Thermal and Mechanistic Study of 2-Amino-1,3,4-Thiadiazoles.

PAOLA LUCERO; WALTER J. PELÁEZ; GUSTAVO ARGÜELLO; E. LAURA MOYANO

Florianópolis - Brazil

Conferencia; 10th Latin American Conference on Physical Organic Chemistry - 10thCLAFQO; 2009

It is well know that 2-amino-1,3,4-Thiadiazole derivatives have wide range of pharmaceutical applications.[1] Nevertheless, the bibliography about thermal stability of these rings is really scarce in comparison with the data found for 1,3,4-oxadiazoles.[2] On the other hand, Flash Vacuum Pyrolysis (FVP) is a suitable technique for the study of reaction mechanics of different heterocycles and also as alternative synthetic tool. In this work we present the thermal behavior of different 2-amino-1,3,4-thiadiazoles under FVP conditions. The substrates studied were the 2-amino-1,3,4-thiadiazoles 1a-c at temperatures between 520-600 ºC, contact time of 10-4 s and system pressure of 10 µtorr. The characterization of the reaction products was performed using GC-MS, IR and 1H NMR techniques. As can be seen in the scheme 1, the major reaction products were nitriles (2a-c), cyanamide (3) and elemental sulfur. The formation of these products could be explained by a unimolecular ring opening of the thiadiazole ring. The question would be if this is a concerted process where the three products are formed simultaneously or whether this is more like a biradical process. This led us to examinate the values of the Arrhenius parameters. The activation parameters for 1a (log A=22 and ∆G‡= 165 KJ/mol) were in agreement with a mechanism involving the formation of a biradical in a first step (rate determining) followed by nitrilimines formation (i and ii) and subsequent fragmentations.[3] When FVP reaction was carried out in presence of large excess of toluene, the reaction products were unaffected according to a non radical process. Thus, the C-S bond in the transition state must be broken and rapidly rearranged to nitrilimines (i and ii) before the C and S atoms acquire a radical character. The intermediacy of nitrilimine ib is explained by the detection of phenylisothiocianate from the thioazirine 4b. In the other hand, the presence of 4d was confirmed by IR spectroscopy in the degradation of this intermediate to more stable cyanamide 3. [1] J. Matysiak, A. Opolski; Bioorg. Med. Chem. 2006, 14, 4483.[2] T. Gilchirst, C. Rees,  C. Thomas; J. Chem. Soc. Perkin Trans. 1, 1975, 12. [3] A. Lifshitz, D. Wohlfeiler, J. Org. Chem. 1992, 43, 4816.