Iodocyclization of S-allyl derivatives of 3-mercapto-4-methyl-1,2,4-triazole

Abstract

Keywords: 3-allylthio-4-methyl-1,2,4-triazole, [1,3]thiazolo [3,2-b][1,2,4]triazolium iodide, [1,2,4]triazolo[5,1-b][1,3]thiazinium iodide, 3-(3-methyl-2-butenyl)thio-4-methyl-1,2,4-triazole, 3-mercapto-4-methyl-1,2,4-triazole, 3-(2-methyl-2-propenyl)thio-4-methyl-1,2,4-triazole, iodocyclization.Derivatives of 3-mercapto-1,2,4-triazoles (1,2,4-triazol-3-thiones) possess a broad spectrum of physiological activity: analgetic, vasodilator, antitumor, bactericidal, and hypotensive effects [1][2][3][4].The reaction of 5-phenyl-, methyl-, and tert-butyl-3-allylthio-1,2,4-triazoles with iodine gave a mixture of products of iodocyclization at the N(2) and N(4) atoms [5,6]. In this work we have synthesized 3-allylthio-(2a), 3-(2-methyl-2-propenyl)thio-(2b), and 3-(3-methyl-2-butenyl)thio-1,2,4-triazole (2c) respectively by the reaction of 3-mercapto-4-methyl-1,2,4-triazole (1) in 2-propanol in the presence of alkali or sodium isopropoxide with 3-bromopropene, 3-chloro-2-methylpropene, and 1-bromo-3-methyl-2-butene, and we have studied their reaction with iodine.It has been established that compound 2a reacted with excess iodine in ether to form a mixture of two products of iodocyclization -6-iodomethyl-3-methyl-5,6-dihydro[1,3]thiazolo[3,2-b][1,2,4]triazolium (3a) and 6-iodo-3-methyl-6,7-dihydro-5H-[1,2,4]triazolo[5,1-b][1,3]thiazinium (4a) polyiodides (a mixture of triiodides and pentaiodides) in a ratio of 0.17:1.00 (according to 1 H NMR spectral data). The salts 3a and 4a were converted into the corresponding monoiodides 3b and 4b. The 1 H NMR spectrum of the mixture of 3b and 4b iodides contains two sets of signals. The signals of the protons of the NCH 2 group of thiazine 4b occur in the 4.60-5.00 region (two doublets of doublets), the signal of proton H-6 in compound 3b forms a multiplet at 5.14 ppm. _______________Celebrating the jubilee of Academician of the Russian Academy of Sciences V. N. Charushin.

Fused bicyclic 1,2,4‐triazoles with one extra sulfur atom: Synthesis, properties, and biological activity

“…The non-selective method for obtaining 5,6-dihydro- [1,3]thiazolo [3,2-b] [1,2,4]triazolium salts was developed by Il'inykh et al [51] via iodination of 3-alkenylsulfanyl-4H-1,-2,4-triazoles 7 in methylene chloride, ether, or chloroform at room temperature. The above electrophilic heterocyclization led to the formation of the mixture of thiazolotriazoles 8 and 5,6-dihydro- [1,2,4]triazolo [5,1-b] [1,3]thiazinium salts 9 (Scheme 6).…”

Synthesis and biological activity of 1,3,4-oxa(thia)diazole, 1,2,4-triazole-5-(thio)one and S-substituted derivatives of 3-((2-carboxyethyl)phenylamino)propanoic acid

“…Activity of S-substituted derivatives of bistriazolethione 13 depends on the nature of the substituent. The free radical scavenging activity of compounds containing alkyl groups (15)(16)(17)(18)(19)(20) was approx. 50 %, whereas that of 22 containing benzyl group was only 3.61 %.…”

“…1,2,4-Triazole scaffold is yet another important pharmacophore since compounds bearing this moiety have been shown to display anti-inflammatory and analgesic [17], antitumor [18], antioxidative [19], antibacterial [13,14,20], and antifungal [21] properties. 1,2,4-Triazole derivatives, e.g., flucarbazone and amicarbazone, are used as herbicides [22].…”

“…Graphical Abstract Synthesis of compounds 2-27. R: 2,5,7,10,13,[15][16][17][18][19][20][21][22][23][24][25][26][27]3,8,4,9,12 …”