Efficient preparation of aldoximes from arylaldehydes, ethylenediamine and Oxone in water

Article abstract of DOI:10.3390/12020231

The one-pot reaction of aromatic aldehydes, ethylenediamine and Oxone (2KHSO₅·KHSO₄·K₂SO₄) in pure water was found to unexpectedly afford aldoximes in excellent yields.

Full text of DOI:10.3390/12020231

Molecules 2007, 12, 231-236
molecules
ISSN 1420-3049
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Communication
Efficient Preparation of Aldoximes from Arylaldehydes,
Ethylenediamine and Oxone® in Water
Jing-Jing Xia and Guan-Wu Wang*
Hefei National Laboratory for Physical Sciences at Microscale and Department of Chemistry,
University of Science and Technology of China, Hefei, Anhui 230026, P. R. China
* Author to whom correspondence should be addressed; E-mail: gwang@ustc.edu.cn
Received: 25 January 2007; in revised form: 14 February 2007 / Accepted: 18 February 2007 /
Published: 21 February 2007
Abstract: The one-pot reaction of aromatic aldehydes, ethylenediamine and Oxone®
(2KHSO5·KHSO4·K2SO4) in pure water was found to unexpectedly afford aldoximes in
excellent yields.
Keywords: Aldoximes, aryl aldehydes, ethylenediamine, Oxone®, water
Introduction
Oximation has attracted intensive attention for several decades as an efficient method for
characterization and purification of carbonyl compounds. Due to the nucleophilic character of oximes,
they have been widely used for the preparation of a variety of nitrogen-containing compounds such as
amides [1], hydroximinoyl chlorides [2], nitrones [3] and nitriles [4]. Oximes were usually prepared by
the reaction of carbonyl compounds and hydroxylamine hydrochloride with adjustment of pH using a
basic aqueous medium. Recently, some new techniques such as microwave irradiation [5] and solvent-
free heating [6] were applied to this reaction. Oxidation of amines or hydroxylamines was another
usual method for the synthesis of oximes [7].
On the other hand, the use of water as a reaction medium has attracted notable interest and offers a
clean, economical and environmentally-safe protocol for many reactions [8]. In fact, more and more
reactions have been reported to proceed smoothly and efficiently in water. In continuation of our
interest in organic reactions in water [9], herein we report the unexpected formation of aldoximes from
the one-pot reaction of aromatic aldehydes and ethylenediamine with Oxone® in water.

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232
Results and Discussion
Fujioka’s, Konwar’s and Sayama’s groups have reported the reactions of aldehydes and
ethylenediamine with oxidation by N-bromo(chloro)succinimide (NXS) [10], I2/KI/K2CO3/H2O
system [11] or pyridinium hydrobromide perbromide (PHPB) [12]. These reactions afforded dihydro-
imidazole-type products. Oxone® has been widely used in organic reactions in recent years as an
efficient and clean oxidant [13]. When we employed Oxone® as the oxidant for the reactions of
aromatic aldehydes 1a-j and ethylenediamine (2) in pure water, to our surprise, no dihydroimidazoles
were observed, and instead, aldoximes 3a-j were produced in excellent yields (Scheme 1).
Scheme 1.
R
R
Oxone (1 eqv)
+
H2O
80 oC, 3h
H2N
NH2
CHO
NOH
3a-j
1a-j
2
The procedure involves addition of ethylenediamine to an aqueous mixture of aldehyde and Oxone®
in water, followed by vigorous stirring in an oil bath to afford the aldoximes. The reaction was affected
prominently by the quantity of Oxone® employed and the optimum amount of this reagent was found
to be one equivalent. If 1.5 equivalents or more of Oxone® were used, the aromatic aldehydes could be
partially oxidized to the corresponding benzoic acids. If 0.5 equivalents or less of Oxone® were used,
the conversions were relatively low. The ethylenediamine was used in slight excess. The reaction
yields for the one-pot synthesis of aldoximes with the optimum molar ratio of 1, 2 and Oxone® as
1:1.1:1 are listed in Table 1, along with the melting points of the products.
Table 1. One-pot synthesis of aldoximes from aldehydes, 2 and Oxone®.
Entry
R
Product Yield / %a
Mp (lit) / oC
1
2
H
3a
3b
3c
3d
3e
3f
92
93
92
90
93
91
95
88
86
88
30-32 (33-35 [5] )
73-74 (76-78 [14] )
47-49 (48-49 [15] )
67-68 (69 [16] )
4-CH3
4-CH3O
3,4-CH3
4-Cl
3
4
5
110-111 (107-109 [14] )
74-75 (74-75 [17] )
120-121
6
2-Cl
7
3,4-Cl
4-NO2
3-NO2
4-CN
3g
3h
3i
8
131-132 (132-133 [17] )
123-124 (121-122 [17] )
180-181 (174-176 [18] )
9
10
3j
a Isolated yields based on aldehydes.

Molecules 2007, 12
233
From Table 1 it can be seen that all of the reactions of aldehydes 1a-j with 2 and Oxone® gave very
good yields of aldoximes 3a-j. All of the products except for 3g were known compounds and their
1
13
structures were confirmed by comparison of their melting points, H- and C-NMR and IR spectra
with reported data [5, 14-18].
The use of other amines replacing ethylenediamine was studied under the same conditions.
Diamines such as 1,3-diaminopropane and 1,3-diaminohexane and aliphatic amines such as
methylamine and butylamine afforded very low yields of the aldoximes, while p-tolylamine and
hydrazine gave no aldoximes. These results demonstrated the advantage and special activity of
ethylenediamine for the formation of aldoximes.
Other oxidants such as FeCl3, (NH4)2Ce(NO3)6, KMnO4, PhI(OAc)2 and K2S2O8 instead of Oxone®
have also been examined. None of these oxidants gave any aldoxime products, but rather generated the
corresponding benzoic acids, thus clearly exhibiting the effectiveness of Oxone® for producing
aldoximes from aldehydes and ethylenediamine. Aliphatic aldehydes have also been used for these
reactions, but unfortunately, they did not react with ethylenediamine and Oxone® to afford aldoximes.
Additional control experiments were conducted to gain insight into the reaction mechanism. If the
aqueous solution of 2 and Oxone® was stirred at 80 oC for 3 h, and then an aldehyde was added and the
resulting mixture stirred for another 3 h, no aldoxime was obtained. When Oxone® was added after the
o
aqueous solution of an aldehyde and 2 was stirred at 80 C for 3 h, the desired aldoxime was
successfully prepared in high yield. Consequently, the reaction mechanism is believed to proceed via
the imine intermediate 4, which was then oxidized by Oxone® to form the aldoxime product 3. Indeed,
the reaction of the imine preformed from an aldehyde and 2 with Oxone® for 3 h at 80 oC (Scheme 2)
gave yields comparable to those obtained with the three-component one-pot process. Thus, for
example, the oxidation of the imine 4a prepared from 1a and 2 with Oxone® for 3 h at 80 oC afforded
3a in 89% yield, close to the 92% yield observed for the one-pot procedure (Table 1, entry 1). In
contrast, the Oxone® oxidation of the imines formed from 1a and 1,3-diaminopropane, 1,3-diamino-
hexane, methylamine or butylamine gave only small amounts of 3a, in contrast with the three-
component one-pot process. These results again demonstrated the unique property of ethylenediamine
for the generation of aldoximes.
Scheme 2.
R
R
R
H2O
Oxone
+
H N
2
NH
2
CHO
NOH
NCH CH NH
2
2
2
1
2
4
3
Conclusions
In summary, we have discovered a novel reaction of aromatic aldehydes, ethylenediamine and
Oxone® in pure water that provides a new route for the preparation of the corresponding aldoximes.
Using this protocol, aldoximes were obtained with excellent yields.

Molecules 2007, 12
234
Experimental
General
13
1H-NMR and C-NMR spectra were recorded at 300 MHz and 75 MHz respectively on a Bruker
Avance-300 spectrometer using CDCl3 as solvent. Chemical shifts (δ) are given in ppm relative to
TMS as an internal standard and coupling constants (J) in Hz. IR spectra were taken on a Bruker
Vector-22 spectrometer in KBr pellets and are reported in cm-1. Melting points were determined on a
XT-4 apparatus and are uncorrected.
General procedure for aldoxime synthesis
Typically, to an aqueous mixture of aldehyde 1a-j (0.5 mmol) and Oxone® (307.4 mg, 0.5 mmol)
in water (2 mL) was added 2 (40 µL, 0.55 mmol), then the reaction mixture was stirred vigorously in
o
an oil bath preset at 80 C for 3 h (monitored by TLC). After the reaction mixture had cooled, the
precipitated-out solid was filtered and washed with water (10 × 2 mL) to give the crude product,
except for 3a and 3c. Because of the lower m.p. of 3a and 3c, the crude product failed to precipitate
out from the reaction mixtures, and required extraction with ethyl acetate (15 mL × 2). The extract was
dried over anhydrous sodium sulfate and then filtered. The filtrate was evaporated under vacuum to
afford the crude product. All of the crude products were purified by column chromatography over
silica gel with petroleum ether/ethyl acetate as the eluent to give pure aldoximes 3a-j. All products 3a-
j, except for the previously unknown compound 3,4-Dichloro-benzaldehyde oxime (3g) have been
1
13
reported previously and their identities have been confirmed by their H-NMR, C-NMR, IR spectra
and melting point. The spectral data of 3g were as follows: IR (KBr) υ 3311, 1632, 1556, 1480, 1460,
1
1377, 1325, 1269, 1215, 1135, 1032, 993, 966, 947, 915, 883, 872, 816, 776, 697, 675, 576, 551; H-
NMR (CDCl3) δ 7.40 (dd, J = 8.2, 1.5 Hz, 1H, ArH), 7.46 (d, J = 8.2 Hz, 1H, ArH), 7.68 (d, J = 1.5
13
Hz, 1H, ArH), 7.68 (s, 1H, CH), 8.06 (s, 1H, OH); C- NMR (CDCl3) 148.5, 134.2, 133.4, 132.1,
131.0, 128.8, 126.2
Acknowledgements
We are grateful for the financial support from National Natural Science Foundation of China (Nos.
20621061 and 20321101).
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Sample Availability: Samples of the compounds 3a-j are available from the authors.
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