329-20-4

Basic information

• Product Name: p-acetamidobenzenesulphonyl fluoride
• Synonyms: p-acetamidobenzenesulphonyl fluoride;4-(Acetylamino)benzenesulfonyl fluoride;4-acetamidobenzenesulfonyl fluoride
• CAS NO: 329-20-4
• Molecular Formula: C₈H₈FNO₃S
• Molecular Weight: 217.2174232
• EINECS: 206-343-4
• Mol File: 329-20-4.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 386°Cat760mmHg
• Flash Point: 187.2°C
• Appearance: /
• Density: 1.417g/cm³
• Vapor Pressure: 3.65E-06mmHg at 25°C
• Refractive Index: 1.548
• CAS DataBase Reference: p-acetamidobenzenesulphonyl fluoride(CAS DataBase Reference)
• NIST Chemistry Reference: p-acetamidobenzenesulphonyl fluoride(329-20-4)
• EPA Substance Registry System: p-acetamidobenzenesulphonyl fluoride(329-20-4)

Safety Data

• Hazardous Substances Data: 329-20-4(Hazardous Substances Data)

Usage

Uses

Sulfonyl fluoride motif can be used as a connector for the assembly of -SO2- linked small molecules with proteins or nucleic acids. This new click chemistry approach through sulfates is a complimentary approach to using amides and phosphate groups as linkers.

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

Downstream Products

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

Relevant articles and documents

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.).

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.

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.