5-Unsubstituted 1,2,3-thiadiazoles

Unsubstituted 1,2,3-thiadiazoles/-selenadiazoles 135 are easily cleaved under the action of strong bases with the liberation of nitrogen to form alkynethiolates/alkyneselenolates 136, which are widely used in the synthesis of heterocycles, or serve as a source of highly reactive ethynylchalco-genols 137 and tautomeric chalcogenoketenes 138 upon protonation. 

Unsubstituted thiadiazole is unstable under basic conditions, and will decompose. 2-Amino-thiadiazole derivatives (45) react with amines to yield triazolinethiones (46). 2-Amino-5-halo-thia-diazole reacts with hydrazine to give a mixture of (47) and (48). 2,5-Dihalo and 2,5-dithio-thiadiazoles yield only (48) under the same conditions. Even a weaker nucleophile such as aniline... 

Although unsubstituted 1,2,5-thiadiazole is stable on heating at 220 °C, 3,4-diphenyl-1,2,5-thiadiazole 1,1-dioxide (26) decomposes into benzonitrile and sulfur dioxide at 250 °C (68AHC(9)107). 

Carbon-13 NMR is often a more useful tool than H NMR for the elucidation of heterocyclic structures in which there are few or no ring protons. For symmetrically substituted 1,2,3-thiadiazoles, the carbon adjacent to the nitrogen atom is expected to have a lower field chemical shift than the carbon atom adjacent to the sulfur atom, as exemplified in CHEC-II(1996) <1996CHEC-II(4)289>. Several examples that follow this rule are illustrated in Table 5. There is now a more extensive body of data available and it is possible to more accurately predict the chemical shift of ring carbons. In the case of monosubstituted 1,2,3-thiadiazoles, the substituted carbon usually has a lower field chemical shift than the unsubstituted carbon. 

Other methods for the synthesis of 3,5-diamino-l,2,4-thiadiazoles discussed in Section 5.08.9.4 are only suitable for the synthesis of mono- or unsubstituted 3,5-diamino-l,2,4-thiadiazoles. 

A special rearrangement in the 1,2,4-thiadiazole series concerns the 2-phenylamino-l,2,4-thiadiazolo [2,3,-a]pyridinium salts (275 R = H, Me), which are obtained by oxidation of N-(2-pyridyl)thioureas (Scheme 45). In the case of the unsubstituted derivative (275 R = H X = Br), neutralization with sodium acetate in ethanol produces directly benzothiazole 277... 

The nucleophilic attack of organometallic species occurs with cleavage of the N—S bond and eventual formation of an a-diketone. This reaction has been shown to proceed through an unsym-metrical diimine (17) (Scheme 2) <90JHC1861>. The 4-unsubstituted series (18) can be functionalized in this way. The diimine product of ring opening (19) can add a nucleophile at carbon (20) and then be recyclized to a 3,4-disubstituted 1,2,5-thiadiazole (21) (Scheme 3) <86H1131>. 

Reaction of the 5-substituted aminothiadiazole (88 R = Bu ) with aryl nitriles produced amidines (89) in yields dependent on the reactivity of the nitriles (Scheme 14). Decreasing the electron density of the cyano group by such electron-withdrawing groups as p-nitrophenyl-, and 2- and 4-cyanopyridyl, led to higher yields as compared to unsubstituted benzonitrile. A bis thiadiazole (92 R = Bu ) was prepared by reacting the sodium salt of (88) with 2-methanesulfonyl-5-(-butyl-1,3,4-thiadiazole (91) <84JHC1377>. 

A greatly improved experimental procedure for the synthesis of thieno[2,3-d]-1,2,3-thiadiazole caiboxylates 68 was reported by Stanetty et al. and involved diazotisation of aminothiophene derivatives 67 <99JHC761>. In these systems, substituents could be introduced into the 5-position by nucleophilic displacement of a chlorine atom or by metallation of the unsubstituted compound (68 R = H) and subsequent electrophilic quenching <99JPR391>. 

Disubstituted and unsubstituted l,2,5-thiadiazolo[3,4- ]quinoxaline-4,9-diones (110) have been prepared in good yield by condensation of 5,6-diaminobenzo[c][l,2,5]thiadiazole with a-dicarbonyl reagents (Equation (62)) <92H(33)337>. These quinones were then converted into 1,2,5-thiadiazolo-, pyrazino-fused TCNQ analogues by condensation with malononitrile in the presence of TiCl4 in dry pyridine. The x-ray crystal structure determination of the product derived from compound (110 R1 = R2 = H) has been accomplished. 

Symmetry species no. Unsubstituted 1,2,5-Thiadiazole 3-Chloro 3,4-Dichloro... 

The reaction of unsubstituted 2-amino-1,3,4-thiadiazole (131) with 1,3-dicarbonyl compounds is dependent on the nature of the dicarbonyl compound (Scheme 13). Thus, reaction of (131) with pentane-2,4-dione gives the 4,6-dimethyl-2-thiocyanatopyrimidine (132). The formation of (132) may proceed via the cation (132a). With ethyl acetoacetate, however, a mixture of (133) and (134) is formed, (133) also being converted into (134) on heating. 

The 1,2,5-thiadiazoles are very stable thermally. The unsubstituted ring is unchanged on heating at 220° and it has been reported that the... 

The 1,2,5-thiadiazole nucleus is stable to both dilute and concentrated mineral acids and to Lewis acids. Certain derivatives, however, are decomposed slowly by base. No decomposition of the parent 1,2,5-thiadiazole was detected after 16 hours at 25° in 1 N sodium hydroxide while at 80° approximately 30 % of the material decomposed in 1 hour. This contrasts with the oxygen analog, furazan, and the monosubstituted furazans which are rapidly decomposed by cold aqueous base to a-cyanooximes. Mono- and dimethyl thia-diazole are both stable in 1 A sodium hydroxide up to 80° but the monochloro and dichloro derivatives are both degraded more rapidly than the unsubstituted compound. Thiadiazoles bearing acidic functions (the hydroxy, carboxy, and sulfonamide derivatives) exhibit complete base stability. In general, 1,2,5-thiadiazoles can be employed in reactions carried out in basic media provided drastic conditions are not required. 

---