1.2.3- Triazoles ring cleavage

Triazole ring cleavage of the 7-amino-5-benzyl-5-mercapto-l,2,4-triazolo-[l,5-c]pyrimidinium iodide 135 at the N3-N4 bond occurred upon treatment with potassium carbonate to give the 4-amino-2-benzylmercapto-l-methyl-... 

The triazole ring cleavage under the influence of sodium hydride serves to synthesize 2-cyanamido-4-amino-5-arylpyrimidines from TPs, such as imine 117 (05WOP30216). 

Very few reports dealt with the triazole ring cleavage of 1,2,4-triazolo-[4.3-fl]pyrimidines [99AHC(73)131] nevertheless, none, so far, were reported to investigate the cleavage of l,2,4-triazolo[4,3-c]pyrimidines at their triazole ring. 

Indene, however, does give four-membered ring adducts with PTAD,69 and phthalazine-t,4-dione.70 The reaction with PTAD proceeds stepwise via the dipolar intermediate 43, which was trapped in the presence of water to give 44, under conditions in which the 1,2-diazetidine (45) was not opened by water to 44 (Scheme 5).69 Hydrolytic cleavage of the triazole ring in 45 using potassium rm-butoxide in wet dimethyl sulfoxide, followed by... 

Very often, a nucleophilic attack on the ring carbon atom leads to ring cleavage with the formation of acyclic intermediates that frequently recyclize into triazoles <2001ARK101, 20050L1039>, particularly in the case of N-nucleophiles, as shown in Scheme 10 and Equation (4) <2000EJM267>. 

Additional examples of the utility of ring cleavage and recyclization of 4(5Ff)-oxazolones to prepare interesting heterocycles have been described (Scheme 6.16). Ttreatment of 4-aminothymol 53 with 54 in refluxing pyridine yields the 4-imidazolidinones 55 evaluated as antimicrobial and antimbercular agents. The authors listed an extensive series of analogues (25 compounds) but reported a yield for only one example, 55 (63% for Ri = Ph, R2 = 4-MeO—CeKt). Condensation of 2-phenyl-4(5F/)-oxazolone 56 with substituted hydrazines affords excellent yields of the 1,2,4-triazoles 57, important precursors to the previously unknown l(r/)-l,2,4-triazole-5-carboxaldehydes 58. Representative examples are shown in Table 6.3 (Fig. 6.8). 

Unsymmetrical systems can in principle undergo cleavage in either ring. Table V shows that benzazoles are more stable than azoles (e.g., in 415, 348, and 405) and that the s-triazole ring is more stable than the oxadiazole or thiadiazole ring (e.g., in 299c, 303, and 183). 

Hydrazinolysis of l,2,4-triazolo[4,3-a]pyrimidines (33) caused pyrimidine ring cleavage and led to the formation of the pyrazole 143 and 3-amino-1,2,4-triazole derivatives 65 (58YZ1395 62ZC369 76KGS706). A probable mechanism of this reaction is shown in Scheme 56. 

It is interesting to note that 3,5-diphenyl-l,2,4-oxadiazole (155) undergoes a slow ring cleavage on irradiation in ether, giving benzoyl-benzamidine (156) and 2-phenyl-4-quinazolone (157) as major products.140 Ring cleavage also occurs in 1,2,5-oxadiazoles, 1,2,5-thia-diazoles, and 25-1,2,3-triazoles.141... 

Protons at positions 4 and 5 of 3-substituted 1,2,3-triazole 1-oxides 456 are more acidic than corresponding protons in the parent 1,2,3-triazoles 478 and are replaced quantitatively with deuterium within 1 h in deuterium oxide solution containing catalytic amounts of potassium carbonate (1987ACSA(B)724). In contrast, abstraction of H5 in 1-phenyl-l,2,3-triazole 478 (R=Ph) requires treatment with bases like n-butyllithium and the anion formed undergoes ring cleavage (1971CJC1792). 

Phenyl-6-acetylisoxazolo[4,5-fiT]-1,2,3-triazole (47), prepared under mild conditions, was unstable in acid solution and changed rapidly to 3-phenyl-4-diazo-5-isoxazolone (48). The mechanism proposed for cleavage of the triazole ring is outlined in Scheme 6 <70T1393>. 

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