S1

Synthesis of 2’-(1,2,3-triazoyl)-acetophenones: molecular docking and in vitro monoamine oxidase activity inhibition

Gabriel P. Costa,a Ítalo F. C. Dias,a Mariana G. Fronza,b Evelyn M. Besckow,c Jenifer Fetter,b José Edmilson R. Nascimento,a Raquel G. Jacob,a Lucielli Savegnago,b Cristiani F. Bortolatto,c César A. Brüningc* and Diego Alvesa*

a Laboratório de Síntese Orgânica Limpa - LASOL - Universidade Federal de Pelotas - UFPel - P.O. Box 354, 96010-900, Pelotas, RS, Brazil.

b Grupo de Pesquisa em Neurobiotecnologia - GPN, CDTec, Universidade Federal de Pelotas - UFPel, Pelotas, RS, Brazil.

c Laboratorio de Bioquímica e Neurofarmacologia Molecular - LABIONEM, Programa de Pós-graduação em Bioquímica e Bioprospecção - PPGBBio, Universidade Federal de Pelotas - UFPel, Pelotas, RS, Brazil.

*Corresponding authors: E-mail: cabruning@yahoo.com.br and diego.alves@ufpel.edu.br, Phone / Fax: (+) 55 53 32757533.

Contents

Optimization of conditions...........................................................................................S2

Table S1 Optimization of conditions using conventional heating to from compound 3a.................................................................................................................S3

Table S2 Optimization conditions reactional using US.............................................S4

Selected spectra of products.......................................................................................S5

Electronic Supplementary Material (ESI) for New Journal of Chemistry.This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2020

S2

Optimization of conditions

Focused on proceed the studies using the thiourea as ligand to form a new class

of 1,2,3-triazoles by CuAAC reactions, the initial conditions were based in a

previous repot in literature by our research group.1 Thus, the 2’-

azidoacetophenone 1a and phenylacetylene 2a were reacted using 10 mol% of

CuI as catalyst, thiourea as a ligand (20 mol%), DMSO as solvent, triethylamine

as base under 100 °C. After 24 h the desired product 3a was obtained in 87% yield

(Table S1, entry 1). Looking for a better condition, we screened different

temperatures from 25 to 120 °C (Table S1, entries 2-7) and we found that 60 °C is

the ideal temperature to reaction, generating the compound 3a in an excellent yield

(Table S1, entry 5).

Different polar solvents such as, ethanol, 1,4-dioxane, DMF and water were

examined, despite the formation of product in most cases, DMSO was better than

the others (Table S1, entry 5 vs. entries 8-12). The use of CuBr or CuBr2 as other

species of copper catalyst resulted in a decrease in the formation of product 3a (Table S1, entries 13-14). An excellent result was obtained when we used

Cu(OAc)2, however in view of the price, we choose CuI that is less expensive

(Table S1, entry 5 vs. entry 15). Increasing the amount of CuI from 10 to 15 mol%

leading to the formation of desired product 3a in similar yield (94%) (Table1, entry

5 vs. entry 16). Unfortunately, a significant decrease in the yield of 3a was

observed when the amount of the CuI was reduced from 10 to 5 mol% (Table S1,

entry 17).

In order to evaluate the base influence, triethylamine was changed to

diethylamine and DBU. However, in both cases the compound 3a was obtained in

lower yield compared that reactions using triethylamine (Table S1, entry 5 vs.

entries 18-19).

Subsequently, we carried out an experiment using a classic ligand in this type

of reaction. However, the use of bipyridine in amount of 20 or 10 mol% yielding the

compound 3a in 60 and 62% yield, respectively. These results suggest that

thiourea is the best ligand for this reaction (Table S1, entry 5 vs. entries 20-21).

1 G.P. Costa, R. Baldinotti, M.G. Fronza, J.E. Nascimento, Í. Dias, M.S. Sonego, F.K. Seixas, T. Collares, G. Perin, R.G.Jacob, L. Savegnago, D. Alves, ChemMedChem 2020, 15, 610-622

S3

We also examined the load of thiourea in the reaction. A decrease in the yield of

compound 3a was observed when we used 10 mol% of thiourea (Table S1, entry

5 vs. entry 22). The excellent yield relates to the use of this ligand, once when

reaction was carried out in the absence of thiourea give the desired product 3a in

only 52% yield, (Table S1, entry 5 vs. entry 23). Finally, when the reaction was

performed under air atmosphere, the compound 3a was obtained with a slight

decrease in the yield (85%) (Table S1, entry 24).Table S1 Optimization of conditions using conventional heating to from compound 3a.a

NN N

O

N3

O

1a 2a3a

+catalyst, ligand

temperature, base,solvent, 24 h

Entry Temp. (°C) Solvent Catalyst (mol%) Yield of 3a (%)

1 100 DMSO CuI (10) 872 120 DMSO CuI (10) 703 80 DMSO CuI (10) 994 70 DMSO CuI (10) 975 60 DMSO CuI (10) 986 50 DMSO CuI (10) 827 25 DMSO CuI (10) 528 60 EtOH CuI (10) 409 60 1,4-dioxane CuI (10) 12

10 60 DMF CuI (10) 7011 60 DMSO:H2O (3:1) CuI (10) 9512 60 H2O CuI (10) traces13 60 DMSO CuBr (10) 6014 60 DMSO CuBr2 (10) 6315 60 DMSO Cu(OAc)2 (10) 9516 60 DMSO CuI (15) 9417 60 DMSO CuI (5) 1218b 60 DMSO CuI (10) 9319c 60 DMSO CuI (10) 5620d 60 DMSO CuI (10) 6021e 60 DMSO CuI (10) 6222f 60 DMSO CuI (10) 7923g 60 DMSO CuI (10) 5224h 60 DMSO CuI (10) 85

a Reaction were performed using 2’-azidoacetophenone (1a) (0.25 mmol), phenylacetylene (2a) (0.25 mmol), thiourea (20 mol%), TEA (0.5 mmol), copper catalyst and solvent (0.5 mL) under N2 atmosphere. b TEA was changed by DEA. c TEA was changed by DBU. d bipy (20 mol%) was used instead thiourea. e bipy (10 mol%) was used instead thiourea. f thiourea (10 mol%) was used instead thiourea (20 mol%). g reaction without ligand. h under air atmosphere.

Since, the use of ultrasound (US) irradiation in organic synthesis

(sonochemistry) as an alternative energy source has gained popularity in the past

decades. This non-conventional energy source has been proved to be able to

S4

accelerate reactions or even to switch product profiles and selectivity’s, as well as

also able to reduce the number and amounts of side reaction products. Beyond

that, it is generally considered as an environmentally sound energy source,

comparatively less energy intensive to conventional heating and microwave

irradiation.2

Even though of good results, we next turned our attention to reduce the reaction

time. Thus, we apply the use of US irradiation as an alternative source of energy

using the same reaction conditions previous optimized, and after 30 min of reaction

under 40% amplitude, the desired 1,2,3-triazole 3a was obtained in 60% yield

(Table S2, entry 1). Aiming to improve the yield of product 3a, a mixture of

DMSO:H2O (3:1) as solvent was used giving the compound 3a in excellent yield

(Table S2, entry 2).

Different amplitude of US were screened for this reaction. When 20, 30, 50 or

60% were applied as amplitude, the compound 3a was obtained in 86, 86, 88 and

93% yield, respectively (Table S2, entries 3-6). We observed that when the

reaction time was reduced to 20 min the 1,2,3-triazole 3a was obtained in 81%

yield (Table S2, entry 7).

Table S2 Optimization conditions reactional using US.a

NN N

O

N3

O

1a 2a3a

+

CuI (10 mol%),thiourea (20 mol%)

Et3N (2 equiv)US, time,

solvent, amplitude

Entry Amplitude (%) Time (min) Yield of 3a (%)1 40 30 602b 40 30 973b 20 30 864b 30 30 865b 50 30 886b 60 30 937b 40 20 81

a Reaction was performed with 2’-azidoacetophenone (1a) (0.25 mmol), phenylacetylene (2a) (0.25 mmol), thiourea (20 mol%), TEA (0.5 mmol), CuI (10 mol%) and DMSO (0.5 mL) under air atmosphere. [b] DMSO was changed by a mixture DMSO:H2O (3:1).

2 a) G. Cravotto, P. Cintas, Chem. Soc. Rev. 2006, 35, 180-196; b) T.J. Mason, Ultrason. Sonochem. 2007, 14, 476-483; c) M. Nüchter, B. Ondruschka, A. Jungnickel, U. Müller, J. Phys. Org. Chem. 2000, 13, 579–586; d) T.J. Mason, Chem. Soc. Rev. 1997, 26, 443-451; e) L. Abenante, F. Penteado, M.M. Vieira, G. Perin, D. Alves, E.J. Lenardão, Ultrason. Sonochem. 2018, 49, 41-46; f) G. Perin, D.R. Araujo, P.C. Nobre, E.J. Lenardão, R.G. Jacob, M.S. Silva, J.A. Roehrs, PeerJ 2018, 6, e4706; g) D.M. Xavier, B.S. Goldani, N. Seus, R.G. Jacob, T. Barcellos, M.W. Paixão, R. Luque, D. Alves, Ultrason. Sonochem. 2017, 34, 107-114.

S5

SELECTED SPECTRA

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.0

1.0

2.0

1.0

2.1

1.0

2.0

1.0

-0.0

0 T

MS

2.22

7.34

7.35

7.35

7.36

7.36

7.37

7.38

7.38

7.39

7.43

7.45

7.47

7.50

7.50

7.52

7.52

7.57

7.57

7.58

7.59

7.60

7.61

7.62

7.62

7.64

7.64

7.66

7.66

7.70

7.71

7.72

7.72

7.89

7.91

8.11

Figure S1: 1H NMR (400 MHz, CDCl3) spectrum of compound 3a.

NN N

O

3a

S6

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

29.4

0

77.1

6 C

DC

l3

121.

0812

5.59

125.

9712

8.64

129.

0312

9.07

130.

0013

0.03

132.

0213

4.48

136.

4814

8.48

199.

75

126127128129130f1 (ppm)

125.

59

125.

97

128.

6412

9.03

129.

07

130.

0013

0.03

Figure S2: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3a.

NN N

O

3a

S7

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.0

3.0

2.3

1.1

2.2

1.0

2.1

1.0

0.00

TM

S

2.20

2.40

7.25

7.27

7.50

7.51

7.52

7.53

7.59

7.59

7.61

7.62

7.64

7.66

7.66

7.70

7.70

7.72

7.72

7.78

7.80

8.06

Figure S3: 1H NMR (400 MHz, CDCl3) spectrum of compound 3b.

NN N

O

3b

S8

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

21.4

4

29.4

1

77.1

6 C

DC

l3

120.

7012

5.56

125.

9112

7.21

129.

0712

9.74

129.

9613

2.00

134.

5713

6.55

138.

6014

8.63

199.

87

Figure S4: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3b.

NN N

O

3b

S9

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.1

3.0

2.1

2.1

1.0

2.1

1.0

2.0

1.0

0.00

TM

S

1.24

1.26

1.28

2.18

2.66

2.68

2.70

2.71

7.27

7.29

7.49

7.49

7.51

7.51

7.55

7.55

7.57

7.57

7.59

7.59

7.60

7.61

7.62

7.63

7.64

7.64

7.69

7.69

7.70

7.71

7.81

7.83

8.08

Figure S5: 1H NMR (400 MHz, CDCl3) spectrum of compound 3c.

NN N

O

3c

S10

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

15.5

9

28.7

729

.33

77.1

6 C

DC

l3

120.

6712

5.46

125.

9512

7.40

128.

5112

9.04

129.

9013

1.97

134.

5113

6.46

144.

9214

8.59

199.

79

Figure S6: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3c.

NN N

O

3c

S11

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

9.0

3.0

2.2

4.5

2.1

1.0

0.00

TM

S

1.35

2.17

7.46

7.48

7.54

7.56

7.59

7.61

7.63

7.65

7.70

7.72

7.84

7.86

8.30

Figure S7: 1H NMR (400 MHz, CDCl3) spectrum of compound 3d.

NN N

O

3d

S12

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

28.6

930

.80

34.1

9

77.1

6 C

DC

l3

120.

3412

4.71

125.

0812

5.34

126.

6612

8.51

129.

3413

1.50

133.

8413

5.66

147.

7615

1.11

199.

01

Figure S8: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3d.

NN N

O

3d

S13

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.0

3.0

2.0

1.0

1.0

1.1

1.0

2.0

1.0

0.00

TM

S

2.21

3.86

6.98

7.00

7.50

7.51

7.52

7.53

7.59

7.59

7.60

7.61

7.63

7.64

7.65

7.70

7.70

7.82

7.84

8.02

Figure S9: 1H NMR (400 MHz, CDCl3) spectrum of compound 3e.

NN N

O

O

3e

S14

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

29.4

2

55.4

7

77.1

6 C

DC

l3

114.

4712

0.22

122.

6912

5.53

127.

3412

9.06

129.

9313

2.00

134.

5813

6.54

148.

42

160.

02

199.

90

Figure S10: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3e.

NN N

O

O

3e

S15

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.0

3.0

1.2

1.2

1.2

2.3

1.1

1.0

1.0

1.0

0.00

TM

S

2.15

3.95

7.00

7.00

7.02

7.02

7.09

7.10

7.11

7.12

7.13

7.14

7.33

7.34

7.35

7.35

7.36

7.36

7.37

7.38

7.58

7.58

7.60

7.60

7.63

7.63

7.64

7.65

7.66

7.67

7.70

7.71

7.72

7.73

8.38

8.41

8.42

8.43

8.44

Figure S11: 1H NMR (400 MHz, CDCl3) spectrum of compound 3f.

NN N

O

O3f

S16

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

29.3

2

55.5

4

77.1

6 C

DC

l3

110.

9411

8.82

121.

1912

4.34

125.

5312

7.89

129.

0912

9.47

129.

8113

1.97

134.

8013

6.62

144.

0215

5.91

200.

00

Figure S12: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3f.

NN N

O

O3f

S17

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.0

2.1

1.0

2.2

1.1

2.1

1.0

0.00

TM

S

2.27

7.42

7.44

7.51

7.53

7.60

7.61

7.63

7.64

7.66

7.68

7.72

7.73

7.74

7.75

7.83

7.85

8.09

Figure S13: 1H NMR (400 MHz, CDCl3) spectrum of compound 3g.

NN N

O

Cl

3g

S18

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

29.5

0

77.1

6 C

DC

l3

121.

2812

5.81

127.

2712

8.64

129.

1112

9.29

130.

1613

2.10

134.

4213

4.45

136.

5014

7.42

199.

72

Figure S14: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3g.

NN N

O

Cl

3g

S19

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.0

1.0

4.2

1.0

1.0

1.0

1.0

0.00

TM

S

2.20

7.42

7.43

7.44

7.45

7.46

7.48

7.50

7.52

7.52

7.52

7.54

7.54

7.55

7.57

7.57

7.59

7.59

7.64

7.65

7.66

7.67

7.99

8.01

8.08

8.12

Figure S15: 1H NMR (400 MHz, CDCl3) spectrum of compound 3h.

NN N

O

CF33h

S20

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

29.4

2

77.1

6 C

DC

l312

0.02

121.

7912

2.69

122.

7312

2.76

122.

8012

5.09

125.

1212

5.16

125.

2012

5.43

125.

8112

8.14

129.

1312

9.57

130.

2113

0.95

131.

2613

1.59

131.

9113

2.13

134.

2713

6.31

147.

00

199.

53

131.0131.5132.0f1 (ppm)

130.

95

131.

26

131.

59

131.

91

125.0125.2125.4f1 (ppm)

125.

0912

5.12

125.

1612

5.20

122.6122.7122.8122.9f1 (ppm)

122.

6912

2.73

122.

7612

2.80

Figure S16: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3h.

NN N

O

CF33h

S21

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.0

4.7

0.9

2.8

0.9

0.9

0.9

0.00

TM

S

2.16

7.38

7.39

7.40

7.42

7.44

7.47

7.49

7.51

7.52

7.54

7.56

7.62

7.62

7.63

7.64

7.74

7.75

7.77

7.79

7.81

7.83

7.88

7.88

7.90

7.90

8.12

8.33

Figure S17: 1H NMR (400 MHz, CDCl3) spectrum of compound 3i.

NN N

O

3i

S22

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

29.4

4

77.1

6 C

DC

l312

1.39

123.

9012

4.89

125.

6312

6.46

126.

6612

7.31

127.

8912

8.35

128.

8012

9.09

130.

0313

2.04

133.

4113

3.59

134.

4613

6.43

148.

47

199.

76

Figure S18: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3i.

NN N

O

3i

S23

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

9.1

3.0

1.0

3.2

1.0

-0.0

0 T

MS

1.42

2.10

7.46

7.47

7.48

7.49

7.53

7.54

7.55

7.56

7.57

7.57

7.59

7.60

7.60

7.61

7.62

7.63

7.63

7.66

7.67

7.68

7.68

Figure S19: 1H NMR (400 MHz, CDCl3) spectrum of compound 3j.

NN N

O

3j

S24

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

29.1

130

.42

30.9

6

77.1

6 C

DC

l3

120.

1912

5.38

128.

9012

9.61

131.

8313

4.81

136.

53

158.

61

199.

98

Figure S20: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3j.

NN N

O

3j

S25

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.0

4.1

2.0

3.0

2.0

1.0

3.0

1.0

-0.0

0 T

MS

0.90

0.91

0.93

1.37

1.38

1.38

1.39

1.40

1.71

1.73

1.75

1.77

1.79

2.12

2.78

2.80

2.82

7.45

7.45

7.47

7.47

7.54

7.54

7.56

7.56

7.58

7.58

7.60

7.60

7.62

7.63

7.64

7.64

7.67

7.68

7.69

7.69

Figure S21: 1H NMR (400 MHz, CDCl3) spectrum of compound 3k.

NN N

O

3k

S26

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

14.0

622

.44

25.5

829

.09

29.1

731

.45

77.1

6 C

DC

l3

122.

2212

5.42

128.

9412

9.67

131.

8713

4.77

136.

46

149.

30

199.

92

Figure S22: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3k.

NN N

O

3k

S27

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

2.1

2.2

3.0

2.1

2.1

1.0

1.0

2.2

1.1

1.0

-0.0

0 T

MS

1.67

1.68

1.69

1.71

1.72

1.77

1.78

1.80

1.81

1.83

2.15

2.22

2.23

2.24

2.24

2.41

2.43

6.64

7.44

7.46

7.54

7.56

7.58

7.59

7.60

7.61

7.62

7.63

7.63

7.67

7.67

7.69

7.69

7.74

Figure S23: 1H NMR (400 MHz, CDCl3) spectrum of compound 3l.

NN N

O

3l

S28

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

22.2

122

.48

25.3

926

.42

29.3

1

77.1

6 C

DC

l3

119.

5812

5.28

126.

1812

6.76

128.

9612

9.69

131.

8813

4.62

136.

42

150.

20

199.

86

Figure S24: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3l.

NN N

O

3l

S29

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

11.0

1.2

0.9

2.0

0.9

0.9

0.00

TM

S

1.75

1.77

1.78

1.89

1.91

1.97

2.01

2.08

2.12

2.13

2.16

2.93

7.38

7.38

7.39

7.40

7.47

7.47

7.48

7.49

7.49

7.50

7.51

7.51

7.52

7.52

7.53

7.54

7.54

7.56

7.60

7.61

7.62

7.63

7.77

Figure S25: 1H NMR (400 MHz, CDCl3) spectrum of compound 3m.

NN N

O

HO

3m

S30

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

23.7

4

29.2

2

41.4

3

77.1

6 C

DC

l378

.98

121.

6812

5.60

129.

0212

9.86

132.

0013

4.55

136.

29

155.

14

199.

81

Figure S26: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3m.

NN N

O

HO

3m

S31

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.0

1.9

1.0

2.1

3.0

2.1

2.0

0.00

TM

S

1.93

4.23

7.08

7.09

7.09

7.10

7.11

7.11

7.12

7.12

7.13

7.17

7.19

7.21

7.27

7.27

7.29

7.29

7.45

7.45

7.47

7.47

7.49

7.49

7.50

7.51

7.51

7.53

7.53

7.57

7.58

7.58

7.60

7.60

Figure S27: 1H NMR (400 MHz, CDCl3) spectrum of compound 3r.

NN N

O

S

3r

S32

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

28.8

329

.03

77.1

6 C

DC

l3

123.

7312

5.55

126.

7712

9.08

129.

1112

9.94

129.

9713

1.96

134.

4313

5.05

136.

3314

5.87

199.

46

Figure S28: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3r.

NN N

O

S

3r

S33

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

3.0

2.1

3.2

1.0

5.2

1.0

0.00

TM

S

1.97

4.17

7.17

7.18

7.19

7.20

7.20

7.26

7.26

7.27

7.28

7.42

7.43

7.44

7.44

7.46

7.46

7.48

7.48

7.50

7.50

7.51

7.52

7.53

7.54

7.54

7.59

7.59

7.61

7.61

Figure S29: 1H NMR (400 MHz, CDCl3) spectrum of compound 3s.

NN N

O

Se

3s

S34

0102030405060708090100110120130140150160170180190200210220f1 (ppm)

20.3

7

29.1

4

77.1

6 C

DC

l3

123.

4212

5.56

127.

7112

9.09

129.

3012

9.51

129.

9713

1.96

133.

6013

4.46

136.

3914

6.52

199.

52

125126127128129130131132133134135f1 (ppm)

125.

56

127.

71

129.

0912

9.30

129.

5112

9.97

131.

96

133.

60

134.

46

Figure S30: 13C{1H} NMR (100 MHz, CDCl3) spectrum of compound 3s.

NN N

O

Se

3s

S35

200250300350400450500550600650700750f1 (ppm)

368.

14

Figure S31: 77Se{1H} NMR (76 MHz, CDCl3) spectrum of compound 3s.

NN N

O

Se

3s