

1.05

14.

070

2.01

6

2.00

0

0.96

5

1−(4−Methoxyphenyl)−4−(phenoxymethyl)−1H−1,2,3−triazole (3k)

ESI - 28

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm56

.014

61.3

59

115.

129

115.

336

121.

385

122.

261

123.

278

130.

013

130.

436

144.

126

158.

451

159.

759

1−(4−Methoxyphenyl)−4−(phenoxymethyl)−1H−1,2,3−triazole (3k)

ESI - 29

9 8 7 6 5 4 3 2 1 0 ppm

2.37

1

5.29

2

6.75

86.

775

6.79

37.

259

7.27

87.

384

7.40

37.

782

8.89

6

2.96

5

1.96

6

0.99

0

1.00

33.

015

2.96

7

0.94

5

4−((2−Iodophenoxy)methyl)−1−p−tolyl−1H−1,2,3−triazole (3l)

ESI - 30

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

21.0

49

62.6

05

87.2

12

113.

726

120.

477

123.

305

123.

565

130.

208

130.

729

134.

722

138.

905

139.

581

143.

896

157.

088

4−((2−Iodophenoxy)methyl)−1−p−tolyl−1H−1,2,3−triazole (3l)

ESI - 31

9 8 7 6 5 4 3 2 1 0 ppm

5.22

9

5.62

3

6.88

26.

899

6.91

67.

303

7.32

07.

349

7.36

77.

554

7.57

38.

300

2.10

3

2.08

8

1.05

7

7.36

41.

073

1.00

0

1−Benzyl−4−((2−bromophenoxy)methyl)−1H−1,2,3−triazole (3m)

ESI - 32

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm53

.285

62.5

64

111.

568

114.

785

122.

844

125.

322

128.

409

128.

629

129.

235

129.

389

133.

508

136.

459

143.

057

154.

698

1−Benzyl−4−((2−bromophenoxy)methyl)−1H−1,2,3−triazole (3m)

ESI - 33

9 8 7 6 5 4 3 2 1 0 ppm3.

812

5.30

5

6.94

86.

967

6.98

67.

109

7.13

17.

295

7.31

37.

331

7.37

97.

404

7.42

57.

792

7.81

4

8.83

9

3.00

0

1.99

0

1.05

32.

009

1.03

31.

886

1.96

5

0.95

8

4−((2−Chlorophenoxy)methyl)−1−(4−methoxyphenyl)−1H−1,2,3−triazole (3n)

ESI - 34

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

56.0

09

62.3

81

114.

896

115.

337

121.

953

122.

296

122.

394

123.

493

128.

746

130.

385

130.

500

143.

605

153.

841

159.

807

4−((2−Chlorophenoxy)methyl)−1−(4−methoxyphenyl)−1H−1,2,3−triazole (3n)

ESI - 35

9 8 7 6 5 4 3 2 1 0 ppm

0.29

3

7.09

07.

112

7.77

17.

793

8.71

2

9.12

4

3.01

4

2.00

0

1.99

0

0.96

5

1−(4−Methoxyphenyl)−4−(trimethylsilyl)−1H−1,2,3−triazole (3o)

ESI - 36

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

55.9

52

115.

244

122.

252

129.

085

130.

508

146.

310

159.

481

1−(4−Methoxyphenyl)−4−(trimethylsilyl)−1H−1,2,3−triazole (3o)

ESI - 37

9 8 7 6 5 4 3 2 1 0 ppm3.

811

7.10

67.

128

7.77

77.

798

7.91

2

8.68

9

3.16

7

2.10

5

2.07

10.

895

1.00

0

1−(4−Methoxyphenyl)−1H−1,2,3−triazole (3p)

ESI - 38

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

56.0

06

115.

305

122.

257

123.

563

130.

577

134.

622

159.

657

1−(4−Methoxyphenyl)−1H−1,2,3−triazole (3p)

ESI - 39

9 8 7 6 5 4 3 2 1 0 ppm

5.56

15.

894

5.90

46.

010

6.02

0

7.32

27.

348

7.36

3

8.03

8

4.08

5

0.97

50.

985

10.1

86

2.00

0

Bis(1−benzyl−1H−1,2,3−triazol−4−yl)methanol (3q)

ESI - 40

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm53

.170

61.7

24

123.

231

128.

477

128.

579

129.

194

136.

583

150.

409

Bis(1−benzyl−1H−1,2,3−triazol−4−yl)methanol (3q)

ESI - 41

9 8 7 6 5 4 3 2 1 0 ppm

0.82

2

1.25

0

1.83

5

4.34

64.

362

4.37

9

7.28

67.

303

7.32

17.

403

7.42

27.

440

7.81

77.

836

8.55

4

3.28

9

6.64

6

2.09

7

2.07

2

1.16

12.

116

2.10

8

1.00

0

1−Hexyl−4−phenyl−1H−1,2,3−triazole (3r)

ESI - 42

190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

14.2

54

22.3

4425

.947

30.0

1531

.030

49.9

52

121.

637

125.

530

128.

179

129.

298

131.

349

146.

707

1−Hexyl−4−phenyl−1H−1,2,3−triazole (3r)

ESI - 43