Chemistry Letters Vol.34, No.5 (2005)
735
amount of 1-acylimidazole 7a was detected when the reaction
temperature was raised up to the refluxing temperature of tol-
uene (Entry 1). The use of Me2Si(Im)2 3a prepared from a 2:1
molar ratio of 1a and Me2SiCl2 led to an increase in the yield
of 7a although higher reaction temperature was still required
(Entries 2 and 3). On the other hand, several tris(imidazol-1-
yl)alkylsilane derivatives 3b–3d prepared from a 3:1 molar ratio
of 1 and alkyltrichlorosilanes (R2SiCl3) smoothly reacted with 4
at room temperature to afford the corresponding 7 in good yields
(Entries 4–7). The reaction by using tetrakis(imidazol-1-yl)si-
lane [Si(Im)4] 3e prepared from a 4:1 molar ratio of 1a and SiCl4
hardly afforded 7a because of its extremely low solubility (En-
try 8). However, tetrakis(2-methylimidazol-1-yl)silane [Si(2-
Me–Im)4] 3f prepared from a 4:1 molar ratio of 2-methyl-1-tri-
methylsilylimidazole [Me3Si(2-Me–Im)] 1b and SiCl4 readily
reacted with 4 at room temperature to give the corresponding
1-acyl-2-methylimidazole 7b in good yields even when the
amount of 3f was reduced to 0.5 equivalents (Entries 9–11).
Then, the condensation of free carboxylic acids with various
amines was further tried by using BuSi(Im)3 3d or Si(2-Me–Im)4
3f as condensation reagents in THF (Table 2).12 In most cases,
the reactions proceeded smoothly under mild conditions to pro-
vide the corresponding carboxamides in good to high yields. It is
noted that the work-up procedure is quite simple and almost pure
carboxamides are obtained when 3f is used since the by-product
of the reaction is silica [(SiO2)n], which is insoluble in all com-
mon solvents and thereby can be removed easily by filtration.
Thus, novel types of imidazol-1-ylsilanes, particularly tris-
and tetrakis(imidazol-1-yl)silane derivatives, reacted readily
with free carboxylic acids to give the corresponding 1-acylimi-
dazoles, which smoothly underwent the subsequent condensa-
tion with amines to form carboxamides in good to high yields.
Further investigations on the preparation of silicon-containing
heterocycles and their application to various dehydration reac-
tions are now in progress.
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.
References and Notes
1
2
3
M. A. Brook, ‘‘Silicon in Organic, Organometallic, and Polymer
Chemistry,’’ John Wiley & Sons, New York (2000).
H. Vorbruggen, ‘‘Silicon-mediated Transformations of Functional
Groups,’’ Wiley-VCH, Weinheim (2004).
a) W.-C. Chou, M. C. Chou, Y.-Y. Lu, and S.-F. Chen, Tetrahedron
Lett., 40, 3419 (1999). b) R. Peelegata, M. Pinza, and G. Pifferi,
Synthesis, 1978, 614. c) B. D. Harris, K. L. Bhat, and M. M. Joullie,
Synth. Commun., 16, 1815 (1986). d) J. W. Lampe, P. F. Hughes,
C. K. Biggers, S. H. Smith, and H. Hu, J. Org. Chem., 59, 5147
(1994).
4
a) T. H. Chan and L. T. L. Wong, J. Org. Chem., 34, 2766 (1969).
b) I. Azumaya, H. Kagechika, K. Yamaguchi, and K. Shudo, Tetra-
hedron Lett., 37, 5003 (1996).
5
6
7
S. H. van Leeuwen, P. J. L. M. Quaedflieg, Q. B. Broxterman, and
R. J. J. Liskamp, Tetrahedron Lett., 43, 9203 (2002).
E. P. Krysin, V. N. Karel’skii, A. A. Antonov, and G. E.
Rostovskaya, Khim. Prir. Soedin., 1979, 684.
a) H. A. Staab, H. Bauer, and K. M. Schneider, ‘‘Azolides in
Organic Synthesis and Biochemistry,’’ Wiley-VCH, Weinheim
(2004), pp 129–208. b) H. A. Staab, Angew. Chem., Int. Ed. Engl.,
1, 351 (1962). c) T. Kitagawa, H. Kuroda, H. Sasaki, and K.
Kawasaki, Chem. Pharm. Bull., 35, 4294 (1987). d) A. K. Saha,
P. Schultz, and H. Rapoport, J. Am. Chem. Soc., 111, 4856 (1989).
a) L. D. Rowe, R. C. Beier, M. H. Elissalde, L. H. Stanker, and
R. D. Stipanovic, Synth. Commun., 23, 2191 (1993). b) Y. Tanabe,
M. Murakami, K. Kitaichi, and Y. Yoshida, Tetrahedron Lett.,
35, 8409 (1994).
8
9
A. Frenzel, M. Gluth, R. Herbst-Irmer, and U. Klingebiel, J. Orga-
nomet. Chem., 514, 281 (1996).
10 S. Vepachedu, R. T. Stibrany, S. Knapp, J. A. Potenza, and H. J.
Schugar, Acta Crystallogr., C51, 423 (1995).
11 Typical procedure for the preparation of tetrakis-, tris-, and bis(imi-
dazol-1-yl)silane derivatives by a trans-silylation technique is as
follows: a) Si(2-Me–Im)4 3f; To a solution of 1b (7.85 g, 50.9
mmol) in toluene (5 mL) (or without using any solvent) was added
slowly SiCl4 (1.46 mL, 12.7 mmol) at room temperature under ar-
gon. The precipitation of a white solid was observed. After the mix-
ture was stirred at 80 ꢁC for 1 h, the generated Me3SiCl and the sol-
vent were removed under reduced pressure to give a white powder
in almost quantitative yield. The reagent can be handled for brief
periods in the air though it is sensitive to moisture. 1H NMR
(270 MHz, CDCl3) ꢀ 2.09 (s, 12H), 6.84 (s, 4H), 7.18 (s, 4H);
13C NMR (67.8 MHz, CDCl3) ꢀ 15.4, 120.9, 132.3, 149.7; HRMS
(EIþ) calcd for C16H20N8Si [M]þ 352.1580, found m=z 352.1582.
b) MeSi(2-Me–Im)3 3c; Following the procedure used to prepare
3f, reaction was performed between 1b and MeSiCl3 in a 3:1 molar
ratio. 1H NMR (270 MHz, CDCl3) ꢀ 1.38 (s, 3H), 2.29 (s, 9H), 6.50
(s, 3H), 7.07 (s, 3H); 13C NMR (67.8 MHz, CDCl3) ꢀ 0.1, 15.7,
120.8, 131.1, 149.4. c) Me2Si(Im)2 3a;9 Following the procedure
used to prepare 3f, reaction was performed between 1a and
Me2SiCl2 in a 2:1 molar ratio. 1H NMR (270 MHz, CDCl3) ꢀ
0.95 (s, 6H), 6.95 (s, 2H), 7.23 (s, 2H), 7.61 (s, 2H); 13C NMR
(67.8 MHz, CDCl3) ꢀ ꢂ1:8, 119.5, 131.7, 139.7.
Table 2. Preparation of various carboxamides using 3d or 3f
BuSi(Im)3 3d
Method A:
O
(1.2 equiv.)
O
HNR4R5
+
R3
(1.0 equiv.)
OH
R3
NR4R5
Si(2-Me–Im)4 3f
Method B:
(0.6 equiv.)
(1.2 equiv.)
THF, rt
Entry Carboxylic acid
Amine
Method Yielda/%
1
2
3
4
5
A
B
A
B
A
B
A
B
A
B
88
90
70
73
96
92
96
96
53b
71b
Ph(CH2)3NH2
PhCHMeNH2
Ph(CH2)2CO2H PhCH2NHMe
6
7
12 General procedure for the preparation of carboxamides using 3f
(Table 2, Method B); To a stirred suspension of 3f (0.3 mmol) in
THF (1.0 mL) was successively added a carboxylic acid (0.5 mmol)
and a solution of an amine (0.6 mmol) in THF (0.5 mL) at room
temperature. The reaction mixture was stirred for 8–24 h at the
same temperature, followed by the addition of water. Precipitated
silica was filtered 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 afford an almost pure (by 1H NMR and TLC) carbox-
amide.
Piperidine
PhNH2
8
9
10
11
12
13
14
A
B
A
B
71
76
82
87
Ph(CH2)3NH2
PhCO2H
Piperidine
b
aIsolated yield. Reaction was carried out at 50 ꢁC for 6 h.
Published on the web (Advance View) April 22, 2005; DOI 10.1246/cl.2005.734