One-pot synthesis of oxime ethers from benzaldehyde or acetophenone, hydroxylamine salt, potassium hydroxide, and alkyl halides

Article abstract of DOI:10.1081/SCC-120015807

Oxime ethers were synthesized in one-pot reaction from benzaldehyde or acetophenone, hydroxylamine hydrogen chloride, alkyl halides and KOH in aqueous DMSO. The reactions were completed in 15-50 min with yields in 80-96%.

Full text of DOI:10.1081/SCC-120015807

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One-Pot Synthesis of Oxime Ethers from Benzaldehyde
or Acetophenone, Hydroxylamine Salt, Potassium
Hydroxide, and Alkyl Halides
a
a
a
a
a
Chunbao Li , Hang Zhang , Yi Cui , Shuanming Zhang , Zheyuan Zhao , Michael C. K.
b
b
Choi & Albert S. C. Chan
a
Department of Chemistry, School of Science, Tianjin University, Tianjin, P.R. China
Open Laboratory of Chirotechnology, Department of Applied Biology and Chemical
b
Technology, The Hong Kong Polytechnic University, Hong Kong, P.R. China
Version of record first published: 16 Aug 2006.
To cite this article: Chunbao Li , Hang Zhang , Yi Cui , Shuanming Zhang , Zheyuan Zhao , Michael C. K. Choi & Albert S.
C. Chan (2003): One-Pot Synthesis of Oxime Ethers from Benzaldehyde or Acetophenone, Hydroxylamine Salt, Potassium
Hydroxide, and Alkyl Halides, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 33:4, 543-546
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2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 4, pp. 543–546, 2003
One-Pot Synthesis of Oxime Ethers from
Benzaldehyde or Acetophenone, Hydroxylamine
Salt, Potassium Hydroxide, and Alkyl Halides
1
,
1
1
1
Chunbao Li, * Hang Zhang, Yi Cui, Shuanming Zhang,
1
Zheyuan Zhao, Michael C. K. Choi,
2
2
and Albert S. C. Chan
1
Department of Chemistry, School of Science,
Tianjin University, Tianjin, P.R. China
2
Open Laboratory of Chirotechnology, Department of
Applied Biology and Chemical Technology,
The Hong Kong Polytechnic University,
Hong Kong, P.R. China
ABSTRACT
Oxime ethers were synthesized in one-pot reaction from benzalde-
hyde or acetophenone, hydroxylamine hydrogen chloride, alkyl
halides and KOH in aqueous DMSO. The reactions were completed
in 15–50 min with yields in 80–96%.
*
Correspondence: Chunbao Li, Department of Chemistry, School of Science,
Tianjin University, Tianjin 300072, P.R. China; Fax: 0086-22-27403475; E-mail:
lichunbao08@sina.com.
5
43
DOI: 10.1081/SCC-120015807
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
5
44
Li et al.
Oxime ethers are bioactive compounds, used as medicine and
[1]
pesticide. In asymmetric synthesis, they are good precursors for chiral
[2]
amines. In most of the cases, they are synthesized in two steps; e.g.,
condensation between carbonyl compound and hydroxylamine followed
by alkylation with alkyl halide in the presence of a base or under PTC
[1]
conditions. They have also been made by condensation of O-alkyl
[
3,4]
hydroxylamine with carbonyl compounds.
Recently, Lukevics
et al. reported synthesis oxime ethers under PTC conditions from
carbonyl compounds, hydroxylamine and alkyl halides with moderate
[5]
yields.
In this communication, we describe a high yield and simple one-pot
synthesis of oxime ethers directly from benzaldehyde or acetophenone,
hydroxylamine hydrochloride, potassium hydroxide and alkyl halides in
aqueous DMSO.
The reaction is simply by adding excess KOH to a mixture of
acetophenone or benzaldelyde with hydroxylamine hydrochloride and
alkyl halide in aqueous DMSO. For 42 mmol of acetophenone or
benzaldelyde, 1.2 equiv. each of hydroxylamine saltand alkyl halide,
2
8
0 g of KOH were used. Addition of KOH caused temperature raise to
ꢀ
0–100 C. The results are summarized in Table 1. In general, methyl
iodide reacted fastest than all other halides. Primary bromide reacted
faster than secondary bromide. Alkyl chloride did not react except
benzyl chloride. With 1,3-dibromopropane, we got bisoxime ether.
Methyl sulfate was less reactive than methyl iodide, 1.8 equiv. was
indeed required to give similar yield. After aqueous work-up, most of
the products except bisoxime ether which was purified by filtration
through silica gel eluted with petroleum ether and ether (3:1), were
pure enough as checked by HPLC. All reactions gave only one spot on
TLC. The reactions were fast with high yields.
If the reaction was carried out in scale less than 42 mmol of benzal-
dehyde or acetophenone, the heat liberated from KOH and water was not
Table 1. Yield in % and reaction time (min) of oxime ethers.
RX
Oximes CH I Me SO EtBr BuBr CH (CH ) Br Br(CH ) Br iPrBr BzlCl
3
2
4
3
2 6
2 3
1
2
85
15)
84
80
(30)
81
92
(30) (30)
88 85
(35) (40)
88
88
(40)
85
96
(30)
84
87
(50) (30)
90 89
(50) (30)
95
(
(
25)
(30)
(50)
(30)

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One-Pot Synthesis of Oxime Ethers
545
sufficient for completion of the reaction. In this case, the reaction was
ꢀ
heated to maintain at 80 C for 20 to 30 min.
Replacing KOH with NaOH in the reaction of acetophenone with
hydroxylamine hydrogen chloride and ethyl bromide gave oxime ether in
84% yield in 10 min. Replacing DMSO with DMF in the same reaction
resulted in 82% yield of oxime ether in 30 min.
EXPERIMENTAL
DMSO was used as received. Other solvents were distilled before use.
IR spectra were recorded by Bio-Rad Exalibur FTS3000 with absorption
ꢁ
1
in cm . H NMR spectra were measured by Varian Unity-Plus 400
1
spectrometers using CDCl as solventwi ht J values in Hertz. Chemical
3
shifts are expressed in ppm downfield from internal tetramethylsilane.
Microanalysis were carried outon a Yanaco CHNCORDER MF-3
instrument.
Typical procedure for the preparation of oxime ethers: To the stirred
mixture of acetophenone (5.000 g, 41.60 mmol), hydroxylamine hydrogen
chloride (3.47 g, 49.92 mmol), ethyl bromide (5.440 g, 49.92 mmol), 50 mL
of DMSO and 20 mL of H O were added 20.0 g of KOH. The
2
ꢀ
reaction temperature rose to 80 C. The reaction was monitored by
TLC and was completed in 30 min. Extraction between ethyl acetate
(160 mL) and brine (40 mL) followed by washing the organic layer with
brine three times and concentration gave crude oxime ether, which was
subject to bulb to bulb distillation, giving acetophenone-O-ethyloxime
1
5.680 g, 34.85 mmol) as colorless oil in 92% yield. H NMR and IR
(
confirmed the structure.
O-Heptyl acetophenoneoxime: Colorless liquid; IR (thin film) 2926,
1497, 1447, 1366, 1304; ꢀH 7.65–7.63 (2H, m), 7.37–7.35 (3H, m), 4.19

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5
46
Li et al.
(
2H, t, J ¼ 6.8, OCH ), 2.24 (3H, s, Me), 1.75–1.70 (2H, m), 1.38–1.30
2
(
C H NO requires C, 77.20; H, 9.93; N, 6.00%).
m, 8H), 0.89 (3H, t, J ¼ 7.2, Me); (Found: C, 77.10; H, 9.93; N, 5.95.
1
5
23
O-Heptyl benzaldehydeoxime: Colorless liquid; IR (thin film) 2929,
1455, 1378; ꢀH 8.09 (1H, s), 7.60–7.58 (2H, m), 7.37–7.36 (3H, m), 4.17
(
2H, t, J ¼ 6.8, OCH ), 1.74–1.68 (2H, m), 1.38–1.31 (m, 8H), 0.90 (3H, t,
2
J ¼ 6.8, Me); (Found: C 76.42; H, 9.93; N, 6.48. C H NO requires
1
4
21
C, 76.67; H, 9.65; N, 6.39%).
,3-O-Propylidene bisacetophenoneoxime: Colorless liquid; IR
thin film) 2929, 1455, 1378; ꢀH 7.70–7.65 (4H, m), 7.44–7.38 (6H, m),
.38 (4H, t, J ¼ 6.5, 2 ꢂ OCH ), 2.33 (6H, s, 2 ꢂ Me), 2.19 (2H, t, J ¼ 6.6);
1
(
4
2
(
Found: C, 73.86; H, 7.32; N, 9.31. C H N O requires C, 73.52;
19 22 2 2
H, 7.14; N, 9.03%).
1,3-O-Propylidene bisbenzaldehydeoxime: Colorless liquid; IR (thin
film) 2929, 1455, 1378; ꢀ 8.10 (2H, s), 7.59–7.56 (4H, m), 7.39–7.35 (6H,
H
m), 4.31 (4H, t, J ¼ 6.8,2 ꢂ OCH ), 2.16 (2H, t, J ¼ 6.4); (Found: C, 72.58;
2
H, 6.53; N, 9.88. C H N O requires C, 72.32; H, 6.43; N, 9.92%).
2
1
7
18
2
ACKNOWLEDGMENT
We thank the ASD fund of The Hong Kong Polytechnic University
for financial support.
REFERENCES
1
2
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of ketoxime O-alkyl ethers with chirally modified NaBH –ZrCl .
4
4
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Int. 2000, 32 (2), 153–159.
5
Received in the UK July 26, 2001