1.2.4- Thiadiazole. ring expansion

However, there are some cases when an unpaired electron is localized not on the n, but on the o orbital of an anion-radical. Of course, in such a case, a simple molecular orbital consideration that is based on the n approach does not coincide with experimental data. Chlorobenzothiadiazole may serve as a representative example (Gul maliev et al. 1975). Although the thiadiazole ring is a weaker acceptor than the nitro group, the elimination of the chloride ion from the 5-chlorobenzothiadiazole anion-radical does not take place (Solodovnikov and Todres 1968). At the same time, the anion-radical of 7-chloroquinoline readily loses the chlorine anion (Fujinaga et al. 1968). Notably, 7-chloroquinoline is very close to 5-chlorobenzothiadiazole in the sense of structure and electrophilicity of the heterocycle. To explain the mentioned difference, calculations are needed to clearly take into account the o electron framework of the molecules compared. It would also be interesting to exploit the concept of an increased valency in the consideration of anion-radical electronic structures, especially of those anion-radicals that contain atoms (fragments) with available d orbitals. This concept is traditionally derived from valence-shell expansion through the use of d orbital, but it is also understandable in terms of simple (and cheaper for calculations) MO theory, without t(-orbital participation. For a comparative analysis refer the paper by ElSolhy et al. (2005). Solvation of intermediary states on the way to a final product should be involved in the calculations as well (Parker 1981). 

Butler and co-workers studied the quatemisation of 3,5-diaryl-l,2,4-thiadiazoles 77 with trimethylsilylmethyl triflate at 40 °C and observed reaction at N-2 to give salt 78. Desilyation of 78 with caesium fluoride resulted in ring expansion to 2ff-l,3,5-thiadiazines 79 which on heating in ethanolic sodium ethoxide gave 2,4-... 

Ring expansion of 1,2,5-thiadiazole hydrochloride 185, using no more than a molar amount of cyanide ion, gives 1,2,5-thiadiazine 187, possibly via ring-opened intermediate 186. Although product 187 is stable in the... 

Certain 1,2,4-thiadiazoles undergo ring expansion on treatment with dialkyl acylphosphonates. Thus, the action of diethyl acetyl(or benzoyl)-phosphonates (383, R = Me, Ph) on 4-benzyl-3-methyl-l,2,4-thiadiazolium bromide (382) produces substituted 1,2,4-thiadiazines (384), albeit in low yield. The pyrimidyl analog (385, formally comparable with thiamin) behaves similarly, but a cyclization (to 387) competes with the ring expansion (to 386). The structure of these and other complex products, and the mechanism of their formation, were discussed in detail.286... 

Reactions of 1,2,5-Thiadiazoles. The 2-methyl-3-methylamino-l,2,5-thiadi-azolium salt (13 X = N) undergoes ring-expansion on treatment with cyanide ion to give (14 Z = NH) and with MeOjCC C to give (14 Z = CHC02Me) see Scheme 1... 

The desilylation of 3,5-diaryl-l,2,4-thiadiazole quarternary ammonium salts 7 with CsF results in ring expansion to afford substituted 277-1,3,5-thiadiazines 10 in moderate yield (Equation 56) <1999J(P1)1709>. Ab initio studies have been carried out for this transformation and the details are presented in Section 9.09.2. 

Ring Expansion to Thiazines. In continuation of their extensive work on the ring expansion of thiazoles to 1,4-thiazines (see p. 605), Takamizawa et have extended their studies to the comparable reaction of the 1,3,4-thiadiazole ring system. Thus, treatment of 4-substituted 1,3,4-thiadia-zolium iodides (173) with dialkylbenzoylphosphonates in dimethyl-formamide yields products identified by their spectral properties as 5,6-dihydro-4-substituted-5-oxo-2,6-diphenyl-477-l,3,4-thiadiazines (174). The course of this reaction is explained, in line with the one previously proposed for thiazolium salts, by the mechanism shown in Scheme 3. 

Phenyl-substituted 1,2,4-thiadiazoles (see Table 98.3) undergo a variety of photoreactions, including photofi agmentation, phototransposition, and a unique photo-ring expansion reaction. As shown in Scheme 19, irradiation of 5-phenyl-1,2,4-thiadiazole 35 in acetonitrile solvent with Kght of > 290 nm results in the formation of benzonitrile 39, the photofragmentation product, 3-phenyl-l,2,4-thiadiazole 36, the phototransposition product, and phenyl-1,3,5-triazine 41 and diphenyl-1,3,5-triazine 42, the two photo-ring expansion products. 3-Methyl-5-phenyl-l,2,4-thiadiazole 37 reacted similarly to yield... 

PavHk, J.W., Changtong, C., and Tsefrikas, V.M., Photochemistry of phenyl substituted 1,2,4-thiadiazoles. Phototransposition, photofragmentation and photo-ring expansion. N-labeling studies, /. Org. Chem., 68, 4855, 2003. 

The development of 1,3,4-thiadiazole chemistry is linked to the discovery of phenylhydrazine by Emil Fischer and of hydrazine by Th. Curtins in the late nineteenth century. The first 1,3,4-thiadiazole was described by Fischer in 1882, but the true nature of the ring system was demonstrated first in 1890 by Freund and Kuh. From 1894 Busch and his school took up work in this field, and they came to play a leading part in the rapid expansion during the first decades of the twentieth century. After a period of relatively low activity between the wars, interest was renewed due to the discovery of sulfa drugs... 

---