4-Nitrophenyl Chloroformate: A Versatile Coupling Reagent

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]

References

• 1 Anderson GW. McGregor AC. J. Am. Chem. Soc.  1957,  79:  6180 
• 2 Miller K. Erez R. Segal E. Shabat D. Satchi-Fainaro R. Angew. Chem. Int. Ed.  2009,  48:  2949 ; Angew. Chem. 2009, 12, 2993
• 3 Van den Dolder J. Jansen JA. J. Biomed. Mat. Res. Part A  2007,  83A:  712 
• 4 Heredia KL. Maynard HD. Org. Biomol. Chem.  2007,  5:  45 
• 5 Zhang Z. Tanabe K. Hatta H. Nishimoto S. Org. Biomol. Chem.  2005,  3:  1905 
• 6 Letsinger RL. Ogilvie KK. J. Org. Chem.  1967,  32:  296 
• 7 Mallakpour S. Rafiee Z. Synth. Comm.  2007,  37:  1927 
• 8 Chong PY. Janicki SJ. Petillo PA. J. Org. Chem.  1998,  63:  8515 
• 9 Kopach ME. Fray AH. Meyers AI. J. Am. Chem. Soc.  1996,  118:  9876 
• 10 Jones AD. Zelle RE. Silverman RI. PCT Int. Appl. WO 2009035652 2009, 
• 11 Hobson JD. McCluskey JG. J. Chem. Soc. C.  1967,  2015 
• 12 Phillips D. OŽNeill BT. Tetrahedron Lett.  1990,  31:  3291 
• 13 Brown D. Brown GA. Martel SR. Planchenault D. Turmes E. Walsh KE. Wisedale R. Hales NJ. Fishwick CWG. Gallagher T. J. Chem Soc., Perkin Trans. 1  2001,  1270 
• 14 Li J.-J. Bugg TDH. Org. Biomol. Chem.  2007,  5:  507 
• 15 Gooßen LJ. Paetzold J. Angew. Chem. Int. Ed.  2002,  41:  1237;   Angew. Chem. 2002, 114, 1285
• 16 Kita R. Svec F. Fréchet JMJ. J. Comb. Chem.  2001,  3:  564