1.3.4- Thiadiazoles, amino-, diazotization

Amino-l,2,4-thiadiazoles are diazotized at — 10°C in phosphoric acid, and couple with naphthol to give moderate yields of diazo dyes.182,388 In their limited stability, the 3-diazonium salts resemble those of 3-aminoiso-thiazole, but differ from the more stable 1,2,4-thiadiazole- and isothiazole-5-diazonium salts a consideration of the 7t-electron densities leads to the opposite conclusion.182... 

Attempted diazotization in dilute acid sometimes yields primary nitroso compounds. Reactions of 3- and 5-amino-1,2,4-thiadiazoles with sodium nitrite and acid give primary nitrosamines (e.g. 432->433) (65AHC(5)n9) which can be related to the secondary nitrosamines (434) prepared in the normal way. 1-Substituted 5-aminotetrazoles with nitrous acid give stable primary nitrosamines (435). Primary nitrosamines have been isolated in the imidazole series. 

A rearrangement involving a fluctuating 1,2,3-thiadiazole ring has been found by Haddock et al. (1970) after diazotization of 7-amino-6-substituted 1,2,3-benzothia-diazoles (Scheme 6-46). 

In Section 3.4 we discussed the problem of reversibility of diazotization of aromatic and heteroaromatic amines. Simple stoichiometric considerations indicate that the reverse reaction (ArNJ -> ArNH2) may take place under strongly acidic conditions. Experimentally the reverse reaction was found only with heteroaromatic diazonium salts (Kavalek et al., 1989). Reaction conditions of hydroxy-de-diazonia-tion are comparable to those used for the reverse reactions of diazotization (e.g., 10 m H2S04, but at 0°C for the formation of 2-amino-5-phenyl-l,3,4-thiadiazol from the corresponding diazonium salt, Kavalek et al., 1979). So far as we know, however, amines have never been detected in aromatic hydroxy-de-diazoniations, not even in small amounts. 

Amino- and 5-amino-l,2,4-thiadiazoles can be diazotized and they can be coupled under standard conditions <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>. 

Diazonium Salts from 3-Amino-1,2,4-thiadiazoles The 3-amino group in 1,2,4-thiadiazoles (e.g. in the 5-phenyl homolog) is also capable of being diazotized, preferably in concentrated phosphoric acid. The resulting diazonium salt may be coupled in the usual way, but with sufficiently reactive partners only (e.g. phenol and 0-naphthol).126... 

Amino-1,2,4-thiadiazoles79 and their 3-alkoxy-, 3-alkylmercapto-, and 3-dialkylamino derivatives84 have been claimed to be useful intermediates in the manufacture of dyes,84 pharmaceuticals,84 and materials valuable in pest control.79 Mono-azo dyes derived from diazotized 5-amino-l,2,4-thiadiazoles and coupling components of the benzene series are especially suitable for dyeing polymeric materials such as acetate rayon, polyamides, polyurethanes, polyesters, and... 

The largest proportion of the dyes of this type, which can range from yellow to blue in colour, is of the homocyclic type. Examples such as those derived from 5-amino-l,2,4-thiadiazoles (32), 2-aminobenzothiazoles and 3-amino-2,l-benzisothiazoles (74MI11201) are in the minority. Synthesis is usually via diazotization of the appropriate heteroaromatic amino group and coupling with quaternary aniline derivatives. 

Amino-5-phenyl-l,3,4-thiadiazole (112 R = NH2) on diazotization gives the 2-chloro derivative (112 R = Cl), which on treatment with hydrazine followed by benzoylation gives (112 R = NHNHCOPh). Cyclization with phosphorus oxychloride yields the triazolo derivative (113) in moderate yield (66JOC3528). 

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>. 

Azine approach. Diazotization of 5-amino-4-mercaptopyrimidines is a simple way of preparing the fused 1,2,3-thiadiazoles (740) (64JOC2121). 

Alkoxy-5-amino-1,3,4-thiadiazoles (41) are not particularly stable to hydrolysis. They were hydrolyzed by hot hydrochloric acid, first to 2-amino-l,3,4-thiadiazolin-5(4)-one (108) (or the tautomeric imine) and then to thiosemicarbazide. On diazotization in hydrochloric acid 41 gave 2-chloro-l,3,4-thiadiazolin-5(4)-one (107), and by hot alkali it was cleaved to 1-alkoxythiocarbonylsemicarbazide (109). ... 

However, a 2-amino group does activate the ring towards electrophilic agents, since Bak et al. could prepare 2-amino-5-bromo-1,3,4-thiadiazole by bromination of 2-amino-l,3,4-thiadiazole in 40% hydrobromic acid. The product was not isolated but was diazotized in situ to give 2,5-dibromo-l,3,4-thiadiazole. 

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