METHYLATION OF 4-NIТRO-1,2,3-TRIAZOLE IN NEUTRAL ENVIRONMENTS

Алкилирование NH-гетероцикла4-нитро-1,2,3-триазола диметилсульфатом сопровождается тандемными реакциями алкилирования–кватернизации и приводит к образованию сложной смеси продуктов N-моноалкилирования по всем трем гетероатомам N-1, N-2 и N-3 с существенным преобладанием неизвестного ранее N3-производного, а также продукта их дальнейшего превращения – соли 1,3-диметил-4-нитро-1,2,3-триазолия. Alkylation of the NH-heterocycle of 4-nitro-1,2,3-triazole with dimethyl sulfate is accompanied by tandem alkylation-quaternization reactions and leads to the formation of a complex mixture of N-monoalkylation products at all three heteroatoms N-1, N-2, and N-3 with a significant predominance previously unknown N3-derivative, as well as the product of their further conversion - 1,3-dimethyl-4-nitro-1,2,3-triazolium salts.

Development of Triazoles and Triazolium Salts Based on AZT and Their Anti-Viral Activity against HIV-1

We report herein a set of 3′-azido-3′-deoxythymidine (AZT) derivatives based on triazoles and triazolium salts for HIV-1 infection. The compounds were synthesized via click chemistry with Cu(I) and Ru(II) catalysts. Triazolium salts were synthesized by reaction with methyl iodide or methyl triflate in good yields. The antiviral activity of the compounds was tested using two methodologies: In method one the activity was measured on infected cells; in method two a pre-exposure prophylaxis experimental model was employed. For method one the activity of the compounds was moderate, and in general the triazolium salts showed a decreased activity in relation to their triazole precursors. With method two the antiviral activity was higher. All compounds were able to decrease the infection, with two compounds able to clear almost all the infection, while a lower antiviral activity was noted for the triazolium salts. These results suggest that these drugs could play an important role in the development of pre-exposure prophylaxis therapies.

Triazolium Salt Organocatalysis: Mechanistic Evaluation of Unusual Ortho-Substituent Effects on Deprotonation

Organocatalysis by N-heterocyclic carbenes is normally initiated by the deprotonation of precursor azolium ions to form active nucleophilic species. Substituent effects on deprotonation have an impact on catalytic efficiency and provide insight into general catalytic mechanisms by commonly used azolium systems. Using an NMR kinetic method for the analysis of C(3)-H/D exchange, we determined log kex–pD profiles for three ortho-substituted N-aryl triazolium salts, which enables a detailed analysis of ortho-substituent effects on deprotonation. This includes N-5-methoxypyrid-2-yl triazolium salt 7 and di-ortho-methoxy and di-ortho-isopropoxyphenyl triazolium salts 8 and 9, and we acquired additional kinetic data to supplement our previously published analysis of N-pyrid-2-yl triazolium salt 6. For 2-pyridyl triazoliums 6 and 7, novel acid catalysis of C(3)-H/D exchange is observed under acidic conditions. These kinetic data were supplemented by DFT analyses of the conformational preferences of 6 upon N-protonation. A C(3) deprotonation mechanism involving intramolecular general base deprotonation by the pyridyl nitrogen of the N(1)-deuterated dicationic triazolium salt is most consistent with the data. We also report kDO values (protofugalities) for deuteroxide-catalyzed exchange for 6–9. The protofugalities for 8 and 9 are the lowest values to date in the N-aryl triazolium series.