Study of 1,2,4-triazole-3(5)-thiol Behavior in Reactions with 1-phenyl-1H-pyrrole-2,5-dione Derivatives and 3-bromodihydrofuran-2(3H)-one and Antimicrobial Activity of Products

Abstract

In present work we report our studies of the interaction of 1-phenyl-1H-pyrrole-2,5-dione derivatives (N-arylmaleimides) and 3-bromodihydrofuran-2(3H)-one (α-bromo-γ-butyrolactone) as possible [C2] 2+ synthons with 1,2,4-triazole-3(5)-thiole targeting on synthesis of novel 5substituted thiazolo[3,2-b][1,2,4]triazole-6-ones. According to obtained results was establish that in above-mentioned interactions (conditions: convenient heating, range of solvents/reaction time) the thiol-ene click (for N-arylmaleimides) and SN (for α-bromo-γ-butyrolactone) processes take place, but not [2+3]-cyclocondensation reaction. The structure of compounds was studied using 1 H, 13 C NMR spectroscopy, LC-MS spectrometry and X-ray analysis. The prescreening of antimicrobial activity for synthesized compounds was performed against Gram-positive and Gram-negative bacteria, as well as yeasts.

New Aspects of the Reaction of Thioacetamide and N-Substituted Maleimides

“…The reaction of N-arylmaleimides with heterocyclic 1,3-N,S-binucleophiles (for example, 2-thioquinazolines [7] and 2-mercapto-1,2,4-triazoles [5]) leads to the formation of condensed systems, such as thiazolo [2,3-b]quinazolines and thiazolo [3,2-b] [1,2,4]triazoles, respectively. Thioethers-products of sulfur atom addition to the double bond of N-arylmaleimides by the Michael reaction type were isolated for 2-mercapto-1,2,4-triazole [6].…”

“…The addition of S-nucleophiles by the Michael reaction to the double bond of N-substituted maleimides is widely used in organic synthesis [24][25][26][27]. Similar intermediates are also formed in reactions with other binucleophilic substrates [6,19,21].…”

“…N-substituted maleimides are promising organic substrates that are used to build a wide range of fused and linearly linked heterocyclic scaffolds with biologically active properties [1][2][3][4][5][6][7][8][9]. The reactive feature of maleic acid imides is their ability to enter into 1,3-dipolar addition reactions [8][9][10][11][12] and into recyclization reactions under the action of binucleophilic reagents-in particular, 1,3-S,N-binucleophiles [1][2][3][4][5][6][7][13][14][15][16][17][18][19][20][21][22][23].…”

“…N-substituted maleimides are promising organic substrates that are used to build a wide range of fused and linearly linked heterocyclic scaffolds with biologically active properties [1][2][3][4][5][6][7][8][9]. The reactive feature of maleic acid imides is their ability to enter into 1,3-dipolar addition reactions [8][9][10][11][12] and into recyclization reactions under the action of binucleophilic reagents-in particular, 1,3-S,N-binucleophiles [1][2][3][4][5][6][7][13][14][15][16][17][18][19][20][21][22][23]. In such reactions, the addition of a more nucleophilic sulfur atom to the activated double bond of N-substituted maleimide usually occurs at the first stage, and the recyclization of the succinimide ring under the action of the nucleophilic nitrogen atom occurs at the second stage [19,21] (Scheme 1, adduct A).…”

Recyclization of Maleimides by Binucleophiles as a General Approach for Building Hydrogenated Heterocyclic Systems

“…Lesyk R. et al [42], as a result of boiling an equimolar mixture of reagents for 2 h in acetic acid, were able to isolate N-(R-phenyl)-(6-oxo-5,6-dihydro [1,3]thiazole [3,2-b] [1,2,4]triazol-5-yl)acetamides 51 based on the example of 1,2,4-triazole-3(5)-thiol 50. However, S. Holota [43], when investigating the same interaction, showed that boiling an equimolar mixture in the range of 30 min-24 h and the use of such solvents as acetic acid, acetone, acetonitrile, benzene, and toluene in the presence or absence of sodium acetate only led to the formation of linearly-bound product 52. At the same time, attempts at the cyclization of 52 did not lead to success.…”