N-Fluorobenzenesulfonimide

• Catalog: OFC133745752
• CAS: 133745-75-2
• Category: Electrophilic Fluorination Agents
• Synonyms: N-Fluorobis(phenylsulfonyl)amine; NFSI; NFBS
• Purity: >98.0%(T)(HPLC)
• MDL Number: MFCD00144885

• IUPAC Name: N-(benzenesulfonyl)-N-fluorobenzenesulfonamide
• InChI: InChI=1S/C12H10FNO4S2/c13-14(19(15,16)11-7-3-1-4-8-11)20(17,18)12-9-5-2-6-10-12/h1-10H
• InChI Key: RLKHFSNWQCZBDC-UHFFFAOYSA-N
• Isomeric SMILES: C1=CC=C(C=C1)S(=O)(=O)N(F)S(=O)(=O)C2=CC=CC=C2
• EC Number: 431-940-3
• Reaxys Registry Number: 5348902

• Molecular Formula: C12H10FNO4S2
• Molecular Weight: 315.33
• Melting Point: 115.0-119.0 °C
• Appearance: White to light yellow powder to crystal

• XLogP3-AA: 2.6
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 4
• Exact Mass: 315.00352831 g/mol
• Monoisotopic Mass: 315.00352831 g/mol
• Topological Polar Surface Area: 88.3Ų
• Heavy Atom Count: 20
• Formal Charge: 0
• Complexity: 4

• HS Number: 2935.90.9500

Case Study

N-Fluorobenzenesulfonimide as an Efficient Nitrogen Source for Regioselective Amidation Reactions

Bai L, et al. RSC Advances, 2024, 14(47), 34811-34815.

N-Fluorobenzenesulfonimide (NFSI) has emerged as a highly effective reagent for the amidation of electron-rich arenes, enabling efficient nitrogen incorporation without the need for catalysts or additives. Previous studies have highlighted the regioselectivity of NFSI-mediated amidation reactions in indoles, pyrroles, quinolones, and imidazoheterocycles. These reactions occur under mild conditions, relying solely on a base or hypervalent iodine reagents, and further emphasize NFSI's versatility in enabling efficient, metal-free synthesis routes. Furthermore, NFSI has been successfully applied to fluorination reactions, including its reaction with C60, yielding high-efficiency adducts through a concerted (2 + 2) cycloaddition mechanism. These findings solidify NFSI as a powerful, environmentally friendly alternative for nitrogen incorporation in organic synthesis, broadening its applicability in both academic and industrial settings.

N-Fluorobenzenesulfonimide as a Catalytic Reagent for the Efficient Synthesis of β-Keto Sulfones via Electrophilic Cascade Reaction

Bao F, et al. Asian Journal of Organic Chemistry, 2023, 12(12), e202300407.

N-Fluorobenzenesulfonimide (NFSI) plays a pivotal role in a selenium-catalyzed electrophilic cascade reaction for the synthesis of β-keto sulfones from readily available vinylarenes. This process involves an electrophilic addition followed by deprotonation, sulfonyl migration, and hydrolysis, enabling efficient transformation under mild, air-compatible conditions. The reaction has been shown to proceed effectively with both electron-withdrawing and electron-donating substituted vinylarenes, achieving product yields up to 94%. Mechanistic studies reveal that vinyl amines, generated via oxidative amination, act as intermediates, with subsequent N-S bond cleavage and sulfonyl radical recombination leading to the key 1,3-migration of the sulfonyl group. This cascade reaction offers a highly efficient, one-step method for the synthesis of β-keto sulfones, which are valuable intermediates in organic synthesis and pharmaceutical development.

N-Fluorobenzenesulfonimide for Metal-Free Sulfonylation of Arenes in Diarylsulfone Synthesis

Zhang X, et al. Organic & Biomolecular Chemistry, 2022, 20(4), 768-772.

N-Fluorobenzenesulfonimide (NFSI) has emerged as an effective metal-free sulfonyl donor for the synthesis of diarylsulfones, enabling the selective cleavage of S-N bonds in unactivated arenes. This reaction, which utilizes NFSI as a sulfonylating agent, represents a novel approach to sulfonylation and offers an efficient, acid-mediated pathway to produce pharmaceutically and biologically significant diarylsulfones. The reaction is notably advantageous in its simplicity and environmental sustainability, as it avoids the use of metal catalysts. Its application has been demonstrated in the functionalization of natural products such as β-estradiol and in the synthesis of key intermediates, including a precursor to a farnesyl-protein transferase inhibitor. Additionally, NFSI has been applied on a gram scale in the production of an EPAC2 antagonist.

Experimental Method for N-Fluorobenzenesulfonimide-Promoted Metal-Free Oxidative Trideuteromethylthiolation

Wang W, et al. Org. Lett. 2023, 25, 39, 7078-7082.

In the metal-free oxidative trideuteromethylthiolation reaction, N-fluorobenzenesulfonimide (NFSI) acts as a key oxidant, facilitating the generation of a thiyl radical from CD3SSO3Na, thereby enabling the selective incorporation of the trideuteromethylthiol (-SCD3) group onto styrene substrates. In the experimental procedure, 4-fluorostyrene, CD3SSO3Na, and NFSI were dissolved in N,N-dimethylacetamide (DMA) and heated under a nitrogen atmosphere at 80 °C for 24 hours, yielding the desired product with an 80% yield. Further studies revealed that solvent selection is crucial, as alternative solvents such as dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) failed to facilitate the reaction. Additionally, replacing CD3SSO3Na with PhSO2SCD3 did not produce the desired product, confirming the necessity of CD3SSO3Na in this system. Reaction condition optimization showed that changing the reaction atmosphere from nitrogen to oxygen or air significantly reduced the product yield, while variations in reaction temperature (70 °C or 90 °C) also affected efficiency. Control experiments further confirmed that NFSI is an indispensable oxidant for this oxidative trideuteromethylthiolation.