A simple and efficient method for trifluoroacetylation of arylamines using trifluoroacetic acid and triphosgene

Article abstract of DOI:10.2174/157017811797249317

A simple and efficient one-pot procedure for trifluoroacetylation of arylamines using trifluoroacetic acid and triphosgene is reported. A mixed trifluoroacetic anhydride generated in situ reacts with a variety of arylamines to give the corresponding trifluroacetamides in high yields.

Full text of DOI:10.2174/157017811797249317

Letters in Organic Chemistry, 2011, 8, 559-561
559
A Simple and Efficient Method for Trifluoroacetylation of Arylamines
Using Trifluoroacetic Acid and Triphosgene
Ki-Jong Hana and Misoo Kim*,b
aDepartment of Molecular Science and Technology, Ajou University, Suwon 442-749, South Korea
bDepartment of Basic Science, Hankyong National University, Ansung 456-749, South Korea
Received April 11, 2011: Revised May 05, 2011: Accepted June 20, 2011
Abstract: A simple and efficient one-pot procedure for trifluoroacetylation of arylamines using trifluoroacetic acid and
triphosgene is reported. A mixed trifluoroacetic anhydride generated in situ reacts with a variety of arylamines to give the
corresponding trifluroacetamides in high yields.
Keywords: Trifluoroacetylation, trifluoroacetamides, trifluoroacetic acid, arylamines, triphosgene.
INTRODUCTION
trifluoroacetamides from their corresponding arylamines
(Scheme 1).
Trifluoroacetylation is an important transformation for
the protection of a number of functional groups in organic
synthesis due to the ease of their removal under mild condi-
tions [1]. Several procedures are reported in the literature for
the trifluoroacetylation of amines using trifluoroacetic anhy-
dride [2], ethyl trifluorothioacetate [3], N-trifluoroacetyli-
midazole [4], N-(trifluoroacetoxy)succinimide [5], 2-
(trifluoroacetyloxy)pyridine [6], ethyl trifluoroacetate [7],
(trifluoroacetyl)benzotriazole [8], poly-phosphoric acid
trimethylsilylester [9], trichloroacetonitrile/triphenylphos-
RESULTS AND DISCUSSION
Various arylamines were converted into trifluoro-
acetamides in the presence of trifluoroacetic acid and
triphosgene in high yields and the results are summarized in
Table 1 [14,15]. Aniline was treated with trifluoroacetic acid,
triphosgene, triethylamine and dichloroemethane as a solvent
to isolate trifluoroacetamide in 95 % yield (entry 1). A vari-
ety of structurally diverse anilines with electron-donating
O
NH2
HN
CF3
CF3CO2H
(Cl3CO)2CO/Et3N
R
R
Scheme 1.
phine [10], and other methods [11]. However, some of the
above reported methods require long reaction times, high
temperatures, and inconvenience in handling the reagents.
There still exists a need for the development of new efficient
and readily available reagents for this conversion.
(entries 2-7) and withdrawing groups (entries 8-12) provided
good yields of the trifluoroacetamides under the same reac-
tion conditions. All the reactions were completed within 20
min at room temperature. The procedure for trifluoroacetyla-
tion of arylamines using trifluoroacetic acid is very clean and
produces high yields of the desired trifluoroacetamides. The
structures of all the products were characterized by their ana-
lytical and spectral (IR, 1H NMR and 13C NMR) data and by
direct comparison with authentic samples [16].
Triphosgene is commercially available as a white solid.
The synthetic utility of triphosgene has been extensively
investigated over the last two decades [12]. However, to the
best of our knowledge, its use for the formation of
trifluoroacetamides has never been reported in the literature.
As part of our research program to develop new synthetic
methodologies using triphosgene [13], we undertook the
study of direct conversion of arylamines to trifluoro-
acetamides. In this Letter, we report a simple and efficient
one-pot trifluoroacetylation for the preparation of
According to our observations, the present method occurs
by in situ generation of a mixed trifluoroacetic anhydride
from trifluoroacetic acid and triphosgene in the presence of
triethylamine [17]. The mixed trifluoroacetic anhydride re-
acts with arylamines to give the trifluoroacetamides.
CONCLUSION
*Address correspondence to this author at the Department of Basic Science,
Hankyong National University, Ansung 456-749, South Korea; Tel: +82-31-
670-5488; Fax: +82-31-670-5499; E-mail: mkim@hknu.ac.kr
In conclusion, we have developed a simple and efficient
one-pot procedure for trifluoroacetylation of arylamines.
1570-1786/11 $58.00+.00
© 2011 Bentham Science Publishers

560 Letters in Organic Chemistry, 2011, Vol. 8, No. 8
Han and Kim
Table 1. One-Pot Trifluoroacetylation of Arylamines
Yielda
Amine
Entry
Product
Time (min)
H
N
NH2
CF3
1
15
95 %
O
Me
Me
H
N
NH2
CF3
2
20
92 %
O
H
Me
NH2
Me
N
CF3
3
4
15
15
94 %
96 %
O
H
N
NH2
CF3
O
Me
Me
H
N
NH2
CF3
5
6
7
15
20
15
96 %
92 %
95 %
O
Ph
Ph
MeO
MeO
H
N
NH2
CF3
O
H
NH2
N
CF3
O
MeO
MeO
H
NH2
N
CF3
8
15
15
15
15
15
95 %
95 %
95 %
95 %
97 %
O
O
Cl
Br
Cl
Br
F
H
N
NH2
NH2
NH2
CF3
CF3
CF3
CF3
9
H
N
10
11
12
O
F
H
N
O
F3C
F3C
H
N
NH2
O
O2N
O2N
aYields refer to isolated products.

Trifluoroacetyltion of Arylamines
Letters in Organic Chemistry, 2011, Vol. 8, No. 8
561
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Typical experimental procedure for the preparation of
trifluoroacetamide: To a stirred solution of trifluoroacetic acid (2
mmol) in CH2Cl2 (10 mL) at 0 oC were added triphosgene (1 mmol)
and triethylamine (10 mmol). And then arylamine (2 mmol) was
added and the reaction mixture was stirred at room temperature un-
til completion. Removal of the solvent by rotary evaporation fol-
lowed by short path silica gel column chromatography purification
using 10 % ethyl acetate in hexane as the mobile phase afforded the
pure product in high yield.
This procedure works well for a variety of arylamines to
produce their corresponding trifluoroacetamides in high
yields. Availability of the reagents, short reaction times, easy
work-up, operations at room temperature make this method a
general and useful method for this transformation.
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