RT journal article
T1 Microwave-Assisted One-Pot Synthesis of Isothiouronium Salts: Experimental and DFT Insights into Silica-Promoted Cyclization toward Thiazolidinium and Thiazole Frameworks
A1 Macías Benítez, Pablo
A1 García Algarra, Andrés
A1 Moreno Dorado, Francisco Javier
A1 Guerra Martínez, Francisco Miguel
A2 Ciencia de los Materiales e Ingeniería Metalúrgica y Química Inorgánica
A2 Química Orgánica
K1 Alkylation
K1 Carbon disulfide
K1 Cyclization
K1 Free energy
K1 Isomerization
K1 Microwave irradiation
K1 Scaffolds
K1 Scaffolds (biology)
K1 Sulfur
AB Isothiouronium and thiazolidinium salts are sulfur-containing scaffolds commonly found in bioactive molecules. We report an expeditive one-pot, two-step procedure for the rapid synthesis of isothiouronium salts from carbon disulfide under microwave irradiation, allowing their isolation in less than 30 min and in good to excellent yields, without the need for a catalyst. When propargyl bromide is used as an alkylating agent, the corresponding isothiouronium salt undergoes an intramolecular cyclization during silica gel chromatography, affording a thiazolidinium salt. This rearrangement, not observed under the reaction conditions, was investigated via DFT calculations. Computations show that the uncatalyzed isomerization is not feasible but becomes accessible in the presence of silica gel, which acts as a proton shuttle. The rearrangement is shown to comprise two main steps that can take place in any order, i.e., [1,3] hydrogen shift and C–N bond formation. This leads to two alternative mechanisms with similar free energy barriers of ca. 18–19 kcal·mol–1, in both cases associated with the rate-determining C–N bond formation step.
PB American Chemical Society
SN 1520-6904
YR 2025
FD 2025-09-05
LK http://hdl.handle.net/10498/38126
UL http://hdl.handle.net/10498/38126
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 21-sep-2026