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J. S. Yadav et al. / Tetrahedron Letters 49 (2008) 2381–2383
2383
8. Hantzsch, A. R.; Weber, J. H. Ber 1887, 20, 3118.
9. Potewar, T. M.; Ingale, S. A.; Srinivasan, K. V. Tetrahedron 2007, 63,
11066.
S
N
O
NH2
Thiourea
Cl
Cl
N2
10. George, W. K.; Arjun, R. M. Tetrahedron Lett. 2006, 47, 5171.
11. Siddiqui, H. L.; Iqbal, A.; Ahmed, S.; Weaver, G. Molecules 2006, 11,
206;.
CF3
CF3
Cu(OTf)2, DCE, 80 °C
3i
Scheme 2. Synthesis of 2-aminothiazole 3i.
12. Karade, H.; Sathe, M.; Kaushik, M. P. Catal. Commun. 2007, 8,
741.
13. Bailey, N.; Dean, A. W.; Judd, D. B.; Middlemiss, D.; Storer, R.;
Watson, S. P. Bioorg. Med. Chem. Lett. 1996, 6, 1409.
14. Gorczynski, M. J.; Leal, R.; Mooberry, S. L.; Bushweller, J. H.;
Brown, M. L. Bioorg. Med. Chem. Lett. 2004, 12, 1029.
15. Rudolph, J.; Theis, H.; Hanke, R.; Endermann, R.; Johannsen, L.;
Geschke, F. U. J. Med. Chem. 2001, 44, 619.
16. Smith, C. W.; Chakrabarti, J. K.; Williamson, W. R. N. Bioorg. Med.
Chem. Lett. 1994, 4, 1673.
17. Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds from Cyclopropanes to
Ylides; Wiley Inter-Science: New York, 1998.
H2N
N
Ph
S
Cu(OTf)2
-H2O
O
+
+
N2
N2
-
NH2
Ph
H N
2 ..
S
Ph
-
N
Ph
N
+
H2N
N2
H2N
S
S
18. Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94, 1091.
19. Padwa, A.; Hornbuckle, S. A. Chem. Rev. 1991, 91, 263.
20. Doyle, M. P. Chem. Rev. 1986, 86, 919.
Scheme 3. A plausible reaction mechanism.
21. Regitz, M.; Mass, G. In Diazo Compounds—Properties and Synthesis;
Academic Press: New York, 1986; p 90.
This method provides direct access to a wide range of 2-
aminothiazoles from readily available diazoketones and
thiourea. The present method offers significant advantages
including mild reaction conditions, high conversions, short
reaction times, cleaner reaction profiles and high selectivity
making it a useful and attractive strategy for the prepara-
tion of biologically relevant 2-aminothiazole derivatives
in a single step operation.
22. Jones, K.; Toutounji, T. Tetrahedron 2001, 57, 2427.
23. General procedure: (i) Preparation of a-diazoketones: The starting a-
diazoketones were prepared by the condensation of the respective acid
chlorides (1 eq) with diazomethane (4 eq) at 0 °C in diethyl ether. (ii)
Synthesis of thiazoles: A mixture of a-diazoketone (1 mmol), thiourea
(1 mmol) and Cu(OTf)2 (0.1 mmol) in dichloroethane (10 mL) was
stirred at 80 °C for the appropriate time (Table 1). After the
completion of the reaction as indicated by TLC, the reaction mixture
was quenched with water and extracted with ethyl acetate
(2 Â 15 mL). The combined organic layers were dried over anhydrous
Na2SO4 and the solvent was evaporated. The crude residue was
purified on silica gel (Merck, 100–200 mesh, ethyl acetate–hexane, 2:8)
to afford the pure 2-aminothiazole. Spectral data for selected
products: 4-Phenylthiazol-2-amine (entry a): Pink coloured solid.
Mp 149–150 °C. IR (KBr): m 3434, 3254, 3154, 3113, 2924, 2368, 1598,
1517, 1480, 1439, 1332, 1196, 1070, 1023, 909, 843, 770, 713 cmÀ1. 1H
NMR (300 MHz, CDCl3 + DMSO): d 7.73 (d, 2H, J = 7.8 Hz), 7.36–
7.17 (m, 3H), 6.63 (s, 1H) 6.21 (br s, 2H). 13C NMR (proton
decoupled, 75 MHz, CDCl3 + DMSO): d 167.3, 149.1, 133.7, 127.2,
126.0, 124.5, 100.1. ESIMS: m/z: (M++H): 177. HRMS calcd for
C9H8N2S: 177.0486. Found: 177.0488. 4-[3-(Z-2-Chloro-3,3,3-triflu-
oroprop-1-enyl)-2,2-dimethylcyclopropyl]thiazol-2- amine (entry i):
Brown coloured solid. Mp 76–77 °C, IR (KBr): m 3285, 3125, 2957,
1615, 1523, 1458, 1295, 1186, 1141, 1048, 955, 893, 846, 817, 761,
Acknowledgement
Y.G.R. thanks CSIR, New Delhi, for the award of
fellowship.
References and notes
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Steinbaugh, B. A.; Batley, B. L.; Painchaud, C. A.; Rapundalo, S. T.;
Michniewicz, B. M.; Olson, S. C. J. J. Med. Chem. 1992, 35, 2562.
3. Haviv, F.; Ratajczyk, J. D.; DeNet, R. W.; Kerdesky, F. A.; Walters,
R. L.; Schmidt, S. P.; Holms, J. H.; Young, P. R.; Carter, G. W. J.
Med. Chem. 1988, 31, 1719.
4. Clemence, F.; Martret, O. L.; Delevallee, F.; Benzoni, J.; Jouanen, A.;
Jouquey, S.; Mouren, M.; Deraedt, R. J. Med. Chem. 1988, 31, 1453.
5. Jaen, J. C.; Wise, L. D.; Caprathe, B. W.; Tecle, H.; Bergmeier, S.;
Humblet, C. C.; Heffner, T. G.; Meltzner, L. T.; Pugsley, T. A. J.
Med. Chem. 1990, 33, 1453.
6. Tsuji, K.; Ishikawa, H. Bioorg. Med. Chem. Lett. 1994, 4, 1601.
7. Bell, F. W.; Cantrell, A. S.; Ho¨berg, M.; Jaskunas, S. R.; Johansson,
N. G.; Jordon, C. L.; Kinnick, M. D.; Lind, P.; Morin, J. M., Jr.;
Noren, R.; Oberg, B.; Palkowitz, J. A.; Parrish, C. A.; Pranc, P.;
Sahlberg, C.; Ternansky, R. J.; Vasileff, R. T.; Vrang, L.; West, S. J.;
Zhang, H.; Zhou, X.-X. J. Med. Chem. 1995, 38, 4929.
730 cmÀ1 1H NMR (300 MHz, CDCl3): d 1.18 (s, 3H), 1.32 (s, 3H),
.
2.00 (t, 1H, J = 9.0 Hz), 2.19 (d, 1H, J = 8.7 Hz), 5.35 (br s, 2H), 6.09
(s, 1H), 6.55 (d, 1H, J = 9.8 Hz). 13C NMR (proton decoupled,
75 MHz, CDCl3): d 166.9, 147.7, 133.1, 122.4, 118.8, 119.6, 105.3,
33.1, 29.6, 26.2, 28.7, 16.9. ESIMS: m/z: (M++H): 297. HRMS calcd
for C11H13ClF3N2S: 297.0440. Found: 297.0452. 4-Pentadecylthiazol-
2-amine (entry k): Colourless solid. Mp 65–66 °C. IR (KBr): m 3430,
3233, 3065, 2920, 2850, 1607, 1541, 1511, 1467, 1377, 1317, 1112,
1021, 967, 847, 720, 698, 632 cmÀ1 1H NMR (300 MHz, DMSO): d
.
0.91 (t, 3H, J = 7.0 Hz), 1.29 (br s, 24H), 1.55–1.65 (m, 2H), 2.43 (t,
2H, J = 7.0 Hz), 5.90 (s, 1H), 6.31 (br s, 2H). 13C NMR (proton
decoupled, 75 MHz, CDCl3 + DMSO): d 167.1, 151.5, 99.0, 33.2,
30.5, 30.3, 28.3, 27.4, 23.7, 21.3, 12.9. EIMS m/z: (M++H): 311.40.
HRMS calcd for C18H35N2S: 311.2520. Found. 311.2536.