One-Pot Synthesis of Benzimidazo[2,1-b]thiazoline Derivatives through an Addition/Cyclization/Oxidative Coupling Reaction

Abstract

A novel and efficient approach to the synthesis of benzimidazo[2,1-b]thiazoline derivatives has been developed through an addition/cyclization/intramolecular oxidative C−H functionalization process. A variety of alkylene benzimidazo[2,1-b] thiazolines were conveniently assembled from the reaction of aryl isothiocyanate and propargylic amine in the presence of Cu(OAc) 2 and PIFA at room temperature. The product could be further converted to substituted benzimidazo[2,1-b]thiazole derivatives.

Copper-Catalyzed One-Pot Synthesis of Thiazolidin-2-imines

“…The case of thiazolines, thiazolidinones, and thiazolidines is of particular interest, given that they have important biological applications against neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, as well as anticonvulsant, anti-inflammatory, anticancer, antiviral, antihypertensive, and antiparasitic properties, among others . Examples include etozoline A (Figure A), which exhibits antihypertensive activity, ralitoline B (Figure B), which exhibits anticonvulsant properties, 4-adamantyl-2-thiazolylimino-5-arylidene-4-thiazolidinones C (Figure C), which exhibit antibacterial activity, 3-thiazolidine-benzoic acid derivative D (Figure D), which exhibits anticancer activity, , specifically acting as a PPARγ antagonist, benzimidazo-thiazolinone-ylidine derivatives E (Figure E), which exhibit antifungal activity, and thiazolidine-ylidene derivative F (Figure F), which exhibits antibacterial activity against Salmonella enterica . When the carbonyl group in the five-membered thiazolidinone core of compound C , D , or F is replaced with carbon-based substituents, compounds with antiproliferative activity against breast cancer are obtained …”

Cascade Nucleophilic Addition/cyclization/C−N Coupling of o‐Iodo‐phenyl Isothiocyanates with Propargylamines: Access to Benzimidazo[2,1‐b]thiazole Derivatives

“…[5] Due to the prominent bioactive properties of benzimidazo [2, 1-b]thiazole compounds, the development of facile and efficient synthetic methods for this privileged architecture has attracted great attentions and many elegant methodologies have been developed during the last few decades. General pathways to benzimidazo[2, 1-b]thiazoles skeletons including the reactions of benzimidazole-2-thiols with carbonyl compounds, [6] alkynes, [7] propargyl bromides/tosylates [8] or active alkenes [9] (Scheme 1a). Despite these significant progresses have been made, present available synthetic methods have some limitations, such as high reaction temperature and restricted starting materials (benzimidazole-2-thiols).…”