[100-02-7]  · C6H5NO3  · p-Nitrophenol  · (MW 139.12)

(preparation of active esters for peptide synthesis1)

Physical Data: mp 114 °C; pKa 7.15 (at 25 °C); dimorphous.

Solubility: moderately sol cold water; sol alcohol, chloroform, ether.

Form Supplied in: generally obtained as a mixture of the two crystalline forms.

Purification: recystallization from toluene gives the metastable a-form if performed at >63 °C; the b-form is obtained as yellow prisms at <63 °C.

Handling, Storage, and Precautions: the a-form is light stable, whereas the yellow b-form gradually turns red in light. Moderately toxic by inhalation and skin absorption.

Preparation of Active Esters for Peptide Synthesis.

p-Nitrophenyl esters, prepared by 1,3-Dicyclohexylcarbodiimide-mediated coupling between N-protected amino acids and p-nitrophenol, are among the most useful activated esters for peptide synthesis (eq 1).1 They are readily purified by recrystallization, often from alcoholic solvents with which they do not react. Aminolysis occurs at a reasonable rate, generally at room temperature without a catalyst. The p-nitrophenol generated as a byproduct in this step is easily removed. o-Nitrophenyl esters can be used similarly (see o-Nitrophenol); a study of the rates of aminolysis of Boc-L-leucine nitrophenyl esters showed the o-isomer to react 4-9 times faster than the p-isomer.2

1. Bodanszky, M.; Du Vigneaud, V. JACS 1959, 81, 5688; Bodanszky, M.; Meienhofer, J.; Du Vigneaud, V. JACS 1960, 82, 3195.
2. Bodanszky, M.; Bath, R. J. CC 1969, 1259.

Alan Armstrong

University of Bath, UK

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.