M. Kodomari et al. / Tetrahedron Letters 46 (2005) 5841–5843
5843
Weaner, L. E.; Reynolds, B. E.; Hood, A. R.; Hecker, L.
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to the reaction mixture and stirred for 1 h. Finally,
hydrazine hydrate (10 mmol) was added and the result-
ing mixture was stirred for 1 h. The products were
extracted with 1,2-dichloroethane followed by isolation
of N-phenylthiourea (84%) by flash column chromato-
graphy. N-Benzylthiourea was obtained in 85% yield
by this method.
9. Moor, M. L.; Crossely, F. S. Org. Synth. Coll. Vol. III,
1955, 617.
10. Erickson, J. G. J. Org. Chem. 1956, 21, 483–484.
11. Bernstein, J.; Yale, H. L.; Losee, K.; Holsing, M.;
Martins, J.; Lott, W. A. J. Am. Chem. Soc. 1951, 73,
906–912.
In conclusion, we have developed a mild, simple, and
efficient method for the synthesis of mono- and N,N-
disubstituted thioureas by debenzoylation of N-substi-
tuted- and N,N-disubstituted-N0-benzoylthioureas with
hydrazine hydrate under solvent-free conditions. The
starting materials, N-substituted-N0-benzoylthioureas,
can be easily prepared in one-pot from benzoyl chloride,
NH4SCN/SiO2 and an amine.19
12. Kotetsu, M.; Fukuta, Y.; Ishihara, H. Tetrahedron Lett.
2001, 42, 6333–6335.
13. Cressman, H. W. J. Org. Synth. Coll. Vol. III, 1955, 609.
14. (a) Vazquez, J.; Bernes, Sylvain; Reyes, Yasmi; Maya,
Monica; Sharma, Pankaj; Alvarez, C.; Gutierrez Synthesis
2004, 1955–1958; (b) Katritzky, A. R.; Kirichenko, N.;
Rogovoy, B. V.; Kister, J.; Tao, H. Synthesis 2004, 1799–
1805; (c) Ciszewski, L.; Xu, D.; Repic, O.; Blacklock, T. J.
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References and notes
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17. Marquez, H.; Perez, E. R.; Plutin, A. M.; Mdrales, M.;
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18. Silica gel-supported ammonium thiocyanate was prepared
as follows. Silica gel (18.48 g) was added to a solution of
ammonium thiocyanate (20 mmol 1.52 g) in dry aceto-
nitrile (50 mL), and the mixture was stirred at room
temperature for 30 min. The acetonitrile was removed
under reduced pressure. The resulting reagent was dried in
vacuo (15 mmHg) at room temperature for 3 h.
19. Typical procedure for N-substituted-N0-benzoylthioureas:
To a slurry of NH4SCN/SiO2 (20 mmol, 20 g) in 1,2-
dichloroethane (100 mL) was added benzoyl chloride
(10 mmol). The mixture was stirred at 25 °C for 2 h, and
then an amine (20 mmol) was added to it and stirred for an
additional 1 h. The reaction mixture was filtered to remove
the supported reagent, and the filtrate was washed with 5%
HCl, brine, and dried over Na2SO4. The solvent was
evaporated under reduced pressure to leave the crude
product, which was purified by recrystallization
(methanol).
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