p-Nitrophenyl Trifluoroacetate

[658-78-6]  · C8H4F3NO4  · p-Nitrophenyl Trifluoroacetate  · (MW 235.13)

(preparation of active esters for peptide synthesis1,2)

Physical Data: mp 36-38 °C (sublimed material).

Form Supplied in: commercially available solid.

Preparative Method: prepared in quantitative yield by heating at reflux a mixture of p-Nitrophenol and Trifluoroacetic Anhydride in benzene. Evaporation gives crude, crystalline material (mp 37-39 °C) of sufficient purity for use in peptide synthesis.1

Purification: by vacuum sublimation.

Handling, Storage, and Precautions: water sensitive; should be stored in a tightly closed bottle.

Preparation of Active Esters for Peptide Synthesis.

p-Nitrophenyl trifluoroacetate reacts readily with N-Cbz protected amino acids in pyridine to give the corresponding p-nitrophenyl esters (eq 1),1,2 without racemization; these activated esters can be employed in peptide synthesis (see also p-Nitrophenol). Protection of side-chain functionality such as hydroxyl or amino groups is necessary in order to avoid side reactions. The only coproduct, trifluoroacetic acid, is water soluble. Isolation of the active ester is not necessary; direct addition of an amino component and 2 equiv of Triethylamine allows amide formation in the same reaction vessel as active ester formation.2 This procedure is particularly useful when the activated ester will not crystallize. Formation of the active esters of N-Cbz protected peptides by this method is slower and requires heating or longer reaction times. Presumably for this reason, complete racemization is observed in the Anderson test (coupling of CbzGly-L-Phe to Gly-OEt).3

1. Sakakibara, S.; Inukai, N. BCJ 1964, 37, 1231.
2. Sakakibara, S.; Inukai, N. BCJ 1965, 38, 1979.
3. Sakakibara, S.; Inukai, N. BCJ 1966, 39, 1567.

Alan Armstrong

University of Bath, UK

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