Solid-phase synthesis of 3-amino-1,2,4-triazoles

Exploring recent developments on 1,2,4‐triazole: Synthesis and biological applications

“…3‐Amino‐1,2,4‐triazoles were synthesized from 4‐nitrophenylcarbonate resin ( I ) using the solid‐phase method in good yield and purity (Scheme ) …”

Negishi Approach to 1,5-Disubstituted 3-Amino-1H-1,2,4-triazoles

“…Various synthetic methods have been developed for 3-amino-1 H -1,2,4-triazoles in the literature . The conventional strategies for the synthesis of 1,5-disubstituted 3-amino-1 H -1,2,4-triazoles usually involve the formation of the aminotriazole core by employing a strategically functionalized electrophile with a nitrogen containing nucleophile, for example, N -acylguanidine or N -acyl carbamimidothioate with hydrazines or 1,3,4-oxadiazolium salt with cyanamide (Scheme ). , While a number of 1,5-disubstituted 3-amino-1 H -1,2,4-triazoles have been synthesized by these methods, they suffered from either long synthesis or low yields or very limited scope.…”

A Safe Synthesis of 1,5-Disubstituted 3-Amino-1H-1,2,4-triazoles from 1,3,4-Oxadiazolium Hexafluorophosphates

“…8 Only a few methods have been developed for the synthesis of 1,5-disubsituted 3-amino-1H-triazoles in the literature. 2,[9][10][11] For example, the reaction of (benzotriazolyl)methanimines and substituted hydrazines readily generates N,N-disubstituted 3-amino-1H-1,2,4-triazoles; 9,10 however, this chemistry is unable to produce N,N-unsubstituted triazole compounds (Scheme 1, A). Condensation of resin-bound S-methyl-N-acylisothioureas with hydrazines led to the desired 1,5-disubstituted 3-aminotriazles after acid-promoted resin cleavage (Scheme 1, B).…”

“…Condensation of resin-bound S-methyl-N-acylisothioureas with hydrazines led to the desired 1,5-disubstituted 3-aminotriazles after acid-promoted resin cleavage (Scheme 1, B). 11 This solid-phase synthesis provides a rapid entry to 1,5-disubstituted 3-amino-1H-1,2,4-triazoles but has only been demonstrated on a very small scale. 11 Szilagyi has reported a synthesis of 1,5-disubstituted 3-amino-1H-1,2,4-triazoles through the reaction of 1,3,4-oxadiazolium perchlorates with cyanamide in 2-methoxyethanol (methyl cellosolve) at 120 °C (Scheme 1, C).…”

“…11 This solid-phase synthesis provides a rapid entry to 1,5-disubstituted 3-amino-1H-1,2,4-triazoles but has only been demonstrated on a very small scale. 11 Szilagyi has reported a synthesis of 1,5-disubstituted 3-amino-1H-1,2,4-triazoles through the reaction of 1,3,4-oxadiazolium perchlorates with cyanamide in 2-methoxyethanol (methyl cellosolve) at 120 °C (Scheme 1, C). 2 Unfortunately, the use of perchloric acid and perchlorate salts raises serious safety concerns due to their explosive nature and shock sensitivity, 12 making them poorly suited for large-scale synthesis.…”