RuCl3 catalyzed facile conversion of arylalkyl ketoximes to amides

Article abstract of DOI:10.1081/SCC-200030648

A variety of aromatic ketoximes undergo Beckmann rearrangement upon treatment with a catalytic amount of RuCl₃ in refluxing acetonitrile to furnish the corresponding amides in excellent yield and high selectivity.

Full text of DOI:10.1081/SCC-200030648

This article was downloaded by: [University of Saskatchewan Library]
On: 03 October 2012, At: 05:54
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T
3JH, UK
Synthetic Communications:
An International Journal
for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
RuCl3 Catalyzed Facile
Conversion of Arylalkyl
Ketoximes to Amides
Surya Kanta De a
a Department of Medicinal Chemistry and
Molecular Pharmacology, Purdue University, West
Lafayette, Indiana, 47907, USA
Version of record first published: 12 Jan 2011.
To cite this article: Surya Kanta De (2004): RuCl3 Catalyzed Facile Conversion of
Arylalkyl Ketoximes to Amides, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 34:18, 3431-3434
To link to this article: http://dx.doi.org/10.1081/SCC-200030648
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study
purposes. Any substantial or systematic reproduction, redistribution,
reselling, loan, sub-licensing, systematic supply, or distribution in any form
to anyone is expressly forbidden.

The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should
be independently verified with primary sources. The publisher shall not
be liable for any loss, actions, claims, proceedings, demand, or costs or
damages whatsoever or howsoever caused arising directly or indirectly in
connection with or arising out of the use of this material.

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 18, pp. 3431–3434, 2004
RuCl3 Catalyzed Facile Conversion
of Arylalkyl Ketoximes to Amides
*
Surya Kanta De
Department of Medicinal Chemistry and Molecular Pharmacology,
Purdue University, West Lafayette, Indiana, USA
ABSTRACT
A variety of aromatic ketoximes undergo Beckmann rearrangement upon
treatment with a catalytic amount of RuCl3 in refluxing acetonitrile to
furnish the corresponding amides in excellent yield and high selectivity.
Key Words: Amides; Ketoximes; Rearrangement.
The acid-mediated isomerization of ketoximes to the corresponding
amides, known as the Beckmann reaction, is a common method in
organic chemistry[1] and a topic of current interest. The rearrangement pro-
ceeds through antimigration and is usually stereospecific. The classical
Beckmann rearrangement[2] requires an excess or stoichiometric amount
of strong protic acids (such as sulfuric acid, phosphoric acid) or strong
*
Correspondence: Surya Kanta De, Department of Medicinal Chemistry and Molecular
Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
3431
DOI: 10.1081/SCC-200030648
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

3432
De
Lewis acids, which cause formation of a large amount of by-products and
serious corrosion problems.[1] Recently, this reaction has been studied with
various modified reagents,[3] solid acid catalysts such as metal oxides,
clay,[4] and zeolites.[5] However, most of these reactions are under vapor
phase conditions and proceed in a rather sluggish manner. The preparation
procedures for these catalysts often involves various tedious steps, such as
precipitation, ion exchange, hypothermal treatment, and prolonged acti-
vation time at higher temperature, and reproducibility is another problem.
On these bases, milder conditions were tried and several variants such as
chloral,[6] solid metaboric acid[7] developed, and these reactions were per-
formed at higher temperature. Until now, only a few methods were avail-
able for the conversion of ketoximes to amides under mild and catalytic
conditions. Thus, there is still a need to develop a new and facile procedure
for preparation of amides from ketoximes. Most recently, I have reported[8]
that ruthenium chloride is a mild Lewis acid for the acetylation of alcohols.
In this paper I wish to report that ruthenium chloride is a mild reagent for
the conversion of aromatic ketoximes to amides.
Treatment of acetophenone oxime with a catalytic amount of RuCl3 in
refluxing acetonitrile afforded acetanilide in 95% yield. Similarly, several
ketoximes converted to the corresponding amides in high yields. Thus, I
developed a new method for conversion of aromatic ketoximes to amides
using a catalytic amount of ruthenium chloride. Furthermore, aliphatic
oximes required longer reaction times and high temperatures (1108C) to
give low yields. It may be explained by steric or electronic factors, since it
is known that substitution of an electron-donating group on the aromatic
ring facilitates the reaction.
On examination of Table 1 some observations can be made. In all cases
only one of the two possible amides were obtained. Simple and electron-
rich aryl-ketoximes gave excellent yields in a short time, whereas nitro-
substituted acetophenone oximes took a longer time. Generally, migration
of an aryl group predominates over that of an alkyl group. The experimental
procedure is very simple and more convenient and has the ability to tolerate a
variety of substrates. This method can be successfully applied on a large scale.
The conversions were clean and no deoximation of ketoximes to ketones was
observed. Moreover, the results obtained suggest that the stereochemistry of
oximes has very little effect as in other Beckmann rearrangements.[9] Possibly
the E- and Z-oximes interconverted under the reaction conditions, since all
oximes used were prepared by standard procedure and no separation of E
and Z was made.
In conclusion, I have developed a novel and practical method for the con-
version of aromatic ketoximes to amides using a catalytic amount of ruthe-
nium chloride in excellent yield with high selectivity.

RuCl3 Catalyzed Facile Conversion of Arylalkyl Ketoximes to Amides
3433
Table 1. RuCl3 catalyzed conversion of ketoximes to amides.
Product
Yield (%)
Time (h)
mp (8C)
lit. mp (8C)a
2a
2b
2c
2d
2e
2f
905
91
80
84
72
72
92
75
87
52
48
2.5
1.5
2
114–115
164–166
209–210
178–179
215–216
147–149
125–126
132–134
104–106
37–39
112–113
161–165
208–209
175–176
217–218
147–148
128–129
133–135
103–105
39–40
3
5
8
2g
2h
2i
1.5
4
2
2j
2k
8b
9b
70–72
71–73
aAll these amides are known and commercially available from Aldrich Chemical Co.
bCarried out in toluene as solvent.
EXPERIMENTAL
All products are known compounds and were identified by comparison of
their spectral data and physical properities with those of authentic samples.
The progress of reaction was monitored by thin-layer chromatography on
silica gel. All yields refer to isolated products.
General Procedure for the Conversion of Ketoximes to Amides
A mixture of substrate (1 mmol) and ruthenium chloride trihydrate
(10 mol%) in acetonitrile (10 mL) was refluxed for the specified time
Scheme 1. (a) R ¼ Me, R1 ¼ C6H5 (b) R ¼ R1 ¼ C6H5 (c) R ¼ Me, R1 ¼ o-HOC6H4
(d) R ¼ Me, R1 ¼ p-ClC6H4 (e) R ¼ Me, R1 ¼ p-NO2C6H4 (f) R ¼ Me, R1 ¼ m-
NO2C6H4 (g) R ¼ Me, R1 ¼ p-CH3OC6H4 (h) R ¼ Me, R1 ¼ 2-naphthyl (i)
R ¼ CH2CH3, R1 ¼ C6H5 (j) R ¼ R1 ¼ 2(CH2)4– (k) R ¼ R1 ¼ –(CH2)5–.

3434
De
(Table 1). After completion of reaction thin layer chromatography (TLC),
solvent was removed in vacuo and the residue was purified by short-column
filtration over silica gel (hexane :
ethyl acetate, 7 : 3) to afford pure product in good to excellent yields. I have
also observed that both ruthenium chloride trihydrate and commercially avail-
able anhydrous ruthenium chloride gave similar results. Less than 10 mol%
catalyst (1 to 5 mol%) can be converted the ketoximes to amides in some
cases but required longer time to give the comparable yield.
REFERENCES
1. (a) Gawley, R.E. Org. React. 1988, 35, 26; (b) Smith, M.B.; March, J. In
Advanced Organic Chemistry, 5th Ed.; John Wiley and Sons: New York,
2001; 1415.
2. (a) Beckmann, E. Chem. Ber. 1886, 19, 988; (b) Izumi, Y.; Sato, S.;
Urabe, K. Chem. Lett. 1983, 1649.
3. (a) Jung, M.E.; Zeng, L.M. Reactions of oximes with trimethylsilyl iodide:
dehydration and rearrangements. Trimethylsilyl polyphosphate, a useful
reagent for the Beckmann rearrangement. Tetrahedron Lett. 1983, 24,
4533; (b) Imamato, H.; Yokoyama, H.; Yokoyama, M. Tetrahedron Lett.
1981, 22, 1803; (c) Kamijo, T.; Harada, H.; Lizuka, K. Chem. Pharm.
Bull. 1984, 32, 2560.
4. (a) Meshram, H.M. Clay-catalyzed facile Beckmann rearrangement of
ketoximes. Synth. Commun. 1990, 20, 3253; (b) Pai, S.G.; Bajpai, A.R.;
Deshpande, A.B.; Samant, S.D. Beckmann rearrangement of substituted
diaryl ketoximes using FeCl3 impregnated montmorrilonite K10. Synth.
Commun. 1997, 27, 379.
5. (a) Kath, H.; Glaser, R.; Weitkamp, J. Beckmann rearrangement of cyclo-
hexanone oximes on MF1-type zeolites. Chem. Eng. Technol. 2001, 24, 2;
(b) Camblor, M.A.; Corma, A.; Garquimica, U.P. J. Catal. 1988, 177, 267.
6. Chandrasekhar, S.; Gopalaiah, K. Beckmann reaction of oximes catalyzed
by chloral: mild and neutral procedures. Tetrahedron Lett. 2003, 44, 755.
7. Chadrasekhar, S.; Gopalaiah, K. Beckmann rearrangement of ketoximes on
solid metaboric acid: a simple and effective procedure. Tetrahedron Lett.
2002, 43, 2455.
8. De, S.K. Ruthenium(III) chloride catalyzed acylation of alcohols, phenols,
thiols, and amines. Tetrahedron Lett. 2004, 45, 2919.
9. Chakraborti, J.K.; Hotten, T.M. J. Chem. Soc., Chem. Commun. 1972,
1226.
Received in the USA May 27, 2004