Sequential MCR via Staudinger/Aza-Wittig versus Cycloaddition Reaction to Access Diversely Functionalized 1-Amino-1H-Imidazole-2(3H)-Thiones

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 20; p. 3785
• Main Authors: Ciccolini, Cecilia, Mari, Giacomo, Favi, Gianfranco, Mantellini, Fabio, De Crescentini, Lucia, Santeusanio, Stefania
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 21.10.2019; MDPI
• Subjects: 1h-imidazole-2(3h)-thione; 2h-imidazo[2,1-b][1,3,4]thiadiazine; Acetone; Acetophenone; Aliphatic compounds; Aqueous solutions; aza-wittig; Carbon; Chromatography; Cycloaddition; Imidazole; multicomponent reaction; Potassium; Potassium carbonate; Room temperature; staudinger reaction; Substitution reactions; Sulfur; Tautomerism; α-halohydrazones; United States > US
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24203785

A multicomponent reaction (MCR) strategy, alternative to the known cycloaddition reaction, towards variously substituted 1-amino-1H-imidazole-2(3H)-thione derivatives has been successfully developed. The novel approach involves α-halohydrazones whose azidation process followed by tandem Staudinger/aza-Wittig reaction with CS2 in a sequential MCR regioselectively leads to the target compounds avoiding the formation of the regioisomer iminothiazoline heterocycle. The approach can be applied to a range of differently substituted α-halohydrazones bearing also electron-withdrawing groups confirming the wide scope and the substituent tolerance of the process for the synthesis of the target compounds. Interestingly, the concurrent presence of reactive functionalities in the scaffolds so obtained ensures post-modifications in view of N-bridgeheaded heterobicyclic structures.