[7497-12-3] · C13H6N4O11 · Bis(2,4-dinitrophenyl) Carbonate · (MW 394.21)
(peptide and azapeptide coupling reagent that functions by activating amines, forming derivatives suitable for condensation with N-protected amino acids;1-4 converts carboxylic acids to activated esters2)
Alternate Names: carbonic acid bis(2,4-dinitrophenyl) ester; 2,4-dinitrophenyl 2,4-dinitrophenoxyformate.
Solubility: sol EtOAc, pyridine, DMF, CHCl3; moderately sol benzene; insol hexane; dec hot H2O, EtOH.
Preparative Method: diphenyl carbonate (20 g) is added to a stirred mixture of conc HNO3 (100 mL) and conc H2SO4 (120 mL) at 50-55 °C over 1 h. The resulting suspension is stirred at 50 °C for 3 h, left at rt for 90 h and poured onto ice. The precipitate is washed with iced water and dried in vacuo over P2O5. This affords bis(2,4-dinitrophenyl) carbonate (31.2 g, 85%) which recrystallizes from hexane/benzene giving crystals, mp 144-146 °C.3
Handling, Storage, and Precautions: store in a cool dry place to preclude contact with moisture; the hazardous and toxicological properties have not been investigated; may explode if heated rapidly.
The reagent is used to activate amino groups (eq 1) for subsequent coupling with N-protected amino acids and hydrazides, affording peptide (eq 2) and azapeptide (eq 3) derivatives, respectively.1-4 Cbz-protected amino acids are coupled without racemization but N-acylated amino acids lose all optical activity.2
Attempts to prepare azapeptides by activating hydrazides have proved unsuccessful because of the propensity of the intermediate to undergo base-catalyzed cyclization and elimination to stable oxadiazolones (eq 4).3
The reagent is attacked by carboxylate ions, forming unstable intermediates which spontaneously decarboxylate to dinitrophenyl esters (eq 5).2 These activated esters are good acylating agents and undergo transesterification on reaction with alkoxide or aryloxide ions (eq 6).2 The mild conditions under which these activated dinitrophenyl esters can be formed makes them preferable intermediates to the analogous 4-mononitrophenyl esters which are less active towards nucleophiles; also 2,4-dinitrophenol is more acidic than 4-nitrophenol and consequently may be easier to separate from the desired reaction product during workup.
Niall M. Hamilton
Organon Laboratories Ltd, Newhouse, Lanarkshire, UK