Iodine-promoted 2-arylsulfanylphenol Formation Using Cyclohexanones As Phenol Source

Aryl thioethers are important structural motifs which widely present in agrochemicals, functional materials and pharmaceutical products. Therefore, the development of efficient methods for the preparation of aryl thioethers has stimulated considerable interest. Among various thioether derivatives, 2-arylsulfanylphenols play an important role in biologically and pharmaceutically active molecules due to they also contain a phenol structural motif. However, procedures for preparation of aryl thioethers with a hydroxyl group at the ortho position are still rare, and the majors are based on the metal-catalyzed cross-coupling of thiols with 2-halophenols. Although there are other few methods available for 2-arylsulfanylphenol preparation, most of the approaches require two aromatic coupling partners. Aryl thioether preparation from non-aromatic coupling partners is still rare.Cyclohexanones are cheap, readily available, and able to convert into other important organic materials. Thus, cyclohexanones can be used as an ideal aryl source for coupling reaction via dehydrogenation strategy. Due to the importance of 2-arylsulfanylphenols in pharmaceutical drugs and biologically active compounds, it’s highly desirable to develop reliable and general procedures for preparation of them using readily available starting materials. Herein, we describe the iodine-promoted C-S bond formation from cyclohexanones using aryl sulfonyl chlorides and sodium sulfinates as the sulfur sources. The main results achieved are as follows:A novel method for the synthesis of 2-arylsulfanylphenols has been developed using cyclohexanones as a reliable phenol source under transition-metal-free conditions. Iodine was used as an effective catalyst in this transformation. Under the optimized reaction conditions, Various sulfonyl chlorides and sodium sulfinates were used as the sulfur source to smoothly couple with cyclohexanones. The C-S bond formation, dehydrogenation and tautomerization were realized in one-pot in the absence of transition-metals. Since sulfonyl chlorides and sulfinic acid sodium salts are readily available starting materials, this method affords an efficient approach for 2-arylsulfanylphenols with a broad range of functional groups.