Synthesis of Biologically Active Natural Products ... · Dehydrogenation of N-heterocycles in...

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Supporting Information

Reusable, Homogeneous Water Soluble Photoredox Catalyzed Oxidative Dehydrogenation of N-heterocycles in Biphasic System: Applications to

Synthesis of Biologically Active Natural Products

S. Srinatha, R. Abinayaa, Arun Prasanthb, M. Mariappanb, R. Sridharc, B. Baskara*aLaboratory of Sustainable Chemistry, Department of Chemistry, SRM Institute of Science and Technology, Kattankulatur, 603 203, Kancheepuram (Dt), Tamilnadu, India. bBioiorganic laboratory, Department of Chemistry, SRM Institute of Science and Technology, Kattankulatur, 603 203, Kancheepuram (Dt), Tamilnadu, India. cCancer Science Institute of Singapore, National University of Singapore, Singapore - 117599

Table of Contents

1. General information and mechanistic investigation S2-S62. Copy of 1H and 13C Spectra S7-S47

Electronic Supplementary Material (ESI) for Green Chemistry.This journal is © The Royal Society of Chemistry 2020

2

a) b)

Figure 1.a) Photochemical reaction set up b) Biphasic layer of the reaction mixture

Figure 2 IR spectra of CoPc (3a) and different water soluble MPc(SO3Na)4 [M = Co (3b), Fe (3c), Ni (3d) and Cu (3e)] photoredox catalysts measured using KBr pellet.

3

Figure 3 UV-Visible spectral absorbance of CoPc (3a) photoredox catalyst measured in

DMSO.

Cyclic Voltammetric Experiment:The Voltammetric experiments are analyzed in Biologic SP-300 electrochemical workstation

using Glassy carbon as working electrode, Standard calomel electrode as reference electrode,

Pt wire as counter electrode and 0.1 M TBAPF6 as supporting electrolyte in DMF with 2.0

mM solution of the sample. Ferrocene was used as an internal standard (Fig. 4). All the

experiments are performed using argon purged solutions at room temperature. High purity

dimethylformamide (DMF) was purchased from SRL. The supporting electrolyte,

tetrabutylammoniumhexafluoro phosphate (TBAPF6), was purchased from Sigma Aldrich.

4

Figure 4. Cyclic Voltammogram of Ferrocene

Figure 5. Cyclic Voltammogram of CoPc(SO3Na)4 [CoPcTs]

5

Figure 6. Cyclic voltammogram of substrate 1a measured in DMF

Calculation of the Excited State Potential of the Catalyst:The excited state potential of the catalyst can be calculated using the Rehm–Weller

formalism by employing the following equation.

(E(I*/I·‾) = E(I/I·‾) + E0,0(I*/I))

E(I/I.-) is the ground state reduction potential of the catalyst. E0-0(I*/I) is the excited state

energy of catalyst which was estimated spectroscopically. E0-0(I*/I) was calculated to be 2.74

eV.

Thereby,

E(I*/I·‾ ) = -1.01+2.74 = +1.73V (vs SCE)

6

Figure 7 Detection of superoxide anion radical through KI experiment

The produced H2O2 can be detected in the photocatalyzed dehydrogenation of tetrahydro--carboline using the procedure reported in the literature1. The color of the dehydrogenation reaction after using KI solution denotes the presence of H2O2 which can be compared to non-illuminated reactions.

The experimental steps are:

1) Four of ethanol:water (2:1) solutions (3 mL) each containing tetrahydro--carboline (10

mM) and Co catalyst (500 µM, catalyst) were prepared. Then two of them were illuminated

under standard conditions in white LED. The remaining samples are placed as such without

illumination.

2) Each of the four solutions (0.04 ml) above was diluted with water (0.9 ml).

3) 0.06 ml of KI aqueous solution (0.6M) was added into one of the diluted irradiated (IV)

and non-irradiated (I) samples respectively. The other two samples are diluted with 0.06 ml

water (II and III). It can be clearly observed that the solution in sample IV gets deeper

yellow colour than the other samples which is due to the presence of H2O2 produced in the

reaction. The sample irradiated under light without KI doesn’t produce any colour change due

to the absence of the reaction between KI and H2O2.

References:

1. S. Chen, Q. Wan, A. K. Badu-Tawiah, Angew. Chem. Int. Ed., 2016, 55, 9345-9349.

I- (Without Irradiation) Photocatalyst + Substrate + KI

II-(Without Irradiation) Photocatalyst + Substrate

III-(Irradiation) Photocatalyst + Substrate

IV-(Irradiation) Photocatalyst + Substrate + KI

7

1-Phenyl-9H-pyrido[3,4-b]indole (2a):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

1.34

1.15

1.10

2.06

1.00

2.05

1.00

1.03

1.00

2.51

2.53

7.23

7.25

7.26

7.48

7.50

7.51

7.53

7.54

7.56

7.58

7.59

7.61

7.65

7.66

7.97

7.99

8.08

8.09

8.21

8.22

8.42

8.43

7.27.47.67.88.08.28.48.6f1 (ppm)

0102030405060708090100110120130140150160170180190f1 (ppm)

-2000

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

13000

14000

15000

16000

17000

18000

19000

2000039.5

039

.67

39.8

340

.00

40.1

740

.33

40.5

0

112.

9511

4.38

120.

0112

1.35

122.

0812

8.66

128.

9112

9.01

129.

23

138.

8713

8.93

141.

6414

2.70

NH

N

HN

N

8

1-(Naphthalen-1-yl)-9H-pyrido[3,4-b]indole (2b):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1.04

3.17

1.04

1.88

0.98

1.01

1.03

1.00

2.51

7.24

7.25

7.27

7.39

7.40

7.42

7.49

7.51

7.52

7.54

7.55

7.69

7.71

7.72

8.03

8.05

8.08

8.09

8.19

8.20

8.26

8.28

8.48

8.49

7.27.47.67.88.08.28.48.68.8f1 (ppm)

0102030405060708090100110120130140150160170180190200f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

39.1

339

.30

39.4

739

.55

39.6

439

.72

39.8

0

112.

6211

4.57

120.

0612

1.17

122.

2012

5.77

126.

1812

6.59

126.

8812

7.94

128.

8212

9.02

129.

2813

1.51

134.

0413

4.94

135.

6513

8.42

141.

1914

3.02

NH

N

NH

N

9

1-(4-Methoxyphenyl)-9H-pyrido[3,4-b]indole (2c):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

2E+05

3.19

2.17

1.06

1.07

1.03

2.07

1.02

1.00

2.51

2.53

3.84

7.14

7.15

7.23

7.25

7.26

7.52

7.54

7.55

7.65

7.66

7.93

7.95

8.04

8.05

8.20

8.38

8.39

0102030405060708090100110120130140150160170180190f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

39.1

339

.29

39.4

639

.54

39.6

339

.71

39.8

0

55.7

0

112.

7911

3.86

114.

6812

0.10

121.

1812

2.01

128.

7012

9.50

130.

0813

0.95

138.

6414

1.31

142.

49

160.

05

NH

N

OMe

NH

N

OMe

10

1-(p-tolyl)-9H-pyrido[3,4-b]indole (2d)

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

55000

60000

65000

70000

75000

80000

85000

3.17

1.07

2.18

1.13

1.08

2.15

1.08

1.06

1.00

1.10

2.43

2.50

7.24

7.26

7.27

7.41

7.42

7.53

7.55

7.56

7.65

7.67

7.93

7.95

8.08

8.09

8.24

8.25

8.44

8.45

11.5

0

0102030405060708090100110120130140150160170180190200f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

21.3

9

39.5

839

.75

39.9

140

.08

40.1

740

.25

40.4

1

112.

9011

4.12

119.

9612

1.30

122.

0312

8.60

128.

7412

9.57

129.

7813

3.39

136.

0013

8.46

138.

7014

1.56

142.

72

NH

N

Me

NH

N

Me

11

1-(4-Isopropylphenyl)-9H-pyrido[3,4-b]indole (2e):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)

-20000

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

2E+05

6.34

1.03

1.02

2.07

1.04

1.00

2.04

1.03

1.02

1.00

1.22

1.24

2.51

2.92

2.94

2.95

7.23

7.24

7.26

7.42

7.43

7.52

7.54

7.55

7.64

7.66

7.89

7.90

8.06

8.07

8.20

8.22

8.39

8.40

7.07.27.47.67.88.08.28.48.6f1 (ppm)

0102030405060708090100110120130140150160170180190200f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

650024.2

1

33.7

539

.13

39.3

039

.46

39.5

539

.63

39.7

239

.80

112.

8111

4.16

120.

1112

1.15

122.

0112

7.22

128.

7112

8.74

129.

5913

3.20

136.

0613

8.67

141.

3714

2.64

149.

47

NH

N

NH

N

12

6-Methoxy-1-phenyl-9H-pyrido[3,4-b]indole (2f):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

3.10

1.09

1.10

3.16

1.03

2.06

1.01

1.00

2.51

3.85

7.18

7.19

7.20

7.56

7.57

7.59

7.97

7.98

8.09

8.37

8.38

0102030405060708090100110120130140150160170180190200f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

650039.1

239

.29

39.4

639

.54

39.6

339

.71

39.7

9

56.0

5

103.

67

113.

7411

4.48

118.

8712

1.48

128.

6612

9.11

129.

3012

9.55

133.

7813

6.27

138.

1613

8.48

142.

59

153.

99

HN

NMeO

HN

NMeO

13

1-(4-Nitrophenyl)-9H-pyrido[3,4-b]indole (2g):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

0.94

0.96

0.95

3.86

1.87

1.00

2.51

7.27

7.29

7.30

7.56

7.58

7.59

7.65

7.66

8.19

8.20

8.22

8.24

8.27

8.40

8.42

8.48

8.49

0102030405060708090100110120130140150160170180190200f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

38.9

639

.13

39.2

939

.46

39.6

339

.79

39.9

6

112.

7511

5.63

120.

4612

0.97

122.

1912

4.34

129.

2112

9.89

130.

3713

3.61

139.

0514

1.49

144.

6914

7.54

HN

N

NO2

HN

N

NO2

14

1-(4-Bromophenyl)-9H-pyrido[3,4-b]indole (2h):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

0

50000

1E+05

2E+05

Srinath-SRM-CHE-SS-EX-Br-AROMATIZEDSrinath-SRM-CHE-SS-EX-Br-AROMATIZED

1.02

1.07

2.10

2.11

1.00

1.05

1.00

2.49

2.50

2.51

2.52

3.82

7.23

7.25

7.26

7.53

7.54

7.56

7.62

7.64

7.74

7.76

7.90

7.92

8.10

8.11

8.21

8.23

8.40

8.41

NH

N

Br

0102030405060708090100110120130140150160170180190f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

7000

39.1

339

.30

39.4

739

.55

39.6

339

.72

39.8

0

112.

7611

4.76

120.

2712

2.12

122.

50

128.

9712

9.89

130.

8013

2.20

133.

2113

7.61

138.

8514

1.27

141.

39

NH

N

Br

15

6-Methoxy-1-(4-nitrophenyl)-9H-pyrido[3,4-b]indole (2i)

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-2000

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

26000

28000

30000

32000

34000

3.30

1.00

1.12

0.99

3.17

3.05

2.50

3.67

7.21

7.22

7.55

7.57

7.80

8.18

8.19

8.22

8.24

8.40

8.42

8.44

8.45

7.58.08.5f1 (ppm)

0102030405060708090100110120130140150160170180190200f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

39.1

339

.30

39.4

739

.55

39.6

439

.72

39.8

0

56.0

7

103.

84

113.

7111

5.75

119.

2612

1.38

124.

37

129.

8613

0.27

134.

1313

6.37

138.

5013

9.84

144.

7614

7.56

154.

19

100110120130140150160f1 (ppm)

HN

NMeO

NO2

HN

NMeO

NO2

16

1-(Thiophen-2-yl)-9H-pyrido[3,4-b]indole (2j):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

1.11

1.22

1.06

0.96

1.09

1.98

0.98

1.00

2.50

7.25

7.26

7.27

7.29

7.30

7.31

7.55

7.56

7.58

7.66

7.67

7.71

7.73

8.03

8.05

8.19

8.21

8.31

8.32

0102030405060708090100110120130140150160170180190f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

39.1

339

.29

39.4

639

.55

39.6

339

.71

39.8

0

112.

9711

4.39

120.

5312

1.08

122.

0312

6.16

128.

4612

9.04

129.

08

136.

8313

8.53

141.

4814

3.69

HN

N

S

HN

N

S

17

Methyl 1-phenyl-9H-pyrido[3,4-b]indole-3-carboxylate (2k):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)

-20000

0

20000

40000

60000

80000

1E+05

2E+05

3E+05

3.12

1.01

1.11

3.15

1.12

2.03

1.00

0.93

2.51

2.52

2.53

3.91

7.31

7.32

7.34

7.53

7.55

7.56

7.59

7.60

7.61

7.62

7.63

7.68

7.70

7.96

7.98

8.34

8.36

8.86

7.58.08.59.0f1 (ppm)

0102030405060708090100110120130140150160170180190200f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

39.1

239

.29

39.4

639

.54

39.6

339

.71

39.7

9

52.6

2

113.

1611

7.05

121.

0512

1.42

122.

3112

8.94

129.

3312

9.57

134.

8313

7.06

137.

7214

1.68

142.

60

166.

63

HN

N

OO

HN

N

OO

18

Methyl 1-(4-isopropylphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate (2l):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

-2000

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

26000

28000

30000

6.36

1.18

3.32

1.13

2.22

1.22

1.15

2.24

1.01

1.00

1.22

1.23

2.50

2.91

2.92

2.94

2.95

2.96

3.89

7.28

7.30

7.31

7.40

7.42

7.55

7.57

7.58

7.66

7.67

7.84

7.85

8.31

8.32

8.80

0102030405060708090100110120130140150160170180190f1 (ppm)

0

100

200

300

400

500

600

700

800

900

1000

24.8

6

34.4

539

.75

39.9

240

.09

40.2

540

.33

40.4

2

53.2

6

113.

8211

7.50

121.

6812

2.09

122.

9412

7.87

129.

6012

9.87

135.

4213

6.02

137.

6614

2.31

143.

37

150.

64

167.

33

HN

N

CO2Me

HN

N

CO2Me

19

Methyl 1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole-3-carboxylate (2m):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

55000

60000

65000

70000

75000

80000

3.11

2.22

1.09

2.12

1.04

1.05

1.00

2.59

3.99

7.40

7.42

7.43

7.68

7.70

7.71

7.82

7.83

7.85

8.16

8.41

8.43

8.88

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

39.1

239

.29

39.4

639

.54

39.6

339

.71

39.7

9

52.7

1

113.

3211

6.85

121.

3812

2.29

127.

0812

9.07

129.

2812

9.49

130.

1413

2.71

136.

7213

6.78

141.

7514

2.54

166.

20

110120130140150160170f1 (ppm)

HN

N

COOMe

S

HN

N

COOMe

S

20

Methyl 1-methyl-9H-pyrido[3,4-b]indole-3-carboxylate (2n):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

3.17

3.31

1.14

1.13

1.11

1.06

1.00

2.50

2.51

2.52

2.53

2.78

3.87

7.27

7.28

7.30

7.56

7.57

7.58

7.63

7.64

8.26

8.27

8.70

0102030405060708090100110120130140150160170180190200f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

700021.0

839

.50

39.6

639

.83

39.9

240

.00

40.0

840

.17

40.2

540

.33

40.4

240

.50

53.0

0

113.

2911

6.90

121.

3612

2.15

122.

9612

7.74

129.

54

136.

7013

7.01

141.

5714

3.31

167.

20

NH

NMeO2C

HN

N

CO2Me

21

Quinoline (5a) :

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

1.04

1.03

2.02

1.00

7.31

7.32

7.33

7.48

7.50

7.51

7.67

7.68

7.70

7.75

7.76

8.07

8.09

8.11

8.13

8.89

8.90

0102030405060708090100110120130140150160170180190200f1 (ppm)

-2000

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

26000

28000

30000

32000

34000

36000

38000

40000

77.0

377

.28

77.5

4

121.

0112

6.47

127.

7612

9.38

129.

40

135.

97

148.

2115

0.33

N

7.07.17.27.37.47.57.67.77.87.98.08.18.28.38.48.58.68.78.88.99.09.1f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

1.04

1.03

2.02

1.00

7.31

7.32

7.33

7.48

7.50

7.51

7.67

7.68

7.70

7.75

7.76

8.07

8.09

8.11

8.13

8.89

8.90

22

6-Methoxyquinoline (5b):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

0

50000

1E+05

2E+05

3E+05

4E+05

3.30

1.04

2.06

0.99

1.10

1.00

3.44

6.57

6.58

6.86

6.87

6.89

7.50

7.52

7.55

7.56

8.27

8.28

0102030405060708090100110120130140150160170180190200f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

55.5

4

76.7

977

.05

77.3

0

105.

13

121.

3712

2.28

129.

3113

0.87

134.

79

144.

45

147.

95

157.

74

N

H3CO

N

H3CO

23

6-Bromoquinoline (5c):

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

2E+05

1.07

1.03

1.02

0.97

1.11

1.00

7.26

7.39

7.40

7.41

7.75

7.76

7.77

7.95

7.96

7.97

8.89

8.90

0102030405060708090100110120130140150160170180190200f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

76.8

477

.09

77.3

4

120.

4812

1.90

129.

3412

9.81

131.

1813

2.97

135.

10

146.

78

150.

71

N

Br

N

Br

24

2-Methylquinoline (5d):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-20000

0

20000

40000

60000

80000

1E+05

2E+05

3E+05

3.18

1.00

0.98

0.97

0.98

1.91

2.75

7.27

7.28

7.47

7.48

7.50

7.67

7.68

7.70

7.76

7.77

8.03

8.04

0102030405060708090100110120130140150160170180190f1 (ppm)

0

500

1000

1500

2000

2500

3000

3500

4000

4500

Srinath-2-Methyl QuinolineSrinath-2-Methyl Quinoline 25

.36

76.8

477

.10

77.3

5

122.

0012

5.66

126.

4812

7.49

128.

6112

9.42

136.

17

147.

86

158.

98

N

25

7-Chloro-2-methylquinoline (5e):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

3.23

1.18

1.03

1.05

2.00

2.75

7.29

7.30

7.44

7.46

7.71

7.72

8.02

8.03

8.04

0102030405060708090100110120130140150160170180190f1 (ppm)

0

500

1000

1500

2000

2500

3000

25.3

8

76.8

077

.05

77.3

1

122.

2512

4.85

126.

7412

7.71

128.

72

135.

2313

5.99

148.

20

160.

24

NCl

26

6,7-dimethoxyisoquinoline (5f):

N

MeO

N

MeO

27

6,7-Dimethoxy-1-phenylisoquinoline (5g):

N

MeO

N

MeO

28

6,7-Dimethoxy-1-(4-methoxyphenyl)isoquinoline (5h):

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

-20000

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

2E+05

2E+05Srinath-SRM-CHE-SS-EX-DIMETHOXY-ANISASrinath-SRM-CHE-SS-EX-DIMETHOXY-ANISA

3.23

3.02

3.14

2.03

1.03

1.35

1.02

2.03

1.00

-0.0

0

3.81

3.83

3.97

6.98

7.00

7.04

7.19

7.34

7.39

7.40

7.59

7.60

8.38

8.39

0102030405060708090100110120130140150160170180190200f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

7000

7500

8000

8500

Srinath-SRM-CHE-SS-EX-DIMETHOXY-ANISASrinath-SRM-CHE-SS-EX-DIMETHOXY-ANISA 55

.38

55.9

356

.09

76.8

177

.06

77.3

1

105.

0110

5.71

113.

8711

8.45

122.

55

130.

9313

2.54

133.

81

141.

33

149.

9115

2.58

158.

0015

9.83

N

MeO

OMe

N

MeO

OMe

29

1-(4-Isopropylphenyl)-6,7-dimethoxyisoquinoline (5i):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-20000

0

20000

40000

60000

80000

1E+05

2E+05

3E+05

3E+05Srinath-SRM-CHE-SS-EX-DIMETHOXY IPASrinath-SRM-CHE-SS-EX-DIMETHOXY IPA

6.25

1.14

3.34

3.17

1.14

2.10

2.06

2.07

1.00

1.21

1.22

2.87

2.88

2.90

2.91

2.93

3.76

3.90

6.98

7.27

7.29

7.33

7.34

7.53

7.55

8.34

8.35

0102030405060708090100110120130140150160170180190f1 (ppm)

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

55000

60000

65000

70000

75000Srinath-SRM-CHE-SS-EX-DIMETHOXY IPASrinath-SRM-CHE-SS-EX-DIMETHOXY IPA 23

.98

34.0

0

55.9

056

.00

76.9

577

.21

77.4

6

104.

9910

5.73

118.

5412

2.44

126.

5312

9.59

133.

7613

7.51

141.

31

149.

1614

9.89

152.

55

158.

27

N

MeO

N

MeO

30

1-(4-Chlorophenyl)-6,7-dimethoxyisoquinoline (5j):

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

0

50000

1E+05

2E+05

Srinath-SRM-CHE-SS-EX-DIMETHOXY CHLOROSrinath-SRM-CHE-SS-EX-DIMETHOXY CHLORO

3.17

3.13

1.03

1.04

3.05

2.05

1.00

3.70

3.85

6.92

7.12

7.31

7.32

7.34

7.36

7.49

7.50

8.29

8.30

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

Srinath-SRM-CHE-SS-EX-DIMETHOXY CHLOROSrinath-SRM-CHE-SS-EX-DIMETHOXY CHLORO 55

.76

55.9

3

77.0

877

.34

77.5

9

104.

9010

4.98

118.

9612

2.25

128.

5613

0.94

133.

6913

4.37

138.

4614

1.23

150.

0915

2.61

156.

72

N

MeO

Cl

N

MeO

Cl

31

6,7-Dimethoxy-1-(4-nitrophenyl)isoquinoline (5k):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

0

50000

1E+05

2E+05

3E+05

4E+05

5E+05

Srinath-SRM-CHE-SS-EX-DIMETHOXY NITRO-FASrinath-SRM-CHE-SS-EX-DIMETHOXY NITRO-FA

3.13

3.17

1.02

1.03

1.02

2.03

1.99

1.00

3.80

3.99

7.09

7.14

7.50

7.51

7.82

7.83

8.32

8.33

8.42

8.43

0102030405060708090100110120130140150160170180190200f1 (ppm)

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

Srinath-SRM-CHE-SS-EX-DIMETHOXY NITRO-FASrinath-SRM-CHE-SS-EX-DIMETHOXY NITRO-FA 55

.99

56.2

1

76.8

177

.07

77.3

2

104.

3210

5.21

119.

8312

2.35

123.

74

130.

65

133.

95

141.

4614

6.51

147.

8115

0.65

153.

0015

5.56

N

MeO

NO2

N

MeO

NO2

32

6,7-Dimethoxy-1-(thiophen-2-yl)isoquinoline (5l):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

Srinath-Dimethoxy ThiopheneSrinath-Dimethoxy Thiophene

3.24

1.06

1.01

1.06

0.95

1.04

1.10

1.00

3.90

3.95

7.01

7.02

7.12

7.36

7.43

7.44

7.52

7.72

8.33

8.35

0102030405060708090100110120130140150160170180190f1 (ppm)

-200

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

1900

2000

2100

56.0

056

.08

76.8

377

.08

77.3

4

105.

0710

5.17

118.

80

122.

0812

7.41

127.

5112

7.61

134.

02

141.

2914

3.45

150.

5115

1.10

152.

69

MeO

MeON

S

MeO

MeON

S

33

Indole (7a):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

55000

60000

65000

70000

75000

80000

85000

90000Srinath-SRM-CHE-SS-EX-INDOLESrinath-SRM-CHE-SS-EX-INDOLE

0.99

0.98

1.07

1.01

1.00

0.98

1.62

6.63

7.20

7.24

7.28

7.44

7.45

7.72

7.74

8.13

0102030405060708090100110120130140150160170180190200f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

Srinath-SRM-CHE-SS-EX-INDOLESrinath-SRM-CHE-SS-EX-INDOLE 77

.02

77.2

877

.53

102.

57

111.

32

119.

9912

0.90

122.

1212

4.49

127.

96

135.

88

NH

34

2-Methylindole (7b):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

3.31

0.94

1.98

1.15

1.11

1.00

2.46

6.27

7.11

7.15

7.18

7.30

7.31

7.56

7.58

7.83

0102030405060708090100110120130140150160170180190f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

300013

.72

76.8

477

.10

77.3

5

100.

39

110.

28

119.

6612

0.95

129.

09

135.

1313

6.08

NH

35

5-Methoxyindole (7c):

3.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.28.48.6f1 (ppm)

0

50000

1E+05

2E+05

3E+05

4E+05

5E+05

3.29

1.00

1.01

0.98

1.01

0.97

1.02

3.87

6.49

6.50

6.87

6.89

7.12

7.13

7.18

7.19

7.26

7.28

7.29

8.07

0102030405060708090100110120130140150160170180190200f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

55.9

5

76.9

277

.17

77.4

3

102.

3310

2.40

111.

9011

2.37

125.

0912

8.34

131.

07

154.

20

NH

MeO

NH

MeO

36

5-Nitroindole (7d):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

0.98

1.01

0.99

1.00

0.83

1.67

6.73

6.74

7.26

7.38

7.39

7.44

7.46

8.10

8.11

8.12

8.13

8.61

8.62

8.71

0102030405060708090100110120130140150160170180190200f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

3200Srinath-SRM-CHE-SS-EX-NO2 INDOLESrinath-SRM-CHE-SS-EX-NO2 INDOLE 76

.80

77.0

577

.31

105.

09

111.

08

117.

7211

8.05

127.

2612

7.42

138.

8314

1.95

NH

O2N

NH

O2N

37

5-Cyanoindole (7e):

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

2E+05

1.04

0.10

1.02

1.03

1.00

1.01

1.80

6.63

6.64

7.35

7.36

7.42

7.47

7.48

7.99

8.78

0102030405060708090100110120130140150160170180190200f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

76.8

577

.10

77.3

6

102.

6010

3.37

112.

12

121.

0112

4.82

126.

4312

6.63

127.

69

137.

60

NH

NC

NH

NC

38

5- Bromoindole (7f):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

2E+05

1.03

0.96

1.80

1.00

0.89

1.58

6.50

6.51

7.21

7.22

7.26

7.27

7.78

8.20

0102030405060708090100110120130140150160170180190f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

600076.7

577

.00

77.2

5

102.

19

112.

4311

2.92

123.

1212

4.74

125.

3712

9.54

134.

31

NH

Br

NH

Br

39

5-Bromo-7-nitro indole (7g):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

55000

60000

65000

70000

1.04

1.05

1.02

1.00

1.05

-0.0

0

6.60

6.61

7.35

7.36

8.02

8.03

8.21

9.87

0102030405060708090100110120130140150160170180190200f1 (ppm)

-200

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

1900

2000

76.7

777

.02

77.2

8

103.

60

111.

35

121.

64

127.

9212

8.14

131.

1113

3.16

NH

Br

NO2

NH

Br

NO2

40

7-Azaindole (7h):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

0.98

1.01

1.00

0.93

2.37

6.52

6.53

7.11

7.12

7.40

7.41

7.98

8.35

8.36

11.4

9

0102030405060708090100110120130140150160170180190200f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

240076.8

277

.07

77.3

3

100.

57

115.

7512

0.59

125.

4012

9.10

142.

31

148.

86

HNN

41

Ethyl indole-2-carboxylate (7i):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

3.29

2.14

1.03

1.02

1.00

0.99

1.44

1.45

1.47

4.44

4.45

4.47

4.48

7.17

7.18

7.20

7.27

7.34

7.35

7.37

7.45

7.47

7.72

7.73

9.17

0102030405060708090100110120130140150160170180190f1 (ppm)

-200

-100

0

100

200

300

400

500

600

700

800

900

1000

1100

1200

1300

1400

1500

1600

1700

1800

1900

2000

210014.4

2

61.0

9

76.8

177

.06

77.3

2

108.

68

111.

93

120.

7912

2.61

125.

3512

7.51

136.

93

162.

21

NH

O

NH

O

42

Eudistomin U (9a)

NH

N

HN

NH

N

HNH

43

9H-pyrido[3,4-b]indole (11a):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

1.06

1.07

0.96

1.07

1.05

1.06

1.00

2.51

7.22

7.23

7.54

7.55

7.59

7.61

8.09

8.19

8.20

8.31

8.89

0102030405060708090100110120130140150160170180190f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

39.1

239

.29

39.4

639

.54

39.6

239

.71

39.7

9

112.

3611

5.29

119.

9512

0.87

122.

27

128.

1612

8.86

134.

0913

6.21

138.

2914

0.90

HN

N

HN

N

44

1-Methyl-9H-pyrido[3,4-b]indole (13a):

0102030405060708090100110120130140150160170180190f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

20.3

8

39.1

339

.30

39.4

739

.55

39.6

339

.72

39.8

0

112.

3911

3.34

119.

9412

1.30

122.

2512

7.62

128.

61

134.

7313

7.51

140.

7714

2.37

105110115120125130135140145f1 (ppm)

NH

N

CH3

NH

N

CH3

45

1-(Furan-2-yl)-9H-pyrido[3,4-b]indole (15a):

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-20000

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

2E+05

0.98

1.99

1.04

1.00

0.93

1.04

1.02

1.00

2.50

6.75

7.24

7.26

7.54

7.56

7.57

7.74

7.76

7.95

8.03

8.04

8.19

8.20

8.32

8.33

6.87.07.27.47.67.88.08.28.4f1 (ppm)

0102030405060708090100110120130140150160170180190200f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

3200

3400

39.1

239

.29

39.4

639

.54

39.6

239

.71

39.7

9

109.

4111

2.74

112.

9711

4.36

120.

2912

0.78

122.

03

129.

0313

0.02

130.

8813

3.35

138.

4314

1.43

144.

35

153.

25

NH

N

O

NH

N

O

46

Methyl 1-(furan-2-yl)-9H-pyrido[3,4-b]indole-3-carboxylate (18a):

.

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-20000

0

20000

40000

60000

80000

1E+05

2E+05

3E+05

3.08

1.04

1.10

1.03

1.10

1.08

1.02

1.09

1.00

2.49

2.50

2.51

3.89

6.74

6.75

7.26

7.31

7.32

7.75

7.76

7.95

8.23

8.25

8.70

0102030405060708090100110120130140150160170180190f1 (ppm)

-500

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

5500

6000

6500

7000Srinath-SRM-CHE-SS-EX-TRY ESTFLSrinath-SRM-CHE-SS-EX-TRY ESTFL 39

.67

39.8

340

.00

40.0

840

.17

40.2

540

.34

53.1

7

111.

0011

3.33

113.

8311

7.21

121.

5912

1.62

122.

68

129.

8713

0.37

132.

8713

3.76

137.

1814

2.22

145.

24

153.

00

166.

83

NH

N

CO2Me

O

NH

N

CO2Me

O

47

1-(3,4-Dihydroquinolin-1(2H)-yl)ethanone (20)

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

55000

60000

65000

70000

75000

80000

85000Srinath-1-Acetyl quinolineSrinath-1-Acetyl quinoline

2.12

3.30

2.01

2.00

3.90

1.85

1.86

1.88

1.89

1.90

2.15

2.62

2.64

2.65

3.70

3.71

7.02

7.04

7.06

7.08

7.09

7.10

7.12

0102030405060708090100110120130140150160170180190200f1 (ppm)

0

1000

2000

3000

4000

5000

6000

7000

8000

900023.1

424

.05

26.8

8

76.9

177

.17

77.4

2

124.

5812

5.15

126.

0712

8.42

170.

06

N

OH3C

N

OH3C

Synthesis of Biologically Active Natural Products ... · Dehydrogenation of N-heterocycles in...

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