Selective synthesis of E and Z isomers of oximes

Article abstract of DOI:10.1055/s-2001-9719

The highly stereoselective conversion of aldehydes and ketones to their corresponding oximes with hydroxylamin hydrochloride are catalyzed by CuSO₄ and K₂CO₃. This method occurs under mild reaction conditions with high yields.

Full text of DOI:10.1055/s-2001-9719

LETTER
99
Selective Synthesis of E and Z Isomers of Oximes
Hashem Sharghi,* Mona Hosseini Sarvari
Department of Chemistry, College of Science, Shiraz University, Shiraz 71454, I.R. Iran
Fax +98(071)20027; E-mail:sharghi@chem.susc.ac.ir
Received 14 September 2000
Table 1 Reaction of (1) with (2) in the presence of different
catalysts.
Abstract: The highly stereoselective conversion of aldehydes and
ketones to their corresponding oximes with hydroxylamin hydro-
chloride are catalyzed by CuSO4 and K2CO3.This method occurs
under mild reaction conditions with high yields.
Key words: E and Z Isomers, oxime, hydroxylamine hydrochlo-
ride, CuSO4, K2CO3
The addition of hydroxylamine hydrochloride to carbon-
yls to yield oximes is not only one of the best understood
examples of
a
nonenzymatic addition-elimination
reaction1 but also an important reaction in organic syn-
thesis.2 Except in the case of symmetrical ketones, both
isomeric oximes (Z and E) are usually produced which
a) Ratio of products was determined by 1H NMR.
have different physical properties and biological As shown in Table 1 (Entries 1-6), a mixture of Z and E
activities3 and should be separated by chromatography or isomer of 4-chlorobenzaldoxime was obtained by the use
recrystallization techniques.
of various types of catalysts. In the comparison, the reac-
tion proceeded rapidly to give exclusively the correspond-
ing Z/E isomer of 4-chlorobenzaldoxime (3,4) in excellent
yields when K2CO3 / CuSO4 were employed (Table 1, En-
tries 7,8). Similarly, as shown in Scheme 2 and in Tables
2 and 3, the reactions of hydroxylamine hydrochloride
with different aldehydes and ketones, including those with
electron-withdrawing and donating substituents in the
presence of these new catalysts, gave oximes in high
yields and stereoselectivity.
Very few methods are available for the synthesis of E and
Z isomer of oximes.4,5 In many cases, E isomers were ob-
tained from the Z forms by either the hydrochloride
method6 or purified by column chromatography.7 The re-
agents which have been used for oximation of aldehydes
and ketones, also catalyze the interconvertion of Z and E
isomers. The rate of equilibration of a mixture of Z and E
isomers and the position of the equilibrium is temperature
dependent,8 therefore, temperature control of the experi-
ment is critical.
Having the above facts in mind, we wish to report a con-
venient method for controlling the stereochemistry of the
reaction of hydroxylamine hydrochloride with aldehydes
or ketones in solid state.
In order to find a simple and suitable catalyst for control-
ling the stereochemistry of oximes, the reaction of 4-chlo-
robenzaldehyde (1) with hydroxylamine hydrochloride
(2) was chosen as a model and its behavior was studied
under a variety of conditions via TLC and 1H NMR spec-
troscopy (Scheme 1, Table 1).
Scheme 2
As shown in Table 2, various types of aromatic aldehydes
with electron donating and withdrawing groups were
cleanly and rapidly condensed with hydroxylamine hy-
drochloride at 90 °C, giving the corresponding E-isomer
of oximes (OH anti to aryl) in excellent yields in the pres-
ence of CuSO4 (Entries 1-12). However, aromatic ketones
such as benzophenone and others did not afford the corre-
sponding oximes under these conditions. In order to show
the chemoselectivity of the presented reagent toward the
condensation of different carbonyl groups, a mixture of
benzophenone and benzaldehyde was treated with hy-
droxylamine hydrochloride in the presence of CuSO4 at
Scheme 1
Synlett 2001, No. 1, 99–101 ISSN 0936-5214 © Thieme Stuttgart · New York

100
H. Sharghi, M. H. Sarvari
LETTER
Table 2 Convertion of aldehydes and ketones to E-isomer oximes
Table 3 Convertion of aldehydes and ketones to Z-isomer oximes
using CuSO4.
using K2CO3.
a) 1H NMR yields.
a) 1H NMR yields.
90 °C for 30 min. The E-benzaldoxime was obtained in
85% yield and benzophenone was recovered unchanged.
General procedure for preparation of Z isomer of aldoximes
and ketoximes in the presence of K2CO3:
Hydroxylamine hydrochloride (0.6 g 8.6 mmol) was added to a
stirred mixture of K2CO3 (1 g) and aldehydes or ketones (1 mmol)
in an oil bath at 90 °C for the periods of time reported in Table 3.
Then, the reaction mixture was washed with CH2Cl2 (2 ¥ 10 mL)
and water (2 ¥ 50 mL). The organic layer was dried over Na2SO4
and evaporated to give the crude Z isomer of oxime. The products
were identified by comparison of their physical data with those pre-
pared in accordance with the literature procedures.
Table 3 also shows that various types of aromatic alde-
hydes and ketones with electron-donating and electron-
withdrawing groups were cleanly and rapidly condensed
with hydroxylamine hydrochloride at 90 °C, giving their
corresponding Z oximes (OH cis to aryl) in high yields in
the presence of K2CO3 (Entries 1-18).
The advantages of the presented methods may be summa-
rized as: use of commercial and available catalysts, mild
reaction conditions, and high stereoselectivities good
yields of the desired products.
Acknowledgement
We gratefully acknowledge the support of this work by the Shiraz
University Research Council.
General Procedure for preparation of E isomer of aldoximes in
the presence of CuSO4:
References and Notes
Hydroxylamine hydrochloride (0.6 g, 8.6 mmol) was added to a
stirred mixture of CuSO4 (1 g) and aldehydes (1 mmol) at 90 °C in
an oil bath. The progress of reaction was monitored by TLC. After
complete disappearance of the starting material, the reaction mix-
ture was cooled, and washed with cold diethyl ether and filtered to
remove CuSO4. Then the mixture was poured into ice-water and ex-
tract with cold diethyl ether (2 ¥ 25 mL).The organic solution was
dried over Na2SO4 and evaporated over ice to give the crude E
oximes. The process of work-up was carried out at 0 °C, otherwise,
the Z isomer was obtained.
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Article Identifier:
1437-2096,E;2001,0,01,099,0101,ftx,en;L17500ST.pdf
Synlett 2001, No. 1, 99–101 ISSN 0936-5214 © Thieme Stuttgart · New York