Synthesis, spectroscopy, and theoretical calculations of some 2-thiohydantoin derivatives as possible new fungicides

Abstract

We present the synthesis and structure determination for two thiohydantoin compounds (5-benzylidene-2sulfanylideneimidazolidin-4-one and 5-cinnamylidene-2-sulfanylideneimidazolidin-4-one), proposed as potential novel fungicides. The exact chemical structure of these molecules has not yet been determined since they can potentially exist in several tautomeric and geometric forms (Z-E isomerism). The geometries of all the theoretically possible structures of the studied compounds were optimised. The calculations were performed at the density functional theory level using the B3LYP functional and the 6-311++G** basis set. Based on our calculations, the most probable structures of the studied compounds were proposed. The theoretical predictions were verified by comparing the calculated IR as well as the 1 H and 13 C NMR spectra with the experimental data. It was documented that both the studied compounds exist predominantly in the tautomeric structure, in which the movable hydrogen is connected to the nitrogen atom in the hydantoin ring. It has been experimentally proven that one of the studied compounds occurs only as a single structure, whereas the other one exists as a mixture of two geometric isomers.

Novel imidazolium-thiohydantoin hybrids and their Mn(iii) complexes for antimicrobial and anti-liver cancer applications

“…Noteworthy, a singlet NMR peak at 9.98 ppm corresponding to the proton from the thioamide (H–N–C S) segment of the T NH tautomer. 48 Conversely, the appearance of a 1.85 ppm S–H singlet peak in the deuterated solution of thiohydantoin revealed that the T SH tautomer had a role in maintaining the equilibrium of the ligand's tautomers. 48 Using the NH/SH peak intensity ratio, we may deduce that the core backbone of 4b exists in solution mostly as the thiol form (T SH ) (55%), with some input from the thione form (T NH ) (45%).…”

“… 48 Conversely, the appearance of a 1.85 ppm S–H singlet peak in the deuterated solution of thiohydantoin revealed that the T SH tautomer had a role in maintaining the equilibrium of the ligand's tautomers. 48 Using the NH/SH peak intensity ratio, we may deduce that the core backbone of 4b exists in solution mostly as the thiol form (T SH ) (55%), with some input from the thione form (T NH ) (45%). Meanwhile, 13 C NMR spectroscopy gives more proof for the co-existence of the TSH and TNH tautomeric forms in these thiohydantoin solutions.…”

“…Kobyka et al reported that the 13 C resonance of these tautomers changes from 179 ppm, distinctive of thione groups (C]S) for a pure thione form, to 160 ppm, distinctive of thiol groups (C-S-H) for a pure thiol form. 48 The 13 C NMR spectra of thiohydantoin ligands (Fig. 2) show four low-eld peaks at the chemical shis of $179, $175, $160, and $154 ppm, which can be ascribed to the resonance of carbon atoms in the thiocarbonyl (C]S), carbonyl (C]O), azomethine (HC]N), and C-S groups.…”

A recent update on new synthetic chiral compounds with antileishmanial activity

“…Thiohydantoins have emerged as an important class of compounds due to their biological activity, [68][69][70][71][72][73][74] with particular focus on the antiparasitic behavior. [75][76][77][78] Wowk and Pavanelli explored the antileishmanial (L. amazonensis) effect, determining the key mechanism presented in parasite death, of various thiohydantoins bearing an acetyl group at the N1-position of the heterocyclic ring.…”

NMR as a “Gold Standard” Method in Drug Design and Discovery

“…For these reasons, NMR spectroscopy is highly sought after in drug development [ 37 , 38 , 39 , 40 , 41 ], for both molecule identification [ 11 , 13 , 14 , 18 , 42 , 43 , 44 , 45 , 46 ] and structural elucidation [ 15 , 16 , 17 , 45 , 47 , 48 , 49 , 50 , 51 ]. NMR has been successfully applied in stereochemistry [ 52 , 53 , 54 , 55 , 56 ] and isomer determination [ 57 , 58 , 59 , 60 , 61 ], in drug-protein interactions studies [ 62 , 63 , 64 ], and in the evaluation of drug toxicity [ 65 , 66 , 67 , 68 ].…”