Synlett 2009(18): 3050-3051  
DOI: 10.1055/s-0029-1218291
SPOTLIGHT
© Georg Thieme Verlag Stuttgart ˙ New York

4-Nitrophenyl Chloroformate: A Versatile Coupling Reagent

Benedikt Sammet*
Department of Chemistry, Organic and Bioorganic Chemistry, ­Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany
e-Mail: benedikt.sammet@uni-bielefeld.de;
Further Information

Publication History

Publication Date:
23 October 2009 (online)

Introduction

4-Nitrophenyl chloroformate (4-NPC; CAS: 7693-46-1) is one of the most common reagents for the activation of alcohols, thiols and amines for the formation of carbonates and carbamates. It is a colorless, crystalline solid, which is easy to handle and well-storable. It was introduced into literature for the synthesis of t-butyl 4-nitrophenyl carbonate as a reagent for the Boc-protection of amines. [¹] Today, however, its range of application is very broad and has led to considerably safer chemistry, replacing phosgene in many reactions. The obtained 4-NP carbonates and carbamates are often stable and can be purified by column chromatography or recrystallization. Nevertheless, one-pot procedures for the in situ substitution of the 4-nitrophenyl moiety are regularly employed. Due to the increasing demand for bioconjugates containing different natural product classes, stable carbonate and carbamate linker systems are conveniently synthesized by applying this reagent. [²] In addition, the substance is used for covalent protein immobilization on surfaces [³] and polymer peptide linkages. [4]

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