Some transformations in a series of 4-amino-1,2,4-triazole-3-thion derivatives

Abstract

The continuous improvement of synthesis methods enables the optimization of the process for developing and obtaining target products of chemical transformation. Derivatives of 1,2,4-triazole-3-thiol present a convenient object for chemical transformation, facilitating the creation of promising biologically active compounds. Combining the structure of this heterocyclic system with pharmacophore fragments of different natures allows for more effective work on the development of molecules with high pharmacological potential. To implement this strategy, 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazol-3-thiones were utilized as starting structures. This molecule possesses three reaction centers, facilitating a wide range of chemical transformations involving these substances. The aim of the work was to create a series of 4-amino-2-((R1,R2-amino)methyl)-5-((2-,3-,4)-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones as a promising source for the preparation of biologically active substances. Materials and methods. The structure of the target compounds has been formed using well-known methods of organic chemistry. The starting materials used were 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazol-3-thiones, which were previously obtained. The first stage of the work involved the temporary protection of the amino group with a tert-butoxycarbonyl group. The second stage of the work involved the realization of Mannich reactions involving primary and secondary amines. The reaction has been carried out with formalin in an alcohol-dioxane medium. The products of the chemical transformation have been recrystallized in methanol. The third stage of the work was based on the removal of Boc-protection, which was realized using hydrochloric acid in a dioxane medium. The structures of all synthesized substances have been determined by 1H NMR spectroscopy and elemental analysis. The individuality of the compounds has been confirmed by high-performance liquid chromatography. Results. The successful study of the mechanisms of Mannich reactions for 4-amino-1,2,4-triazole-3-thione derivatives allowed us to obtain 4-amino-2-((R1,R2-amino)methyl)-5-((2-,3-,4)-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones in quantitative yields. The studies made it possible to establish the favorable effect of protecting the amino group of the 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazole-3-thione of the tert-butyloxycarbonyl group on the course and direction of the reaction. Conclusions. The optimal conditions for the Mannich reactions involving 2-,3-,4-fluorophenyl-4-amino-1,2,4-triazole-3-thione with intermediate Boc-protection of the amino group have been determined, which allowed us to create the theoretical basis for the successful use of Mannich reactions to expand the range of promising 4-amino-1,2,4-triazole-3-thione derivatives.

Keywords

• mannich bases
• physicochemical properties
• spectral characteristics