Flash Vacuum Thermolysis of 1,2,3-Thiadiazoles

A series of 5-alkyl-, 5-aryl-, 5-aryloxy-, 5-arylthio-and 5-benzotriazolyl-4-phenyl-1,2,3-thiadiazoles were subjected to flash vacuum thermolysis. Depending on the 5-substituent, the products were 1,4-dithiins, benzodithiins, benzothiophenes, disulfides or benzimidazoliumides

FVT of 5-aryloxy-4-phenyl-1,2,3-thiadiazoles (8).FVT of 5-(4-methylphenoxy)-4-phenyl-1,2,3-thiadiazole (8a) was carried out between 170−250 o C. In the reaction mixture, 2-(4methylphenoxy)benzothiophene (9a) and p-cresol (10a) were detected as the major products (Scheme 3).Formation of benzothiophene 9a can be explained by the formation of diradical 8(i), which then rearranges via insertion of the sulfur-centered radical into the C-H bond of the phenyl ring.p-Cresol may be formed by a competitive radical reaction from the starting material when the C-O bond is broken under thermal conditions.The presence of radicals was confirmed by formation of dibenzyl in reactions where toluene was used as a carrier gas.
FVT of 4-phenyl-5-[(2,5-dimethylphenyl)thio]-1,2,3-thiadiazole (11c) was carried out between 250−300 ºC.Thiadiazole 11c was completely converted to products at 300 ºC.At lower temperatures (250 ºC) dithiin 12c and benzothiophene 13c are the main products (Scheme 4).Dithiin 12c and benzothiophene (13c) are formed by nitrogen extrusion and rearrangement of diradical intermediates.The pyrolysates at 250−300 ºC showed a deep green color, which disappeared at high temperatures.The coloration changed to yellow when the crude reaction mixture was kept at RT for several hours.When the 1 H-NMR spectrum was run immediately after the reaction, a typical signal at 4.52 ppm was detected, corresponding to H-3 in the thione 16c.In this experiment, only one dithiin was observed probably due to fast isomerization of diradical 11(i) to carbene 11(iv) avoiding the cyclization of diradical 11(i) to the thiirene intermediate.

FVT of 4-phenyl-5-(heteroaryl)-1,2,3-thiadiazole (17).
Thermolysis of 1-(4-phenyl-1,2,3thiadiazol-5-yl)-1H-1,2,3-benzotriazole (17) was carried out between 200−300 ºC (Scheme 5).Nitrogen extrusion and subsequent rearrangements gave the zwitterion product 18 in good yield (18-72%).It is proposed that this reaction proceeds through the mechanism shown in Scheme 5. Formation of the diradical 17(iii) is followed by opening of the benzotriazole ring, a transannular cyclization then gives the final product 18.This type of ring contraction has been observed in the thermolysis of eight and nine-membered rings. 6,10It should be noted that the zwitterion 18 was also obtained as the main product in the thermal reactions of thiadiazole 17 using DMF at 150-170ºC.9b In that case the structure of this compound was determined by single crystal X-ray analysis and the yield of those reactions were about 39%.

Conclusions
In summary, we have shown that substituted thiadiazoles undergo a nitrogen extrusion reaction at fairly low temperatures (150 o C for 5-aryloxythiadiazoles) under FVT conditions to give diradical intermediates that can undergo different rearrangements depending upon the substituents present.Products formed are in accordance with the earlier observations such as involvement of thiirenes, and coupling of diradicals.Our observations further demonstrate the formation of products via insertion of sulfur-centered radicals or thioketenes into a C-H bond of the aromatic ring and transannular cyclizations involving heteroaryl rings.

Experimental Section
General Procedures.Thermolysis was carried out in a glass FVT equipment using a GAYNOR PRDH temperature controller and a Thermolyne 21100 tube furnace, 30 cm (length) and 1 cm (diameter).Oxygen free dry nitrogen or a mixture of nitrogen/toluene was used as carrier gas.Flow rates of carrier gas were between 0.1-0.09ml sec -1 .Samples to be pyrolyzed were 20−80 mg.Contact times were around 10 -2 sec and the pressure from 0.02−0.01Torr (with and without carrier gas) was measured with a McLeod manometer.Products were trapped at liquid air temperature, extracted with solvent and submitted to different analyses or separation techniques.Quantification of products by 1 H-NMR spectroscopy was made using exact amounts of 2,4dinitro-chlorobenzene as an internal standard.Gas chromatography/mass spectrometry (GC/MS) analyses were performed with a Perkin Elmer Q-Mass 910 spectrometer equipped with an SE-30 column, using helium as eluent at a flow rate of 1ml/min and a heating rate of 40 o C for 5 min and 400 o C to 280 o C for 40 min. 1 H-NMR and 13 C-NMR spectra were recorded in CCl 4 solution with a capillary tube filled with acetone-d 6 inside the NMR tube or CDCl 3 using a Bruker 200 FT spectrometer (working at 200 and 75MHz respectively).Chemical shifts are reported in parts per million (ppm) downfield from TMS. Elemental analyses were performed on a Perkin-Elmer 240C microanalyser.The product was a mixture of 3 and 4. 1 H-NMR δ 0.88 (t, J = 7 Hz, 6H), 0.91 (t, J = 7 Hz, 6H), 1.40 (q, J = 7 Hz, 4H), 1.42 (q, J = 7 Hz, 4H), 2.32 (t, J = 7 Hz, 4H), 2.35 (t, J = 7 Hz, 4H), 7.18-7.40(m, 20H). 13C-NMR δ 13.6, 13.9, 21.