New synthesis of 2-aroylbenzothiazoles via metal-free domino transformations of anilines, acetophenones, and elemental sulfur.

Tien V Huynh,Son H Doan,Khang V Doan,Duyen T P Nguyen,Ngoc T K Luong,Tung T Nguyen,Nam T S Phan

doi:10.1039/d0ra01750g

Abstract

A new synthesis of 2-aroylbenzothiazoles via iodine-promoted domino transformations of anilines, acetophenones, and elemental sulfur was demonstrated. The highlights of this tandem synthesis are (1) easily available anilines and acetophenones as feedstock; (2) transition metal-free conditions; (3) inexpensive, nontoxic, easy handling, and abundant elemental sulfur as a building block. This synthetic strategy would complement the existing methods in the synthesis of this important heterocyclic scaffold. To our best knowledge, the formation of 2-aroylbenzothiazoles from simple anilines, acetophenones, and elemental sulfur was not previously reported in the literature.

Highlights

Several methods have been investigated for the synthesis of 2-aroylbenzothiazoles, including (i) transitional metalcatalyzed sp[2] C–H bond functionalization of benzothiazoles, and (ii) cyclization with or without sulfuration of orthosubstituted anilines
The study commenced with the three-component reaction of aniline (1a), acetophenone (2a), and elemental sulfur to generate benzo[d]thiazol-2-yl(phenyl)methanone (3aa)
The research scope was subsequently extended to the synthesis of many 2-aroylbenzothiazoles via threecomponent reactions of anilines, acetophenones, and elemental sulfur (Table 2)

Summary

Introduction

Benzothiazoles have emerged as ubiquitous scaffolds with diverse biological and pharmacological activities, commonly found in numerous commercial drugs, agricultural chemicals, and functional materials.[1,2,3] Among these structures, 2-aroylbenzothiazoles have attracted signi cant attention owing to their pharmaceutical and medicinal applications.[4,5,6] several methods have been investigated for the synthesis of 2-aroylbenzothiazoles, including (i) transitional metalcatalyzed sp[2] C–H bond functionalization of benzothiazoles, and (ii) cyclization with or without sulfuration of orthosubstituted anilines. Environmentally benign metal-free strategy in organic synthesis.[35,36,37] In this work, we would like to report a new synthesis of 2-aroylbenzothiazoles via metal-free domino transformations of anilines, acetophenones, and elemental sulfur in the presence of molecular iodine (Scheme 1c). The formation of 2-aroylbenzothiazoles from simple anilines, acetophenones, and elemental sulfur was not previously reported in the literature.

Results

Conclusion