A simple synthesis of oximes

Article abstract of DOI:10.1007/s00706-005-0427-3

The conversion of alicyclic and aliphatic carbonyl compounds as well as aromatic aldehydes into the corresponding oximes (up to quantitative yields) was achieved by simply grinding these reactants, hydroxylamine hydrochloride and sodium hydroxide without solvent. However, this procedure was unsuccessful in the case of aromatic ketones. In this case it was necessary to add silica gel as a catalyst. Springer-Verlag 2006.

Full text of DOI:10.1007/s00706-005-0427-3

Monatshefte f €u r Chemie 137, 301–305 (2006)
DOI 10.1007/s00706-005-0427-3
A Simple Synthesis of Oximes
Ivan Damljanovi c´ , Mirjana Vuki c´ evi c´ , and Rastko D. Vuki c´ evi c´ ꢀ
Department of Chemistry, Faculty of Science, University of Kragujevac,
R. Domanovi c´ a 12, 34000 Kragujevac, Serbia and Montenegro
Received June 27, 2005; accepted July 4, 2005
Published online February 3, 2006 # Springer-Verlag 2006
Summary. The conversion of alicyclic and aliphatic carbonyl compounds as well as aromatic alde-
hydes into the corresponding oximes (up to quantitative yields) was achieved by simply grinding these
reactants, hydroxylamine hydrochloride and sodium hydroxide without solvent. However, this proce-
dure was unsuccessful in the case of aromatic ketones. In this case it was necessary to add silica gel as
a catalyst.
Keywords. Solid-phase synthesis; Hydroxyimination; Aldehydes; Ketones; Oximes.
Introduction
Numerous functional group transformations of oximes make them very im-
portant in synthetic organic chemistry. Among other synthesis applications,
these compounds were successfully transformed into amides [1], amines [2],
hydroxylamines [3], hydroxylamine O-ethers [4], nitroalkanes [5], 1,3-ox-
azoles, -thiazoles, and -diazoles [6], etc. Therefore, synthetic organic chemists
are interested in a facilitation of oxime synthesis. Although alternative meth-
ods exist [7] reaction of carbonyl compounds with hydroxylamine hydrochlo-
ride remains still the most important route. The classical method involves
refluxing of an alcoholic solution of these reactants in the presence of sodium
acetate or hydroxide [8].
Many improvements of this methodology have been described. Thus, treatment
of ketones with hydroxylamine hydrochloride in the presence of an ion-exchange
resin (Amberlyst A-21) as the catalyst in ethanol gave oximes in high yields at room
temperature and with a simple work-up procedure [9]. Recently, it has been report-
ed that silica gel in the presence of a base [10], or without any base, but coupled
with microwave irradiation [11], could be a useful catalyst for this condensation.
Similarly to that, irradiation of carbonyl compounds and hydroxylamine hydro-
chloride impregnated on wet basic Al O , or grinding them with molecular sieves
2
3
ꢀ Corresponding author. E-mail: vuk@kg.ac.yu

3
02
I. Damljanovi c´ et al.
gave the corresponding oximes [12]. High yields of hydroxyiminocycloalkanes
could be also achieved by treatment of the corresponding ketones with hydroxyl-
amine or its salts in ionic liquids and in the presence of additives, such as sodium
acetate [13].
Recently, we required considerable amounts of several oximes of aliphatic and
alicyclic ketones as starting materials in a more comprehensive synthesis project
and carried out extensive re-examination of this reaction. Herein, we report on our
findings, which resulted in a quick, simple, and extremely efficient method of
oxime synthesis without a solvent, in most cases also without a catalyst, heating,
or microwave irradiation.
Results and Discussion
First of all, we found that cyclic ketones, such as cyclopentanone (1a), cyclohex-
anone (1b), 4-tert-butylcyclohexanone (1c), and cycloheptanone (1d) could be
transformed into the corresponding oximes by simple grinding (30–40 min) at room
temperature (in a mortar with a pestle) with 1.2 equivalents of hydroxylamine
hydrochloride and sodium hydroxide without any catalyst and solvent. Also, there
was no need to heat the reaction mixture or to expose it to microwave irradiation.
Oximes of very high purity were isolated in excellent yields (85–100%) working
in 1, 10, and 50 mmol scales (Scheme 1 and Table 1).
Very similar results were obtained with aliphatic unsaturated carbonyls 1e–1h
as well as aromatic aldehydes 1i–1l. These were converted into mixtures of the
corresponding (E)- and (Z)-oximes in 75–98% yields.
In contrast to that, aromatic ketones like acetophenone (1m), 2-hydroxyaceto-
phenone (1n), and benzophenone (1o) did not undergo this reaction even after
several hours grinding, so that the corresponding substrates were recovered un-
changed. However, if a small amount of silica gel (0.4, 2.0, and 8.0 g for 1, 10, and
50 mmol scales) was added these ketones also could be transformed into their
oximes in good yields (up to 98%).
In order to evaluate the preparative value of the present methodology we
carried out this reaction with 0.5 mol of cyclohexanone. Hydroxyiminocyclohex-
ane was obtained in high yield, but because of gentle heat production the proce-
dure was slightly modified: to the grinded mixture of cyclohexanone and
hydroxylamine hydrochloride sodium hydroxide was added in portions (2–3 g)
during one hour.
Scheme 1

A Simple Synthesis of Oximes
303
a
Table 1. Synthesis of oximes from the corresponding carbonyls
0
b
Substrate
R
R
Time=min
Silica gel
None
Products
Yield=%
1
a
30
2a
95–100
c
1
b
30
40
None
None
2b
2c
95–100
89–96
1
c
1
d
40
None
2d
85–90
1
e
–CH3
–CH3
30
40
None
None
2e
2f
85–91
85–91
1
f
1
g
–CH3
–H
40
40
None
None
2g
2h
75–80
95–97
1
h
1
i
–H
–H
–C H
6
120
60
60
30
60
60
60
None
None
None
None
2i
2j
87–93
87–91
91–95
93–98
72–75
93–98
92–97
5
1
j
–C H OH-4
6 4
1
k
–H
–C H OCH -4
6
2k
2l
4
3
d
1
l
–H
–C H N(CH ) -4
6
4
3 2
e
1
m
–CH3
–CH3
–C H
–C H
6
Yes
1m
1n
1o
5
e
1
n
–C H OH-4
6
Yes
4
e
1
o
–C H
6 5
Yes
6
5
a
Reactions were carried out in 1, 10, and 50 mmol scales in a molar ratio of reactants sub-
b
strate=NH OHꢁHCl=NaOH ¼ 1=1.2=1.2, if it is not noted differently; isolated yields based on
2
c
the starting substrate; the reaction was carried out also in a 0.5 mol scale (see text); molar ratio
d
of reactants substrate=NH OHꢁHCl=NaOH ¼ 1=3=3; after noted grinding time the reaction mixture
2
e
was allowed to react over night; 0.4, 2.0, and 8.0 g for 1, 10, and 50 mmol scales
In conclusion, these results point to an extremely simple, suitable, and effi-
cient method for the conversion of carbonyl compounds to the corresponding
oximes.
Experimental
All chemicals used were commercially available and were used as received. IR spectra were measured
with a Perkin-Elmer 457 grating FT instrument. NMR spectra were recorded on a Varian Gemini 200
spectrometer using CDCl as the solvent. Chemical shifts are expressed in ppm using TMS as an
3
internal standard.

3
04
I. Damljanovi c´ et al.
General Procedure
In a typical procedure for 1, 10, and 50 mmol range, the reactants in the molar ratio carbonyl
compound=NH OHꢁHCl=NaOH ¼ 1=1.2=1.2 were grinded in a mortar with a pestle at room tem-
2
perature for 10 min. Then the mixture was ground from time to time for the time indicated in
Table 1. The reaction mixture was then washed with H O to remove inorganic salts and the residue
2
1
dried on air. The corresponding oximes were pure enough for spectral characterization (IR, H and
1
3
C NMR), but purification by recrystallization was necessary for melting points determinations.
In the case of liquid products the reaction mixture was carefully extracted with ether or CH Cl ,
2
2
the organic phase washed with H O, dried (Na SO ), and the solvent evaporated. Yields are given
2
2
4
in Table 1.
In the 0.5mol range hydroxyimination of cyclohexanone, 49g of this ketone and 41.7g
NH OHꢁHCl were ground and 24 g of NaOH were added subsequently in ten portions (1h), grinding
2
the mixture continuously. The solid obtained was washed with H O and dried on air giving 56.5g
2
(97%) of hydroxyiminocyclohexane.
Almost all derived oximes are known compounds and their spectral data, as well as melting points
of solids, were in agreement with those known. Herein we give spectral data only for 2g and 2h, which
could not be found in literature.
(E)- and (Z)-2-Hydroxyimino-6-methyl-6-heptene (2g, C H NO)
8 15
Educt 1g (1.26 g) afforded 1.13 g (80%) 2g as a colorless liquid. IR (film): ꢀꢀ ¼ 3234, 3076, 1651, 1446,
ꢂ1
1
1
374, 1255, 1151, 1074, 953, 886, 741 cm ; H NMR (200 MHz, CDCl ): ꢁ ¼ 9.22 (br. s, OH), 4.70
3
(
m, CH -7), 2.37 and 2.19 (2m, altogether 2H at C2 of both isomers in a 3:1 ratio), 2.02 (t, J ¼ 7.7 Hz,
2
CH -5), 1.89 and 1.87 (2s, altogether 3H at C1 of both isomers in a 3:1 ratio), 1.51–1.72 (m, CH -
2
2
13
4
3
þ CH ) ppm; C NMR (50 MHz, CDCl ): ꢁ ¼ 13.4, 19.9, 22.3, 23.4, 24.1, 28.3, 35.3, 37.1,
3
3
7.6110.2, 110.3, 145.1, 159.4, 159.6ppm.
(1E,5E)- and (1Z,5E)-1-Hydroxyimino-5-decene (2h, C H NO)
10 19
Educt 1h (0.154g) afforded 0.162 g (96%) 2h as a colorless liquid. IR (film): ꢀꢀ ¼ 3253, 2956, 2924,
ꢂ1
1
2
855, 1665, 1444, 1378, 1339, 1139, 1073, 967, 930, 726 cm ; H NMR (200MHz, CDCl ): ꢁ ¼ 8.67
3
(
br. s, OH), 7.42 and 6.72 (2t, J ¼ 5.8 and 5.2 Hz, altogether CH-1 of both isomers in a 1:1.07 molar
ratio), 5.45 (m, 2H olefinic), 2.44 and 2.21 (2m, altogether 4H at C2 and one of the allylic position of
both isomers), 1.97 (m, 2H at the other allylic position), 1.28 (m, 6H at C7, C8, and C9), 0.88
1
3
(
t, J ¼ 6.7 Hz, CH ) ppm; C NMR (50 MHz, CDCl ): ꢁ ¼ 14.0, 22.5, 24.7, 28.8, 29.1, 29.2, 29.5,
3
3
3
1.3, 32.5, 127.9, 128.1, 132.0, 132.1, 151.7, 152.3ppm.
Acknowledgements
This work was supported by the Ministry of Science and Environment Protection of the Republic of
Serbia (grant 2042).
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