Kasagani Veera Prasad, Kurma Siva Hariprasad, Bhimapaka ... · Kasagani Veera Prasad, Kurma Siva Hariprasad, Bhimapaka China Raju* Organic Synthesis and Process Chemistry Division,

A facile construction of oxygen heterocycles by the reaction of benzoxepine-4-carboxylates with dihaloalkanes

and activated alkynesKasagani Veera Prasad, Kurma Siva Hariprasad, Bhimapaka China Raju*

Organic Synthesis and Process Chemistry Division,

CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India.

E-mail: [email protected]

Homepage: http://www.iictindia.org

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

mailto:[email protected]

http://www.iictindia.org/

Supporting Information

1. General information S2

2. General Procedure for the preparation of benzoxepine-4-carboxylates &

Spectrums S2-S5

3. 1H & 13C NMR spectras of Naphthoate S6-S7

4. Optimization of reaction conditions for the preparation of 8a S7

3. 1H NMR, 13C NMR and HRMS spectras of the compounds S8-S60

1. General information:

Salicylaldehydes and ethyl 4-chloro-3-oxobutanoate were procured from Sigma-Aldrich.

Triphenylphosphine, 2-bromopropionate, dichloromethane, 1,2-dichloroethane, 1,3-

dibromopropane, 1,4-dibromobutane, TBAB, KHCO3, 18-crown-6, TBAI and solvents were

obtained from local suppliers. 1H NMR and 13C NMR spectra were recorded on a Avance 400

MHz and 500 MHz spectrometer in CDCl3 using TMS as internal standard. IR spectra were

recorded on a Nicollet 740 FTIR spectrometer. Mass spectra were obtained on Agilent LCMS

instrument. HRMS were measured on Agilent Technologies 6510, Q-TOFLC/MS ESI-

Technique. Melting points were determined in open glass capillary tubes on a Stuart melting

point apparatus and are uncorrected. All reactions were monitored by thin layer

chromatography (TLC) on pre-coated silica gel 60 F254 (mesh); spots were visualized under

UV light. Merck silica gel (60-120 mesh) was used for chromatography.

2. General Procedure for the reparation of benzoxepine-4-carboxylates 1a-h: A mixture

of ethyl 2-(chloromethyl)-2-hydroxy-2H-chromene-3-carboxylate (268 mg, 1.0 mmol) and

(1-ethoxycarbonylethylidene)triphenylphosphorane (506 mg, 1.4 mmol) in dry CH2Cl2 (4

mL) were stirred at the room temperature for 6 h (TLC) under nitrogen atmosphere. After

completion of the reaction (TLC), the solvent was evaporated under reduced pressure, crude

residue was purified by column chromatography (hexane/ethyl acetate 9:1) afforded (E)-ethyl

3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate 1a (190 mg, 90% yield) as yellow liquid.

The remaining benzoxepine compounds 1b-h have been prepared by the reaction of 2H-

chromene-3-carboxylates with Wittig salt.

(E)-Ethyl 3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1a):

Pale yellow liquid, Yield: 90%; FT-IR (KBr): 3451, 2981, 2925, 1728, 1675, 1605, 1565,

1482, 1447, 1394, 1284, 1250, 1189, 1115, 1041 cm-1. 1H NMR (CDCl3) : δ 1.33 (t, J = 6.9

Hz, 3H, CH3), 4.34 (q, J = 6.9 Hz, 2H, OCH2), 4.58 (s, 2H, OCH2), 7.12-7.24 (m, 2H,

aromatic), 7.38-7.52 (m, 2H, aromatic), 7.89 (s, 1H, aromatic) ppm. 13C NMR (CDCl3): δ

14.21, 61.28, 78.15, 120.46, 124.25, 125.7, 132.14, 133.45, 134.87, 145.39, 159.46, 165.30,

191.50 ppm. MS-ESI: 233 [M+H]+, 255 [M+Na]+. HRMS-ESI: Calcd for C13H13O4 [M+H]+

233.0808; found 233.0812.

(E)-Ethyl 7-bromo-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1b):

Colourless solid, Yield: 73%; FT-IR (KBr): 2923, 2854, 2854, 1711, 1680, 1605, 1474,

1379, 1285, 1255, 1224, 1191, 1115, 1038 cm-1. 1H NMR (CDCl3) : δ 1.38 (t, J = 7.0 Hz, 3H,

CH3), 4.33 (q, J = 7.0 Hz, 2H, OCH2), 4.57 (s, 2H, OCH2), 7.05 (d, J = 8.7 Hz, 1H, aromatic),

7.50 (dd, J = 2.5, J = 8.7 Hz, 1H, aromatic), 7.63 (d, J = 2.0 Hz, 1H, aromatic), 7.77 (s, 1H,

aromatic) ppm. 13C NMR (CDCl3): δ 14.26, 61.90, 78.54, 116.92, 122.58, 127.46, 131.74,

136.43, 136.82, 144.01, 158.48, 165.21, 192.10 ppm. MS-ESI: 333, 335 [M+Na]+. HRMS-

ESI : Calcd for C13H11BrO4Na [M+Na]+ 332.9733; found 332.9741.

(E)-Ethyl 7-chloro-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1c):

Colourless solid, Yield: 88%; FT-IR (KBr) : 2922, 1714, 1681, 1607, 1477, 1384, 1274,

1193, 1105 cm-1.1H NMR (CDCl3): δ 1.37 (t, J = 7.3 Hz, 3H, CH3), 4.32 (q, J = 7.3 Hz, 2H,

OCH2), 4.56 (s, 2H, OCH2), 7.09 (d, J = 8.5 Hz, 1H, aromatic), 7.35 (d, J = 8.5 Hz, 1H,

aromatic), 7.47 (s, 1H, aromatic), 7.76 (s, 1H, aromatic) ppm. 13C NMR (CDCl3) : δ 14.26,

61.84, 78.40, 122.18, 126.80, 129.60, 130.52, 133.34, 133.81, 143.75, 157.96, 165.01, 191.81

ppm. MS-ESI: 267, 269[M+H]+, 289, 291 [M+Na]+. HRMS-ESI : Calcd for C13H11ClO4Na

[M+Na]+ 289.0238; found 289.0236.

(E)-Ethyl 3-oxo-7-phenyl-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1d): The title

compound 1d was prepared by the reaction of ethyl 2-(chloromethyl)-2-hydroxy-6-phenyl-

2H-chromene-3-carboxylate (1.0 mmol) with Ph3P=C(CH3)CO2C2H5 (3.0 mmol). The crude

compound was directly utilized for the further reaction, since the compound was rearranging

in to its corresponding ethyl 3,4-dihydroxy-2-naphthoate during the column chromatography.

(E)-Ethyl 7-methoxy-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1e):


1389, 1244, 1209, 1164, 1039 cm-1. 1H NMR (CDCl3): δ 1.38 (t, J = 7.0 Hz, 3H, CH3), 3.81

(s, 3H, OCH3), 4.32 (q, J = 7.0 Hz, 2H, OCH2), 4.54 (s, 2H, OCH2), 6.91-6.98 (m, 2H,

aromatic), 7.06 (d, J = 8.8 Hz, 1H, aromatic), 7.80 (s, 1H, aromatic) ppm. 13C NMR (CDCl3):

δ 14.29, 55.70, 61.62, 79.21, 117.64, 120.05, 121.67, 126.46, 128.13, 132.66, 145.24, 153.50,

155.91, 165.50 ppm. MS-ESI: 263 [M+H]+, 285 [M+Na]+. HRMS-ESI: Calcd for

C14H14O5Na [M+Na]+5.0733; found 285.0726.

(E)-Ethyl 8-methoxy-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1f): Pale yellow

liquid, Yield: 61%; FT-IR (KBr): 3056, 2986, 1728, 1671, 1608, 1438, 1186, 1119, 1027

cm-1. 1H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 7.1 Hz, 1H), 7.44 (d, J = 8.7 Hz, 1H), 6.76

(dd, J = 8.7, 2.5 Hz, 1H), 6.67 (d, J = 2.4 Hz, 1H), 4.58 (s, 2H), 4.39-4.29 (m, 2H), 3.87 (s,

3H), 1.42-1.34 (m, 3H) ppm. 13C NMR (126 MHz, CDCl3): δ 191.0, 165.9, 164.6, 161.8,

147.3, 137.2, 128.4, 118.3, 111.5, 104.8, 77.7, 61.5, 55.8, 14.2 ppm. MS-ESI: m/z 263

[M+H]+; HRMS-ESI: calcd for C14H15O5 [M+H]+ 263.0914; found 263.0906.

(E)-Ethyl 7-methyl-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1g):


1390, 1241, 1201, 1163, 1036 cm-1. 1H NMR (CDCl3): δ 1.37 (t, J = 7.0 Hz, 3H, CH3), 2.54

(s, 3H, CH3), 4.28 (q, J = 7.0 Hz, 2H, OCH2), 4.52 (s, 2H, OCH2), 6.90-6.97 (m, 2H,

aromatic), 7.03 (d, J = 8.8 Hz, 1H, aromatic), 7.75 (s, 1H, aromatic) ppm. 13C NMR (CDCl3):

δ 14.18, 54.74, 61.16, 78.25, 116.40, 119.02, 121.21, 126.28, 127.94, 132.18, 145.12, 153.08,

154.91, 165.30 ppm. MS-ESI: 247 [M+H]+. HRMS-ESI: Calcd for C14H14O4Na [M+Na]+

269.0813; found 269.0826.

(E)-Ethyl- 9-methyl-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1h):

Yellow colour liquid; Yield: 72%; FT-IR (KBr): 2924, 1729, 1672, 1604, 1573, 1491, 1460,

1391, 1241, 1207, 1165, 1034 cm-1. 1H NMR (CDCl3): δ 7.89 (s, 1H, aromatic), 7.26 (d, J =

7.7 Hz, 2H, aromatic), 7.03 (t, J = 7.6 Hz, 1H, aromatic), 4.55-4.52 (q, J = 7.0 Hz, 2H,

OCH2), 4.32-4.24 (m, 2H, OCH2), 2.24 (s, 3H, CH3), 1.33-1.27 (t, J = 7.0 Hz, 3H, CH3) ppm. 13C NMR (CDCl3) : δ 193.00, 165.81, 157.87, 146.65, 135.45, 132.88, 131.56, 129.96,

125.65, 124.04, 78.30, 61.69, 16.12, 14.25 ppm. MS-ESI : 247 [M+H]+.

3. 1H NMR & 13C NMR spectras of Naphthoate

Intermediate compound Naphthoate

0011223344556677889910101111

1.0 1.0 1.0

1.1

1.1

1.0

2.0

3.0

1.0

30-07.13-238-BCR-CATECHOL

CO2C2H5

OHOH

-1-10011223344556677889910101111

1.8 2.0

3.2

1.0

2.2

05.07.13-212-BCR-DO-CAT

CO2C2H5

ODOD

1H NMR Spectrum of D2O exchange Naphthoate compound

13C NMR Spectrum of intermediate Naphthoate compound

4. Optimization of reaction conditions for the preparation of 8a

Entry Base (equiv.) Time [h] Yieldc

01a

02a

03a

05a

06a

08a

13a

11a

12a

KHCO3 (3.0)KHCO3 (3.0)

KHCO3 (3.0)

KHCO3 (3.0)

Et3N (2.0)DBU (2.0)

Cs2CO3 (3.0)K2CO3 (3.0)

1624

1618

18

2012

1618

0800

1219

24

1000

05

____________________________________________________________________

____________________________________________________________________

____________________________________________________________________

Additive (equiv.)

TBAB (1.0)TPP (1.0)

TBAB (1.0)TBAB (1.0)

------

------

a Reflux, bRoom temperature,c Isolated yield.

05

O

CO2C2H5

O O

O

CO2C2H5

+

CO2C2H5

CO2C2H5

CO2C2H5

CO2C2H5

1a 7a 8a

Solvent

MeCN

EtOHtert-Butanol

---

KHCO3 (3.0)

tert-Butanol

tert-Butanoltert-Butanoltert-Butanoltert-Butanol

10aNaHCO3 (3.0) 24 17--- tert-Butanol09bKHCO3 (3.0) 32 05tert-Butanol

07aKHCO3 (3.0) 16 1118-Crown-6 (1.0) tert-Butanol

---

04aKHCO3 (3.0) 14 05TBAB (1.0) Toluene

MeCN

5. 1H-NMR, 13C-NMR and HRMS Spectras of target compounds 3a-g, 4a-h, 4ha, 5a-c,

6a-c, 8a-f

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.25

2.16

2.13

1.06

1.07

0.99

1.10

1.00

0.00

1.43

1.45

1.46

4.44

4.45

4.47

4.48

6.29

7.26

7.36

7.36

7.36

7.37

7.38

7.50

7.50

7.51

7.51

7.51

7.53

7.79

7.85

7.87

8.09

1H-NMR Spectrum of compound 3a

0102030405060708090100110120130140150160170

14.4

1

61.3

1

76.7

977

.05

77.3

0

102.

53

114.

53

119.

7312

1.65

124.

2412

4.77

128.

2212

8.95

129.

49

142.

49

164.

58

13C-NMR Spectrum of compound 3a

O

O

CO2C2H5

O

O

CO2C2H5

O

O

CO2C2H5

HRMS Spectrum of Compound 3a

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0

3.19

2.16

2.14

1.01

1.02

1.00

1.04

0.00

1.42

1.44

1.46

4.43

4.45

4.47

4.48

6.29

7.26

7.56

7.57

7.66

7.68

7.98

8.01

8.02

1H-NMR Spectrum of compound 3b

-100102030405060708090100110120130140150160170

14.3

8

61.4

9

76.7

477

.05

77.3

7

102.

82

115.

4311

8.53

119.

7912

1.50

123.

14

129.

7913

1.23

131.

45

142.

8714

2.97

164.

17

13C-NMR Spectrum of compound 3b

O

O

CO2C2H5

Br

O

O

CO2C2H5

Br

HRMS Spectrum of Compound 3b

O

O

CO2C2H5

Br

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.11

2.18

2.21

1.00

1.01

1.01

1.00

0.00

1.43

1.44

1.46

4.44

4.45

4.46

4.48

7.26

7.42

7.43

7.44

7.44

7.73

7.75

7.83

7.83

7.98

1H-NMR Spectrum of compound 3c

0102030405060708090100110120130140150160170

14.3

8

61.4

8

76.7

377

.05

77.3

6

102.

79

115.

4911

9.65

121.

4912

3.14

127.

9012

9.11

129.

3413

0.53

142.

85

164.

22

13C-NMR Spectrum of compound 3c

O

O

CO2C2H5

Cl

O

O

CO2C2H5

Cl

HRMS Spectrum of compound 3c

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.15

2.12

1.02

2.08

2.07

1.05

1.02

1.04

1.00

0.00

1.44

1.45

1.47

4.44

4.46

4.48

4.50

6.30

7.26

7.37

7.39

7.40

7.47

7.49

7.51

7.67

7.69

7.78

7.80

7.86

7.88

8.05

8.15

1H-NMR Spectrum of compound 3d

O

O

CO2C2H5

Cl

O

O

CO2C2H5

Ph

0102030405060708090100110120130140150160170

14.4

3

61.3

6

76.7

577

.06

77.3

8

102.

64

114.

9112

0.36

120.

6412

4.56

127.

2112

7.57

128.

1312

8.97

129.

29

137.

5314

0.52

142.

5414

2.64

164.

54

13

C-NMR Spectrum of compound 3d

HRMS Spectrum of compound 3d

O

O

CO2C2H5

Ph

O

O

CO2C2H5

Ph

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.05

3.16

2.14

2.15

1.04

1.06

0.99

1.00

0.00

1.42

1.44

1.46

3.90

4.42

4.44

4.46

4.48

6.24

7.13

7.13

7.18

7.18

7.20

7.21

7.26

7.70

7.72

7.95

1H-NMR Spectrum of compound 3e

0102030405060708090100110120130140150160170

14.4

2

55.3

1

61.2

4

76.8

077

.05

77.3

1

102.

35

106.

49

114.

7011

7.34

121.

3112

1.96

122.

13

130.

09

141.

1314

2.84

156.

76

164.

71

13C-NMR Spectrum of compound 3e

O

O

CO2C2H5

H3CO

O

O

CO2C2H5

H3CO

HRMS Spectrum of compound 3e

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.03

3.09

2.02

2.01

2.01

1.01

1.00

0.00

1.42

1.43

1.45

3.93

4.42

4.44

4.45

4.46

6.26

7.00

7.00

7.02

7.02

7.26

7.73

7.75

8.02

1H NMR Spectrum of compound 3f

O

O

CO2C2H5

H3CO

CO2C2H5

H3COO

O

0102030405060708090100110120130140150160170

14.4

0

55.4

4

61.1

0

96.9

7

102.

28

111.

97

118.

6412

2.94

124.

2412

4.67

131.

23

141.

4914

2.98

159.

69

164.

67

13C NMR Spectrum of compound 3f

HRMS Spectrum of compound 3f

CO2C2H5

H3COO

O

CO2C2H5

H3COO

O

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.10

3.07

2.06

2.08

1.02

1.01

0.99

1.00

0.00

1.42

1.44

1.46

2.47

4.42

4.44

4.46

4.48

6.26

7.26

7.33

7.34

7.36

7.36

7.62

7.69

7.71

7.99

1

H-NMR Spectrum of compound 3g

0102030405060708090100110120130140150160170

14.4

1

21.6

7

61.2

3

76.8

077

.06

77.3

1

102.

39

114.

45

119.

5611

9.98

123.

33

128.

1212

9.30

130.

7113

4.34

141.

8714

2.47

164.

70

13

C-NMR Spectrum of compound 3g

O

O

CO2C2H5

H3C

O

O

CO2C2H5

H3C

HRMS Spectrum of compound 3g

-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5

f1 (ppm)

SAI-M0009

3.03

3.05

2.01

2.02

2.00

1.01

1.00

-0.0

8

1.34

1.36

1.38

2.68

4.35

4.36

4.38

4.40

6.13

7.09

7.11

7.12

7.12

7.13

7.18

7.54

7.55

7.57

7.95

1H-NMR Spectrum of compound 3h

O

O

CO2C2H5

H3C

OO

CO2C2H5

CH3

0102030405060708090100110120130140150160170180f1 (ppm)

SAI-M0009

14.2

4

24.4

6

60.9

163

.46

63.9

0

76.7

577

.00

77.2

5

120.

7012

4.37

124.

5412

6.86

127.

1112

8.91

130.

3713

3.54

138.

2014

0.13

165.

48

13C-NMR Spectrum of compound 3h

OO

CO2C2H5

CH3

OO

CO2C2H5

CH3

HRMS Spectrum of compound 3h

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.16

2.16

4.21

1.04

1.06

1.04

1.00

1.02

0.00

1.41

1.43

1.45

4.39

4.41

4.43

4.44

4.44

4.45

4.45

4.48

4.48

4.49

4.49

4.49

4.50

7.26

7.37

7.37

7.39

7.39

7.39

7.41

7.41

7.50

7.50

7.51

7.52

7.52

7.53

7.54

7.77

7.80

7.95

8.03

8.03

8.05


0102030405060708090100110120130140150160170180190

14.3

8

61.1

264

.27

64.5

5

76.6

477

.07

77.4

9

120.

3212

1.19

124.

1312

4.90

127.

2912

7.63

128.

61

137.

4613

7.87

165.

65


CO2C2H5

O

O

CO2C2H5

O

O

HRMS Spectrum of compound 4a

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0

3.12

6.46

1.02

1.00

1.00

0.99

1.40

1.42

1.44

4.39

4.41

4.43

4.44

4.47

4.48

7.55

7.57

7.83

7.90

7.92

7.94


CO2C2H5

O

O

Br

CO2C2H5

O

O

0102030405060708090100110120130140150160170

14.3

6

61.3

364

.29

64.5

3

76.7

577

.07

77.3

9

118.

7912

2.32

122.

9012

5.63

128.

6813

0.39

130.

79

137.

7413

8.19

165.

30

1


HRMS Spectrum of compound 4b

CO2C2H5

O

O

Br

CO2C2H5

O

O

Br

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.08

2.21

2.06

2.16

0.99

1.00

1.00

1.02

0.00

1.41

1.42

1.44

4.40

4.41

4.43

4.43

4.43

4.44

4.44

4.47

4.47

4.48

4.48

7.26

7.43

7.43

7.44

7.45

7.76

7.76

7.83

7.97

7.98


0102030405060708090100110120130140150160170

14.3

5

61.3

164

.31

64.5

2

76.7

577

.06

77.3

8

122.

2312

2.43

122.

8912

5.41

127.

0912

8.22

128.

3413

0.73

137.

7113

8.10

165.

33


CO2C2H5

O

O

Cl

CO2C2H5

O

O

Cl

HRMS Spectrum of Compound 4c

CO2C2H5

O

O

Cl

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.13

2.11

2.31

2.14

1.04

2.15

2.11

1.04

1.02

1.00

1.02

0.00

1.42

1.44

1.46

4.41

4.42

4.44

4.45

4.45

4.45

4.46

4.46

4.47

4.49

4.50

4.50

4.51

4.51

7.26

7.36

7.37

7.39

7.46

7.48

7.50

7.68

7.68

7.70

7.71

7.78

7.78

7.80

7.80

7.99

7.99

8.01

8.10

8.12


0102030405060708090100110120130140150160170

14.4

0

61.1

864

.33

64.6

1

76.7

577

.07

77.3

9

121.

0012

1.61

124.

4312

6.41

127.

2512

7.35

127.

4412

7.94

128.

9213

7.54

137.

6513

8.04

140.

68

165.

62

13C-NMR Spectrum of compound 4d

CO2C2H5

O

O

Ph

CO2C2H5

O

O

Ph


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.24

3.13

4.48

2.14

1.07

1.03

1.02

1.00

1.41

1.42

1.44

3.89

4.39

4.41

4.42

4.42

4.43

4.45

4.46

4.46

4.46

4.47

7.08

7.09

7.17

7.18

7.19

7.19

7.26

7.84

7.94

7.95


CO2C2H5

O

O

H3CO

CO2C2H5

O

O

Ph

0102030405060708090100110120130140150160170

14.1

514

.39

55.3

3

61.0

764

.40

64.4

5

76.8

077

.05

77.3

0

106.

43

120.

4412

1.53

122.

0112

2.58

128.

78

136.

5613

7.88

157.

02

165.

75



CO2C2H5

O

O

H3CO

CO2C2H5

O

O

H3CO

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0

3.05

3.07

2.04

2.04

2.17

1.00

1.02

1.02

1.00

0.00

1.41

1.42

1.43

3.94

4.38

4.40

4.41

4.42

4.44

4.44

4.45

4.47

4.48

4.49

7.02

7.03

7.04

7.05

7.26

7.29

7.29

7.67

7.69

7.93

1H NMR Spectrum of compound 4f

0102030405060708090100110120130140150160170180

14.3

5

55.3

4

60.8

864

.14

64.5

3

76.7

577

.00

77.2

5

98.3

6

117.

9111

8.20

122.

8612

4.33

128.

7213

0.36

136.

4713

8.69

159.

46

165.

56

13C NMR Spectrum of compound 4f

CO2C2H5

H3COO

O

HRMS Spectrum of compound 4f

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.21

3.24

4.22

2.13

1.04

1.05

1.00

1.02

1.41

1.42

1.44

2.48

4.39

4.41

4.42

4.43

4.43

4.46

4.47

4.47

4.48

7.26

7.34

7.35

7.36

7.36

7.55

7.86

7.92

7.94

1H-NMR Spectrum of compound 4g

CO2C2H5

O

O

H3C

CO2C2H5

H3COO

O

0102030405060708090100110120130140150160170

14.3

9

21.4

9

61.0

764

.31

64.5

2

76.8

077

.06

77.3

1

120.

2112

1.11

123.

4912

5.51

127.

5212

7.91

129.

9813

4.47

137.

2913

7.53

165.

78

13C-NMR Spectrum of compound 4g

CO2C2H5

O

O

H3C

HRMS Spectrum of Compound 4g

CO2C2H5

O

O

H3C

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

SAI M0009

3.05

3.04

4.14

2.04

2.02

1.02

1.00

0.00

1.39

1.41

1.43

2.83

4.38

4.39

4.41

4.44

7.18

7.20

7.25

7.54

7.56

7.58

7.87

1H-NMR Spectrum of compound 4h

0102030405060708090100110120130140150160170180190f1 (ppm)

SAI-M0009

14.2

4

24.4

6

60.9

163

.46

63.9

0

76.7

577

.00

77.2

5

120.

7012

4.37

124.

5412

6.86

127.

1112

8.91

130.

3713

3.54

138.

2014

0.13

165.

48

13C-NMR Spectrum of compound 4h

CO2C2H5

CH3 OO

CO2C2H5

CH3 OO

HRMS Spectrum of compound 4h

CO2C2H5

CH3 OO

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0

3.18

3.16

1.07

4.31

1.05

1.11

1.05

1.00

1.00

0.00

1.41

1.43

1.45

1.47

1.48

4.02

4.03

4.05

4.05

4.07

4.07

4.39

4.40

4.40

4.41

4.41

4.42

4.42

4.43

4.43

4.44

4.44

4.45

4.46

4.47

7.26

7.36

7.36

7.38

7.38

7.38

7.40

7.40

7.49

7.49

7.51

7.51

7.51

7.53

7.53

7.77

7.79

7.95

8.03

8.03

8.05

8.05

1H-NMR Spectrum of compound 4i

0102030405060708090100110120130140150160170180190

14.3

216

.50

61.0

2

68.8

869

.46

120.

3112

1.30

124.

0912

4.71

127.

0412

7.49

128.

56

136.

8613

7.60

165.

83

13C-NMR Spectrum of compound 4i

CO2C2H5

OO

CH3

CO2C2H5

OO

CH3

HRMS Spectrum of Compound 4i

CO2C2H5

OO

CH3

CO2C2H5

OO

CH3

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.30

3.27

1.13

4.11

1.07

1.15

1.05

1.00

1.00

0.00

1.41

1.43

1.45

1.49

1.51

3.93

3.95

3.96

3.98

3.98

4.39

4.41

4.43

4.44

4.44

4.45

4.46

4.47

4.47

4.49

7.26

7.26

7.26

7.26

7.37

7.37

7.39

7.39

7.39

7.41

7.41

7.49

7.50

7.51

7.51

7.52

7.53

7.53

7.78

7.80

7.95

8.07

8.07

8.09

8.09

1H-NMR Spectrum of compound 4ia

0102030405060708090100110120130140150160170180

14.3

516

.69

61.0

7

69.2

7

120.

3712

0.91

123.

9112

4.82

127.

2512

7.48

127.

6512

8.55

137.

33

165.

68

13C-NMR Spectrum of compound 4ia

CO2C2H5

OO

CH3

CO2C2H5

OO

CH3

HRMS Spectrum of Compound 4ia

CO2C2H5

OO

CH3

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5

3.12

2.18

2.11

4.13

1.05

1.08

1.02

1.00

1.00

0.00

1.41

1.43

1.44

2.31

2.33

2.34

4.32

4.34

4.35

4.39

4.39

4.40

4.41

4.41

4.43

4.45

7.26

7.41

7.41

7.43

7.43

7.44

7.45

7.45

7.51

7.51

7.53

7.53

7.53

7.55

7.55

7.80

7.82

7.92

8.16

8.16

8.18

8.18

8.18


0102030405060708090100110120130140150160170180

14.3

3

31.8

2

61.1

4

71.0

071

.10

76.6

877

.00

77.3

2

121.

6012

5.04

125.

5412

7.50

128.

2812

9.31

129.

79

145.

2114

6.57

166.

52


CO2C2H5

O

O

CO2C2H5

O

O


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.17

2.21

2.07

4.31

1.01

1.00

1.02

1.05

1.41

1.42

1.44

2.31

2.32

2.33

2.34

2.35

4.33

4.34

4.35

4.39

4.39

4.40

4.41

4.41

4.42

4.44

7.26

7.56

7.57

7.58

7.58

7.78

7.95

7.95

8.02

8.04


CO2C2H5

O

O

Br

CO2C2H5

O

O

0102030405060708090100110120130140150160170

14.3

5

31.6

6

61.3

6

71.0

571

.22

76.8

077

.05

77.3

1

119.

6412

3.66

123.

7512

6.95

128.

2413

0.11

130.

3813

0.75

145.

3714

6.69

166.

20



CO2C2H5

O

O

Br

CO2C2H5

O

O

Br

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.12

2.08

3.15

2.09

2.08

2.08

1.03

1.04

1.00

1.00

1.40

1.42

1.43

2.27

2.28

2.30

2.31

2.32

2.47

7.25

7.34

7.34

7.36

7.36

7.56

7.82

8.04

8.06


0102030405060708090100110120130140150160170

14.3

9

21.5

1

32.0

1

61.1

4

71.0

571

.17

76.8

577

.10

77.3

6

121.

5612

4.46

125.

5912

7.27

128.

0512

9.70

129.

91

135.

28

144.

6914

6.78

166.

72


CO2C2H5

O

O

H3C

CO2C2H5

O

O

H3C


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0

3.04

4.34

4.15

2.08

1.01

1.02

1.01

1.00

1.00

0.00

1.41

1.42

1.44

1.92

1.93

1.94

1.94

1.95

1.97

1.98

1.99

2.01

2.01

2.02

2.02

4.39

4.41

4.43

4.43

4.44

4.46

4.56

4.57

4.59

7.25

7.39

7.39

7.41

7.41

7.41

7.43

7.43

7.49

7.49

7.51

7.51

7.51

7.53

7.53

7.78

7.80

7.94

8.13

8.13

8.15


CO2C2H5

O

O

CO2C2H5

O

O

H3C

0102030405060708090100110120130140150160170180

14.2

9

26.5

328

.05

61.0

6

72.0

874

.00

76.7

577

.00

77.2

5

121.

7712

5.05

125.

4112

5.97

127.

3312

8.40

129.

4612

9.98

142.

7914

5.12

166.

49



CO2C2H5

O

O

CO2C2H5

O

O

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0

3.07

2.12

2.16

4.19

2.09

1.00

1.01

1.00

1.02

0.00

1.41

1.42

1.44

1.94

1.94

1.95

1.95

1.97

1.98

2.00

2.02

2.03

2.04

2.05

4.39

4.41

4.43

4.43

4.44

4.46

4.58

4.59

4.60

7.26

7.55

7.56

7.57

7.58

7.80

7.95

7.95

8.01

8.03


0102030405060708090100110120130140150160170180

-0.0

1

14.3

0

26.3

228

.04

61.3

2

72.0

974

.07

76.6

877

.00

77.3

2

119.

5112

3.59

123.

8512

7.42

128.

3813

0.18

130.

54

142.

7514

5.39

166.

24


CO2C2H5

Br

O

O

CO2C2H5

Br

O

O


CO2C2H5

Br

O

O

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.20

2.28

2.37

3.18

4.32

2.16

1.04

1.05

1.00

1.02

1.41

1.42

1.44

1.93

1.93

1.94

2.00

2.01

2.01

2.02

2.48

4.39

4.41

4.41

4.42

4.43

4.43

4.56

4.57

4.58

7.26

7.34

7.35

7.36

7.37

7.57

7.87

8.03

8.05


102030405060708090100110120130140150160170

14.3

8

21.4

9

26.5

228

.30

61.1

1

72.0

874

.23

76.7

677

.08

77.4

0

121.

8112

4.54

126.

0312

7.43

128.

2012

9.77

129.

90

135.

18

142.

12

145.

49

166.

70


CO2C2H5

H3C

O

O

CO2C2H5

H3C

O

O


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.26

3.54

3.22

1.14

1.12

2.24

2.24

2.21

1.08

1.12

2.09

1.00

0.00

1.20

1.21

1.23

1.28

1.30

1.31

1.41

1.42

1.43

3.39

3.43

3.51

3.54

4.16

4.17

4.19

4.20

4.29

4.31

4.32

4.34

4.41

4.42

4.44

4.45

7.26

7.36

7.37

7.39

7.50

7.52

7.52

7.54

7.85

7.87

8.11


O

O

CO2C2H5

CO2C2H5CO2C2H5

CO2C2H5

H3C

O

O

0102030405060708090100110120130140150160170

13.9

614

.02

14.3

2

41.0

4

61.2

461

.26

62.7

2

76.8

177

.07

77.3

2

111.

74

114.

59

119.

9612

1.42

124.

7512

5.02

128.

3412

9.13

129.

39

141.

4514

1.79

164.

2416

5.23

167.

37


O

O

CO2C2H5

CO2C2H5CO2C2H5

O

O

CO2C2H5

CO2C2H5CO2C2H5

HRMS Spectrum of Compound 8a

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.11

3.29

3.04

2.10

2.12

2.04

2.09

1.01

1.04

0.94

1.00

0.00

1.19

1.21

1.22

1.28

1.30

1.31

1.40

1.41

1.43

3.39

3.42

3.52

3.55

4.16

4.17

4.19

4.20

4.29

4.31

4.32

4.33

4.41

4.42

4.42

4.43

4.44

4.45

7.27

7.56

7.58

7.58

7.73

7.75

8.01

8.02

8.02


O

O

CO2C2H5

CO2C2H5CO2C2H5

Br

0102030405060708090100110120130140150160170

13.8

913

.96

14.2

3

40.8

7

61.2

461

.40

62.7

7

76.7

577

.00

77.2

5

111.

9711

5.47

118.

7711

9.54

121.

6712

3.62

129.

9513

1.10

131.

55

141.

9114

2.17

163.

7916

4.93

167.

18


O

O

CO2C2H5

CO2C2H5CO2C2H5

Br

O

O

CO2C2H5

CO2C2H5CO2C2H5

Br

HRMS Spectrum of Compound 8b

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.02

3.39

2.98

1.00

0.98

2.05

2.02

1.93

1.00

0.95

0.95

1.00

1.20

1.21

1.23

1.28

1.30

1.31

1.40

1.42

1.43

3.39

3.42

3.52

3.55

4.16

4.17

4.19

4.20

4.29

4.31

4.32

4.34

4.41

4.42

4.44

4.44

4.45

7.27

7.44

7.44

7.45

7.46

7.80

7.82

7.83

7.84

8.01


O

O

CO2C2H5

CO2C2H5CO2C2H5

Cl

0102030405060708090100110120130140150160170

13.9

414

.02

14.1

414

.28

40.9

3

61.2

861

.43

62.8

1

76.7

477

.06

77.3

8

112.

0011

5.60

119.

4412

1.70

123.

6612

7.82

129.

2412

9.56

130.

81

141.

8714

2.19

163.

8716

4.99

167.

22


O

O

CO2C2H5

CO2C2H5CO2C2H5

Cl

O

O

CO2C2H5

CO2C2H5CO2C2H5

Cl

HRMS Spectrum of Compound 8c

-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0

3.14

3.02

3.19

2.11

2.12

2.10

2.03

1.09

2.19

2.08

1.05

1.02

1.01

1.00

0.00

1.21

1.22

1.24

1.25

1.29

1.31

1.33

1.41

1.43

1.45

3.40

3.44

3.53

3.57

4.17

4.18

4.20

4.22

4.30

4.32

4.33

4.35

4.41

4.43

4.45

4.47

7.26

7.26

7.39

7.41

7.47

7.49

7.51

7.67

7.68

7.69

7.70

7.79

7.79

7.81

7.82

7.93

7.95

8.05

8.06

8.06

8.17


O

O

CO2C2H5

CO2C2H5CO2C2H5

Ph

0102030405060708090100110120130140150160170

13.9

314

.00

14.2

9

40.9

9

61.2

261

.27

62.7

1

76.7

577

.00

77.2

5

111.

80

114.

9512

0.56

125.

0212

7.05

127.

2112

7.59

128.

2312

8.94

129.

45

137.

7714

0.44

141.

5914

1.85

164.

1716

5.17

167.

33

13C-NMR Spectrum of compound 8d


O

O

CO2C2H5

CO2C2H5CO2C2H5

Ph

O

O

CO2C2H5

CO2C2H5CO2C2H5

Ph

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5

3.26

3.54

3.11

1.09

1.10

3.15

2.21

2.47

2.15

1.05

1.01

1.03

1.00

0.00

1.20

1.21

1.23

1.26

1.28

1.30

1.31

1.40

1.41

1.43

3.37

3.40

3.50

3.53

3.90

4.16

4.17

4.19

4.20

4.29

4.29

4.30

4.31

4.32

4.33

4.40

4.41

4.43

4.44

7.13

7.13

7.19

7.19

7.21

7.21

7.26

7.76

7.78

7.97


0102030405060708090100110120130140150160170

13.9

514

.02

14.3

2

41.0

4

55.3

4

61.2

062

.67

76.7

277

.04

77.3

6

106.

48

111.

5611

4.79

117.

10

121.

5412

2.02

122.

67

130.

34

140.

1414

2.16

156.

95

164.

3816

5.30

167.

41


O

O

CO2C2H5

CO2C2H5CO2C2H5

H3CO

O

O

CO2C2H5

CO2C2H5CO2C2H5

H3CO


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0

3.32

3.71

3.11

3.15

1.08

1.05

2.17

2.17

2.10

1.11

1.05

1.04

1.00

1.19

1.21

1.23

1.28

1.29

1.31

1.40

1.41

1.43

2.47

3.38

3.42

3.50

3.54

4.15

4.17

4.19

4.21

4.28

4.30

4.32

4.33

4.39

4.41

4.43

4.45

7.26

7.35

7.35

7.37

7.37

7.62

7.75

7.78

8.01

1H-NMR Spectrum of compound 8f

O

O

CO2C2H5

CO2C2H5CO2C2H5

H3C

O

O

CO2C2H5

CO2C2H5CO2C2H5

H3CO

0102030405060708090100110120130140150160170

13.9

514

.01

14.3

1

21.6

7

41.0

6

61.1

962

.66

76.7

677

.07

77.3

9

111.

60

114.

52

119.

7912

3.86

128.

0312

9.49

130.

8213

4.64

140.

8614

1.79

164.

3716

5.31

167.

42

13C-NMR Spectrum of compound 8f

O

O

CO2C2H5

CO2C2H5CO2C2H5

H3C

O

O

CO2C2H5

CO2C2H5CO2C2H5

H3C

HRMS Spectrum of Compound 8f

Documents

Kasagani Veera Prasad, Kurma Siva Hariprasad, Bhimapaka ... · Kasagani Veera Prasad, Kurma Siva Hariprasad, Bhimapaka China Raju* Organic Synthesis and Process Chemistry Division,