Microwave-promoted trifluoroacetylation of amines with TiO(CF3CO2)2

Article abstract of DOI:10.1039/a807426g

Conversion of amines to their corresponding trifluoroacetamides was performed with TiO(CF₃CO₂)₂ in a conventional microwave oven under solvent-free conditions in excellent yields.

Full text of DOI:10.1039/a807426g

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124 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 124±125$
Microwave-promoted Trifluoroacetylation of Amines
with TiO(CF3CO2)2$
Nasser Iranpoor* and Behzad Zeynizadeh
Chemistry Department, College of Sciences, Shiraz University, Shiraz 71454, Iran
Conversion of amines to their corresponding trifluoroacetamides was performed with TiO(CF3CO2)2 in a conventional
microwave oven under solvent-free conditions in excellent yields.
Protection of primary and secondary amines is important in
organic synthesis1,2 due to their susceptibility to oxidation
and replacement reactions. Conversion of amines into an
amide is the most convenient and widely used method
for protection of amino groups. In this respect, acetylation1
and tri¯uoroacetylation3±7 of amines have been the subject
of many studies. Owing to the ease of removal, use of
tri¯uoroacetyl as a protecting group has found wide appli-
cations in organic synthesis, especially for peptides,8 amino-
sugars9 and steroid glucosides.10,11 The use of tri¯uoroacetic
anhydride for conversion of amines to tri¯uoroacetamides,
apart from the disadvantages of the low boiling point,
volatility, and the corrosive and hygroscopic nature of tri-
¯uoroacetic anhydride, su€ers also from generation of
tri¯uoroacetic acid in the reaction mixture. In the course of
our studies12 on the reactions of TiO(CF3CO2)2,13 it was
observed that TiO(CF3CO2)2 can eciently convert amines
to their corresponding tri¯uoroacetamides using micro-
wave irradiation. Owing to the diculties of using of tri-
¯uoroacetic anhydride for acetylation reactions, we decided
to study the applicability of TiO(CF3CO2)2 as a highly
stable solid, non-hygroscopic and new tri¯uoroacetylating
agent for amines.
When we performed the reaction of aniline with
TiO(CF3CO2)2 under microwave irradiation in the absence
of solvent, only 0.5 mol. equiv. of the reagent was required
to give N-phenyltri¯uoroacetamide in 95% yield after 5 min.
Since the ratio of TiO(CF3CO2)2 to amine in this reaction
was 1:2, tri¯uoroacetic acid was produced and, instead,
TiO2 and water were formed in the reaction. Dramatic
acceleration in the rate of reaction due to microwave
irradiation was established in comparison with conventional
heating. This reaction was completed at 100 8C in a sealed
tube only after 48 h. We therefore studied the conversion of
both primary and secondary amines to their corresponding
tri¯uoroacetamides with this reagent under microwave
irradiation. Di€erent classes of amines were converted to
their corresponding tri¯uoroacetamides with TiO(CF3CO2)2
within 5±15 min in high to excellent yields. The results are
shown in Table 1. In most cases, 0.5 mol. equiv. of the
reagent was enough to complete the reaction, except in
the cases of amines carrying electron-withdrawing groups
Table 1 Microwave-assisted trifluoroacetylation of amines with TiO(CF3CO2)2 under solvent-free conditionsa
Mol. equiv. of
TiO(CF3CO2)2
Entry
1
Substrate
Product
t min
Yield (%)b
97
0.5
5
2
3
0.5
0.5
6
6
96
94
4
0.8
15
85
5
6
7
0.6
0.7
0.5
15
10
5
86
90
93
8
0.5
6
98
9
0.5
0.5
5
97
88
10
10
11
0.7
15
60
aAll reactions were performed with 700 W microwave energy. bYield refers to isolated product.
(Table 1, entries 4±6) and diphenylamine (entry 11) which
required 0.6±0.8 mol. equiv. of the reagent. Owing to the
formation of TiO2 in the reaction mixture, the mechanism in
Scheme 1 is a possibility.
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).

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J. CHEM. RESEARCH (S), 1999 125
We are grateful to Shiraz University Research Council for
partial support of this work and Professor H. Firouzabadi
for discussion and assistance.
Received, 23rd September 1998; Accepted, 23rd October 1998
Paper E/8/07426G
Scheme 1
References
In conclusion, owing to the stability, ease of preparation
and handling and non-hygroscopic nature of TiO(CF3CO2)2,
this compound can be regarded as new bench top reagent
for conversion of amines to tri¯uoroacetamides under
neutral reaction conditions.
1 J. F. W. McOmie, Protective Groups in Organic Chemistry,
Plenum, London and New York, 1973.
2 T. W. Greene and P. G. M. Wuts, Protective Groups in Organic
Synthesis, Wiley, New York, 1991.
3 L. Kisfaludy, T. Mohacsi, M. Low and F. Drexler, J. Org.
Chem., 1979, 44, 654.
4 A. G. M. Barrett and J. C. A. Lana, J. Chem. Soc., Chem.
Commun., 1978, 471.
Experimental
Products were characterized by their IR, NMR and mass spectral
data or comparison with known samples. Infrared spectra were
5 F. Kanai, T. Kaneko, H. Morishima, K. Isshiki, T. Takita,
T. Takeuchi and H. Umezawa, J. Antibiotics (Tokyo), 1985, 38,
39.
recorded on
a Perkin Elmer 781 spectrometer. NMR spectra
were recorded on a Bruker Avance DPX-250. Mass spectra were
recorded on a Shimadzu GCMS-QP 1000 EX. The reactions moni-
toring was accomplished by TLC on silica gel polygram SILG/UV
254 plates or GLC on a Shimadzu GC-10A instrument.
6 G. A. Dilbeck, L. Field, A. A. Gallo and R. J. Gargiulo, J. Org.
Chem., 1978, 43, 4593.
7 D. D. Keith, J. A. Tortora and R. Yang, J. Org. Chem., 1978,
43, 3711.
Typical Procedure for Microwave-assisted Tri¯uoroacetylation of
Aniline with TiO(CF3CO2)2.ÐA mixture of aniline (1 mmol, 0.093 g)
and TiO(CF3CO2)2 (0.5 mmol, 0.145 g) was irradiated with micro-
waves (700 W) for 5 min. The residue was dissolved in CH2Cl2,
dried with anhydrous sodium sulfate and ®ltered. The organic
solvent was evaporated and the crude product was chromato-
graphed on a short column of silica gel using CCl4±CH2Cl2 (3:2) as
eluent. Pure N-phenyltri¯uoroacetamide was obtained in 97% yield
(0.183 g).
8 F. Weygand and E. Frauendorefer, Chem. Ber., 1970, 103, 2437.
9 M. L. Wolfrom and H. B. Bhat, J. Org. Chem., 1967, 32, 1821.
10 H. Newman, J. Org. Chem., 1965, 30, 1287.
11 R. A. Lucas, D. F. Dickel, R. L. Dziemian, M. J. Ceglowski,
B. L. Heusle and H. B. MacPhillamy, J. Am. Chem. Soc., 1960,
82, 5688.
12 N. Iranpoor and B. Zeynizadeh, J. Chem. Res. (S), 1998, 664.
13 P. Sartori, Angew. Chem., 1964, 76, 376.
14 A. Jacques and D. Claude, Bull. Soc. Chim. Fr., 1975, 1933.