s-Butyl Chloroformate

[17462-58-7]  · C5H9ClO2  · s-Butyl Chloroformate  · (MW 136.58)

(reagent for preparation of mixed anhydrides for peptide synthesis1,2)

Physical Data: bp 115-117 °C; n24D 1.4037.

Preparative Method: prepared (50% yield) by reaction of s-butanol with 1.5 equiv of phosgene.1

Purification: purified by distillation.

Handling, Storage, and Precautions: no information available.

Mixed Anhydrides for Peptide Synthesis.

s-Butyl chloroformate (1) reacts with N-protected amino acids to give the mixed anhydride (2); treatment with an amino acid ester (or an alkaline aqueous solution of an unprotected amino acid) results in amide bond formation, affording (3) (eq 1).1,2 The method is rapid and clean; since the only byproducts of the reaction are CO2 and s-butanol, the products are obtained in a high state of purity, and sometimes crystallize directly from the reaction mixture. Other simple alkyl chloroformates may of course be used in place of (1), but Vaughan and Osato noted that (1) and i-butyl chloroformate provided highest yields, with a slight advantage for the former.1

While racemization is generally not observed in the synthesis of dipeptides, careful choice of conditions is necessary for the preparation of higher peptides. The use of THF as solvent in the anhydride formation step is recommended, along with shorter reaction times (5-10 min at -5 °C) if racemization is likely to be a problem.3

1. Vaughan, J. R., Jr.; Osato, R. L. JACS 1952, 74, 676.
2. Vaughan, J. R., Jr. JACS 1951, 73, 3547.
3. (a) Vaughan, J. R., Jr. JACS 1952, 74, 6137. (b) Vaughan, J. R., Jr.; Eichler, J. A. JACS 1953, 75, 5556.

Alan Armstrong

University of Bath, UK

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