1.2.4- Thiadiazole amino-, nitrosamines

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. 

Amino-l,2,4-thiadiazoles fail to yield nitrosamines under the usual conditions but the more stable 5-nitrosamines (123) can be prepared easily (Scheme 29) <65ahc(5)H9>. The nitrosamino group in 5-nitrosamino-l,2,4-thiadiazoles (123) is fairly reactive and may be converted into various functional groups with the appropriate reagents <84CHEC-I(6)463>. 

Although 3-amino-l,2,4-thiadiazoles (e.g. the 5-phenyl homolog) fail to yield nitrosamines under the usual conditions,126 5-nitrosamines are well known.81, 5,190,191 Thus, 3-alkoxy-,8 3-alkylthio-,85 3-dialkyl-amino-,87 and 3-alkylsulfonyl-5-amino-86 (243) as well as 3-aryl-5-arylamino-l,2,4-thiadiazoles,74 on treatment with the calculated quantity of sodium nitrite in dilute mineral acid, or concentrated formic acid, yield crystalline nitrosamines (244). Their unusual stability has permitted a close study of their formation and properties. 170 Their positive Liebermann reaction85,87,170 and the results of their methylation (outlined in the reaction scheme) show that nitro-sation occurs in the side-chain and not in the nucleus.170... 

Substituted amino groups in the 5-position interfere with the course of the reaction, possibly because of nitrosamine formation thus, 3-amino-5-methylamino- and 3-amino-5-anilino-l,2,4-thiadiazole afford the corresponding 3-chloro derivatives (311 R = MeNH PhNH X = Cl) in only minute yields (5 and 8%, respectively).178... 

Amino-l,2,4-thiadiazoles fail to yield nitrosamines under the usual conditions but relatively stable 5-nitrosamines (150) are easily prepared as indicated in Scheme 59 <65AHC(5)119>. 

Nitrosamines derived from 5-amino-1,2,4-thiadiazoles are readily accessible stable compounds.3 Thermolysis of the substituted 5-nitrosoimino-1,2,4-thiadiazolines (48574 and 486383) produces the corresponding 5-ketones (487, 488) with evolution of nitrogen almost quantitatively. Their photolysis, involving n- n excitation, proceeds less uniformly. Irradiation of 486 in various solvents yields, as primary products, Hector s base (14b) and phenyl-cyanamide subsequent changes produce their 1 1-adduct, as well as 3,5-dianilino-l,2,4-thiadiazole, phenylurea, and other compounds, all in variable moderate yield. The photolytic fragmentation is more complex than that of comparable heterocyclic nitrosimines.384... 

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