212
A. S. Shawali, S. Elsheikh and C. Párkányi
Vol. 40
then the solvent was evaporated. The residue was dissolved in
chloroform and the resulting solution was extracted three times
with water. The chloroform layer was separated, dried over anhy-
drous sodium sulfate, and filtered. The solvent was distilled off,
the remaining solid was collected and crystallized from ethanol
to give the pure benzothiazine derivative 8 (90% yield). The
physical constants of 8 are shown in Table 3.
Methylation of 4f.
To an ethanolic solution of sodium ethoxide, prepared by dis-
solving sodium metal (0.12 g, 5 g-atom) in absolute ethanol (30
mL), compound 4f (1.5 g, 3 mmol) was added with stirring.
Methyl iodide (0.7 g, 5 mmol) was added to the resulting solu-
tion, the mixture was refluxed on a water bath for 1 h, and then
left in a refrigerator for 24 h. The precipitated solid was collected
by filtration, washed with water, dried, and crystallized from
ethanol to afford 9f (Tables 1-3).
Preparation of 2,3-Dihydro-2-arylhydrazono-4H-1,4-benzoth-
iazin-3-ones (4) [9].
Method A.
REFERENCES AND NOTES
The appropriate thiohydrazonate ester 3 (0.01 mol) was added
to ethanol (30 mL, already saturated with hydrogen chloride)
with stirring. The solution was stirred for 3 h at room temperature
and the solvent was evaporated. Water was added to the residue
and the mixture was neutralized with a solution of sodium bicar-
bonate. The aqueous solution was extracted with chloroform
three times and the extracts were collected, dried over anhydrous
sodium sulfate, and filtered. The solvent was distilled off from
the filtrate and the remaining solid residue was collected and
crystallized from the appropriate solvent to give the respective
benzothiazine derivative 4. Information about these products and
their physical constants are summarized in Table 6.
[1a] C. Párkányi, A. O. Abdelhamid and A. S. Shawali,
J. Heterocyclic Chem., 21, 521 (1984); [b] A. O. Abdelhamid, H. M.
Hassaneen, A. S. Shawali and C. Párkányi, J. Heterocyclic Chem., 20,
639 (1983).
[2] M. A. Abdallah, M. A. N. Mosselhi, I. M. Abbas, A. A. Fahmi
and A. S. Shawali, J. Chem. Res. (S), 370 (1995).
[3] M. A. N. Mosselhi, M. A. Abdallah, S. M. Riyadh, A. E.
Harhash and A. S. Shawali, J. Prakt. Chem., 340, 160 (1994).
[4] M. A. Abdallah, M. A. N. Mosselhi, S. M. Riyadh, A. E.
Harhash and A. S. Shawali, J. Chem. Res. (S), 700, (M), 3038 (1998).
[5a] S. A. Khattab, A. S. Shawali and A. M. Farag, J. Chem. Eng.
Data, 22, 104 (1974); [b] C. Párkányi and A. S. Shawali, J. Heterocyclic
Chem., 17, 897 (1980).
Method B.
[6a] A. S. Shawali, H. M. Hassaneen and M. A. Hanna,
Heterocycles, 15, 697 (1981); [b] A. S. Shawali, A. O. Abdelhamid, N. F.
Ahmed, and C. Párkányi, Heterocycles, 19, 2331 (1982).
[7a] B. E. Elanadouli, A. O. Abdelhamid and A. S. Shawali, J.
Heterocyclic Chem., 21, 1087 (1984); [b] A. S. Shawali, S. S. Alkaabi
and M. A. Abdallah, Arch. Pharm. Res., 14, 237 (1991).
[8] A. S. Shawali, N. M. S. Harb and K. O. Badahdah, J.
Heterocyclic Chem., 22, 1397 (1985).
To a mixture of equimolar amounts of 1 and 2-aminothiophe-
nol (2) (5 mmol each) in ethanol (50 mL), triethylamine (0.96
mL, 0.7 g, 5 mmol) was added with stirring. The mixture was
refluxed for 6 h and then cooled. The precipitated solid material
was collected by filtration, washed with water, and crystallized
from the appropriate solvent (Table 6) to afford the respective
benzothiazine derivatives 4. The physical constants of the com-
pounds obtained by this method are shown in Table 6.
When the same procedure was repeated using the labeled com-
pound 1d' instead of 1d, the labeled product 4d' was obtained in
73% yield (mp 288 °C), with no depression of the mp when
mixed with the unlabeled derivative 4d.
[9] N. Almirante and L. Forti, J. Heterocyclic Chem., 20, 1523
(1983).
[10] M. K. A. Ibrahim, M. S. El-Gharib, A. M. Farag and A. H.
Elghandour, Indian J. Chem., Sect. B, 27B, 836 (1988).
[11] R. R. Philips, Organic Reactions, 10, 143 (1959).
[12a] A. S. Shawali and H. M. Hassaneen, Bull. Chem. Soc. Jpn.,
50, 2827 (1977); [b] A. J. Elliott, M. S. Gibson, M. M. Kayser and G. A.
Pawelchak, Can. J. Chem., 51, 4115 (1973).
Method C.
To a stirred solution of 8 (1.9 g, 0.01 mol) in ethanol (30 mL),
a solution of sodium hydroxide (0.6 g, 0.015 mol) in water (10
mL) was gradually added with stirring. The solution was stirred
for an additional 1 h and then chilled in an ice bath at 0-5 °C. A
cold solution of the appropriate benzenediazonium chloride was
prepared in the usual fashion by diazotization of the respective
aniline derivative (0.01 mol) in 6 M hydrochloric acid (4 mL)
with a solution of 1 M sodium nitrite (10 mL). Then the cold
solution of the diazonium salt was added to a stirred cold solution
of 8 described above. When the addition of the diazonium salt
was completed (20 min), the mixture was stirred for 2 h and then
left in a refrigerator for 24 h. The precipitated solid was collected
by filtration, washed with water, and crystallized from the appro-
priate solvent to give 4 identical in all respects with the products
obtained by methods A and B (Table 6).
[13] G. D. Searle & Co. (M. Zimmermann), U.S. Pat. 2841582
(1956); Chem. Abstr., 56, 3496 (1962).
[14] P. Baudet and C. Otten, Helv. Chim. Acta, 53, 1683 (1970).
[15] W. Ried and G. Sell, Liebigs Ann. Chem., 1917 (1980).
[16] H. Tawada, Y. Sugiyama, H. Ikeda, Y. Yamamoto and
K. Meguro, Chem. Pharm. Bull., 38, 1238 (1990); Chem. Abstr., 113,
132112z (1990).
[17] A. R. Katritzky, M. Karelson and P. A. Harris, Heterocycles,
32, 329 (1991).
[18] P. Frohberg, U. Baumeister, D. Stroehl and H. Danz,
Heterocycles, 45, 1183 (1997).
[19] R. Jones, A. J. Ryan, S. Sternhell and S. E. Wright,
Tetrahedron, 19, 1497 (1963).
[20] G. E. Wright, J. Heterocyclic Chem., 20, 1037 (1983).
[21] N. E. MacKenzie, R. H. Thompson and C. W. Greenhalgh,
J. Chem. Soc., Perkin Trans. 1, 2923 (1980).
15
Coupling of 8 with diazotized N-aniline under the same con-
15
ditions gave 4d' - the N- isotopomer of 4d, identical in all
[22] G. J. Lestina and T. H. Regan, J. Org. Chem., 34, 1685 (1969).
[23] A. S. Shawali and H. A. Albar, Can. J. Chem., 64, 871 (1986).
respects with that obtained by method A.