1
32
LETTERS
SYNLETT
yield was slightly decreased. The reaction is completely inhibited by the
addition of a free galvinoxyl radical (entry 2 in Table 2), while N-
benzyl- and other N-alkyl(o-methylarene)sulfonamides did not give the
corresponding saccharin derivatives efficiently (Table 3). Here, the
compound 4 is not an intermediate which is formed via the Hofmann-
Loeffler-Freytag type reaction pathway, because it was not converted to
the saccharin skeleton under the same conditions. However, the
Hlasta, D. J.; Subramanyam, C.; Bell, M. R.; Carabateas, P. M.;
Court, J. J.; Desai, R. C.; Drozd, M. L.; Eickhoff, W. M.;
Ferguson, E. W.; Gordon, R. J.; Johnson, J. A.; Kumar, V.;
Maycock, A. L.; Mueller, K. R.; Pagani, E. D.; Robinson, D. T. ;
Saindane, M. T.; Silver, P. J.; Subramanian, S. J. Med. Chem.,
1995, 38, 739.
(
3) Lombardino, J. G. J. Org. Chem., 1971, 36, 1843; Watanabe, H.;
Gay, R. L.; Hauser, C. R. J. Org. Chem., 1968, 36, 900; Hlasta, D.
J.; Court, J. J.; Desai, R. C. Tetrahedron Lett., 1991, 32, 7179;
Desai, R. C.; Hlasta, D. J.; Monsour, G.; Saindane, M. T. J. Org.
Chem., 1994, 59, 7161.
compound
5 is an intermediate. The reaction of N-methyl(o-
methyl)benzeneamide, instead of N-methyl(o-methyl)arenesulfonamide,
was not clean and gave the N-methyl phthalimide in only 25% yield.
Thus, the present reaction is very useful for the direct preparation of
various
N-methylsaccharins
from
N-methyl(o-methyl)arene-
(
4) Giese, B. Radicals in Organic Synthesis: Formation of Carbon-
Carbon Bonds, Ed. Baldwin, J. E. Pergamon Press, 1986; Fossey,
J.; Lefort, D.; Sorba, J. Free Radicals in Organic Chemistry, John
Wiley & Sons, 1995.
sulfonamides, which are easily prepared by the chlorosulfonation of
methylarenes and subsequent amidation with methylamine. Here, the N-
methyl group in product 3 was easily removed by treatment with excess
trimethylsilyl iodide. Study on further elaboration of the method and
clarification of the reaction mechanism is now under way.
(
5) Armas P. de; Carrau, R.; Concepción, J. I.; Francisco, C. G.;
Hernández, R.; Suárez, E. Tetrahedron Lett., 1985, 26, 2493;
Armas, P. de; Francisco, C. G.; Hernández, R.; Salazar, J. A.;
Suárez, E. J. Chem. Soc., Perkin Trans 1, 1988, 3255; Carrau, R.;
Hernández, R.; Suárez, E. J. Chem. Soc., Perkin Trans 1, 1987,
Acknowledgement: Financial support from a Grant-in-Aid (No.
08640670) for Scientific Research from Ministry of Education, Science,
and Culture of Japan is gratefully acknowledged (H.T.).
9
37.
(
6) Hernández, R.; Medina, M. C.; Salazar, J. A.; Suárez, E.
Tetrahedron Lett., 1987, 28, 2533; Dorta, R. L.; Francisco, C. G.;
Suárez, E. J. Chem. Soc., Chem. Commun., 1989, 1168.
References
(
1) Davis, M. "Organic Compounds of Sulfur, Selenium, and
Tellurium", Vol. 5, Chap 10, Ed by The Chemical Society,
London (1979); Pain, D. L.; Peart, B. J.; Wooldridge, K. R. H.
(7) Togo, H.; Muraki, T.; Yokoyama, M. Tetrahedron Lett., 1995, 36,
7089; Muraki, T.; Togo, H.; Yokoyama, M. ibid., 1996, 37, 2441;
Togo, H.; Hoshina, Y.; Yokoyama, M. ibid., 1996, 37, 6129.
"
Comprehensive Heterocyclic Chemistry", Eds Katritzky A. R.;
Rees, C. W., Vol. 6, Pergamon Press, Oxford (1984); Svahn C.
M.; Jönsson, N. Å. Acta Chem. Scand., (B), 1978, 32, 137~140;
Drug of the Future, 1986, 11, 565.
(
8) All the compounds gave satisfactory spectroscopic and
microanalytical data.
(2) Desai. R. C.; Farrell, R. P.; Kuo, G-H.; Hlasta, D. J. Synlett, 1994,
933; Court, J. J.; Lessen, T. A.; Hlasta, D. J. ibid., 1995, 423;