A remarkably simple α-oximation of ketones to 1,2-dione monooximes using the chlorotrimethylsilane-isoamyl nitrite combination

Article abstract of DOI:10.1016/S0040-4039(03)00248-X

Ketones undergo α-oximation by NOCl formed in situ from Me₃SiCl and isoamyl nitrite, either in solution or under solvent-free conditions, to produce 1,2-dione monooximes in excellent yields. The oximation is regiospecific in appropriate cases.

Full text of DOI:10.1016/S0040-4039(03)00248-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2753–2755
A remarkably simple a-oximation of ketones to 1,2-dione
monooximes using the chlorotrimethylsilane–isoamyl nitrite
combination
†
Abdulkarim H. A. Mohammed and Gopalpur Nagendrappa*
Department of Chemistry, Bangalore University (Central College Campus), Bangalore 560001, India
Received 18 November 2002; revised 15 January 2003; accepted 24 January 2003
Abstract—Ketones undergo a-oximation by NOCl formed in situ from Me SiCl and isoamyl nitrite, either in solution or under
3
solvent-free conditions, to produce 1,2-dione monooximes in excellent yields. The oximation is regiospecific in appropriate cases.
©
2003 Published by Elsevier Science Ltd.
R SiX reagents, according to Fleming’s analysis, react
analogously to, but more selectively than HX. Treat-
ing chlorotrimethylsilane (TMSCl) with isoamyl nitrite
There is much patent literature describing the prepara-
tion of a-oximino ketones and their conversion to
dioximes. a-Oximino ketones hydrolyze to synthetically
3
1
,2
(
AmONO) is an effective method for the in situ genera-
tion of NOCl in aprotic solvent media as well as under
solvent free conditions. We have shown earlier that
NOCl thus produced adds to vinylsilanes in a regiospe-
Table 1. a-Oxidation of ketones using TMSCl–AmONO
3
cific and stereoselective manner. This, to our knowl-
edge, is the most convenient method for the generation
and reaction of NOCl particularly for laboratory scale
preparations. Conventional procedures for obtaining
NOCl under anhydrous condition are rather
4
cumbersome.
The direct a-oximation of ketones, esters, and alde-
4
a
hydes by NOCl is known. Rasmussen and Hassner
argue that the methods used are associated with many
shortcomings and showed that silylenol ethers are supe-
5
,6
rior for achieving better yields and selectivity. How-
ever, the handling of silylenol ethers needs special care,
and their preparation is an avoidable extra step. There-
fore, earlier procedures are preferred even now for the
7
preparation of a-oximino ketones.
a-Oximino ketones find many applications. They are
used as starting compounds for the synthesis of imida-
7
8
4
zoles, oxazoles, a-amino acids and esters, a-amino
9
10
alcohols, pharmaceutically useful heterocycles like
luciferin analogues, and other valuable products.
1
1
12
Keywords: oximation; TMSCl; amyl nitrite; 1,2-diketone monooxime;
NOCl.
*
Corresponding author. E-mail: nagendrappa@vsnl.net
On leave from Sana’a University, Sana’a, Yemen.
†
0
040-4039/03/$ - see front matter © 2003 Published by Elsevier Science Ltd.
doi:10.1016/S0040-4039(03)00248-X

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A. H. A. Mohammed, G. Nagendrappa / Tetrahedron Letters 44 (2003) 2753–2755
Scheme 1.
1
3
important a-diketones, and serve as ligands for transi-
partly supported by UGC-DRS and UGC-COSIST
programmes, New Delhi. Some equipment used for the
work is a donation to G.N. by the Alexander von
Humboldt Foundation, Germany.
1
4
tion metal complexes.
We have found that ketones undergo a-oximation read-
ily on treatment with TMSCl and AmONO in solvents
or under solvent-free conditions. The results are
reported.
References
a-Oximation was carried out with aryl alkyl ketones
1. Fleming, I. Chem. Soc. Rev. 1981, 10, 83.
1
–6, alkyl ketones 7–9, and the cyclic ketone 10. One
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molar equivalent of TMSCl was added to the substrate
either neat or in CH Cl solution) at −20°C, followed
(
2
2
by the dropwise addition of an equivalent quantity of
isoamyl nitrite. The reaction was found to be instanta-
neous, but the mixture was stirred for an additional
period of 30 min before working up. The products were
purified on a silica gel column using 5% ethyl acetate in
petroleum ether (bp 45–55°C) as eluant, and identified
1
13
by their mp, IR, H and C NMR spectra, which were
compared with literature data. The a-ketooxime 18,
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dioxime by reacting with NH OH·HCl. The results are
2
given in Table 1.
6. It is claimed that a general method using t-butyl thioni-
trate has been developed. It seems, however, to apply
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PhCOCH(NOH)CH from PhCOCH CH by old meth-
The reactions run in the absence of solvent were found
to give slightly better yields (about 2–5% more) than
those from reactions run in solution. This observation
makes the procedure particularly attractive because of
1
5
its eco-friendly character.
The oximation is brought about by NOCl formed in
3
2
3
situ as shown previously by the reaction of Me SiCl
with isoamyl nitrite. It is to be noted that only one
ods; (b) Hossbach, R.; Lettau, H.; Nuhn, P.; Schneider,
R.; Stenger, P.; Stiebitz, B. Pharmazie 1991, 46, 412.
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3
3
a-position of the ketones 7–10 is oximated, though both
are susceptible, and that monooximation occurs
regiospecifically in 7 and 9 on the more readily enoliz-
able a-position. This indicates that the reaction starts
with enolization (facilitated by TMSCl/HCl), and fol-
lows the route depicted in Scheme 1.
In conclusion, a-ketooximes can be prepared from
10. (a) Canpillo, N.; Garcia, C.; Goya, P.; Paez, J. A.;
Carrasco, E.; Grau, M. J. Med. Chem. 1999, 42, 1698; (b)
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1
6
run on preparative scale. No extra precaution was
needed except to avoid the entry of moisture. This work
discloses a new application of the organsilicon reagent,
Me SiCl, for an important organic transformation.
3
1987, 24, 441; (d) Mendoza, J. S.; Jagdmann, G. E., Jr.;
Acknowledgements
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A.H.A.M. thanks ICCR, New Delhi, for a fellowship
under Cultural Exchange Programme. The work was

A. H. A. Mohammed, G. Nagendrappa / Tetrahedron Letters 44 (2003) 2753–2755
2755
1
1
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5
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1
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(1.2 g, 11.0 mmol) was added slowly to the ketone in 5 mL
3
1
1
of CH
a CaCl
g, 12.0 mmol). The mixture turned blue and then yellow.
After stirring for 30 min more, ether or CH Cl (20 mL)
2
Cl
2
at −20°C in a 50 mL two-necked flask fitted with
guard tube, followed by dry isoamyl nitrite (1.4
2
2
2
was added and the reaction worked up in the usual way.
The product was eluted on a silica gel column using pet.
ether (bp 50–55°C) containing 5% ethyl acetate to get pure
product.