329-20-4

Usage

Uses

Used in Chemical Synthesis:
p-Acetaminobenzenesulphonyl fluoride is used as a connector in chemical synthesis for the assembly of -SO2linked small molecules with proteins or nucleic acids. Its sulfonyl fluoride motif allows for the formation of stable and functional linkages, which can be beneficial in various applications.
Used in Click Chemistry:
In the field of click chemistry, p-acetamidobenzenesulphonyl fluoride is used as a connector to facilitate the formation of -SO2linked small molecules with proteins or nucleic acids. This new approach through sulfates complements the traditional use of amides and phosphate groups as linkers, offering an alternative method for creating stable and functional molecular constructs.
Used in Pharmaceutical Industry:
p-Acetaminobenzenesulphonyl fluoride is used as a key intermediate in the synthesis of various pharmaceutical compounds. Its ability to form stable linkages with proteins and nucleic acids makes it a valuable component in the development of new drugs and therapeutic agents.
Used in Biochemical Research:
In biochemical research, p-acetamidobenzenesulphonyl fluoride is used as a tool to study the interactions between small molecules, proteins, and nucleic acids. Its sulfonyl fluoride motif allows for the creation of stable and functional linkages, which can help researchers better understand the mechanisms of various biological processes.
Overall, p-acetamidobenzenesulphonyl fluoride is a versatile compound with a range of applications in chemical synthesis, click chemistry, pharmaceutical development, and biochemical research. Its unique sulfonyl fluoride motif provides a valuable alternative to traditional linkers, enabling the formation of stable and functional molecular constructs.

InChI:InChI=1/C8H8FNO3S/c1-6(11)10-7-2-4-8(5-3-7)14(9,12)13/h2-5H,1H3,(H,10,11)

Upstream product

• 121-60-8 p-acetylaminobenzenesulfonyl chloride 
• 122-80-5 N-acetyl-p-phenylenediamine 
• 1126-81-4 4-acetamidothiophenol 
• 15898-43-8 sodium 4-acetamidobenzenesulfinate 
• 3989-50-2 4-acetamidobenzenesulfonylhydrazine 

Downstream Products

• 98-62-4 4-aminobenzenesulfonyl fluoride 
• 2284-35-7 4-isocyanatobenzenesulfonyl fluoride 

Relevant academic research and scientific papers

Visible-Light-Mediated Synthesis of Sulfonyl Fluorides from Arylazo Sulfones

Sulfonyl fluorides are useful motifs for a wide range of applications in organic synthesis including sulfur (VI) fluoride exchange-based “click chemistry.” Herein, a visible-light-mediated synthesis of sulfonyl fluorides from arylazo sulfones is described. In the present study, K2S2O5 and N-fluorobenzenesulfonimide (NFSI) were used as the sulfonyl source and fluorinating agent, respectively, for visible-light-mediated fluorosulfonylation of arylazo sulfones to prepare various sulfonyl fluorides in 60–85% yield. This protocol is a synthetic approach to provide useful sulfonyl fluoride structures at room temperature. (Figure presented.).

Arenesulfonyl Fluoride Synthesis via Copper-Catalyzed Fluorosulfonylation of Arenediazonium Salts

We report herein a general and practical copper-catalyzed fluorosulfonylation reaction of a wide range of abundant arenediazonium salts to smoothly prepare various arenesulfonyl fluorides using the 1,4-diazabicyclo[2.2.2]octane-bis(sulfur dioxide) adduct as a convenient sulfonyl source in combination with KHF2 as an ideal fluorine source and without the need for additional oxidants. Interestingly, the electronic character of the arene ring in the starting arenediazonium salts has a significant impact on the reaction mechanistic pathway.

Copper-free Sandmeyer-type Reaction for the Synthesis of Sulfonyl Fluorides

A copper-free Sandmeyer-type fluorosulfonylation reaction is reported. Utilizing Na2S2O5 and Selectfluor as the sulfur dioxide and fluorine sources, respectively, aryldiazonium salts were transformed into sulfonyl fluorides. The one-pot direct synthesis of sulfonyl fluorides from aromatic amines was also realized via in situ diazotization. The practicality of this method was demonstrated by the broad functional group tolerance, gram-scale synthesis, and late-stage fluorosulfonylation of natural products and pharmaceuticals.

Sulfonyl Fluoride Synthesis through Electrochemical Oxidative Coupling of Thiols and Potassium Fluoride

Sulfonyl fluorides are valuable synthetic motifs for a variety of applications, among which sulfur(VI) fluoride exchange-based "click chemistry" is currently the most prominent. Consequently, the development of novel and efficient synthetic methods to access these functional groups is of great interest. Herein, we report a mild and environmentally benign electrochemical approach to prepare sulfonyl fluorides using thiols or disulfides, as widely available starting materials, in combination with KF, as an inexpensive, abundant and safe fluoride source. No additional oxidants nor additional catalysts are required and, due to mild reaction conditions, the reaction displays a broad substrate scope, including a variety of alkyl, benzyl, aryl and heteroaryl thiols or disulfides.

A study of the reactivity of S(VI)-F containing warheads with nucleophilic amino-acid side chains under physiological conditions

Sulfonyl fluorides (SFs) have recently emerged as a promising warhead for the targeted covalent modification of proteins. Despite numerous examples of the successful deployment of SFs as covalent probe compounds, a detailed exploration of the factors influencing the stability and reactivity of SFs has not yet appeared. In this work we present an extensive study on the influence of steric and electronic factors on the reactivity and stability of the SF and related SVI-F groups. While SFs react rapidly with N-acetylcysteine, the resulting adducts were found to be unstable, rendering SFs inappropriate for the durable covalent inhibition of cysteine residues. In contrast, SFs afforded stable adducts with both N-acetyltyrosine and N-acetyllysine; furthermore, we show that the reactivity of arylsulfonyl fluorides towards these nucleophilic amino acids can be predictably modulated by adjusting the electronic properties of the warhead. These trends were largely conserved when the covalent reaction occurred within a protein binding pocket. We have also obtained a crystal structure depicting covalent modification of the catalytic lysine of a tyrosine kinase (FGFR1) by the ATP analog 5′-O-3-((fluorosulfonyl)benzoyl)adenosine (m-FSBA). Highly reactive warheads were demonstrated to be unstable with respect to hydrolysis in buffered aqueous solutions, indicating that warhead reactivity must be carefully tuned to provide optimal rates of protein modification. Our results demonstrate that the reactivity of SFs complements that of more commonly studied acrylamides, and we hope that this work spurs the rational design of novel SF-containing covalent probe compounds and inhibitors, particularly in cases where a suitably positioned cysteine residue is not present.

Catalyst-free radical fluorination of sulfonyl hydrazides in water

The first catalyst-free fluorination of sulfonyl hydrazides for the synthesis of sulfonyl fluorides has been developed via a free-radical pathway. This protocol presents a broad substrate scope and does not require any metal catalyst and additive. All these transformations proceed smoothly in water under mild conditions, which enables a straightforward, practical and environmentally benign fluorination for S-F bond formation.

Ascertaining the suitability of aryl sulfonyl fluorides for [18F]radiochemistry applications: A systematic investigation using microfluidics

Optimization of [18F]radiolabeling conditions and subsequent stability analysis in mobile phase, PBS buffer, and rat serum of 12 aryl sulfonyl chloride precursors with various substituents (electron-withdrawing groups, electron-donating groups, increased steric bulk, heterocyclic) were performed using an Advion NanoTek Microfluidic Synthesis System. A comparison of radiochemical yields and reaction times for a microfluidics device versus a conventional reaction vessel is reported. [18F]Radiolabeling of sulfonyl chlorides in the presence of competing nucleophiles, H-bond donors, and water was also assessed and demonstrated the versatility and potential utility of [18F]sulfonyl fluorides as synthons for indirect radiolabeling. Published 2013 by the American Chemical Society.