Chemistry Letters Vol.34, No.12 (2005)
1587
Table 2. Preparation of carboxamides by using Si[OCH-
(CF3)2]4
Table 3. Preparation of perfluoroalkyl esters
Base
O
O
(1.0 equiv.)
Si[OCH(CF3)2]4
+
Si(OR')4
O
O
(1.0 equiv.)
THF, rt, 24h
Ph
OH
Ph
OR'
HNR2R3
+
R1
OH
THF, rt
R1
NR2R3
3
1a
(1.0 equiv.)
4a: R' = CH2CF3
4c: R' = CH(CF3)2
(1.0 equiv.)
1
2
(1.0 equiv.)
(1.2 equiv.)
Entry
Tetraalkoxysilane
Base
Yielda/%
Entry Carboxylic acid
Amine
Yielda/%
1
2
3
4
5
Si(OCH2CF3)4
Si(OCH2CF3)4
Si(OCH2CF3)4
Si[OCH(CF3)2]4
Si[OCH(CF3)2]4
none
Et3N
DMAP
Et3N
DMAP
N.D.
93
91
N.D.
83
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Ph(CH2)2CO2H 1a PhCH2NH2 2a
92
86
91
83
92
97
85
90
90
89
81
56b
72
81
1a
1a
1a
1a
PhCHMeNH2 2b
Ph(CH2)3NH2 2c
PhCH2NHMe 2d
Piperidine
PhNH2
2a
2e
2f
6
7
Si(OMe)4
Si(OMe)4
Et3N
DMAP
N.D.
N.D.
1a
PhCHMeCO2H 1b
1b
c-C6H11CO2H 1c
1c
t-BuCO2H
1d
PhCO2H
1e
aIsolated yield.
2f
2a
2f
2a
2f
2a
2f
1,1,1,3,3,3-hexafluoro-2-propanol (bp 58 ꢁC) can be easily re-
moved in vacuo.
1d
1e
This study was supported in part by the Grant of the 21st
Century COE Program from Ministry of Education, Culture,
Sports, Science and Technology (MEXT), Japan.
aIsolated yield. bReaction was carried out at 50 ꢁC for 10 h.
References and Notes
a) H. Vorbruggen, ‘‘Silicon-mediated Transformations of Functional
¨
1
accompanying the undesired by-products, 1,1,1,3,3,3-hexa-
fluoro-2-propyl esters, even when 1-phenylmethylamine 2b
was used (Entry 10).
Groups,’’ Wiley-VCH, Weinheim (2004). b) W.-C. Chou, M. C. Chou,
Y.-Y. Lu, and S.-F. Chen, Tetrahedron Lett., 40, 3419 (1999). c) R.
Peelegata, M. Pinza, and G. Pifferi, Synthesis, 1978, 614. d) B. D. Harris,
K. L. Bhat, and M. M. Joullie, Synth. Commun., 16, 1815 (1986). e) J. W.
Lampe, P. F. Hughes, C. K. Biggers, S. H. Smith, and H. Hu, J. Org.
Chem., 59, 5147 (1994). f) T. H. Chan and L. T. L. Wong, J. Org. Chem.,
34, 2766 (1969). g) I. Azumaya, H. Kagechika, K. Yamaguchi, and
K. Shudo, Tetrahedron Lett., 37, 5003 (1996). h) S. H. van Leeuwen,
P. J. L. M. Quaedflieg, Q. B. Broxterman, and R. J. J. Liskamp, Tetra-
hedron Lett., 43, 9203 (2002).
Several examples of the formation of carboxamides 3 by
using Si[OCH(CF3)2]4 as a dehydrating reagent are listed in
Table 2.6 In all cases, the undesired by-products, 1,1,1,3,3,3-
hexafluoro-2-propyl esters, were not detected at all and the con-
densation reactions proceeded to form the corresponding carbox-
amides 3 in good to high yields at room temperature even when a
weak nucleophile such as aniline 2f was used (Entries 6, 8, 10,
and 14).
Based on the above results, tetrakis(perfluoroalkoxy)silanes
were also applied to the direct transformation of carboxylic acid
1a into the corresponding perfluoroalkyl esters (Table 3). When
the reaction of 1a with Si(OCH2CF3)4 in THF at room temper-
ature was carried out in the presence of bases such as triethyl-
amine or 4-(dimethylamino)pyridine (DMAP), the desired
2,2,2-trifluoroethyl ester 4a was obtained in high yield (Entries
2 and 3). Similarly, the reaction of 1a with Si[OCH(CF3)2]4 pro-
ceeded smoothly to form the corresponding 1,1,1,3,3,3-hexa-
fluoro-2-propyl ester 4c in 83% yield when DMAP was used
as a base (Entry 5). On the other hand, it was shown that the
simple tetraalkoxysilane such as Si(OMe)4 was not reactive
enough to promote the transformation of 1a at room temperature
(Entries 6 and 7).
Thus, an effective dehydrating reagent, Si[OCH(CF3)2]4,
was easily prepared from commercially available SiCl4 and
1,1,1,3,3,3-hexafluoro-2-propanol, and was used conveniently
for the preparation of various carboxamides from carboxylic
acids and amines in good to high yields under mild conditions.
It is noted that the simple work-up procedure is one of the advan-
tages of the present reaction, and the desired carboxamides are
obtained in almost pure form since the co-products of the reac-
tion are silica [(SiO2)n] and 1,1,1,3,3,3-hexafluoro-2-propanol.
Thus formed silica can be removed by filtration, and also
2
3
T. Tozawa, Y. Yamane, and T. Mukaiyama, Chem. Lett., 34, 734 (2005).
T. Tozawa, Y. Yamane, and T. Mukaiyama, Chem. Lett., 34, 1334
(2005).
4
a) C. H. Froberger, J. Org. Chem., 25, 311 (1960). b) K. C. Kumara
Swamy, V. Chandrasekhar, J. J. Harland, J. M. Holmes, R. O. Day,
and R. R. Holmes, J. Am. Chem. Soc., 112, 2341 (1990). c) K. S.
Mazdiyasni, B. J. Schaper, and L. M. Brown, Inorg. Chem., 10, 889
(1971).
5
Si[OCH(CF3)2]4 was prepared according to a slight modification of
Mazdiyasni’s procedure.4c Sodium (4.0 g, 175 mmol) was dissolved
carefully in 80 mL of 1,1,1,3,3,3-hexafluoro-2-propanol under argon
with stirring. After the solution was cooled to 0 ꢁC, SiCl4 (5.0 mL,
43.7 mmol) was added slowly, then the precipitation of a white solid
was observed. The mixture was kept 0.5 h at room temperature, and then
was refluxed for 4 h. After cooling to room temperature, the mixture was
allowed to stand overnight and filtered. The filtrate was evaporated and
the crude product was purified by distillation (57–58 ꢁC/15 mmHg) to
give Si[OCH(CF3)2]4 (16.0 g, 53%). This reagent can be stored for a
long time within a sealed bottle at room temperature. 1H NMR (270
MHz, neat) ꢀ 4.68 (brs, 4H); 13C NMR (67.8 MHz, neat) ꢀ 122.3 (q,
1JðC, FÞ ¼ 280 Hz), 73.4 (septet, 2JðC, FÞ ¼ 36:3 Hz); Tetramethyl-
silane was used as an internal standard.
6
General procedure for the preparation of carboxamides by using
Si[OCH(CF3)2]4 (Table 2); To a stirred solution of Si[OCH(CF3)2]4
(0.5 mmol) in THF (0.6 mL) were successively added a carboxylic acid
(0.5 mmol) and a solution of an amine (0.6 mmol) in THF (0.6 mL) at
room temperature. The reaction mixture was stirred for 24 h at the same
temperature, followed by the addition of water. Precipitated silica was
filtered off and washed with EtOAc, and then the filtrate was extracted
with EtOAc. The organic layer was washed with 1 M HCl aq, saturated
NaHCO3 aq, and brine, dried over anhydrous Na2SO4. After filtration,
the solvent was removed under reduced pressure to give a carboxamide
in almost pure form.
Published on the web (Advance View) October 27, 2005; DOI 10.1246/cl.2005.1586