desulfurized with Raney nickel to produce the corresponding
ethers.13 The synthesis of 1,3,4-oxadiazoles,14 which possess
significant activity as herbicides, fungicides, and plant cell
growth factors, require thionoesters as precursors.5,15 Conse-
quently, we have broadened the scope of this solvent-free
protocol by preparing valuable thionoesters (Table 3).16 In
this case, our process requires 0.8 equiv of the Lawesson’s
reagent for complete conversion to the corresponding
thioesters, which is a dramatic improvement over existing
methods. Normally, 2.0-3.0 equiv of the reagent is needed
in lengthy reactions (20-25 h) which is presumably respon-
sible for the decomposition of the Lawesson’s reagent.
In conclusion, we have developed a general, rapid, and
solvent-free protocol17 for the synthesis of thio analogues
of ketones, flavones, isoflavones, lactones, amides and esters
which are widely used in organic synthesis. Our eco-friendly
solventless method avoids the use of excess amount of
Lawesson’s reagent and precludes the use of dry hydrocarbon
solvents such as benzene, xylene, triethylamine, or pyridine.
(11) Welton, A. F.; Tobias, L. D.; Fiedler-Nagy, C.; Anderson, W.; Hope,
W.; Meyers, K.; Coffey, J. W. In Plant FlaVonoids in Biology and Medicine;
Cody, V., Middelton Jr, E., Jr., Harborne, J. B.,Eds.; Alan R. Liss: New
York, 1986; p 231. (b) Havsteen, B. Biochem. Pharmacol. 1983, 32, 1141.
(12) (a) Baker, W.; Clarke, G. G.; Harborne, J. B. J. Chem. Soc. 1954,
998. (b) Dudley, K. H.; Miller, H. W.; Corley, R. C.; Wall, M. E. J. Med.
Chem. 1967, 10, 985. (c) Dean, F. M.; Goodchild, J.; Hill, A. W. J. Chem.
Soc. C 1969, 2192. (d) Baker, W.; Harborne, J. B.; Ollis, W. D. J. Chem.
Soc. 1952, 1303. (e) Baruah, A. K.; Prajapati, D.; Sandhu, J. S. Tetrahedron
1988, 44, 6137.
(13) (a) Baxter, S. L.; Bradshaw, J. S. J. Org. Chem. 1981, 46, 831. (b)
Bradshaw, J. S.; Jones, B. A.; Gebhard, J. S. J. Org. Chem. 1983, 48, 1127.
(c) Jones, B. A.; Bradshaw, J. S.; Brown, P. R.; Christensen, J. J.; Izatt, R.
M. J. Org. Chem. 1983, 48, 2635.
(14) Reynaud, P.; El Hamad, Y.; Davrinche, C.; Nguyen-Tri-Xuong, E.;
Tran, G.; Rinjard, P. J. Heterocycl. Chem. 1992, 29, 991.
(15) Kraemer, I.; Schunack, W. Arch. Pharm. (Weinheim, Ger.) 1986,
319, 1091.
Acknowledgment. We are grateful for financial support
to the Texas Research Institute for Environmental Studies
(TRIES).
(16) (a) Latif, K. A.; Ali, M. Y. Tetrahedron 1970, 26, 4247. (b)
Pedersen, B. S.; Scheibye, S.; Clausen, K.; Lawesson, S.-O. Bull. Soc. Chim.
Belg. 1978, 87, 293. (c) Misharev, A. D.; Takhistov, V. V. Org. Mass
Spectrom. 1981, 16, 99. (d) Raap, R. Can. J. Chem. 1968, 46, 2251. (e)
Hartke, K.; Kunze, O.; Hoederath, W. Synthesis 1985, 960. (f) Couture,
A.; Huguerre, E.; Grandclaudon, P. J. Org. Chem. 1990, 55, 4337.
(17) Experimental Section: General Procedure. The preparation of
6,7-dimethoxythiocoumarin is representative of the method employed. A
mixture of 6,7-dimethoxycoumarin (1 mmol) and Lawesson’s reagent (0.5
mmol, in the case of esters, 0.8 mmol), was taken in a glass tube and mixed
thoroughly with a spatula. The glass tube was then placed in an alumina
bath inside the microwave oven (900 W) and irradiated for 3 min (see Tables
1-3 for the time required for individual compounds). On completion of
the reaction, followed by TLC examination, the colored material was
OL990629A
dissolved in dichloromethane and adsorbed on silica gel and purified by
silica gel column chromatography using hexane as initial eluent followed
by ethyl acetate/hexane (1:9 v/v) which afforded the pure 6,7-dimethoxy-
thiocoumarin: yield 94%; mp 195-96 °C; 1H NMR (CDCl3) δ 3.94 (s,
6H, OCH3), 6.86 (s, 1H, C8-H), 7.01 (s, 1H, C5-H), 7.15 (d, 1H, J )
9.3, C3-H), 7.38 (d, 1H, J ) 9.3, C4-H); 13C NMR (CDCl3) δ 57.21,
57.36,f 100.57, 107.10, 108.09, 114.61, 128.02, 135.93, 148.18, 154.18,
197.80; Mass: [M+] 222. In the case of flavone (entry 6, Table 1) and
coumarin (entry 8, Table 2), the reactions were conducted on relatively
larger scale (5 mmol) with reproducible results in terms of yields.
700
Org. Lett., Vol. 1, No. 5, 1999