Electronic Supplementary Material (ESI) for Green Chemistry. This journal is © The Royal Society of Chemistry 2019

Supplementary Information

Highly regioselective and sustainable solar click reaction: A new Post-synthetic modified triazole organic polymer as recyclable photocatalyst for regioselective azide-alkyne cycloaddition reaction Dolly Yadav,a Nem Singh,a Tae Wu Kim,b Jae Young Kim,a No-Joong Parka and Jin-Ook Baeg*a

aArtificial Photosynthesis Research Group, Korea Research Institute of Chemical Technology (KRICT), 100 Jang-dong, Yuseong, Daejeon 34114, Republic of Korea E-mail:[email protected]

bCenter for Nanomaterials and Chemical Reactions, Institute for Basic Science (IBS), Daejeon 34141, Korea.

S. N. Contents Page no.

1. Experimental section S2-S3

2. Safety issues for handling azide compounds S3

3. Synthetic procedure S4-S18

4. Tables S1-S3 S19-S21

5. Figures S1-S12 S20-S28

6. Crystallographic data of 3bd- figure S12, table S4-S5 S29-S31

7. 1H, 13C and 19F NMR figure S13- S28 S32-S86

8. References S86

S1 Experimental Section

1.1 Materials

All the reagents utilized in synthesis were purchased from commercial suppliers, unless or

otherwise stated. Sodium Azide, disodium 4,4’-diaminostilbene disulfonate, sodium nitrite, 1,8-

diazabicyclo[5,4,0]undec-7-ene, propargyl alcohol, propargyl bromide (80% in toluene), perylene

tetracarboxylic anhydride were purchased from Sigma Aldrich Korea. 2,6-difluorobenzylbromide,

2,4-difluorobenzylbromide, 3,5-Dimethylbenzylbromide, 4-bromobenzylbromide, 4-

fluorobenzylbromide propiolic acid and methyl propiolate were also purchased from Sigma

Aldrich. The solvents DMF, DCM, acetone, ethyl acetate were purchase from Junsei Chemicals

Company. Caution sodium azide is considered to be explosive, hence necessary precautions fume

hood, safety glasses etc should be taken while carrying out the reaction. Also the reaction should

not be carried out on large scale. Please refer to section 2 of the supplementary information for

safe handling of azides.

1.2 Instruments and Measurements:

Single-crystal X-ray crystallography: The X-ray crystal structure analysis was carried out using a

Bruker Kappa APEX II CCD detector equipped Mo K ( = 0.71073 Å) microsource with Quazar

optics or Cu K ( = 1.54178 Å) microsource with MX optics. The single crystals were mounted on MicroMesh (MiTeGen) with paratone oil. The structure was solved by direct methods (SHELXT-

2014/5), using the SAINT PLUS and SHELXT data package. The refinement results are summarized

in Table S4 and S5. The crystallographic data has been deposited in the Cambridge

Crystallographic Data Centre (CCDC) in CIF format under deposition numbers 1889079. The

S2 copies of the CIF data can be obtained via www.ccdc.cam.ac.uk/data_request/cif and/or from

The Director, CCDC, 12 Union Street, Cambridge CB2 1EZ, U.K. (fax, +44-1223- 336-033; e-mail, [email protected]) free of charges.

2. The safety issues for handling of azido compounds:1,2

2.1. Sodium azide (NaN3)

Sodium azide is a toxic chemical (LD50 oral = 27 mg/kg for rats) and can be easily absorbed through the skin. Appropriate protection is needed for the safe handling of the chemical (gloves, safety glasses). Heating sodium azide above 275 °C leads to explosion. Sodium azide are relatively

safe especially in aqueous solution, unless acidified to form HN3, which is volatile and highly toxic.

2.2. Organic azide

Organic azides are potentially explosive substances that decomposed with the slight input of energy from external sources (heat, light, pressure, etc). When the designed organic azides used for the project, we keep in mind the following equation. It is noted that this equation takes into account all nitrogen atoms in the organic azide, not just those in the azido group.

All organic azides are stable enough to be stored under –20 ˚C at least for 6 months.

S3 3. Synthetic Procedure:

3 3.1 Synthesis of tetra(prop-2-yn-1-yl) 3,6a-dihydroperylene-3,4,9,10-tetracarboxylate (L1):

1,8-Diazabicyclo[5,4,0]undec-7-ene (114 mL, 0.76 mmol) and propargyl alcohol (88 µL, 1.52

mmol) were added to a stirred solution of perylene tetracarboxylic anhydride (74.5 mg, 0.19

mmol) in DMF (3.5 mL) at 60 ˚C and the resulting mixture was stirred for 30 min. Then, a solution

of propargyl bromide (80% in toluene, 115 µL, 1.52 mmol) in DMF (0.5 mL) was added dropwise and the solution was stirred for 3 h at the same temperature. A change in the color of solution changed to bright orange was observed as the reaction proceeded. After the completion of the reaction, the crude product was precipitated in water (50 mL) and the solid was filtered out using a G4 glass filter. The solid obtained was dissolved in DCM (30 mL) and washed with water (2 x10 mL) and brine. The organic phase was dried over Na2SO4 and concentrated in vacuum. The

1 residue was purified by thin layer chromatography (TLC) with DCM to afford L1 as a red solid. H

NMR (CDCl3, 500 MHz): δ = 8.51 (2H, d, PDI-H), 8.41(2H, t, PDI-H), 8.28 (2H, dd, PDI-H), 8.10 (2H,

d, PDI-H), 4.90 (8H, s, -CH2-), 2.10 (4H, s, CH).

3.2 Synthesis of 4,4'-diazidostilbene-2,2’-disulfonic acid disodium salt (L2):

3.7 g 4,4'-diaminostilbene-Z,2'-disulfonic acid was suspended in 10 mL of water in a three neck round bottom flask equipped with a stirrer, thermometer and dropping funnel. 0.8 g of sodium hydroxide was added to the solution. With continuous stirring 1.4g of sodium nitrite in 4 ml of water was added to the reaction. The reaction was cooled to 0° C. and 8 ml. of 6 N hydrochloric acid are added dropwise so that the reaction temperature could be kept in between 0°- 5° C.

Thereafter a solution of 1.4 g. of sodium azide in 4 ml. of water is added dropwise at a temperature between 5 ° and 15° C. Stirring is continued for 5 hour. The precipitate was filtered,

S4 washed with alcohol and dried. FTIR (cm-1): 2117.4, 1705.4, 1590.6, 1486.6, 1446.4, 1327.0,

1 1293.7, 1190.4, 1081.0, 1025.4, 830.4, 703.9, 623.5. H NMR (DMSO-d6, 500 MHz): δ = 8.05 (1H,

13 s, ArH), 7.65 (1H, d, ArH), 7.52 (1H, d, ArH), 7.13 (1H, dd, ArH). C NMR (DMSO-d6, 125 MHz): δ

= 147.56, 137.56, 132.39, 127.63, 127.08, 120.12, 117.88.

3.3 Synthesis of 4,4'-diazidostilbene-2,2’-disulfonochloride(L3):

10 mL of thionyl chloride was added to 1.3 g. of L2 and refluxed for 8 hours. After completion of reaction the excess of thionyl chloride is evaporated and the residue was extracted with 100 ml. of trichloroethane. The solution was evaporated and the residue obtained was washed with ether. Yield: 0.25g. FTIR (cm-1): 2117.4, 1705.4, 1590.6, 1486.6, 1446.4, 1327.0, 1293.7, 1190.4,

1 1081.0, 1025.4, 830.4, 703.9, 623.5. H NMR (DMSO-d6, 500 MHz): δ = 8.05 (1H, s, ArH), 7.65 (1H,

13 d, ArH), 7.52 (1H, d, ArH), 7.13 (1H, dd, ArH). C NMR (DMSO-d6, 125 MHz): δ = 147.56, 137.56,

132.39, 127.63, 127.08, 120.12, 117.88.

3.4 Synthesis of propiolamide (1a): Methyl propiolate (5 mL, 40 mmol) was added to aqueous ammonia (35%, 100 ml) at -10° C for 2 hr. The reaction mixture was extracted with ethyl acetate

(50 x 3 mL), passed over MgSO4. The solvent was removed via rotatory evaporation to yield white

1 13 crystalline solid. H NMR (CDCl3, 500 MHz): δ = 5.78 (2H, s, NH2), 2.80 (1H, s, CH). C NMR (CDCl3,

125 MHz): δ = 172.96, 74.26, 22.65.

3.5 General synthesis of representative azide substrates:

(a) General synthesis of benzyl azides: Representative benzyl bromide (1 mmol) is suspended in

10 mL acetone, followed by addition of NaN3 (1.5 mmol) in 15 ml DIW. The reaction mixture was stirred overnight. The completion of reaction was conferred through TLC, after which the product

S5 was extract with ethyl acetate (15 mL x 3). The organic layer was washed with DIW (20 mL x 5).

The organic layer was passed through magnesium sulfate and the solvent was removed through

rotatory evaporation to obtain corresponding azides. Precautionary steps for handling of azides

should was thoroughly followed (see section 2, ESI).

(b) General synthesis of aromatic azides:

Into a 100 mL round bottom flask the representative aniline derivative (10 mmol) was suspended in DIW (15 mL), followed by addition of concentrated HCl (4 mL). The reaction mixture was stirred vigorously in an ice-water bath to maintain a temperature of 0 °C for 20-30 min. After which, a freshly prepared, ice cold solution of NaNO2 (10 mmol) in DIW (3 mL) was added dropwise to the reaction mixture, maintaining the reaction temperature between 0-5 °C. After the complete addition of NaNO2, the reaction mixture was further stirred for an additional 30 min. Then a solution of sodium azide (12 mmol) in DIW (5 mL) was added drop wise to the reaction mixture via additional funnel, maintaining the reaction temperature below 5 °C. Upon complete addition of the sodium azide solution, the reaction mixture was stirred for an additional 1h at 0 °C, followed by stirring at rt for another 3 h. The reaction mixture was then extracted with CH2Cl2

(2×50 mL), and combined organic layers was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude azido derivative was further purified by flash column chromatography over a short plug of silica gel using using petroleum ether /EtOAc (15:1) as eluent to afford pure azido derivative.

1. Synthesis of 2,6-difluorobenzylazide (2a): 2,6-difluorobenzyl bromide (207 mg, 1 mmol),

1 NaN3 (97.5 mg, 1.5 mmol). Colorless oil, 95 %. H NMR (CDCl3, 500 MHz): δ 7.32 (1H, m

S6 13 ArH), 6.93 (2H, t, ArH), 4.43 (2H, s, -CH2-). C NMR (CDCl3, 125 MHz): δ 162, 160, 130,

19 111, 42. F NMR (CDCl3, 470 MHz): δ -114.73.

2. Synthesis of 2,4-difluorobenzyl azide (2b): 2,4-difluorobenzyl bromide (207 mg, 1 mmol),

1 NaN3 (97.5 mg, 1.5 mmol). Colorless oil, Yield: 87 %. H NMR (CDCl3, 500 MHz): δ 7.29 (1H,

13 m ArH), 6.85 (2H, dtd, ArH), 4.33 (2H, s, -CH2-). C NMR (CDCl3, 125 MHz): δ 164.27,

19 162.30, 160.31, 131.59, 119.07, 111.88, 104.45, 48.22. F NMR (CDCl3, 470 MHz): δ = -

113.54, -109.15.

3. Synthesis of 3,5-Dimethylbenzylazide (2c): 3,5-Dimethylbenzyl bromide (199 mg, 1

1 mmol) NaN3 (97.5 mg, 1.5 mmol). Colorless oil, Yield: 90 %. H NMR (CDCl3, 500 MHz): δ

13 = 6.86 (1H, d ArH), 6.81 (2H, d, ArH), 4.12 (2H, s, -CH2-), 2.21 (6H, d, -CH3). C NMR (CDCl3,

125 MHz): δ = 138.49, 135.35, 130.01, 126.11, 54.90, 21.30.

4. Synthesis of 4-bromobenzylazide (2d): 4-bromomethylbenzyl bromide (250 mg, 1 mmol)

1 NaN3 (97.5 mg 1.5 mmol). Colorless oil, Yield: 92 %. H NMR (CDCl3, 500 MHz): δ = 7.42

13 (2H, d ArH), 7.09 (2H, d, ArH), 4.20 (2H, s, -CH2-). C NMR (CDCl3, 125 MHz): δ = 134.43,

132.00, 129.82, 122.35, 54.10.

5. Synthesis of 2-fluorobenzylazide (2e): 2-fluorobenzyl bromide (189 mg, 1 mmol) NaN3

1 (97.5 mg, 1.5 mmol). Oily product with 75 % yield. H NMR (CDCl3, 500 MHz): δ = 7.26

13 (21H, m ArH), 7.09 (1H, td, ArH), 7.03 (1h, dd, ArH), 4.33 (2H, s, -CH2-). C NMR (CDCl3,

19 125 MHz): δ = 162.17, 160.20, 130.74, 130.57, 124.75, 115.97, 48.79. F NMR (CDCl3, 470

MHz): δ = -117.98.

6. Synthesis of 4-fluorobenzylazide (2f): 4-fluorobenzyl bromide (189 mg, 1 mmol) NaN3

1 (97.5 mg, 1.5 mmol). Oily product with 85 % yield. H NMR (CDCl3, 500 MHz): δ = 7.63 (2H,

S7 13 d, ArH), 7.54 (2H, d, ArH), 4.52 (2H, s, -CH2-). C NMR (CDCl3, 125 MHz): δ = 163.64,

19 161.67, 131.21, 131.18, 123.73, 115.80, 54.07. F NMR (CDCl3, 470 MHz): δ = -113.57.

7. Synthesis of 1-(azidomethyl)-2-(trifluoromethyl)benzene (2g): 1-(bromomethyl)-2-

(trifluoromethyl)benzene (240 mg, 1 mmol) and NaN3 (97.5 mg, 1.5 mmol). Colorless oil,

1 Yield: 90 %. H NMR (CDCl3, 500 MHz): δ = 7.68 (1H, d ArH), 7.63 (1H, d, ArH), 7.58 (1H, t,

19 ArH), 7.44 (1h, t, ArH), 4.67 (2H, s, -CH2-). F NMR (CDCl3, 470 MHz): δ = -59.58.

8. Synthesis of 1-(azidomethyl)-3-(trifluoromethyl)benzene (2h): 1-(bromomethyl)-3-

(trifluoromethyl)benzene (240 mg, 1 mmol) and NaN3 (97.5 mg, 1.5 mmol). Colorless oil,

1 Yield: 92 %. H NMR (CDCl3, 500 MHz): δ = 7.51 (2H, m, ArH), 7.42 (2H, m, ArH), 4.34 (2H,

13 s, -CH2-). C NMR (CDCl3, 125 MHz): δ = 136.85, 131.68, 129.68, 127.48, 125.42, 125.10,

19 123.15, 120.98, 54.48. F NMR (CDCl3, 470 MHz): δ = -62.75.

9. Synthesis of 1-(azidomethyl)-4-(trifluoromethyl)benzene (2i): 1-(bromomethyl)-4-

(trifluoromethyl)benzene (240 mg, 1 mmol) and NaN3 (97.5 mg, 1.5 mmol). Colorless oil,

1 Yield: 95 %. H NMR (CDCl3, 500 MHz): δ = 7.63 (2H, d ArH), 7.54 (2H, d, ArH), 4.52 (2H, s,

13 19 -CH2-). C NMR (CDCl3, 125 MHz): δ = 139.43, 130.50, 128.26, 125.81, 125.04, 54.09. F

NMR (CDCl3, 470 MHz): δ = -62.67.

10. Synthesis of (2-azidoethyl)benzene (2j): (2-bromoethyl)benzene (185 mg, 1 mmol) NaN3

1 (97.5 mg 1.5 mmol). Colorless oil, Yield: 85 %. H NMR (CDCl3, 500 MHz): δ = 7.25 (2H, d,

13 ArH), 7.15 (3H, m, ArH), 3.49 (2H, t, -CH2-), 3.09 (2H, t, -CH2-). C NMR (CDCl3, 125 MHz):

δ = 138.92, 138.04, 128.68, 128.64, 126.81, 52.50, 35.39.

11. Synthesis of 4-(2-azidoethyl)phenol (2k): 4-(2-bromoethyl)phenol (201 mg, 1 mmol)

1 NaN3 (97.5 mg, 1.5 mmol). Golden yellow color oil, Yield: 97 %. H NMR (CDCl3, 500 MHz):

S8 13 δ = 7.09 (2H, d, ArH), 6.79 (2H, d, ArH), 3.46 (2H, t, -CH2-), 2.83 (2H, t, -CH2-). C NMR

(CDCl3, 125 MHz): δ = 154.42, 130.18, 130.00, 115.59, 52.74, 34.50.

12. Synthesis of 3-fluoro-(2-azidoethyl)benzene (2l): 4-fluoro-(2-bromoethyl)benzene (203

1 mg, 1 mmol) NaN3 (97.5 mg, 1.5 mmol). colorless oil, Yield: 95 %. H NMR (CDCl3, 500

13 MHz): δ = 7.31 (1H, m, ArH), 7.00 (3H, m, ArH), 3.54 (2H, t, -CH2-), 2.91 (2H, t, -CH2-). C

NMR (CDCl3, 125 MHz): δ = 163.92, 140.54, 130.15, 124.38, 115.69, 113.74, 52.13, 35.08.

19 F NMR (DMSO-d6, 470 MHz): δ = -113.13

13. Synthesis of (1-azidoethyl)benzene (2m): (1-bromoethyl)benzene (185 mg, 1 mmol)

1 NaN3 (97.5 mg, 1.5 mmol). colorless oil, Yield: 75 %. H NMR (CDCl3, 500 MHz): δ = 7.36

13 (5H, m, ArH), 4.62 (1H, q, -CH-), 1.53 (3H, d, -CH3). C NMR (CDCl3, 125 MHz): δ = 140.90,

128.81, 128.17, 126.42, 125.42, 61.14, 21.62.

14. Synthesis of 1-azido-4-methylpentane (2n): 1-bromo-4-methylpentane (165 mg, 1

1 mmol) NaN3 (97.5 mg, 1.5 mmol). colorless oil, Yield: 70 %. H NMR (CDCl3, 500 MHz): δ =

3.33 (1H, m, -CH-), 3.18 (2H, t, -CH2-), 1.52 (2H, m, -CH2-), 1.18 (2H, m, -CH2-), 0.83 (6H, d,

13 -CH3). C NMR (CDCl3, 125 MHz): δ = 51.78, 35.86, 27.73, 26.76, 22.48.

15. Synthesis of 2-(azidomethyl)naphthalene (2o): 2-(bromomethyl)naphthalene (221 mg,

1 1 mmol) NaN3 (97.5g 1.5 mmol). H NMR (CDCl3, 500 MHz): δ = 7.86 (3H, m, ArH), 7.81

13 (1H, d, ArH), 7.54 (2H, m, ArH), 7.46 (1H, dd, ArH), 4.53 (2H, s, -CH2-). C NMR (CDCl3, 125

MHz): δ = 128.80, 127.97, 127.78, 127.21, 126.49, 126.37, 125.88, 55.05.

16. Synthesis of benzylazide (2p): benzyl bromide (171 mg, 1 mmol) NaN3 (97.5 mg, 1.5

1 13 mmol). H NMR (CDCl3, 500 MHz): δ = 7.36 (5H, m, ArH), 4.34 (2H, s, -CH2-). C NMR

(CDCl3, 125 MHz): δ = 135.47, 128.93, 128.43, 128.32, 54.90.

S9 1 17. Synthesis of 1-azido-2-methylbenzene (2q): yellow oil, 82 % yield. H NMR (CDCl3, 500

MHz): δ = 7.24 (1H, m, ArH), 6.96 (1H, dd, ArH), 6.85 (2H, m, ArH), 2.36 (3H, s, -CH3), 1.54

13 (3H, d, -CH3). C NMR (CDCl3, 125 MHz): δ = 139.87, 129.55, 125.76, 119.59, 116.12,

21.36.

1 18. Synthesis of 1-azido-3-methylbenzene (2r): yellow oil, 80 % yield. H NMR (CDCl3, 500

MHz): δ = 7.24 (1H, m, ArH), 7.17 (1H, dd, ArH), 7.12 (1H, dd, ArH), 7.05 (1H, td, ArH), 2.22

13 (2H, s, -CH3). C NMR (CDCl3, 125 MHz): δ = 138.37, 131.13, 129.58, 127.07, 124.57,

117.90, 17.24.

1 19. Synthesis of 1-azido-4-(tert-butyl)benzene (2s): colorless oil, 75% yield. H NMR (CDCl3,

13 500 MHz): δ = 7.38 (2H, d, ArH), 6.98 (2H, d, ArH), 1.32 (9H, s, -CH3). C NMR (CDCl3, 125

MHz): δ = 148.05, 137.10, 126.70, 118.64, 34.46, 31.36.

20. Synthesis of 2-azido-1,3,5-trichlorobenzene (2t): crystalline solid. 90 % yield. 1H NMR

13 (CDCl3, 500 MHz): δ = 7.19 (3H, m, ArH). C NMR (CDCl3, 125 MHz): δ = 133.05, 130.00,

128.97.

3.6 General procedure for photocatalytic alkyne-azide click reaction:

In a cuvette, photocatalyst (5 mg) and alkenyl derivative (1 mmol) were stirred at room temperature for 5 mins followed by addition of azido derivative (1 mmol) and NaCl (4M, 250μl).

The reaction mixture was then irradiated with vigorous stirring until completion of reaction. The product was isolated by dissolving the residue in organic solvent (CHCl3) and simple filtration followed by drying. The photocatalyst recovered via filtration was successively washed with

CHCl3, acetone and water and dried under vacuum before recycling.

S10 3.7 Procedure for gram scale synthesis of Rufinamide:

In a cuvette, photocatalyst (10 mg), propiolamide (0.5 g, 1.1 eq) were stirred at room temperature for 5 mins followed by addition of 2,6-difluorobenzylazide (1.34 g, 1eq) and NaCl

(4M, 500μl). The reaction mixture was stirring vigorous under visible light irradiation for 1.5h.

The product was isolated by dissolving the residue in CHCl3 (10mL x 3) followed by simple filtration. The solvent was evaporated and the solid product obtained was dried under vacuum.

Yield: 0.85g.

1. 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3aa):

2,6-difluorobenzylazide (169 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 95%,

1 colorless block shaped crystals. H NMR (DMSO-d6, 500 MHz): δ = 13.15 (1H, s, COOH),

13 8.74 (1H, s, triazole H), 7.53 (1H, m, ArH), 7.20 (2H, dq, Ar H), 5.73 (2H, s,-CH2-), C NMR

(DMSO-d6, 125 MHz):162.26, 161.02, 160.33, 138.95, 132.26, 129.93, 112.38, 111.29,

19 52.29. F NMR (DMSO-d6, 470 MHz): δ = -114.55.

2. 1-(2,4-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3ab):

2,4-difluorobenzylazide (169 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 80%,

1 crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 13.15 (1H, s, COOH), 8.86 (1H, s,

13 triazole H), 7.53 (1H, m, ArH), 7.20 (2H, dq, Ar H), 5.71 (2H, s,-CH2-), C NMR (DMSO-d6,

125 MHz):164.00, 161.89, 161.79, 159.80, 139.15, 138.13, 132.78, 129.80 119.15, 112.59,

19 104.09, 52.28, and 47.84. F NMR (DMSO-d6, 470 MHz): δ = -113.05, -108.97.

3. 1-(3,5-dimethylbenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3ac):

3,5-Dimethylbenzylazide (161 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 90%,

1 crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 13.07 (1H, s, COOH), 8.74 (1H, s,

S11 13 triazole H), 6.96 (2H, d, ArH), 5.55 (2H, s,-CH2-), 2.25 (6h, s, -CH3). C NMR (DMSO-d6, 125

MHz):162.08, 140.31, 138.41, 135.84, 130.11, 129.40, 126.18, 53.49, and 21.26

4. 1-(4-bromobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3ad): 4

4-bromobenzylazide (340 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 95%,

1 crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 8.78 (1H, s, triazole H), 7.59 (2H, d,

13 ArH), 7.31 (2H, d, ArH), 5.64 (2H, s,-CH2-). C NMR (DMSO-d6, 125 MHz):162.02, 140.39,

135.44, 132.21, 130.75, 130.18, 129.57, 122.05, 52.76.

5. 1-(2-fluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3ae):

2-fluorobenzylazide (151 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 92%,

1 crystalline solid. H NfMR (DMSO-d6, 500 MHz): δ = 8.74 (1H, s, triazole H), 7.59 (1H, d,

13 ArH), (1H, d, ArH), (2H, d, ArH), 5.72 (2H, s,-CH2-). C NMR (DMSO-d6, 125 MHz):162.01,

161.52, 159.55, 140.23, 131.34, 129.66, 125.36, 122.87, 116.23, 47.60. 19F NMR (DMSO-

d6, 470 MHz): δ = -117.2.

6. 1-(4-fluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3af):

4-fluorobenzylazide (151 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 80%, white

1 crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 8.77 (1H, s, triazole H), 7.43 (2H, dd,

13 19 ArH), 7.22 (2H, t, ArH), 5.65 (2H, s,-CH2-). C NMR (DMSO-d6, 125 MHz): . F NMR (DMSO-

d6, 470 MHz): δ = -113.81.

7. 1-(2-trifluoromethylbenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3ag):

1-(azidomethyl)-2-(trifluoromethyl)benzene (201 mg, 1mmol) and propiolic acid (70 mg,

1 1mmol) Yield: 95%, white solid. H NMR (DMSO-d6, 500 MHz): δ = 8.76 (1H, s, triazole H),

7.82 (1H, d, ArH), 7.70 (1H, t, ArH), 7.59, (1H, t, ArH), 7.22 (1H, d, ArH), 5.86 (2H, s,-CH2-).

S12 13 C NMR (DMSO-d6, 125 MHz):162.03, 140.30, 133.63, 130.82, 130.17, 129. 47, 127.18,

19 126.94, 126.73, 125.65, 123.47, 52.29. F NMR (DMSO-d6, 470 MHz): δ = -58.92.

8. 1-(3-trifluoromethylbenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3ah):

1-(azidomethyl)-3-(trifluoromethyl)benzene (201 mg, 1mmol) and propiolic acid (70 mg,

1 1mmol) Yield: 90%, white solid. H NMR (DMSO-d6, 500 MHz): δ = 8.85 (1H, s, triazole H),

13 7.79 (1H, s, ArH), 7.74 (1H, td, ArH), 7.64, (2H, m, ArH), 5.78 (2H, s,-CH2-). C NMR (DMSO-

d6, 125 MHz):162.02, 140.42, 137.38, 132.75, 130.49, 130.01, 129. 57, 125.57, 125.28,

19 123.37, 52.78. F NMR (DMSO-d6, 470 MHz): δ = -61.14.

9. 1-(4-trifluoromethylbenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3ai):

1-(azidomethyl)-4-(trifluoromethyl)benzene (201 mg, 1mmol) and propiolic acid (70 mg,

1 1mmol) Yield: 95%, crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 8.85 (1H, s, triazole

13 H), 7.79 (1H, s, ArH), 7.74 (1H, td, ArH), 7.64, (2H, m, ArH), 5.78 (2H, s,-CH2-). C NMR

(DMSO-d6, 125 MHz): δ = 162.01, 140.66, 140.44, 129.84, 129.36, 129.19, 126.19, 123.46,

19 52.82. F NMR (DMSO-d6, 470 MHz): δ = -61.09.

10. 1-(phenethyl)-1H-1,2,3-triazole-4-carboxylic acid (3aj):

(2-azidoethyl)benzene (147 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 90% as

1 crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 13.13 (1H, s, COOH), 8.86 (1H, s,

13 triazole H), 7.36 (4H, m, ArH), 7.32 (1H, m, ArH), 6.01 (1H, q, -CH-), 1.92 (3H, s,-CH3). C

NMR (DMSO-d6, 125 MHz): δ = 162.17, 140.97, 140.26, 129.25, 128.66, 128.13, 126.89,

60.15, 21.23.

11. 1-(4-hydroxyphenethyl)-1H-1,2,3-triazole-4-carboxylic acid (3ak):

S13 4-(2-azidoethyl)phenol (163 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 85% as

1 crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 13.06 (1H, s, COOH), 9.25 (1H, s, OH),

8.55 (1H, s, triazole H), 6.96 (1H, d, ArH), 6.66 (2H, d, ArH), 4.59 (2H, s, -CH2-), 3.06 (2H,

13 s,-CH2-). C NMR (DMSO-d6, 125 MHz): δ = 162.20, 156.47, 139.84, 130.08, 129.29,

127.77, 115.68, 51.52, 35.16.

12. 1-(3-fluorophenethyl)-1H-1,2,3-triazole-4-carboxylic acid (3al):

3-fluoro-(2-azidoethyl)benzene (165 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield:

1 98% as crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 13.06 (1H, s, COOH), 9.25 (1H,

s, OH), 8.55 (1H, s, triazole H), 6.96 (1H, d, ArH), 6.66 (2H, d, ArH), 4.59 (2H, s, -CH2-), 3.06

13 (2H, s,-CH2-). C NMR (DMSO-d6, 125 MHz): δ = 162.20, 156.47, 139.84, 130.08, 129.29,

127.77, 115.68, 51.52, 35.16.

13. 1-(1-phenylethyl)-1H-1,2,3-triazole-4-carboxylic acid (3am):

(1-azidoethyl)benzene (147 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 87% as

1 crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 13.13 (1H, s, COOH), 8.86 (1H, s,

13 triazole H), 7.36 (4H, m, ArH), 7.32 (1H, m, ArH), 6.01 (1H, q, -CH-), 1.92 (3H, s,-CH3). C

NMR (DMSO-d6, 125 MHz): δ = 162.17, 140.97, 140.26, 129.25, 128.66, 128.13, 126.89,

60.15, 21.23.

14. 1-(4-methylpentyl)-1H-1,2,3-triazole-4-carboxylic acid (3an):

1-azido-4-methylpentane (127 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 80%

1 as crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 13.09 (1H, s, COOH), 8.70 (1H, s,

triazole H), 4.38 (2H, t, -CH2-), 1.84 (2H, m, -CH2-), 1.54 (1H, s, -CH-), 1.11 (2H, m,-CH2-)

S14 13 0.84 (6H, d, -CH3). C NMR (DMSO-d6, 125 MHz): δ = 162.22, 140.06, 129.22, 50.32, 39.49,

35.33, 31.92, 27.92, 27.43, 22.78.

15. 1-(naphthalen-1-ylmethyl)-1H-1,2,3-triazole-4-carboxylic acid (3ao):

1 1-(azidomethyl)naphthalene (183 mg, 1 mmol) and NaN3 (70 mg 1.5 mmol). H NMR

(DMSO-d6, 500 MHz): δ = 8.84 (1H, s, triazole H), 7.93 (3H, m, ArH), 7.89 (1H, d, ArH), 7.55

13 (2H, m, ArH), 7.49 (1H, dd, ArH), 5.83 (2H, s, -CH2-). C NMR (DMSO-d6, 125 MHz): δ =

162.08, 133.55, 133.20, 133.00, 129.62, 129.03, 128.32, 128.09, 127.49, 127.07, 126.99,

126.16, 53.67.

16. Synthesis of 1-benzyl-1H-1,2,3-triazole-4-carboxylic acid (3ap):

benzyl azide (133 mg, 1 mmol) NaN3 (70 mg 1.5 mmol). 8.78 (1H, s, triazole H), 7.37 (5H,

m, ArH), 5.65 (2H, s, -CH2-).

17. 1-(o-tolyl)-1H-1,2,3-triazole-4-carboxylic acid (3aq):

1-azido-2-methylbenzene (133 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 80%,

pale solid. 9.07 (1H, s, triazole H), 7.50 (3H, m, ArH), 7.43 (1H, d, ArH), 2.16 (3H, s, -CH3)

13 C NMR (DMSO-d6, 125 MHz): δ = 162.10, 140.36, 136.19, 133.71, 131.80, 130.82, 127.47,

126.68, 118.69, 17.75.

18. 1-(m-tolyl)-1H-1,2,3-triazole-4-carboxylic acid (3ar):

1-azido-3-methylbenzene (133 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 85%,

1 pale solid. H NMR (DMSO-d6, 500 MHz): δ = 9.35 (1H, s, triazole H), 7.82 (1H, s, ArH), 7.76

13 (1H, d, ArH), 7.48 (1H, t, ArH), 7.34 (1H, d, ArH), 2.41 (3H, s, -CH3) C NMR (DMSO-d6, 125

MHz): δ = 159.88, 138.96, 138.06, 138.05, 128.09, 125.28, 119.26, 115.89, 19.21.

S15 19. 1-(4-(tert-butyl)phenyl)-1H-1,2,3-triazole-4-carboxylic acid (3as): 1-azido-4-(tert-

butyl)benzene (175 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 95%, crystalline

1 solid. H NMR (DMSO-d6, 500 MHz): δ = 9.35 (1H, s, triazole H), 7.88 (2H, d, ArH), 7.61 (2H,

13 d, ArH), 1.32 (9H, s, -CH3) C NMR (DMSO-d6, 125 MHz): δ = 162.03, 152.35, 141.05,

134.32, 127.39, 127.07, 120.69, 35.00, 31.42.

20. 1-(2,4,6-trichlorophenyl)-1H-1,2,3-triazole-4-carboxylic acid (3at): 2-azido-1,3,5-

trichlorobenzene (222 mg, 1mmol) and propiolic acid (70 mg, 1mmol) Yield: 98%,

1 crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 9.20 (1H, s, triazole H), 8.12 (3H, s,

13 ArH). C NMR (DMSO-d6, 125 MHz): δ = 161.61, 140.64, 137.38, 133.94, 132.19, 131.71,

129.59.

21. Methyl 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylate (3ba):

2,6-difluorobenzylazide (169 mg, 1mmol) and methyl propiolate (84 mg, 1mmol) Yield:

1 95%, crystalline solid. H NMR (DMSO-d6, 500 MHz): δ= 8.03 (1H, s, triazole H), 7.33 (1H,

13 tt, ArH), 6.29 (2H, m, Ar H), 5.62 (2H, s,-CH2-), 3.86 (3H, s, OCH3). C NMR (DMSO-d6, 125

MHz): δ = 162.31, 160.31, 140.24, 131.90, 127.49, 112.10, 111.89, 110.07, 52.57, 41.76.

19 F NMR (DMSO-d6, 470 MHz): δ= 113.97.

22. Methyl 1-(2,4-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylate (3bb):

2,4-difluorobenzylazide (169 mg, 1mmol) and methyl propiolate (84 mg, 1mmol) Yield:

1 85%, crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 8.86 (1H, s, triazole H), 7.51 (1H,

13 td, ArH), 7.32 (2H, ddd, ArH), 7.14 (1H, td, ArH), 5.71 (2H, s,-CH2-), 3.83 (3H, s, -CH3). C

NMR (DMSO-d6, 125 MHz): δ = 164.00, 161.84, 159.80, 139.15, 138.13, 132.78, 129.80,

19 119.15, 112.48, 104.79, 52.28, 74.23. F NMR (DMSO-d6, 470 MHz): δ= -108.99, -113.06.

S16 23. Methyl 1-(3,5-dimethylbenzyl)-1H-1,2,3-triazole-4-carboxylate (3bc):

3,5-dimethylbenzylazide (161 mg, 1mmol) and methyl propiolate (84 mg, 1mmol) Yield:

1 87%, crystalline solid. H NMR (DMSO-d6, 500 MHz): δ= 8.86 (1H, s, triazole H), 6.97 (3H,

13 d, ArH), 5.57 (2H, s,-CH2-), 3.83 (3H, s, -OCH3), 2.25 (6H, s, -CH3). C NMR (DMSO-d6, 100

MHz): δ = 161.13, 139.22, 138.43, 135.71, 130.15, 129.62, 126.19, 53.59, 52.23, 21.25.

24. Methyl 1-(4-bromobenzyl)-1H-1,2,3-triazole-4-carboxylate (3bd):

4-bromobenzylazide (340 mg, 1mmol) and methyl propiolate (84 mg, 1mmol) Yield: 89%,

1 crystalline solid. H NMR S5(CDCl3, 500 MHz): δ= 8.91 (1H, s, triazole H), 7.59 (2H, d, ArH),

13 7.32 (2H, d, Ar H), 5.66 (2H, s, -CH2-), 3.83 (3H, s, -OCH3). C NMR (DMSO-d6, 100 MHz) δ

= 161.08, 139.29, 135.31, 132.22, 130.77, 129.81, 122.10, 52.85, 52.27.

25. 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4- carboxamide (3ca):

2,6-difluorobenzylazide (169 mg, 1mmol) and propiolamide (69 mg, 1mmol) Yield: 0.89%

1 as white fibrous solid. H NMR (DMSO-d6, 500 MHz): δ= 8.55 (1H, s, triazole H), 7.85 (1H,

13 s, NH), 7.53 (1H, dt, Ar H), , 7.48 (1H, s, NH), 7.18 (2H, td, ArH), 5.73 (2H, s,-CH2-), C NMR

(DMSO-d6, 125 MHz): δ = 162.28, 161.73, 160.30, 143.29, 132.30, 127.25, 112.50, 111.52,

19 41.66. F NMR (DMSO-d6, 470 MHz): δ= 114.56.

26. 1-(2,4-difluorobenzyl)-1H-1,2,3-triazole-4- carboxamide (3cb):

2,4-difluorobenzylazide (169 mg, 1mmol) and propiolamide (69 mg, 1mmol) Yield: 0.75 %

1 crystalline solid. H NMR (DMSO-d6, 500 MHz): δ= 8.56 (1 , s, triazole H), 7.58 (1H, s, NH),

7.51 (1H, m, Ar H), 7.48 (1H, s, NH), 7.33 (1H, m, ArH), 7.15 (1H, td, ArH), 5.69 (2H, s,-

13 CH2-), C NMR (DMSO-d6, 125 MHz): δ = 163.96, 161.79, 159.79, 143.49, 135.77, 127.18,

19 119.55, 112.55, 104.80, 47.14 . F NMR (DMSO-d6, 470 MHz): δ = -109.10, -113.10.

S17 27. 1-(3,5-dimethylbenzyl)-1H-1,2,3-triazole-4-carboxamide (3cc):

dimethylbenzylazide (161 mg, 1mmol) and propiolamide (69 mg, 1mmol) Yield: 89% as

1 white fibrous solid. H NMR (DMSO-d6, 500 MHz): δ = 8.57 (1H, s, triazole H), 7.84 (1H, s,

13 NH), 7.45 (1H, s, NH), 6.98 (1H, s, ArH), 6.96 (2H, s, ArH), 5.55 (2H, s,-CH2-). C NMR

(DMSO-d6, 125 MHz): δ= 161.93, 153.74, 143.55, 138.41, 135.96, 130.09, 126.17, 125.71,

53.50, 21.27.

28. 1-(4-bromobenzyl)-1H-1,2,3-triazole-4- carboxamide (3cd):

4-bromobenzylazide (340 mg, 1mmol) and propiolamide (69 mg, 1mmol) Yield: 85% as

1 crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 8.63 (1H, s, triazole H), 7.87 (1H, s, NH),

13 7.59 (2H, d, ArH), 7.49 (1H, s, NH), 7.31 (2H, d, Ar H), 5.65 (2H, s,-CH2-). C NMR (DMSO-d6,

125 MHz): δ = 161.88, 143.64, 135.55, 132.55, 130.72, 127.24, 122.02, 52.78.

29. 2-(1-(benzyl)-1H-1,2,3-triazol-4-yl)pyridine (3et):

2-ethynylpyridine (103 mg, 1mmol) and benzyl azide (133 mg, 1mmol) Yield: 90%,

1 crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 8.70 (1H, s, triazole H), 8.60 (1H, d,

PyH), 8.05 (1H, d, PyH), 7.86, (1H, m, PyH), 7.40 (4H, t, ArH), 7.35 (3S, dt, ArH), 5.70 (2H,

13 s,-CH2-). C NMR (DMSO-d6, 125 MHz): δ =150.37, 150.08, 147.98, 137.66, 136.43,

129.27, 128.67, 128.48, 123.88, 123.46, 119.88, 53.51.

30. 3-(1-(2,6-difluorobenzyl)-1H-1,2,3-triazol-4-yl)pyridine (3dp):

3-ethynylpyridine (103 mg, 1mmol) and 2,6-difluorobenzyl azide (169 mg, 1mmol) Yield:

1 95%, white crystalline solid. H NMR (DMSO-d6, 500 MHz): δ = 8.85 (1H, s, triazole H), 7.79

13 (1H, s, ArH), 7.74 (1H, td, ArH), 7.64, (2H, m, ArH), 5.78 (2H, s,-CH2-). C NMR (DMSO-d6,

S18 125 MHz): δ = 162.36, 160.32, 149.41, 146.92, 144.18, 132.93, 132.34, 122.77, 112.54,

19 112.38, 111.56, 41.71. F NMR (DMSO-d6, 470 MHz): δ = -114.41.

Table S1: Optimization of reaction condition for azide-alkyne cycloaddition reaction under visible light irradiation:

F h F Ni-TLOP N N OH N3 OH 4M NaCl N O F O F

General reaction condition: catalyst (Ni-TLOP) variable amount, azide (2a, 1mmol) and alkyne (1b, 1 mmol), 4 Mol of NaCl in deionized water (150μl) under 1h of visible light irradiation. (a) Conversion was estimated by 1H NMR analysis.

Table S2: Effect of co-solvent:

S19 General reaction condition: photocatalyst (Ni-TLOP) 5mg , azide (2a, 1mmol) and alkyne (1b, 1 mmol), 4 Mol of NaCl in deionized water (150 μL), co-solvent (100 μL) under 6hr of visible light irradiation (a) Conversion by 1H NMR analysis.

Triazole based Pharmaceutical Compounds

NH2 O N NH H O H F S N S N N N O N N HO N O N N N S O NH2 COOH O F COOH Tazobactam Cefatrizine Inovelon/Banzel (Rufinamide) (antibiotic) (1st gen antibiotic) Lennox-Gastaut Syndrome (Epilepsy),

NH2 N N O N OH N N N O N O O O NH N N H S N O N N N O N N O O N S N O O H N HO O HHO COOH O O

Azor O O N H OH Cefoperazone O O F

Solithromycin (fluoroketolide antibiotic for S.Pneumonia & mycoplasma Pneumonia antibiotic)

Figure S1: Representative triazole based pharmaceutical compounds

S20 Figure S2: Recycling experiment for the synthesis of 1-(2,6-difluorobenzyl)-1H-1,2,3- triazole-4-carboxylate (3aa) using Ni-TLOP.

Table S3: ICP analysis of the nickel content in the triazole product (3aa) after each photocatalytic run.

The amount of nickel found in the triazole product obtained from each cycle at the end

of the photocatalytic reaction as determined by ICP analysis

S21 Figure S3: EDS Elemental mapping for Ni-TLOP.

S22

Figure S4: XPS high resolution spectra (a-g) and XPS survey analysis (h) of Ni-TLOP photocatalyst.

S23 Figure S5: HRTEM images of TLOP.

Figure S6: FESEM images of TLOP.

S24 Figure S7: FTIR spectra of Ni-TLOP before and after catalysis.

Figure S8: FESEM Analysis of Ni-TLOP before and after catalysis.

S25 Figure S9: HRTEM images of Ni-TLOP before (a, b) and after (c, d) catalysis.

Figure S10: PXRD spectra of Ni-TLOP (a) before and (b) after catalysis.

S26 Figure S11: XPS spectra of Ni-TLOP for Ni2P (a) before and (b) after catalysis.

S27 Figure S12: Crystal structure of methyl 1-(4-Bromobenzyl)-1H-1,2,3-triazole-4- carboxylate (3dd) showing ORTEP diagram with 50% probability. The hydrogen atoms are omitted for clarity.

S28 Table S4: Crystallographic data of methyl 1-(4-Bromobenzyl)-1H-1,2,3-triazole-4- carboxylate (3bd)

Methyl 1-(4-Bromobenzyl)-1H-1,2,3-triazole-4-carboxylate

Formula C11H10BrN3O Formula weight 296.12 Temperature (K) 296 Wavelength (Å) 0.71073 Crystal system Orthorhombic

Space group P212121 a (Å) 5.9656 b (Å) 12.4421 c (Å) 16.3174 α (º) 90 β (º) 90 γ (º) 90 V (Å3) 1211.15 Z 4 Calcd Density (g/cm3) 1.624 μ (mm-1) 3.387 F(000) 592.0 Crystal size (mm3) 0.24 x 0.06 x 0.06 Total reflections 2192 Unique reflections 1059 Goodness-of-fit 1.054

R1[I>2σ(I)] 0.046

wR2 (all reflections) 0.0242 CCDC deposition number 1889079

S29 Table S5: Selected bond length (Å) and bond angles (˚):

Bond Length (Å)

Br1- C1 1.890(7) C8-C7 1.451(9)

N3-C9 1.372(9) C10-O1 1.204(8)

N3-N2 1.387(8) C10-O2 1.327(8)

N3-C10 1.480(9) C7-C4 1.526(9)

C9-C8 1.310(9) C7-H7A 0.9700

C9-H9 0.9300 C7-H7B 0.9700

C1-C6 1.350(10) O2-C11 1.464(9)

C1-C2 1.372(10) C4-C5 1.365(10)

C2-C3 1.408(9) C6-C5 1.391(11)

C2-H2 0.9300 C6-H6 0.9300

C3-C4 1.365(8) C5- H5 0.9300

C3-H3 0.9300 C11-H11A 0.9600

N2-N1 1.290(9) C11-H11B 0.9600

N1- C8 1.328(8) C11-H11C 0.9600

S30 Bond Angle (˚)

C9-N3-N2 107.1(6) C8-C7-C4 112.3(6)

C9-N3-C10 132.9(6) C8-C7-H7A 109.1

N2-N3-C10 119.9(6) C4-C7-H7A 109.1

C8-C9-N3 106.0(6) C8-C7-H7B 109.1

C8-C9-H9 127.0 C4-C7-H7B 109.1

N3-C9-H9 127.0 H7A-C7-H7B 107.9

C6-C1-C2 121.3(7) C10-O2-C11 114.8(6)

C6-C1-Br1 119.1(5) C5-C4-C3 118.3(6)

C2-C1-Br1 119.6(6) C5-C4-C7 120.5(6)

C1-C2-C3 118.4(7) C3-C4-C7 121.2(6)

C1-C2-H2 120.8 C1-C6-C5 119.0(7)

C3-C2-H2 120.8 C1-C6-H6 120.5

C4-C3-C2 121.1(6) C5-C6-H6 120.5

C4-C3-H3 119.5 C4-C5-C6 121.9(7)

C2-C3-H3 119.5 C4-C5-H5 119.1

N1-N2-N3 106.7(6) C6-C5-H5 119.1

N2-N1-C8 109.9(6) O2-C11-H11A 109.5

C9-C8-N1 110.2(6) O2-C11-H11B 109.5

C9-C8-C7 129.0(6) H11A-C11-H11B 109.5

N1-C8-C7 120.8(6) O2-C11-H11C 109.5

O1-C10-O2 124.8(7) H11A-C11-H11C 109.5

O1-C10-N3 123.9(7) H11B-C11-H11C 109.5

O2-C10-N3 111.2(6)

S31 S32 Figure S13: 1H, 13C and 19F NMR of 2,6-difluoro-benzylazide (1a).

S33 Figure S14: 1H NMR, 13C and 19F NMR of 2,4-difluorobenzylazide (1b).

S34 Figure S15: 1H and 13C NMR of 3,5-dimethylbenzylazide (1c).

S35 Figure S16: 1H and 13C NMR of 4-bromobenzylazide (1d).

S36 S37 Figure S17: 1H NMR, 13C and 19F NMR 1-(azidomethyl)-2-(fluoro)benzene (1e).

S38 F

N3

Figure S18: 1H NMR, 13C and 19F NMR 1-(azidomethyl)-4-(fluoro)benzene (1f).

S39 S40 Figure S19: 1H NMR, 13C and 19F NMR of 1-(azidomethyl)-2-(trifluoromethyl)benzene (1g).

S41 Figure S20: 1H NMR, 13C and 19F NMR of 1-(azidomethyl)-3-(trifluoromethyl)benzene (1h).

S42 S43 Figure S21: 1H NMR, 13C and 19F NMR of 1-(azidomethyl)-4-(trifluoromethyl)benzene (1l).

S44 Figure S22: 1H NMR and 13C NMR of 4-(2-azidoethyl)phenol (3k).

S45 Figure S23: 1H NMR and 13C NMR of 2-(azidomethyl)naphthalene (2o).

S46 Figure S24: 1H NMR and 13C NMR benzyl azide (3p).

S47 Figure S25: 1H and 13C NMR of 1-azido-2-methylbenzene (1q).

S48 Figure S26: 1H and 13C NMR of 1-azido-3-methylbenzene (1r).

S49 Figure S27: 1H and 13C NMR of 2-azido-1,3,5-trichlorobenzene (1s).

S50 Figure S28: 1H and 13C NMR of 1-azido-4-(tert-butyl)benzene (1t).

S51 Figure S29: 1H, 13C NMR and 19F NMR of 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3aa).

S52 S53 Figure S30: 1H, 13C NMR and 19F NMR of 1-(2,4-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3ab).

S54 Figure S31: 1H and 13C NMR of 1-(3,5-dimethylbenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3ac).

S55 Figure S32: 1H and 13C NMR of 1-(4-bromobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3ad).

S56 Figure S33: 1H, 13C NMR and 19F NMR of 1-(2-fluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3ae).

S57 Figure S34: 1H, 13C NMR and 19F NMR of 1-(4-fluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (3af).

S58 S59 Figure S35: 1H, 13C NMR and 19F NMR of 1-(2-trifluoromethylbenzyl)-1H-1,2,3-triazole-4- carboxylic acid (3ag).

S60 Figure S36: 1H, 13C NMR and 19F NMR of 1-(3-trifluoromethylbenzyl)-1H-1,2,3-triazole-4- carboxylic acid (3ah).

S61 S62 Figure S37: 1H, 13C NMR and 19F NMR of 1-(4-trifluoromethylbenzyl)-1H-1,2,3-triazole-4- carboxylic acid (3ai).

S63 Figure S38: 1H and 13C NMR NMR of 1-(phenethyl)-1H-1,2,3-triazole-4-carboxylic acid (3aj):

S64 Figure S39: 1H and 13C NMR NMR of 1-(4-hydroxyphenethyl)-1H-1,2,3-triazole-4-carboxylic acid (3ak).

S65 Figure S40: 1H, 13C and 19F NMR of 1-(3-fluorophenethyl)-1H-1,2,3-triazole-4-carboxylic acid (3al).

S66 Figure S41: 1H and 13C NMR NMR of 1-(phenethyl)-1H-1,2,3-triazole-4-carboxylic acid (3am).

S67 S68 Figure S42: 1H and 13C NMR NMR of 1-(4-methylpentyl)-1H-1,2,3-triazole-4-carboxylic acid (3an):

.

S69 Figure S43: 1H and 13C NMR NMR of 1-(naphthalen-2-ylmethyl)-1H-1,2,3-triazole-4-carboxylic acid (3ao).

S70 Figure S44: 1H and 13C NMR NMR of 1-(o-tolyl)-1H-1,2,3-triazole-4-carboxylic acid (3aq)

S71 Figure S45: 1H and 13C NMR NMR of 1-(m-tolyl)-1H-1,2,3-triazole-4-carboxylic acid (3ar)

S72 Figure S46: 1H and 13C NMR NMR of 1-(4-(tert-butyl)phenyl)-1H-1,2,3-triazole-4-carboxylic acid (3as)

S73 Figure S47: 1H and 13C NMR NMR of 1-(2,4,6-trichlorophenyl)-1H-1,2,3-triazole-4-carboxylic acid (3at)

S74 Figure S48: 1H, 13C NMR and 19F NMR of methyl 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4- carboxylate (3ba).

S75 S76 Figure S49: 1H, 13C NMR and 19F NMR of methyl 1-(2,4-difluorobenzyl)-1H-1,2,3-triazole-4- carboxylate (3bb).

S77 Figure S50: 1H, 13C NMR and 19F NMR of methyl 1-(3,5-dimethylbenzyl)-1H-1,2,3-triazole-4- carboxylate (3bc).

S78 Figure S51: 1H, 13C NMR and 19F NMR of methyl 1-(4-Bromobenzyl)-1H-1,2,3-triazole-4- carboxylate (3dd).

S79 Figure S52: 1H and 13C NMR of 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4- carboxamide (3ca)

S80 S81 Figure S53: 1H and 13C NMR of 1-(2,4-difluorobenzyl)-1H-1,2,3-triazole-4- carboxamide (3cb)

S82 Figure S54: 1H and 13C NMR of 1-(3,5-dimethylbenzyl)-1H-1,2,3-triazole-4- carboxamide (3cc).

S83 Figure S55: 1H and 13C NMR of 1-(4-bromobenzyl)-1H-1,2,3-triazole-4- carboxamide (3cd).

S84 Figure S56: 1H, 13C NMR and 19F NMR of 3-(1-(2,6-difluorobenzyl)-1H-1,2,3-triazol-4-yl)pyridine (3da)

S85 Figure S57: 1H and 13C NMR of 2-(1-benzyl-1H-1,2,3-triazol-4-yl)pyridine (3et)

S86 References:

1. See http://www.ehs.ucsb.edu/units/labsfty/labrsc/factsheets/Azides_FS26.pdf. Date

accessed: 01-Aug-2017

2. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int. Ed. 2001, 40, 2004.

3. Aydin, E.; Nisanci, B.; Acar, M.; Dastan, A.; Bozdemir, Ö. A. New J. Chem, 2015, 39, 584-

554.

4. Zhao, J.; Zhao, H.; Hall, J. A.; Brown, D.; Brandes, E.; Bazzill, J.; Grogan, P. T.; Subramanium,

C.; Vielhauer, G.; Cohen, M. S.; Blagg, B. S. J. Med. Chem. Commun., 2014, 5, 1317-1323.

S87