Silica sulfuric acid/NaNO2 as a novel heterogeneous system for the chemoselective α-nitrosation of β-diketones under mild conditions

Article abstract of DOI:10.1080/10426500307868

A combination of silica sulfuric acid 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-nitroso or α-oximinoketones under mild and heterogenous conditions in moderate to excellent yields.

Full text of DOI:10.1080/10426500307868

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Phosphorus, Sulfur, and Silicon and the Related
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Silica Sulfuric Acid/NaNO 2 as a Novel Heterogeneous
System for the Chemoselective α-Nitrosation of β-
Diketones Under Mild Conditions
Mohammad Ali Zolfigol a & Arash Ghorbani Choghamarani a
a University of Bu-Ali Sina , Hamadan, Iran
Published online: 27 Oct 2010.
To cite this article: Mohammad Ali Zolfigol & Arash Ghorbani Choghamarani (2003) Silica Sulfuric Acid/NaNO 2 as a Novel
Heterogeneous System for the Chemoselective α-Nitrosation of β-Diketones Under Mild Conditions, Phosphorus, Sulfur, and
Silicon and the Related Elements, 178:7, 1623-1629, DOI: 10.1080/10426500307868
To link to this article: http://dx.doi.org/10.1080/10426500307868
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Phosphorus, Sulfur, and Silicon, 178:1623–1629, 2003
C
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print
DOI: 10.1080/10426500390213031
SILICA SULFURIC ACID/NaNO2 AS A NOVEL
HETEROGENEOUS SYSTEM FOR THE
CHEMOSELECTIVE -NITROSATION OF
-DIKETONES UNDER MILD CONDITIONS
Mohammad Ali Zolfigol and Arash Ghorbani Choghamarani
University of Bu-Ali Sina, Hamadan, Iran
(Received February 18, 2003)
A combination of silica sulfuric acid and sodium nitrite in the presence
of wet SiO2 was used as an effective nitrosating agent for the nitrosa-
tion of -diketones to their corresponding -nitroso or -oximinoketones
under mild and heterogenous conditions in moderate to excellent yields.
Keywords: -Oximination; -diketones; nitrosation; silica sulfuric acid
Acids are catalysts which are used the most in industry for produc-
ing more than 1 108 Mt/year of products. Among the acid catalysts,
the most commonly used are HF, H2SO4, HClO4, and H3PO4 (in liquid
form or supported on Kieselguhr). Solid acids have many advantages
such as simplicity in handling, decreasing reactor and plant corrosion
problems, and environmentally safe disposal.1,2 Also, wastes and by-
products can be minimized or avoided by developing cleaner synthesis
routes.3 On the other hand, any reduction in the amount of sulfuric acid
needed and/or any simplification in handling procedures is required for
risk reduction, economic advantage and environment protection. In ad-
dition, there is current research and general interest in heterogeneous
systems because of the importance such systems have in industry and
in developing technologies.4
Very recently, we among many others have demonstrated that het-
erogeneous reagent systems have many advantages such as simple
This research project has been supported by from the National Research Projects
(grant No. NRCI 32-296) and with support of the National Research Council of Islamic
Republic of Iran.
Address correspondence to Mohammad Ali Zolfigol, Department of Chemistry,
College of Science, University of Bu-Ali Sina, PO Box 4135, Hamadan 65174, Iran.
E-mail: Zolfi@basu.ac.ir
1623

1624
M. A. Zolfigol and A. G. Choghamarani
experimental procedures, mild reaction conditions and minimization of
chemical wastes as compared to the liquid phase counterparts.5–7
Therefore, we decided to apply a completely heterogeneous system and
we have investigated a number of different reaction conditions based
upon the in situ generation of HNO2 by relatively strong inorganic
acidic salts or inorganic acidic resins and sodium nitrite in the presence
of wet SiO2, used as an effective nitrosating agent for the nitrosation
of -diketones. In continuation of our studies on the application of in-
organic acidic salts5 and silica chloride6 we found that silica gel reacts
with chlorosulfonic acid to give a white powder namely silica sulfuric
acid (I). It is interesting to note that the reaction is easy and clean
without any work-up procedure because HCl gas is evolved from the
reaction vessel immediately (Scheme 1).
SCHEME 1
We hoped that the silica sulfuric acid (I) would be a superior pro-
ton source to all of the reported acidic solid supports or acidic resins
such as polystyrene sulfonic acid and Nafion-H (Nafion has the handi-
cap of low surface area which renders it unrealistic for practical use)2
for running reactions under heterogeneous conditions. On developing
cleaner organic reactions and also applications of this new solid acid,7
we were interested in using this inorganic acidic resin (I) for the in-
situ generation of HNO2 when used in conjunction with NaNO2, wet
SiO2 and an organic solvent. Since the nitrosoketones are highly toxic
and carcinogenic chemicals, its production with any dispersion is very
interesting for organic and biological chemists. Although a key feature
of the present paper is its clean work-up with easy removal of nitroso
adducts due to the heterogeneous nature of the reaction, all due pre-
caution should be taken. We report a simple, cheap, and chemoselective
method for the effective nitrosation of -diketones under mild and het-
erogeneous conditions.
The -oximinoketones have been known to be an important
intermediate for the synthesis of aminoacids,8 nitrosopyrazoles,9
2-vinylimidazole,10 and so on. Although nitrous acid or one of its
esters,11 alkyl thionitrite or thionitrate,12 nitrosyl halides,13 sodium
nitrite and oxalic acid14 are used for the synthesis of -oximinoketones
but the yields, selectivity for mono oximination and chemoselectivity on
the methylene carbon where there are two possible sites of nitrosation
are low.12 This situation contrasts markedly with N-nitrosation and

Silica Sulfuric Acid/NaNO2 as a Novel Heterogeneous System
1625
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 threefold: (a) to overcome the limitations and drawbacks of the re-
ported methods such as tedious work-up, low yields, and selectivity; (b)
to replace labor-extensive trial and error improvement with rational
design; and (c) moreover, constraining a reaction to the surface of solid
habitually allows to use milder conditions and increases its reactivity.
However, we report an one-pot heterogeneous procedure for chemose-
lective mono oximination of -diketones by silica sulfuric acid (I) and
sodium nitrite.
Different kinds of -diketones (1) were subjected to the nitrosation
reaction in the presence of silica sulfuric acid (I), NaNO2 (II), and
wet SiO2 (50% w/w) in dichloromethane (Scheme 2). The nitrosation
reactions proceeded under mild and completely heterogeneous condi-
tions at room temperature in moderate to excellent yields (Table I).
When reaction occurs at the methylene group, the nitroso compound for-
med initially rapidly rearranges to form the oxime. This method is very
mild because a retro-Claisen C C bond cleavage or hydrolysis of the
-keto esters were not observed.15
The present nitrosation reaction can be readily carried out only
by placing silica sulfuric acid (I), NaNO2 (II), -diketones (1), wet
SiO2 (50% w/w), and CH2Cl2 as the inert usable solvent in a reaction
vessel and efficiently stirring the resultant heterogeneous mixture
TABLE I Nitrosation of -Diketones (1) to Their Corresponding
-Nitrosoketones (2) or -Oximinoketones (3) with a Combination of Silica
Sulfuric Acid (I), NaNO2 (II) and Wet SiO2 (50% w/w) in Dichloromethane at
Room Temperature
Reagent/Substratea
Time
(min)
Yieldsb
%
Entry
Substrate
Product
I (g)
II (mmol)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
3a
3b
3c
3d
3e
3f
3g
2h
2i
0.4
0.8
0.8
1.2
1.2
0.4
0.4
0.4
0.4
4
8
8
12
12
4
4
4
4
75
90
155
120
120
45
85
60
75
61
92
99
83
60
60
70
80
80
aWet SiO2/substrate (0.2 g/1 mmol).
bIsolated yields.

1626
M. A. Zolfigol and A. G. Choghamarani
SCHEME 2
at room temperature for 45–155 min. The -nitrosoketones (2) or
-oximinoketones (3) can be obtained by simple filtration and evapo-
ration of the solvent. The results and reaction conditions are given in
Table I.
Although the nitrosation (some of the nitroso products were con-
verted to the corresponding -oximinoketones immediately, entries

Silica Sulfuric Acid/NaNO2 as a Novel Heterogeneous System
1627
1–7) 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 pro-
viding a heterogeneous effective surface area for in situ generation of
HNO2 in low concentrations. It also makes work-up easy.
In order to show the chemoselectivity of this method a competitive
reaction was performed between acetylacetone and 2,5-hexadione. It
was observed that exclusively acetylacetone nitrosation was performed.
2,5-Hexadione remained intact in the reaction mixture after 2 h
(Scheme 3).
SCHEME 3
Similarly, this new system in situ generates HNO2 and NO+, re-
spectively, and acts as N2O4 because a number of reactions are known
in which nitrogen tetroxide (N2O4 ⇔ NO+NO3 ) acts as a nitrosat-
ing agent. Therefore, on the basis of our observations, the previ-
ously reported results about the applications of N2O4,16 we think that
in situ generation of NO+ is an effective factor for the nitrosation
reactions.17–19
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 contam-
ination by products is avoided. In contrast to the reported procedures in
aqueous media20 isolation of products containing multifunctional polar
groups i.e., 2 and 3 are very simple and practical. We are expecting the
number of reactions carried out on silica sulfuric acid to enormously in-
crease in the future and to substitute other less environment-friendly
acids such as H2SO4. We also believed that the present methodology is
an important addition to existing methodologies.
EXPERIMENTAL
General: Chemicals were purchased from the Fluka, Merck, and
Aldrich chemical companies. Proton and carbon nuclear magnetic

1628
M. A. Zolfigol and A. G. Choghamarani
resonance spectra were recorded on a JEOL NMR-Spectrometer FX
90Q. IR spectra were recorded on a Shimadzu 435 IR spectropho-
tometer. Thin layer chromatography (TLC) on commercial aluminium-
backed plates of silica gel 60 F254 was used to monitor the progress of the
reactions. The nitrosation products were characterized by comparison
of their spectral (IR, 1H-NMR), TLC and physical data with authentic
samples which were obtained by H2SO4/NaNO2/dioxan-water.20
General Procedure for -Nitrosation of -Diketones
A suspension of sodium nitrite, solid acid (the molar ratio of silica sul-
furic acid (I) and sodium nitrite (II) to the substrate 1 were given in
the Table I), -diketones 1 (10 mmol) and wet SiO2 (50 w/w, 2 g) in
dichloromethane (50 ml) was stirred vigorously magnetically at room
temperature. The progress of the reaction was followed by TLC. Re-
actions were completed after 45–155 min (Table I). After the reac-
tion was completed, dry silica gel (5 g) was added to the reaction
mixture, the solid materials were removed by filtration and washing
with dichloromethane (50 ml). The solvent was evaporated and the
-
nitrosoketones (2) or -oximinoketones (3) was obtained (Table I). If
further purification is needed, flash chromatography on silica gel was
used [eluent: acetone/petroleum ether (1:5)] to give highly pure 2 or 3.
REFERENCES
[1] A. Corma, Current Chemistry, 2, 63–75 (1997).
[2] A. Corma and H. Garcia, Cat. Today, 38, 257 (1997).
[3] S. K. Sikdar and S. G. Howell, Journal of Cleaner Production, 6, 253 (1998).
[4] R. A. Sheldon and R. S. Downing, Applied Catalysis A: General, 189, 163 (1999).
[5] a) M. A. Zolfigol, M. Bagherzadeh, E. Madrakian, E. Ghaemi, and A. Taqian-Nasab,
J. Chem. Res.(S)., 140 (2001); b) M. A. Zolfigol, E. Ghaemi, and E. Madrakian,
Molecules, 6, 614 (2001); c) F. Shirini, M. A. Zolfigol, B. Mallakpour, S. E. Mallakpour,
and A. Hagipour, Tetrahedron Lett, 43, 1555 (2002).
[6] a) M. A. Zolfigol, M. Torabi, and S. E. Mallakpour, Tetrahedron, 57, 8381 (2001);
b) M. A. Zolfigol, F. Shirini, and A. Ghorbani-Choghamarani, Synth. Commun., 32,
1809 (2002).
[7] a) M. A. Zolfigol, Tetrahedron, 57, 9509 (2001); b) B. F. Mirjalili, M. A. Zolfigol,
and A. Bamoniri, J. Korian Chem. Soc., 45, 546 (2001); c) M. A. Zolfigol, and
A. Bamoniri, Synlett, 1621 (2002); d) B. F. Mirjalili, M. A. Zolfigol, and A.
Bamoniri, Molecules, 7, 751 (2002); e) M. A. Zolfigol, E. Ghaemi, and E. Madrakian,
Molecules, 7, 734 (2002); e) M. A. Zolfigol, F. Shirini, A. Ghorbani Choghamarani,
and I. Mohammadpoor-Baltork, Green Chem., 4, 562 (2002).
[8] J. F. W. McOmie, Protective Groups in Organic Chemistry (Plenum Press, London,
1973), pp. 46–47.

Silica Sulfuric Acid/NaNO2 as a Novel Heterogeneous System
1629
[9] M. Cameron, B. G. Gowenlock, and A. S. F. Boyd, J. Chem. Soc. Perkin Trans, 2,
2271 (1996).
[10] A. C. Veronese, G. Vecchiati, and P. Orlandini, Synthesis, 300 (1985).
[11] a) R. G. Fuson, Reaction of Organic Compounds: A Textbook for the Advanced Stu-
dent (John Wiley & Sons, New York, 1962), pp. 535–538; b) O. Touster, Org. Re-
actions, 7, 327–378 (1953); c) R. B. Wagner and H. D. Zook, Synthetic Organic
Chemistry (John Wiley & Sons, New York, 1953), pp. 739–745.
[12] Y. H. Kim, Y. J. Park, and K. Kim, Tetrahedron Lett., 30, 2833 (1989).
[13] a) A. Graham and D. L. H. Williams, J. Chem. Soc. Perkin Trans., 2, 747 (1992); b)
E. Iglesias and D. L. H. Williams, J. Chem. Soc. Perkin Trans., 2, 343 (1989); c) P.
Roy and D. L. H. Williams, J. Chem. Res.(S)., 122 (1988); d) J. R. Leis, M. E. Pena,
D. L. H. Williams, and S. D. Mawson, J. Chem. Soc. Perkin Trans., 2, 157 (1988).
[14] M. A. Zolfigol, Molecules, 6, 694 (2001).
[15] M. M. Rogic, J. Vitrone, and M. D. Swerdloff, J. Am. Chem. Soc., 99, 1156 (1977).
[16] S. E. Mallakpour and M. A. Zolfigol, Indian J. Chem., 34B, 183 (1995).
[17] M. A. Zolfigol, M. H. Zebarjadian, G. A. Chehardoli, H. Keypour, S. Salehzadeh, and
M. Shamsipur, J. Org. Chem., 66, 3619 (2001).
[18] M. A. Zolfigol, M. H. Zebarjadian, M. M. Sadeghi, H. R. Memarian, I.
Mohammadpoor-Baltork, and M. Shamsipur, Synth. Commun., 30, 929 (2001).
[19] M. A. Zolfigol, M. Zebarjadian, G. A. Chehardoli, S. E. Mallakpour, and M.
Shamsipur, Tetrahedron, 57, 1627 (2001).
[20] B. W. Ford and P. Watts, J. Chem. Soc. Perkin Trans., 2, 1009 (1974).