Page 7 of 11
1
The Journal of Organic Chemistry
1.13 (ddt, J = 13.6, 11.2, 4.2 Hz, 4H). 13C {1H} NMR (100
131.09, 131.05, 130.66, 130.64, 122.30, 121.98, 33.52,
23.24. HRMS (ESI-TOF) m/z: [M+H]+ calcd for
C18H16Br2NS 437.9343; found 437.9344.
2
3
4
5
6
MHz, CDCl3) δ 171.4, 149.1, 135.1, 132.4, 130.4, 129.6,
129.0, 128.6, 128.2, 127.8, 127.6, 14.6, 11.0. HRMS (ESI-
TOF) m/z: [M+H]+ calcd for C18H16NS 278.0998; found
278.1008.
4,5-bis(3-methoxyphenyl)-2-phenylthiazole (5j). Light
yellow oil (43.6 mg, 39%, 15 h), petroleum ether/ethyl
acetate = 40:1, Rf = 0.45, H NMR (400 MHz, CDCl3) δ
8.02 – 7.90 (m, 2H), 7.44 – 7.33 (m, 3H), 7.19 – 7.10 (m,
4H), 6.92 (d, J = 7.6 Hz, 1H), 6.86 (s, 1H), 6.83 – 6.67 (m,
2H), 3.65 (s, 3H), 3.65 (s, 3H). 13C {1H} NMR (100 MHz,
CDCl3) δ 165.4, 159.6, 159.5, 150.6, 136.2, 133.5, 133.2,
133.1, 130.1, 129.8, 129.3, 128.9, 126.5, 122.1, 121.7,
114.9, 114.2, 114.1, 55.3, 55.2. HRMS (ESI-TOF) m/z:
[M+H]+ calcd for C23H20NO2S 374.1209; found 374.1216.
7
1
8
9
2-phenyl-4,5-di-p-tolylthiazole (5d). White solid (91.4 mg,
67%, 15 h), petroleum ether/ethyl acetate = 60:1, Rf = 0.5,
mp: 197.3–199.1 oC, 1H NMR (400 MHz, CDCl3) δ 8.04 –
7.97 (m, 2H), 7.50 (d, J = 8.1 Hz, 2H), 7.47 – 7.38 (m, 3H),
7.28 (d, J = 8.1 Hz, 2H), 7.12 (t, J = 7.6 Hz, 4H), 2.36 (s,
3H), 2.34 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ
165.0, 150.6, 138.1, 137.5, 133.8, 132.7, 132.3, 129.9,
129.5, 129.3, 129.0, 128.9, 126.4, 21.3, 21.3. HRMS (ESI-
TOF) m/z: [M+H]+ calcd for C23H20NS 342.1311; found
342.1323.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2-isopropyl-4,5-di(thiophen-2-yl)thiazole (5k).
Light
yellow oil (42 mg, 48%, 18 h), petroleum ether/ethyl
1
acetate = 60:1, Rf = 0.35, H NMR (400 MHz, CDCl3) δ
4,5-bis(4-methoxyphenyl)-2-phenylthiazole (5e). Light
7.42 – 7.39 (dd, J = 5.2, 1.2 Hz, 1H), 7.26 – 7.23 (dd, J =
5.2, 1.2 Hz, 1H), 7.21 – 7.16 (m, 2H), 7.08 (dd, J = 5.2, 3.6
Hz, 1H), 6.94 (dd, J = 5.1, 3.6 Hz, 1H), 3.26 (hept, J = 6.8
Hz, 1H), 1.44 (d, J = 6.8 Hz, 6 H). 13C {1H} NMR (100
MHz, CDCl3) δ 176.7, 145.1, 137.4, 132.3, 129.2, 127.6,
127.5, 127.2, 126.3, 126.0, 122.3, 33.5, 23.1. HRMS (ESI-
TOF) m/z: [M+H]+ calcd for C14H14NS3 292.0283; found
292.0286.
yellow oil (98.4 mg, 66%, 15 h), petroleum ether/ethyl
1
acetate = 40:1, Rf = 0.5, H NMR (400 MHz, CDCl3) δ
7.96 – 7.88 (m, 2H), 7.47 (d, J = 8.7 Hz, 2H), 7.36 (d, J =
7.7 Hz, 3H), 7.24 (d, J = 8.7 Hz, 2H), 6.78 (t, J = 8.8 Hz,
4H), 3.75 (s, 3H), 3.73 (s, 3H). 13C {1H} NMR (100 MHz,
CDCl3) δ 164.8, 159.5, 159.2, 150.0, 133.7, 131.8, 130.8,
130.3, 129.9, 128.9, 127.7, 126.4, 124.5, 114.2, 113.7,
55.3, 55.2. HRMS (ESI-TOF) m/z: [M+H]+ calcd for
C23H20NO2S 374.1209; found 374.1216.
2-isopropyl-4-phenyl-5-propylthiazole (5n) and 2-ethyl-5-
phenyl-4-propylthiazole (5n’). Colorless oil (38.2 mg,
52%, 5n:5n’ = 4:1, 24 h), petroleum ether/ethyl acetate =
60:1, Rf = 0.5, 1H NMR (400 MHz, CDCl3) δ 7.59-7.57 (m,
1.8 H), 7.45 – 7.38 (m, 3H), 7.35 – 7.29 (m, 1.5 H), 3.43 –
3.18 (m, 1.25 H), 2.90 – 2.81 (m, 2H), 2.74 – 2.68 (m, 0.5
H), 1.75 – 1.66 (m, 2.5 H), 1.41–1.40 (m, 7.5 H), 0.98 (t, J
= 7.3 Hz, 3H), 0.94–0.92 (t, J = 7.6 Hz, 0.75 H). 13C {1H}
NMR (100 MHz, CDCl3) δ 175.7, 174.0, 151.5, 149.8,
135.6, 133.1, 129.5, 128.8, 128.6, 128.3, 127.6, 127.4, 33.4,
31.6, 29.7, 29.3, 25.6, 23.4, 23.3, 14.0, 13.9. HRMS (ESI-
TOF) m/z: [M+H]+ calcd for C15H20NS 246.1311; found
246.1318.
2-isopropyl-4,5-bis(4-methoxyphenyl)thiazole (5f). Light
yellow oil (58 mg, 57%, 18 h), petroleum ether/ethyl
1
acetate = 40:1, Rf = 0.5, H NMR (400 MHz, CDCl3) δ
7.48 – 7.42 (m, 2H), 7.27 – 7.22 (m, 2H), 6.87 – 6.77 (m,
4H), 3.81 (s, 3H), 3.79 (s, 3H), 3.34 (hept, J = 6.8 Hz, 1H),
1.45 (d, J = 6.8 Hz, 6H). 13C {1H} NMR (100 MHz, CDCl3)
δ 175.1, 159.2, 158.9, 148.3, 130.8, 130.2, 130.1, 127.9,
124.9, 114.1, 113.6, 55.3, 55.2, 33.5, 23.3. HRMS (ESI-
TOF) m/z: [M+H]+ calcd for C20H22NO2S 340.1366; found
340.1378.
4,5-bis(4-(tert-butyl)phenyl)-2-isopropylthiazole
(5g).
White solid (68 mg, 58%, 24 h), petroleum ether/ethyl
o
1
2-isopropyl-5-(4-methoxyphenyl)-4-(4-
acetate = 60:1, Rf = 0.55, mp: 112.3-113.1 C. H NMR
(600 MHz, CDCl3) δ 7.57 – 7.47 (m, 2H), 7.44 – 7.29 (m,
6H), 3.42 – 3.32 (d, J = 6.9 Hz, 1H), 1.47 (d, J = 6.9 Hz,
6H), 1.36 (s, 9H), 1.33 (s, 9H). 13C {1H} NMR (150 MHz,
CDCl3) δ 175.2, 150.8, 150.3, 148.6, 132.4, 131.0, 129.6,
129.1, 128.6, 125.5, 125.2, 34.7, 34.6, 33.5, 31.3, 31.3,
23.3. HRMS (ESI-TOF) m/z: [M+H]+ calcd for C26H34NS
392.2406; found 392.2416.
(trifluoromethyl)phenyl)thiazole (5o). Light yellow oil
(54.3 mg, 48%, 24 h), petroleum ether/ethyl acetate = 50:1,
Rf = 0.4, 1H NMR (600 MHz, CDCl3) δ 7.68 (t, J = 6.9 Hz,
2H), 7.55 (t, J = 6.8 Hz, 2H), 7.28 – 7.24 (m, 2H), 6.92 –
6.86 (m, 2H), 3.84 (s, 3H), 3.44 – 3.32 (hept, J = 6.9 Hz,,
1H), 1.48 (d, J = 6.9 Hz, 6H). 13C {1H} NMR (150 MHz,
CDCl3) δ 175.8, 159.7, 146.9, 138.8, 133.2, 130.8, 129.2 (q,
J = 31.5 Hz), 129.1, 125.2 (q, J = 3.9 Hz), 124.2 (q, J =
270.3 Hz), 124.0, 114.3, 55.3, 33.5, 23.2. HRMS (ESI-TOF)
m/z: [M+H]+ calcd for C20H19NOS 378.1134; found
378.1137.
4,5-bis(4-bromophenyl)-2-isopropylthiazole (5i). Light
yellow solid (79 mg, 60%, 24 h), petroleum ether/ethyl
acetate = 60:1, Rf = 0.5, mp: 114.2-115.0 oC. 1H NMR (600
MHz, CDCl3) δ 7.57 – 7.46 (m, 2H), 7.46 – 7.42 (m, 2H),
7.42 – 7.33 (m, 2H), 7.26 – 7.14 (m, 2H), 3.37 (d, J = 6.9
Hz, 1H), 1.47 (d, J = 6.9 Hz, 6H). 13C {1H} NMR (150
MHz, CDCl3) δ 176.54, 148.22, 133.67, 132.03, 131.56,
Typical experimental procedure for the synthesis of 6a.
27
To a solution of aniline (3.0 mmol, 1.0 equiv.) and Et3N
(6.0 mmol, 2.0 equiv.) in DCM (10 mL) was slowly added
ACS Paragon Plus Environment