Ultrasound promoted one-pot synthesis of gem -chloronitro compounds from oximes

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Ultrasound Promoted One-Pot Synthesis
of gem-Chloronitro Compounds from
Oximes
a
a
b
Ardeshir Khazaei , Mohammad Ali Zolfigol , Eskandar Kolvari
,
b
a
Nadiya Koukabi & Maryam Gilandoust
a
Faculty of Chemistry, Bu-Ali Sina University, Hamedan,
517838683, Iran
6
b
Department of Organic Chemistry, Faculty of Chemistry, Semnan
University, P. O. Box 35195-363, Semnan, Iran
Published online: 01 Aug 2012.
To cite this article: Ardeshir Khazaei , Mohammad Ali Zolfigol , Eskandar Kolvari , Nadiya Koukabi &
Maryam Gilandoust (2012): Ultrasound Promoted One-Pot Synthesis of gem-Chloronitro Compounds
from Oximes, Organic Preparations and Procedures International: The New Journal for Organic
Synthesis, 44:4, 375-380
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Organic Preparations and Procedures International, 44:375–380, 2012
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2012.697719
Ultrasound Promoted One-Pot Synthesis
of gem-Chloronitro Compounds from Oximes
1
1
2
Ardeshir Khazaei, Mohammad Ali Zolfigol, Eskandar Kolvari,
2
1
Nadiya Koukabi, and Maryam Gilandoust
1
Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
2
Department of Organic Chemistry, Faculty of Chemistry, Semnan University,
P. O. Box 35195-363 Semnan, Iran
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
16
either by the direct halogenation of nitronate salts or from oximes via a halogenation-
oxidation sequence.7 The utility of the gem-halonitro intermediates has been demon-
strated by their transformation to nitro compounds via a reductive dehalogenation process
–21
8,14
(
Scheme 1). They have also functioned as important elements for assembling polycyclic
frameworks by an intramolecular reductive coupling of two suitably located gem-halonitro-
6,18
substituted carbons to yield compounds possessing dinitro substituents (Scheme 1).
NO
2
X NO
2
X
R
NO2 reduction
R
H
R
NO2
R
reduction
X NO2
NO2
1
2
(
X = Cl
X = Br
)
(
)
Scheme 1
The conversion of an oxime to a gem-halonitro compound is believed to occur in two
distinct steps (Scheme 2).
The initial halogenation of the oxime 3 generates a gem-halonitroso intermediate, which
is oxidizedinasubsequent steptothe gem-halonitrocompound 1or 2. Twodistinct 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
Received May 20, 2011; in final form March 9, 2012.
Address correspondence to Ardeshir Khazaei, Faculty of Chemistry, Bu-Ali Sina Univer-
sity, Hamedan 6517838683, Iran. E-mail: khazaei 1326@yahoo.com (Khazaei); zolfi@basu.ac.ir
(Zolfigol); kolvari@semnan.ac.ir (Kolvari)
375

376
Khazaei and Zolfigol
HO
R
N
+ X-Y
- H-Y
oxidation
X
R
NO
R
X
R
NO2
R
R
1
2
X = Cl
(
(
)
)
3
X = Br
Scheme 2
5
,7,17
12,14,17,22
11
that have been used for the first step include elemental chlorine,
bromine,
2
6
aqueous hypochlorous acid , t-butyl hypochlorite or N-bromosuccinimide (NBS).
The oxidizing agents that have proven successful for the second step are nitric acid,
1
2–14
7
6
trifluoroperoxyacetic acid,
ozone, hydrogen peroxide, aqueous sodium hypochlo-
5
9
rite solution or n-butylammonium hypochlorite, m-chloroperbenzoic acid. The second
strategy involves the use of a combination halogenating-oxidizing reagent that is capable
of performing the overall conversion. The combination reagents that have been investi-
gated include hypochlorous acid/hypochlorite ion, hypobromous acid/hypobromite ion,
the enzyme chloroperoxidase/hydrogen peroxide/NaCl or NaBr, oxone/NaCl or NaBr
systems, NBS12 and N,N,N-trihalo-1,3,5-triazines. The reported methods have some lim-
itations such as the use of toxic or expensive reagents, low yields, long reaction times and
transformation of most of the oxime into the parent ketone. Therefore, there is considerable
interest in developing new simple methodologies for the preparation of the gem-halonitro
compounds.
9
19
21
15
20
Ultrasound is an efficient and virtually innocuous means of activation in synthetic
chemistry and has been employed for decades with varying success. Some advantages of
ultrasound procedure are short reaction times and mild reaction conditions, formation of
purer products and waste minimization. Ultrasonic irradiation can also be used to influence
selectivity and yields of reactions.2
3–27
In order to expand the application of ultrasound
irradiation in organic synthesis and reactions, herein we report the preparation of gem-
chloronitro compounds from corresponding oximes using nitric acid and sodium chloride
under sonication. Our interest in finding a convenient and reliable combination reagent
prompted us to examine the halogenation and oxidation properties of HNO3/NaCl system.
The most convenient procedure involves stirring the oxime in a solution of sodium
chloride/nitric acid at room temperature. Addition of excess amount of nitric acid to the
blue mixture (nitroso compound) and stirring the solution for 2 and 5 h, lead to formation of
desired product (Scheme 3). Shorter reaction times and the higher yields were achieved by
employing ultrasound irradiation. The results of the investigation are summarized in Table 1.
HO
N
1
HNO / NaCl Cl
NO
R2
2
)
3
R1
R2
R1
2 HNO3
)
Scheme 3

Synthesis of gem-Chloronitro Compounds from Oximes
377
Table 1
gem-Chloronitro Compounds from Oximes
Method Aa
Method Ba
Product
Yield (%)
Time (min)
120
Yield (%)
79
Time (min)
60
Cl NO2
75
86
Cl
Cl
NO2
150
180
92
94
60
90
NO2
NO2
85
80
Cl
180
85
100
Cl
83
180
300
98
79
90
NO2
75
165
Cl
NO2
Cl
Cl
NO2
63
165
67
60
NO2
65
81
300
180
68
88
180
75
NO2
Cl
Cl
NO2
80
240
84
120
a)Method A: without sonication; method B: with sonication.
It is important to note that bromination–oxidation of oximes by HNO3 and KBr leads to
formation of a complex mixture of compounds including gem-bromonitro and ketones,
in which, often, ketones are the major products. For example, halogenation-oxidation of
4-methylcyclohexanone oxime, by HNO3 and KBr under sonication leads to a mixture
containg 4-methylcyclohexanone (80%) and 1-bromo-1-nitrocyclohexane (20%).

378
Khazaei and Zolfigol
In summary, nitric acid in the presence of sodium chloride has proven to be useful com-
bination halogenating-oxidizing reagent for the conversion of oximes to gem-chloronitro
compounds. The procedure is simple and the yields are good to excellent. Additionally,
ultrasound may be used in this procedure to accelerate the conversion and increase yields.
Experimental Section
All chemicals were purchased from Merck and Fluka companies and used without any
1
further purification. The products were characterized by their spectral data (IR and H
13
NMR and C NMR) in some cases, and by 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 gem-Chloronitro Compounds
Method A (Without Sonication): The oxime (1 mmol) was added to a stirred solution
of nitric acid (68%, 1 mL) and sodium chloride (233.7 mg, 4 mmol) at room temperature.
The reaction mixture developed a distinct blue color immediately. Then nitric acid (68%,
10–15 mL) was added to the reaction mixture and stirring was continued at room tem-
perature until the reaction mixture became colorless (generally between 2 and 5 h). The
reaction mixture was transferred to a separatory funnel and a 10% aqueous Na2CO3 solu-
tion (25 mL) was added. After extraction with dichloromethane (3 × 15 mL), the organic
layer was dried over anhydrous Na2SO4. The solution evaporated under reduced pressure
to give the desired gem-chloronitro compound. All products were isolated as colorless oil
◦
20
◦
except 2-chloro-2-nitroadamantane (white crystal, mp. 189–191 C, lit. mp. 192–193 C).
Method B (With Sonication): The procedure above was followed with sonication
after the addition of nitric acid.
Spectral Data of the Products
1
1
-Chloro-1-nitrocyclopentane: Colorless oil; H NMR (CDCl3): δ 1.41–1.59 (m, 4
13
−1,20
H), 2.20–2.47 (m, 4 H); C NMR (CDCl3): δ 20.4, 34.5, 108.2; IR (Nujol): 1550 cm
Anal. Calcd for C5H8ClNO2: C, 40.15; H, 5.39; N, 9.36. Found: C, 40.10; H. 5.34; N,
.37.
-Chloro-1-nitrocyclohexane: Colorless oil; H NMR (CDCl3): δ 1.42–1.79 (m, 6 H),
.20–2.53 (m, 4 H); C NMR (CDCl3): δ 22.9, 23.9, 38.2, 103.7; IR (Nujol): 1548 cm ,
Anal. Calcd for C6H10ClNO2: C, 44.05; H, 16.16; N, 8.56. Found: C, 43.93; H, 16.12;
9
2
1
1
13
−1 20
N, 8.51.
-Chloro-1-nitrocycloheptane: Colorless oil; H NMR (CDCl3): δ 1.50–1.83 (m,
1
1
13
8
1
H), 2.40–2.62 (m, 4 H); C NMR (CDCl3): δ 22.7, 28.2, 42.4, 108.6; IR (Nujol):
−1 28
561 cm ,
Anal. Calcd for C7H12ClNO2: C, 47.33; H, 6.81; N, 7.89. Found: C, 47.30; H’ 6.76;
N, 7.86.
-tert-Butyl-1-chloro-l-nitrocyclohexane: colorless solid, mp. 52–53 C; H NMR
◦
1
4
−1
(
CDCl3): δ 0.98 (s, 9 H), 1.20–1.52 (m, 5 H), 2.15–2.40 (m, 4 H); IR (thin film): 1560 cm .
Anal. Calcd for C9H18ClNO2: C, 54.67; H, 8.26; N, 6.38. Found: C, 54.61; H, 8.31;
N, 6.36.

Synthesis of gem-Chloronitro Compounds from Oximes
379
1
-Chloro-2,6-dimethyl-1-nitrocyclohexane: 13C NMR (CDCl3): δ 11.1, 19.9, 26.7,
−1
3
3.0, 118.3; IR (Nujol): 1552 cm .
Anal. Calcd for C8H14ClNO2: C, 50.13; H, 7.36; N, 7.31. Found: C, 50.13; H, 7.30;
N, 7.34.
-Chloro-2-methyl-1-nitrocyclohexane: Colorless oil; H NMR (CDCl3): δ 0.96 (s,
1
1
13
3
2
H), 1.20–1.57 (m, 6 H), 1.8 (m, 1 H), 2.11–2.40 (m, 2 H); C NMR (CDCl3): δ 11.7,
3.2, 24.0, 26.2, 33.6, 35.4, 111.6; IR (Nujol): 1557 cm ;
−1 28
Anal. Calcd for C7H12ClNO2: C, 47.33; H, 6.81; N, 7.89. Found: C, 47.30; H, 6.82;
N, 7.85.
-Chloro-2-nitrobutane: colorless oil; H NMR (CDCl3): δ 0.85–0.94 (t, 3 H),
1
2
−1
2
.11–2.20 (q, 2 H), 2.30 (s, 3 H); IR (Nujol): 1563 cm .
Anal. Calcd for C4H8ClNO2: C, 34.92; H, 5.86; N, 10.18. Found: C, 34.94; H, 5.81;
N, 10.12.
-Chloro-2-nitroadamantane: colorless solid, mp. 192–193 C; 13C NMR (CDCl3):
◦
−
2
1
δ 25.4, 25.9, 34.1, 34.8, 37.0, 37.4, 107.9; IR (thin film): 1553 cm .
Anal. Calcd for C10H14ClNO2: C, 55.69; H, 6.54; N, 6.49. Found: C, 55.63; H, 6.50;
N, 6.44.
5
-Chloro-5-nitrononane: colorless oil; 1H NMR (CDCl3): δ 0.74–0.85(t, 6H),
.10–1.42 (m, 8H), 2.20–2.46 (m, 4H); C NMR (CDCl3): δ 13.80, 22.45, 26.01, 41.82,
13
1
1
−1
10.02; IR (Nujol): 1551 cm .
Anal. Calcd for C9H18ClNO2: C, 52.05; H, 8.74; N, 6.74. Found: C, 51.92; H, 8.78;
N, 6.71.
-Chloro-l-nitrocycloctane: colorless oil; HNMR (CDCl3): δ 1.20–1.37 (m, 10H),
1
1
13
1
1
.90–2.30 (m,4H); C NMR (CDCl3): δ 22.91, 24.36, 27.30, 37.09, 108.66; IR (Nujol)
559 cm .
Anal. Calcd for C8H14ClNO2: C, 50.14; H, 7.36; N, 7.31. Found: C, 50.13; H, 7.33;
−1
N, 7.35.
Acknowledgments
The authors acknowledge Bu-Ali Sina University Research Council and Center of Excel-
lence in Development of Chemical Methods (CEDCM) and National Foundation of Elites
(BMN) and Grant Number 32–1716, and Semnan University Research Council for support
of this work.
References
1
2
3
4
5
6
. G. A. Russell and D. F. Dedolph, J. Org. Chem., 50, 2498 (1985).
. A. Lechevallier, R. A. Beugelmans and A. Amarollah-Madjdabadi, Synthesis, 828 (1986).
. S. Ranganathan, H. Raman and C. V. Srinivaean, Tetrahedron, 34, 3129 (1973).
. B. R. Fishwick, D. K. Rowles and C. J. M. Stirling, J. Chem. Soc., Perkin Trans. I, 1171 (1986).
. T. G. Archibald, L. G. Garver, K. Baum and M. C. Cohen, J. Org. Chem., 54, 2869 (1989).
. P. A. Wade, W. P. Dailey and P. J. Carroll, J. Am. Chem. Soc., 109, 5452 (1987).

380
Khazaei and Zolfigol
7. M. W. Barnes and J. M. Patterson, J. Org. Chem., 41, 733 (1976).
8. K. Baum and T. G. Archibald, J. Org. Chem., 53, 4645 (1988).
9. E. J. Corey and H. Estreicher, Tetrahedron Lett., 21, 1117 (1980).
1
0. D. C. Iffland, C. X. Criner, F. J. Lotapeich, M. D. Koval, Z. B. Papanastassiou and S. M. White,
J. Am. Chem. Soc., 75, 4044 (1953).
1
1
1
1
1
1
1. D. C. Iffland and G. X. Criner, J. Am. Chem. Soc., 75, 4047 (1953).
2. A. P. Marchand, B. E. Arney, Jr. and P. R. Dave, J. Org. Chem., 53, 443 (1988).
3. A. P. Marchand and D. S. Reddy, J. Org. Chem., 49, 4078 (1984).
4. A. P. Marchand and S. C. Suri, J. Org. Chem., 49, 2041 (1984).
5. C. Massimo, E. Francesco, C. M. Maria, R. Ornelio and R. Monia, Tetrahedron, 55, 6211 (1999).
6. C. Paolo, C. Massimo, E. Francesco, C. M. Maria and R. Ornelio, Tetrahedron Lett., 39, 4385
(1998).
1
1
1
2
2
7. A. T. Nielsen, J. Org. Chem., 27, 1993 (1962).
8. L. A. Paquette, J. W. Fischer and P. Engel, J. Org. Chem., 50, 2524 (1985).
9. S. Ranganathan and H. H. Raman, Tetrahedron, 30, 63 (1974).
0. R. T. Walters, W. W. Zajac and J. M. Woods, J. Org. Chem., 56, 316 (1991).
1. A. Zaks, A. V. Yabannavar, D. R. Dodds, C. A. Evans, P. R. Das and R. Malchow, J. Org. Chem.,
61, 8692 (1996).
2
2
2
2
2
2
2
2. L. A. Paquette, J. W. Fischer and P. Engel, J. Org. Chem., 50, 2524 (1985).
3. Y. Kegelaers, O. Eulaerts, J. Reisse and N. Segebarth, Eur. J. Org. Chem., 3683 (2001).
4. C. Giancarlo and C. Pedro, Chem. Soc. Rev., 35, 180 (2006).
5. R. Cella and H. A. Stefani, Tetrahedron, 65, 2619 (2009).
6. M. Ashokkumar and F. Grieser, Rev. Chem. Eng., 15, 41 (1999).
7. D. Peters and R. Miethchen, J. Prakt. Chem.-Chem. Ztg., 337, 615 (1995).
8. A. O. Terent’ev, I. B. Krylov, Y. N. Ogibin and G. I. Nikishin, Synthesis, 3819 (2006).