4-Allyl-5-phenyl-1,2,4-triazole-3(4H)-thione (1). Mixture of KSCN (3.92 g, 40.0 mmol) and allyl
bromide (3.90 ml, 45.0 mmol) in dry acetone (20 ml) was boiled in a round-bottomed flask for 2 h. Acetone was
distilled off on a rotary evaporator, xylene (30 ml) was added to the residue, KBr was filtered off, and the
resulting solution boiled for a further hour. Solution of benzoic acid hydrazide (5.44 g, 40.0 mmol) in hot xylene
(20 ml) was added to the obtained solution of allyl isothiocyanate. The precipitated solid was filtered off, washed
with pentane, and dried. 1-Allyl-4-benzoylthiosemicarbazide (8.93 g, 95%) was obtained, which was dissolved
in 2.5% NaOH solution (80 ml) and heated on a water bath for 3 h. The obtained solution was acidified with
glacial acetic acid (7.0 ml) to pH 6. An oil separated, which crystallized. After two recrystallizations of the
product from a benzene–hexane mixture (50 ml) thione 1 (6.60 g, 70% on benzoic acid hydrazide) was obtained
having mp 120°C (mp 118°C [1]), Rf 0.47 (ethyl acetate–hexane, 1:3).
6-Iodomethyl-3-phenyl-5,6-dihydrothiazolo[2,3-c]-1,2,4-triazole (2) and 6-Iodo-3-phenyl-6,7-
dihydro-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine (3). 4-Allyl-5-phenyl-1,2,4-triazole-3-thione (2.17 g, 10.0 mmol)
was dissolved in CH2Cl2 (100 ml) and sublimed iodine (6.34 g, 25.0 mmol) was added. The mixture was left to
stand at room temperature in the dark for several days, then CH2Cl2 was evaporated under reduced pressure.
Further treatment may be carried out by two procedures.
A. The residue was dissolved in acetone (20 ml) and poured with cooling into solution of Na2S2O3·5H2O
(8.69 g, 35.0 mmol) and Na2CO3 (1.27 g, 12.0 mmol) in water (150 ml). The solid which precipitated was a
mixture (3.29 g, 96%) of cyclization products. A sample (500 mg) of the mixture was separated
chromatographically on a column of silica gel (eluent was ethyl acetate) and thiazole 2 (388 mg, 77.6%) and
thiazine 3 (96 mg, 19.2%) were obtained. It is possible to obtain the individual products by fractional extraction
of the more soluble isomer 2 from the mixture of isomers with chloroform. From the mixture (3.00 g) of isomers
compound 2 (2.04 g, 68%) and product 3 (0.40 g, 13%) were obtained.
6-Iodomethyl-3-phenyl-5,6-dihydrothiazolo[2,3-c]-1,2,4-triazole (2). Mp 156°C (acetonitrile), Rf 0.28
(ethyl acetate). Found, %: I 36.6; S 9.40. C11H10IN3S. Calculated, %: I 36.98; S 9.34.
6-Iodo-3-phenyl-6,7-dihydro-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine (3). Mp 194°C (70% AcOH),
Rf 0.21 (ethyl acetate). Found, %: I 36.50; S 9.30. C11H10IN3S. Calculated, %: I 36.98; S 9.34.
B. The reaction mixture was dissolved in acetone and treated with NaI·2H2O (3.72 g, 20.0 mmol) in
acetone (20 ml). The precipitated hydroiodide was filtered off, washed with acetone, and the solid obtained was
dried in the dark. Mixture (4.19 g, 89%) of hydroiodides of compounds 2 and 3 was obtained, which was stirred
for 1 h in solution of NaHCO3 (0.84 g, 10 mmol) in water (50.0 ml). The obtained solid was filtered off, washed
with water, and dried in the dark. Mixture (2.99 g, 98%) of compounds 2 and 3 was obtained. Separation of the
isomers was carried out as in method A.
6-Methyl-3-phenylthiazolo[2,3-c]-1,2,4-triazole (4). Compound 2 (343 mg, 1.0 mmol) was dissolved
in 5% solution (15 ml) of KOH in methanol, the solution was heated to boiling, then left for several hours at
room temperature. MeOH was evaporated under reduced pressure, the residue was extracted with CHCl3
(3 × 10 ml), the combined extracts dried over anhydrous Na2SO4, CHCl3 was evaporated, and the residue
recrystallized from benzene–hexane. Thiazole 4 (185 mg, 86%) was obtained; mp 196°C, Rf 0.26 (ethyl acetate).
Found, %: S 14.80. C11H9N3S. Calculated, %: S 14.89.
Mixture of 3-Phenyl-5H-1,2,4-triazolo[3,4-b]-1,3-thiazine (5a) and 3-Phenyl-7H-1,2,4-triazolo[3,4-b]-
1,3-thiazine (5b). Elimination of HI from thiazine 3 (100 mg, 0.29 mmol) was carried out analogously to the
preparation of compound 4. After evaporation of the solvent the mixture (59 mg, 95%) of isomers 5a and 5b was
obtained. Found, %: S 14.71. C11H9N3S. Calculated, %: S 14.89.
REFERENCES
1.
2.
3.
M. N. Tsitsika, S. M. Khripak, and I. V. Smolanka, Ukr. Khim. Zh., 42, 841 (1976).
S. Ernst, S. Jelonek, J. Silez, and K. Schulze, Tetrahedron, 52, 791 (1996).
L. Strzemecka, Polish J. Chem., 57, 567 (1983).
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