4
Tetrahedron
8.
(a) Kidwai, M.; Venkataramanan, R.; Dave, B. Green Chem.
2001, 3, 278–279; (b) Paul, S.; Gupta, M.; Gupta, R.; Loupy, A.
Synthesis 2002, 75–78.
Anshu, D.; Kapil, A.; Meha, S. Synth. Commun. 2004, 34, 1141–
1155.
activity was also examined under optimized reaction conditions,
but unfortunately no reaction was observed. Later, the same
reaction was tested using strong base, anhydrous potassium
carbonate (K2CO3) and no target product could observe.
Subsequent optimization for the reaction led to increase in yield;
we did the reaction with anhydrous potassium carbonate (K2CO3)
at 80 °C. Very interestingly the reaction could produce target
product in moderate yield (Table 4, entry 10). Disubstituted and
ortho-substituted aryl rings could obtain their respective
thioureas in good yield (Table 4, entries 5 and 8). Finally we
have also studied about aliphatic anilines. The aliphatic
substrates readily underwent the reaction to produce the target
products in high yields (Table 4, entries 9 and 10-11).
9.
10. Heinelt, U.; Schultheis, D.; Jager, S.; Iindenmaire, M.; Pollex, A.;
Beckmann, H. S. g. Tetrahedron 2004, 60, 9883–9888.
11. Loev, B.; Bender, P. E.; Bowman, H.; Helt, A.; McLean, R.; Jen,
T. J. Med. Chem. 1972, 15, 1024–1027.
12. (a) Frank, R. L.; Smith, P. V. Org. Synth. Coll. Vol. III, 1955, 735;
(b) Rasmussen, C. R.; Villani, F. J., Jr.; Weaner, L. E.; Reynolds,
B. E.; Hood, A. R.; Hecker, L. R.; Nortey, S. O.; Hanslin, A.;
Costanzo, M. J.; Powell, E.T.; Molinari, A. J. Synthesis 1988,
456–459.
13. Moor, M. L.; Crossely, F. S. Org. Synth. Coll. Vol. III, 1955, 617.
14. (a) Erickson, J. G. J. Org. Chem. 1956, 21, 483–484. (b)
Bernstein, J.; Yale, H. L.; Losee, K.; Holsing, M.; Martins, J.;
Lott, W. A. J. Am. Chem. Soc. 1951, 73, 906–912. (c) Kotetsu, M.;
Fukuta, Y.; Ishihara, H. Tetrahedron Lett. 2001, 42, 6333–6335.
(d) Vazquez, J.; Bernes, Sylvain; Reyes, Yasmi; Maya, Monica;
Sharma, Pankaj; Alvarez, C.; Gutierrez Synthesis 2004, 1955–
1958; (e) Katritzky, A. R.; Kirichenko, N.; Rogovoy, B. V.;
Kister, J.; Tao, H. Synthesis 2004, 1799–1805.
The substrate scope was also developed using another optimal
reaction DMF/H2O (2:1) (Table 5). As we shown in Table 5, both
electron donating and electron withdrawing substituents on aryl
ring could give their respective target products in 56-87% yields.
Following similar methodology, aliphatic amines such as n-butyl,
cyclohexyl and benzyl amines could give their respective target
products in 78%, 82% and 83% yield.
We proposed the mechanism of formation of phenyl thiourea
from aniline (Scheme 2). The reaction of aniline with carbon
disulfide catalyzed by base (B) gave thiocarbamate salt (K).
Then, cobalt co-ordinates to sulfur in thiocarbamate and another
chloride anion is abstracted to give thiocarbamate N.
Desulfurization of N afforded thioisocynate X that reacts with
ammonium to give target thiourea Y.
Conclusion
We have developed methodology for the synthesis of both
aromatic and aliphatic thioureas in one pot three step reaction
using cheap, readily available and air stable cobalt catalyst under
mild reaction conditions. All reactions could give their target
products in good to excellent yield. The reactions are rapid and
facile and accomplished at room temperature.
Acknowledgements
The authors thankful to Department of Chemistry, Bapatla
engineering college, Bapatla for providing work space and the
authors are grateful to Icon Pharmaceutical Lab for providing
instrumental support.
References and notes
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