Structural elucidation of propargylated products of 3‐substituted‐1,2,4‐triazole‐5‐thiols by NMR techniques

Abstract

Propargylation of 3-substituted-1,2,4-triazole-5-thiols, which predominantly exist as their thione tautomers, was carried out with the view to synthesize different heterocycles and study their biological activity. Three different products namely, a mono S-propargyl and two S,N-dipropargyl regioisomers, arising from N1/N2 substitution, were isolated and characterized. Unambiguous structural elucidation of the regioisomers of S,N-dipropargyl derivatives was achieved by means of (13)C-(1)H HMBC technique. The proportion of the regioisomers was found to vary with the substituent on the 1,2,4-triazole thiols. No product corresponding to N4 substitution was isolated from any of the reactions carried out.

GIAO/DFT studies on 1,2,4‐triazole‐5‐thiones and their propargyl derivatives

“…The propargylation of thiones of interest, although in principle can give rise to three di-substituted products 3a, 3b, and 3c (Scheme 1), gave only two di-substituted products 5-substituted-1-(prop-2-ynyl)-3-(prop-2-ynylthio)-1H-1,2,4-triazole (3a) and 3-substituted-1-(prop-2-ynyl)-5-(prop-2-ynylthio)-1H-1,2,4-triazole (3b). [14] The results of the theoretical calculation presented in Table 5 showed that 3c is the least stable regioisomer in R 1 = H case. The energy difference between 3a and 3b for this case is very small (~0.5 kcal/mol) in favor of 3a, whereas it is large between 3b and 3c (10.60 kcal/mol).…”

“…Information about the presence of tautomer 2a could be established from 1 H- 13 C HMBC spectra where the NH proton showed correlations only to the carbons in the heterocyclic ring and not to the carbon on the substituent R 1 . [14] For the mono-substituted cases, chemical shifts for some of the nitrogen atoms (e.g. N4 atom) in the heterocyclic ring could not be obtained because of the absence of cross peak in HSQC/HMBC spectra under the measurement conditions.…”

“…This is in good agreement with the NMR data of some of the cases studied (R 1 = H, t-Bu), where the observed signals are broadened as a result of chemical exchange and showed positive exchange cross peaks in their NOESY spectra. [14] We have also calculated 13 C and 15 N chemical shifts of these S-propargylated compounds, which are given in Table 4 along with the experimental chemical shifts (correlation plot is given in Fig. S2, Supporting information).…”

“…Although in principle, the propargylation of the thiones of interest can give rise to different mono-and di-substituted products, only one monoand two di-substituted products were isolated. [14] The S-propargylated compounds can exist in three tautomeric forms depending on the location of the annular NH. They are 3-substituted-5-(prop-2-yn-1-sulfanyl)-1H-1,2,4-triazoles (2a), 5-substituted-3-(prop-2-yn-1-sulfanyl)-1H-1,2,4-triazoles (2b) and 5-substituted-2-(prop-2-yn-1-sulfanyl)-1H-1,2,4-triazoles (2c).…”

“…[12,13] Reaction of substituted 1,2,4-triazole thiols with propargyl bromide and the products formed have been recently investigated by multinuclear magnetic resonance techniques. [14] Quantum chemical and density functional theory (DFT) calculation packages available now are capable of providing very good estimation of NMR shielding parameters. [15][16][17] The observed NMR chemical shifts are statistical averages of various dynamic events such as conformational, tautomeric or rotameric equilibria present in the system.…”