Regioselective Synthesis of 1,5-Disubstituted 1,2,3-Triazoles by reusable

1 Regioselective Synthesis of 1,5-Disubstituted 1,2,3-Triazoles by reusable immobilized AlCl 3 on γ-al 2 O 3 SUPPLEMETARY DATA Typical Procedure to the preparation of Azides Phenyl azide Phenyl azide was prepared by the diazotization of aniline with nitrous acid, followed by the reaction of phenyldiazonium salt with aqueous sodium azide (20%, 1.5 equiv.) for 5h at 0 C, the reaction mixture was extracted thrice with ethyl acetate, the combined extracts dried over anhydrous sodium sulphate and the solvent was evaporated off under reduced pressure to obtain crude which may be purified by a short silica gel column chromatography using petroleum ether as an eluent, the pure product as may be stored at 2-8 C. Benzyl azide Benzyl bromide (10 mmol) is taken in 100 ml round bottomed flask and is added 80% aqueous acetone (50 ml) followed by sodium azide (1.5 equiv), the reaction mixture was stirred at 18 C for 24h, extracted with dichloromethane 5 times (20 ml), the combined extract was dried over anhydrous sodium sulphate and the solvent was evaporated off under reduced pressure to obtain crude which may be purified by a short silica gel column chromatography using petroleum ether as an eluent, the pure product as colourless oil may be stored at 2-8 C. Preparation of the catalyst

2 Immobilization of AlCl 3 on γ-al 2 O 3 : AlCl 3 generated by the reaction of CCl 4 and γ- Al 2 O 3 at 600 C was carried to the reactor containing activated γ-al 2 O 3 and reacted for 3 h at 400 C, the excess AlCl 3 was removed by flushing with itrogen at 400 C for 1h. The reaction product was cooled and stored under vacuum. Recycling the catalyst: On completion of the reaction, the reaction mixture was filtered off and washed with 10 ml of acetonitrile. Solvents were removed by rotary evaporation and the catalyst reused directly for the next run. The recovered catalyst was utilized for five subsequent reactions without any loss in catalytic activity. When the catalyst was filtered off, washed with acetone (4 X 10 ml) and activated at 400 C under itrogen stream, results of eleven subsequent reactions did not have significant changes in terms of yield and purity of the products. Characterization data: 2c. Methyl 4-(1-Phenyl-1H-1,2,3-triazol-5-yl)phenyl Ether: Yellow oil [21], 1 H MR (400 MHz, CDCl 3 ) δ 7.79 (s, 1H), 7.45 7.35 (m, 5H), 7.18 7.12 (m, 2H), 6.87 6.84 (m, 2H), 3.80 (s, 3H) ppm; 13 C MR (100 MHz, CDCl 3 ) δ 161.2, 137.5, 136.4, 133.1, 130.0, 129.4, 129.2, 125.1, 119.0, 114.2, 55.1 ppm. 3c. 5-(4-itrophenyl)-1-phenyl-1H-1,2,3-triazole: Yellow solid, mp 144 145 C (144 145 C) [22] ; 1 H MR (400 MHz, CDCl 3 ) δ 8.22 8.19 (m, 2H), 7.97 (s, 1H), 7.51 7.43 (m, 3H), 7.45 7.40 (m, 2H), 7.38 7.32 (m, 2H) ppm; 13 C MR (100 MHz, CDCl 3 ) δ 147.7, 135.5, 134.2, 133.1, 129.8, 129.6, 129.3, 125.4, 124.4, 124.1 ppm.

3 4c. 5-(4-Bromophenyl)-1-phenyl-1H-1,2,3-triazole: Yellow solid, mp 150 151 C (149 151 C) [17] ; 1 H MR (400 MHz, CDCl 3 ) δ 7.86 (s, 1H), 7.51 7.43 (m, 5H), 7.37 7.31 (m, 2H), 7.14 7.07 (m, 2H) ppm; 13 C MR (100 MHz, CDCl 3 ) δ 136.4, 133.3, 132.6, 132.3, 130.2, 129.8, 129.5, 125.7, 125.2, 123.4 ppm. 5c. 1-Phenyl-5-(2-thienyl)-1H-1,2,3-triazole: Brown oil [17], 1 H MR (400 MHz, CDCl 3 ) δ 7.89 (s, 1H), 7.55 7.48 (m, 3H), 7.49 7.40 (m, 2H), 7.36 (d, J = 5.1 Hz, 1H), 7.03 6.95 (m, 1H), 6.94 (d, J = 3.7 Hz, 1H) ppm; 13 C MR (100 MHz, CDCl 3 ) δ 136.5, 133.2, 132.4, 130.1, 129.5, 128.2, 127.7, 127.7, 127.1, 126.3 ppm. 6c. 1-Benzyl-5-phenyl-1H-1,2,3-triazole: White solid, mp 72 73 C (72 74 C) [21] ; 1 H MR (400 MHz, CDCl 3 ) δ 7.77 (s, 1H), 7.46 7.33 (m, 3H), 7.34 7.26 (m, 5H), 7.12 7.01 (m, 2H), 5.58 (s, 2H) ppm; 13 C MR (100 MHz, CDCl 3 ) δ 138.1, 135.3, 133.2, 129.7, 129.0, 128.8, 128.7, 128.3, 128.1, 127.1, 126.8, 52.1 ppm. 7c. 1-Benzyl-5-(4-methylphenyl)-1H-1,2,3-triazole: Colourless oil [21], 1 H MR (400 MHz, CDCl 3 ) δ 7.73 (s, 1H), 7.31 7.27 (m, 3H), 7.22 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.1 Hz, 2H), 7.05 7.02(m, 2H), 5.54 (s, 2H), 2.40 (s, 3H) ppm; 13 C MR (100 MHz, CDCl 3 ) δ 139.5, 138.2, 135.7, 133.2, 129.7, 128.8, 128.8, 128.1, 127.2, 123.9, 51.6, 21.3 ppm. 8c. 1-Benzyl-5-(4-methoxyphenyl)-1H-1,2,3-triazole: Pale yellow oil [21], 1 H MR (400 MHz, CDCl 3 ) δ 7.71 (s, 1H), 7.32 7.28 (m, 3H), 7.16 7.13 (m, 2H), 7.08 7.05 (m, 2H), 6.95 6.91 (m, 2H), 5.54 (s, 2H), 3.83 (s, 3H) ppm; 13 C MR (100 MHz,

4 CDCl 3 ) δ 160.6, 137.9, 135.6, 133.1, 130.3, 128.8, 128.1, 127.3, 118.9, 114.4, 55.8, 51.3 ppm. 9c. 4-(1-Benzyl-1H-1,2,3-triazol-5-yl)phenol: Yellow solid, mp 179 181 C (179 181 C) [17] ; 1 H MR (400 MHz, CDCl 3 ) δ 7.70 (s, 1H), 7.41 7.23 (m, 4H), 7.12 7.09 (m, 3H), 6.97 6.83 (m, 2H), 5.53 (s, 2H), 5.30 (s, 1H) ppm; 13 C MR (100 MHz, CDCl 3 ) δ 157.5, 138.3, 135.3, 132.8, 130.4, 128.9, 128.2, 127.4, 118.4, 116.1, 51.5 ppm. 10c. 1-Benzyl-5-(4-nitrophenyl)-1H-1,2,3-triazole: Yellow solid, mp 96 99 C (96 99 C) [23] ; 1 H MR (400 MHz, CDCl 3 ) δ 8.25 (d, J = 8.7 Hz, 2H), 7.81 (s, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.30 7.28 (m, 3H), 7.10 7.03 (m, 2H), 5.61 (s, 2H) ppm; 13 C MR (100 MHz, CDCl 3 ) δ 148.3, 134.6, 134.1, 131.2, 129.7, 129.0, 128.6, 127.6, 126.9, 124.1, 52.5 ppm. 11c. 1-Benzyl-5-(2-nitrophenyl)-1H-1,2,3-triazole: Yellow solid, mp 149 151 C (149 151 C) [24] ; 1 H MR (400 MHz, CDCl 3 ) δ 8.12 8.05 (m, 1H), 7.67 7.60 (m, 2H), 7.56 7.51 (m, 1H), 7.22 7.17 (m, 5H), 7.02 (dd, J = 7.6, 1.3 Hz, 1H), 5.42 (s, 2H) ppm; 13 CMR (100 MHz, CDCl 3 ) δ 148.4, 134.2, 133.7, 133.4, 133.2, 133.1, 131.1, 128.7, 128.4, 127.7, 124.9, 122.3, 52.6 ppm. 12c. 4-(1-Benzyl-1H-1,2,3-triazol-5-yl)Benzonitrile: Yellow solid, mp 85 86 C (84 86 C) [17] ; 1 H MR (400 MHz, CDCl 3 ) δ 7.78 (s, 1H), 7.74 7.66 (m, 2H), 7.39 7.33 (m, 2H), 7.31 7.25 (m, 3H), 7.06 6.95 (m, 2H), 5.56 (s, 2H) ppm; 13 C

5 MR (100 MHz, CDCl 3 ) δ 136.3, 134.9, 133.8, 132.7, 131.4, 129.5, 129.2, 128.3, 126.8, 117.7, 113.2, 52.5 ppm. 13c. 1-Benzyl-5-(2-chlorophenyl)-1H-1,2,3-triazole: White solid, mp 58 59 C (58 60 C) [17] ; 1 H MR (400 MHz, CDCl 3 ) δ 7.71 (s, 1H), 7.49 (dd, J = 8.1, 1.0 Hz, 1H), 7.41 7.38 (m, 1H), 7.28 7.16 (m, 4H), 7.01 (dd, J = 7.6, 1.6 Hz, 1H), 6.95 (dd, J = 7.5, 1.7 Hz, 2H), 5.44 (s, 2H) ppm; 13 C MR (100 MHz, CDCl 3 ) δ 134.8, 134.8, 134.4, 134.3, 132.0, 131.2, 129.9, 128.6, 128.2, 127.7, 126.9, 126.4, 52.5 ppm. 14c. 1-Benzyl-5-(2-thienyl)-1H-1,2,3-triazole: Yellow solid, mp 78 79 C (77 79 C) [17] ; 1 H MR (400 MHz, CDCl 3 ) δ 7.81 (s, 1H), 7.44 (dd, J = 5.1, 1.2 Hz, 1H), 7.34 7.26 (m, 3H), 7.13 7.05 (m, 3H), 7.02 (dd, J = 3.6, 1.2 Hz, 1H), 5.66 (s, 2H) ppm; 13 C MR (100 MHz, CDCl 3 ) δ 135.2, 133.7, 131.9, 128.9, 128.4, 128.2, 128.1, 127.9, 126.8, 126.4, 52.3 ppm. REFERECES 21 Hong, L.; Lin, W.; Zhang, F.; Liu, R.; Zhou, X. Ln[(SiMe 3 ) 2 ] 3 -catalyzed cycloaddition of terminal alkynes to azides leading to 1,5-disubstituted 1,2,3- triazoles: new mechanistic features. Chem. Commun. 2013, 49, 5589-5591. 22. Kadaba, P. K.; Edelstein, S. B. Triazolines. 19. ickel peroxide oxidation of DELTA 2-1,2,3-triazolines. A versatile general synthetic route to 1H-1,2,3- triazoles. J. Org. Chem. 1990, 55, 5891-5894.

6 23. Wang, D.; Salmon, L.; Ruiz, J.; Astruc, D. A recyclable ruthenium(ii) complex supported on magnetic nanoparticles: a regioselective catalyst for alkyne-azode cycloaddition. Chem. Commun. 2013, 49, 6956-6958. 24. McIntosh, M. L.; Johnston, R. C.; Pattawong, O.; Ashburn, B. O.; affziger, M. R.; P; Cheong, Ha-Y.; Carter, R. G. Synthesis and computational analysis of densely functinalized triazoles using o-nitrophenylalkynes. J. Org. Chem. 2012, 77, 1101-1112.

7 1 H MR Spectra of compounds 1c-14c 1c

8 2c OCH 3

9

10 3c O 2

11 4c Br

12

13 S 5c

14 6c

15

16 7c CH 3

17 8c OCH 3

18

19 9c OH

20 10c O 2

21

22 O 2 11c

23 12c C

24

25 Cl 13c

26 S 14c

27

28 1 H MR 13 C Spectra of compounds 1c-14c 1c

29

30

31 3c O 2

32 4c Br

33

34 S 5c

35 6c

36

37 7c CH 3

38 8c OCH 3

39

40 9c OH

41 10c O 2

42

43 O 2 11c

44 12c C

45

46 Cl 13c

47 S 14c

48