t-Butyl 2,4,5-Trichlorophenyl Carbonate

[16965-08-5]  · C11H11Cl3O3  · t-Butyl 2,4,5-Trichlorophenyl Carbonate  · (MW 297.57)

(reagent for the Boc protection of amino groups;1 preparation of active esters for peptide synthesis1)

Physical Data: mp 67-68.5 °C.

Form Supplied in: commercially available solid.

Preparative Method: reaction between 2,4,5-trichlorophenol and Phosgene in toluene at -10 °C in the presence of dimethylaniline gives 2,4,5-trichlorophenyl chloroformate. Treatment with t-butanol and quinoline in CH2Cl2 then affords t-butyl 2,4,5-trichlorophenyl carbonate.1

Purification: recrystallization from methanol/water (charcoal).

Preparation of Active Esters for Peptide Synthesis.

t-Butyl 2,4,5-trichlorophenyl carbonate (1) reacts with amino acids in the presence of Triethylamine to give the N-Boc-protected amino acid (2), along with 2,4,5-trichlorophenol (eq 1).1 High yields are obtained (often 90-95%), except for the hydroxy amino acids. Reagent (1) is more easily prepared than t-Butyl Azidoformate, commonly used for introduction of the Boc group, but seems otherwise to offer little advantage if protection is the only aim. The utility of (1) arises because (2) and the 2,4,5-trichlorophenol may be extracted together from the reaction mixture into ethyl acetate; addition of 1,3-Dicyclohexylcarbodiimide then affords the N-Boc-protected 2,4,5-trichlorophenyl ester (3) of the amino acid. These activated esters may be employed for peptide synthesis; they are generally crystalline solids, stable in alcoholic solvents and on storage, and their reactivity towards amino groups is at least as high as that of the corresponding p-nitrophenyl esters (see also p-Nitrophenol). Following peptide formation, the 2,4,5-trichlorophenol coproduct is readily removed.

1. Broadbent, W.; Morley, J. S.; Stone, B. E. JCS(C) 1967, 2632.

Alan Armstrong

University of Bath, UK

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