Chemistry Reference
In-Depth Information
Carbamates are generally prepared from isocyanates or chloroformates (see Scheme
4.2). Since isocyanates and chloroformates are usually prepared with phosgene,
the corresponding synthetic routes are subject to the relevant safety considerations
regarding the phosgene source (for a safe phosgene source, see Chapter 7). Moreover,
the handling of several lower alkyl isocyanates is associated with a similar hazard
level (toxicity), and therefore the search for a less hazardous procedure has been
intense.
Several synthetic methods are available for the preparation of cyclic carbamates
such as oxazolidin-2-ones or thiazolidin-2-ones. General reviews on the synthesis
and chemistry of 2-oxazolidinones detailing the reactions of N,O-orN,S-binucleo-
philic substrates with various carbonylating agents have been published [363, 364].
4.3.2.1
Phosgene and Haloformates as Reagents
Many procedures for carbamate preparation have been developed in connection
with the high demand for amine group protection of amino acids in peptide syn-
thesis [155, 365]. Some examples of reported procedures employing phosgene,
alkyl- or alkylene chloroformates are given below.
N-Alkyloxycarbonyl derivatives of amino acids [366, 367] are of increasing interest
owing to the fact that they can be submitted to deprotection by mild acidolysis,
aminolysis or hydrogenolysis (Table 4.22).
The choice of protecting group is usually determined by the compatibility of the
cleavage reaction that is appropriate for each protected substrate. In the special
Tab. 4.22.
Cleavage of alkyl carbamates (deprotection methods for the most common
alkoxycarbonylamines).
N-Protecting group
Short name
Cleavage method
Methoxy- and ethoxycarbonyl
Alkaline hydrolysis under vigorous
conditions, or with powerful
nucleophiles such as thiolates
tert-Butoxycarbonyl
Boc
Acidolysis (CF
3
COOH)
Benzyloxycarbonyl
Cbz, Z
Hydrogenolysis (H
2
/Pd-C), or acidolysis
(48% HBr/AcOH)
4-Nitro benzyloxycarbonyl
4-NO
2
-Z
Hydrogenolysis (easier than Cbz, more
resistant to acidic cleavage)
9-Fluorenylmethoxycarbonyl
Fmoc
Mild aminolysis (20% piperidine in
DMF)
Allyloxycarbonyl
Aloc
Pd(0)-dimedone, or 2-Et-hexanoic acid/
Pd(Ph
3
P)
4
/Ph
3
P
2-(Trimethylsilyl)ethoxycarbonyl
Teoc
Tetra-n-butylammonium chloride and
KF
2H
2
O in MeCN
2,2,2-Trichloroethoxycarbonyl
Troc
Zn in AcOH at room temp. or in EtOH
at reflux
2,2,2-Trichloro-tert-butoxycarbonyl
TCBoc
Zn in AcOH at room temp., or
supernucleophiles such as Li[Co
I
Pc],
Pc
ΒΌ
phthalocyanine
