N-tert-Butyl-N-chlorocyanamide: A new reagent for the efficient preparation of gem-chloronitroso compounds

Article abstract of DOI:10.1016/j.tetlet.2005.09.131

A new reagent for the efficient preparation of gem-chloronitroso compounds has been developed. The reaction of ketoximes with N-tert-butyl-N- chlorocyanamide takes place instantaneously in carbon tetrachloride at room temperature with excellent yields under mild conditions.

Full text of DOI:10.1016/j.tetlet.2005.09.131

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8121–8123
N-tert-Butyl-N-chlorocyanamide: a new reagent for the
efficient preparation of gem-chloronitroso compounds
Vinod Kumar and M. P. Kaushik*
Process Technology Development Division, Defence R&D Establishment, Jhansi Road, Gwalior 474002, MP, India
Received 7 August 2005; revised 14 September 2005; accepted 21 September 2005
Available online 7 October 2005
Abstract—A new reagent for the efficient preparation of gem-chloronitroso compounds has been developed. The reaction of ketox-
imes with N-tert-butyl-N-chlorocyanamide takes place instantaneously in carbon tetrachloride at room temperature with excellent
yields under mild conditions.
Ó 2005 Elsevier Ltd. All rights reserved.
gem-Chloronitroso compounds have proven to be versa-
tile synthons in organic chemistry for the preparation of
a variety of compounds1 and in the cyclization reac-
tions.2 The synthesis of these compounds is generally
achieved from oximes and is performed with good
results by the use of elemental chlorine,3 aqueous
hypochlorous acid,3 alkyl hypochlorite4 and N-halo-
compounds,5 but often results in the formation of
over-oxidized nitro derivatives along with the title com-
pounds. It is always the aim to stop the reaction at the
nitroso stage by controlling the reaction temperature
and by slow addition of the reagent, but these require-
ments are often hard to meet and failure results in
over-oxidation to nitro compounds. Therefore, there is
still considerable interest in the development of selective
methods/reagents for this transformation. Although,
various methods are known for the synthesis of nitroso
compounds, very few are sufficiently selective to termi-
nate the reaction at the nitroso stage. Some of these
methods invariably result in contamination of the prod-
ucts, involve pH-dependent reactions requiring stringent
precautions, are limited to specific substrates and result
in the formation of several by-products, thereby leading
to low yields of the desired compounds. Furthermore,
these methods are useful only for the synthesis of
aliphatic gem-chloronitroso compounds and are not
suitable for aromatic gem-chloronitroso compounds.
Thus a mild, selective and inexpensive reagent is still
in demand. During the course of our systematic study
and research on the oxidation of organic compounds
with N-tert-butyl-N-chlorocyanamide,6 we investigated
it as a novel, rapid and convenient reagent for selective
conversion of oximes to their corresponding gem-chloro-
nitroso derivatives.
The reaction of various oximes possessing alkyl, aryl or
cyclic moieties with 2 in CCl4 at room temperature affor-
ded the corresponding products almost immediately
with chemoselectivity and without the formation of
by-products. The reaction was monitored by TLC and
the results are presented in Table 1. The procedure
was sufficiently selective to terminate the reaction at
the nitroso stage and prevent over-oxidation to the nitro
compounds. Even a sterically hindered ketoxime (Table
1, entry 6) was successfully converted into the corre-
sponding gem-chloronitroso derivative in excellent yield
(Scheme 1). Fenchone oxime was found to react with an
equimolar quantity of 2 at the same rate as camphor
oxime to give the corresponding gem-chloronitroso
derivative (Table 1, entry 5) even though it is more hin-
dered (Scheme 1).
All the aliphatic and aromatic gem-chloronitroso com-
pounds prepared were stable at low temperature. It has
already been reported that aromatic oximes react at a
slower rate with chlorinating agents3 as compared to ali-
phatic oximes. Thus another important feature of this
method is that aromatic oximes formed gem-chloronitr-
oso compounds immediately on mixing. This indicates
that aromaticity did not apparently affect the rate of
Keywords: N-tert-Butyl-N-chlorocyanamide; Ketoximes; gem-Chloro-
nitroso compounds.
*
Corresponding author. Tel.: +91 751 234 3972; fax: +91 751 234
1148; e-mail: mpkaushik@rediffmail.com
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.09.131

8122
V. Kumar, M. P. Kaushik / Tetrahedron Letters 46 (2005) 8121–8123
Table 1. Preparation of gem-chloronitroso compounds from oximes using 2
CN
H
CN
R
Cl
R
tC4H9
CCl4
tC4H9
N
NOH
N
R'
< 1 min
NO
R'
Cl
1
2
3
4
Entry
1
Substrate
Product
Yielda
94
NOH
Cl
ON
NOH
Cl
ON
2
3
93
95
Cl
NOH
NO
Cl
NOH
NO
4
92
NO2
NO2
5
6
7
8
96
95
90
85
Cl
NO
NOH
Cl
NO
NOH
NOH
NO
Cl
O
O
Cl
Cl
NOH
NO
NO
NOH
All the products were compared with authentic samples and gave satisfactory IR, NMR and MS data.
a Isolated yields.
2, CCl4
< 1 min
2, CCl4
< 1 min
Cl
Cl
NO
NOH
camphor oxime
NOH
;
NO
fenchone oxime
Scheme 1.
reaction. All the oximes were prepared by standard
methods7 in which the ketone and hydroxylamine hydro-
gen chloride reacted at pH 7–8 by adding saturated aque-
ous sodium carbonate. The purity of compounds was
checked by TLC. N-tert-Butyl-N-chlorocyanamide was
prepared by the reported method.8

V. Kumar, M. P. Kaushik / Tetrahedron Letters 46 (2005) 8121–8123
8123
In conclusion, we have described an efficient reagent9 for
the rapid and convenient conversion of oximes to gem-
chloronitroso compounds under mild conditions. This
reagent has advantages over the conventional reagents
in terms of high yields, shorter reaction times, easy work
up and no side products. In addition to these, the
dechlorinated product 4 can be recycled to 2 for further
use.
Tordeux, M.; Boumizane, K.; Wakselman, C. J. Org.
Chem. 1993, 58, 1939–1940.
2. Wang, Y. C.; Lu, T. M.; Elango, S.; Lin, C. K.; Tsai, C. T.;
Van, T. H. Tetrahedron: Asymmetry 2002, 13, 691–695.
3. Archibald, T. G.; Garver, L. G.; Baurn, K.; Cohen, M. C.
J. Org. Chem. 1989, 54, 2869–2873.
4. Corey, E. J.; Estreicher, H. Tetrahedron Lett. 1980, 21,
1117–1120.
5. Walters, T. R.; Zajac, W. W., Jr.; Woods, J. M. J. Org.
Chem. 1991, 56, 316–321.
6. Kumar, V.; Kaushik, M. P. Chem. Lett. 2005, 34, 1230–1231.
7. Fournar, P.; Cointet, P.; Laviron, E. Bull. Soc. Chim. Fr.
1968, 6, 2438–2446.
Acknowledgement
8. Neale, R. S.; Marcus, N. L. J. Org. Chem. 1969, 34, 1808–
1816.
We thank Shri K. Sekhar, Director, DRDE, Gwalior,
for his keen interest and encouragement.
9. Typical experimental procedure: To a stirred solution of
oxime (5 mmol) in dry carbon tetrachloride (10 ml), at room
temperature, was slowly added N-tert-butyl-N-chlorocyan-
amide (1.0 equiv) in dry carbon tetrachloride (5 ml). The
reaction took place immediately on mixing, as monitored by
TLC and confirmed by the appearance of a blue colour in the
reaction mixture (in the case of aliphatic oximes). If the
products were liquid, the solution was concentrated and kept
in a refrigerator overnight. Compound 4 precipitated (mp
12–13 °C) and was filtered off immediately. The filtrate was
evaporated to give the crude product, which on distillation
under vacuum, afforded the pure product. If the products
were solid, purification was carried out by recrystallization
using DCM/petroleum ether (40–60 °C) in a 3:7 ratio.
References and notes
1. (a) Kruglyak, Y. L.; Landau, M. A.; Leibovskaya, G. A.;
Martynov, I. V.; Saltykova, L. I. Zh. Obshch. Khim. 1971,
41, 2338–2339; (b) Cecherelli, P.; Curini, M.; Epifano, F.;
Marcotullio, M. C.; Rosati, O. Tetrahedron Lett. 1998, 39,
4385–4386; (c) Sabuni, M.; Kresz, G.; Braun, H. Tetra-
hedron Lett. 1984, 25, 5377–5380; (d) Martynov, I. V.;
Chepakova, L. A.; Brel, V. K.; SokoIov, V. B. Zh. Obshch.
Khim. 1986, 56, 2420–2421; (e) Walters, T. R.; Zajac, W.,
Jr.; Woods, J. M. J. Org. Chem. 1991, 56, 316–321; (f)