Syrota N.O. 4,5-Difunctionalized [1,2,3]-triazoles in the synthesis of new [1,2,3]-triazoloannelated pyridines, diazepines and thiazepines. – Qualifying scientific work equated to manuscript.
Dissertation for the degree of Doctor of Philosophy in specialty 102 "Chemistry", specialization "Organic Chemistry". – National University of Kyiv- Mohyla Academy, Kyiv, 2022.
The dissertation research is devoted to development of efficient and preparatively convenient methods of synthesis of 4,5-bifunctionalized derivatives of 1,2,3-triazole and investigation of their synthetic potential in processes of construction of bioattractive derivatives of [1,2,3]-triazoleannelated middle heterocycles.
Optimal conditions were developed for obtaining 4-(N-Boc-amino)-1,2,3- triazole-5-carbaldehydes, 4-amino-1,2,3-triazole-5-carboxylic acids, 5-amino-N-(2,2- dimethoxyethyl)-1H-1,2,3-triazole-4-carboxamides and 4-(N-Boc-amino)-1H-1,2,3- triazolecarbothioamides, promising building blocks for the construction of new functional-substituted types of condensed triazoles.
It was determined that the interaction of 4-(N-Boc-amino)-1,2,3-triazole-5- carbaldehydes with acetylacetone, malonitrile, cyclic ketones and β-diketones under the conditions of the Friedlander reaction leads to the formation of functionalized and carbocyclic derivatives of [1,2,3]triazolo[4,5-b]pyridines, while cyclocondensation with malonic acid or Meldrum's acid gives 5-oxo-4,5-dihydro-1H-[1,2,3]triazolo[4,5- b]pyridine-6-carboxylic acids.
It was shown that 5-amino-N-(2,2-dimethoxyethyl)-1H-1,2,3-triazole-4- carboxamides in formic acid solution at room temperature are prone to intramolecular cyclization to 5-hydroxy-substituted [1,2,3]triazolo[4,5-e][1,4]diazepines.
It was found that the synthesized 5-hydroxy-containing triazolo[4,5- e][1,4]diazepines under the action of S-nucleophilic reagents are easily converted into the corresponding 5-sulfanyltriazolodiazepines which can also be obtained by single- reactor conversion of N-functionally substituted aminotriazolecarboxamides in formic acid in the presence of S-nucleophiles.
A new approach to the derivatives of 1,4,6,7-tetrahydro[1,2,3]triazolo[4,5- e][1,4]diazepine-5,8-dione is proposed which consists in the transformation of 4- amino-1,2,3-triazole-5-carboxylic acids under the action of ethyl glycinate hydrochloride in the presence of excess carbonyldiimidazole (CDI) in the corresponding amides and intramolecular cyclocondensation of the latter to the target products by removing the protective N-Boc group and treatment with NaOEt.
Scientific novelty of the obtained results. Preparatively available 4,5- bifunctionalized 1,2,3-triazole derivatives were shown to be convenient synthetic scaffolds for the construction of promising triazoloannelated heterocycles for biomedical research.
Cyclocondensation of 4-(N-Boc-amino)-1,2,3-triazole-5-carbaldehydes with methylene active compounds was found an effective method for producing functionalized and carboannelated triazolo[4,5-b]pyridines.
An original variant of the synthesis of 5-hydroxy- and 5-sulfanyl-[1,2,3]- triazolo[4,5-e][1,4]diazepines was developed based on intramolecular cyclization of 5-amino-N-(2,2-dimethoxyethyl)-1H-1,2,3-triazole-4-carboxamides in formic acid solution and under the action of S-nucleophiles, respectively.
Optimal conditions were determined for the selective reduction of the hydroxyl and carbonyl groups of 5-hydroxytriazolodiazepines to the corresponding tetrahydro- and hexahydro[1,2,3]triazolo[4,5-e][1,4]diazepines the synthetic potential of which was studied in acylation reactions.
It was shown that 4-(N-Boc-amino)-1,2,3-triazole-5-carboxylic acids are fundamentally new reagents in the two-stage synthesis of previously unknown triazolo[4,5-e][1,4]diazepine-5,8-diones.
A preparatively convenient and efficient way to derivatives of the new heterocyclic system [1,2,3]triazolo[4,5-e][1,4]thiazepine was suggested by 5- thiocarbamoylation of 4-(N-Boc-amino)-1,2,3-triazoles and subsequent S-alkylation and intramolecular cyclization of obtained 5-thioimidates.
Practical significance of the results is the development of new and preparatively available methods for the synthesis of [1,2,3]-triazoloannelated pyridines, diazepines and thiazepines, the investigation of their chemical and biological potential.
Substances with moderate antibacterial and antifungal activity were found among the synthesized compounds by bioscreening methods.
Keywords: 4-(N-Boc-amino)-1,2,3-triazoles, 4-(N-Boc-amino)-1,2,3-triazole- 5-carbaldehydes, 5-amino-N-(2,2-dimethoxyethyl)-1H-1,2,3-triazole-4- carboxamides, 4-(N-Boc-amino)-1H-1,2,3-triazolecarbotothioamides, 4-(N-Boc-
amino)-5-thioimidates, 4-amino-1,2,3-triazole-5-carboxylic acids, intramolecular cyclization, Friedlander reaction, [1,2,3]triazolo[4,5-b]pyridines, [1,2,3]triazolo[4,5- b]pyridine-6-carboxylic acids, [1,2,3]triazolo[4,5-e][1,4]diazepines, [1,2,3]triazolo[4,5-e][1,4]thiazepines .
