1.2.3- Thiadiazoles, 5-azido

L abbe has studied the rearrangement reactions of 1,2,3-thiadiazoles to differently substituted 1,2,3-thiadiazoles <1983CC588>. He also studied many 5-azido-l,2,3-thiadiazoles 33 that rearranged to 1,2,3,4-thiatriazoles 34 (Equation 5) <1988BSB163>. He even found that l,2,3-thiadiazole-4-carboxaldehydes 35 upon treatment with amines underwent thermal rearrangement to 1,2,3-triazoles 36 (Equation 6) <1993J(P1)1719>. 

Azido-5-phenyl-l,2,4-thiadiazole 3-Amino-5-phenyl-1,2,4-thiadiazole 5-Cyano-3-phenyl-l,2,4-thiadiazole-4-oxide... 

The enhanced reactivity of 5-halogeno-l,2,4-thiadiazoles over 3-halogeno-l,2,4-thiadiazoles has been mentioned before (see Section 5.08.7.1). Nucleophilic substitution at this center is a common route to other 1,2,4-thiadiazoles, including 5-hydroxy, alkoxy, mercapto, alkylthio, amino, sulfonamido, hydrazino, hydroxylamino, and azido derivatives. Halogens in the 3-position of 1,2,4-thiadiazoles are inert toward most nucleophilic reagents, but displacement of the 3-halogen atom can be achieved by reaction with sodium alkoxide in the appropriate alcohol <1996CHEC-II(4)307>. 

Amino-l,2,4-thiadiazoles (129) are diazotised at — 10°C in phosphoric acid, and couple in the usual way with reactive aromatic compounds such as naphthol, giving moderate yields of diazo dyes <82AHC(32)285>. Diazotization of (129) (R = H and Ph) may be accomplished using aqueous sodium nitrite and hydrochloric acid. Treatment of the resulting salt with sodium azide yields the 3-azido derivative (130) (Equation (17)) <86CC800>. 

The first synthesis of an azido substituted 1,2,4-thiadiazole has been reported <86CC800>. When l-alkyl-5-aminotetrazoles (284) are heated with an excess of thionyl chloride, 3-azido-l,2,4-thia-diazoles (130) are formed via the proposed intermediate (285) (Scheme 65). 

Photoelectron spectroscopy was used by French workers to follow the thermolysis of 2-azido-thiadiazoles <88CJC2830> (see also Section 4.10.6.1). No publications related to fluorescence were found. 

Azido-2-nitrosamino- 1,3,4-thiadiazole under Aminothiadiazole and Derivatives, p A262... 

Thiadiazoles rearrange to variously substituted 1,2,3-thiadiazoles (83CC588). Many 5-azido-1,2,3-thiadiazoles rearrange to 1,2,3,4-thiatriazoles (Scheme 9) (88BSB163). 

A-Azidocarbonylazepine, 2724 Azidocarbonylguanidine, 0816 4-Azidocarbonyl-1,2,3-thiadiazole, 1066 4-Azido-3-diazo-3//-pyrazolo[3,4-b]quinoline, 3231b 2-trans-1 -Azido-1,2-di hydroacenaphthyl nitrate, 3460 /V-Azidodimethylamine, 0911... 

The 5-position in 1,2,4-thiadiazoles is most reactive in nucleophilic substitution reactions. Chlorine, for example, may be displaced by nucleophiles (Nu) such as fluoride, hydroxide, thiol, amino, hydrazino, sulfite and azido groups (Scheme 11). Active methylene compounds such as malonic, acetoacetic and cyanoactic esters as their sodio derivatives also displace the 5-halo substituent (65AHC(5)ll9). The reaction follows second-order kinetics, the rate determining step being addition of the nucleophile at C-5 followed by rapid elimination of X. 

In five-membered a-azido N-heterocycles, the effect of the azole ring is completely in favor of the azide form. All azidoazoles which are known have spectroscopic properties typical of azido derivatives. However, an azidomethine unit as part of the thiazole and 1,3,4-thiadiazole rings may exist in either the cyclized or open-chain form under normal conditions both forms are usually detected (77AHC(2l)323, 75BSB1189). 

The effects of solvent (polarity), temperature, and substituents (the Hammet cr constants) have been studied in the azide-tetrazole equilibrium for thiazolo [2,3 -e]tetrazoles (75BSB1189 77CJC1728, 77JHC1299) oxazolo[2,3-e]- and isoxazolo[2,3-d]-tetrazoles (77CJC1728) and tetra-zolo[4,5- >]-1, 3,4-thiadiazoles (81CHE721). A rough parallelism has been proposed between the azido-tetrazole isomerism and prototropic tau-tomerism (75BSB1189). 

Azidouminopropone. See under Aminopropane and Derivatives, p A230 Azidoaminothiadiazole, Nitroso. See 3-Azido-2-nitrosamino-l,3,4-thiadiazole under Aminothiadiazole and Derivatives, p A262... 

Azido-1,3,4-thiadiazoles (87) can be prepared by reaction of hydra-zinothiadiazoles (86) with nitrous acid, and by reaction of halogeno-thiadiazoles with sodium azide. Like similar heterocyclic azides - they may exist as true azides (87) or as tetrazolothiadiazoles (88). Kanaoka prefers the bicyclic formulation when R = Ph, but Bacchetti et al. have shown that in the solid state the compound... 

X = S) to DMAD to yield dimethyl 5-phenylisothiazole-3,4-dicarboxylate is much slower than the corresponding oxathiazolone (282) (X = O) <89JCS(Pl)2489>. The thermal decomposition of ethyl 2-azido-3-(3-azido-2-thienyl)propenoate (283) results in the formation of ethyl 5-cyano-isothiazole-3-carboxylate (284) together with the thienopyridazine (285) <84JCS(P1)915>. The addition of benzyne to 3,4-dimethyl-1,2,5-thiadiazole (286) gives 3-methyl-1,2-benzisothiazole <82CC299>. 

Chemical Properties. - Cyclocondensation of 4-amino-1,2,3-thiadi-azoles with R1COCHR2COR3 gave 1,2,3-thiadiazolof3,4-aJpyrimidinium salts [317 R,R1, R2,R3 = mix of H,Me,Ph (for R2-R1< only)] in 17-7 yield333. 5-Amino-1,2,3-thiadiazole is converted to the Na or Ba salt of (318) with aqueous NaOH 1 or Ba(0H)2 8H2033, respectively. 5-Azido-4-carbethoxy-1,2,3-thiadiazole could not be prepared from NaN3 and the 5-chloro analogue the diazo compound (319) was isolated in 73 yield. Confirmation for (319) was derived from its spectral data and its thermolysis to ethyl a-... 

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