Supporting Information
Substrate-Directable Heck reactions with Arenediazonium Salts. The Regio- and Stereoselective Arylation of Allylamine Derivatives and Applications in the Synthesis of Naftifine and Abamines Patrícia Prediger,† Laís Ferreira Barbosa,† Yves Génisson‡ and Carlos Roque Duarte Correia*,† †
Instituto de Química, Universidade Estadual de Campinas, UNICAMP, C.P. 6154, CEP. 13084-971, Campinas, São Paulo, Brazil. ‡
UMR5068, CNRS-Université Paul Sabatier, Toulouse, France.
[email protected] CONTENTS Chromatographic separation of isomers 6e, 7e and 8e
S2
NMR Spectra
S4
S1
Chromatographic separation of isomers 6e, 7e and 8e
Analytical chromatographic separation of the isomers 6e, 7e and 8e was performed on a commercial UPLC system containing a sample manager, a binary solvent manager pump, a UV detector and a UPLC BECH C18 (1.7µm 2.1x50 mm) column. Resolution was achieved under the following conditions: solvent mixture of water/acetonitrile = 55/45 applying a constant flow of 0.5 mL/min, at 25 oC, at 240 nm. Retention Times (RT): 8e = 2.27 min, 6e = 2.41 min, 7e = 2.62 min. Ratio 8e/6e/7e = 3.3/92.5/3.8.
Table 1. HPLC separation of the isomers 6e, 7e and 8e.
8e 6e 7e
Preparative HPLC separation of compounds 6e, 7e and 8e was performed using a preparative chromatograph, containing a PDA-UV detector, a sample manager and a Bridge S2
C18 (19 x 150mm) column. Resolution of the isomers was achieved under the following conditions: solvent mixture of water/acetonitrile = 55/45 applying a constant flow of 20 mL/min. at 25 oC, at 240 nm. Retention Times: 8e = 15.79 min, 6e = 16.80 min, 7e = 18.40 min.
S3
NMR SPECTRA
O N 4 O
6.0
2.04
7.0
2.13
1.00
8.0
2.16
2.17
ppm (t1)9.0
5.0
4.0
3.0
H NMR spectrum of compound 4 in CDCl3, 300 MHz.
1
ppm (t1)
150
100
50
C NMR spectrum of compound 4 in CDCl3, 75 MHz.
13
S4
1H trans isomer
1H traces diarylated product
peak 1H cis isomer
5.50
5.0
3.08
6.0
2.04
7.0
5.00
1.00
8.0
1.00 2.03
2.20
2.08 2.07
9.0 (t1) ppm
1.43
6.00
1.54
1.00
19.75
ppm (t1)
peaks 2H β-substituted isomer
4.0
3.0
2.0
1.0
H NMR spectrum of compound 6a in CDCl3, 250 MHz.
1
150
ppm (t1)
100
50
C NMR spectrum of compound 6a in CDCl3, 62.5 MHz.
13
S5
O N OMe O
6b
1.42
5.50
5.00
6.0
5.0
3.08
2.01
1.00
7.0
2.03
0.99
1.04
1.04
2.12
2.03
8.0 (t1) ppm
1.29
1.00
26.69
6.00 ppm (t1)
4.0
H NMR spectrum of compound 6b in CDCl3, 250 MHz.
1
ppm (t1)
ppm (t1)
129.00
123.50 ppm (t1)
150
123.00
100
50
C NMR spectrum of compound 6b in CDCl3, 62.5 MHz.
13
S6
1.13
1.99
7.0
5.50
1.00
1.00
5.19
2.02 1.98
ppm8.0 (t1)
1.00
1.75
21.02
6.00
ppm (t1)
6.0
5.0
4.0
3.0
2.0
H NMR spectrum of compound 6c in CDCl3, 250 MHz.
1
134.50 134.00 133.50 133.00 132.50 132.00 ppm (t1)
123.50 123.40 123.30 123.20 ppm 123.60 (t1)
150
ppm (t1)
100
50
C NMR spectrum of compound 6c in CDCl3, 62.5 MHz.
13
S7
2.04
7.0
5.50
1.01
8.0
1.00
1.00 1.00 0.99
2.04 1.95
9.0 (t1) ppm
1.00
2.70
45.57
6.00
ppm (t1)
6.0
5.0
4.0
3.0
H NMR spectrum of compound 6d in CDCl3, 250 MHz.
1
ppm (t1) 135.0
130.0
150
ppm (t1)
125.0
100
50
0
C NMR spectrum of compound 6d in CDCl3, 62.5 MHz.
13
S8
1.72
7.0
1.90
8.0
5.50
2.02
2.28
2.05 2.18
9.0(t1) ppm
1.81
1.00
50.80
ppm (t1) 6.00
6.0
5.0
4.0
3.0
H NMR spectrum of compound 6e in CDCl3, 250 MHz.
1
ppm (t1)
128.50 ppm (t1)
128.00
122.50
122.00
127.50
150
ppm (t1)
100
50
C NMR spectrum of compound 6e in CDCl3, 62.5 MHz.
13
S9
F O N 7e
O
6.550
ppm (t1) 5.700
5.650
2.09
1.00
7.0
6.600
1.05
2.17
2.35
2.17 2.11
ppm 8.0 (t1)
1.00
1.05
6.650 ppm (t1)
6.0
5.0
4.0
3.0
H NMR spectrum of compound 7e in CDCl3, 500 MHz.
1
132.30 132.20 132.10 132.00 ppm (t1)
ppm (t1) 115.50
131.00 ppm (t1)
ppm (t1)
150
130.50
125.850 ppm (t1) 125.800 125.750
100
50
C NMR spectrum of compound 7e in CDCl3, 125 MHz.
13
S10
F
5.50 ppm (t1)
N
5.40
1.00
1.00
O
5.30
5.20
5.10
8e O
6.0
2.03
7.0
1.00
1.00
8.0
2.07
2.07
2.09 2.04
ppm (t1) 9.0
5.0
4.0
3.0
H NMR spectrum of compound 8e in CDCl3, 500 MHz.
1
114.350 ppm (t1) 114.300 114.250 114.200
128.50 ppm (t1)
180 ppm (t1)170
160
150
140
130
120
110
100
90
128.00
80
70
116.00 ppm (t1)115.50 115.00
60
50
40
30
20
10
0
C NMR spectrum of compound 8e in CDCl3, 125 MHz.
13
S11
5.50
1.94
0.99
7.0
1.00
8.0
0.99 1.99 1.39
2.02 1.97
9.0 ppm (t1)
1.00
1.54
30.51
6.00
ppm (t1)
6.0
5.0
4.0
3.0
2.0
H NMR spectrum of compound 6f in CDCl3, 250 MHz.
1
132.70 ppm (t1)
132.60
132.50
132.40
ppm (t1)
ppm (t1)
138.50
122.50
122.00
138.00
150
ppm (t1)
100
50
C NMR spectrum of compound 6f in CDCl3, 62.5 MHz.
13
S12
1.00
6.00
5.50
2.01
7.0
1.00
8.0
0.99
2.70 1.99
2.06 1.99
9.0 (t1) ppm
1.54
25.71
ppm (t1)
6.0
5.0
4.0
3.0
2.0
H NMR spectrum of compound 6g in CDCl3, 250 MHz.
1
150
ppm (t1)
100
50
C NMR spectrum of compound 6g in CDCl3, 62.5 MHz.
13
S13
5.50
2.03
0.99
7.0
1.00
8.0
2.02
1.96 2.07 1.99
9.0(t1) ppm
1.00
1.63
16.48
6.00
ppm (t1)
6.0
5.0
4.0
3.0
2.0
H NMR spectrum of compound 6h in CDCl3, 250 MHz.
1
150
ppm (t1)
100
50
C NMR spectrum of compound 6h in CDCl3, 62.5 MHz.
13
S14
1.00
5.50
2.04
7.0
6.00
1.00
1.00
8.0
5.58
2.03 1.96
9.0 ppm (t1)
1.10
28.26
ppm (t1)
6.0
5.0
4.0
3.0
2.0
H NMR spectrum of compound 6i in CDCl3, 250 MHz.
1
150
ppm (t1)
100
50
C NMR spectrum of compound 6i in CDCl3, 62.5 MHz.
13
S15
5.50
7.0
2.05
1.01
8.0
1.00
2.03 1.03 6.04 1.96
ppm (t1)9.0
6.00
1.08
1.00
46.35
6.50 ppm (t1)
6.0
5.0
4.0
3.0
H NMR spectrum of compound 6j in CDCl3, 250 MHz.
1
134.0
170
160
133.5
150
128
ppm
140
130
120
127
110
126
125
100
124
ppm
90
80
70
60
50
40 ppm
C NMR spectrum of compound 6j in CDCl3, 62.5 MHz.
13
S16
1.03
5.50
7.0
1.91
0.94
8.0
1.00
1.10 4.15 4.33 2.10 2.07
9.0(t1) ppm
6.00
1.00
1.23
25.67
ppm (t1)
6.0
5.0
4.0
3.0
2.0
H NMR spectrum of compound 6k in CDCl3, 250 MHz.
1
140.8
170
160
140.6
127.5
ppm
150
140
130
120
110
127.0
100
ppm
90
80
70
60
50
40
ppm
C NMR spectrum of compound 6k in CDCl3, 62.5 MHz.
13
S17
1.02
2.07
7.0
5.50
1.00
1.00
8.0
2.05
2.09 2.00
2.00
ppm (t1) 9.0
6.00
1.00
2.22
35.90
6.50 (t1) ppm
6.0
5.0
4.0
3.0
2.0
H NMR spectrum of compound 6l in CDCl3, 250 MHz.
1
124.50 ppm (t1)
124.00
123.50
123.00
150
ppm (t1)
100
50
0
C NMR spectrum of compound 6l in CDCl3, 62.5 MHz.
13
S18
6.0
5.50
1.97
7.0
2.01 1.02
8.0
1.00 2.02 1.00
2.05 1.99
ppm9.0 (t1)
1.00
1.02
12.07
ppm (t1) 6.00
5.0
4.0
3.0
2.0
H NMR spectrum of compound 6m in CDCl3, 250 MHz.
1
150
ppm (t1)
100
50
0
C NMR spectrum of compound 6m in CDCl3, 62.5 MHz
13
S19
O N O
6n Me
1.07
5.50
6.0
5.0
3.01
2.04
7.0
6.00
1.01
8.0
1.00
2.01 2.55
2.05 1.97
9.0 (t1) ppm
1.00
20.45
ppm (t1)
4.0
3.0
2.0
H NMR spectrum of compound 6n in CDCl3, 250 MHz.
1
134.0
170
160
133.5
150
ppm
140
130
120
110
100
90
80
70
60
50
40
30
ppm
C NMR spectrum of compound 6n in CDCl3, 62.5 MHz.
13
S20
5.0
4.0
9.28
3.10
2.08
2.07
1.00
6.0 ppm (t1)
3.0
2.0
H NMR spectrum of compound 9a in CDCl3, 250 MHz.
1
ppm (t1) 150
100
50
C NMR spectrum of compound 9a in CDCl3, 62.5 MHz.
13
S21
5.0
18.63
2.08
2.00
0.95
ppm6.0 (t1)
4.0
3.0
2.0
1.0
H NMR spectrum of compound 9b in CDCl3, 250 MHz.
1
ppm150 (t1)
100
50
C NMR spectrum of compound 9b in CDCl3, 62.5 MHz.
13
S22
N
6.0
5.0
4.0
3.0
9.59
1.00
7.0 ppm (t1)
3.24
O 9c
Me
2.19
Boc
2.0
H NMR spectrum of compound 9c in CDCl3, 250 MHz.
1
ppm (t1)
150
100
50
C NMR spectrum of compound 9c in CDCl3, 62.5 MHz.
13
S23
6.0
5.0
4.0
9.00
2.03
0.93
2.05
1.00
7.0 ppm (t1)
3.0
2.0
H NMR spectrum of compound 9d in CDCl3, 250 MHz.
1
150 ppm (t1)
100
50
C NMR spectrum of compound 9d in CDCl3, 62.5 MHz.
13
S24
4.0
2.02
5.0
2.01
2.02
6.0
2.02
1.00
ppm (t1) 7.0
3.0
2.0
H NMR spectrum of compound 9e in CDCl3, 250 MHz.
1
ppm (t1)
150
100
50
C NMR spectrum of compound 9e in CDCl3, 62.5 MHz.
13
S25
1.00
1.16
21.88
ppm (t1) 6.00
5.50
4.0
8.19
5.0
6.20
6.0
1.89
7.0
0.97
1.00
2.10
2.08
ppm 8.0 (t1)
3.0
2.0
1.0
H NMR spectrum of compound 10a in CDCl3, 250 MHz.
1
150
ppm (t1)
100
50
C NMR spectrum of compound 10a in CDCl3, 62.5 MHz.
13
S26
5.00
4.0
8.45
5.0
3.10
1.78
6.0
0.95
5.50
1.00
1.09
4.07
ppm (t1) 7.0
6.00
1.00
2.03
40.91
ppm (t1)
3.0
2.0
H NMR spectrum of compound 10b in CDCl3, 250 MHz.
1
ppm150 (t1)
100
50
C NMR spectrum of compound 10b in CDCl3, 62.5 MHz.
13
S27
MeO Boc
O
Br
N 10c
5.0
9.01
6.0
2.97
1.91
7.0
0.97
8.0
5.50
1.00
1.04 1.13 1.02 0.97
ppm (t1)
1.00
1.73
38.70
ppm (t1) 6.00
4.0
3.0
2.0
1.0
H NMR spectrum of the compound 10c in CDCl3, 250 MHz.
1
180 (t1) 170 ppm
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
C NMR spectrum of compound 10c in CDCl3, 62.5 MHz.
13
S28
2.05
6.40
6.30
6.20
6.10
5.00
6.00
5.0
4.0
18.13
6.0
3.26
1.91
0.97
1.00
2.19
2.30
ppm (t1) 7.0
5.50
0.97
1.00
6.60 6.50 ppm (t1)
2.04
1.00
37.03
6.00 ppm (t1)
3.0
2.0
H NMR spectrum of compound 10d in CDCl3, 250 MHz.
1
ppm (t1)150
100
50
C NMR spectrum of compound 10d in CDCl3, 62.5 MHz.
13
S29
2.67
5.50
2.63
1.00
44.32
ppm 6.00 (t1)
5.00
3.0
8.97
4.0
3.23
5.0
3.25
6.0
1.96
1.00
1.02
2.17
2.21
7.0 ppm (t1)
2.0
H NMR spectrum of compound 10e in CDCl3, 250 MHz.
1
ppm (t1) 150
100
50
C NMR spectrum of compound 10e in CDCl3, 62.5 MHz.
13
S30
5.50
4.0
3.0
9.17
3.09
5.0
2.64
6.0
6.00
1.99
7.0
1.00
1.02
4.05
9.0 ppm (t1)8.0
1.00
41.55
ppm (t1)
2.0
1.0
0.0
H NMR spectrum of compound 10f in CDCl3, 250 MHz.
1
ppm (t1)
150
100
50
C NMR spectrum of compound 10f in CDCl3, 62.5 MHz.
13
S31
4.62
4.0
9.24
5.0
5.50
3.19 1.98
6.0
0.87
1.00
1.00
2.10
2.13
ppm (t1)7.0
4.60
1.00
45.07
6.00 ppm (t1)
3.0
2.0
H NMR spectrum of compound 10g in CDCl3, 250 MHz.
1
150 ppm (t1)
100
50
C NMR spectrum of compound 10g in CDCl3, 62.5 MHz.
13
S32
1.00
1.52
25.11
6.10(t1)6.00 5.90 5.80 5.70 5.60 5.50 ppm
2.07
5.0
3.53
6.0
2.00
2.16
1.00
7.0
1.04
2.32
2.01
8.0 ppm (t1)
4.0
3.0
2.0
H NMR spectrum of compound 10h in CDCl3, 250 MHz.
1
150
ppm (t1)
100
50
C NMR spectrum of compound 10h in CDCl3, 62.5 MHz.
13
S33
2.03
6.0
1.98
7.0
1.00
8.0
0.89
1.97
1.95
ppm 9.0 (t1)
5.0
4.0
3.0
H NMR spectrum of compound 13a in CDCl3, 250 MHz.
1
200(t1) ppm
150
100
50
0
C NMR spectrum of compound 13a in CDCl3, 62.5 MHz.
13
S34
O
H N 13b
2.13
6.0
2.11
7.0
1.00
0.99
3.28
2.08
8.0 ppm (t1)
5.0
4.0
3.0
H NMR spectrum of compound 13b in CDCl3, 250 MHz.
1
135.00 ppm (t1)
134.50
190 (t1) 180 170 160 150 140 130 120 110 100 90 ppm
134.00
80
133.50
70
60
50
40
30
20
C NMR spectrum of compound 13b in CDCl3, 62.5 MHz.
13
S35
5.0
4.0
3.11
6.0
2.06
7.0
3.04
0.98
2.05
2.00
8.0 ppm (t1)
3.0
2.0
H NMR spectrum of compound 13c in CDCl3, 250 MHz.
1
150 ppm (t1)
100
50
C NMR spectrum of compound 13c in CDCl3, 62.5 MHz.
13
S36
O H
13d
2.09
2.05
1.00
0.97
1.08
10.0(t1) ppm
N H
5.0
H NMR spectrum of compound 13d in CDCl3, 250 MHz.
1
190(t1) 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
C NMR spectrum of compound 13d in CDCl3, 62.5 MHz.
13
S37
5.0
4.0
3.12
2.11
6.0
2.00
1.97
ppm (t1) 7.0
3.0
2.0
H NMR spectrum of compound 13e in CDCl3, 250 MHz.
1
ppm (t1)
150
100
50
C NMR spectrum of compound 13e in CDCl3, 62.5 MHz.
13
S38
2.04
6.0
2.02
7.0
1.00
0.90
8.0 ppm (t1)
5.0
4.0
3.0
2.0
1.0
H NMR spectrum of compound 13f in CDCl3, 250 MHz.
1
159.0 ppm (t1)158.0 157.0 156.0
ppm (t1)
150
100
50
C NMR spectrum of compound 13f in CDCl3, 62.5 MHz.
13
S39
H N
O
13g F
5.0
4.0
2.01
6.0
2.02
1.99
7.0
1.00
0.93
2.05
2.04
9.0 ppm (t1) 8.0
3.0
2.0
H NMR spectrum of compound 13g in CDCl3, 250 MHz.
1
131.00 ppm (t1)130.50 130.00 129.50 129.00
ppm (t1)
166.50 ppm (t1)
190 ppm (t1)
180
115.50
166.00
170
160
150
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
C NMR spectrum of compound 13g in CDCl3, 62.5 MHz.
13
S40
OMe H N
O
14a F
6.0
5.0
3.09
1.95
1.00
7.0
1.09 0.88
8.0
2.05 2.05 2.13
1.99
9.0 ppm (t1)
4.0
3.0
2.0
H NMR spectrum of compound 14a in CDCl3, 250 MHz.
1
130.50 ppm (t1)
130.00
129.50
150
ppm (t1)
115.50 115.00 114.50 114.00 ppm (t1)
100
50
C NMR spectrum of compound 14a in CDCl3, 62.5 MHz.
13
S41
OMe H N
O
14b
6.0
5.0
3.10
1.95
1.00
7.0
0.88 1.06
2.01
2.19 3.03
1.96
ppm (t1)8.0
4.0
3.0
2.0
1.0
H NMR spectrum of compound 14b in CDCl3, 250 MHz.
1
135.0 ppm (t1)
133.3
131.7
130.0
128.3
126.7
ppm180 (t1)170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20
C NMR spectrum of compound 14b in CDCl3, 62.5 MHz.
13
S42
5.0
4.0
3.03
6.0
5.03
1.00
1.00
7.0
1.01
2.00
8.0
4.09
1.94
9.0 ppm (t1)
3.0
2.0
1.0
H NMR spectrum of compound 14c in CDCl3, 250 MHz.
1
130.0 129.0 128.0 127.0 ppm (t1)
ppm (t1)
150
100
50
C NMR spectrum of compound 14c in CDCl3, 62.5 MHz.
13
S43
H N
O
14d F
1.98
1.90
7.0
1.00
1.95
8.0
3.00
5.94
10.0 ppm (t1) 9.0
6.0
5.0
4.0
3.0
2.0
H NMR spectrum of compound 14d in CDCl3, 250 MHz.
1
130.0
ppm (t1)
150
ppm (t1)
125.0
100
50
C NMR spectrum of compound 14d in CDCl3, 62.5 MHz.
13
S44
5.0
3.05
6.0
2.04
7.0
1.00
1.00
1.00
8.0
2.08 3.03 1.03
5.00
9.0 (t1) ppm
4.0
3.0
2.0
H NMR spectrum of compound 14e in CDCl3, 250 MHz.
1
134.00 ppm (t1) 133.50
133.00 130.0 ppm (t1)129.0
100
ppm (t1)
128.0
127.0
50
C NMR spectrum of compound 14e in CDCl3, 62.5 MHz.
13
S45
7.0
2.03
1.00
1.98
4.29
8.0
2.20
2.00
9.0 ppm (t1)
6.0
5.0
4.0
3.0
H NMR spectrum of compound 14f in CDCl3, 250 MHz.
1
132.50 132.00 131.50 131.00 130.50 ppm (t1) 129.50 ppm (t1)
165.0
ppm (t1)
129.00
125.00
ppm (t1)
124.90
150
128.00
160.0
ppm (t1) 116.00
125.10 ppm (t1)
128.50
115.50
115.00
124.80
100
50
0
C NMR spectrum of compound 14f in CDCl3, 62.5 MHz.
13
S46
Br H N
O
14g F
2.02
7.0
1.87
1.00
2.48 1.01 1.00 1.19 1.14
2.16
ppm (t1) 8.0
6.0
5.0
4.0
3.0
H NMR spectrum of compound 14g in CDCl3, 250 MHz.
1
ppm131.00 (t1)
130.50
130.00
129.50
129.00
116.00 115.50 115.00 ppm (t1)
167.00 ppm (t1)
166.50
166.00
190(t1) 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
C NMR spectrum of compound 14g in CDCl3, 62.5 MHz.
13
S47
5.0
4.0
3.05
6.0
2.06
1.00
1.00
7.0
1.00
2.00
4.30
1.96
ppm (t1)8.0
3.0
2.0
1.0
H NMR spectrum of compound 14h in CDCl3, 250 MHz.
1
ppm 130.0 (t1)
129.0
128.0
127.0 ppm (t1) 115.50
ppm (t1) 132.00
ppm (t1)
115.00
131.50
150
100
50
C NMR spectrum of compound 14h in CDCl3, 62.5 MHz.
13
S48
1.92
7.0
1.00 1.88
8.0
2.01 5.02
1.98
ppm (t1)9.0
6.0
5.0
4.0
3.0
2.0
H NMR spectrum of compound 14i in CDCl3, 250 MHz.
1
150
ppm (t1)
100
50
0
C NMR spectrum of compound 14i in CDCl3, 62.5 MHz.
13
S49
3.06
5.0
2.07
6.0
0.98
7.0
1.01
1.00
8.0
7.25
2.00
ppm9.0 (t1)
4.0
3.0
2.0
H NMR spectrum of compound 14j in CDCl3, 250 MHz.
1
ppm129.0 (t1) 128.0 127.0 126.0 125.0
100
ppm (t1)
50
C NMR spectrum of compound 14j in CDCl3, 62.5 MHz.
13
S50
OMe H N
O
Major rotamer
14k
H
Minor rotamer
Major rotamer 4.72
1.00
Minor rotamer
ppm 3.800 (t1) 3.790 3.780 3.770 3.760 1.00
4.80
4.100 ppm (t1) 4.050 4.000 3.950 3.900
6.0
3.08 2.11
1.88
7.0
1.00
8.0
2.08
9.0
2.17
1.04
10.0 ppm (t1)
5.0
4.0
3.0
H NMR spectrum of compound 14k in CDCl3, 250 MHz.
1
Major rotamer
Major rotamer Major rotamer Minor rotamer
Minor rotamer
Minor rotamer
123.00 ppm (t1) 122.50
114.00 ppm (t1)
132.0 ppm (t1) 131.0 130.0 129.0 128.0
180 ppm (t1)170 160 150 140 130 120 110 100 90
80
70
60
50
40
30
20
C NMR spectrum of compound 14k in CDCl3, 62.5 MHz.
13
S51
Major rotamer
H N
O
Minor rotamer
14l
H
1.00
4.96
ppm4.150 (t1) 4.100 4.050 4.000 3.950
2.03
0.93
7.0
1.01
8.0
1.00
9.0
5.27
0.99
10.0 (t1) ppm
6.0
5.0
4.0
3.0
H NMR spectrum of compound 14l in CDCl3, 250 MHz.
1
Major rotamer
Major rotamer
Minor rotamer
Major rotamer
Major rotamer
Minor rotamer Minor rotamer
136.0 135.0 134.0 133.0 ppm (t1)
Minor rotamer
126.50 ppm (t1) 126.00 125.50 125.00
Major rotamer
Minor rotamer
170(t1) 160 150 140 130 120 110 100 90 ppm
80
70
60
50
40
30
20
C NMR spectrum of compound 14l in CDCl3, 62.5 MHz.
13
S52
0.98
5.50
4.0
3.02
5.0
3.10
1.89
6.0
0.96
0.94
1.00
2.17
2.04
ppm (t1) 7.0
1.00
9.01
103.76
6.00 ppm (t1)
3.0
2.0
H NMR spectrum of compound 14m in CDCl3, 250 MHz.
1
ppm (t1)
150
100
50
C NMR spectrum of compound 14m in CDCl3, 62.5 MHz.
13
S53
5.0
3.26
6.0
2.17
1.01
7.0
1.00
8.0
2.26
5.50
2.18 1.04 2.09
9.0 ppm (t1)
2.23
1.00
22.06
6.00 ppm (t1)
4.0
3.0
2.0
1.0
H NMR spectrum of compound 14n in CDCl3, 250 MHz.
1
ppm200 (t1)
175
150
125
100
75
50
25
C NMR spectrum of compound 14n in CDCl3, 62.5 MHz.
13
S54
H N
O
OMe
14o F 1.73
5.0
1.85
6.0
1.97
3.13
1.17 0.97
7.0
5.50
1.00
2.21
2.64
1.95
1.99
ppm (t1)8.0
1.74
1.00
13.48
ppm6.00 (t1)
4.0
3.0
2.0
H NMR spectrum of compound 14o in CDCl3, 250 MHz.
1
ppm (t1)
116.00
115.50
115.00
131.00 ppm (t1) 130.50 130.00 129.50 129.00
170 (t1) 160 150 140 130 120 110 100 ppm
90
80
70
60
50
40
C NMR spectrum of compound 14o in CDCl3, 62.5 MHz.
13
S55
H N
16
5.0
4.0
2.13
6.0
2.13
7.0
2.09
1.00
8.0
4.13
2.08
1.05
ppm9.0 (t1)
3.0
2.0
1.0
H NMR spectrum of compound 16 in CDCl3, 250 MHz.
1
175 (t1) ppm
150
125
100
75
50
25
0
C NMR spectrum of compound 16 in CDCl3, 62.5 MHz.
13
S56
MeO
O N
17
6.0
5.0
3.25 2.22
7.0
2.07 2.14
8.0
1.00
1.19 3.23
2.20 1.10
9.0 ppm (t1)
4.0
3.0
2.0
H NMR spectrum of compound 17 in CDCl3 (250 MHz), at 120 oC.
1
135.0(t1) 132.5 ppm
130.0
127.5
125.0
180 170 ppm (t1) 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10
0
C NMR spectrum of compound 17 in DMSOd6 (62.5 MHz), at 120 oC.
13
S57
MeO
O N 18
3.23 2.04
6.0
2.04
7.0
0.99 1.00
8.0
5.16 4.68
2.29 1.09
ppm9.0 (t1)
5.0
4.0
3.0
2.0
1.0
H NMR spectrum of compound 18 in DMSOd6 (250 MHz), at 120 oC.
1
129.0 ppm (t1) 128.0 127.0 126.0
48.50 ppm (t1)
48.00
47.50
170 (t1) 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
0
C NMR spectrum of compound 18 in DMSOd6 (62.5 MHz), at 120 oC.
13
S58
0.99
1.00
6.70(t1) 6.60 ppm
6.40
5.0
4.0
3.00
6.0
1.91
7.0
1.92
0.99
1.00
9.94
2.09
1.00
ppm (t1)8.0
6.50
3.0
H NMR spectrum of compound 1 in CDCl3, 300 MHz.
1
ppm60.50 (t1)
ppm 128.0 (t1)
127.0
126.0
60.00
59.50
125.0
100
ppm (t1)
50
C NMR spectrum of compound 1 in CDCl3, 75 MHz.
13
S59
6.0
5.0
6.03
1.99
7.0
1.00
3.02 2.02
8.0
1.90
1.98
9.0 ppm (t1)
4.0
3.0
2.0
1.0
H NMR spectrum of compound 20 in CDCl3, 300 MHz.
1
166.50 ppm (t1) 166.00
115.50 ppm (t1) 56.00 ppm (t1) 55.50
ppm129.50 (t1)
190(t1) 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm
C NMR spectrum of compound 20 in CDCl3, 75 MHz.
13
S60
OMe OMe H N
21 F
5.0
4.0
1.99
6.0
2.04 6.09
1.00
7.0
1.01
8.0
1.02 4.06
2.08
9.0(t1) ppm
3.0
2.0
1.0
H NMR spectrum of compound 21 in CDCl3, 300 MHz.
1
131.00 ppm (t1)130.50130.00
115.50 ppm (t1) 115.00
56.00 ppm (t1) 55.50
148.50 ppm149.00 (t1)
190 180 ppm (t1) 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20
C NMR spectrum of compound 21 in CDCl3, 75 MHz.
13
S61
6.0
5.0
4.04
3.00 2.09 6.15
7.0
1.00
1.00
8.0
1.03 2.13 2.16
2.02
ppm9.0 (t1)
4.0
3.0
2.0
H NMR spectrum of compound 2 in CDCl3, 500 MHz.
1
ppm56.00 (t1) 55.90 55.80
149.00 ppm (t1)
115.50 ppm (t1)
ppm (t1) 130.50
180 (t1) 170 ppm
160
150
140
130
120
110
100
90
80
115.00
70
60
50
40
30
20
10
0
C NMR spectrum of compound 2 in CDCl3, 125 MHz.
13
S62
2.20
2.14
2.05
ppm 2.50 (t1)
3.0
2.20
2.14
2.05
4.0
2.00
5.0
3.04
6.0
6.09
1.00
1.00
2.11
2.02
7.0 ppm (t1)
2.00
2.0
H NMR spectrum of compound 3 in CDCl3, 500 MHz.
1
130.50 ppm (t1)
130.00
115.50 ppm (t1)115.00 114.50 56.10(t1)56.00 55.90 55.80 ppm
ppm (t1)149.00
ppm (t1)
148.50
150
100
50
C NMR spectrum of compound 3 in CDCl3, 125 MHz.
13
S63
