COMMUNICATIONS
more, perrhenic acid could be used as a dehydration catalyst
in the presence of basic nitrogen-containing compounds:
nicotinaldoxime was smoothly dehydrated with the catalyst
system to give 3-cyanopyridine in 84% yield (Table 4,
entry 12).
The applicability of the present protocol to a large-scale
process was then investigated. Complete dehydration of
o-toluamide (100 mmol) and o-methoxybenzaldoxime
(40 mmol) was observed in the presence of aqueous perrhenic
acid (< 1mol%), and the corresponding nitriles were isolated
in high yields [Eqs. (1) and (2)].
clear why trimethylsilylperrhenate is more active than per-
rhenic acid and rhenium(vii) oxide. Pure perrhenic acid has
not been isolated because it exists preferentially as the
dimeric anhydride [O3ReOReO3] under anhydrous condi-
tions,[16] whereas trimethylsilylperrhenate is monomeric.
Therefore, monomeric rhenium(vii) oxo species may be more
active than dimeric or oligomeric complexes.
In conclusion, we have reported herein several noteworthy
features of new catalysts for the dehydration of primary
amides and aldoximes. The reaction proceeds under essen-
tially neutral conditions, and the catalyst is recoverable and
reusable. This protocol can be readily applied to large-scale
processes with high efficiency and selectivity, making it an
economical and environmentally benign process for the
preparation of nitriles.
aqueous [(HO)ReO3] (0.45–0.5 mol%)
(1)
CONH2
(100 mmol)
CN
97% yield
mesitylene (40 mL)
azeotropic reflux, 1 day
Experimental Section
General procedure (Tables 3 and 4):[10] A solution of primary amides
(1mmol) or aldoximes (1mmol), perrhenic acid (65 70 wt% solution in
water, 1.66 mL, 0.009 0.010 mmol, 0.9 1.0 mol%), and solvent (2 mL) was
heated at azeotropic reflux with the removal of water. After several hours,
the mixture was cooled to ambient temperature and saturated aqueous
NaHCO3 (100 mL) was added. After stirring for 10 min, the mixture was
dried over MgSO4, filtered, and concentrated under vacuum. The crude
product was purified by flash column chromatography on silica gel.
OMe
OMe
CN
aqueous [(HO)ReO3] (0.9–1 mol%)
(2)
toluene (20 mL)
azeotropic reflux, 4.5 h
C=NOH
(40 mmol)
91% yield
Based on the reactivities of primary amides and aldoximes
in perrhenic acid catalyzed dehydrations, we propose the
mechanism shown in Scheme 1. The reaction of the substrates
and perrhenic acid leads to six-membered cyclic transition
states A and B (upon dehydration) or to the analogous
transition states A’ and B’ (without dehydration)[3c,d]. Dehy-
dration of primary amides and aldoximes to produce nitriles
Received: March 25, 2002 [Z18977]
[1] a) R. E. Kent, S. M. McElvain, Org. Synth. 1945, 25, 61 ; b) D. T.
Mowry, Chem. Rev. 1948, 42, 189.
[2] a) S. Patai in The Chemistry of Functional Groups: Amides (Ed.: J.
Zabicky), Wiley, New York, 1970; b) R. C. Larock, Comprehensive
Orgaanic Transformations, VCH Publishers, New York, 1989.
[3] a) Y. Watanabe, F. Okuda, Y. Tsuji, J. Mol. Catal. 1990, 58, 87; b) M.-P.
Heck, A. Wagner, C. Mioskowski, J. Org. Chem. 1996, 61, 6486;
c) D. S. Bose, B. Jayalakshmi, J. Org. Chem. 1999, 64, 1713; d) D. S.
Bose, B. Jayalakshmi, Synthesis 1999, 1724; for other dehydration
methods of primary amides, see references in refs. [3b] and [3c].
[4] a) K. Ishihara, S. Ohara, H. Yamamoto, J. Org. Chem. 1996, 61, 4196;
b) K. Ishiahra, S. Ohara, H. Yamamoto, Macromolecules 2000, 33,
3511.
[5] a) K. Ishihara, S. Ohara, H. Yamamoto, Science 2000, 290, 1140; b) K.
Ishihara, M. Nakayama, S. Ohara, H. Yamamoto, Synlett 2001, 1 1 1 7;
c) K. Ishihara, M. Nakayama, S. Ohara, H. Yamamoto, Tetrahedron
2002, in press..
[6] a) K. Ishihara, H. Kurihara, H. Yamamoto, Synlett 1997, 597; b) S.
Saito, T. Nagahara, H. Yamamoto, Synlett 2001, 1690.
Scheme 1. Proposed mechanism for the dehydration of primary amides
and aldoximes to form nitriles.
[7] For isomerization of allylic alcohols or allylic ethers catalyzed by
[(R3SiO)ReO3], see: a) S. Bellemin-Laponnaz, H. Gisie, J. P. Le Ny,
J. A. Osborn, Angew. Chem. 1997, 109, 1011; Angew. Chem. Int. Ed.
Engl. 1997, 36, 976; b) S. Bellemin-Laponnaz, J. P. Le Ny, J. A. Osborn,
Tetrahedron Lett. 2000, 41, 1549.
should be promoted by selective coordination of rhenium(vii)
oxo complexes with their oxygen atoms. On the contrary, the
coordination of the catalyst with the nitrogen atom of primary
amides should give the corresponding imides. Therefore, the
oxophilicity of rhenium(vii) oxo complexes is a significant
factor in obtaining nitriles as major products.[13,14] The high
reactivity of sterically congested aldoximes and the low
reactivity of less hindered aldoximes can be explained
through B or B’, which is generated from a syn isomer of
aldoximes. Syn/anti isomerization of aldoximes is known to
occur under thermal or acidic conditions.[15] Therefore, the
reactivity of aldoximes for dehydration may depend on their
syn/anti equilibrium under the reaction conditions. It is not
[8] For
a Beckmann rearrangement catalyzed by [Bu4NReO4] and
trifluoromethanesulfonic acid, see: a) K. Narasaka, H. Kusama, Y.
Yamasita, H. Sato, Chem. Lett. 1993, 489; b) H. Kusama, Y.
Yamashita, K. Narasaka, Bull. Chem. Soc. Jpn. 1995, 68, 373.
[9] Trimethylsilylperrhenate was purchased from Gelest-Azmax; per-
rhenic acid and rhenium(vii) oxide were purchased from Aldrich.
[10] The catalysts, aqueous [(HO)ReO3] (colorless), and [(Me3SiO)ReO3]
(white), were often recovered as a dark solid by partial reduction to
lower valent rhenium oxides such as [ReO3¥xH2O](black), [ReO2]
(brown), [ReO3] (red), or [Re2O5] (blue). However, the recovered
catalyst was still active for the dehydration. Lower valent rhenium
oxides could be oxidized to perrhenic acid (colorless) or its anhydride
(yellow) by treatment with hydrogen peroxide (35%) at 508C for 12 h
and removal of excess hydrogen peroxide and water under vacuum at
Angew. Chem. Int. Ed. 2002, 41, No. 16
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0044-8249/02/4116-2985 $ 20.00+.50/0
2985