Fluorenylmethyloxycarbonyl chloride

From Wikipedia, the free encyclopedia
  (Redirected from Fmoc chloride)
Jump to: navigation, search
Fluorenylmethyloxycarbonyl chloride[1]
Ball-and-stick model of the fluorenylmethyloxycarbonyl chloride molecule
IUPAC name
Chloroformic acid 9H-fluoren-9-ylmethyl ester
Other names
9-Fluorenylmethyl chloroformate; 9-Fluorenylmethoxycarbonyl chloride; Fmoc-chloride
3D model (JSmol)
ECHA InfoCard 100.044.816
Molar mass 258.70 g·mol−1
Melting point 62 to 64 °C (144 to 147 °F; 335 to 337 K)
Corrosive (C)
R-phrases (outdated) R34
S-phrases (outdated) S26 S36/37/39 S45
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
YesY verify (what is YesYN ?)
Infobox references

Fluorenylmethyloxycarbonyl chloride (FMOC-Cl) is a chloroformate ester. It is used to introduce FMOC group as the FMOC carbamate.


This compound may be prepared by reacting 9-fluorenylmethanol with phosgene:[2]

Preparation of Fmoc-Cl.png


The FMOC carbamate is often used as a protecting group for amines. The FMOC group can be introduced by reacting the amine with FMOC-Cl, e.g.:[3]

Scheme showing addition of an Fmoc group to an amino acid

The other common method for introducing the FMOC group is through 9-fluorenylmethylsuccinimidyl carbonate (FMOC-OSu), which may itself be obtained by the reaction of FMOC-Cl with the dicyclohexylammonium salt of N-hydroxysuccinimide.[4]

It may be cleaved by bases, typically a solution of piperidine:

Mechanism of the deprotection of the Fmoc group with piperidine.

FMOC protection has found significant use in solid phase peptide synthesis because its removal with piperidine solution does not disturb the acid labile linker between the peptide and the resin.[5]

Because the fluorenyl group is highly fluorescent, certain UV-inactive compounds may be reacted to give the FMOC derivatives, suitable for analysis by reversed phase HPLC. Analytical uses of FMOC-Cl that do not use chromatography may be limited by the requirement that excess FMOC-Cl be removed before an analysis of fluorescence.

Amine Protection - Fluorenylmethyloxycarbonyl (Fmoc)[edit]


Fluorenylmethyloxycarbonyl (Fmoc) group is used as a protecting group for amines in organic synthesis.

Common amine protection methods[edit]

Common amine deprotection methods[edit]


  1. ^ Fmoc chloride at Sigma-Aldrich
  2. ^ Carpino, Louis A.; Han, Grace Y. (1972). "9-Fluorenylmethoxycarbonyl amino-protecting group". The Journal of Organic Chemistry. 37 (22): 3404. doi:10.1021/jo00795a005. 
  3. ^ Yamada, Kazuhiko; Hashizume, Daisuke; Shimizu, Tadashi; Ohki, Shinobu; Yokoyama, Shigeyuki (2008). "A solid-state 17O NMR, X-ray, and quantum chemical study of N-α-Fmoc-protected amino acids". Journal of Molecular Structure. 888: 187. doi:10.1016/j.molstruc.2007.11.059. 
  4. ^ Paquet, A. (1982). "Introduction of 9-fluorenylmethyloxycarbonyl, trichloroethoxycarbonyl, and benzyloxycarbonyl amine protecting groups into O-unprotected hydroxyamino acids using succinimidyl carbonates". Canadian Journal of Chemistry. 60 (8): 976. doi:10.1139/v82-146. Archived from the original on 2012-07-26. 
  5. ^ J. Jones, Amino Acid and Peptide Synthesis, 2nd edn., Oxford University Press, 2002.
  6. ^ Carpino, Louis A.; Han, Grace Y. "9-Fluorenylmethoxycarbonyl amino-protecting group". The Journal of Organic Chemistry. 37 (22): 3404–3409. doi:10.1021/jo00795a005. 
  7. ^ Wuts, P; Green, T (2006); "Greene's Protective Groups in Organic Synthesis"; DOI: 10.1002/9780470053485.
  8. ^ Farrera-Sinfreu, Josep; Royo, Miriam; Albericio, Fernando (2002-10-21). "Undesired removal of the Fmoc group by the free ε-amino function of a lysine residue". Tetrahedron Letters. 43 (43): 7813–7815. doi:10.1016/S0040-4039(02)01605-2.