Thiadiazoles and Triazoles

For protection against nonferrous and copper ahoy corrosion, thiadiazole and triazole derivatives have been found especiahy useful (22). 

Dipolar cyclization of (421) through X leads to oxadiazoles, thiadiazoles and triazoles (70CB1918, 65CB2966) (see also Chapter 4.13). 

Azine approach. Diazotization of 2-amino-3-hydroxypyridines might be expected to yield the bicyclic ring system (631) by bond formation between the oxygen and the diazonium group in the first formed diazonium salt fused 1,2,3-thiadiazoles and -triazoles are formed by this type of reaction. Compounds prepared by this method, however, are highly unstable and have spectroscopic properties consistent with the pyridodiazooxide structure (630) (74CS(6)222>. 

Dimroth rearrangement also occurs between the 5-mercapto-l,2,3-triazoles (109) and the 5-amino-l,2,3-thiadiazoles (110). If the thiadiazoles (110) are heated in basic solvents they are converted into the triazoles, whereas the reverse reaction is observed in acidic media (67LA(710)118, 69CB417, 72ACS1243). Thermal equilibria of thiadiazoles and triazoles, with both isomers present, have been reported (62Acs(B)1800, 66CB1618). 

Synthesis, structural features, and acid-base interactions in non-central symmetric thiadiazole and triazole porphyrin analogs 04MI24. 

Meso-ionic 1,3,4-Thiadiazoles.—It is well known that acylated thiosemicar-bazides are readily cyclizable to five-membered heterocycles, especially oxadiazoles, thiadiazoles, and triazoles. Reactants (172) incorporating at N-1 an additional firmly held substituent react analogously, but give rise to the corresponding meso-ionic heterocycles (173)—(176). 

For both azole and benzazole rings the introduction of further heteroatoms into the ring affects the ease of quaternization. In series with the same number and orientation of heteroatoms, rate constants increase in the order X = 0requires stronger reagents and conditions methyl fluorosulfonate is sometimes used (78AHC(22)71). The 1-or 2-substituted 1,2,3-triazoles are difficult to alkylate, but methyl fluorosulfonate succeeds (7IACS2087). 

Contrasting with the reported formation of fused [l,3,4]thiadiazole rings in the course of the reaction of 3-substituted-4-amino-5-thio-47/-[l,2,4]triazoles 83 with various isothiocyanates (cf. Section 11.07.8.3, Table 3), the reactions with methyl isothiocyanate and with phenylisocyanate afford 3,7-disubstituted-6,7-dihydro-57/-[l,2,4]triazolo[4,3-f] [l,2,4]triazole-6-thiones 110 and -triazole-6-ones 111, respectively (Equation 29) <1986MI607, 1992IJB167>.The same reaction of 4-amino-l-methyl-3,5-bis(methylthio)[l,2,4]triazolium iodide 112 with aryl isothiocyanates yields the mesoionic compounds 113 (Equation 30) <1984TL5427, 1986T2121>. 

Synthetic routes to [l,3]thiazines or their benzologues fused to [l,2,4]thiadiazoles and [l,2,4]triazoles are shown in Scheme 42. 

Three different ring systems with 3-fusion of the [l,2,4]triazine ring (a fused thiadiazole and two different triazoles) have been described during the past period. 

The syntheses of only three members of this family of compounds, viz. pyrazolo[3,4- 1[l,2,3]triazoles, imidazo[4,5-f]-[l,2,5]thiadiazoles, and [l,3,2]dioxaborolo[4,5-, imidazoles, have been reported by more than one approach. The pyr-azolo[3,4- [l,2,3]triazoles remain the most common synthetic target among this family of compounds and have been accessed from monocyclic precursors by [5+0], [4+1], and [3+2] atom fragments. 

Diazo ketones are converted by amines into 1,2,3-triazoles and by hydrogen sulfide into 1,2,3-thiadiazoles (371 — 372 Z = NR, S). The intramolecular cyclization of suitable precursors is a most useful method for the preparation of the 1,2,3-triazole ring, including (V-amino- and (V-imino-triazoles and triazole N-oxides. 

Glutaminyl cyclase (hQC) represents a new potential target for the treatment of AD, since inhibition of hQC prevents the formation of the Ap3(pE)-40,42-species. Novel molecules containing benzimidazole as the metal binding group connected to 1,3,4-oxadiazole as the central scaffold were identified. Benzimidazolyl-1,3,4-thiadiazoles and -1,2,3-triazoles display inhibitory potency in the nano-molar range [557]. 

Electroluminescent conjugated polymers can be synthesized by incorporating high electronegative heterocyclic groups, such as 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole moieties. These electroluminescent polymers are obtained by polymerization of a bis-(halomethyl) aromatic monomer modified with a heterocyclic group. ... 

---