PAPER
Preparation of 2- and 5-Aryl Substituted Thiazoles
133
1
13
H NMR (CDCl ): d = 5.32 (s, 2 H), 7.20 (d, 1 H, J = 1.2 Hz), 7.32-
C NMR (CDCl ): d = 125.1, 125.4, 126.7, 127.4, 127.5, 128.8,
3
3
7
1
.40 (m, 5 H), 7.47 (d, 1 H, J = 1.2 Hz), 7.79 (s, 1 H, H-4), 8.66 (s,
129.1, 130.1, 132.0, 134.0, 136.0, 140.6, 141.7.
H, H-2).
2
-Iodo-5-(1-naphthyl)thiazole (9b)
1
3
C NMR (CDCl ): d = 80.8, 109.3, 119.8, 127.8, 128.5, 128.8,
The procedure described for preparation of 9a was followed using
iodine monochloride (0.65 g, 4 mmol) instead of bromine.
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1
30.6, 132.4, 137.6, 149.9.
Anal. calcd for C H N OS: C, 60.82; H, 4.32; N, 16.37. Found C,
CC (0-10% EtOAc in heptane) gave 0.84 g (62%) of 9b as a yellow
13
11
3
6
0.36; H, 4.08; N, 16.05.
oil; R 0.25 (20% EtOAc in heptane).
f
1
5
-(5-Indolyl)thiazole (6i)
H NMR (CDCl ): d = 7.50-7-56 (m, 4 H), 7.70 (s, 1 H, H-4),
3
Prepared by following the general procedure II using 5-bromoin-
dole as the heteroaryl halide.
7.90-7.94 (m, 2 H), 8.03-8.05 (m, 1 H).
13
C NMR (CDCl ): d = 100.5, 124.9, 125.2, 126.4, 127.1, 127.3,
3
CC (20-40% EtOAc in heptane) gave 52 mg (26%) of 6i as pale
128.6, 128.8, 129.8, 131.7, 133.7, 142.8, 143.5.
yellow crystals; mp 184-185 ∞C (heptane/EtOAc); R 0.25 (50%
f
HRMS: m/z calcd 337.9495; found 337.9492.
EtOAc in heptane).
2
-(4-Methylphenyl)-5-(1-naphthyl)thiazole (10)
The general procedure I using 9a (290 mg, 1 mmol) (instead of
-bromothiazole (1)) and 4-iodotoluene as the aryl halide with the
1
H NMR (CDCl ): d = 6.60-6.61 (m, 1 H), 7.26-7.28 (m, 1 H),
3
7
.43-7.44 (m, 2 H), 7.86 (s, 1 H, H-4), 8.06 (s, 1 H), 8.34 (br s, 1
2
H), 8.73 (1 H, s, H-2)
exception of performing the oxidative insertion of zinc for 24 h at
r.t.
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3
C NMR (CDCl ): d = 103.3, 111.9, 119.8, 121.8, 123.1, 125.7,
3
1
28.6, 136.0, 138.0, 141.3, 151.3.
CC (10-40% EtOAc in heptane) followed by preparative HPLC
Anal. calcd for C H N S: C, 65.97; H, 4.03; N, 13.99. Found C,
6
gave 66 mg (22%) of 10 as crystals; mp 75-76 ∞C; R 0.45 (20%
1
1
8
2
f
5.43; H, 4.11; N, 13.60.
EtOAc in heptane).
1
5
-(4-Methylphenyl)-2-(1-naphthyl)thiazole (8a)
H NMR (CDCl ): d = 2.42 (s, 3 H), 7.28-7.30 (m, 2 H), 7.50-7.56
3
The general procedure II using 3g (211 mg, 1 mmol) (instead of
-TST (4)) and 4-iodotoluene as the aryl halide was followed.
(m, 3 H), 7.56-7.62 (m, 1H), 7.89-7.93 (m, 4 H); 7.94 (s, 1 H,
H-4), 8.18-8.22 (m, 1 H).
2
1
3
CC (0-15% EtOAc in heptane) gave 239 mg (79%) of 8a as yellow
C NMR (CDCl ): d = 21.8, 125.5, 125.5, 126.5, 126.6, 127.1,
3
crystals; mp 118-119 ∞C (heptane/EtOAc); R 0.20 (10% EtOAc in
128.7, 128.8, 128.9, 129.5, 130.0, 131.0, 132.1, 134.0, 136.1, 140.8,
142.4, 169.0.
f
heptane).
1
H NMR (CDCl ): d = 2.43 (s, 3 H), 7.29 (d, 2 H, J = 8 Hz), 7.51-
HRMS: m/z calcd 302.0998; found 302.0985.
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7
2
.57 (m, 3 H), 7.60-6.62 (m, 1 H), 7.90-7.95 (m, 2 H), 7.91 (d,
H, J = 8 Hz), 7.95 (s, 1 H, H-4), 8.20-8.22 (m, 1 H).
References
1
3
C NMR (CDCl ): d = 21.1, 124.9, 125.7, 126.2, 126.5, 127.2,
3
1
1
28.2, 129.3, 129.6, 130.2, 130.3, 130.6, 133.8, 138.2, 138.4, 139.9,
65.9.
(1) Katritzky, A. R.; Strah, S.; Belyakov, S. A. Tetrahedron 1998,
54, 7167, and references cited therein.
(
2) Dondoni, A. Synthesis 1998, 1681.
Anal. calcd for C H NS: C, 79.70; H, 5.02; N, 4.65. Found C,
20
15
(
3) Wiley, R. H.; England, D. C.; Behr, L.C. Org. React. 1951, 6,
7
9.68; H, 4.99; N, 4.64.
367.
5
-(4-Aminophenyl)-2-(1-naphthyl)thiazole (8b)
(
(
4) Erlenmeyer, H.; Eckenstein, J.; Sorkin, E.; Meyer, H. Helv.
Chim. Acta 1950, 33, 1271.
5) Vernin, G.; Metzger, J. Bull. Soc. Chim. Fr. 1963, 2498.
The general procedure II using 3g (211 mg, 1 mmol) (instead of
-TST (4)) and 4-iodoaniline as the aryl halide was followed.
2
CC (40-50% EtOAc in heptane) gave 116 mg (38%) of 8b as yel-
(6) Katritzky, A. R.; Chen, J.; Yang, Z. J. Org. Chem. 1995, 60,
5638.
(7) Kearney, P. C.; Fernandez, M.; Flygare, J. A. J. Org. Chem.
low crystals; mp 124-125 ∞C (heptane/EtOAc); R 0.30 (50%
f
EtOAc in heptane).
1998, 63, 196.
1
H NMR (CDCl ): d = 3.84 (br s, 2 H, NH ), 6.72-6.76 (m, 2 H),
3
2
(
(
8) Goff, D.; Fernandez, J. Tetrahedron. Lett. 1999, 40, 423.
9) McLean, J.; Muir, G. D. J. Chem. Soc. 1942, 383, and
references cited therein.
7
(
.44-7.48 (m, 2 H), 7.51-7.62 (m, 3 H), 7.83-7.94 (m, 3 H), 8.04
s, 1 H, H-4), 8.87-8.89 (m, 1 H).
1
3
C NMR (CDCl ): d = 115.2, 121.4, 124.9, 125.8, 126.2, 127.1,
(10) Dondoni, A.; Mastellari, A. R.; Medici, A.; Negrini, E.;
3
1
27.9, 128.2, 130.0, 130.4, 130.9, 133.9, 137.2, 140.5, 146.6, 164.7.
Pedrini, P. Synthesis 1986, 757.
(
11) For a review on cross-coupling reactions, see: Stanforth, S. P.
Tetrahedron 1998, 54, 263.
12) Dondoni, A.; Fogagnolo, M.; Medici, A.; Negrini, E.
Synthesis 1987, 185.
13) Bailey, T. R. Tetrahedron. Lett. 1986, 27, 37, 4407.
14) Peters, D. Hörnfeldt, A.-B., Gronowitz, S. J. Heterocycl.
Chem. 1990, 27, 2165.
Anal. calcd for C H N S: C, 75.47; H, 4.67; N, 9.26. Found C,
19
14
2
7
5.29; H, 4.69; N, 9.16.
(
2
-Bromo-5-(1-naphthyl)thiazole (9a)
The general procedure II was followed using 2-TST (4; 0.63 mL,
mmol) and 1-bromonaphthalene (6 mmol) as the aryl halide. After
(
(
4
cross-coupling for 24 h at reflux, the mixture was cooled to r.t. and
Br (0.205 mL, 4 mmol) was added and stirring was continued for
2
(15) Gronowitz, S.; Peters, D. Heterocycles 1990, 30, 645.
(16) Peters, D.; Hörnfeldt, A.-B.; Gronowitz, S. J. Heterocycl.
Chem. 1991, 28, 529.
4
8 h. The mixture was quenched with a 1 M aq solution of Na SO
2 3
(
10 mL) and worked up as described in general procedure II.
CC (0-10% EtOAc in heptane) gave 563 mg (48%) of 9a; mp 61-
(17) Peters, D.; Hörnfeldt, A.-B.; Gronowitz, S. J. Hetereocycl.
Chem. 1991, 28, 1613.
(18) Malm, J.; Björk, P.; Gronowitz, S.; Hörnfeldt, A.-B.
Tetrahedron. Lett. 1992, 33, 2199.
6
2 ∞C (heptane/EtOAc). Compound 9a was used in the next step
without further purification; R 0.45 (20% EtOAc in heptane).
f
1
H NMR (CDCl ): d = 7.49-7.56 (m, 4 H), 7.67 (s, 1 H, H-4), 7.90-
3
(
19) Sharp, M. J.; Snieckus, V. Tetrahedron. Lett. 1985, 26, 49,
997.
7
.93 (m, 2 H), 8.05-8.08 (m, 1 H).
5
Synthesis 2001, No. 1, 128–134 ISSN 0039-7881 © Thieme Stuttgart · New York