1016
Vol. 55, No. 7
1
mp 138 °C; IR (KBr): 3426, 3206, 1641, 1534, 1411, 1023, 529 cmꢁ1. H-
140.7, 155.1, 169.7; MS m/z: 256 [Mꢀꢀ2], 254 [Mꢀ]. Anal. Calcd for
C9H7BrN2S: C, 42.37; H, 2.77; N, 10.98; Found: C, 42.35; H, 2.75; N,
10.97.
NMR (DMSO-d6), d: 3.51 (s, 4H, NH2), 7.03—7.59 (m, 8H, ArH); 13C-
NMR (DMSO-d6) d: 110.4, 126.6, 129.4, 129.8, 131.4, 132.2, 133.3, 156.4,
171.2; MS m/z: 486 [Mꢀꢀ4], 484 [Mꢀꢀ2], 482 [Mꢀ]. Anal. Calcd for
C18H12Cl2N4S4: C, 44.72; H, 2.50; N, 11.59; Found: C, 44.70; H, 2.51; N,
11.62.
2-Amino-4-(2-chlorophenyl)-1,3-thiazole (2d): Light pink crystalline
1
solid, mp 126 °C; IR (KBr): 3328, 3304, 1520, 1461, 1052 cmꢁ1. H-NMR
(MeOH-d4), d: 4.90 (s, 2H, NH2), 6.87 (s, 1H, thiazole H-5), 7.37—7.69 (m,
4H, ArH); 13C-NMR (MeOH-d4) d: 106.9, 124.0, 128.9, 130.6, 131.8,
132.9, 134.6, 144.1, 171.6; MS m/z: 212 [Mꢀꢀ2], 210 [Mꢀ]. Anal. Calcd
for C9H7ClN2S: C, 51.31; H, 3.35; N, 13.30; Found: C, 51.28; H, 3.34; N,
13.33.
[2-Amino-4-(3-chlorophenyl)-5-thiazolyl] Disulfide (3e): Light yellow
solid, mp 112 °C; IR (KBr): 3428, 3210, 1645, 1537, 1417, 1026, 532 cmꢁ1
.
1H-NMR (DMSO-d6), d: 3.38 (s, 4H, NH2), 7.34—7.84 (m, 8H, ArH); 13C-
NMR (DMSO-d6) d: 110.5, 127.0, 127.8, 128.2, 129.8, 132.4, 135.8, 150.7,
170.9; MS m/z: 486 [Mꢀꢀ4], 484 [Mꢀꢀ2], 482 [Mꢀ]. Anal. Calcd for
C18H12Cl2N4S4: C, 44.72; H, 2.50; N, 11.59; Found: C, 44.72; H, 2.49; N,
11.61.
2-Amino-4-(3-chlorophenyl)-1,3-thiazole (2e): Pale yellow solid, mp
112 °C; IR (KBr): 3323, 3305, 1518, 1459, 1049 cmꢁ1 1H-NMR (MeOH-
.
d4), d: 4.87 (s, 2H, NH2), 6.91 (s, 1H, thiazole H-5), 7.33—7.66 (m, 4H,
ArH); 13C-NMR (MeOH-d4) d: 107.3, 123.8, 130.0, 130.7, 131.6, 133.2,
134.1, 143.8, 172.0; MS m/z: 212 [Mꢀꢀ2], 210 [Mꢀ]. Anal. Calcd for
C9H7ClN2S: C, 51.31; H, 3.35; N, 13.30; Found: C, 51.29; H, 3.31; N, 13.28.
2-Amino-4-(4-chlorophenyl)-1,3-thiazole (2f): Light yellow crystalline
[2-Amino-4-(4-chlorophenyl)-5-thiazolyl] Disulfide (3f): Chocolate
coloured solid, mp 220 °C; IR (KBr): 3432, 3205, 1639, 1534, 1413, 1031,
527 cmꢁ1. H-NMR (DMSO-d6), d: 3.46 (s, 4H, NH2), 7.35—7.74 (m, 8H,
1
ArH); 13C-NMR (DMSO-d6) d: 109.8, 128.0, 130.2, 132.6, 132.7, 151.3,
168.6; MS m/z: 486 [Mꢀꢀ4], 484 [Mꢀꢀ2], 482 [Mꢀ]. Anal. Calcd for
C18H12Cl2N4S4: C, 44.72; H, 2.50; N, 11.59; Found: C, 44.73; H, 2.51; N,
11.57.
1
solid, mp 145 °C; IR (KBr): 3330, 3306, 1522, 1463, 1051 cmꢁ1. H-NMR
(MeOH-d4), d: 4.96 (s, 2H, NH2), 6.74 (s, 1H, thiazole H-5), 7.41—7.70 (m,
4H, ArH); 13C-NMR (MeOH-d4) d: 107.2, 124.4, 128.3, 130.9, 131.7,
133.0, 134.1, 143.7, 171.2; MS m/z: 212 [Mꢀꢀ2], 210 [Mꢀ]. Anal. Calcd
for C9H7ClN2S: C, 51.31; H, 3.35; N, 13.30; Found: C, 51.31; H, 3.34; N,
13.28.
2-Amino-4-(3,4-dichlorophenyl)-1,3-thiazole (2g): Pale green solid, mp
194 °C; IR (KBr): 3450, 3208, 1644, 1545, 1408, 1036 cmꢁ1. 1H-NMR (ace-
tone-d6), d: 2.06 (s, 2H, NH2), 7.16 (s, 1H, thiazole ring), 7.58—7.86 (m,
3H, ArH); 13C-NMR (acetone-d6) d: 108.8, 117.3, 128.5, 130.17, 130.38,
130.9, 137.0, 147.3, 168.1; MS m/z: 248 [Mꢀꢀ4], 246 [Mꢀꢀ2], 244 [Mꢀ].
Anal. Calcd for C9H6Cl2N2S: C, 44.10; H, 2.47; N, 11.43; Found: C, 44.08;
H, 2.48; N, 11.39.
[2-Amino-4-(3,4-dichlorophenyl)-5-thiazolyl] Disulfide (3g): Turmeric
solid, mp 203—204 °C; IR (KBr): 3433, 3216, 1646, 1536, 1423, 1024,
531 cmꢁ1. H-NMR (DMSO-d6), d: 3.38 (s, 4H, NH2), 7.57—7.92 (m, 6H,
1
ArH); 13C-NMR (DMSO-d6) d: 110.7, 128.4, 130.0, 130.2, 130.5, 130.7,
134.3, 150.1, 168.7; MS m/z: 558 [Mꢀꢀ8], 554 [Mꢀꢀ4], 552 [Mꢀꢀ2], 550
[Mꢀ]. Anal. Calcd for C18H10Cl4N4S4: C, 39.14; H, 1.82; N, 10.14; Found:
C, 39.16; H, 1.82; N, 10.13.
[2-Amino-4-(2,5-dichlorophenyl)-5-thiazolyl] Disulfide (3h): Turmeric
solid, mp 143—145 °C; IR (KBr): 3434, 3211, 1644, 1530, 1419, 1020,
535 cmꢁ1. H-NMR (DMSO-d6), d: 3.50 (s, 4H, NH2), 7.46—7.77 (m, 6H,
1
ArH); 13C-NMR (DMSO-d6) d: 111.0, 128.1, 128.9, 129.7, 131.2, 132.1,
135.2, 154.9, 172.0; MS m/z: 558 [Mꢀꢀ8], 554 [Mꢀꢀ4], 552 [Mꢀꢀ2], 550
[Mꢀ]. Anal. Calcd for C18H10Cl4N4S4: C, 39.14; H, 1.82; N, 10.14; Found:
C, 39.11; H, 1.82; N, 10.13.
2-Amino-4-(2,5-dichlorophenyl)-1,3-thiazole (2h): Chocolate coloured
1
solid, mp 152 °C; IR (KBr): 3445, 3211, 1639, 1542, 1411, 1032 cmꢁ1. H-
NMR (acetone-d6), d: 2.08 (s, 2H, NH2), 7.11 (s, 1H, thiazole ring), 7.32—
7.56 (m, 3H, ArH); 13C-NMR (acetone-d6) d: 106.7, 118.2, 129.1, 130.20,
130.41, 131.3, 136.7, 147.7, 169.5; MS m/z: 248 [Mꢀꢀ4], 246 [Mꢀꢀ2], 244
[Mꢀ]. Anal. Calcd for C9H6Cl2N2S: C, 44.10; H, 2.47; N, 11.43; Found: C,
44.10; H, 2.44; N, 11.48.
[2-Amino-4-(3,4-dimethoxy phenyl)-5-thiazolyl] Disulfide (3i): Light yel-
low solid, mp 199—200 °C; IR (KBr): 3413, 3206, 1650, 1543, 1417,
1022 cmꢁ1. 1H-NMR (DMSO-d6), d: 3.50 (s, 4H, NH2), 3.70 (s, 12H, OCH3,
6.92—7.07 (m, 6H, ArH); 13C-NMR (DMSO-d6) d: 56.1, 56.2, 102.3, 111.7,
116.1, 120.5, 127.1, 149.7, 150.9, 151.4, 171.7; MS m/z: 534 [Mꢀ]. Anal.
Calcd for C22H22N4O4S4: C, 49.42; H, 4.15; N, 10.48; Found: C, 49.41; H,
4.16; N, 10.45.
2-Amino-4-(3,4-dimethoxyphenyl)-1,3-thiazole (2i): Light yellow
coloured solid, mp 200 °C; IR (KBr): 3313, 3276, 1511, 1450, 1045 cmꢁ1
.
1H-NMR (DMSO-d6), d: 3.01 (s, 2H, NH2), 3.64 (s, 6H, OCH3), 6.90 (s, 1H,
thiazole H-5), 7.08—7.13 (s, 3H, ArH); 13C-NMR (DMSO-d6) d: 56.3, 56.4,
100.2, 111.9, 116.1, 120.9, 128.2, 149.3, 149.9, 151.0, 170.2; MS m/z: 236
[Mꢀ]. Anal. Calcd for C11H12N2O2S: C, 55.91; H, 5.12; N, 11.86; Found: C,
55.93; H, 5.10; N, 11.85.
Acknowledgements We greatly acknowledge the Higher Education
Commission of Pakistan, Islamabad, as well as University of the Punjab, La-
hore and Loughborough University for financial support. We thank Mr. John
C. Kershaw for running mass spectra and Mr. J. Alastair Daley for elemental
analysis.
General Procedure of Synthesis of [2-Amino-4-phenyl-5-thiazolyl]
Disulfides Sulfur monochloride (0.01 mol, 1.35 g) was added cautiously to
a mixture of 2-amino-4-phenyl-1,3-thiazole (2a—i) (0.02 mol) and acetic
acid (15 ml) followed by stirring of the contents at room temperature (for re-
action conditions, see Table 2). Aqueous ammonium hydroxide (25%) was
added drop wise till the pH was approximately 10. The precipitated disul-
fides were collected by filtration, washed with cold water and crystallized
from hot ethanol.
References
1) Lednicer D., Mitscher L. A., George G. I., “Organic Chemistry of
Drug Synthesis,” Vol. 4, Wiley, New York, 1990, pp. 95—97.
2) Rehman M. Z., Anwar C. J., Ahmad S., Bull. Korean Chem. Soc., 26,
1771—1775 (2005).
3) Knadler M. P., Bergstrom R. F., Callaghan J. T., Rubin A., Drug
Metab. Dispos., 14, 175—182 (1986).
[2-Amino-4-(2-bromophenyl)-5-thiazolyl] Disulfide (3a): Pale green
solid, mp 172 °C; IR (KBr): 3425, 3203, 1638, 1531, 1408, 1019, 522 cmꢁ1
.
1H-NMR (MeOH-d4), d: 4.97 (s, 4H, NH2), 7.03—7.66 (m, 8H, ArH); 13C-
NMR (MeOH-d4) d: 113.0, 124.8, 128.1, 131.4, 132.7, 133.8, 136.5, 157.8,
173.2; MS m/z: 574 [Mꢀꢀ4], 572 [Mꢀꢀ2], 570 [Mꢀ]. Anal. Calcd for
C18H12Br2N4S4: C, 37.77; H, 2.11; N, 9.79; Found: C, 37.78; H, 2.10; N,
9.80.
4) Rover S., Cesura M. A., Huguenin P., Szente A., J. Med. Chem., 40,
4378—4385 (1997).
5) Kim K. S., Kimball S. D., Misra R. N., Rawlins D. B., Hunt J. T., Xiao
H.-Y., Lu S., Qian L., Han W.-C., Shan W., Mitt T., Cai Z.-W., Poss M.
A., Zhu H., Sack J. S., Tokarski J. S., Chang C. J., Pavletich N., Ka-
math A., Humphreys W. G., Marathe P., Bursuker J., Kellar K. A.,
Roongta U., Batorsky R., Mulheron J. G., Bol D., Fairchild C. R., Lee
F. Y., Webster K. R., J. Med. Chem., 45, 3905—3927 (2002).
6) Kosower E. M. “Glutathione,” Part A, ed. by Dolphin D., Poulson R.,
Avvamovic O., Jhon Wiley, New York, 1989, pp. 115—120.
7) Parry R. J., Tetrahedron, 39, 1215—1238 (1983).
[2-Amino-4-(3-bromophenyl)-5-thiazolyl] Disulfide (3b): Dirty brown
solid, mp 110—111 °C; IR (KBr): 3430, 3207, 1643, 1532, 1420, 1022,
1
527 cmꢁ1. H-NMR (MeOH-d4), d: 4.93 (s, 4H, NH2), 7.21—7.71 (m, 8H,
ArH); 13C-NMR (MeOH-d4) d: 111.1, 122.7, 128.9, 130.6, 132.0, 132.9,
137.3, 158.2, 173.5; MS m/z: 574 [Mꢀꢀ4], 572 [Mꢀꢀ2], 570 [Mꢀ]. Anal.
Calcd for C18H12Br2N4S4: C, 37.77; H, 2.11; N, 9.79; Found: C, 37.76; H,
2.11; N, 9.80.
8) Davidson B. S., Chem. Rev., 93, 1771—1791 (1993).
9) Abas S. A., Hossain M. B., van der Helm D., Schmitz F. J., Laney M.,
Cabuslay R., Schatzman R. C., J. Org. Chem., 61, 2709—2712 (1996).
10) Kang H., Fenical W., Tetrahedron Lett., 37, 2369—2372 (1996).
11) Lindquist N., Fenical W., Tetrahedron Lett., 31, 2389—2390 (1990).
12) Popov A. M., Novikov V. L., Radchenko O. S., Elyakov G. B., Doklady
Biochem. Biophys., 385, 213—218 (2002).
[2-Amino-4-(4-bromophenyl)-5-thiazolyl] Disulfide (3c): Turmeric solid,
1
mp 238 °C; IR (KBr): 3430, 3207, 1637, 1532, 1410, 1027, 524 cmꢁ1. H-
NMR (DMSO-d6), d: 3.44 (s, 4H, NH2), 7.37—7.70 (m, 8H, ArH); 13C-
NMR (DMSO-d6) d: 111.8, 127.6, 128.1, 130.1, 132.7, 132.8, 133.4, 151.2,
168.3; MS m/z: 574 [Mꢀꢀ4], 572 [Mꢀꢀ2], 570 [Mꢀ]. Anal. Calcd for
C18H12Br2N4S4: C, 37.77; H, 2.11; N, 9.79; Found: C, 37.75; H, 2.12; N,
9.78.
13) Radechenko O. S., Novikov V. L., Willis R. H., Murphy P. T., Elyakov
[2-Amino-4-(2-chlorophenyl)-5-thiazolyl] Disulfide (3d): Turmeric solid,