An efficient and chemoselective method for oximination of β-diketones under mild and heterogeneous conditions

Article abstract of DOI:10.3390/60800694

A combination of oxalic acid dihydrate and sodium nitrite in the presence of wet SiO₂ was used as an effective nitrosating agent for the nitrosation of β-diketones to their corresponding α-oximinoketones in moderate to excellent yields under mild and heterogenous conditions.

Full text of DOI:10.3390/60800694

Molecules 2001, 6, 694-698
molecules
ISSN 1420-3049
http://www.mdpi.org
An Efficient and Chemoselective Method for Oximination of
β-Diketones Under Mild and Heterogeneous Conditions
Mohammad Ali Zolfigol
Department of Chemistry, College of Science, University of Bu-Ali Sina, Postal code 65174, P.O.
Box No. 4135, Hamadan, I.R. Iran; Fax: (+98) 811 8272404; e-Mail: Zolfi@basu.ac.ir
Received: 26 August 2000; in revised form: 10 June 2001 / Accepted: 10 July 2001 / Published: 31
July 2001
Abstract: A combination of oxalic acid dihydrate and sodium nitrite in the presence
of wet SiO2 was used as an effective nitrosating agent for the nitrosation of β-
diketones to their corresponding α-oximinoketones in moderate to excellent yields
under mild and heterogenous conditions.
Keywords: Nitrosation, α-Oximination, β-diketones, oxalic acid dihydrate
Introduction
The α-oximinoketones are known to be important intermediates for the synthesis of aminoacids
[1], nitrosopyrazoles [2], 2-vinylimidazoles [3] and so on. Although nitrous acid or one of its esters
[4], alkyl thionitrite or thionitrate [5], nitrosyl halides [6] and sodium nitrite in acetic acid [7] are
all used for the synthesis of α-oximinoketones, the yields, selectivity for mono oximination and
chemoselectivity on the methylene carbon where there are two possible sites of nitrosation are low
[5]. This situation contrasts markedly with N-nitrosation and also to a lesser extent with O and S-
nitrosation. It is clear that, on the basis of the above facts there is a need for more regioselective
control of nitrosation of carbonyl compounds. Therefore, we decided to choose a new system for
this purpose. Our goal, in undertaking this line of work, was three-fold: a) to overcome the
limitations and drawbacks of the reported methods such as tedious work-up, low yields and
selectivity (b) to replace labor-extensive trial and error improvements with a rational design, (c)
moreover, constraining a reaction to the surface of solid habitually allows to use milder conditions
and increases its reactivity [7]. We now wish to report a one-pot heterogeneous procedure for

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Molecules 2001, 6
chemoselective mono oximination of β-diketones by oxalic acid dihydrate (C2H2O4·2H2O, k ~2)
P a
and sodium nitrite.
Results and Discussion
Different kinds of β-diketones (1) were subjected to the nitrosation reaction in the presence of
NaNO2 (I), wet SiO2 (50% w/w) and C2H2O4·2H2O (II) in dichloromethane (Scheme 1). The
nitrosation reactions were performed under mild and completely heterogeneous conditions at room
temperature and gave moderate to excellent yields (Table). When reaction occurs at the methylene
group, the nitroso compound formed initially rapidly rearranges to form the oxime. This method is
very mild because retro-Claisen C-C bond cleavege or hydrolysis of β-keto esters were not
observed [8].
O
O
O
O
I , II
R1
R2
R1
R2
N
OH
1
2
1 or 2
a
b
c
d
e
f
g
h
R1
R2
Me
Ph
Ph
Ph
Ph
Me
-CH2C(CH3)2CH2-
-(CH2)3-
-C6H4-
Me Me
OEt
OEt
Scheme 1
The reported nitrosation reaction can be readily carried simply by placing NaNO2 (I),
C2H2O4·2H2O (II), β-diketones (1), wet SiO2 (50% w/w) and CH2Cl2 as the inert solvent in a
reaction vessel and efficiently stirring the resultant heterogeneous mixture at room temperature for
0.25-3 hours. The initial nitroso products were converted to the corresponding α-oximinoketones
(2) immediately and the products can be isolated by simple filtration and evaporation of the
solvent. The results and reaction conditions are given in Table 1.
Although the nitrosation reaction also occurs in the absence of wet SiO2, the reaction times are
very long and the reactions only go to completion after several days. Therefore, we think that the
wet SiO2 acts as a reaction medium providing a heterogeneous effective surface area for in situ
generation of HNO2 in low concentrations. It also makes work-up easy.

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Molecules 2001, 6
Table 1. Nitrosation of β-Diketones to
the Corresponding α-Oximinoketones (2)
(mmol)a
Time Yieldsb
Entry
1
2
Substrate NaNO2
C2H2O4·2H2O
(h)
1
%
88
86
75
81
84
88
90
50
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
1
2
6
2
a
b
c
a
b
c
6
1
7
7
1.5
3
12
12
2
12
12
2
d
e
d
e
2.5
1
f
f
2
2
0.25
2
g
h
g
h
2
2
a Wet SiO2/substrate (0.2 g/1mmol) . b Isolated Yields.
In order to show the chemoselectivity of this method a competitive reaction was performed
between acetylacetone and 2,5-hexadione. It was observed that exclusive nitrosation of
acetylacetone occurred, whereas the 2,5-hexadione remained intact in the reaction mixture, even
after 5 hours (Scheme 2).
O
O
O
O
O
O
I , II
+
+
N
O
O
N
OH
OH
0%
100%
Scheme 2
Similarly, this new system generates HNO2 and NO+ respectively, in-situ, and thus acts as
a N2O4 equivalent because a number of reactions are known in which nitrogen tetroxide
−
( N2O4 NO+ NO3 ) acts as a nitrosating agent. Therefore, on the basis of our observations, the
previously reported results about the applications of N2O4 [9], we show that in situ generation of
NO+ is an effective factor for the nitrosation reactions [7].
In conclusion, the low cost and the availability of the reagents, easy and clean work-up, and
high yields make this an attractive method for organic synthesis. This simple procedure is highly
selective and contamination by products is avoided. We believed that the present methodology is
an important addition to existing methodologies.

697
Molecules 2001, 6
Acknowledgments
Financial support for this work by the research affair of Bu-Ali Sina University, Hamadan, Iran,
is gratefully acknowledged.
Experimental
General
1
Chemicals were purchased from the Fluka, Merck and Aldrich chemical companies. H- and
13C-NMR spectra were recorded on a JEOL FX 90Q NMR spectrometer. IR spectra were recorded
on a Shimadzu 435 IR spectrophotometer. Thin layer chromatography (TLC) on commercial
aluminium-backed plates of silica gel 60 F254 was used to monitor the progress of the reactions.
1
13
The nitrosation products were characterized by comparison of their spectral (IR, H-NMR, C-
NMR), TLC and physical data with authentic samples obtained by the H2SO4/NaNO2/dioxane-
water method [10].
WARNING: The nitroso diketones reported in this paper are highly toxic and although a key
feature of the procedure is its clean workup with easy removal of nitroso adducts due to the
heterogeneous nature of the reaction, all due precautions should be taken.
General Procedure for Oximination of β-Diketones
A suspension of sodium nitrite, solid acid (the molar ratios of oxalic acid dihydrate and sodium
nitrite to the substrate 1 were given in the Table), β-diketones 1 (10 mmol) and wet SiO2 (50 w/w,
2 g) in dichloromethane (40 mL) was stirred vigorously magnetically at room temperature. The
progress of the reaction was followed by TLC. Reactions went to completion after 0.25-3 hours
(Table). After the reaction was complete, dry silica gel (5 g) was added to the reaction mixture, the
solid materials were removed by filtration and washed with dichloromethane (40 mL). The solvent
was evaporated from the combined filtrate and washings and the α-oximinoketones 2 were
obtained (Table). If further purification is needed, flash chromatography on silica gel [eluent:
acetone / petroleum ether ( 1:5 )] give highly pure 2.
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Sample availability: Not available.
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