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Supporting Information
PhI(OAc)2/NaX-mediated Halogenation Providing Access to Valuable Synthons 3-Haloindole derivatives
Vittam Himabindua,b, Sai Prathima Parvathaneni*a, and Vaidya Jayathirth Rao*a,b
aFluoro Agro Chemicals(Org.Chem. II) Division and bAcSIR, Indian Institute of Chemical Technology, Uppal Road Tarnaka, Hyderabad-500007, India, Tel: (+) 91 40 27193933
[email protected]; [email protected]
Contents
1. General Information 2
2. Halogenation of Indoles 3
3. Characterization Data for the Products 3-13
4. 1H NMR and 13C NMR Spectra of the Products 14-50
5. References 51
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 2018
2
1. General Information
The starting materials and reagents were purchased from various commercial sources and used without
further purification. The reactions were performed at room temperature. ACME silica gel (60-120 mesh) was
used for column chromatography. Analytical thin-layer chromatography (TLC) was performed on pre-coated
TLC plates with silica gel 60-F254 plates and visualized by UV-light. 1H NMR and 13C NMR spectra were
recorded, using tetramethylsilane (TMS) in the solvent of CDCl3+DMSO as the internal standard on a 300,
500 MHz spectrometer (1H NMR: TMS at 0.00 ppm, CDCl3 at 7.26 ppm; 13C NMR: CDCl3 at 77.0 ppm,
DMSO at 39.43). Chemical shifts (δ) were recorded in ppm with respect to TMS as an internal standard and
coupling constants are quoted in Hertz (Hz). Mass spectra were recorded on a mass spectrometer by the
electron spray ionization (ESI) and the data acquired in positive ionization mode. HRMS spectra were
determined on TOF type mass analyzer.
3
2. Halogenation of Indoles
General Procedure for Chlorination:
In a 25 mL round bottom flask, substrates 1a-1j (1.0 mmol, 1 equiv) and NaCl (58 mg, 1.0 mmol, 1.0 equiv),
PhI(OAc)2 (322 mg, 1.0 mmol, 1equiv) were dissolved in 2 mL of CH3CN:H2O (1:1). The reaction mixture
was stirred at room temperature for 1-2h as monitored by TLC. The reaction mixture was diluted with 20 mL
of ethyl acetate and then treated with 10 mL of saturated Na2S aqueous solution. The organic layer was dried
over Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography on silica
gel with a gradient eluent of hexane and ethyl acetate to give the chlorinated product.
3. Characterization Data for the Products:
3-chloro-1H-indole (2a) 1
Isolated yield: 72%; mp: 58-60 oC (lit)13 ; 1H NMR (500 MHz, CDCl3): δ 8.10 (s, 1H),
7.66-7.63 (d, 1H, J = 7.7 Hz), 7.39-7.36 (d, 1H, J = 7.7 Hz), 7.28-7.18 (m, 3H); 13C
NMR (500 MHz, CDCl3): δ 133.94, 124.38, 122.10, 119.79, 119.44, 117.26, 110.44,
105.48;MS (EI-MS) =151.0 (M+ ), 153.0 (M+2).
3-chloro-5-fluoro-1H-indole (2b) 1
Isolated yield: 62%; mp: 69-72 oC; 1H NMR (500 MHz, CDCl3): δ 8.01 (s, 1H), 7.22-
7.18 (m, 2H), 7.13-7.12 (d, 1H, J = 2.5 Hz), 6.94-6.89 (m, 1H); 13C NMR (500 MHz,
CDCl3): δ 159.24 (s), 157.36 (s), 131.47 (s), 125.88 (d, J = 10.4 Hz), 122.61 (s), 112.12
(dd, J = 70.7, 18.1Hz), 106.53 (s), 103.26 (d, J= 24.8.6 Hz);MS (EI-MS) = 169 (M+).
3, 5-dichloro-1H-indole (2c) 2
Isolated yield: 67%; mp: 97-99 oC (lit)6; 1H NMR (500 MHz, CDCl3): δ 8.09 (s, 1H),
7.61 (s, 1H,), 7.28-7.25 (m, 1H), 7.21-7.18 (m, 2H); 13C NMR (500 MHz, CDCl3): δ
133.32, 126.48, 126.42, 123.64, 122.22, 117.89, 112.61, 106.21;MS (EI-MS) = 184
(M+).
NH
Cl
2a
NH
Cl
2b
F
NH
Cl
2c
Cl
4
5-bromo-3-chloro-1H-indole (2d)1, 3
Isolated yield: 64%; mp: 111-113 oC; 1H NMR (500 MHz, CDCl3): δ 8.22 (s, 1H),
7.56 (s, 1H), 7.30-7.29 (d, 1H, J = 8.5 Hz), 7.26-7.25 (d, 1H, J = 2.5 Hz), 7.21-7.19
(dd, 1H, J = 8.6, 10.6 Hz); 13C NMR (500 MHz, CDCl3): δ 133.59, 127.06, 126.16,
122.09, 120.96, 113.81, 113.04, 106.01; MS (EI-MS) = 229 (M+1).
3-chloro-5-iodo-1H-indole (2e)
Isolated yield: 74%; 1H NMR (500 MHz, CDCl3): δ 8.18 (s, 1H), 7.98 (s, 1H), 7.50-
7.48 (d, 1H, J = 8.8 Hz), 7.15-7.13 (d, 2H, J = 8.0 Hz); 13C NMR (400 MHz, CDCl3):
134.07, 131.57, 127.80, 127.28, 121.63, 113.42, 83.83, 60.46;MS (EI-MS) = 277
[M+], 279 [M + 2].
3-chloro-5-nitro-1H-indole (2f) 1
Isolated yield: 65%; mp: 150-152 oC; 1H NMR (300 MHz, CDCl3+d6-DMSO): δ 8.63
(s, 1H), 8.49 (s, 1H), 8.18-8.16 (dd, 1H, J = 8.9, 11.2 Hz), 7.45-7.42 (d, 1H, J = 9.0 Hz),
7.36-7.35 (d, 1H, J = 8.9 Hz ); 13C NMR (300 MHz, CDCl3+d6-DMSO): δ 140.32,
138.49, 127.49, 126.28, 116.67, 115.84, 110.65, 103.14; MS (EI-MS) = 198 (M+2).
3-chloro-5-methyl-1H-indole (2g) 1
Isolated yield: 79%; mp: 65-67 oC; 1H NMR (500 MHz, CDCl3): δ 8.00 (s, 1H), 7. 45
(s, 1H), 7.28 (s, 1H), 7.16-7.09 (m, 2H), 1.51 (s, 3H); 13C NMR (400 MHz, CDCl3): δ
133.34, 129.95, 125.60, 124.84, 120.87, 117.78, 111.16, 106.04, 21.44; MS ( EI-MS)
=166 (M+1).
3-chloro-5-methoxy-1H-indole (2h) 1, 3
Isolated yield: 78%; mp: 75-77 oC; 1H NMR (500 MHz, CDCl3): δ 8.10 (s, 1H),
7.27-7.20 (t, 2H), 7.00-6.99 (d, 1H, J = 2.5 Hz), 6.91-6.89 (dd, 1H, J = 8.8, 11.2
NH
Cl
2d
Br
NH
Cl
2e
I
NH
Cl
2f
O2N
NH
Cl
2h
MeO
NH
Cl
2g
5
Hz), 3.8 (s, 3H); 13C NMR (400 MHzCDCl3): δ 154.87, 129.99, 125.79, 121.32, 113.98, 112.43, 106.04,
99.27, 29.72; MS (EI-MS) = 182 (M+1).
3-chloro-2-methyl-5-nitro-1H-indole (2i) 3
Isolated yield: 58%; mp: 170-172 oC; 1H NMR (300 MHz, CDCl3+d6-DMSO): δ
8.50 (s, 1H), 8.28 (s, 1H), 8.11-8.08 (d, 1H, J = 8.9 Hz), 7.33-7.31 (d, 1H, J = 8.9
Hz), 2.49 (s, 3H); 13C NMR (300 MHz, CDCl3+d6-DMSO): δ 140.70, 137.62,
136.58, 126.19, 116.07, 113.82, 110.49, 89.91, 11.51; MS (EI-MS) = 210 (M+).
3-chloro-1-phenyl-1H-indole (2j)4
Isolated yield: 64%; 1H NMR (400 MHz, CDCl3): δ 7.62-7.58 (m, 1H), 7.55-7.49
(m, 5H), 7.37-7.33 (m, 1H), 7.25-7.16 (m, 3H); 13C NMR (400 MHz, CDCl3): δ
200.10, 164.56, 140.52, 138.28, 132.79, 132.15, 130.51, 129.33, 127.75, 127.01,
113.06, 93.59; MS (EI-MS)=227 (M+).
General Procedure for bromination:
In a 25 mL round bottom flask, substrates 3a-31 (1.0 mmol, 1 equiv) and NaBr (103 mg, 1.0 mmol, 1.0
equiv), PhI(OAc)2 (322 mg, 1.0 mmol, 1 equiv) were dissolved in 2 mL of CH3CN:H2O (1:1). The reaction
mixture was stirred at room temperature for 1-2 h, monitored by TLC. The reaction mixture was diluted with
20 mL of ethyl acetate and then treated with 10 mL of saturated Na2S aqueous solution. The organic layer
was dried over Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography
on silica gel with a gradient eluent of hexane and ethyl acetate to give the brominated product.
NH
Cl
2i
O2N
N
Cl
2j
6
3-Bromo-1H-indole (3a) 1
Isolated yield: 78%; mp: 65-67 oC; 1H NMR (500 MHz, CDCl3): δ 8.19 (s, 1H), 7.61-
7.58 (d, 1H, J = 7.7 Hz), 7.39-7.37 (d, 1H, J = 7.1 Hz), 7.28-7.18 (m, 3H); 13C NMR
(500 MHz, CDCl3): δ 133.60, 127.09, 126.18, 122.03, 121.02, 113.83, 112.98, 106.09;
MS (EI-MS) = 195 (M+).
3-bromo-5-fluoro-1H-indole (3b) 1
Isolated yield: 61%; mp: 75-78 oC; 1H NMR (500 MHz, CDCl3): δ 8.45 (s, 1H), 7.53
(s, 1H,), 7.26-7.15 (m, 3H); 13C NMR (500 MHz, CDCl3): δ 139.42 (s), 134.41 (s),
131.62 (s), 129.28 (d, J = 102.9 Hz), 126.13 (s), 123.69 (s), 114.12 (s), 112.83 (s); MS
(EI-MS) = 212 (M+).
3-bromo-5-chloro-1H-indole (3c) 5
Isolated yield: 69%; mp: 81-83 oC (lit)12; 1H NMR (500 MHz, CDCl3): δ 8.22 (s, 1H),
7.57-7.56 (d, 1H, J = 8.5 Hz), 7.30-7.28 (d, 1H,J = 2.5 Hz), 7.25-7.19 (m, 2H,); 13C
NMR (400 MHz, CDCl3): δ 134.17, 128.99, 125.62, 125.49, 122.35, 120.15, 112.07,
102.43; MS (EI-MS) = 230 (M+2).
3, 5-dibromo-1H-indole (3d) 1
Isolated yield: 65%; mp: 91-93 oC (lit)12; 1H NMR (500 MHz, CDCl3): δ 8.21 (s, 1H),
7.72 (s, 1H), 7.34-7.31 (dd, 1H, J = 8.6, 10.5 Hz), 7.25-7.21 (m, 2H); 13C NMR (400
MHz, CDCl3): δ 133.98, 128.59, 126.19, 124.55, 121.90, 113.99, 112.91, 90.99; MS
(EI-MS) = 274 (M+2).
3-bromo-5-iodo-1H-indole (3e):
NH
Br
3a
NH
Br
3b
F
NH
Br
3c
Cl
NH
Br
3d
Br
7
Isolated yield: 79%; mp: 90-93 oC; 1H NMR (400 MHz, CDCl3): δ 8.25 (s, 1H), 7.93
(s, 1H), 7.51-7.49 (dd, 1H, J = 8.5, 10.2 Hz), 7.20-7.14 (m, 2H); 13C NMR (500 MHz,
CDCl3):δ 134.45, 131.62,129.30, 128.19, 124.11, 113.31, 90.69, 84.04; MS (EI-MS) =
320 (M+), 321 (M+2), HRMS (EI-HRMS) (M+H)+m/z calcd for C8H5BrIN = 320.8650,
found = 320.8620.
3-bromo-5-nitro-1H-indole (3f) 6
Isolated yield: 59%; mp: 190-192 oC; 1H NMR (300 MHz, CDCl3): δ 11.31 (s, 1H),
8.19 (s, 1H), 7.83-73.79 (d, 1H, J = 8.5 Hz),7.28-7.16 (m, 2H);13C NMR (300 MHz,
CDCl3): δ 141.20, 138.20, 126.99, 125.60, 117.04, 115.48, 111.69, 91.61; MS (EI-MS)
= 241.
3-bromo-5-methyl-1H-indole (3g) 7
Isolated yield: 82%; mp: 66-68 oC; 1H NMR (500 MHz, CDCl3): δ 8.14 (s, 1H), 7.36
(s, 1H), 7.27-7.25 (t, 1H), 7.19-7.18 (d, 1H, J = 8.6 Hz), 7.08-7.06 (dd, 1H, J = 8.3, 10.2
Hz), 2.47 (s, 3H); 13C NMR (500 MHz, CDCl3): δ 134.15, 129.03, 128.18, 124.27,
123.65, 120.38, 110.70, 102.13, 21.48; MS (EI-MS) = 208 (M+).
3-bromo-5-methoxy-1H-indole (3h) 1
Isolated yield: 81%; mp: 74-76 oC; 1H NMR (500 MHz, CDCl3): δ 8.04 (s, 1H), 7.20-
7.18 (t, 1H), 7.13-7.12 (d, 1H, J = 2.4 Hz), 6.92 (s, 1H), 6.84-6.82 (dd, 1H, J = 8.8,
11.2 Hz), 3.8 (s, 3H). 13C NMR (500 MHz, CDCl3): δ 154.24, 131.14, 131.03, 128.34,
124.95, 112.39, 111.78, 102.40, 55.54; MS (EI-MS) = 226 (M+2).
3-bromo-2-methyl-5-nitro-1H-indole (3i)
Isolated yield: 62%; mp: 161-165 oC; 1H NMR (300 MHz, CDCl3+d6-DMSO): δ
11.60 (s, 1H), 8.31 (s, 1H), 8.01-7.97 (dd, 1H, J = 9.0, 11.0 Hz), 7.39-7.36 (d, 1H, J
= 8.8 Hz), 3.14 (s, 3H); 13C NMR (300 MHz, CDCl3+d6-DMSO): δ 140.70, 137.62,
NH
Br
3e
I
NH
Br
3f
O2N
NH
Br
3g
NH
Br
3h
MeO
NH
Br
3i
O2N
8
136.58, 126.19, 116.07, 114.01, 110.49, 89.91, 11.51; MS (EI-MS) = 254 (M+1), HRMS (EI-HRMS) =calcd
for C8H5BrN2O2 = 253.9690, found = 253.9690.
3-bromo-1-phenyl-1H-indole (3j) 12
Isolated yield: 74%; mp: 91-93 oC; 1H NMR (400 MHz, CDCl3): δ 7.55-7.52 (t, 2H), 7.48-
7.42 (m, 4H), 7.28-7.24 (m, 1H), 7.15-7.12 (m, 1H), 6.80-6.78 (s, 1H, J = 7.9 Hz), 5.43 (s,
1H) ; 13C NMR (400 MHz, CDCl3): δ 171.73, 143.94, 133.83, 130.33, 129.78, 128.54,
126.44, 126.36, 125.98, 123.83, 110.10; MS (EI-MS) = 272 (M+2).
1-benzyl-3-bromo-1H-indole (3k) 8
Isolated yield: 71%; mp: 55-60 oC; 1H NMR (500 MHz, CDCl3+d6-DMSO): δ 7.60-7.57
(m, 1H), 7.33-7.17 (m, 7H), 7.13-7.10 (m, 2H), 5.28 (s, 2H); 13C NMR (400 MHz, CDCl3+d6-
DMSO): δ 136.79, 135.94, 128.92, 127.94, 127.56, 127.08, 126.97, 122.88, 120.39, 119.47,
109.93, 90.36, 50.37; MS (EI-MS) = 285 (M+), HRMS (EI-HRMS) =calcd for C15H12BrN=
285.0179, found = 285.0153.
3-bromo-1-methyl-2-phenyl-1H-indole (3l) 6
Isolated yield: 94%; 1H NMR (400 MHz, CDCl3+d6-DMSO): δ 7.62-7.60 (d, 1H, J =
8.6 Hz), 7.50-7.44 (m, 5H), 7.34-7.27 (m, 2H), 7.24-7.22 (m, 1H), 3.63 (s, 3H); 13C NMR
(400 MHz, CDCl3+d6-DMSO): δ 141.81, 137.84, 131.70, 131.00, 130.46, 128.88, 128.74,
128.51, 123.00, 121.54, 120.81, 109.95, 58.98, 32.10; MS (EI-MS) = 285 (M+).
General Procedure for iodination:
N
Br
3j
N
Br
3k
N
Br
3l
9
In a 25 mL round bottom flask, substrates 4a-4m (1.0 mmol, 1 equiv) and NaI (150 mg, 1.0 mmol, 1.0 equiv),
PhI(OAc)2 (322 mg, 1.0 mmol, 1 equiv) were dissolved in 2 mL of CH3CN:H2O (1:1). The reaction mixture
was stirred at room temperature for 1-2 has monitored by TLC. The reaction mixture was diluted with 20 mL
of ethyl acetate and then treated with 10 mL of saturated Na2S aqueous solution. The organic layer was dried
over Na2SO4 and concentrated under vacuum. The residue was purified by column chromatography on silica
gel with a gradient eluent of hexane and ethyl acetate to give the iodinated product.
3-Iodo-1H-indole (4a)
Isolated yield: 91%; mp: 66 oC (lit)16; 1H NMR (500 MHz, CDCl3): δ 8.28 (s, 1H),
7.47-7.45 (d, 1H, J = 7.6 Hz), 7.35-7.34 (d,1H, J = 7.9 Hz) 7.26-7.19 (m, 3H); 13C NMR
(500 MHz, CDCl3): δ 135.65, 129.83, 128.42, 123.23, 121.05, 120.85, 111.28, 57.64;
MS (EI-MS) = 242 (M+).7
3-Iodo-5-Fluoro-1H-indole (4b) 10
Isolated yield: 75%; mp: 73-75 oC; 1H NMR (500 MHz, CDCl3): δ 8.34 (s, 1H), 7.32-
7.28 (m, 2H), 7.14-7.12 (d, 1H, J = 9.3 Hz), 7.01-6.97 (m, 1H); 13C NMR (500 MHz,
CDCl3): δ 159.57 (s), 157.69 (s), 132.14 (s), 130.57 (d, J = 10.5 Hz), 130.11 (s), 111.98
(dd, J = 34.6, 18.1 Hz), 106.17 (d, J = 24.6 Hz), 57.03 (d, J = 4.5 Hz); MS (EI-MS) =
261 (M+1)
3-Iodo-5-Chloro-1H-indole (4c) 10
Isolated yield: 82%; mp: 81-84 oC; 1H NMR (500 MHz, CDCl3): δ 8.38 (s, 1H) , 7.45-
7.44 (d, 1H, J = 1.9 Hz), 7.31-7.28 (m, 2H) 7.21-7.18 (dd, 1H, J = 8.6, 10.6 Hz); 13C
NMR (500 MHz,CDCl3): δ 134.08, 131.06, 129.75, 126.75, 123.66, 120.66, 112.37,
56.75; MS (EI-MS) = 277 [M+ ], 279 [M + 2].
3-Iodo-5-Bromo-1H-indole (4d) 6
NH
I
4b
F
NH
I
4c
Cl
NH
I
4a
10
Isolated yield: 85%;mp: 106-108 °C (lit) 6;1H NMR (500 MHz, CDCl3): δ 10.60
(s, 1H), 7.28-7.23 (m, 1H), 7.15-7.09 (m, 2H), 6.88-6.81 (m, 1H);13C NMR (500
MHz, CDCl3): δ 131.46, 130.97, 128.87, 125.94, 122.59, 114.09, 112.34, 103.50;
MS (EI-MS) = 323 (M+2), 321 (M+).
3, 5-diiodo-1H-indole (4e) 6, 8
Isolated yield: 89%; mp: 110-112 °C ; 1H NMR (500 MHz, CDCl3): δ 8.36 (s, 1H),
7.32-7.29 (dd, 1H, J = 8.3, 10.0 Hz), 7.14-7.12 (d, 1H, J = 2.5 Hz), 7.01-6.97 (d, 1H,
J = 8.3 Hz); 13C NMR (400 MHz, CDCl3): δ 134.84, 132.30, 131.64, 129.98, 129.20,
113.22, 84.28, 56.33; MS (EI-MS) = 368 (M+ ), HRMS (EI-HRMS) =calcd for
C8H5BrN2O2 = 368.8511, found = 368.8510.
3-Iodo-5-nitro-1H-indole (4f) 9
Isolated yield: 68%; mp: 199-201 °C; 1H NMR (300 MHz, CDCl3+d6-DMSO): δ
11.73 (s, 1H), 8.38 (s, 1H), 8.12-8.08 (dd, 1H, J = 8.8, 11.0 Hz), 7.54-7.51 (m, 2H);
13C NMR (300 MHz, CDCl3+d6-DMSO): δ 143.91, 140.79, 138.45, 131.88, 128.26,
116.51, 111.27, 56.87; MS (EI-MS) = 230.5.
3-Iodo-5-methyl-1H-indole (4g) 9
Isolated yield: 94%; mp: 70-72 °C; 1H NMR (500 MHz, CDCl3): δ 8.28 (s, 1H), 7.29-
7.26 (m, 3H), 7.11-7.08 (dd, 1H, J = 8.2, 9.6 Hz), 2.51 (s, 3H); 13C NMR (500 MHz,
CDCl3): δ 133.94, 130.33, 129.97, 128.43, 124.88, 120.58, 110.98, 57.07, 21.44; MS
(EI-MS) = 257 (M+1).
NH
I
4e
I
NH
I
4g
4d
NH
IBr
NH
I
4f
O2N
11
3-Iodo-5-methoxy-1H-indole (4h) 9
Isolated yield: 92%; mp:106-108 °C; 1H NMR (500 MHz, CDCl3): δ 7.98 (s,
1H), 7.25-7.04 (m, 3H), 6.92-6.88 (dd, 1H, J = 8.8, 11.2 Hz), 3.88 (s, 3H). 13C
NMR (500 MHz, CDCl3): δ 154.23, 130.99, 128.32, 124.90, 112.39, 111.74,
102.41, 55.90, 30.99; MS (EI-MS) = 272 (M+).
3-Iodo-2-methyl-5-nitro-1H-indole (4i)
Isolated yield: 71%; mp: 180-182 oC; 1H NMR (300 MHz, CDCl3+d6-DMSO): δ
11.58 (s, 1H), 8.23-8.22 (d, 1H, J = 2.2 Hz), 8.02-7.98 (dd, 1H, J = 8.8, 11.2 Hz),
7.36-7.33 (d, 1H, J = 8.8 Hz), 2.49 (s, 3H); 13C NMR (300 MHz, CDCl3+d6-DMSO):
δ 140.91, 140.59, 139.14, 129.58, 116.31, 115.93, 110.45, 58.65, 13.60; MS
(EI-MS) = 301.95500.
3-iodo-1-phenyl-1H-indole (4j)
Isolated yield: 90%; mp: 99-102 oC; 1H NMR (400 MHz, CDCl3+d6-DMSO): δ 7.62-7.48
(m, 7H), 7.57 (s, 1H), 7.35-7.30 (m, 1H), 7.25-7.16 (m, 2H),; 13C NMR (400 MHz, CDCl3+d6-
DMSO): δ 168.49, 139.44132.89, 129.80, 128.81, 127.73, 126.87, 122.59, 120.45, 119.61,
117.70, 117.30, 109.74, 50.15; MS (EI-MS) = 318 (M+), HRMS (EI-HRMS) =calcd for
C14H10BrIN= 318.9850, found = 318.9857.
1-benzyl-3-iodo-1H-indole (4k) 11
Isolated yield: 82%; mp: 77-80 oC; 1H NMR (500 MHz, CDCl3+d6-DMSO): δ 7.58-7.56
(d, 1H, J = 7.8 Hz), 7.33 (s, 1H), 7.29-7.24 (m, 5H), 7.20-7.17 (m, 1H), 7.13-7.10 (m, 3H),
5.26 (s, 2H); 13C NMR (400 MHz, CDCl3+d6-DMSO): δ 168.58, 137.25, 133.39, 129.80,
NH
I
4i
O2N
4h
NH
IMeO
N
I
4j
N
I
4k
12
128.81, 127.73, 126.87, 122.59, 120.45, 119.61, 117.70, 117.30, 109.74, 50.15, 29.73; MS (EI-MS): 333
(M+).
3-iodo-1-methyl-2-phenyl-1H-indole (4l) 6
Isolated yield: 94%; 1H NMR (500 MHz, CDCl3+d6-DMSO): δ 7.51-7.43 (m, 6H), 7.30-
7.28 (m, 2H), 7.24-7.19 (m, 1H), 3.64 (s, 3H); 13C NMR (400 MHz, CDCl3+d6-DMSO):
δ 141.81, 137.84, 131.70, 131.00, 130.65, 130.46, 128.88, 128.74, 128.51, 123.00, 121.54,
120.81, 109.95, 58.98, 32.10; MS(EI-MS) = 333(M+).
3-iodo-1-methyl-1H-indole (4m) 13
Isolated yield: 94%; 1H NMR (500 MHz, CDCl3+d6-DMSO): δ 7.43-7.41 (d, 1H, J = 7.8
Hz), 7.24-7.23 (m, 2H), 7.19-7.15 (m, 1H), 7.03 (s, 1H), 3.69 (s, 3H); 13C NMR (500 MHz,
CDCl3+d6-DMSO): δ 136.82, 132.77, 130.46, 122.68, 121.18, 120.31, 109.47, 54.81, 33.15;
MS (EI-MS) = 256 (M+).
2-chloro-1H-imidazole (5a) 14
Isolated yield: 88%; 1H NMR (400 MHz, CDCl3): δ 11.81 (s, 1H), 7.84 (s, 1H), 7.09 (s, 1H); 13C NMR (400 MHz, CDCl3): δ 177.74, 134.60, 120.99; MS (EI-MS) =102 (M+).
2-chloro-1H-imidazole (5b) 15
5a
NH
N
Cl
N
I
4l
N
I
4m
13
Isolated yield: 90%; 1H NMR (400 MHz, CDCl3): δ 11.69 (s, 1H), 7.78 (s, 1H), 7.09 (s,
1H); 13C NMR (400 MHz, CDCl3): δ 177.82, 134.80, 121.28; MS (EI-MS) =145 (M+).
4. 1H NMR and 13C NMR Spectra of the Products
1H NMR and 13C NMR Spectra of Compound 2a
5b
NH
N
Br
14
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
3.64
1.43
1.34
1.00
7.18
7.19
7.23
7.26
7.28
7.36
7.39
7.63
7.66
8.10
0102030405060708090100110120130f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
75.6
976
.01
76.3
2
105.
57
110.
44
117.
2611
9.44
119.
7912
2.10
124.
38
133.
94
1H NMR and 13C NMR Spectra of Compound 2b
15
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-2E+08
0
2E+08
4E+08
6E+08
8E+08
1E+09
1E+09
1E+09
2E+09
2E+09
2E+09
2E+09
2E+09
3E+09
3E+09
1.14
1.11
2.38
1.00
6.89
6.90
6.91
6.92
6.94
6.94
7.13
7.13
7.18
7.18
7.19
7.20
7.21
7.21
7.22
8.01
6.906.957.007.057.107.157.207.25f1 (ppm)
0
5E+08
1.14
1.11
2.38
6.89
6.90
6.91
6.92
6.94
6.94
7.13
7.13
7.18
7.18
7.19
7.20
7.21
7.21
7.22
0102030405060708090100110120130140150160f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
76.8
077
.05
77.3
1
103.
2610
3.46
106.
5311
1.74
111.
9511
2.37
112.
44
122.
6112
5.84
125.
92
131.
47
157.
3615
9.24
1H NMR and 13C NMR Spectra of Compound 2c
16
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.5f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
1E+09
2E+09
2E+09
2E+09
2.43
1.65
1.12
1.00
7.18
7.18
7.19
7.20
7.21
7.25
7.26
7.28
7.61
7.61
8.09
0102030405060708090100110120130140150f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
76.7
477
.06
77.3
8
106.
21
112.
61
117.
89
122.
2212
3.64
126.
4212
6.48
133.
32
1H NMR and 13C NMR Spectra of Compound 2d
17
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
1.19
1.09
1.27
1.21
1.00
7.19
7.19
7.21
7.21
7.25
7.25
7.26
7.29
7.30
7.56
7.57
8.22
0102030405060708090100110120130140150f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
7E+0876.7
777
.09
77.4
1
106.
01
113.
0411
3.81
120.
9612
2.09
126.
1612
7.06
133.
59
1H NMR and 13C NMR Spectra of Compound 2e
18
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
2.30
1.50
0.96
1.00
7.13
7.15
7.26
7.48
7.50
7.98
8.18
0102030405060708090100110120130140150f1 (ppm)
-2E+07
0
2E+07
4E+07
6E+07
8E+07
1E+08
1E+08
1E+08
2E+08
2E+08
2E+08
2E+08
2E+08
3E+08
3E+08
3E+0860.4
6
76.7
377
.05
77.2
577
.36
83.8
3
113.
42
121.
63
127.
2812
7.80
131.
5713
4.07
1H NMR and 13C NMR Spectra of Compound 2f
19
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-2E+07
0
2E+07
4E+07
6E+07
8E+07
1E+08
1E+08
1E+08
2E+08
2E+08
2E+08
2E+08
2E+08
3E+08
3E+08
3E+08
3E+08
3E+08
4E+08
4E+08
1.08
1.18
1.09
0.83
1.00
7.26
7.35
7.36
7.42
7.45
8.16
8.16
8.18
8.18
8.49
8.63
8.63
0102030405060708090100110120130140150f1 (ppm)
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+0838
.27
38.5
538
.83
39.1
039
.38
39.6
639
.94
76.5
777
.00
77.2
077
.43
103.
14
110.
65
115.
8411
6.67
126.
2812
7.49
138.
4914
0.32
1H NMR and 13C NMR Spectra of Compound 2g
20
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
7E+08
3.00
1.44
1.35
1.57
1.39
1.11
7.09
7.09
7.11
7.11
7.15
7.16
7.26
7.28
7.45
8.00
0102030405060708090100110120130140150f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
21.4
4
76.7
377
.04
77.3
6
106.
04
111.
16
117.
7812
0.87
124.
8412
5.60
129.
95
133.
34
1H NMR and 13C NMR Spectra of Compound 2h
21
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
7E+08
8E+08
8E+08
3.00
0.91
0.91
1.58
0.85
3.89
6.89
6.89
6.91
6.91
6.99
7.00
7.20
7.20
7.25
7.26
7.27
8.10
0102030405060708090100110120130140150160f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+0829
.72
76.7
877
.04
77.2
9
99.2
7
106.
14
112.
4311
3.98
121.
32
125.
79
129.
99
154.
87
1H NMR and 13C NMR Spectra of Compound 2i
22
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
1E+09
3.00
0.96
0.90
0.74
0.75
2.49
7.26
7.31
7.33
8.08
8.11
8.28
8.50
0102030405060708090100110120130140150f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+0911.5
1
38.3
638
.64
38.9
239
.20
39.4
839
.75
40.0
3
76.5
677
.00
77.4
0
89.9
1
110.
4911
3.82
116.
07
126.
19
136.
5813
7.62
140.
70
1H NMR and 13C NMR Spectra of Compound 2j
23
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
0.89
2.91
1.00
5.01
1.59
7.16
7.17
7.18
7.20
7.20
7.22
7.23
7.24
7.25
7.26
7.33
7.34
7.35
7.35
7.36
7.36
7.37
7.49
7.50
7.51
7.51
7.53
7.55
7.58
7.60
7.62
7.507.557.60f1 (ppm)
0
1E+08
2E+08
3E+08
5.01
1.59
7.49
7.50
7.51
7.51
7.53
7.55
7.58
7.60
7.62
0102030405060708090100110120130140150160170180190200f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
93.5
9
113.
06
127.
0112
7.75
129.
3313
0.51
132.
1513
2.79
138.
2814
0.52
164.
56
200.
10
1H NMR and 13C NMR Spectra of Compound 3a
24
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
3.00
1.26
1.23
0.93
7.18
7.21
7.23
7.24
7.26
7.28
7.37
7.39
7.58
7.61
8.19
0102030405060708090100110120130140150f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
1E+09
2E+09
2E+0976.7
977
.05
77.3
0
106.
09
112.
9811
3.83
121.
0212
2.03
126.
1812
7.09
133.
60
1H NMR and 13C NMR Spectra of Compound 3b
25
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
3.77
1.10
1.00
7.15
7.17
7.19
7.21
7.21
7.23
7.24
7.26
7.26
7.53
7.53
8.45
7.157.257.357.457.55f1 (ppm)
0
1E+07
2E+07
3E+07
4E+07
5E+07
6E+07
3.77
1.10
7.15
7.17
7.19
7.21
7.21
7.23
7.24
7.26
7.26
7.53
7.53
0102030405060708090100110120130140150f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+0876.8
277
.08
77.3
3
112.
8311
4.12
123.
6912
6.13
128.
8712
9.69
131.
6213
4.41
139.
42
1H NMR and 13C NMR Spectra of Compound 3c
26
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
2.26
1.27
1.13
1.00
7.19
7.19
7.21
7.21
7.25
7.25
7.26
7.29
7.30
7.56
7.57
8.22
7.207.257.307.357.407.457.507.557.60f1 (ppm)
0
1E+08
2E+08
3E+08
2.26
1.27
1.13
7.19
7.19
7.21
7.21
7.25
7.25
7.26
7.29
7.30
7.56
7.57
0102030405060708090110130150f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
Inte
nsi
ty
76
.79
77
.11
77
.42
10
2.4
3
11
2.0
7
12
0.1
51
22
.35
12
5.4
91
25
.62
12
8.9
91
34
.17
1H NMR and 13C NMR Spectra of Compound 3d
27
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
1E+09
2.24
1.00
0.95
0.81
7.21
7.22
7.22
7.24
7.25
7.31
7.31
7.33
7.34
7.72
7.72
8.21
7.207.247.287.327.36f1 (ppm)
0
2E+08
4E+08
6E+08
2.24
1.00
7.21
7.22
7.22
7.24
7.25
7.31
7.31
7.33
7.34
0102030405060708090100110120130140150f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+0976.7
577
.07
77.3
8
90.9
9
112.
9111
3.99
121.
9012
4.55
126.
1912
8.59
133.
98
1H NMR and 13C NMR Spectra of Compound 3e
28
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
1E+09
2E+09
2.35
1.19
1.06
1.00
7.14
7.17
7.19
7.20
7.26
7.49
7.49
7.51
7.51
7.93
7.93
7.93
8.25
7.207.307.407.50f1 (ppm)
0
1E+08
2E+08
2.35
1.19
7.14
7.17
7.19
7.20
7.26
7.49
7.49
7.51
7.51
0102030405060708090110130150f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
Inte
nsi
ty
76
.73
77
.05
77
.36
84
.04
90
.69
11
3.3
1
12
4.1
11
28
.19
12
9.3
01
31
.62
13
4.4
5
1H NMR and 13C NMR Spectra of Compound 3f
29
0.01.02.03.04.05.06.07.08.09.010.011.012.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
2.46
1.08
0.96
1.00
7.16
7.17
7.21
7.24
7.28
7.79
7.83
8.19
11.3
1
6.97.07.17.27.37.4f1 (ppm)
0
1E+08
2E+08
3E+08
2.46
7.16
7.17
7.21
7.24
7.28
0102030405060708090100110120130140150f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
38.6
138
.88
39.1
639
.44
39.7
239
.99
40.2
7
76.5
776
.67
77.0
077
.10
77.4
277
.53
91.6
1
111.
6911
5.48
117.
04
125.
6012
6.99
138.
20
141.
20
1H NMR and 13C NMR Spectra of Compound 3g
30
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
3.00
0.95
0.88
1.04
0.93
0.85
7.06
7.06
7.08
7.08
7.18
7.19
7.25
7.26
7.27
7.36
8.14
7.107.207.30f1 (ppm)
0
5E+07
1E+08
2E+08
0.95
0.88
1.04
0.93
7.06
7.06
7.08
7.08
7.18
7.19
7.25
7.26
7.27
7.36
0102030405060708090100110120130140150f1 (ppm)
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
21.4
8
76.8
377
.08
77.3
4
102.
13
110.
70
120.
3812
3.65
124.
2712
8.18
129.
03
134.
15
1H NMR and 13C NMR Spectra of Compound 3h
31
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
1E+09
2E+09
2E+09
2E+09
3.00
1.87
0.87
0.85
3.92
6.92
6.92
6.93
6.94
7.02
7.02
7.23
7.23
7.28
7.29
7.30
6.957.057.157.257.35f1 (ppm)
0
1E+08
2E+08
1.87
0.87
6.92
6.92
6.93
6.94
7.02
7.02
7.23
7.23
7.28
7.29
7.30
0102030405060708090100110120130140150160f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
7E+08
8E+08
55.5
4
76.8
577
.10
77.3
6
102.
40
111.
7811
2.39
124.
9512
8.34
131.
0313
1.14
154.
24
1H NMR and 13C NMR Spectra of Compound 3i
32
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.5f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
3.23
1.15
1.13
1.08
1.00
3.14
7.36
7.39
7.97
8.01
8.31
11.6
0
0102030405060708090100110120130140150f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
11.5
1
38.3
638
.64
38.9
239
.20
39.4
839
.75
40.0
3
76.5
677
.00
77.4
0
89.9
1
110.
4911
4.01
116.
07
126.
19
136.
5813
7.62
140.
70
1H NMR and 13C NMR Spectra of Compound 3j
33
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
7E+08
8E+08
8E+08
1.09
1.15
1.58
7.00
6.79
6.80
7.12
7.14
7.16
7.25
7.26
7.27
7.28
7.42
7.44
7.45
7.47
7.48
7.53
7.54
7.56
0102030405060708090100110120130140150160170180f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
7E+08
76.7
377
.05
77.3
7
110.
10
123.
8312
5.98
126.
3612
6.44
128.
5412
9.78
130.
3313
3.83
143.
94
171.
73
1H NMR and 13C NMR Spectra of Compound 3k
34
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
1E+09
2E+09
2.28
2.96
6.79
1.00
5.28
7.11
7.13
7.17
7.17
7.19
7.19
7.20
7.21
7.22
7.22
7.24
7.27
7.29
7.30
7.32
7.33
7.57
7.57
7.58
7.59
7.59
7.59
7.60
0102030405060708090100110120130140150f1 (ppm)
-2E+07
0
2E+07
4E+07
6E+07
8E+07
1E+08
1E+08
1E+08
2E+08
2E+08
2E+08
2E+08
2E+08
3E+08
3E+08
3E+08
3E+08
3E+0850.3
7
76.7
577
.07
77.3
8
90.3
6
109.
93
119.
4712
0.39
122.
8812
6.97
127.
0812
7.56
127.
9412
8.92
135.
9413
6.79
1H NMR and 13C NMR Spectra of Compound 3l
35
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
3.20
1.17
2.16
5.10
1.00
3.63
7.22
7.23
7.24
7.27
7.29
7.31
7.32
7.34
7.44
7.49
7.49
7.50
7.60
7.62
7.257.357.457.557.65f1 (ppm)
0
5E+07
1E+08
2E+08
1.17
2.16
5.10
1.00
7.22
7.23
7.24
7.27
7.29
7.31
7.32
7.34
7.44
7.49
7.49
7.50
7.60
7.62
0102030405060708090100110120130140150f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
32.1
0
58.9
8
76.8
377
.15
77.3
677
.47
109.
95
120.
8112
1.54
123.
0012
8.51
128.
7412
8.88
130.
4613
1.00
131.
7013
7.84
141.
81
1H NMR and 13C NMR Spectra of Compound 4a
36
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
3.00
0.93
0.94
0.82
7.19
7.19
7.21
7.22
7.22
7.23
7.23
7.24
7.24
7.25
7.26
7.26
7.34
7.35
7.45
7.47
8.28
7.157.207.257.307.357.407.457.50f1 (ppm)
0
1E+08
2E+08
3E+08
4E+08
3.00
0.93
0.94
7.19
7.19
7.21
7.22
7.22
7.23
7.23
7.24
7.24
7.25
7.26
7.26
7.34
7.35
7.45
7.47
1H NMR and 13C NMR Spectra of Compound 4b
0102030405060708090100110120130140150f1 (ppm)
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
57.6
4
76.7
577
.07
77.3
9
111.
28
120.
8512
1.05
123.
23
128.
4212
9.83
135.
65
37
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-2E+08
0
2E+08
4E+08
6E+08
8E+08
1E+09
1E+09
1E+09
2E+09
2E+09
2E+09
2E+09
2E+09
3E+09
3E+09
3E+09
1.13
1.13
2.16
1.00
6.97
6.98
6.99
7.00
7.01
7.01
7.12
7.12
7.14
7.14
7.26
7.29
7.30
7.31
7.31
7.32
8.35
0102030405060708090100110120130140150160170f1 (ppm)
-2E+07
0
2E+07
4E+07
6E+07
8E+07
1E+08
1E+08
1E+08
2E+08
2E+08
2E+08
2E+08
2E+08
3E+08
3E+08
3E+08
3E+08
3E+0857.0
157
.05
76.7
977
.04
77.3
0
106.
0710
6.27
111.
7411
1.95
112.
0811
2.16
130.
1113
0.53
130.
6113
2.14
157.
6915
9.57
1H NMR and 13C NMR Spectra of Compound 4c
38
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.5f1 (ppm)
-2E+08
0
2E+08
4E+08
6E+08
8E+08
1E+09
1E+09
1E+09
2E+09
2E+09
2E+09
2E+09
2E+09
1.10
2.51
1.09
1.00
7.18
7.19
7.20
7.21
7.26
7.28
7.30
7.30
7.31
7.45
7.45
8.38
7.207.257.307.357.407.45f1 (ppm)
0
2E+08
4E+08
6E+08
8E+08
1.10
2.51
1.09
7.18
7.19
7.20
7.21
7.26
7.28
7.30
7.30
7.31
7.45
7.45
0102030405060708090100110120130140f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
56.7
5
76.7
377
.05
77.3
6
112.
37
120.
6612
3.66
126.
7512
9.75
131.
0513
4.08
1H NMR and 13C NMR Spectra of Compound 4d
39
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.5f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
1E+09
2E+09
2E+09
2E+09
1.11
1.82
1.12
1.00
6.81
6.82
6.84
6.85
6.87
6.88
7.09
7.10
7.12
7.13
7.14
7.15
7.23
7.25
7.26
7.28
10.6
0
6.86.97.07.17.27.3f1 (ppm)
0
2E+08
4E+08
6E+08
8E+08
1.11
1.82
1.12
6.81
6.82
6.84
6.85
6.87
6.88
7.09
7.10
7.12
7.13
7.14
7.15
7.23
7.25
7.26
7.28
0102030405060708090100110120130140f1 (ppm)
-2E+07
0
2E+07
4E+07
6E+07
8E+07
1E+08
1E+08
1E+08
2E+08
2E+08
2E+08
2E+08
2E+08
3E+08
3E+08
3E+08
3E+08
3E+0876.7
277
.04
77.3
6
103.
50
112.
3411
4.09
122.
5912
5.94
128.
8713
0.97
131.
46
1H NMR and 13C NMR Spectra of Compound 4e
40
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
1E+09
2E+09
2E+09
2E+09
1.07
1.09
2.01
1.00
0.00
6.97
6.98
6.99
7.00
7.01
7.01
7.12
7.12
7.14
7.14
7.26
7.29
7.30
7.31
7.31
7.32
8.35
0102030405060708090100110120130140150f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
56.3
3
76.7
777
.08
77.4
0
84.2
8
113.
22
129.
2012
9.98
131.
6413
2.30
134.
84
1H NMR and 13C NMR Spectra of Compound 4f
41
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.5f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
7E+08
2.19
1.04
0.92
1.00
7.51
7.52
7.52
7.54
8.08
8.09
8.11
8.12
8.38
11.7
3
0102030405060708090100110120130140150f1 (ppm)
-1E+07
0
1E+07
2E+07
3E+07
4E+07
5E+07
6E+07
7E+07
8E+07
9E+07
1E+08
1E+08
1E+08
1E+08
1E+08
2E+08
38.0
638
.34
38.6
238
.90
39.1
839
.46
39.7
3
56.8
7
76.5
777
.00
77.4
4
111.
27
116.
51
128.
26
131.
88
138.
4514
0.79
143.
91
1H NMR and 13C NMR Spectra of Compound 4g
42
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
3.38
1.00
3.56
0.76
2.51
7.08
7.08
7.11
7.11
7.26
7.27
7.28
7.29
8.28
0102030405060708090100110120130140150160f1 (ppm)
-2E+07
0
2E+07
4E+07
6E+07
8E+07
1E+08
1E+08
1E+08
2E+08
2E+08
2E+08
2E+08
2E+08
3E+08
3E+0821.4
4
57.0
7
76.8
077
.06
77.3
1
110.
98
120.
58
124.
8812
8.43
129.
9713
0.33
133.
94
1H NMR and 13C NMR Spectra of Compound 4h
43
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
3.00
0.95
3.23
0.87
3.88
6.88
6.89
6.91
6.92
7.04
7.05
7.13
7.14
7.22
7.25
7.98
0102030405060708090100110120130140150160f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+0830
.99
55.9
0
76.7
677
.08
77.3
9
102.
41
111.
7411
2.39
124.
9012
8.32
130.
99
154.
23
1H NMR and 13C NMR Spectra of Compound 4i
44
0.01.02.03.04.05.06.07.08.09.010.011.012.0f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
7E+08
8E+08
3.34
1.07
1.05
0.94
1.00
2.49
7.33
7.36
7.98
8.02
8.23
8.23
11.5
8
0102030405060708090100110120130140150f1 (ppm)
-2E+07
0
2E+07
4E+07
6E+07
8E+07
1E+08
1E+08
1E+08
2E+08
2E+08
2E+08
2E+08
2E+08
3E+08
3E+08
3E+08
13.6
0
38.4
638
.74
39.0
139
.29
39.5
739
.85
40.1
3
58.6
5
76.5
777
.00
77.4
3
110.
45
115.
9311
6.31
129.
58
139.
1414
0.59
140.
91
1H NMR and 13C NMR Spectra of Compound 4j
45
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
2.26
1.01
7.00
7.16
7.18
7.20
7.21
7.22
7.23
7.25
7.30
7.31
7.33
7.34
7.35
7.48
7.49
7.52
7.54
7.57
7.60
7.62
7.157.207.257.307.357.407.457.507.557.607.65f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
2.26
1.01
7.00
7.16
7.18
7.20
7.21
7.22
7.23
7.25
7.30
7.31
7.33
7.34
7.35
7.48
7.49
7.52
7.54
7.57
7.60
7.62
0102030405060708090110130150170f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
Inte
nsit
y
76.7
477
.05
77.3
7
110.
6111
7.05
117.
8512
0.44
123.
2712
4.45
126.
5112
9.65
131.
5413
2.89
139.
44
168.
41
1H NMR and 13C NMR Spectra of Compound 4k
46
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
2.21
3.16
1.15
4.53
0.95
1.00
5.26
7.10
7.12
7.13
7.13
7.17
7.19
7.20
7.24
7.26
7.27
7.29
7.30
7.33
7.56
7.58
7.107.157.207.257.307.35f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
3.16
1.15
4.53
0.95
7.10
7.12
7.13
7.13
7.17
7.19
7.20
7.24
7.26
7.27
7.29
7.30
7.33
0102030405060708090100110120130140150160170f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+0829.7
3
50.1
5
76.7
377
.05
77.3
7
109.
74
117.
3011
7.70
119.
6112
0.45
122.
5912
6.87
127.
7312
8.81
129.
8013
3.39
137.
25
168.
58
1H NMR and 13C NMR Spectra of Compound 4l
47
0102030405060708090100110120130140150f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
32.1
0
58.9
8
76.8
377
.15
77.3
677
.47
109.
95
120.
8112
1.54
123.
0012
8.51
128.
7412
8.88
130.
4613
1.00
131.
7013
7.84
141.
81
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.5f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
7E+08
8E+08
8E+08
8E+08
3.00
1.36
1.95
6.05
3.64
7.19
7.20
7.21
7.21
7.22
7.23
7.23
7.24
7.28
7.28
7.29
7.30
7.43
7.44
7.45
7.46
7.47
7.49
7.51
7.207.257.307.357.407.457.50f1 (ppm)
0
1E+08
2E+08
3E+08
4E+08
1.36
1.95
6.05
7.19
7.20
7.21
7.21
7.22
7.23
7.23
7.24
7.28
7.28
7.29
7.30
7.43
7.44
7.45
7.46
7.47
7.49
7.51
1H NMR and 13C NMR Spectra of Compound 4m
48
0102030405060708090100110120130140150f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
7E+08
8E+08
8E+08
8E+08
33.1
5
54.8
1
76.8
477
.09
77.3
5
109.
47
120.
3112
1.18
122.
68
130.
4613
2.77
136.
82
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
3.00
0.99
1.05
1.91
1.02
3.69
7.15
7.16
7.17
7.17
7.18
7.19
7.19
7.23
7.23
7.24
7.24
7.24
7.24
7.41
7.43
7.057.157.257.357.45f1 (ppm)
0
5E+07
1E+08
0.99
1.05
1.91
1.02
7.15
7.16
7.17
7.17
7.18
7.19
7.19
7.23
7.23
7.24
7.24
7.24
7.24
7.41
7.43
1H NMR and 13C NMR Spectra of Compound 5a
49
0.01.02.03.04.05.06.07.07.58.59.510.511.5f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
1E+09
2E+09
2E+09
2E+09
7.09
7.84
11.8
1
0102030405060708090100110120130140150160170180f1 (ppm)
-5E+07
0
5E+07
1E+08
2E+08
2E+08
2E+08
3E+08
4E+08
4E+08
4E+08
5E+08
6E+08
6E+08
6E+08
7E+08
8E+08
8E+08
8E+0876.8
477
.10
77.3
5
120.
99
134.
60
177.
74
1H NMR and 13C NMR Spectra of Compound 5b
50
0.01.02.03.04.05.06.07.08.09.010.011.012.013.0f1 (ppm)
-2E+08
0
2E+08
4E+08
6E+08
8E+08
1E+09
1E+09
1E+09
2E+09
2E+09
2E+09
2E+09
2E+09
3E+09
3E+09
3E+09
3E+09
Inte
nsity
1.12
0.57
1.00
7.09
7.78
11.6
9
0102030405060708090100110120130140150160170180190f1 (ppm)
-1E+08
0
1E+08
2E+08
3E+08
4E+08
5E+08
6E+08
7E+08
8E+08
9E+08
1E+09
1E+09
1E+09
1E+09
1E+09
2E+09
2E+09
76.7
977
.10
77.4
2
121.
28
134.
80
177.
82
5. References:
51
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