Improved procedures for the Beckmann rearrangement: The reaction of ketoxime carbonates with boron trifluoride etherate

Article abstract of DOI:10.1016/S0040-4039(00)00875-3

A variety of ketoxime ethyl carbonates-easily prepared from the oximes and ethyl chloroformate-undergo the Beckmann rearrangement upon treatment with 1 equivalent of boron trifluoride etherate, in dichloromethane solution at room temperature in excellent yields (generally 75-99%). (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00875-3

Tetrahedron Letters 41 (2000) 5427±5429
Improved procedures for the Beckmann rearrangement:
the reaction of ketoxime carbonates with boron
tri¯uoride etherate
R. Anilkumar and Sosale Chandrasekhar*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Received 28 April 2000; accepted 23 May 2000
Abstract
A variety of ketoxime ethyl carbonatesÐeasily prepared from the oximes and ethyl chloroformateÐ
undergo the Beckmann rearrangement upon treatment with 1 equivalent of boron tri¯uoride etherate, in
dichloromethane solution at room temperature in excellent yields (generally 75±99%). # 2000 Elsevier
Science Ltd. All rights reserved.
Keywords: Beckmann rearrangement; boron tri¯uoride; ethyl chloroformate; oxime carbonates.
The Beckmann rearrangement is a venerable reaction that has not only shaped the develop-
ment of both synthetic and mechanistic organic chemistry, but also remains a topic of current
interest.1,2 It accomplishes in one stroke both the cleavage of a carbon±carbon bond and the
formation of a carbon±nitrogen bond; and the speci®city that obtains vis-a-vis both the oxime
geometry and the con®guration at the migrating centre enhances its value. Classically, the reac-
tion was e€ected in strongly acidic and dehydrating media, thus precluding its application to
sensitive substrates. Milder conditions, of course, were sought, and several interesting variants
developed.1,2 These essentially focused on forming activated oxime derivatives (e.g. the sulphonate
esters) which were found to rearrange under relatively mild conditions. However, a drawback in
such methods is the inherent instability of the activated oximes, the use of rather toxic solvents
(e.g. pyridine), expensive reagents (e.g. the Mitsunobu reagent), etc.;1,2 all these diculties preclude
scale-up to larger batches. There is, therefore, a need for relatively simple and mild conditions for
the Beckmann rearrangement, and the present studies were thus directed.
In fact, a consideration of the mechanism of the Beckmann rearrangement uncovers the following
intriguing possibility: since the nucleofuge and the migrating group are mutually anti, a nucleo-
fuge carrying a remote nucleophilic moiety should also be able to assist the migration process via
* Corresponding author. Fax: +91 80 3600 529; e-mail: sosale@orgchem.iisc.ernet.in
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00875-3

5428
coordination to the developing cationic centre, as shown in the putative transition state 1
(Scheme 1). A very simple system in which such interactions are feasible is that of the oxime
carbonate, in which the oxygen atom of the alkoxy group can coordinate as suggested above (2).
Interestingly, the Beckmann rearrangement of oxime carbonates3 was apparently unknown, and
so a detailed study was initiated.
Scheme 1.
A variety of ketoximes 3 was converted to the corresponding ethyl carbonates 4 relatively
simply and in high yields (generally 90±99%), via treatment with ethyl chloroformate in dichloro-
methane solution, in the presence of 1 equivalent of pyridine at room temperature. Treatment of
the oxime ethyl carbonates 4 thus obtained with 1 equivalent of boron tri¯uoride diethyl etherate
in dichloromethane solution, e€ected the Beckmann rearrangement at room temperature (with
one exception). The reaction times varied from 4±18 h, and the yields of the amide or lactam
products 5 from 70±99% (with one exception, Table 1). Although the reaction was originally
envisaged as being catalytic in boron tri¯uoride etherate, it was found that a minimum of 1
equivalent was required for complete conversion: the most likely explanation is its complexation
with the immediate product of the rearrangement (the iminol carbonate, possibly to form the
chelate 6)Ðwhich, of course, leaves it unavailable for the rearrangement itself.
It was also determined that benzophenone oxime acetate also undergoes the Beckmann rear-
rangement but rather sluggishly, upon treatment with boron tri¯uoride etherate under the above
conditions: this con®rms the little literature precedent that does exist.4 6 Of course, this lends
credence to the coordination-assisted transition state 2 envisaged above in the case of the carbonates.
In summary, a set of very mild reaction conditionsÐwith the added virtue of simplicityÐhas
been developed for a two-step process for the Beckmann rearrangement. Further work is planned
to extend the above results.

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Table 1
The Beckmann rearrangement of the ketoxime carbonates 4a to the amides/lactams 5
Acknowledgements
CSIR and UGC (New Delhi) are thanked for generous ®nancial support.
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