Pentafluorophenol | CAS 771-61-9 | ≥98%

Pentafluorophenol — perfluorophenol, PfpOH — is the alcohol used to form pentafluorophenyl (Pfp) active esters for amide and peptide bond formation. Its five ring fluorines strongly acidify the phenolic OH (pKa ≈ 5.5) and stabilise pentafluorophenolate as a leaving group, so pentafluorophenyl esters are reactive yet isolable acylating agents. A carboxylic acid is esterified with pentafluorophenol, typically via carbodiimide-mediated activation, and the resulting pentafluorophenyl ester then acylates an amine in solution- or solid-phase synthesis. Pentafluorophenol is a low-melting white solid, melting just above room temperature, soluble in common organic solvents and only sparingly soluble in water.

Common Scientific Applications

• Pentafluorophenyl active esters for amide and peptide bond formation: condensing a carboxylic acid with pentafluorophenol gives a pentafluorophenyl (Pfp) ester that can often be isolated and handled as a pre-formed active ester; these activated esters acylate amines in solution- and solid-phase peptide synthesis, including stepwise chain assembly.
• Bis(pentafluorophenyl) carbonate: pentafluorophenol is the precursor to bis(pentafluorophenyl) carbonate, a carbonyl-equivalent coupling reagent used especially in azapeptide preparation; in amino-acid chemistry, pentafluorophenyl carbonates can protect an amine as a carbamate and activate the carboxylic acid as a pentafluorophenyl ester in one pot.
• Activated-ester polymers and bioconjugation: pentafluorophenyl (meth)acrylate polymerises to reactive precursor polymers — poly(pentafluorophenyl acrylate) and the methacrylate — that undergo post-polymerisation modification with primary and secondary amines; pentafluorophenyl esters are widely used to conjugate amines and proteins, and relative to N-hydroxysuccinimide esters are generally more soluble in organic solvents and more resistant to hydrolysis.
• Pentafluorophenyl formate as a formylating agent: pentafluorophenol is converted to pentafluorophenyl formate, used to formylate amines and amino acids in organic synthesis.
• Organoaluminium reagents for selective acetal cleavage: pentafluorophenol is used to prepare bulky aluminium pentafluorophenoxide reagents that effect highly selective, diastereoselective cleavage of acetals.

Further Reading

For guidance on selecting between carbodiimides, aminium/uronium salts, phosphonium salts and other reagent classes for amide and peptide bond formation, see NorrChemica's Lab Journal guide: Choosing a Coupling Reagent for Amide and Peptide Bond Formation.