Iron-CatalyzedN-Arylsulfonamide Formation through Directly Using Nitroarenes as Nitrogen Sources

Abstract

One-step, catalytic synthesis of N-arylsulfonamides via the construction of N-S bonds from the direct coupling of sodium arylsulfinates with nitroarenes was realized in the presence of FeCl2 and NaHSO3 under mild conditions. In this process, stable and readily available nitroarenes were used as nitrogen sources, and NaHSO3 acted as a reductant to provide N-arylsulfonamides in good to excellent yields. A broad range of functional groups were very well-tolerated in this reaction system. In addition, mechanistic studies indicated that the N-S bond might be generated through direct coupling of nitroarene with sodium arylsulfinate prior to the reduction of nitroarenes by NaHSO3. Accordingly, a reaction mechanism involving N-aryl-N-arenesulfonylhydroxylamine as an intermediate was proposed.

Straightforward and Sustainable Synthesis of Sulfonamides in Water under Mild Conditions

“…As mentioned above, only electron‐poor nitroarenes are reactive under our optimized conditions. This is in agreement with the mechanism proposed by Zhang et al Indeed, the key step of the reaction is the nucleophilic attack of the sulfur atom on the nitro function to create the S–N bond before the N–O is reduced by the sodium bisulfite to generate a sulfate ion and the sulfonamide function. Accordingly, electron‐poor nitroarenes are more reactive than the electron‐rich analogues.…”

“…In addition, catalysts play essential roles in sulfonamide synthesis, as mentioned by Zhang et al; reactions can proceed without catalyst in DMSO but with poor yields . Furthermore, metallic residues resulting from the catalytic process may not be suitable for use in the pharmaceutical industry .…”

“…Zhao et al described a sulfonamide synthesis involving the coupling of nitroarenes and arylsulfonyl hydrazide in DMF using palladium hydroxide as the catalyst in the presence of pyridine and molecular sieves. Another catalytic system was developed by Zhang et al It uses 10 % of FeCl 2 and trans ‐ N , N′ ‐dimethylcyclohexane‐1,2‐diamine as the catalyst under argon in the presence of an excess of arylsulfinate salts in DMSO. Using these conditions, they obtained sulfonamides in good yields (Scheme ).…”

Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry

“…reported their FeCl 2 -catalyzed system for the construction of sulfonamide directly from nitroarenes and sodium arylsulfinates under mild conditions [14]. It’s noteworthy that they use nitroarenes instead of conventional aromatic amines as nitrogen source.…”

Magnetically Recyclable Metal–Organic Framework@Fe3O4 Composite‐Catalyzed Facile Reduction of Nitroarene Compounds in Aqueous Medium

“…Generally, the reduction of nitroarene compounds in the presence of a catalyst and a reductant is one of the most fundamental and straightforward processes to prepare anilines. Various reductants such as H 2 , NH 2 NH 2 , NH 4 Cl, alcohols, acids, NaHSO 3 , NaBH 4 , LiAlH 4 and ammonia‐borane have already been successfully employed. Despite these significant progress, there are still some issues to be addressed.…”