Solvent-free and one-step Beckmann rearrangement of ketones and aldehydes by zinc oxide

Article abstract of DOI:10.1055/s-2002-31964

In the presence of zinc oxide and without any additional organic solvents, Beckmann rearrangement of several ketones and aldehydes were performed in good yields.

Full text of DOI:10.1055/s-2002-31964

PAPER
1057
Solvent-Free and One-Step Beckmann Rearrangement of Ketones and
Aldehydes by Zinc Oxide
Solvent-Free
O
ne
-
a
Step Beckm
s
ann Rea
r
h
rangement em Sharghi,* Mona Hosseini
Department of Chemistry, College of Science, Shiraz University, Shiraz 71454, I.R. Iran
E-mail: sharghi@chem.susc.ac.ir
Received 28 January 2002; revised 18 April 2002
and selectivity were obtained for the transformation of cy-
clohexanone into -caprolactam (Scheme).
Abstract: In the presence of zinc oxide and without any additional
organic solvents, Beckmann rearrangement of several ketones and
aldehydes were performed in good yields.
Key words: zinc oxide, Beckmann rearrangement, oxime, alde-
hyde, ketone
Recently considerable attention has been paid to solvent-
free reactions.1,2 These reactions are not only of interest
from an environmental point of view, but in many cases
also offer considerable synthetic advantages in terms of
yield, selectivity and simplicity of the reaction procedure.
Scheme
The Beckmann rearrangement is a fundamental and useful
reaction, long recognized as an extremely valuable and
versatile method for the preparation of amides or lactams,
and often employed even in industrial processes.3 The
conventional Beckmann rearrangement usually requires
the use of strong Brönsted or Lewis acids, i.e. concentrat-
ed sulfuric acid, phosphorus pentachloride in diethyl
ether, hydrogen chloride in acetic anhydride, causing
large amounts of byproducts and serious corrosion prob-
lems.4
For each Beckmann rearrangement reaction, the ketone or
aldehyde, hydroxylamine hydrochloride and ZnO were
mixed throughly. Then the mixture was heated in an oil
bath at 140–170 °C; there was no requirement for any oth-
er additional solvent. The experimental results are sum-
marized in Table 1.
The Beckmann rearrangement of symmetrical ketones
proceed effectively to afford the corresponding amides in
good to excellent yields (entries 1–3, Table 1). In the case
of unsymmetrical ketones the reaction was selective and
one of the two possible amides was produced (entries 4,5
Table 1).
In the present method, as shown in Table 1, aromatic and
aliphatic aldehydes were converted to the corresponding
amides in good yields. According to Table 1, aldehydes
gave only the primary amides. The Beckmann rearrange-
ment is generally suggested to proceed through anti mi-
gration, wherein, the Z-forms of oximes are expected to
give the corresponding amides.
We have also found that various types of aldehydes in the
presence of ZnO were condensed cleanly, rapidly and se-
lectively with hydroxylamine hydrochloride at 80 °C in
5–15 min to afford the corresponding Z-isomer of the
oximes (OH syn to aryl) in excellent yields. Only a small
amount of E-isomer, i.e. ca. 10–20% was obtained. These
results are summarized in Table 2 and can be compared
with our previous work.13
Although a large number of vapour-phase Beckmann re-
arrangement processes have been reported, low selectivity
for -caprolactam and rapid decay of activity generally re-
sulted because of high reaction temperatures.4–7 Liquid-
phase catalytic rearrangement under milder conditions,
can afford high selectivity, in which solvent plays an im-
portant role.8 A relatively large amount of organic solvent
such as DMF,9,10 however, was needed, which would
cause environmental problems due to volatility and toxic-
ity. Relatively few solid-phase methods have been devel-
11
oped and very few methods are available for one-step
Beckmann rearrangement of aldehydes and ketones.12
Therefore, there still exists a need for novel and facile
methods for efficient conversion of ketones and aldehydes
into the corresponding amides via Beckmann rearrange-
ment. Our new approach reported herein involves the use
of the cheap and commercially available ZnO in the ab-
sence of solvent as catalyst for Beckmann rearrangement
of several ketones and aldehydes. Satisfactory conversion
It is interesting to note that the yield were obviously re-
duced when meta-substituted aromatic aldehydes were
used (entries 11,14 and 17, Table 1). Schofield and his co-
workers14 have shown that the rates of rearrangement for
meta-substituted aromatic oximes were lower than the
para- and ortho-substituted ones in 98.2% sulfuric acid at
80 °C.
Synthesis 2002, No. 8, 04 06 2002. Article Identifier:
1437-210X,E;2002,0,08,1057,1060,ftx,en;Z02502SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

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H. Sharghi, M. Hosseini
PAPER
Table 1 Beckmann Rearrangement of Ketones and Aldehydes into Amides by ZnO
a
Entry
Substrate
Time/Temp. Product
(h/°C)
1H NMR,
IR (KBr) (Lit.)
Mp
Yieldb
(%)
CONH (Lit.)
(Lit.18,19
)
1
1/140
8.1
3346 (NH), 1657 (C=O)
(3345, 165719)
156
(163)
95
(8.119)
2
3
1/150
7.4
3212 (NH), 1658 (C=O)
(3212, 165819)
30
85
(7.419)
(30)
1/150
6.9
3231 (NH), 1663 (C=O)
(3231, 166319)
69
(67)
83
(6.919)
4
5
1/140
1/140
7.79
3297 (NH), 1665 (C=O)
(3297, 166519)
156
90
85
(7.7918,19
)
(157)
(7.818)
3296 (NH),1662 (C=O)
(3298, 166418)
150
(151)
6
7
8/170
8/170
n.r.c
n.r.c
–
–
–
–
–
–
–
–
8
9
1/140
3/140
1/140
6.2
3385, 3190 (NH2), 1665
(C=O)
132
86
60
90
(6.2619)
(132.5)
(3385, 3190, 166519)
6.45
3340, 3140 (NH2), 1640
(C=O)
140
(142.4)
(6.519)
(3340, 3140, 164019)
10
5.97
3333, 3226 (NH2), 1660
(C=O)
178
(179)
(7.515)b
(3333, 3226, 166715)
11
12
8/170
1/140
6.4
3340, 3180 (NH2), 1550
(C=O)
135
70
75
(7.618)b
(135.5)
(3361, 3182, 155018)
5.85
3140, 3210 (NH2), 1650
(C=O)
162
(162)
(5.8519)
(3140, 3210, 165019)
13
14
2/140
7/170
6.02
3420,3210 (NH2), 1685
(C=O)
140
80
70
(7.015)b
(142)
(3397, 3191, 165318)
6.4
3340, 3180 (NH2), 1550
(C=O)
170
(170)
(7.015)
(3361, 3182, 155015)
15
3/150
7.00
3420, 3210 (NH2), 1685
(C=O)
142
(147)
60
(7.515)
(3443, 3168, 167115)
Synthesis 2002, No. 8, 1057–1060 ISSN 0039-7881 © Thieme Stuttgart · New York

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Solvent-Free One-Step Beckmann Rearrangement
1059
Table 1 Beckmann Rearrangement of Ketones and Aldehydes into Amides by ZnO (continued)
a
Entry
Substrate
Time/Temp. Product
(h/°C)
1H NMR,
IR (KBr) (Lit.)
Mp
Yieldb
(%)
CONH (Lit.)
(Lit.18,19
)
16
1/140
6.12
3343, 3168 (NH2), 1671
(C=O)
160
(160)
90
(7.515)b
(3343, 3168, 167119)
17
18
9/170
7.22
3377, 3197 (NH2), 1651
(C=O)
95
70
80
(6.618)
(97)
(3377, 3197, 165118)
3/140
5.34
3360, 3180 (NH2), 1630
(C=O)
113
(114.8)
(6.718)b
(3366, 3184, 163418)
a Solvent: DMSO-d6–TMS.
b Isolated yields.
c n.r. = no reaction.
Table 2 Convertion of Aldehydes to Oximes in the Presence of ZnO
Entry
R
Time (min)
Yield (%)a
1H NMR, Ha13 Mp of a (Lit.)
a
b
1
p-MeC6H4
p-OHC6H4
p-ClC6H4
p-MeOC6H4
m-MeC6H4
m-OHC6H4
m-ClC6H4
m-MeOC6H4
o-OHC6H4
o-ClC6H4
Ph
5
5
90
10
8.49
8.07
8.12
8.00
8.13
8.09
8.11
8.10
8.22
8.57
8.17
72 (8015)
94 (7215)
2
90
10
3
5
90
10
146 (14516)
132 (13316)
56 (6015)
4
10
15
15
15
15
5
90
10
5
80
20
6
80
20
90 (9015)
7
80
20
100 (10015)
110 (11215)
63 (6315)
8
80
20
9
>98
>98
85
trace
trace
15
10
5
103 (10017)
125 (12816)
11
5
a Isolated yields.
b Solvent: DMSO-d6–TMS.
Finally, ZnO as catalyst, is remarkably easy to use, non- Beckmann Rearrangement; General Procedure
The appropriate ketone or aldehyde (1 mmol), NH2OH HCl (0.3 g,
4.3 mmol) and ZnO (0.16 g, 2 mmol) were mixed sufficiently. Then
the mixture was charged into a 10 mL round-bottomed flask
equipped with a magnetic stirrer and heated in an oil bath at 140–
170 °C; there was no requirement for any other additional solvent.
At the end of the reaction (see Table 1), the resulting mixture was
extracted with EtOAc (2 5 mL) and filtered to remove ZnO. The
solvent was removed in vacuo to give the product which was recrys-
hazardous, inexpensive for use in Beckmann rearrange-
ment. Also, the present procedure not only has the
chemical, economical and environmental advantages of
solvent-free reactions but also constitutes a method to pre-
pare directly amides in good yields from the correspond-
ing aldehydes and ketones without the previous need to
prepare the aldo- and ketoximes.
Synthesis 2002, No. 8, 1057–1060 ISSN 0039-7881 © Thieme Stuttgart · New York

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H. Sharghi, M. Hosseini
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tallized from a suitable solvent or purified by column chromatogra-
phy (EtOAc–hexane). All of the products are known and gave
satisfactory physical data compared with those of authentic samples
(Table 1).
(5) Ko, Y.; Kim, M. H.; Kim, S. J.; Seo, G.; Kim, M. Y.; Uh, Y.
S. Chem. Commun. 2000, 829.
(6) Dai, L. X.; Koyama, K.; Miyamoto, M.; Tatsumi, T. Appl.
Catal. A: Gen. 1999, 189, 237.
(7) Ushikubo, T.; Wada, K. J. Catal. 1994, 148, 138.
(8) Nguyen, M. T.; Raspoet, G.; Vanquickenborn, L. G. J. Am.
Chem. Soc. 1997, 119, 2552.
Preparation of Aldoximes in the Presence of ZnO; General Pro-
cedure
NH2OH HCl (0.3 g, 4.3 mmol) was added to a stirred mixture of
ZnO (0.16 g, 2 mmol) and aldehyde (1 mmol) at 80 °C in an oil bath.
The progress of the reaction was monitored by TLC. After complete
disappearance of the starting material (see Table 2), the mixture was
washed with CH2Cl2 (2 10 mL) and H2O (2 50 mL). The organ-
ic layer was dried (Na2SO4) and evaporated to give the oxime. The
products were identified by comparison of their physical data with
those prepared in accordance with the literature procedures
(Table 2).
(9) Sato, H.; Yoshioka, H.; Izumi, Y. J. Mol. Catal A: Chem.
1999, 149, 25.
(10) Izumi, Y. Chem. Lett. 1990, 2171.
(11) Khodaei, M. M.; Meybodi, F. A.; Rezai, N.; Salehi, P. Synth.
Commun. 2001, 31, 941.
(12) Ganboa, I.; Palomo, C. Synth. Commun. 1983, 13, 941.
(13) Sharghi, H.; Hosseini Sarvari, M. Synlett 2001, 99.
(14) Schofield, K.; Gregory, B. J.; Moodie, R. B. J. Chem. Soc. B
1970, 338.
(15) (a) Rappoport, Z. CRC Handbook of Tables for Organic
Compound Identification, 3 rd ed.; The Chemical Rubber
Co.: Ohio, 1967. (b) CRC Handbook of Chemistry and
Physics, 54 th ed.; Weast, R. C., Ed.; The Chemical Rubber
Co.: Ohio, 1983.
Acknowledgement
We gratefully acknowledge the support of this work by the Shiraz
University Research Council.
(16) Brehm, L. Acta Cryst. 1972, B28, 3646.
(17) Brady, O. L.; Jarrett, S. G. Acta Cryst. 1951, 4, 1227.
(18) www.aist.go.jp/RIODBS/SDBS/sdbs/owa/
sdbs_sea.ere_frame-sea.
References
(1) Metzger, J. D. Angew. Chem., Int. Ed. 1998, 37, 2975.
(2) Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025.
(3) Gawley, R. E. Org. React. 1988, 35, 1.
(19) Sharghi, H.; Hosseini Sarvari, M. J. Chem. Research (S)
2001, 446.
(4) Izumi, Y.; Sato, S.; Urabe, K. Chem.Lett. 1983, 1649.
Synthesis 2002, No. 8, 1057–1060 ISSN 0039-7881 © Thieme Stuttgart · New York