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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 reactionDolly 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:jobaeg@krict.re.kr

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

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

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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

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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,

deposit@ccdc.cam.ac.uk) 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.

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3. Synthetic Procedure:

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

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

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

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,

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

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

s, ArH), 7.65 (1H, d, ArH), 7.52 (1H, d, ArH), 7.13 (1H, dd, ArH). 13C 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,

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

d, ArH), 7.52 (1H, d, ArH), 7.13 (1H, dd, ArH). 13C 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

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

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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),

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

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

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

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

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

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

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

113.54, -109.15.

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

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

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

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

(2H, d ArH), 7.09 (2H, d, ArH), 4.20 (2H, s, -CH2-).13C 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

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

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

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

MHz): δ = -117.98.

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

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

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

161.67, 131.21, 131.18, 123.73, 115.80, 54.07. 19F 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,

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

ArH), 7.44 (1h, t, ArH), 4.67 (2H, s, -CH2-). 19F 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,

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

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

123.15, 120.98, 54.48. 19F 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,

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

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

NMR (CDCl3, 470 MHz): δ = -62.67.

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

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

ArH), 7.15 (3H, m, ArH), 3.49 (2H, t, -CH2-), 3.09 (2H, t, -CH2-).13C 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)

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

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

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

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

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

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

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

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

(5H, m, ArH), 4.62 (1H, q, -CH-), 1.53 (3H, d, -CH3).13C 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

mmol) NaN3 (97.5 mg, 1.5 mmol). colorless oil, Yield: 70 %. 1H 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,

-CH3).13C 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 mmol) NaN3 (97.5g 1.5 mmol). 1H NMR (CDCl3, 500 MHz): δ = 7.86 (3H, m, ArH), 7.81

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

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

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

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

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

21.36.

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

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

117.90, 17.24.

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

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

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

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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%,

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

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

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

52.29. 19F 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%,

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

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

104.09, 52.28, and 47.84. 19F 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%,

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

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triazole H), 6.96 (2H, d, ArH), 5.55 (2H, s,-CH2-), 2.25 (6h, s, -CH3). 13C 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%,

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

ArH), 7.31 (2H, d, ArH), 5.64 (2H, s,-CH2-). 13C 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%,

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

ArH), (1H, d, ArH), (2H, d, ArH), 5.72 (2H, s,-CH2-). 13C 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

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

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

1mmol) Yield: 95%, white solid. 1H 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-).

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

126.94, 126.73, 125.65, 123.47, 52.29. 19F 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,

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

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

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

123.37, 52.78. 19F 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,

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

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

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

52.82. 19F 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

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

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

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):

S14

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

crystalline solid. 1H 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,

s,-CH2-). 13C 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:

98% as crystalline solid. 1H 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, s,-CH2-). 13C 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

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

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

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%

as crystalline solid. 1H 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-)

S15

0.84 (6H, d, -CH3). 13C 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-(azidomethyl)naphthalene (183 mg, 1 mmol) and NaN3 (70 mg 1.5 mmol). 1H NMR

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

(2H, m, ArH), 7.49 (1H, dd, ArH), 5.83 (2H, s, -CH2-).13C 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)

13C 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%,

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

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

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

S16

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

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

d, ArH), 1.32 (9H, s, -CH3) 13C 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%,

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

ArH). 13C 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:

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

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

19F 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:

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

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

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

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

S17

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:

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

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

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

7.32 (2H, d, Ar H), 5.66 (2H, s, -CH2-), 3.83 (3H, s, -OCH3). 13C 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%

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

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

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

41.66. 19F 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 %

crystalline solid. 1H 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,-

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

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

S18

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

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

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

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

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

crystalline solid. 1H 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,

s,-CH2-). 13C 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:

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

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

S19

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

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

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

light irradiation:

N3

O

OH Ni-TLOP

h

NNN

O

OH4M NaCl

F

F

F

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:

S20

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.

HOO

HN

NO

NH2

COOH

S

S

NHNN

Cefatrizine(1st gen antibiotic)

NO

SO OH

COOH

N NN

Tazobactam(antibiotic)

F

F

NNN

NH2

O

Inovelon/Banzel (Rufinamide)Lennox-Gastaut Syndrome

(Epilepsy),

NN

OH

OO

OO

O

NNNNH

Azor

HOO

HN

NO

NH

COOH

S

S

NNN

N

N

O

N

O

O

CefoperazoneO

O

O O

NHHO

O

N

NN

NH2

F

O

O O

HN

OH

Solithromycin(fluoroketolide antibiotic forS.Pneumonia & mycoplasma

Pneumoniaantibiotic)

Triazole based Pharmaceutical Compounds

Figure S1: Representative triazole based pharmaceutical compounds

S21

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

S22

Figure S3: EDS Elemental mapping for Ni-TLOP.

S23

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

S24

Figure S5: HRTEM images of TLOP.

Figure S6: FESEM images of TLOP.

S25

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

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

S26

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.

S27

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

S28

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.

S29

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

S30

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

S31

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)

S32

S33

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

S34

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

S35

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

S36

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

S37

S38

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

S39

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

N3

F

S40

S41

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

S42

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

S43

S44

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

S45

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

S46

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

S47

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

S48

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

S49

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

S50

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

S51

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

S52

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

S53

S54

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

S55

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

S56

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

S57

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

S58

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

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

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

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

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

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

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

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

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

.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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.