CAS 349-89-3

p-chlorobenzenesulfonyl fluoride

Sulfonyl Fluorides

About This Compound

Sulfonyl fluorides are key building blocks in Sulfur(VI) Fluoride Exchange (SuFEx) click chemistry — one of the most robust click reactions introduced by Sharpless and colleagues. The SO₂F group reacts selectively with nucleophiles such as phenols, amines, and silyl ethers under mild conditions, forming stable sulfonate or sulfonamide linkages. These compounds are widely used in chemical biology for covalent protein labeling, activity-based protein profiling (ABPP), and the construction of molecular probes.

Related Reactions: Nucleophilic Ring-Opening
Molecular FormulaC6H4ClFO2S Molecular Weight194.614 g/mol InChIKeyPCTLRVPDZBVCMP-UHFFFAOYSA-N CAS Registry349-89-3 Literature Refs105 references

Synthesis Routes

Showing 3 of 50 available routes, sorted by yield.

Route 1

1 step Yield: 99%
p-chlorobenzenesulfonyl fluoride
CAS 349-89-3
C6H4ClFO2S
+
phenol
C6H6O
p-chlorobenzenesulfonyl fluoride
Conditions With 1,8-diazabicyclo[5.4.0]undec-7-ene; 1,3-bis(mesityl)imidazolium chloride In acetonitrile at 20℃
Reference Lin, Muze; Luo, Jinyun; Xie, Yu; Du, Guangfen; Cai, Zhihua; Dai, Bin; He, Lin [ACS Catalysis, 2023, vol. 13, # 22, p. 14503 - 14512] DOI
Source Reaxys

Route 2

1 step Yield: 99%
p-chlorobenzenesulfonyl fluoride
CAS 349-89-3
C6H4ClFO2S
+
benzylamine
C7H9N
p-chlorobenzenesulfonyl fluoride
Conditions With benzotriazol-1-ol; 1,8-diazabicyclo[5.4.0]undec-7-ene; 1,3-bis(mesityl)imidazolium chloride In
Reference Lin, Muze; Luo, Jinyun; Xie, Yu; Du, Guangfen; Cai, Zhihua; Dai, Bin; He, Lin [ACS Catalysis, 2023, vol. 13, # 22, p. 14503 - 14512] DOI
Source Reaxys

Route 3

1 step Yield: 98%
p-chlorobenzenesulfonyl fluoride
CAS 349-89-3
C6H4ClFO2S
+
4-chloro-phenol
CAS 106-48-9
C6H5ClO
p-chlorobenzenesulfonyl fluoride
Conditions With caesium carbonate In acetonitrile at 20℃; for 8h;
Reference Tao, Guang; Fayad, Eman; Abu Ali, Ola A.; Oyom, Bright; Qin, Hua-Li [Synthesis (Germany), 2025, vol. 57, # 5, p. 991 - 998] DOI
Source Reaxys
47 additional routes available in the full dataset. Contact us for complete synthesis route data.

Related Compounds

Other Sulfonyl Fluorides in our catalog:

Frequently Asked Questions

How should sulfonyl fluoride compounds be stored?

Store in a sealed container at room temperature, protected from moisture. Sulfonyl fluorides are generally stable to ambient humidity for weeks, but prolonged exposure to water can lead to hydrolysis of the SO₂F group. For long-term storage, keep under inert atmosphere (N₂ or Ar) at −20 °C.

What nucleophiles are compatible with SuFEx reactions?

SuFEx reactions selectively target silyl ethers, phenols, primary and secondary amines, and activated alcohols. Thiols and carboxylic acids generally do not react with sulfonyl fluorides under standard conditions, providing excellent chemoselectivity in complex biological environments.

What catalysts are commonly used for SuFEx?

Common SuFEx catalysts include BTMG (2-tert-butyl-1,1,3,3-tetramethylguanidine), BEMP, and 4-dimethylaminopyridine (DMAP). Base-catalyzed SuFEx typically proceeds at room temperature in organic solvents such as DMSO, DMF, or MeCN.

Are sulfonyl fluorides safe to handle in the lab?

Sulfonyl fluorides are generally safer and more stable than sulfonyl chlorides. However, standard PPE (gloves, goggles, fume hood) should be used. Avoid contact with strong bases and nucleophilic solvents. Small-molecule sulfonyl fluorides may have acute toxicity — always consult the SDS before use.

How do I purify sulfonyl fluoride products?

Most sulfonyl fluorides can be purified by silica gel column chromatography using hexane/ethyl acetate gradients. They are generally stable to standard chromatographic conditions. Alternatively, recrystallization from EtOAc/hexane works well for crystalline products.

Last updated: July 27, 2026