SCHEME 1
Beck m a n n Rea r r a n gem en t of Oxim es
u n d er Ver y Mild Con d ition s
Lidia De Luca, Giampaolo Giacomelli,* and
Andrea Porcheddu
Dipartimento di Chimica, Universita` degli Studi di Sassari,
Via Vienna 2, I-07100 Sassari, Italy
very mild and selective procedure for the quantitative
conversion of ketoximes into the corresponding amides.
The procedure is based on the reaction of a complex
formed by 2,4,6-trichloro[1,3,5]triazine (cyanuric chloride,
TCT), a very inexpensive reagent, and DMF,6 with a
DMF solution of 1 mol equiv of the ketoxime (Scheme
1).7
The complex is easily prepared by dissolving the TCT
in the least volume of commercial DMF at room temper-
ature,8 followed by the addition of the oxime9 in DMF,
after disappearance of free TCT (TLC monitoring). The
mixture is stirred at room temperature for the required
time and then quenched with water. The triazine byprod-
ucts are then removed by aqueous workup. The corre-
sponding amides can be recovered chemically pure in
high yields (Table 1) without any purification.
ggp@uniss.it
Received May 23, 2002
Abstr a ct: A variety of ketoximes, easily prepared from the
corresponding ketones, undergo the Beckmann rearrange-
ment upon treatment with 2,4,6-trichloro[1,3,5]triazine in
N,N-dimethylformamide at room temperature in excellent
yields. This procedure can be applied to aldoximes for
obtaining the corresponding nitriles.
The rearrangement of ketoximes to the corresponding
amide, known as the Beckmann reaction, is a common
method in organic chemistry1 and is a topic of current
interest. It accomplishes in one stroke both the cleavage
of a carbon-carbon bond and the formation of a carbon-
nitrogen bond. It represents a powerful method particu-
larly for manufacturing ꢀ-caprolactam in the chemical
industry. The reaction generally requires high reaction
temperatures and strongly acidic and dehydrating me-
dia.1 Thus, the reaction can lead to large amounts of
byproducts and preclude its application to sensitive
substrates. On these bases milder conditions were tried
and several interesting variants developed.2,3 Recently
the Beckmann rearrangement was reported to occur in
ionic liquids at room temperature.4 Nevertheless until
now the occurrence of mild conditions was related to the
use of rather toxic solvents and expensive reagents or
solvents.
The reaction is reasonably fast (less than 4 h) only with
acetophenone and cyclohexanone oximes and requires
almost 24 h for completion in most of the cases. However,
this method can be successfully applied on a large scale.
Moreover no deoximation of the oximes to carbonyl
compounds occurs.
On examination of Table 1 some observations can be
made. In all cases only one of the two possible amides
were recovered. Contrary to what was observed in most
of the conventional Beckmann rearrangement,1 electron-
donating groups on the aromatic ring seem to reduce the
reaction rate, in particular when the substituent is on
the ortho-para positions (runs 2, 3, and 4). Generally,
migration of an aryl group predominates over that of an
alkyl group. However, in the case of both tert-butyl
phenyl ketone oxime and the oxime of 3,3-dimethylbutan-
2-one (runs 8 and 9) the rearrangement gives rise to
migration of the tert-butyl group. Moreover the results
obtained suggest that the stereochemistry of the oximes
has very little effect on the reaction as in other Beckmann
rearrangements.10
As part of an ongoing program directed to the develop-
ment of efficient reagents for use under mild conditions
and following our latest interest in the use of [1,3,5]-
triazine derivatives in organic synthesis,5 we report a
(1) Gawly, R. E. Org. React. 1988, 35, 1 and references therein.
Smith, M. B.; March, J . In Advanced Organic Chemistry, 5th ed.; J ohn
Wiley & Sons: New York, 2001; p 1415 and references therein.
(2) Arisawa, M.; Yamaguchi, M. Org. Lett. 2001, 3, 311. Kikugawa,
Y.; Tsuji, C.; Miyazawa, E.; Sakamoto, T. Tetrahedron Lett. 2001, 42,
2337. Anilkumar, R.; Chandrasekhar, S. Tetrahedron Lett. 2000, 41,
5427. Sato, H.; Yoshioka, H.; Izumi, Y J . Mol. Catal. A: Chemical 1999,
149, 25. Laurent, A.; J acquault, P.; Di Martino, J . L.; Hamelin, J . J .
Chem. Soc., Chem. Commun. 1995, 1101.
The results obtained with the oximes of cyclic ketones
are noteworthy and indicate a simple and mild approach
to lactams11 which are particularly important molecules
as synthetic intermediates for biologically important
compounds.12 The conversion of the cyclohexanone oxime
(3) Thakur, A. J .; Boruah, A.; Prajapati, D.; Sandhu, J . S. Synth.
Commun. 2000, 30, 2105.
(4) Peng, J .; Deng, Y. Tetrahedron. Lett. 2001, 42, 403. Ren, R. X.;
Zueva, L. D.; Ou, W. Tetrahedron. Lett. 2001, 42, 8441.
(5) (a) Falorni, M.; Porcheddu, A.; Taddei, M. Tetrahedron Lett. 1999,
40, 4395. (b) Falorni, M.; Giacomelli, G.; Porcheddu, A.; Taddei, M. J .
Org. Chem. 1999, 64, 8962. (c) Falchi, A.; Giacomelli, G.; Porcheddu,
A.; Taddei, M. Synlett 2000, 275. (d) De Luca, L.; Giacomelli, G.;
Taddei, M. J . Org. Chem. 2001, 66, 2534. (e) De Luca, L.; Giacomelli,
G.; Porcheddu, A. Org. Lett. 2001, 3, 1519. (f) De Luca, L.; Giacomelli,
G.; Porcheddu, A. Org. Lett. 2001, 3, 3041. (g) De Luca, L.; Giacomelli,
G.; Porcheddu, A. J . Org. Chem. 2001, 66, 7907. (h) De Luca, L.;
Giacomelli, G.; Porcheddu, A. Org. Lett. 2002, 4, 553. (i) De Luca, L.;
Giacomelli, G.; Porcheddu, A. J . Org. Chem. 2002, 67, in press.
(6) (a) Gold, H. Angew. Chem. 1960, 72, 956. (b) Gupton, J . T.; Colon,
C.; Harrison, C. R.; Lizzi, M. J .; Polk, D. E. J . Org. Chem. 1980, 45,
4522.
(7) No reaction was observed operating with solvents different from
DMF, such as dichloromethane or THF. Furthermore, the reaction rate
decrease noticeably operating with a reduced amount of TCT with
respect to the oxime.
(8) No gas evolution (CO2) was noted.
(9) The oximes were either obtained from commercial sources or
prepared by standard procedures. No separation of the E:Z isomer was
made.
(10) Probably the E- and Z-oximes interconvert under the reaction
conditions (see also ref 13).
(11) Evans, P. A.; Modi, D. P. J . Org. Chem. 1995, 60, 6662.
10.1021/jo025960d CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/25/2002
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J . Org. Chem. 2002, 67, 6272-6274