New reagent for a one-step synthesis of gem-chloronitro compounds from oximes

Article abstract of DOI:10.1007/BF03246563

The use of chlorine bleach (5% NaOCl) for the halogenation-oxidation of oximes to gem-chloronitro compounds is reported. Chlorine bleach afforded satisfactory yields when employed alone either at room temperature or under ultrasonic irradiation.

Full text of DOI:10.1007/BF03246563

J. Iran. Chem. Soc., Vol. 8, No. 4, December 2011, pp. 1058-1062.
JOURIrNaAnLiaOnF THE
Chemical Society
ꢀꢀꢀꢀꢀꢀ
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New Reagent for a One-Step Synthesis of Gem-Chloronitro Compounds from Oximes
M.A. Zolfigola,*, A. Khazaeia,*, E. Kolvarib,*, N. Koukabia and M. Gilandousta
aFaculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
bDepartment of Chemistry, Faculty of Science, Semnan University, Semnan, Iran
(Received 21 January 2011, Accepted 24 May 2011)
The use of chlorine bleach (5% NaOCl) for the halogenation-oxidation of oximes to gem-chloronitro compounds is reported.
Chlorine bleach afforded satisfactory yields when employed alone either at room temperature or under ultrasonic irradiation.
Keywords: Chlorine bleach, Gem-chloronitro compounds, Halogenation, Oxidation, Ultrasonic
INTRODUCTION
Gem-Halonitro compounds 1 and 2 have proven to be
versatile intermediates in the synthesis of molecules
possessing one or more nitro groups. They have been prepared
traditionally either by the direct halogenation of nitronate salts
Scheme 1
[1-6] or from oximes via a halogenation-oxidation sequence
[7-21]. The utility of the gem-halonitro intermediates has been
demonstrated by their transformation to gem-dinitro
compounds via a reductive dehalogenation-nitration sequence
(Scheme 1) [9,16]. They have also functioned as important
Scheme 2
elements for assembling the polycyclic framework by an
intramolecular reductive coupling of two suitably located
gem-halonitro-substituted carbons to yield compounds
possessing dinitro substituents (Scheme 2) [6-7].
Therefore, there is considerable interest among researchers
to develop new simple methodologies for the preparation of
gem-halonitro compounds. The conversion of an oxime to a
gem-halonitro compound is believed to occur in two distinct
steps (Scheme 3).
The initial halogenation of oxime 3 generates a gem-
halonitroso intermediate which is oxidized in a subsequent
step to the gem-halonitro compound 1 or 2. Two distinct
ꢀ
Scheme 3
strategies have evolved to convert the oxime 3 to gem-
halonitro 1 or 2. One strategy uses a simple halogenating agent
to generate the gem-halonitroso intermediate and then relies
upon the use of a supplemental oxidant to oxidize the nitroso
to the nitro group. The halogenating agents that have been
*Corresponding author. E-mail: zolfi@basu.ac.ir

Zolfigol et al.
used for the first step include bromine [7-10], elemental
chlorine [10-12], aqueous hypochlorous acid [11], t-butyl
hypochlorite [13] and N-bromosuccinimide (NBS) [14].
The oxidizing agents that have proven to be useful for the
second step are nitric acid, trifluoroperoxyacetic acid [8-9],
ozone [12], hydrogen peroxide [6], aqueous sodium [11], n-
butylammonium hypochlorite [13] and m-chloroperbenzoic
acid. The second strategy involves the use of a combination
halogenating-oxidizing reagent that is capable of effecting the
overall conversion. The combination reagents that have been
investigated include both the hypochlorous acid/hypochlorite
ion [13] and hypobromous acid/hypobromite ion [15], the
enzyme chloroperoxidase/hydrogen peroxide/NaCl or NaBrꢀ
[19], oxone/NaCl or NaBr [20-21] systems, NBS [8] and
N,N,N-trihalo-1,3,5-triazines [18].
chromatography.
Method B (with sonication). Oxime (1 mmol) was added
to a solution of chlorine bleach (1 ml) whereupon the reaction
mixture developed a distinct blue color immediately. Chlorine
bleach (10-15 ml) was added to the reaction mixture which
was sonicated in an ultrasonic bath (between 0.5 to 6 h) until it
became colorless. The reaction mixture was transferred to a
separatory funnel and a 10% aqueous Na2CO3 solution (25 ml)
was added. The aqueous fraction was extracted with
dichloromethan (3 × 15 ml). The organic layer (Na2SO4) was
dried; the solvent removed by distillation and the product was
purified by column chromatography.
RESULTS AND DISCUSSION
Our interest in developing a convenient and reliable
combination reagent prompted us to examine the halogenation
and oxidation properties of cosmetic bleach. The cosmetic
bleach is found in a large number of commercial products that
are employed as sources of stabilized chlorine for swimming
pool disinfection. However, this reagent has received only
limited scrutiny as an oxidizing agent in the laboratory despite
its widespread usage [22-25].
The methods reported above have some drawbacks such as
the use of strong and non-selective oxidizing agents, toxic or
expensive reagents, low yields, long reaction times and
transformation of most of the oxime into the parent ketone.
EXPERIMENTAL
General
The most convenient procedure involves stirring the oxime
in the aqueous media containing chlorine bleach at room
temperature to create a blue color, adding excess amount of
bleach and stirring the solution between 2 to 10 h which leads
to the formation of the desired product (method A, Scheme 4).
The results of the investigation are summarized in Table 1.
Ultrasound is found to be an efficient and virtually
innocuous means of activation in synthetic chemistry and has
been employed for decades with varying degrees of success.
The findings of numerous experiments revealed that
ultrasound had no effect on the chemical pathways and
reaction rates and was often comparable to those of non-
irradiated processes. Thus, in many heterogeneous reactions
the application of ultrasound, whether by bath or probe, has
All chemicals were purchased from Merck and Fluka
companies and used without any further purification. The
1
products were characterized by their spectral data (IR and H
NMR and 13C NMR) in some cases, and comparison with
authentic samples. Sonication was performed in ELMA
Transsonic 660/H (with a frequency of 35 KHz).
General Procedure for the Conversion of Oximes to
the Corresponding Gem-Chloronitro Compounds
Method A (without sonication). Oxime (1 mmol) was
added to a solution of chlorine bleach (1 ml) whereupon the
reaction mixture developed a distinct blue color immediately.
Chlorine bleach (10-15 ml) was added to the reaction mixture
which was stirred at room temperature (between 2 and 10 h)
until the reaction mixture became colorless. The reaction
mixture was transferred to a separatory funnel and a 10%
aqueous Na2CO3 solution (25 ml) was added. The aqueous
fraction was extracted with dichloromethane (3 × 15 ml). The
organic layer (Na2SO4) was dried; the solvent removed by
distillation, and the product was purified by column
Scheme 4
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New Reagent for a One-Step Synthesis of Gem-Chloronitro Compounds
Table 1. Conversion of Oximes to Corresponding Gem-chloro-nitro Compounds Using Chlorine Bleach at Room
Temperature (Method A) and under Ultrasound Irradiation (Method B)
Yield (%)a
Time (h)
Entry Substrate
Product
Ref.
[20]
Method
A
Method
B
Method Method
A
B
1
Cyclohexanone oxime
3
1
83
90
Cl
NO
2
2
3
4
5
Cycloheptanone oxime
Cyclopantanone oxime
4-t-Buylcyclohexanone oxime
2-Octanone oxime
10
4
6
1
3
2
83
78
81
73
91
80
98
79
[8]
[8]
8
[8]
5
[26]
6
7
2-Methylcyclohexanone oxime
2-Butanone oxime
2
4
1
1
61
65
65
68
[8]
[19]
8
Adamantanone oxime
6
2.5
80
82
[23]
9
5-Nonanone oxime
Cycloctanone oxime
5
3
80
82
84
85
[23]
[23]
10
10
6.5
aRefers to isolated yields (the products were characterized by comparison of their spectroscopic and physical data
with those of samples synthesized by reported procedures).
Table 2. Chlorine Bleach Converted Cyclohexanone Oxime to the Corresponding Gem-chloro-nitro Compound
in Comparison with other Methods
Solvent
requirement
H2O
Conditions
Time(h)
Yeild(%)
Ref.
Present work
[20,21]
[18]
Chlorine bleach
Oxone®/NaC1/wet basic
alumina
NaHCO3Ldioxane
Chloroperoxidase C
fumago/KCl/H2O2
HOCl
A: 3, B: 1
A: 83, B: 90
CHCl3
4
48
79
78
29
93
H2O
H2O
5
[19]
10 min
C6H6/H2O
[13]
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Zolfigol et al.
the same effect as a high-speed agitator or homogenizer in
which fluids do not cavitate
Accordingly we became interested in studying the
synergistic effect of ultrasonic irradiation in the conversion of
oximes to gem-chloronitro compounds using bleach as both
chlorinating and oxidizing agent.
Research Council, Bu-Ali Sina University Research Council
(Grant Number 32-1716), and the Center of Excellence in the
Development of Chemical Methods (CEDCM).
REFERENCES
Ultrasound was employed in a procedure similar to method
A. The corresponding results are summarized in Table 1
(method B). The shortest reaction times and the highest yields
using method B were achieved by employing ultrasound. The
conversion of the oximes to the gem-halonitro compounds is
assumed to follow the steps outlined in Scheme 3. The initial
step is thought to be the halogenation of the oxime either
directly by the sodium hypochlorite or by molecular halogen,
which is present in the solution of the bleach. The
intermediacy of the halonitroso species in the reaction
sequence is suggested when the color of the mixture evolves
rapidly to the characteristic blue of monomeric C-nitroso
compounds. The disappearance of the blue color serves as a
convenient method for monitoring the progress of the nitroso
to nitro (blue to colorless) transformation. This oxidation is the
overall rate-determining step using methods A or B, where it
is thought to be accomplished by the sodium hypochlorite in
the aqueous medium.
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
G.A. Russell, D.F. Dedolph, J. Org. Chem. 50 (1985)
2498.
A. Amrollah-Madjdabadi, R. Beugelmans, A.
Lechevallier, Synthesis 1986 (1986) 828.
A. Amrollah-Madjdabadi, R. Beugelmans, A.
Lechevallier, Synthesis 1986 (1986) 826.
S. Ranganathan, H. Raman, C.V. Srinivaean,
Tetrahedron 34 (1973) 3129.
B.R. Fishwick, D.K. Rowles, C.J.M. Stirling, J. Chem.
Soc., Perkin Trans. I (1986) 1171.
P.A. Wade, W.P. Dailey, P.J. Carroll, J. Am. Chem.
Soc. 109 (1987) 5452.
L.A. Paquette, J.W .Fischer, P. Engel, J. Org. Chem. 50
(1985) 2524.
A.P. Marchand, B.E. Arney, Jr., P.R. Dave, J. Org.
Chem. 53 (1988) 443.
A.P. Marchand, S.C. Suri, J. Org. Chem. 49 (1984)
2041.
[10] A.T. Nielsen, J. Org. Chem. 27 (1962) 1993.
CONCLUSIONS
[11] T.G. Archibald, L.G. Garver, K. Baum, M.C. Cohen, J.
Org. Chem. 54 (1989) 2869.
In summary, chlorine bleach has proven to be a useful
combination halogenating-oxidizing reagent for the
conversion of oximes to gem-chloronitro compounds. The
procedure is simple and the yields are favorable to high.
Additionally, ultrasound may be used in this procedure to
make the conversion take place in a stepwise manner. Using
sonication leads to the increase in the yield and decrease in the
reaction time. Briefly speaking, by comparing the findings of
our reseach, as illustrated in Table 2, with the results of other
reports in the literature, we venture to suggest that our metho
is a better alternative for conversion of cyclohexanone oxime
to the corresponding gem-chloro-nitro compounds.
[12] M.W. Barnes, J.M. Patterson, J. Org. Chem. 41 (1976)
733.
[13] E.J. Corey, H. Estreicher, Tetrahedron Lett. 21 (1980)
1117.
[14] D.C. Iffland, G.X. Criner, J. Am. Chem. Soc. 75 (1953)
4047.
[15] S. Ranganathan, H.H. Raman, Tetrahedron 30 (1974)
63.
[16] K. Baum, T.G. Archibald, J. Org. Chem. 53 (1988)
4645.
[17] D.C. Iffland, C.X. Criner, F.J. Lotapeich, M.D. Koval,
Z.B. Papanastassiou, S.M. White, J. Am. Chem. Soc. 75
(1953) 4044.
ACKNOWLEDGMENTS
[18] R.T. Walters, W.W. Zajac, J.M. Woods, J. Org. Chem.
56 (1991) 316.
The authors gratefully acknowledge Semnan University
[19] A. Zaks, A.V. Yabannavar, D.R. Dodds, C.A. Evans,
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New Reagent for a One-Step Synthesis of Gem-Chloronitro Compounds
P.R. Das, R. Malchow, J. Org. Chem. 61 (1996) 8692.
[24] J. Liang, J.R. Owens, T.S. Huang, S.D. Worley, J.
[20] C. Paolo, C. Massimo, E. Francesco, C.M. Maria, R.
Ornelio, Tetrahedron Lett. 39 (1998) 4385.
[21] C. Massimo, E. Francesco, C.M. Maria, R. Ornelio, R.
Monia, Tetrahedron 55 (1999) 6211.
[22] B.J. Staskun, J. Org. Chem. 53 (1988) 5287.
[23] B.J. Staskun, J.L.C. Marais, W. Pickl, J. Org. Chem. 55
(1990) 1969.
Appl. Polym. Sci. 101 (2006) 3448.
[25] J. Liang, R. Wu, T.S. Huang, S.D. Worley, J. Appl.
Polym. Sci. 97 (2005) 1161.
[26] P. Butler, B.T. Golding, G. Laval, H. Loghmani-
Khouzani, R. Ranjbar-Karimi, M.M. Sadeghi,
Tetrahedron 63 (2007) 11160.
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